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    Cell and Molecular Biology
    miR-9-5p-induced autophagy and apoptosis in multiple myeloma cells by targeting TIMP2
    FANG Jie, HUANG Rui, ZHENG Honghui, JIA Qianqian, BAO Jing
    2024, 52 (8):  785-790.  doi: 10.11958/20240086
    Abstract ( 332 )   HTML ( 3 )   PDF (1854KB) ( 37 )  

    Objective To investigate the mechanism of the interaction between miR-9-5p and tissue metalloproteinase inhibitor 2 (TIMP2) on autophagy and apoptosis in multiple myeloma (MM) cells. Methods Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect expression levels of miR-9-5p and TIMP2 in bone marrow samples of 9 patients with newly diagnosed MM and 9 patients with recurrent MM. The correlation of expression levels between the two were analyzed. U266 cells were divided into the miR-control group, the miR-9-5p group, the pcDNA3.1 group, the pcDNA3.1-TIMP2 group, the miR-9-5p+pcDNA3.1 group, and the miR-9-5p+pcDNA3.1-TIMP2 group. The effects of overexpressed miR-9-5p and TIMP2 on autophagy and apoptosis in U266 cells were detected by flow cytometry, immunofluorescence staining and Western blot experiments. The dual luciferase report experiment verified the interaction between miR-9-5p and TIMP2. Results Compared with newly diagnosed MM patients, the expression level of miR-9-5p was increased and the expression level of TIMP2 was decreased in patients with recurrent MM. The expression levels of miR-9-5p and TIMP2 were negatively correlated (P<0.05). Compared with the miR-control group, the miR-9-5p group showed a decrease in the expression level of MAP1LC3B-Ⅱ, an increase in expression levels of MAP1LC3B-Ⅰ and SQSTM1, and a decrease in cell apoptosis rate (P<0.05). Compared with the pcDNA3.1 group, the expression level of MAP1LC3B-Ⅱwas increased in the pcDNA3.1-TIMP2 group, while the expression levels of MAP1LC3B-Ⅰand SQSTM1 were decreased, and the apoptosis rate of cells increased (P<0.05). Bioinformatics and dual luciferase reporter experiments confirmed that TIMP2 was the target gene of miR-9-5p. Conclusion miR-9-5p inhibits autophagy and apoptosis in MM cells by targeting TIMP2, thereby promoting the occurrence and development of MM.

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    Experimental Research
    Mechanism of microglia ferroptosis in smoke inhalation-induced brain injury
    LIU Bin, YANG Long, LI Wenli, SHAO Ningning, DONG Jinrui
    2024, 52 (8):  791-797.  doi: 10.11958/20231628
    Abstract ( 408 )   HTML ( 4 )   PDF (1250KB) ( 14 )  

    Objective To investigate the underlying mechanism of microglia ferroptosis in smoke inhalation-induced (SII) brain injury. Methods Twenty SPF-grade male C57BL/6 mice were randomly divided into the control group, the SII group, the ferrostatin-1 group (Fer-1, 2.5 mmol/kg) and the deferoxamine group (DFO, 200 mg/kg), with 5 mice in each group. Mice in the Fer-1 group and the DFO group were intraperitoneally injected with Fer-1 and DFO 1, 3 and 5 day after smoke exposure, respectively. The pathological changes of brain tissue were examined by HE staining and Prussian blue staining on the 6th day after smoke exposure. RT-qPCR was used to detect levels of inflammatory factors, brain tissue damage markers and ferroptosis markers. The contents of iron in mouse brain tissue were determined by double pyridine colorimetric assay. The contents of malondialdehyde (MDA) and lipid peroxide (LPO) in mouse brain tissue were determined by thiobarbituric acid (TBA) colorimetric assay. Superoxide dismutase (SOD) activity in mouse brain tissue was measured by xanthine oxidase assay kit. The contents of glutathione (GSH) in mouse brain tissue were determined by direct method of dithiodinitrobenzoic acid (DTNB) assay. BV2 cells were cultured in complete DMEM medium and divided into the control group, the erastin group (10 μmol/L), the Fer-1 group (erastinc stimulation combined with 5 mmol/L Fer-1 treatment) and the DFO group (erastinc stimulation combined with 50 mmol/L DFO treatment). After 24 h, cell viability was detected by CCK-8 assay, cell apoptosis was detected by Annexin V-FITC/PI flow cytometry, intracellular reactive oxygen species (ROS) production was detected by DCFDA staining, and mitochondrial membrane potential was detected by MitoTracker Red CMXRos staining. Results Compared with the control group, enhanced iron deposition and inflammation in brain tissue, elevated mRNA expression of inflammatory markers and damage markers in brain tissue, up-regulated ACSL4 and NCOA4 mRNA levels, down-regulated GPX4 and SLC7A11 mRNA levels, decreased GSH and SOD contents, and increased LPO and MDA contents were observed in brain tissue of the SII group (P<0.05). The mRNA expression level of 7 member of solute carrier family 11 (SLC7A11) was decreased in mice of the SII group. The contents of GSH and SOD were decreased, and the contents of LPO and MDA were increased (P<0.05). Compared with the SII group, all the above parameters were reversed in the Fer-1 group and the DFO group, and the damage of mouse brain tissue was alleviated (P<0.05). In BV2 cell experiments, compared with the control group, decreased survival rate of BV2 cells and increased apoptosis rate were found in the erastin group (P<0.05), and increased intracellular ROS level and decreased mitochondrial membrane potential were also observed in the erastin-stimulated BV2 cells. The above parameters were opposite to those of the erastin group in the Fer-1 group and the DFO group (P<0.05), and the oxidative damage of BV2 cells was alleviated. Conclusion The ferroptosis inhibitors Fer-1 and DFO can inhibit microglia ferroptosis and alleviate smoke inhalation-induced brain injury.

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    Effects of calycosin on neuronal autophagy and apoptosis in rats with spinal cord injury
    LI Daqiang, LI Jian, LU Zheming, CAO Yang
    2024, 52 (8):  798-803.  doi: 10.11958/20231623
    Abstract ( 287 )   HTML ( 5 )   PDF (1137KB) ( 31 )  

    Objective To explore the effect of calycosin (CAL) on neuronal autophagy and apoptosis in rats with spinal cord injury (SCI) by regulating PI3K/Akt signaling pathway and its mechanism. Methods A total of 32 male or female adult SD rats were randomly divided into the sham group, the SCI group, the CAL low (20 mg/kg) dose group and the CAL high (40 mg/kg) dose group with 8 rats in each group. The rat model of moderate SCI was established by modified Allen’s method. After successful modeling, rats were injected intraperitoneally immediately with different dosage of CAL or equal amount of saline once a day for 7 consecutive days. Basso, Beattie and Bresnahan (BBB) scores were used to evaluate the recovery of motor function of rats at 1, 3 and 7 d after surgery. At 7 d after surgery, Nissl staining was used to detect the surviving number of motor neurons in anterior horn of spinal cord. Western blot assay was used to assess expression levels of p62, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3B), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, Cleaved-Caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) proteins. Immunofluorescence staining was used to measure the expression of LC3B in anterior neurons of spinal cord. Results Compared with the sham group, BBB scores, the surviving number of motor neurons and levels of Bcl-2, Bcl-2/Bax, p-PI3K, p-PI3K/PI3K, p-Akt and p-Akt/Akt were significantly decreased (P<0.05), and levels of p62, Beclin-1, LC3B Ⅱ, LC3B Ⅱ/Ⅰ, Cleaved-Caspase-3 and Bax were significantly increased in the SCI group (P<0.05). Compared with the SCI group, BBB scores, the survival of anterior horn motor neurons and levels of LC3B Ⅱ, LC3B Ⅱ/Ⅰ, Bcl-2, Bcl-2/Bax, p-PI3K, p-PI3K/PI3K, p-Akt and p-Akt/Akt were increased in the CAL low dose group and CAL high dose group, and levels of p62, Cleaved-Caspase-3 and Baxcould were significantly decreased (P<0.05). Conclusion CAL could promote autophagy and inhibit apoptosis of neurons through activating PI3K/Akt signaling pathway, thereby conferring a protective role following SCI in rats.

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    Role of palmitoyltransferase modified NOD2 in brain injury after cardiopulmonary resuscitation in mice
    ZHOU Chengji, TANG Yong, JIANG Peng, HU Zhouquan, WEI Wei, WANG Guoan, FU Xiaofei
    2024, 52 (8):  804-808.  doi: 10.11958/20231874
    Abstract ( 253 )   HTML ( 1 )   PDF (1129KB) ( 17 )  

    Objective To investigate the role of nucleotide-binding oligomerization domain 2 (NOD2) modified by palmitoyltransferase (ZDHHC5) in brain injury after cardiopulmonary resuscitation (CPR) in mice. Methods Twenty-four male C57BL/6J mice were divided into the blank group, the control group, the ZDHHC5-si group and the NOD2-si group, with 6 mice in each group. Except for the blank group without any treatment, CPR modeling was performed in the other three groups. At 24 h before CPR, mice in the ZDHHC5-si group and the NOD2-si group were injected with ZDHHC5 siRNA and NOD2 siRNA via tail vein, respectively. The modified neurological deficit scale (mNSS) was used to evaluate the neurological function at 24 h, 48 h and 72 h in each group. Blood samples and brain tissue were collected 72 h after modeling. Real-time fluorescent quantitative PCR (qPCR) was used to detect ZDHHC5 and NOD2 in brain tissue. The protein expression levels of IL-1β, TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay (ELISA). Colorimetric method and thiobarbituric acid (TBA) method were used to detect protein expression levels of MDA and MPO in brain tissue, respectively. Western blot assay was used to detect expression levels of Cleaved Caspase-3, ZDHHC5 and NOD2 in brain tissue. HE pathological sections of brain tissue were observed under light microscope. The pathological sections of brain tissue were observed by TUNEL under fluorescence microscope. Results Compared with the blank group, the mNSS score, the expression levels of IL-1β, TNF-α, IL-6, MDA and MPO, and the protein expression levels of Cleaved Caspase-3, ZDHHC5 and NOD2 were significantly increased (P<0.05), and brain tissue damage and cell apoptosis were aggravated in the other three groups. Compared with the control group, the above indicators were significantly decreased in the ZDHHC5-si group and the NOD2-si group (P<0.05), and brain tissue damage and cell apoptosis were significantly attenuated. Compared with the NOD2-si group, the above parameters were significantly decreased (P<0.05), and brain tissue damage and cell apoptosis were further attenuated in the ZDHHC5-si group. Conclusion In the mouse CPR model, NOD2 can produce palmitoylated NOD2 after regulated by ZDHHC5, which further promotes the release of inflammatory factors and causes neuronal apoptosis, ultimately damaging brain tissue and affecting neurological function.

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    Study of magnesium isoglycyrrhizinate in ameliorating cisplatin induced myocardial injury in rats
    WANG Xinshuang, AN Yajuan, GUAN Xiuju, LI Jiao, LIU Yue, WEI Liping, QI Xin
    2024, 52 (8):  809-814.  doi: 10.11958/20231833
    Abstract ( 320 )   HTML ( 2 )   PDF (1121KB) ( 20 )  

    Objective To investigate the protective effect and mechanism of magnesium isoglycyrrhizinate (MgIG) on cisplatin (CDDP)-induced myocardial injury in rats. Methods Twenty-four Wistar rats were randomly divided into the normal control group, the cisplatin model group (CDDP group), the cisplatin + magnesium isoglycyrrhizinate low-dose group (MgIG-L group) and the cisplatin + magnesium isoglycyrrhizinate high-dose group (MgIG-H group), with 6 rats in each group. Changes of body mass of rats were monitored daily. At the end of drug administration, cardiac function indexes including left ventricular ejection fraction (LVEF), left ventricular short-axis narrowing rate (LVFS), left ventricular end-systolic internal diameter (LVESD) and left ventricular end-diastolic internal diameter (LVEDD) were detected by echocardiography. The morphology of myocardial tissue was observed by HE staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of creatine kinase isoenzyme MB (CK-MB) and troponin I (cTnI). Levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione synthase (GSH), reactive oxygen species (ROS) and ferrous ion (Fe2+) in homogenates of myocardial tissue were measured biochemically. The protein expressions of nuclear factor E2-associated factor 2 (Nrf2), long-chain fatty acyl coenzyme A synthase 4 (ACSL4), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) protein were detected by Western blot assay. Results The body mass of rats in the control group showed an increasing trend during feeding, and the body mass of rats in the CDDP group showed a decreasing trend. Compared with the CDDP group, the body mass of rats in the MgIG-L group and the MgIG-H group increased after 5 d, 9 d and 13 d of treatment (P<0.05). Compared with the control group, the CDDP group showed decreased LVEF and LVFS, increased LVESD and LVEDD, disturbed myocardial fiber alignment, myocardial fiber degeneration and fracture, increased serum CK-MB and cTnI levels, increased levels of MDA, Fe2+ and ROS in myocardial tissue, decreased levels of SOD and GSH, and decreased levels of Nrf2, GPX4, and decreased FTH1 protein expression levels and increased ACSL4 protein expression levels in myocardial tissue (P<0.05). Compared with the CDDP group, the above indicators and myocardial histopathological changes were significantly improved in the MgIG-L group and the MgIG-H group. Conclusion Magnesium isoglycyrrhizinate can ameliorate cisplatin-induced myocardial injury by regulating myocardial oxidative stress and inhibiting cardiomyocyte iron death in rats.

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    Clinical Research
    The relationship between body mass index and clinicopathologic characteristics of idiopathic membranous nephropathy
    HUANG Hong, LI Heng, FAN Kaiyuan, WEI Li, DING Li, JIA Junya, YAN Tiekun, LI Dong
    2024, 52 (8):  815-819.  doi: 10.11958/20231818
    Abstract ( 276 )   HTML ( 2 )   PDF (806KB) ( 22 )  

    Objective To investigate the effect of body mass index (BMI) on the clinicopathological characteristics of patients with idiopathic membranous nephropathy (IMN). Methods A total of 261 patients with IMN were divided into the normal group (66 cases), the overweight group (105 cases) and the obese group (90 cases) according to BMI. Clinical and renal pathological data of patients were compared between the three groups. The correlation between BMI and clinicopathological indexes was analyzed by Pearson or Spearman's correlation. The influencing factors of estimated glomerular filtration rate (eGFR) were analyzed by multiple linear regression, and the influencing factors of interstitial fibrosis (IF), tubular atrophy (TA), glomerulosclerosis (GS) and mesangial cell proliferation (MCP) were analyzed by binary Logistic regression. Results Compared with the normal group, the prevalence of diabetes mellitus, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were elevated in the overweight group. The prevalence of hypertension, hemoglobin (HGB), uric acid (UA), LDL-C, TG, 24-h urinary protein (UTP) and serum complement 3 (C3) were elevated, and high-density lipoprotein cholesterol (HDL-C) was decreased in the obese group (P<0.05). The prevalence of hypertension, UA, TG and serum C3 were elevated in the obese group compared to the overweight group (P<0.05). The glomerular basement membrane (GBM) thickness was higher in the obese group and the overweight group than that in the normal group, and the proportion of GS and IF was higher in the obese group than that in the normal group (P<0.05). BMI was positively correlated with hypertension, TG, LDL-C, serum C3, UTP, GS, IF, MCP and deposition in the mesangial region of C3, and negatively correlated with HDL-C (P<0.05). Multiple linear regression analysis showed that age, blood urea nitrogen (BUN), anti-phospholipase A2 receptor antibody (anti-PLA2R), UTP and TA were independent risk factors of eGFR. Binary Logistic regression analysis showed that elevated BMI, age, UTP and serum creatinine (Scr) were independent risk factors for IF. Age, Scr and elevated UA were independent risk factors for TA. Elevated BMI and decreased eGFR were independent risk factors for GS. Elevated BMI was an independent risk factor for MCP. There was no significant difference in the treatment protocol of IMN patients between the three groups. Conclusion Obesity can exacerbate multiple clinical and pathological outcomes in IMN patients.

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    Analysis of laboratory indexes and pathological features of crescent formation in children with allergic purpura nephritis
    BAI Mengke, YANG Xiaoqing, LI Hang, WANG Long, MA Jiwei
    2024, 52 (8):  820-824.  doi: 10.11958/20231860
    Abstract ( 297 )   HTML ( 3 )   PDF (820KB) ( 13 )  

    Objective To investigate changes of laboratory indicators and pathological features of Henoch-Schonlein purpura nephritis (HSPN) children after crescent formation, and to explore non-invasive biomarkers for predicting crescent formation. Methods A total of 278 children with HSPN who were hospitalized from January 2018 to July 2023 were selected and divided into the crescent formation group (196 cases) and the non crescent formation group (82 cases) based on their crescent formation status. Patients in the crescent formation group were sub-divided into the cellular crescent formation group (52 cases) and the cellular fibrous crescent formation group (144 cases) based on the type of crescent formation. Laboratory indicators and pathological characteristics were compared between different groups. The correlation between each indicator and the proportion of crescent formation was analyzed. The influencing factors of crescent formation were analyzed by Logistic regression. Receiver operating characteristic (ROC) curves were plotted, and the effectiveness of laboratory indicators in predicting crescent formation was evaluated. Results Compared with the non crescent formation group, 24-hour urine protein quantification (24 hUP), urine immunoglobulin G/creatinine (UGCR), urine red blood cell count (URBC), neutrophil/lymphocyte ratio (NLR), blood urea nitrogen (BUN) and triglycerides (TG) were significantly increased in the crescent formation group. There were increased proportion of diffuse mesangial hyperplasia (Mb), renal tubular atrophy or interstitial fibrosis (T1) (P<0.05). Compared with the cellular crescent group, the proportion of glomerular segmental sclerosis or adhesion (S1) and T1 were increased, and the proportion of crescent formation was higher in the cellular fibrous crescent group. The proportion of capillary endothelial cell proliferation (E1) was decreased in the cellular crescent group (P<0.05). Spearman correlation analysis showed that 24 hUP, UGCR, URBC, NLR, BUN, TG, Mb and T1 were positively correlated with the proportion of crescent formation (all P<0.05). The results of multivariate Logistic regression analysis showed that elevated UGCR and T1 were risk factors for crescent formation. The area under the curve (AUC) predicted by UGCR for crescent formation was 0.731 (95% CI: 0.667-0.795, P<0.05), with an optimal cutoff value of 5.00 mg/mmol, sensitivity of 0.744 and specificity of 0.610. Conclusion UGCR can be used as a non-invasive biomarker to assist in evaluating crescent formation in children with HSPN.

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    Clinical curative effect of HAT therapy on septic shock
    DAI Yao, FANG Xiang, HUANG Kang, FENG Jie, LIU Min, WU Songbai
    2024, 52 (8):  825-829.  doi: 10.11958/20240083
    Abstract ( 301 )   HTML ( 0 )   PDF (769KB) ( 13 )  

    Objective To explore the curative effect of hydrocortisone ascorbic acid, vitamin C and vitamin B1 (HAT) therapy on septic shock and its influence on the time of vasoactive drug application, hemodynamic parameters and short-term prognosis. Methods According to different treatment plans, 92 patients with septic shock were divided into the HAT group and the routine treatment group, 46 cases in each group. The routine treatment group was given routine treatments [anti-infection, fluid replacement, stabling blood pressure and continuous renal replacement therapy (CRRT)], while the HAT group was additionally given HAT therapy. All patients were treated continuously for 3 d. The indexes related the curative effect, scores of acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) and sequential organ failure assessment (SOFA), levels of mean arterial pressure (MAP), heart rate (HR), central arterial pressure (CAP), D-lactic acid (D-Lac), creatinine (Cr), hypersensitive C-reactive protein (hs-CRP) and procalcitonin (PCT) before and after treatment, incidence of adverse reactions and 28 d survival rate by follow-up were compared between the two groups. Results The circulation stabilization time, use time of vasoactive drugs and hormones, mechanical ventilation time, CRRT time, treatment time in ICU and total hospitalization time were shorter in the HAT group than those in the routine treatment group (P<0.05). After 7 d of treatment, scores of APACHE Ⅱand SOFA, levels of HR, D-Lac, Cr, hs-CRP and PCT were lower in the HAT group than those in the routine treatment group, while MAP and CAP were higher than those in the routine treatment group (P<0.05). The 28-day survival rate was 65.22% in the HAT group, which was higher than that in the routine treatment group (45.65%, P<0.05). Conclusion HAT therapy can improve clinical curative effect in patients with septic shock, shorten use time of vasoactive drugs, improve hemodynamic parameters and short-term prognosis.

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    Construction of long term restenosis prediction model for patients with severe subpatellar artery lesions in type 2 diabetes treated with paclitaxel coated balloon
    LIN Feng, CHEN Lingxiong, LIU Yu, ZHANG Xuming, YIN Zhida, LIN Tanhui, LIU Zunrong
    2024, 52 (8):  830-834.  doi: 10.11958/20240057
    Abstract ( 288 )   HTML ( 2 )   PDF (1025KB) ( 26 )  

    Objective To analyze influencing factors of paclitaxel coated ballon (PCB) on long-term restenosis in patients with severe subpatellar artery lesions in type 2 diabetes mellitus (T2DM), and to construct a prediction model. Methods A total of 268 T2DM patients with severe infra-popliteal artery disease and received PCB treatment were selected. Patients were followed up for 1 year after treatment. Patients with target vessel restenosis were included in the observation group, and the other patients were included in the control group. Clinical data of two groups were analyzed.Multivariable Logistic regression analysis was used to analyze influencing factors of long-term restenosis in T2DM patients with severe infra-knee arterial disease, and a nomogram prediction model was constructed. Results A total of 260 patients (97.00%) completed the follow-up, and the incidence of restenosis was 13.85% (36/260). Both univariate and multivariate Logistic regression analysis showed that age, coexisting coronary heart disease, Trans-Atlantic Inter-Society Consensus (TASC) Ⅱ classification, Fontaine staging, glycosylated hemoglobin (HbA1c) and low density lipoprotein cholesterol (LDL-C) were independent influencing factors for the occurrence of long-term restenosis in T2DM patients with severe infra-popliteal artery disease (P < 0.05). The risk factor with the highest score in the constructed nomogram prediction model was HbA1c, followed by age, LDL-C, TASCⅡ classification, Fontaine stage and coronary heart disease. According to the column chart, the total score was 210 points, and the probability of long-term restenosis was 90%. The discrimination of the nomogram model was 0.866, with a Brier score of 0.081 and a calibration slope of 0.733. When the risk threshold was 0.15 to 1.0, the net benefit rate of long-term restenosis in T2DM patients with severe infra-popliteal artery disease was greater than that of individual evaluation. The smaller the risk threshold, the greater the net benefit rate. The benefit was the best when the threshold reached 0.23. Conclusion The influencing factors for long-term restenosis in T2DM patients with severe subknee artery disease treated by PCB include age, combined coronary heart disease, TASCⅡ grade, Fontaine stage, HbA1c and LDL-C. The prediction model based on the above influencing factors has important value in predicting long-term restenosis in patients.

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    Effect and safety of quadruple regimen in preventing multi-day cisplatin-based chemotherapy induced nausea and vomiting
    QIN Hanlin, HU Changlu, ZHAO Yamei, NIU Weina
    2024, 52 (8):  835-839.  doi: 10.11958/20231669
    Abstract ( 293 )   HTML ( 1 )   PDF (752KB) ( 26 )  

    Objective To evaluate the effectiveness and safety of quadruple regimen in preventing multi-day cisplatin-based chemotherapy-induced nausea and vomiting (CINV). Methods A total of 112 patients with malignant tumors who underwent cisplatin-based chemotherapy. According to the random number table method, patients were divided into the experimental group and the control group, with 56 cases in each group. The control group received cisplatin-based chemotherapy and triple therapy of fosapreitant dimeglumine, ondansetron hydrochloride and dexamethasone tablets. On this basis, the experimental group was given quadruple therapy containing olanzapine tablets. The occurrence of nausea and vomiting, as well as changes in FLIE and HAD scores were observed in both groups. Results The incidence of nausea and vomiting was lower from day 1 (D1) to day 9 (D9) after the beginning of chemotherapy in the experimental group than that in the control group (P<0.05). The incidence of nausea and vomiting in the experimental group was lower than that in the control group. On D9 after the beginning of chemotherapy, the nausea score, vomiting score and total score of FILE were higher in the experimental group than those in the control group (P<0.05). There were no significant differences in depression or anxiety score and incidence of adverse reactions on D1 and D9 after the beginning of chemotherapy between the two groups (P>0.05). Conclusion The quadruple antiemetic regimen can improve the control rate of CINV induced by multi-day cisplatin-based chemotherapy, especially for the control of delayed nausea and vomiting, and improve the quality of life of patients during chemotherapy, with good safety.

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    Clinical research of the correlation between hyperkalemia and adverse outcome events in elderly patients with maintenance hemodialysis
    ZHANG Xiyou, GUO Yidan, ZHANG Chunxia, ZHOU Xiaoling, JIA Meng, SHI Zhihua, LUO Yang
    2024, 52 (8):  840-844.  doi: 10.11958/20231765
    Abstract ( 333 )   HTML ( 1 )   PDF (805KB) ( 27 )  

    Objective To explore the relationship between hyperkalemia and adverse outcomes in elderly maintenance hemodialysis (MHD) patients. Methods A retrospective cohort trial was conducted on 177 MHD patients aged ≥60 years in the hemodialysis center of Beijing Shijitan Hospital, Capital Medical University. Baseline data were collected. The mean age was (77.28±14.25) years, among them 109 cases were males (61.6%). According to the peak serum potassium within 4 months, patients were divided into the K+<5.0 mmol/L group (38 cases, 21.5%), the 5.0-5.5 mmol/L group (42 cases, 23.7%) and the K+≥5.5 mmol/L group (97 cases, 54.8%). Based on the frequency of hyperkalemia within 4 months, patients were divided into the 0, 1-2 and 3-4 frequency groups. All of patients were followed up for 1 year. The end point events were all-cause mortality and cardiovascular disease (CVD) mortality. Kaplan-Meier survival analysis was used to compare the cumulative survival rate between the 3 groups. A multivariate Cox regression model was employed to analyze the relationship between the degree and frequency of hyperkalemia with all-cause and CVD mortality. Results The mean follow-up time of 177 patients was 12 (1-12) months, 20 (11.3%) patients died of all-cause death and 14 (7.9%) of CVD death. Kaplan Meier survival curve showed cardiovascular mortality rate and all-cause mortality were significantly increased in the K+ 5.0-5.5 mmol/L group and the K+≥5.5 mmol/L group (both P<0.05). Multivariate Cox regression analysis indicated that, as a continuous variable, peak potassium levels were independently associated with an increased risk of all-cause death and CVD death (P<0.001). As a categorical variable, the all-cause mortality risk and CVD mortality risk were significantly higher in both the K+5.0-5.5 mmol/L group and the K+≥5.5 mmol/L group than those in the K+<5.0 mmol/L group (P<0.05), and those were significantly higher in the 1-2 and 3-4 frequency groups than those in the 0 frequency group of hyperkalemia (P<0.05). Conclusion Serum potassium>5.0 mmol/L in elderly MHD patients is an independent risk factor for all-cause and CVD mortality. It is recommended to adjust the upper limit of the normal range of serum potassium to 5.0 mmol/L.

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    Development and validation of a preoperative nomogram predictive model for proximal gastric cancer with microscopic positive margin
    GUO Zhenjiang, ZHAO Guangyuan, DU Liqiang, LIU Fangzhen
    2024, 52 (8):  845-849.  doi: 10.11958/20231766
    Abstract ( 311 )   HTML ( 1 )   PDF (929KB) ( 135 )  

    Objective To explore the preoperative predictive factors influencing microscopic positive proximal margin in upper gastric cancer, and to establish a nomogram prediction model and to validate it internally. Methods Retrospective analysis of 187 patients with upper gastric cancer operated in the Department of Gastrointestinal Surgery of Hengshui People's Hospital from January 2018 to October 2022 were included in this study. Patients were divided into the microscopic positive proximal margin (the R0 group, n=15) and the negative microscopic proximal margin group (the R1 group, n=172) according to histopathological diagnosis. Preoperative factors that may influence positive upper margin of proximal gastric cancer were collected, including patient age, gender, tumor size, tumor location, Borrmann staging, tumor differentiation, Lauren staging, cT stage and cN stage. Receiver operating characteristic (ROC) curve was used to figure out the optimal cut-off value for predicting positive margin of proximal gastric cancer by tumor length. Multivariate Logistic regression was used to analyze the variables with statistical difference between the two groups, and independent risk factors were screened out, and prediction mode was constructed. The prediction accuracy of the model was verified internally using Bootstrap method. Results The best threshold for predicting positive margin of proximal gastric cancer by tumor length was 4.85 cm. Univariate analysis showed that there were significant differences in tumor length, tumor location, Borrmann staging, Lauren staging, cT staging and cN staging between the two groups (all P<0.05). Multivariate Logistic regression analysis showed that tumor length >4.85 cm (OR=4.000, 95%CI: 1.039-15.399), tumor located in esophagogastric junction (OR=7.108, 95%CI: 1.604-31.494), Borrmann staging Ⅲ—Ⅳ(OR=6.991, 95%CI: 1.538-31.782), Lauren staging as diffuse or mixed (OR=7.583, 95%CI: 1.814-31.701) and cT staging as cT4 (OR=8.249, 95%CI: 1.890-36.007) were independent predictors of microscopic positive proximal margin of advanced upper gastric cancer before surgery, and a prediction model was established based on results of multivariate analysis. The area under ROC curve (AUC) value for subjects with the model was 0.862 after internal validation. The calibration curve showed that the model predicted the probability of microscopic positive proximal margin occurrence in good agreement with the probability of actual microscopic positive proximal margin occurrence (Hosmer-Lemeshow χ2=6.145,P=0.523). Conclusion The established nomogram prediction model can predict the probability of positive upper incisal margin of proximal gastric cancer before operation, and provide clinical guidance for formulating surgical strategy.

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    Analysis of influencing factors of recurrent wheezing in children with bronchopneumonia and construction of prediction model
    WANG Lei, MENG Kun, WANG Bing
    2024, 52 (8):  850-853.  doi: 10.11958/20231879
    Abstract ( 307 )   HTML ( 0 )   PDF (801KB) ( 40 )  

    Objective To explore clinical influencing factors of recurrent wheezing in children with bronchopneumonia, and construct a risk prediction model. Methods A total of 155 children with bronchopneumonia were divided into the recurrent wheezing group (47 cases) and the non-recurrent wheezing group (108 cases) according to the occurrence of recurrent wheezing within 1 year after discharge. General clinical data, including the length of hospital stay, total course of disease, history of eczema, history of other personal allergies (food allergy history, drug allergy history, allergic rhinitis history and allergic dermatitis history), family history of allergies, living environment, frequency of colds and exposure to allergens, and laboratory indexes [T lymphocyte subsets, eosinophils (EOS), 25-hydroxy vitamin D3 and total immunoglobulin E (IgE)] were compared between the 2 groups. Multivariate Logistic regression analysis was conducted to identify influencing factors of recurrent wheezing, and a risk prediction model was constructed. Homser-Lemeshow tested the goodness of fit of the model. The predictive performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results Compared with the non-recurrent wheezing group, the proportions of children with history of other personal allergies, EOS positivity (>9%), vitamin D insufficiency (<30 μg/L) and total IgE positivity (>60 IU/mL) were higher in the recurrent wheezing group (P<0.05). Multivariate Logistic regression analysis showed that history of personal allergies, EOS positive, vitamin D insufficiency and total IgE positive were independent risk factors for recurrent wheezing in children with bronchopneumonia (P<0.05). Homser-Lemeshow showed that prediction model had goodness of fit (χ2=3.055, P=0.692). The model predicted that the area under curve for recurrent wheezing was 0.816, sensitivity and specificity of the model for predicting recurrent wheezing were 70.21% and 80.56%, respectively. Conclusion The prediction model constructed based on history of personal allergies, EOS positive, vitamin D insufficiency and total IgE positive has good predictive performance for recurrent wheezing in children.

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    Clinical effects of Qingke Pingchuan Granule on acute exacerbation of COPD
    LI Dongsheng, QIN Yirong, QIAO Man, CHI Hang, CUI Qingmin, LI Xiaoqiu
    2024, 52 (8):  854-857.  doi: 10.11958/20231914
    Abstract ( 308 )   HTML ( 0 )   PDF (741KB) ( 15 )  

    Objective To study the effect of Qingke Pingchuan Granule on the clinical efficacy in patients with phlegm-heat obstructing lung syndrome (AECOPD). Methods A total of 80 patients with acute exacerbation of chronic obstructive pulmonary disease (syndrome of phlegm-heat stagnation in the lung) hospitalized in the respiratory department of our hospital were selected and divided into the conventional group and the combinational group, with 40 cases in each group. The CAT score, TCM syndrome score, serum IL-6, CRP, lung function FEV1%pred, and FEV1/FVC were retrospectively observed before treatment, at the end of the second week of treatment, and at the follow-up after 1 month of treatment in the two groups. Results The total effective rate was significantly better in the combinational group than that of the conventional group (92.5% vs. 75.0%,P<0.05). At the end of the second week of treatment, the CAT score, each single syndrome score, serum IL-6 and CRP levels were all improved than those before treatment in the two groups (P<0.05), and the improvement degree was better in the combined group than that of the conventional group (P<0.05). The severity of airflow limitation and respiratory failure were significantly improved compared with those before treatment in both groups. At the follow-up after 1 month of treatment, the recovery rate of scores of each single syndrome score and CAT score were significantly lower in the combined group than those in the routine group (P<0.05). There were no significant differences in adverse drug reactions between the two groups (12.5% and 2.5%, P>0.05). Conclusion Qingke Pingchuan Granule can effectively relieve the symptoms and improve lung function and the quality of life of AECOPD patients.

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    Relationship between GBS infection, vaginal microecological changes and adverse pregnancy outcomes of pregnant women
    JIN Caifeng, WU Wei, WU Ke
    2024, 52 (8):  858-861.  doi: 10.11958/20231696
    Abstract ( 286 )   HTML ( 1 )   PDF (772KB) ( 18 )  

    Objective To analyze the relationship between group B streptococcus (GBS) infection, vaginal microecological changes and adverse pregnancy outcomes of pregnant women. Methods The data of 202 pregnant women with GBS infection (the positive group) and 202 pregnant women without GBS infection (the negative group) in the third trimester of pregnancy were collected. The general data, vaginal microecology and adverse pregnancy outcomes were compared between the two groups. According to the results of vaginal microecological examination, patients in the two groups were divided into the positive normal group (76 cases), the positive imbalance group (126 cases), the negative normal group (154 cases) and the negative imbalance group (48 cases). Pregnant women in the positive group were treated with antibiotics immediately after premature rupture of membranes, and pregnant women without premature rupture of membranes were treated with antibiotics after labor. Pregnant women with trichomonas vaginitis or fungal vaginitis or bacterial vaginosis were given nifuratel nystatin vaginal soft capsules for treatment. The adverse pregnancy outcomes were compared between the four groups. Results Compared with the negative group, the proportion of gestational diabetes mellitus, proportion of pH value>4.5, detection rates of mycotic vaginitis and bacterial vaginosis, premature delivery rate, premature membrane rupture rate, postpartum hemorrhage rate and fetal intrauterine distress rate were higher in the positive group (P<0.05). The premature delivery rate, premature membrane rupture rate, puerperal infection rate and fetal intrauterine distress rate were higher in the negative imbalance group than those in the negative normal group (P<0.05), and the positive imbalance group had higher premature delivery rate, premature membrane rupture rate, postpartum hemorrhage rate, puerperal infection rate, fetal intrauterine distress rate, intrauterine infection rate and neonatal infection rate (P<0.05). Compared with the negative imbalance group, the premature delivery rate, premature membrane rupture rate and fetal intrauterine distress rate were lower in the positive normal group, and those were higher in the positive imbalance group (P<0.05). The positive imbalance group had higher rates of premature delivery, premature membrane rupture and fetal intrauterine distress compared to the positive normal group (P<0.05). Conclusion GBS infection in the third trimester of pregnancy increases the incidence of adverse pregnancy outcomes, and vaginal microecological imbalance its synergies promote of adverse pregnancy outcomes.

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    Relationship between expression levels of EGFR, Ki-67, P53 and CTC and the prognosis of triple negative breast cancer
    MAN Yi, XU Ya, HE Xiancheng, SONG Shaofeng, LIU Aiguo
    2024, 52 (8):  862-867.  doi: 10.11958/20231529
    Abstract ( 342 )   HTML ( 0 )   PDF (1008KB) ( 27 )  

    Objective To investigate the relationship between expression levels of epidermal growth factor receptor (EGFR), proliferation marker protein Ki-67 (Ki-67), P53 and circulating tumor cell (CTC) and the prognosis of triple negative breast cancer. Methods A total of 95 patients with triple negative breast cancer were selected. The expression levels of EGFR, Ki-67 and P53 in pathological tissue specimens were detected by immunohistochemistry. All patients underwent 8 cycles of chemotherapy, and the expression of CTC was detected before and after chemotherapy by isolation epithelial tumor cells (ISET). The relationship between CTC expression before and after chemotherapy and efficacy of chemotherapy was analyzed. The correlation between CTC and expression levels of EGFR, Ki-67 and P53 was analyzed. Patients were followed up for progression free survival (PFS). Risk factors of progression for triple negative breast cancer were analyzed by COX regression. Results The positive detection rates of EGFR, Ki-67 and P53 were 44.21% (42/95), 63.16% (60/95) and 56.84% (54/95). The positive detection rate of CTC was lower in patients after chemotherapy than that before chemotherapy (14.74% vs. 61.05%, P<0.05). The efficacy of chemotherapy was negatively correlated with the positive expression of CTC after chemotherapy (P<0.001). COX regression analysis found that clinical stage Ⅲ, positive EGFR and CTC after chemotherapy were independent risk factors of progression of triple negatively breast cancer (P<0.05). PFS of patients at clinical stage Ⅰ, stage Ⅱ, and stage Ⅲ decreased in order (P<0.05). PFS of EGFR positive patients was shorter than that of EGFR negative patients (P<0.05). PFS of CTC positive patients after chemotherapy was shorter than that of CTC negative patients after chemotherapy (P<0.05). Conclusion The positive expression of EGFR before chemotherapy and the positive expression of CTC after chemotherapy are related to the poor survival prognosis of patients with triple negative breast cancer. The lower the positive detection rate of CTC after chemotherapy, the better the efficacy of chemotherapy.

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    Effects of fish collagen oligopeptide on operative prognosis of patients with emergency complex hand trauma
    LI Li, CAO Shuming, YANG Zhongping, HU Ruomei
    2024, 52 (8):  868-871.  doi: 10.11958/20231943
    Abstract ( 323 )   HTML ( 1 )   PDF (736KB) ( 30 )  

    Objective To observe the effect of enteral nutrition with fish collagen oligopeptide on operative prognosis of patients with emergency complex hand trauma. Methods A total of 122 patients who suffered from complex hand trauma and were operated in the emergency department were retrospectively analyzed. Patients were given early enteral nutritional support after the operation, and were divided into two groups according to different formulations. The control group (60 patients) was given balance nutrients and whey protein, and the experimental group (62 patients) was given fish collagen oligopeptide on the same enteral nutrition formula. Clinical data were compared between the two groups, including hemoglobin (Hb),lymphocyte count (Lym), neutrophil-lymphocyte ratio (NLR), albumin (ALB), prealbumin (PA), alanine transaminase (ALT), aspartate transaminase (AST), urea nitrogen (BUN), creatinine (Cr), triglyceride (TG), total cholesterol (TC) and low density lipoprotein-C (LDL-C) before and after treatment. The length of hospital stay and the incidence of postoperative infectious complications were compared between the two groups of patients. Results Compared with before treatment, Hb, ALB, liver and kidney function and lipid metabolism indexes of the control group and the experimental group had no significant changes after nutritional treatment, and PA and Lym were significantly increased, and NLR was significantly decreased. After nutritional treatment, compared with the control group, NLR was decreased more significantly in the experimental group (P < 0.01). The incidence of infectious complications was lower in the experimental group than that in the control group, and the length of hospitalization was significantly shortened (P < 0.05). Conclusion Early enteral nutrition supplemented with fish collagen oligopeptide in patients with emergency complex hand trauma can promote prealbumin synthesis, reduce the incidence of inflammation and wound infection, and shorten hospital stay.

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    Analysis of dyslipidemia associated with myelodysplastic syndrome
    SUN Yanwen, WANG Cong, CHEN Shiliang, ZHANG Ranran
    2024, 52 (8):  872-876.  doi: 10.11958/20231919
    Abstract ( 291 )   HTML ( 1 )   PDF (755KB) ( 21 )  

    Objective To analyze blood lipid levels in patients with myelodysplastic syndrome (MDS) and further explore the factors associated with abnormal blood lipids. Methods Eighty-eight newly diagnosed MDS patients were selected as the study group, and 100 healthy subjects were selected as the control group. Fasting blood lipid levels, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1) and ApoB were detected before treatment in the study group and the control group. The differences of serum lipid levels in MDS patients with different WHO-MDS classification, modified International Prognostic Score System (IPSS-R) karyotype, risk stratification and TP53 mutation were investigated. The correlation between ApoA1 level and clinical indicators of MDS patients was analyzed, and clinical indicators of different ApoA1 level groups were compared. Results The levels of TC, HDL-C, LDL-C, ApoA1 and ApoB were significantly lower in the study group than those in the control group (P<0.01). There were no significant differences in TG, TC, HDL-C, LDL-C, ApoA1 and ApoB levels between different subgroups. The ApoA1 level was lower in the IPSS-R high-risk stratification group than that of the IPSS-R low-risk stratification group (P<0.05). There were no significant differences in lipid levels between the different karyotype groups. The level of ApoA1 was lower in the TP53 mutant group than that in the non-TP53 mutant group (P<0.05). Correlation analysis showed that ApoA1 level was positively correlated with body mass index (BMI, P<0.05), and negatively correlated with patient age, percentage of bone marrow original cells, IPSS-R karyotype grouping, IPSS-R risk grouping and TP53 gene mutation (P<0.05). The BMI level was lower in the low ApoA1 group than that of the high ApoA1 group (P<0.05). The percentage of bone marrow original cells and TP53 gene mutation rate of MDS patients were higher in the low ApoA1 group than those in the high ApoA1 group (P<0.05). Conclusion The plasma lipid level in MDS patients is significantly lower than that of healthy controls, and levels of ApoA1 varied significantly in different disease states, which may be associated with TP53 gene mutation.

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    Review
    Advances in the use of stem cell mechanical sensitivity against osteoporosis
    ZHOU Liyun, WANG Yan, DONG Benchao, YANG Peichuan, SHEN Jiahui, MA Jianxiong, MA Xinlong
    2024, 52 (8):  877-881.  doi: 10.11958/20231662
    Abstract ( 322 )   HTML ( 3 )   PDF (802KB) ( 21 )  

    Osteoporosis is an emerging threat characterized by systemic damage to bone mass and microarchitecture leading to fragility fractures. Exosomes are nanosized vesicular particles secreted by cells into the extracellular compartment with biological activities similar to those of their cell of origin and play an important role in intercellular communication processes. Exosomes from multiple cell sources are involved in the regulation of bone-related cell proliferation and differentiation during bone metabolism, and have the advantages of high stability, non-immunogenicity and strong targeting ability, which make up for the shortcomings of traditional drug and stem cell therapies. Exosomes secreted from bone marrow mesenchymal stem cells (MSCs) can promote bone regeneration and improve morphology, biomechanics and histological damage, and exosomes derived from bone marrow mesenchymal stem cells (BMSCs) in the mechanical microenvironment are more effective in inducing osteogenesis, significantly enhancing the osteogenic effect of BMSCs and promoting bone regeneration. Therefore, this article provides a review on the mechano-sensitivity of MSCs, mechanical responsive functionalized exosomes of MSCs, and explores their potential role in the treatment of osteoporosis.

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    Application of optical coherence tomography angiography in clinical evaluation of chronic kidney disease
    MA Liang, HU Liying, SHI Yu, LONG Gang
    2024, 52 (8):  882-887.  doi: 10.11958/20231571
    Abstract ( 310 )   HTML ( 1 )   PDF (760KB) ( 30 )  

    Chronic kidney disease (CKD) is a common chronic disease. There is homology between retina and kidneys. Diabetic retinopathy and retinal neurovascular injury both reveal common pathophysiological features of ocular retina and kidney. Optical coherence tomography angiography (OCTA) detects chorioretinal microcirculation with near-histological resolution. Changes in microvascular structure and function can promote the development of hypertension, diabetes, CKD and related cardiovascular disease (CVD). The examination of fundus nerve microvessels by OCTA in patients with CKD is helpful to the identification of high-risk groups, and provides a new perspective for the assessment of disease progression and CVD risk prediction of patients with CKD. The combination of the deep learning will further expand this aspect of research and become the forefront of future development.

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    Research progress on signaling pathways and drug intervention in radiation-induced heart disease
    HUANG Yuan, WANG Gang, LI Yanling, XIE Ping
    2024, 52 (8):  888-892.  doi: 10.11958/20231637
    Abstract ( 319 )   HTML ( 3 )   PDF (750KB) ( 21 )  

    Radiation-induced heart disease (RIHD) is a cardiotoxic event secondary to radiotherapy for thoracic tumors, and has become another unfavorable factor affecting the health of cancer patients in addition to cancer cytotoxicity. Signal transduction plays an important role in cellular information exchange. RIHD can induce dysregulation of signaling pathways and hinder the normal function of pathways, thus causing myocardial tissue to undergo lesions such as apoptosis, oxidative stress and fibrosis. Now, we review the relevant pathways that are dysregulated in the development of RIHD, as well as the regulatory effects of drug intervention on these pathways, in order to provide a reference basis for the prevention and treatment of RIHD.

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    Advances in the diagnostic and monitoring value of glycocalyx injury in inflammatory bowel disease
    ZHANG Ledan, JIN Mingxing, LIU Yandi
    2024, 52 (8):  893-896.  doi: 10.11958/20231646
    Abstract ( 280 )   HTML ( 1 )   PDF (733KB) ( 14 )  

    Inflammatory bowel disease (IBD) is no cure at present, and only drugs and surgery can relieve symptoms, delay and reduce recurrence. Therefore, it is very important to monitor the disease activity. Glycocalyx, a polyglycoprotein complex covering luminal side of vascular endothelial cells, is supportive in maintaining the intestinal mucosal barrier, and inflammation leads to its structural damage. This review introduces currently available non-invasive biomarkers of clinical importance for IBD in laboratory testing, and analyzes the value of serum glycocalyx injury markers (syndecan-1, HS and HA) in the diagnosis or monitoring of IBD.

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