Tianjin Medical Journal

Connective tissue disease-associated interstitial lung disease: from pathogenesis to "dual-target" treatment strategies

LI Mengtao, WANG Qian

2024, 52 (7): 673-678. doi: 10.11958/20240260

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Connective tissue diseases (CTD) are a spectrum of heterogeneous diseases with multiple organ involvements. Interstitial lung diseases (ILD) are serious complications of CTD. There is great heterogeneity in pathogenesis, clinical manifestations, and treatment of different CTD-ILD. Previous basic and clinical studies have explored the pathogenesis of CTD-ILD, and the "dual-target" treatment strategy has therefore emerged. The implementation of the "dual-target" treatment strategy helps to control CTD activity and lung inflammation in the early stage, prevent the progression of pulmonary fibrosis, and thus improve patient survival and quality of life.

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Effects of chrysotile on expression of Wnt5a, p16 and p21 in endothelial cells

LI Xin, LI Xue, WANG An

2024, 52 (7): 679-682. doi: 10.11958/20240060

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Objective To investigate the influence of chrysotile on human umbilical vein endothelial cells (HUVECs). Methods HUVECs in the experimental group were treated with 50, 100 and 200 mg/L chrysotile for 24, 48 and 72 h. The control group was cultured with RPMI 1640 medium only. Morphological changes of HUVECs were observed. Cell viability was detected by MTT assay. β-Galactosidase staining was used to analyze the cell senescence. The cell survival rate was determined by tetramethylazolium blue assay. Wnt5a, p16 and p21 expression were investigated by qRT-PCR. Results Cells of the experimental group were oval and irregular, and some of them were round or irregular, with naked nuclei and vacuolar, and dead cells were present. With the increase of chrysotile concentration and exposure time, the level of cell viability decreased and the number of aged cells increased gradually (P<0.05). The cell growth of HUVECs was more active when 100 mg/L chrysotile treated for 24 h. Compared with the control group, the mRNA expression levels of Wnt5a, p16 and p21 were increased in the experimental group (P<0.05). Conclusion Chrysotile can promote HUVECs senescence, and Wnt5a, p16 and p21 are involved in this mechanism.

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Study on the protective effect of vaccine in patients with microscopic polyangiitis-interstitial lung disease complicated with COVID-19 infection

QI Fumin, SU Rui, HAO Jian, SU Li, FAN Qian, LI Xin, WEI Wei

2024, 52 (7): 683-686. doi: 10.11958/20231791

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Objective To analyze the clinical features of microscopic polyangiitis (MPA)-associated interstitial lung disease (ILD) patients infected with coronavirus disease-2019 (COVID-19)，and investigate the protective effect of SARS-CoV-2 vaccine. Methods Patients with MPA-ILD in the General Hospital of Tianjin Medical University were included, and patients also met the diagnostic criteria for COVID-19 in accordance with the COVID-19's diagnosis and treatment plan (10th Edition). All of patients had positive evidence of coronavirus antigens or positive nucleic acid tests. Clinical data of patients, ILD imaging typing, COVID-19 vaccination, clinical typing and prognostic results were collected and analyzed. Results Thirty-seven patients with MPA-ILD were included, including 14 females and 23 males. Thirty-two patients with MPA were in remission at the time of infection with COVID-19, and 31 were maintained on concurrent immunosuppressive/biologic therapy. The original imaging type of MPA-ILD was predominantly usual interstitial pneumonia (UIP, 15 cases) and nonspecific interstitial pneumonia (NSIP, 14 cases). The typing of the remaining 8 cases was inconclusive. Of the COVID-19 subtypes, 27 patients were mild infection, and 5 dead due to COVID-19. Eleven patients were unvaccinated, and 26 received inactivated vaccine. Among them, 11 completed 3-dose of booster immunization. The proportion of patients with mild COVID-19 was significantly higher in MPA-ILD patients with vaccinated patient group than that in the unvaccinated patient group (P=0.038). Multifactorial analysis showed that vaccines were an independent protective factor for MPA-ILD patients with COVID-19 infection (OR=0.045, 95%CI: 0.004-0.472, P=0.010) and non-mild infection (OR=0.049, 95%CI: 0.005-0.517, P=0.012). Moreover, MPA in remission was a protective factor for COVID-19 non-mild infections (OR=0.021, 95%CI: 0.001-0.459, P=0.014). Conclusion Vaccination and MPA in remission may reduce the severity of COVID-19 infection in patients with MPA.

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Clinical analysis of 16 cases of connective tissue disease-associated interstitial lung disease complicated with lung cancer

ZHANG Guohua, ZHANG Lingling, GAO Lan, LUO Junli, SHEN Yawen, LIU Lei, WANG Yuhua

2024, 52 (7): 687-690. doi: 10.11958/20231785

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Objective To investigate the clinical characteristics of 16 patients with connective tissue diseases associated interstitial lung disease (CTD-ILD) complicated with lung cancer, and to improve the cognition of the disease. Methods Clinical data of 16 patients diagnosed as CTD-ILD associated with lung cancer, who were admitted to our center, were retrospectively analyzed, including general conditions, clinical characteristics, auxiliary examinations, pathological classification of lung cancer, TNM type, treatment and clinical outcome. Results Among the 16 CTD-ILD patients with lung cancer, there were 12 males and 4 females. The mean age at diagnosis of CTD-ILD was (64.7±9.2) years, and the mean age at diagnosis of lung cancer was (66.6±8.7) years. Lung occupying space on imaging (62.5%) was the most common initial symptom in lung cancer patients, followed by cough and phlegm (12.5%) and chest pain (12.5%). Of patients with lung cancer, adenocarcinoma (8 cases, 50.0%) was the most common pathological type, followed by small cell lung cancer (4 cases，25.0%). The diagnosis time of CTD-ILD was earlier than that of lung cancer in 8 cases (50.0%), with a median time of 36.0 (11.3，57.0) months, followed by 7 cases (43.8%) of CTD-ILD diagnosed with lung cancer at the same time. The diagnosis time of lung cancer was earlier than that of CTD-ILD in 1 case (6.3%). The most common TNM stage for lung cancer was stage Ⅳ (9 cases, 56.25%). Sixteen patients were followed up from 1 to 64 months, with a median of 8.5 (1.5, 14.3) months. Eleven patients (68.8%) died, including 8 patients (72.7%) died of infection and 3 patients (27.3%) died of end-stage lung cancer. Conclusion For CTD-ILD patients, close follow-up and regular imaging monitoring are necessary to help early detection of lung cancer and improve prognosis.

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The value of cardiac magnetic resonance in evaluating severe pulmonary hypertension associated with connective tissue disease

WU Caixin, YAN Yan, DENG Yuanlin, DU Yamin, YANG Zhenwen, PAN Qing, YANG Fan

2024, 52 (7): 691-694. doi: 10.11958/20231770

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Objective To evaluate the diagnostic value of cardiac magnetic resonance (CMR) in patients with severe connective tissue disease-associated pulmonary hypertension (CTD-PAH). Methods A total of 48 patients diagnosed with CTD-PAH by right heart catheterization (RHC) in Tianjin Medical University General Hospital from June 2018 to July 2021 were retrospectively included. The parameters of right ventricular (RV) morphology, function and ventricular septum (IVS) were obtained by manual delineation on CMR images and corrected by body surface area. The late gadolinium enhancement (LGE) myocardial mass (MM) and its percentage in left ventricular (LV) MM were manually sketched and calculated on LGE images. The patients were divided into the mild-moderate group and the severe group according to mean pulmonary arterial pressure (mPAP). CMR parameters were compared between the two groups. The diagnostic value of CMR for severe CTD-PAH was analyzed by receiver operating characteristic (ROC) curve. Results A total of 48 patients with CTD-PAH were included in this study. The curvature of interventricular septum (CIVS) and RV ejection fraction (EF) were lower in the severe group than those in the mild-moderate group, and the time proportion of IVS deformation, RV end-diastolic volume index (EDVI), RV end-systolic volume index (ESVI) and RV MM were higher than those in the mild-moderate group (P<0.05). ROC curve analysis showed that RV MM, time proportion of IVS deformation and RV ESVI had better diagnostic efficacy in severe CTD-PAH patients (AUC was 0.792, 0.766 and 0.731, respectively). The combined AUC of the three parameters was 0.840, specificity was 85.7% and sensitivity was 79.4%. Conclusion The parameters of RV and IVS measured by CMR can effectively evaluate patients with severe CTD-PAH and directly reflect serverity of cardiac impairment in patients with severe CTD-PAH from the morphological and functional perspective.

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Clinical significance of SS related antibodies in idiopathic inflammatory myopathy and its associated interstitial disease

YIN Weiyu, LIAO Hongli, LIU Yuan

2024, 52 (7): 695-700. doi: 10.11958/20230993

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Objective To investigate the clinical significance of anti-Sj?gren's syndrome type A antibody (SSA) and anti-Sj?gren's syndrome type B antibody (SSB) in idiopathic inflammatory myopathies (IIM) and IIM associated interstitial disease (ILD). Methods A total of 102 patients with IIM were selected. The general information, clinical manifestations and auxiliary examinations were collected. Their positive rates of anti-SSA and anti-SSB antibodies in IIM patients were analyzed. IIM patients were divided into the SS antibody negative group (73 patients) and the SS antibody positive group (29 patients) according to the results of anti SSA and SSB antibody tests. The clinical significance of anti-SSA and anti-SSB antibodies in IIM and IIM related ILD was analyzed. Results Compared with patients in the SS antibody positive group, patients in the SS antibody negative group were more likely to experience dry mouth, increased erythrocyte sedimentation rate (ESR) and increased immunoglobulin A (IgA) levels (P<0.05). The general situation score of the MDAAT (myositis disease activity assessment tool) was significantly higher in the SS antibody positive group than that in the SS antibody negative group (P<0.05), and there were no significant differences in scores of other MDAAT items between the two groups (P>0.05). There were no significant differences in the positive rate of myositis autoantibodies, recurrence rate, hormone therapy and immunosuppressive therapy between the two groups (P>0.05). The proportion of patients treated with intravenous human immunoglobulin was higher in the SS antibody positive group than that of the SS antibody negative group (P<0.05). Non-specific interstitial pneumonia (NSIP) was the most type of ILD in both the SS antibody negative group and the positive group, followed by usual interstitial pneumonia (UIP). Patients with IIM who were positive for anti-SSA/SSB antibodies were more likely to progress to the overlapping syndrome of combined SS. Conclusion Positive anti-SSA and anti-SSB antibodies in IIM patients are associated with dry mouth symptoms, and anti-SSA/SSB antibodies may become one of the important laboratory indicators for judging patient conditions and predicting disease outcomes.

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Analysis of clinical features of mixed connective tissue disease associated with pulmonary arterial hypertension

WANG Hui, PAN Qing, WANG Zhouming, ZHANG Na, YANG Zhenwen, WEI Wei

2024, 52 (7): 701-703. doi: 10.11958/20231786

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Objective To investigate the clinical characteristics and risk factors of mixed connective tissue disease associated with pulmonary arterial hypertension (MCTD-PAH). Methods Twelve MCTD-PAH patients diagnosed by right heart catheterization (RHC) at Tianjin Medical University General Hospital were retrospectively included, and 36 MCTD patients without pulmonary arterial hypertension (MCTD-non-PAH) were randomly selected from the same period of hospitalization based on gender and age. The clinical features and auxiliary examination of the two groups were compared, and the survival status of the two groups was compared. Results The proportion of dyspnea after activity, myositis and pericardial effusion were higher in the MCTD-PAH group than those of the control group. Serum sedimentation rate and immunoglobulin G (IgG) levels were higher in the MCTD-PAH group. Multivariate Logistic regression analysis showed that dyspnea after activity and high level of IgG were risk factors for predicting the occurrence of PAH in MCTD. Three patients (16.7%) died in the MCTD-PAH group, and no patients died in the control group. Conclusion Pulmonary arterial hypertension is one of the serious complications of MCTD. MCTD patients have shortness of breath after activity and high level of IgG should be wary of concomitant PAH.

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Research progress of dermatomyositis-related autoantibodies in interstitial lung disease

LUO Yanran, SHI Xiaofei, HAN Lei, ZHANG Bei, WEN Luyao

2024, 52 (7): 704-708. doi: 10.11958/20231512

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Myositis antibodies are divided into myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA). There are heterogeneity in the mechanism, clinical features and prognosis of interstitial lung disease (ILD) in the different myositis antibodies. In MSA, anti-melanoma differentiation-related gene 5 (MDA5) antibody and anti-aminoacyl synthetase (ARS) antibody are highly correlated with the occurrence of ILD. Patients with MDA5⁺DM-ILD usually have a rapidly progressive and poor prognosis. The progress of ILD in ARS⁺ DM patients was slow, and the response to treatment is good, but it is easy to relapse. In MAA, anti-Ro52 antibodies often coexist with MSA antibodies, and clinical manifestation is closely related to coexisting antibodies. This review has summarized roles of myositis antibodies in ILD.

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Overview of animal models of idiopathic inflammatory myopathy-associated interstitial lung disease

LIU Zhichao, LI Xiaohe, ZHOU Honggang, ZHANG Na

2024, 52 (7): 709-713. doi: 10.11958/20231796

Abstract ( 297 )

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Idiopathic inflammatory myopathy (IIM) is a heterogeneous autoimmune disease of unknown etiology characterized by proximal limb muscle involvement and chronic inflammation. Multiple systems may be involved, with interstitial lung disease (ILD) being the most common manifestation of respiratory system involvement in IIM. This article summarizes the current methods of myositis animal models and myositis-associated ILD model construction methods, so as to provide reference for the subsequent construction and research of IIM-ILD models.

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Effects of hypoxia H9c2 exosome on proliferation，migration and tube formation of HUVEC

YANG Rui, WEI Qiong, SUN Yikun, ZHAO Mengzhu, CHENG Xu, LIU Menghua, ZHANG Dongmei

2024, 52 (7): 714-719. doi: 10.11958/20231930

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Objective To investigate the role of H9c2-derived exosomes in regulating angiogenesis in rat cardiomyocytes under hypoxia. Methods The hypoxia model of H9c2 cells was prepared by mixed gas method (the hypoxia model group), and the normal cultured cells were used as the control group. The exosomes secreted by the two groups of cells were extracted respectively. The concentration and particle size of exosomes were detected by nanoparticle tracking analysis. The morphology and size of exosomes were detected by transmission electron microscopy. Western blot assay was used to verify the exosome marker proteins. The hypoxia model of human umbilical vein endothelial cells (HUVEC) was established. HUVECs were incubated with H9c2 exosomes and divided into the normoxia group, the hypoxia group, the hypoxia + normal H9c2 exosomes (EXO-C) group and the hypoxia + hypoxia H9c2 exosomes (EXO-M) group. The proliferation, migration and tube formation of HUVECs were detected by CCK-8 method, cell scratch test and Matrigel in vitro three-dimensional forming test. Results The results of exosome identification showed that the particle concentration of H9c2 exosome samples was 1×10⁷-1×10¹²particles/mL and the particle size was 40-160 nm in the normoxia group and the hypoxia group. The morphological characteristics were spherical or saucer-like structure, uniform in size and complete in shape. Exosome marker proteins TSG101, CD63 and CD9 were expressed, and there was no expression of negative protein Calnexin. Compared with the normoxic group, the proliferation ability, migration area and migration rate of HUVEC were significantly decreased in the hypoxic group, and the length of tube, the number of branches and the number of nodes were decreased (P<0.01). Compared with the hypoxia group, the proliferation ability of HUVEC cells was decreased, the migration area was decreased, the migration rate was decreased and the length and number of branches involved in tube formation were further decreased in the EXO-M group (P<0.05). Compared with the EXO-C group, the proliferation ability of the EXO-M group decreased, the cell migration area decreased and the migration rate decreased (P<0.01). Conclusion Exosomes derived from hypoxic H9c2 can inhibit the proliferation, migration and tube formation of HUVEC.

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Zinc finger protein 281 inhibits high glucose-induced epithelial-mesenchymal transition and extracellular matrix synthesis in renal tubular epithelial cells

HOU Weiling, QIAO Yunyang, WU Xiaoyun, SHI Huimin, QU Gaoting, ZHANG Aiqing

2024, 52 (7): 720-726. doi: 10.11958/20240031

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Objective To investigate the role and mechanism of zinc finger protein 281 (ZNF281) in high glucose (HG)-induced epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) synthesis in renal tubular epithelial cells (RTECs). Methods HG induced RTECs were used to construct a diabetic kidney disease cell model, and cells were divided into the control group, the HG group and the mannitol group. Cell proliferation viability was detected by CCK-8. The expression of ZNF281 was knocked down in HG-treated RTECs using small interfering RNA (siRNA). HG-induced RTECs after knockdown of ZNF281 were divided into the control group, the HG group, the HG+ZNF281 siRNA group and the HG+ZNF281 vector group. Adenosine monophosphate-activated protein kinase (AMPK) was activated using AMPK agonist, acadexin (AICAR), and then cells were divided into the control group, the HG group, the HG+AICAR group and the HG+dimethyl sulfoxide group. The expression levels of ZNF281, EMT and ECM synthesis-related indexes were detected by qPCR and Western blot assay. Results Compared with the control group, the protein and mRNA expression levels of vimentin, α-smooth muscle actin (α-SMA), fibronectin (FN) and collagen Ⅰ (Col Ⅰ) were significantly higher, and the expression of E-cadherin was significantly lower in the HG group. Compared with the HG group, the protein and mRNA expression levels of EMT and ECM synthesis-related indexes were significantly changed in the HG+ZNF281 siRNA group and the HG+AICAR group. The protein and mRNA expression levels of ZNF281 were significantly reduced in the HG+AICAR group compared with the HG group. In cells co-treated with AICAR and transfected with ZNF281 plasmid, the expression levels of vimentin, α-SMA, FN and Col Ⅰ were significantly higher in the AICAR+ZNF281 group, and E-cadherin was significantly lower compared with that of the vector group. Conclusion AMPK inhibits EMT and ECM synthesis in HG-treated RTECs by negatively regulating the expression level of ZNF281.

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The effect of icariin on apoptosis of ovarian granulosa cells in polycystic ovary syndrome rats by regulating the SDF-1/CXCR4 signaling pathway

XU Qiongfang, ZHONG Fei, LI Zishuai

2024, 52 (7): 727-732. doi: 10.11958/20231504

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Objective To investigate the effect of icariin on apoptosis of ovarian granulosa cells in rats with polycystic ovarian syndrome (PCOS) by regulating stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signal axis. Methods Granular cells successfully isolated from ovarian tissue of rats in the PCOS model group were grouped into the PCOS group, the low-dose icariin group, the medium-dose icariin group, the high-dose icariin group, the Rr-SDF-1 group and the high-dose icariin+Rr-SDF-1 group. Granular cells successfully isolated from ovarian tissue of rats in the normal control group were taken as the control group. Enzyme-linked immunosorbent assay (ELISA) was applied to detect levels of follicle-stimulating hormone (FSH), testosterone (T) and luteinizing hormone (LH) in supernatant of ovarian granulosa cells. CCK-8 method and EdU staining were applied to detect granulosa cell proliferation. Flow cytometry was applied to detect granulosa cell apoptosis. Western blot assay was applied to detect the expression of Bcl-2 associated X (Bax), Cleaved aspartate-specific cysteine protease-3 (Cleaved Caspase-3), SDF-1, and CXCR4 proteins in granulosa cells. Results Compared with the control group, the FSH level, OD₄₅₀ value and EdU positive cell rate were decreased in the PCOS group, and T and LH levels, apoptosis rate, Bax, Cleaved Caspase-3, SDF-1 and CXCR4 protein expression increased (P<0.05). Compared with PCOS group, the FSH level, OD₄₅₀ value and EdU positive cell rate were increased sequentially in the icariin low, medium and high dose groups, T and LH levels, apoptosis rate, Bax, Cleaved Caspase-3, SDF-1 and CXCR4 protein expression levels were decreased sequentially, and change trends of corresponding indicators were opposite to the above in the Rr-SDF-1 group (P<0.05). Compared with the high-dose icariin group, FSH level, OD₄₅₀ value and EdU positive cell rate were decreased in the high-dose icariin+Rr-SDF-1 group, and T and LH levels, apoptosis rate, Bax, Cleaved Caspase-3, SDF-1 and CXCR4 protein expression levels were increased (P<0.05). Conclusion Icariin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by inhibiting the SDF-1/CXCR4 signaling pathway.

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Effects of GABA signaling pathway on endoplasmic reticulum stress and mitochondrial autophagy in septic rats with acute lung injury

ZHONG Min, SHI Zhen, ZHOU Jinsong, LI Jinjie

2024, 52 (7): 733-737. doi: 10.11958/20231352

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Objective To investigate the effect of γ-aminobutyric acid (GABA) signaling pathway on endoplasmic reticulum (ER) stress and mitochondrial autophagy in septic rats with acute lung injury (ALI). Methods SD rats were randomly grouped into the control (CON) group, the model group, the GABA signaling pathway activator Baclofen group (the Baclofen group), the GABA signaling pathway inhibitor dicentrine group (the BIC group), with 6 rats in each group. The Baclofen group received intraperitoneal injection of 5 mg/kg Baclofen, and the BIC group received intraperitoneal injection of 1 mg/kg BIC, once a day, for two consecutive weeks. The CON group and the model group were injected with an equal amount of physiological saline via intraperitoneal injection. Enzyme linked immunosorbent assay was applied to detect serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) and levels of cytochrome C (Cyt.C) and Nicotinamide adenine dinucleotide phosphate (NADPH) in bronchoalveolar lavage fluid (BALF). Transmission electron microscopy (TEM) was applied to observe the ultrastructure of lung tissue cells. HE staining was applied to observe the pathological morphology of lung tissue. TUNEL staining was applied to observe the apoptosis of lung tissue. Western blot assay was applied to detect expression levels of GABAAR, GRP78 and CHOP proteins in lung tissue. Results Compared with the model group, the lung swelling, congestion and inflammatory cell infiltration were improved in the Baclofen group, and the lung injury score, MDA content, apoptosis index, Cyt.C and NADPH levels, GRP78, and CHOP protein levels were reduced (P<0.05). The number of autophagic vacuoles in phagocytic mitochondria, SOD content and GABAAR protein level were increased (P<0.05), however, the trend of above indicators in the BIC group was opposite to that in the Baclofen group. Conclusion Up-regulation of GABA signaling pathway may have an improvement effect on ALI in sepsis rats.

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Changes and clinical significance of plasma free amino acid levels in the development of chronic hepatitis B to hepatocellular carcinoma

WU Jing, FAN Zhijuan, LIU Shuye

2024, 52 (7): 738-742. doi: 10.11958/20231456

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Objective To investigate changes and clinical significance in plasma free amino acid levels during the progression from chronic hepatitis B (CHB) to liver cirrhosis (LC) and ultimately to hepatocellular carcinoma (HCC). Methods The plasma samples of 49 CHB patients, 43 CHB-related LC patients and 50 CHB-related HCC patients were analyzed using the Hitachi L-8900 amino acid analyzer. The differences in amino acid levels were compared between groups. Simultaneously, the MetaboAnalyst website was used to analyze the relevant amino acid metabolism pathways. Results A total of 16 amino acids with different expression levels were identified. During the development from CHB to HCC, plasma levels of cystine, phenylalanine and glycine gradually increased, while the ratio of branched chain amino acids/aromatic amino acids gradually decreased. Compared with the CHB and the LC groups, levels of taurine, methionine, tyrosine, ornithine, glutamate, isoleucine and tryptophan were significantly increased in the HCC group, while the level of arginine was significantly lower. Compared with the CHB group, levels of serine, alanine and proline were higher in the LC and the HCC groups, while the level of valine was also higher in the HCC group (all P<0.05). The metabolic pathway analysis of three groups showed significant changes in various metabolic pathways, including phenylalanine, tyrosine, tryptophan biosynthesis, phenylalanine metabolism, glycine, serine, threonine metabolism, valine, leucine, isoleucine biosynthesis, and taurine metabolism. In addition, by constructing a network diagram of amino acid enzyme gene interactions, a total of 79 metabolic enzyme genes related to amino acid expression were discovered. Conclusion Plasma levels of amino acids are of certain guiding significance for early warning and prognosis of HCC and can provide a theoretical basis and methodological basis for the diagnosis and treatment of HCC in the future.

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Efficacy and safety of ultrafiltration in the treatment for elderly patients with heart failure and frailty

XU Bin, ZHU Yun, CHEN Hao, ZHU Hongjun, GAO Feng, XIA Congyi, ZHONG Ling, SU Wei

2024, 52 (7): 743-747. doi: 10.11958/20231308

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Objective To investigate the efficacy and safety of ultrafiltration therapy in elderly patients with congestive heart failure (CHF) and frailty. Methods A total of 88 hospitalized elderly patients with CHF and frailty were randomly assigned to the ultrafiltration group (n=44) and the control group (n=44). The control group treated with standard drug therapy. The ultrafiltration group treated with ultrafiltration, however, diuretics were not used during ultrafiltration treatment. Efficacy assessment was compared between the two groups, including patient body weight, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at 48 hours after treatment, dyspnea severity scores at 48 hours and 1 week after treatment, hospitalization duration and readmission rate within 3 months. Safety assessment parameters included serum creatinine, urea nitrogen, Na⁺ and K⁺concentration at 48 hours after treatment and creatinine level 1 week after treatment. Results Efficacy assessment indicated that at 48 hours after treatment, both groups showed a significant reduction in patient body weight and NT-proBNP levels compared to pre-treatment levels (P<0.05). However, there were no significant difference in body weight and NT-proBNP levels before and after treatment between the two groups (P>0.05). Dyspnea severity scores for both groups increased at 48 hours after treatment, then decreased at 1 week after treatment. The ultrafiltration group exhibited higher dyspnea severity scores than that of the control group at 48 hours after treatment (P<0.05). The length of hospital stay and the rate of re-hospitalization within 3 months were lower in the ultrafiltration group compared to those of the control group (P<0.05). Safety assessment revealed that there were no significant differences in serum urea nitrogen and Na⁺ levels before and 48 hours after treatment between the two groups (P>0.05). However, serum K⁺ levels were higher after 48-hours treatment in the ultrafiltration group than those of the control group (P<0.05). There were no significant changes in creatinine levels before and after treatment in the control group (P>0.05), while creatinine levels were lower 1 week after treatment in the ultrafiltration group compared to those of pre-treatment and 48 hours after treatment, and were lower than those of the control group (P<0.05). Conclusion Ultrafiltration is a safe and effective method for elderly patients with CHF and frailty.

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Construction and validation of a risk prediction model for bronchopulmonary dysplasia based on early platelet-related parameters

XUE Yuheng, MAO Ning, LIU Wenqiang, YANG Qianqian, XU Yan, WANG Jun

2024, 52 (7): 748-754. doi: 10.11958/20231602

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Objective To develop and validate a risk prediction model based on early platelet-related parameters for bronchopulmonary dysplasia (BPD) in neonates admitted to the neonatal intensive care unit (NICU), and to facilitate early identification and intervention in high-risk populations. Methods Clinical data of 291 preterm infants with a gestational age (GA) ≤32 weeks or a birth weight (BW) <1 500 g, admitted to the NICU, were retrospectively analyzed. Out of these, 214 cases were selected as the modeling group. This group was further categorized into the BPD group (n=76) and the non-BPD group (n=138), based on whether they required oxygen therapy at 28 days post-birth. Perinatal data, platelet-related parameters and other indicators between the two groups. Univariate and multivariate Logistic regression analyses were conducted to identify BPD risk factors, followed by the construction of a nomogram. An additional cohort of 105 preterm infants with GA≤32 weeks or BW<1 500 g, were used to validate the model. This cohort was divided into the BPD group (n=43) and the non-BPD (n=62) group. Receiver operating characteristic (ROC) curve and calibration curve were used to internally verify the efficiency of the prediction model. Results The Logistic regression analysis identified GA, BW, Apgar score at 5 minutes≤7, invasive ventilation, platelet count (PLT) and mean platelet volume (MPV) as significant factors in the model (P<0.05). The constructed nomogram was formulated using R language, and the areas under the ROC curve (AUC) for the three models were 0.908, 0.931 and 0.918, respectively (P<0.05). The verification group was verified by Bootstrap. The calibration curve showed a good fit. The internal validation AUC values of the three models were 0.877, 0.890 and 0.886, respectively. Conclusion GA, BW, invasive ventilation, Apgar score at 5 minutes≤7, MPV and PLT are key risk factors for BPD onset. The risk prediction model based on these indicators can effectively predict BPD, providing clinicians with a valuable tool for early detection and intervention in the development of BPD.

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Analysis of electrocardiographic features and in-hospital mortality in acute total left main artery occlusion and subtotal occlusion

LIU Chunwei, YANG Fan, HU Yuecheng, ZHANG Jingxia, CONG Hongliang, LI Ximing

2024, 52 (7): 755-761. doi: 10.11958/20231546

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Objective To investigate the difference of electrocardiographic (ECG) features between total left main artery (LM) occlusion and subtotal occlusion, and analyze risk factors of in-hospital mortality. Methods A total of 94 patients with left main complete occlusion and 99 patients with subtotal occlusion were included. ECG characteristics, coronary angiography and other clinical data were compared, and factors of hospital death were analyzed. The receiver operating characteristics (ROC) curve was used to analyze the predictive value of ECG characteristics in hospital death risk in patients with LM occlusion. The relationship between ECG characteristics, shock and collateral circulation were analyzed in patients with LM occlusion. Results Compared with the subtotal occlusion group, patients with LM occlusion presented with more ST-segment elevation (STE) in Ⅰ, avL, V2-V5, more STE in avR and avL, more left anterior fascicular block + right bundle branch block, prolonged QRS duration, less STE in avR and less STE in avR+V1.The in-hospital mortality was 46.8% (44/94) in LM occlusion and 14.1% (14/99) in LM subtotal occlusion. STE in avR+avL predicted total LM occlusion with a specificity of 0.97, and left anterior branch + right bundle branch block predicted total LM occlusion with a specificity of 1.00. In patients with total LM occlusion, STE in Ⅰ, avL, V2-V5, prolongation of QRS duration, shock, no collateral circulation, STE in Ⅰ, avL, V2-V5 combined with left anterior fascicular block + right bundle branch block, and STE in Ⅰ, avL, V2-V5 combined with shock predicted in-hospital mortality, with the area under the curve of 0.716, 0.619, 0.766, 0.688, 0.572, 0.785, respectively. The diagnostic specificity of STE in Ⅰ, avL, V2-V5 combined with shock was 0.82, and the sensitivity was 0.75. STE in Ⅰ, avL, V2-V5 combined with left anterior fascicular block+right bundle branch block predicted in-hospital death in LM occlusion with a specificity of 0.94. The proportion of shock was higher in patients with STE in Ⅰ, avL, V2-V5, left anterior fascicular block+right bundle branch block and collateral flow absence (P<0.05). In patients with total occlusion, no collateral flow was observed in patients with STE in Ⅰ, avL, V2-V5. In patients with STE in avR (including avR+V1), 82.4% of patients presented with right coronary collateral circulation supplying the left anterior descending coronary artery and left circumflex artery territory. In patients with STE in avR+avL, 69.2% of patients presented with right coronary collateral circulation supplying left anterior descending coronary artery territory. Conclusion Total LM occlusion presents with different ECG features compared with subtotal occlusion. In LM total occlusion, the ECG features predict in-hospital mortality and are associated with different collateral circulation.

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The impact of preoperative anxiety on anesthesia and postoperative recovery in patients with liver cancer

ZHU Wenzhi, QIU Qian, TAN Hongyu

2024, 52 (7): 762-765. doi: 10.11958/20231376

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Objective To investigate the effect of preoperative anxiety on postoperative recovery and short-term prognosis in patients with liver cancer resection. Methods A total of 96 patients underwent elective open hepatocellular carcinoma resection, with American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ were included in this study. Patients were divided into the control group (41 cases, HAMA < 7 points) and the anxiety group (55 cases, HAMA ≥7 points) according to Hamilton Anxiety Scale (HAMA). Heart rate (HR), mean arterial pressure (MAP) after entering the operating room, operative time, intraoperative bleeding, intraoperative fluid infusion and intraoperative remifentanil consumption were monitored in patients. Recovery time, extubation time, Emergence Agitation (EA) score, the resting and dynamic visual analogue scale ( VAS ) at 5 min after extubation (T₁), 6 h (T₂), 12 h (T₃), 24h (T₄) and 48 h (T₅) after surgery, the cumulative effective pressing times of patient controlled analgesia (PCA), the remedy times of analgesic drugs, the postoperative gastrointestinal reaction, exhaust time, hospital stay, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at the 5th day after operation were recorded. Results Compared with the control group, the heart rate and MAP in the anxious group were significantly increased after entering operating room, and the recovery time and extubation time were significantly prolonged (P<0.05). The incidence of intraoperative remifentanil consumption, EA score, T₁, T₂, T₃ resting and dynamic VAS score, T₄ dynamic VAS score, PCA pressing times, analgesic drug remedy times and postoperative gastrointestinal reactions were significantly higher in the anxious group than those in the control group (P<0.05), and incidence of gastrointestinal reactions, postoperative out of bed time, exhaust time, feeding time and hospital stay were significantly prolonged (P<0.05). Conclusion Preoperative anxiety is not conducive to anesthesia recovery and short-term prognosis in patients with liver tumor resection.

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Construction of a prediction model for lumbar fracture in patients with osteoporosis

WANG Min, WANG Longsheng, CHEN Lei

2024, 52 (7): 766-769. doi: 10.11958/20231883

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Objective To construct a prediction model for lumbar fracture in patients with osteoporosis (OP) based on lumbar bone mineral density measured by quantitative computed tomography (QCT) and bone metabolism indicators. Methods A total of 52 patients with OP and lumbar fracture (the fracture group) and 104 patients with OP without lumbar fracture (the non-fracture group) were selected as study subjects. The correlation between lumbar bone mineral density measured by QCT and serum procollagen type I C-propeptide (P1CP), N-terminal mid-fragment of osteocalcin (N-MID) and beta collagen degradation products (β-CTX) was analyzed. Logistic regression analysis was conducted to identify influencing factors of lumbar fracture. A prediction model was constructed and its predictive value was analyzed. Results Compared with the non-fracture group, the proportions of females and patients with fall history, β-CTX level and vitamin D/ calcium medication history were higher in the fracture group, and lumbar bone mineral density measured by lumbar QCT, P1CP and N-MID levels were lower (P<0.05). Pearson correlation analysis found that lumbar bone mineral density measured by QCT was positively correlated with serum levels of P1CP and N-MID, and negatively correlated with β-CTX (r=0.523, 0.506, -0.536, P<0.05). Multivariate Logistic regression analysis found that higher lumbar bone mineral density measured by QCT, P1CP, N-MID and history of taking vitamin D/calcium were protective factors for lumbar fracture, and igher β-CTX level was a risk factor (P<0.05). The sensitivity and specificity of the prediction model constructed based on Logistic regression analysis results for predicting lumbar fracture were 84.62% and 97.12%. The area under the curve was 0.926 (95%CI: 0.873-0.962). The prediction model had good calibration, and the agreement rate was 0.910. Conclusion OP patients with higher levels of QCT, P1CP and N-MID, and lower level of β-CTX have lower risk of lumbar fracture. Vitamin D and calcium can effectively prevent the occurrence of lumbar fracture in OP patients, especially in women.

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The value of magnetic resonance relaxation time quantitative imaging in predicting molecular subtypes of invasive ductal carcinoma

ZHU Gangming, DONG Yongde, ZHU Ruiting, TAN Yuanman, TAO Juan, LIU Xiao, CHEN Decheng, YANG Gai

2024, 52 (7): 770-774. doi: 10.11958/20231486

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Objective To explore the value of magnetic resonance relaxation time quantitative imaging in predicting molecular subtypes of invasive ductal carcinoma (IDC) of breast. Methods A total of 79 IDC patients underwent routine magnetic resonance imaging (MRI) scanning and relaxation time quantitative imaging. According to immunohistochemical results of lesions, patients were divided into different immunohistochemical index groups and molecular subtype groups. The differences in MRI signs, T₁ values and T₂ values of lesions were statistically compared between each group. Patient operating characteristic (ROC) curve was used to evaluate values of T₁ and T₂ alone and the combination of them in differential diagnosis of IDC molecular subtypes. Results There were 82 samples of lesion in 79 patients, in which, Luminal A type 16 (19.51%), Luminal B1 type 11 (13.41%), Luminal B2 type 27 (32.93%), tyrosine kinase receptor-2 overexpression type (Erb-B2) 14 (17.07%) and TNBC 14 (17.07%). There were no significant differences in patient age, lesion distribution, maximum diameter, morphology, margin and enhancement performance between patients with various molecular subtypes (P > 0.05). Among the immunohistochemical indexes, only the Ki-67 positive group had higher T₁ value than the negative group (P < 0.05). In ROC analysis, the critical T₁ value of Ki-67 positive lesions was 2 145 ms, Yoden index was 0.368, the sensitivity was 53.47%, the specificity was 83.33% and the area under the curve (AUC) was 0.640 (95%CI: 0.527-0.744). There were no significant differences in T₁ and T₂ values between Luminal A, Luminal B1, Luminal B2, Erb-B2 enriched and TNBC subtypes (P < 0.05). T₁ and T₂ values were lower in Luminal type lesion than those of TNBC type lesion (P<0.05). ROC curve analysis showed that the combined T₁ and T₂ values were more effective in differentiating Luminal/TNBC type than those of T₁ and T₂ values alone. Conclusion T₁ mapping can be used as one of the methods to predict the high or low expression levels of Ki-67 in IDC tumors. The combination of T₁ and T₂ values can improve the ability to predict Luminal/TNBC subtypes.

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Construction and verification of prediction model of type 2 diabetic nephropathy based on machine learning

WANG Xian, LIU Xiaming, CHEN Manyu, ZHAO Jun, WANG Lidong

2024, 52 (7): 775-780. doi: 10.11958/20231584

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Objective To search for independent predictive factors of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM), construct and validate an optional machine learning (ML) model for the risk of DKD. Methods A total of 528 patients with T2DM, hospitalized in the Endocrinology Department of Chengde Central Hospital from October 2019 to September 2020, were selected as the study objects, and patients were randomly divided into a training set (370 cases), and a validation set (158 cases). The training set was divided into the DKD group (89 cases) and the non-DKD group (281 cases) according to whether DKD existed. The general data and diagnostic examination of patients were performed by univariate analysis, in which variables with statistical differences were used to screen the best predictors by least absolute shrinkage and selection operator (LASSO) regression analysis. The best predictors were used to establish eight ML algorithms by three cross-validation methods, including Logistic regression (LR), K-nearest neighbor (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), naive Bayes (NB), artificial neural network (ANN), and extreme gradient lift (XGBoost). The optimal prediction model was selected by receiver operating characteristic (ROC) curve, Delong test and GiViTI calibration curve. Decision curve analysis (DCA) was used to evaluate the clinical practicability of the model. Results Age, alanine aminotransferase, creatinine, triglyceride, cystatin C, 25-hydroxy vitamin D and monocyte count were independent predictive factors of DKD. Eight ML models were established based on the above 7 predictors, and the ANN model performed best in the 8 ML models. The GiViTiI calibration curve indicated that the model had good accuracy (P>0.05), and the DCA showed that the prediction model curve had clinical practical value in the threshold probability range of 0.027-0.612. Conclusion In this study, the ANN model constructed in this study to predict the risk of DKD is helpful for early discrimination of high-risk T2DM patients with DKD.

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Research progress on the mechanism of the TGF-β signaling pathway in myelodysplastic syndrome

LIU Qingqing, LI Yiqiang, SHI Yushi, LU Haisong, CHENG Weimin

2024, 52 (7): 781-784. doi: 10.11958/20231620

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Myelodysplastic syndrome (MDS) is a malignant clonal disease with high heterogeneity in cytogenetics and molecular genetics, and the risk of progression to acute myeloid leukemia (AML) is extremely high. Transforming growth factor-β (TGF-β) is closely related to the pathogenesis of MDS. It is a key executor of immune homeostasis and immune tolerance, and can inhibit the expansion and function of many components of immune system. TGF-β signaling pathway can regulate hematopoietic cells and immune cells in microenvironment, inhibit their normal biological functions, and thus accelerate the progression of MDS. This study reviews regulatory effects of TGF-β signaling pathway on MDS blood cells, T lymphocytes, natural killer cells and macrophages in recent years, and provides a new perspective for the pathogenesis and treatment of MDS.

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