Tianjin Medical Journal

Study on the effect and mechanism of bone marrow mesenchymal stem cells on apoptosis of peritoneal mesothelial cells

WANG Funing, DAI Huibo, SHAN Yun, YU Manshu, SHENG Meixiao

2024, 52 (2): 113-118. doi: 10.11958/20231064

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Objective To observe the effect of rat bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of rat peritoneal mesothelium cells (PMCs) induced by high glucose peritoneal dialysis fluid (PDF), and to explore its possible molecular mechanism. Methods The primary BMSCs and PMCs were extracted and identified. Apoptosis of PMCs was induced by high glucose PDF. Cell supernatant from BMSCs after 24 h of culture was collected as the conditioned medium (BMSCs-CM). PMCs were co-cultured with BMSCs by conditioned media or Transwell chambers. PMCs were randomly divided into the control group, the PDF group and the PDF+BMSCs-CM group. The viability of PMCs was measured by CCK-8 in each group. The depolarization of mitochondrial membrane potential was measured by JC-1 method. TUNEL staining was used to detect cell apoptosis. Western blot assay was used to detect the expression levels of apoptosis related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), Cleaved cysteine aspartase-3 (Cleaved Caspase-3) and pathway related protein serine/threonine protein kinase (Raf), mitogen-activated extracellular signal-regulated kinase (MEK), extracellular-signal regulated protein kinase (ERK) and their phosphorylated proteins in each group. Results Compared with the control group, the proliferative activity and mitochondrial membrane potential of PMCs were decreased in the PDF group, while the apoptosis rate and the ratio of Bax/Bcl-2, Cleaved Caspase-3/Caspase-3, p-Raf/Raf, p-MEK/MEK and p-ERK/ERK were increased (P<0.05). Compared with the PDF group, the proliferative activity and mitochondrial membrane potential of PMCs were increased in the PDF+BMSCs-CM group, while the apoptosis rate and the ratio of Bax/Bcl-2, Cleaved Caspase-3/Caspase-3, p-Raf/Raf, p-MEK/MEK and p-ERK/ERK were decreased (P<0.05). Conclusion BMSCs can reduce the apoptosis of PMCs induced by high glucose PDF, and its mechanism maybe related to inhibiting the activation of Raf/MEK/ERK signaling pathway.

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Mechanism of BMAL1 attenuating H₂O₂-induced cardiomyocyte injury

YI Na, XIAO Wen, TIAN Yuan, YUAN Lili

2024, 52 (2): 119-123. doi: 10.11958/20231027

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Objective To investigate the effect of BMAL1 on H₂O₂-induced cardiomyocyte injury through NRF2-regulated ROS/NLRP3 inflammasome pathway. Methods H9c2 cells and H9c2 cells with stable over-expressed BMAL1 were cultured and divided into the control group, the H₂O₂ group, the BMAL1-OE group, the BMAL1-OE+H₂O₂ group, the BMAL1-OE+ML385 group and the BMAL1-OE+ML385+H₂O₂ group. All groups were pre-intervened with corresponding inhibitors, and then treated with 0.2 mmol/L H₂O_2,except for the control group and the BMAL1-OE group. After the intervention, CCK-8 assay was used to measure cell viability, fluorescent probe DCFH-DA was used to measure ROS generation and Western blot assay was used to detect BMAL1, NRF2 and NLRP3 protein expressions. ELISA was used to determine IL-1β release. Results Compared with the control group, the cell viability was decreased, ROS generation was increased, BMAL1 and NRF2 protein expressions were decreased, NLRP3 expression and IL-1β release were increased in the H₂O₂ group (P<0.05). Compared with the H₂O₂ group, the cell viability was increased, ROS generation was decreased, BMAL1-OE and NRF2 protein expressions were increased, NLRP3 expression and IL-1β release were decreased in the BMAL1-OE+H₂O₂ group (P<0.05). Compared with the BMAL1-OE+H₂O₂ group, the cell viability was decreased, ROS generation was increased, NLRP3 expression and IL-1β release were increased in the BMAL1-OE+ML385+H₂O₂ group (P<0.05). Conclusion BMAL1 attenuates H₂O₂-induced H9c2 cardiomyocyte injury, and its mechanism may be related to the regulation of ROS/NLRP3 inflammasome pathway through NRF2.

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The mechanism of miR-10b targeting TGFBR1/SMAD3 pathway on chondrocyte proliferation and hypertrophy in idiopathic short stature

HU Na, LI Zhengyu, YE Chunfeng, WU Ying, YAO Qing, HUANG Shixiang, LI Wen, ZHU Haiqin

2024, 52 (2): 124-128. doi: 10.11958/20230659

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Objective To investigate the effect and mechanism of microRNA-10b (miR-10b) on idiopathic short stature (ISS). Methods A total of 54 children with ISS and 54 healthy children were collected. The serum expression of miR-10b was detected by RT-qPCR, and the relationship between serum miR-10b expression and clinical data of children with ISS was analyzed. miR-10b inhibitor, si-TGFBR1 and their negative control transfection C28/I2 cells were used. CCK-8 experimental detection was used to detect C28/I2 cell proliferation. Western blot assay was used to detect gnome related transcription factor 2 (RUNX2), collagen type X alpha 1 chain (COL10A1), transforming growth factor beta receptor 1 (TGFBR1), SMAD3 and pSMAD3 protein expression. The target of miR-10b was screened in StarBase database, and the targeting relationship between miR-10b and TGFBR1 was verified by dual luciferase reporter gene assay. Results The serum expression of miR-10b was higher in the ISS group than that of the healthy control group, and the higher the miR-10b expression, the more obvious the decrease of child height, IGF-1 and alkaline phosphatase (P<0.05). Compared with the NC group, the cell proliferation ability and RUNX2, COL10A1, TGFBR1, and pSMAD3 protein expression were up-regulated in the miR-10b inhibitor group (P<0.05). StarBase database suggested that miR-10b had a binding site of TGFBR1, and dual luciferase reporter gene assay confirmed that TGFBR1 interacted with miR-10b (P<0.05). Compared with the si-NC group, the expression of TGFBR1 was down-regulated and the cell proliferation ability was decreased in the si-TGFBR1 group (P<0.05). Conclusion miR-10b inhibits chondrocyte proliferation and hypertrophy in idiopathic short stature by targeting TGFBR1/SMAD3 pathway.

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Comparative study on the directed differentiation ability of mouse bone marrow and adipose-derived mesenchymal stem cells

ZHONG Jiashuai, FENG Yumei

2024, 52 (2): 129-135. doi: 10.11958/20230437

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Objective To investigate the targeted differentiation ability of mouse bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs). Methods BM-MSCs and AD-MSCs were isolated and cultured from bone marrow of femur and white adipose tissue of groin of C57BL/6J mice respectively, and the two types of cells were induced by osteogenic, chondrogenic and adipogenic differentiation medium respectively. Alizarin red, alcian blue and oil red O staining were used to detect the differentiated degree of osteogenic, chondrogenic and lipogenic differentiation. Real-time fluorescence quantitative PCR (qPCR) was used to identify MSCs and detected expression levels of directed differentiation-related genes Runx2, Sp7 (osteoblast), Sox9, Col2a1 (chondroblast), Pparg and Cebpa (lipogenesis) to determine the directed differentiation ability of cells. Based on gene expression profiles of mouse and human BM-MSCs and AD-MSCs in GEO database GSE43804 and GSE122778, the differentially expressed genes and their enrichment signal pathways were analyzed. Results The cell morphology of BM-MSCs and AD-MSCs obtained by isolation and culture was different, and spindle-shaped morphology was more obvious in AD-MSCs. Both cells expressed CD29, CD44 and CD90, but did not express CD34 and CD45. AD-MSCs showed higher osteogenic and lipogenic differentiation than those of BM-MSCs after directed induction, while chondrogenic differentiation was lower in AD-MSCs than that of BM-MSCs (P<0.05). After directional induction, expression levels of Runx2, Pparg and Cebpa mRNA were higher in AD-MSCs than those in BM-MSCs, and Sox9 mRNA expression levels were lower than those in BM-MSCs (P<0.05). Highly expressed genes of AD-MSCs in mice and human were enriched in PPAR and WNT signaling pathways. Highly expressed genes of BM-MSCs were enriched in cartilage and bone developmental signaling pathways. Conclusion The osteogenic and adipogenic differentiation ability of mouse AD-MSCs is stronger than those of BM-MSCs, while the chondrogenic differentiation ability AD-MSCs is weaker than that of BM-MSCs. The activation status of PPAR, WNT, cartilages and skeletal system development signaling pathways plays an important regulatory role in determining the different directional differentiation potential of AD-MSCs and BM-MSCs.

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Gentianopsis paludosa xanthone combined with probiotics inhibits colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors

LU Nianhua, JIN Zhanhongye, ZHANG Qian, ZHANG Meng, LI Junke, ZHAO Huiqiao, ZHANG Yongpeng

2024, 52 (2): 136-141. doi: 10.11958/20230462

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Objective To investigate the mechanism of Gentianopsis paludosa xanthone (GPX) combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors. Methods Ninety rats were divided into the normal group, the model group [drinking sodium dextran sulfate (DSS) for 3 days] and the intervention group by random number table method. The model group was subdivided into the inflammatory stage group, the pre-inflammatory cancer group (DMH injection for 4 weeks), the intermediate inflammatory cancer group (DMH injection for 13 weeks) and the advanced inflammatory cancer group (DMH injection for 21 weeks). The administration group was subdivided into the groups (after the first day of drinking DSS, drugs for each group were given by gavage once a day for 8 weeks) on the basis of the advanced inflammatory cancer group, including the GPX group (GPX 69.3 mg/kg), the probiotic group, the combined group (GPX+probiotics 400 mg/kg) and the thalidomide group (thalidomide 13.5 mg/kg). The disease activity index (DAI), colon length and wet mass index were compared between all groups. Characteristics of colon tumors were observed, and pathological changes of colon were observed by HE staining. The expression levels of transforming growth factor (TGF) -β1, Smad4, Smad7, interleukin (IL)-6 and tumor necrosis factor (TNF) -α were detected by Western blot assay and enzyme-linked immunosorbent assay, respectively. Results Compared with the advanced inflammatory cancer group, the administration groups showed an increase in colon length, the expression levels of TGF-β1 and Smad4 protein, a decrease in colon wall thickness, wet mass index, maximum tumor diameter, the levels of Smad7, IL-6, TNF-α, and DAI score decreased in the GPX group and the combined group (P<0.05). The structure and morphology of intestinal mucosa were improved in the GPX group, the probiotic group and the combination group, and the structure of colonic crypt and goblet cell number were increased. Compared with the probiotic group and the GPX group, the colon wall thickness, colon wet mass index and tumor number were decreased, the protein expression levels of TGF-β1 and Smad4 were increased, and levels of IL-6 and TNF-α were decreased in the combination group (P<0.05). Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor, and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.

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Impacts of muscone on malignant progression of ovarian cancer cells by regulating SHH mediated autophagy

WANG Aihua, ZHANG Feizhong, WANG Hongying

2024, 52 (2): 142-147. doi: 10.11958/20230541

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Objective To investigate the effect of muscone on malignant progression of ovarian cancer cells mediated by regulating sonic hedgehog (SHH) mediated autophagy. Methods Survival rates of human ovarian cancer cell line SKOV3 treated with 0, 2, 4, 8, 16, and 24 μmol/L muscone were detected, and the optimal cell action concentration of muscone was selected. SKOV3 cells were cultured in vitro, and their transplanted tumor mouse models were constructed. Cells were randomly grouped into the control group, the muskone group, the muskone+chloroquine (CQ，an autophagy inhibitor) group, the muskone+empty group and the muskone+SHH overexpression group. After grouping and treatment with musconeand, CQ, empty plasmid and SHH overexpression plasmid, the tumor volume and weight in transplanted tumor mice were detected. EdU staining, TUNEL staining, cell scratch, Transwell invasion assay, immunoblotting and real-time fluorescence quantitative PCR were used to detect proliferation, apoptosis, migration and invasion of SKOV3 cells, the expression of autophagy related proteins (LC3Ⅱ/LC3Ⅰ, Beclin-1) and SHH in SKOV3 cells and transplanted tumor mice in each. Results Compared with the control group, the cell proliferation rate, cell migration rate, number of invasions, tumor volume and weight, and the expression of SHH mRNA and protein in tumor tissue were decreased in the muskone group (P<0.05), and the apoptosis rate, LC3Ⅱ/LC3Ⅰ, Beclin-1 protein in cells and tumor tissue were increased (P<0.05). Compared with the muscone group, the cell proliferation rate, cell migration rate, number of invasion, tumor volume and weight were increased in the muscone+CQ group and the muskone+SHH overexpression group (P<0.05), and the apoptosis rate, LC3Ⅱ/LC3Ⅰ and the expression of Beclin-1 protein in cells and tumor tissue were decreased (P<0.05). There were no significant differences in the above indicators in the muscone+empty group (P>0.05). Conclusion Muscone can promote autophagy of ovarian cancer cells by down-regulating SHH, thereby inhibiting their proliferation, in vivo growth, migration and invasion, promoting their apoptosis, and ultimately inhibiting their malignant progression.

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Effect of baicalin regulating cAMP/PKA/CREB signaling pathway on skin barrier function in eczema rats

WANG Shoufan, XU Yihou, XU Aiqin, ZHU Lihong

2024, 52 (2): 148-153. doi: 10.11958/20230416

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Objective To investigate the effect of baicalin (BA) regulating cyclic adenosine phosphate (cAMP)/protein kinase A(PKA)/cAMP response elemen-binding protein (CREB) pathway on skin barrier function in eczema rats. Methods SD rats were randomly divided into the control group (NC group), the model group, the low-dose BA group (BA-L group, 25 mg/kg), the medium-dose BA group (BA-M group, 50 mg/kg), the high-dose BA group (BA-H group, 100 mg/kg), the prednisone group (PNS group, 25 mg/kg), the BA-H+cAMP inhibitor (SQ22536) group (100 mg/kg+2.13 mg/kg) and the BA-H+PKA inhibitor (H-89) group (100 mg/kg+5 mg/kg), 12 animals in each group. Except for the NC group, eczema rat model was constructed in the other groups. Two days after successful modeling, drug administration was performed in groups. Changes of eczema area and severity index (EASI) score, transcutaneous water loss (TEWL) and cuticle water content (WCSC) were detected. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of immunoglobulin E (IgE), interferon-γ (IFN-γ) and interleukin-4 (IL-4) in rat serum and the expression of cAMP protein in rat back lesions. HE staining was used to detect pathological changes of skin lesions on the back of rats. Western blot assay was used to detect aquaporin 3 (AQP3), cathelicidin related antimicrobial peptide (CRAMP), p-PKA, p-CREB protein expression in rat back lesions. Results Compared with the NC group, rats had serious pathological lesions on the back of the tested area, increased EASI score, TEWL, IgE and IL-4 levels, and decreased WCSC, IFN-γ, AQP3, CRAMP, cAMP, p-PKA and p-CREB protein levels in the model group (P < 0.05). Compared with the model group, pathological lesion of the tested area in the back of rats was relieved, and EASI score, TEWL, IgE and IL-4 levels were decreased, WCSC, IFN-γ levels, AQP3, CRAMP, cAMP, p-PKA and p-CREB protein were increased in the BA-L group, the BA-M group, the BA-H group and the PNS group (P<0.05). Changes of above indexes in the BA-L group, the BA-M group, the BA-H group were dose-dependent. SQ22536 or H-89 attenuated the improvement effect of high dose BA on skin barrier function in eczema rats. Conclusion BA may improve skin barrier function in eczema rats by activating cAMP/PKA/CREB signaling pathway.

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Effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen levels in rats with polycystic ovary syndrome

CHEN Junjie, XU Xuemei, LI Yan, FU Jinying

2024, 52 (2): 154-160. doi: 10.11958/20230549

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Objective To study the regulation effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen level in rats with polycystic ovary syndrome. Methods The rat model of polycystic ovary syndrome was established by subcutaneous injection of human chorionic gonadotropin (HCG) combined with insulin. Rats were randomly divided into the polycystic ovary syndrome group, the Baizhu Fuzi Tang group (6.4 g/kg), the Bazhen Tang group (9.2 g/kg), the Bazhen Tang combined with Baizhu Fuzi Tang group (11.55 g/kg) and the diethylstilbestrol group (0.5 mg/kg). A blank control group (unmodulated rats) was set up with 10 rats in each group. The uterine index of rats was determined and calculated. Fasting blood glucose (FBG), 2 h postprandish blood glucose (2 h PBG) and fasting insulin (FINS) were determined and insulin sensitivity index (ISI) and insulin resistance index (IR) were calculated. Serum estradiol (E₂), testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), anti-Mullerian tube hormone (AMH) and insulin-like growth factor 1 (IGF-1), C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, total peroxidase activity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) levels in ovarian tissue were detected by enzyme-linked immunosorbent assay (ELISA). The pathological changes of ovarian tissue were detected by hematoxylin-eosin (HE) staining. Real-time quantitative polymerase chain reaction (qPCR) was used to determine mRNA levels of ARA70, CBP, SCR1 and HOXA10 in endometrium and mRNA expressions of AMPK, GLUT4 and PPARγ in ovarian tissue. Western blot assay was used to determine expression levels of AMPK, GLUT4 and PPARγ in ovarian tissue. Results Compared with the polycystic ovary syndrome group, uterine index, FINS, FBG, 2 h PBG, IR levels, serum T, LH, FSH, PRL, AMH, IGF-1 levels, ovarian tissue CRP, IL-6, TNF-α, T-AOC and MDA level, endometrial ARA70, CBP, SCR1 mRNA level of rats decreased significantly in the Baizhu Fuzi decoction group, the Bazhen decoction group and the Bazhen decoction combined with Baizhu Fuzi decoction group (P<0.05). ISI level, serum E₂ level, ovarian tissue SOD level, endometrial HOXA10 mRNA level, ovarian tissue AMPK, GLUT4 and PPARγ mRNA and protein levels were significantly increased (P<0.05). The above indexes were significantly changed in the Bazhen decoction and Bazhu Fuzi decoction group than those of the Bazhu Fuzi decoction group and the Bazhen decoction group (P<0.05). Conclusion Bazhen Decoction combined with Baizhu Fuzi Decoction can regulate glucose metabolism, inhibit ovarian tissue oxidation and inflammatory damage, improve endometrium tolerance, regulate estrogen level, and improve the progression of polycystic ovary syndrome in rats. The mechanism may be related to the regulation of AMPK/GLUT4/PPARγ pathway.

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Effect of phillyrin regulating NLRP3 inflammatory pathway on exudates and lung injury in rats with acute pleurisy

HAO Jianling, XIN Jingjing, WANG Jing, TIAN Hong, SU Haitao

2024, 52 (2): 161-166. doi: 10.11958/20230399

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Objective To investigate the impacts of phillyrin on exudates and lung injury in rats with acute pleurisy by regulating the NLRP3 inflammatory pathway. Methods Ninety rats were randomly divided into the control group, the model group, the low-dose phillyrin (PH-L, 5 mg/kg) group, the medium-dose phillyrin (PH-M, 10 mg/kg) group, the high-dose phillyrin (PH-H, 20 mg/kg) group and the NLRP3 pathway inhibitor (PJ34, 10 mg/kg) group. FVC, FEV 0.1 and FEV 0.3 were detected by lung function analyzer. Electronic balance was used to weigh the mass of chest exudate. The number of white blood cells in exudate was detected by Wright staining. Contents of prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL) -6 and tumor necrosis factor-α (TNF-α) in exudate were detected by ELISA. Automatic blood gas analyzer was used to detect p (CO₂) and p (O₂) of rats. HE staining was used to observe pathological changes of lung tissue. The expression levels of NLRP3 and Caspase-1 protein were detected by immunohistochemistry. Western blot assay was used to detect the expression of NLRP3 pathway protein. Results Compared with the control group, the quality of pleural exudate and the number of white blood cells, the contents of PGE2, MCP-1, IL-6, TNF-α, the expression of p (CO₂) and NLRP3 pathway proteins in exudate of the model group increased obviously, FVC, FEV 0.1, FEV 0.3 and p (O₂) decreased obviously, and the lung tissue showed obvious pathological damage (P<0.05). Compared with the model group, the quality of pleural exudate and the number of white blood cells, the contents of PGE2, MCP-1, IL-6, TNF-α, the expression of p (CO₂), NLRP3 pathway proteins in the exudate of rats decreased obviously in the PH group and the PJ34 group, FVC, FEV 0.1, FEV 0.3 and p (O₂) increased obviously, the pathological injury of lung tissue was obviously improved (P<0.05). Compared with the PH-H group, there were no significant differences in the above indexes in the PJ34 group (P>0.05). Conclusion PH can improve lung injury induced by acute pleurisy in rats by inhibiting the activation of NLRP3 pathway and inhibiting inflammatory reaction.

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Pathogenic bacteria distribution, drug resistance changes and risk factors of death in patients with acute myeloid leukemia complicated with bloodstream infection

JI Xiaojuan, HAN Hao, ZHANG Lixia

2024, 52 (2): 167-171. doi: 10.11958/20230423

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Objective To explore the distribution and drug resistance changes of pathogenic bacteria in adult acute myeloid leukemia (AML) with bloodstream infection, and to analyze risk factors of death of patients. Methods Changes of detection rate of pathogenic bacteria and drug resistance rate of main pathogenic bacteria of 85 patients with AML and bloodstream infection 30 months before confirmed diagnosis (pathogenic bacteria detected from January 2017 to June 2019) and 30 months after diagnosis (from July 2019 to December 2021) were compared. According to the prognosis at 6 months after bloodstream infection, patients were divided into the death group (33 cases) and the survival group (52 cases). Logistic regression analysis was used to analyze risk factors of death in patients with AML complicated with bloodstream infection. Results A total of 98 strains of pathogenic bacteria were detected in 85 patients with AML complicated with bloodstream infection, mainly gram-negative bacteria (65/98, 66.33%), followed by Gram-positive bacteria (29/98, 29.59%) and fungi (4/98, 4.08%). The proportion of fungi (all were candida) detected in the last 30 months was more than that in the first 30 months (P < 0.05). There were no significant differences in proportions of gram-negative bacteria and gram-positive bacteria and drug resistance rates of Escherichia coli and Staphylococcus aureus between the late 30 months and the first 30 months (P > 0.05). Logistic regression analysis showed that the history of antibiotic use within 1 month before confirmed diagnosis and septic shock were independent risk factors for death in patients with AML complicated with bloodstream infection (P <0.05). Conclusion The main pathogens of adults with AML combined with bloodstream infection are gram-negative bacteria. However, candida infection rate has increased in recent years, and patients with antibiotic use before bloodstream infection and complicated with septic shock are prone to poor prognosis.

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Relationship between serum indexes, pathogenetic condition and prognosis in patients with acute ischemic stroke

DING Bo, GONG Jieqin, SHEN Likui

2024, 52 (2): 172-176. doi: 10.11958/20231051

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Objective To discuss the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2), low-density lipoprotein (LDL), amyloid beta 1-42 (Aβ_1-42) and soluble intercellular adhesion molecule-1 (sICAM-1) levels, the National Institutes of Health Stroke Scale (NIHSS) score and prognosis in patients with acute ischemic stroke (AIS). Methods A total of 106 patients with AIS who underwent intravenous thrombolysis (the thrombolysis group), 30 AIS patients without thrombolysis (the non-thrombolysis group) and 95 healthy individuals (the control group) were included in the study. The thrombolysis group was divided into the recanalization group (n=41) and the non-recanalization group (n=65) according to whether the vein was recanalized after thrombolysis. Patients were divided into the mild group (n=45), the moderate group (n=36) and the severe group (n=25) based on the NIHSS score. They were divided into the good prognosis group (n=65) and the poor prognosis group (n=41) based on the modified Rankin Scale (mRS) score. Serum levels of four indexes in different groups were compared. Their relationship with the NIHSS score and the prognosis was analyzed. Results The vein recanalization rate in 106 patients with thrombolysis was 38.68% (41/106). Serum Lp-PLA2, LDL, Aβ_1-42 and sICAM-1 levels were lower in the recanalization group than those in the non-canalization group (P<0.05). Serum Lp-PLA2, LDL, Aβ_1-42 and sICAM-1 levels increased successively in the control group, the thrombolysis group and the non-thrombolysis group (P<0.05). The 4 serum indexes increased with the aggravation of disease condition, and were positively correlated with NIHSS score (P<0.05). High serum levels of Lp-PLA2, LDL, Aβ_1-42 and sICAM-1 were risk factors for poor prognosis of patients with thrombolysis (P<0.05). The area under the curve (AUC) and specificity of the combination of 4 serum indexes for predicting poor prognosis of patients with thrombolysis were higher than those of prediction with single index (P<0.05). Conclusion The expression levels of serum Lp-PLA2, LDL, Aβ_1-42 and sICAM-1 in patients with AIS are high. They can be used as important reference indexes for disease condition monitoring and prognosis evaluation.

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Clinical study of sacubitril valsartan in the treatment of patients with heart failure of midrange ejection fraction after acute myocardial infarction

ZHANG Xiaoxu, YANG Wenqi

2024, 52 (2): 177-181. doi: 10.11958/20230587

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Objective To investigate the efficacy and safety of sacubitril valsartan in the treatment of heart failure (HF) of midrange ejection fraction（HFmrEF）in patients after acute myocardial infarction (AMI). Methods A total of 102 patients with HFmrEF after AMI were divided into the control group and the experimental group, with 51 cases in each group. The control group was given conventional treatment for AMI and anti-HF treatment, and the angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin Ⅱ receptor blocker (ARB) was used without contraindications. The experimental group was replaced by ACEI/ARB with sacubitril valsartan on the basis of the control group. After 6 months of treatment, the total effective rates of the two groups after treatment were analyzed, and the cardiac function, N-terminal pro-brain natriuretic peptide (NT-proBNP) and serum inflammatory factor C-reactive protein (CRP) were compared before and after treatment. The occurrence of adverse reactions after treatment was recorded. Kaplan-Meier method was used to analyze the cumulative cardiovascular mortality, HF rehospitalization rate and end-event-free survival after 6 months of treatment in two groups. Results After treatment, there was no significant difference in the occurrence of adverse reactions between the two groups (P>0.05). The total effective rate was higher in the experimental group than that of the control group (P<0.05). Compared with before treatment, left ventricular ejection fraction (LVEF), stroke volume (SV), mitral diastolic blood flow velocity E peak and A peak ratio (E/A) and 6 min walking distance (6MWD) were increased in the two groups, and left ventricular end-diastolic diameter (LVEDD) and left atrial diameter (LAD) were decreased in the two groups after treatment (all P<0.05). After treatment, LVEF, SV, E/A and 6MWD were higher in the experimental group than those in the control group (P<0.05). LVEDD and LAD were lower than those in the control group (all P<0.05). Compared with results before treatment, NT-proBNP and CRP were decreased after treatment in the experiment group than those in the control group (P<0.05). There was no significant difference in the cumulative cardiovascular mortality between the experiment group and the control group (3.9% vs. 5.9%，P=0.524). The cumulative HF rehospitalization rate was lower in the experimental group than that of the control group (9.8% vs. 23.5%，P=0.042). The cumulative end-point-free survival rate was higher in the experiment group than that of the control group (86.3% vs. 70.6%, P=0.037). Conclusion Sacubitril valsartan is safer and more effective than ACEI/ARB in the treatment of AMI patients with HFmrEF, and it is worthy of clinical promotion.

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Effect of individualized PEEP combined with regular lung recruitment maneuvers on atelectasis after laparoscopic radical resection of colorectal cancer in elderly patients

JIANG Hongyang, FAN Shiwen, LIU Tielong, XIE Liping

2024, 52 (2): 182-187. doi: 10.11958/20230235

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Objective To evaluate the effect of driving pressure (ΔP)-guided individualized positive end-expiratory pressure (PEEP) combined with regular lung recruitment maneuvers (RMs) on atelectasis in elderly patients undergoing laparoscopic surgery in the Trendelenburg position using lung ultrasound. Methods A total of 62 patients aged 65-85 years old and classified by ASA status Ⅰ-Ⅲ undergoing laparoscopic radical resection of colorectal cancer were included and randomly divided into the experimental group (n=31) and the control group (n=31). Both groups received one RM after the beginning of pneumoperitoneum, followed immediately by titration of individualized PEEP with the lowest ΔP, and both groups received another RM after the end of pneumoperitoneum. The experimental group received additional RM every 30 min from the beginning of pneumoperitoneum, while the control group received no intervention. Recording time points for observation were: before induction of anesthesia (T₀), 30 min after pneumoperitoneum (T₁), 90 min after pneumoperitoneum (T₂), at the end of surgery (T₃) and 45 min after entering the postanesthesia care unit (PACU, T₄). Lung ultrasound score (LUS) was recorded at T₀, T₃ and T₄. Dynamic lung compliance (Cdyn) was recorded at T₁-T₃. Oxygenation index (OI), mean arterial pressure (MAP) and heart rate (HR) were recorded at T₀-T₄. Hypotension during RM, hypoxic saturation events in PACU and the incidence of pulmonary complications (POPC) within the first 7 days after surgery were recorded. Results Compared with the control group, LUSs at T₃ and T₄were significantly decreased in the experimental group (P < 0.05), and OI and Cdyn at T₂ and T₃ were significantly increased (P < 0.05). In addition, the incidence of hypoxia saturation events in PACU was lower in the experimental group than that in the control group (P < 0.05). There were no significant differences in the incidence of hypotension during lung recruitment and the incidence of POPC within 7 days after surgery between the two groups. Conclusion The individualized PEEP combined with regular RMs can effectively reduce the atelectasis observed by lung ultrasound immediately after laparoscopic radical resection of colorectal cancer and in PACU in elderly patients.

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Effect of individualized positive end-expiratory pressure guided by driving pressure on lung protection after laparoscopic radical gastrectomy in elderly patients

ZHONG Xiaoqian, SUN Gaoyue, ZHANG Qianqian, LI Yun

2024, 52 (2): 188-192. doi: 10.11958/20230480

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Objective To explore the effect of individualized positive end expiratory pressure guided by driving pressure on lung protection after laparoscopic radical gastrectomy for elderly patients. Methods A total of 64 patients underwent elective laparoscopic radical gastrectomy for gastric cancer in the Second Affiliated Hospital of Anhui Medical University were selected. According to the random number table method, patients were divided into the driving the pressure guided individualized positive end-expiratory pressure (PEEP) group (experimental group) and the fixed PEEP group (control group), 32 cases in each group. In the control group, PEEP = 5 cmH₂O. In the experimental group, PEEP titration was performed according to the increasing method, and the PEEP corresponding to the lowest driving pressure was selected until extubation. Peak airway pressure (Ppeak), plateau airway pressure (Pplat) and PEEP were recorded at 5 min after intubation (T₁), immediately after PEEP titration (T₂), 1 h after operation (T₃), 2 h after operation (T₄), and 10 min after pneumoperitoneum release (T₅). Driving pressure (ΔP) and lung dynamic compliance (Cdyn) were calculated. Arterial blood was collected at T_1-5 for blood gas analysis, arterial partial pressure of oxygen (PaO₂) was recorded, and oxygenation index (OI) was calculated. The occurrence of pulmonary complications (PPCs) within 7 days after operation was recorded. Modified clinical pulmonary infection score (mCPIS) was recorded on the second day after operation. The pulmonary function was evaluated before operation, 1 day, 3 days and 5 days after operation. Results Compared with T₁, Ppeak, Pplat and ΔP were increased and Cdyn was decreased at T_2-5, while OI was decreased at T₄ in control group (P<0.05). Compared with the control group, Ppeak, Pplat and Cdyn in the experimental group were increased at T_2-5, ΔP was decreased, and OI was increased at T_3-5 (P<0.05). Compared with the preoperative results, FVC at 1, 3 and 5 days after surgery was decreased, and FEV₁ and maximum expiratory flow (PEF) were decreased 1 and 3 days after surgery in the experimental groups (P<0.05). Compared with the control group, FVC, FEV₁ and PEF were higher 1 day after operation in the experimental group (P<0.05). Compared with the preoperative results, mCPIS scores of the two groups were higher on the second day after surgery (P<0.05). Compared with the control group, the mCPIS score was lower on day 2 after surgery in the experimental group (P<0.05). The incidence of PPCs within 7 days after surgery was lower in the experimental group than that in the control group (15.6% vs. 40.6%). Conclusion Individualized PEEP guided by drive pressure can improve lung compliance, reduce drive pressure, improve oxygenation function and early postoperative lung function, reduce the incidence of postoperative lung complications, and has a certain lung protection effect.

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Correlation analysis of serum Chemerin with disease activity and Th17/Treg in patients with rheumatoid arthritis

XU Wenjing, GAO Dongmei, LI Huixin, WANG Li, TONG Shengquan

2024, 52 (2): 193-196. doi: 10.11958/20230505

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Objective To explore the correlation of serum Chemerin level with disease activity and the ratio of T helper 17/regulatory T cells (Th17/Treg) in patients with rheumatoid arthritis (RA). Methods A total of 180 patients with RA who were admitted to our hospital were regarded as the observation group. According to the DAS28 score, the observation group was divided into the high activity group (60 cases), the moderate activity group (60 cases) and the low activity group (60 cases). Another 180 healthy people who underwent physical examination in our hospital during the same period were regarded as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of Chemerin, interleukin-9 (IL-9), interleukin-10 (IL-10) and interleukin-17 (IL-17). Flow cytometry was used to detect the Th17/Treg ratio. Spearman correlation analysis was applied to analyze the correlation between serum Chemerin level and DAS28 score. Pearson correlation analysis was used to analyze the correlation between serum Chemerin level and Th17, Treg cell percentage and Th17/Treg ratio. Results The results of this study showed that the serum level of Chemerin was higher in the observation group than that in the control group (P<0.05). The serum Chemerin level was positively correlated with DAS28 score (P<0.05). Serum Chemerin levels and DAS28 scores decreased in turn in the high, moderate and low activity groups (P<0.05). The percentage of Th17 cells and the ratio of Th17/Treg were higher in the observation group than those in the control group, and the percentage of Treg cells was lower in the observation group than that in the control group (P<0.05). The level of IL-10 was lower in the observation group than that in the control group, while levels of IL-17 and IL-9 were higher in the observation group than those in the control group (P<0.05). The results of Pearson correlation analysis showed that serum Chemerin level was positively correlated with the percentage of Th17 cells and the ratio of Th17/Treg, and negatively correlated with the percentage of Treg cells (P<0.05). Conclusion Serum Chemerin level is elevated in patients with RA, which is closely related to disease activity and Th17/Treg ratio.

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Characteristics of myocardial injury in patients with acute myocardial infarction complicated with pleural effusion and its influence on long-term prognosis

GAO Guangren, FENG Lianrong, FU Jinguo, GUO Run, NIU Heping, LI Fengpeng, ZHANG Qianyu, ZHANG Jun

2024, 52 (2): 197-200. doi: 10.11958/20230377

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Objective To explore the characteristics of myocardial injury in patients with acute myocardial infarction (AMI) complicated by pleural effusion and its effect on long-term prognosis. Methods It was a prospective single-center study. Patients with AMI who were admitted to hospital within 15 days from symptom onset and performed echocardiography and cardiac magnetic resonance imaging (CMR) during hospitalization were consecutively enrolled and assigned to the with-pleural effusion group and the without-pleural effusion group according to the echocardiography result. Baseline data, cardiac magnetic resonance myocardial injury index and echocardiography characteristics were compared between the two groups. The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) was recorded through outpatient follow-up and telephone follow-up, including all-cause death, re-infarction, revascularization, rehospitalization for congestive heart failure and stroke. Cox regression analysis was performed to analyze influencing factors of all-cause death. Results Among 211 patients, 31 (14.7%) patients had pleural effusion and 180 (85.3%) had no pleural effusion. Compared with the group without pleural effusion, the left ventricular end-diastolic diameter was larger, and left ventricular ejection fraction assessed by echocardiography was lower in the group with pleural effusion (P<0.05). There were no significant differences in infarct size, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction and the presence of microvascular obstruction and intramyocardial hemorrhage between the two groups in CMR (all P>0.05). At a median follow-up of 31 months, MACCE occurred in 43 (20.4%) patients, and there was no significant difference between the two groups (χ²=3.160，P=0.075). Six cases (2.8%) had all-cause death. The incidence of all-cause death was higher in the group with pleural effusion than that in the group without pleural effusion (9.7% vs. 1.7%, P < 0.05). There was no significant difference in the incidence of other adverse events between the two groups (P>0.05). Multivariate Cox regression analysis showed that advanced age and presence of pleural effusion were independent risk factors of all-cause death during follow-up. Conclusion Patients with AMI combined with pleural effusion have more severe myocardial injury and higher all-cause mortality.

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Effects of intraoperative blood glucose fluctuation and postoperative insulin resistance on cognitive dyfunction in elderly patients after thoracoscopic radical resection of lung cancer under general anesthesia

CHEN Huimin, JIA Hongfeng, JIANG Tingting, JIA Yaohui

2024, 52 (2): 201-205. doi: 10.11958/20230390

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Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance (IR) on postoperative cognitive dyfunction (POCD) in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia. Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group (n=84) and the non-POCD group (n=268). The covariates between the two groups were balanced by propensity score matching method (PSM). Eighty-four cases in each group were successfully matched. The data between the two groups before and after PSM were compared. After PSM, receiver operating characteristic (ROC) curve of blood glucose fluctuation amplitude for predicting POCD was drawn, and patients were divided into the low-level blood glucose fluctuation group (n=97) and the high-level blood glucose fluctuation group (n=71) according to the cut-off value. According to the existence of postoperative IR, patients were divided into the IR group (n=53) and the non-IR group (n=115). Then, incidences of POCD between groups were compared. Logistic regression was used to analyze the influencing factors of POCD. Results Before PSM, the POCD group had older age, higher blood glucose fluctuation amplitude, IR ratio, operation time, anesthesia time, propofol dosage, remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group (P<0.05). The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM (P<0.05). After PSM, the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group (P<0.05). Logistic regression analysis showed that higher intraoperative blood glucose fluctuation (OR=9.140, 95%CI: 4.338-19.257) and postoperative IR (OR=4.034, 95%CI: 1.163-13.991) were risk factors of POCD. Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.

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The value of new coagulation markers in the diagnosis and prognosis evaluation of neonatal disseminated intravascular coagulation

ZHANG Shijie, MENG Xianchun, SUN Pingping, YANG Jingjing, WU Jing

2024, 52 (2): 206-209. doi: 10.11958/20230564

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Objective To investigate the value of thrombomodulin (TM), thrombin-antithrombin complex (TAT), α2 plasmin inhibitor-plasmin complex (PIC) and tissue plasminogen activator-inhibitor complex (t-PAIC) in the diagnosis and prognosis of neonatal disseminated intravascular coagulation (DIC). Methods Eighty-seven DIC neonates (the observation group) were included and divided into the survival group (66 cases) and the death group (21 cases) based on their outcomes at discharge. And 50 healthy newborns born in the same period were selected as the control group. The clinical data of neonates were collected, and risk factors of neonatal DIC were analyzed by Logistic regression. The differences of TM, TAT, PIC and t-PAIC levels in different groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze values of TM, TAT, PIC and t-PAIC in the diagnosis and prognosis of neonatal DIC. Results The incidence of low Apgar score, birth asphyxia, IVH, sepsis and maternal pregnancy induced hypertension syndrome (PIH) were higher in the observation group than those in the control group (P<0.05). Multivariate Logistic regression analysis showed that low Apgar score, birth asphyxia, sepsis and PIH were independent risk factors for neonatal DIC. TM, TAT, PIC and t-PAIC levels were higher in the observation group than those in the control group (P<0.05). ROC curve showed that the combined diagnosis value of TM, TAT, PIC and t-PAIC was better than that of single diagnosis of neonatal DIC. TM and TAT levels were higher in the death group than those in the survival group (P<0.05), and there were no significant differences in PIC and t-PAIC levels between the two groups. Multivariate Logistic regression analysis showed that elevated TAT level was an independent risk factor for neonatal DIC prognosis. ROC curve showed that when TAT was 21.72 μg/L, the area under the curve for predicting neonatal DIC prognosis was 0.772 (95%CI: 0.666-0.878), and the sensitivity and specificity were 76.2% and 71.2%, respectively. Conclusion The combined application of TM, TAT, PIC and t-PAIC has important clinical value in diagnosis and prognosis evaluation of neonatal DIC.

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Relationship between left ventricular hypertrophy diagnosed by Peguero-Lo-Presti index and recurrence after radiofrequency catheter ablation of paroxysmal atrial fibrillation

ZHANG Minglong, FANG Yuanyuan, SUI Xiaopeng, CHEN Xinxin, LI Liudong, WANG Haitao

2024, 52 (2): 210-214. doi: 10.11958/20230627

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Objective To investigate the relationship between left ventricular hypertrophy (LVH) diagnosed by Peguero-Lo-Presti index and recurrence of paroxysmal atrial fibrillation (AF) after radiofrequency ablation. Methods A total of 652 patients with paroxysmal atrial fibrillation who underwent radiofrequency ablation were selected. According to Peguero-Lo-Presti index, patients were divided into the LVH group (167 cases) and the normal left ventricle group (485 cases). Baseline data were collected, and regular follow-up was performed at 3, 6 and 12 months after radiofrequency catheter ablation. The recurrence of AF was assessed. Kaplan-Meier survival curve was used to analyze the recurrence rate of AF in the two groups. Cox proportional hazard model was used to assess risk factors for recurrent atrial fibrillation. Results The median follow-up time was 20.5 (15.0, 26.0) months. A total of 155 patients (23.8%) developed recurrence of AF, including 95 patients in the LVH group and 60 patients in the LVN group. The recurrence rate without AF was significantly lower in the LVH group than that in the LVN group (64.1% vs. 80.4%, Log-rank χ²=26.361, P<0.01). After adjusting for age, sex, body mass index, hypertension, diabetes, coronary heart disease, cardiac dysfunction, left anteroposterior and posterior atrial diameter, left ventricular end-diastolic diameter, and left ventricular ejection fraction, LVH diagnosed by Peguero-Lo-Presti index was still a risk factor for recurrent AF [HR (95%CI) : 2.359 (1.663-3.345), P<0.01]. Conclusion In patients with paroxysmal AF, LVH diagnosed by Peguero-Lo-Presti index is a risk factor of AF recurrence after radiofrequency catheter ablation.

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Research progress of mesenchymal stem cells in endometriosis

WANG Xinyao, YANG Hui, LI Bingbing

2024, 52 (2): 215-219. doi: 10.11958/20231271

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Endometriosis is a common chronic gynecological disease, and its pathogenesis has not been fully elucidated. Mesenchymal stem cells are a kind of pluripotent stem cells with multi-directional differentiation potential derived from mesoderm, which can differentiate into a variety of tissues and organs. Endometrial mesenchymal stem cells, menstrual blood-derived mesenchymal stem cells, adipose mesenchymal stem cells, bone marrow mesenchymal stem cells and umbilical cord blood mesenchymal stem cells can participate in the pathogenesis of endometriosis from cell proliferation and differentiation, ectopic migration, angiogenesis, inflammatory response and fibrosis formation, and play a certain role in progression of the disease. Mesenchymal stem cells provide new ideas for elucidating the pathogenesis of endometriosis, and may also become a potential method for the treatment of endometriosis.

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Research progress of diabetes mellitus complicated with chronic inflammatory demyelinating polyneuropathy

FU Xiujuan, LU Zuneng

2024, 52 (2): 220-224. doi: 10.11958/20230448

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In recent years, the results of epidemiological research findings on chronic inflammatory demyelinating polyneuropathy (CIDP) in patients with diabetes mellitus (DM) are quite different, and its correlation is still controversial. Nevertheless, due to the high incidence and treatability of CIDP in DM patients, accurate diagnosis and differentiation of DM-CIDP are of great value for guiding clinical drug use. In terms of clinical manifestations, it can be distinguished by age of onset, disease duration, blood glucose control level and main symptom characteristics. Supplementary diagnostic methods frequently involve evaluating cerebrospinal fluid protein levels, demyelination patterns in electrophysiological tests and neuroimaging studies. Additionally, neuropathological examination and specific serum antibodies can provide more diagnostic support for distinguishing DM-CIDP. Furthermore, a positive response to immunomodulatory and/or immunosuppressive therapies supports the diagnosis of DM-CIDP. By comprehensively evaluating clinical manifestations, electrophysiological characteristics, laboratory tests, neuropathology, imaging, and treatment responses, the accuracy of the differential diagnosis for DM-CIDP can be improved.

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