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  • Shan Zhang, Song-Hai Chen, Yan Liu, Chun-Yan Wang, Yi-Ming Fu, Yin-Ying Lu, Dong Ji, Guo-Feng Chen
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 157-162.

    Objective To investigate the effect of non-alcoholic fatty liver disease (NAFLD) on the overall survival of patients with hepatitis B virus-related hepatocellular carcinoma (HCC). Methods The hospitalized patients from June 2008 to December 2020 were screened according to inclusive and exclusive criteria, the clinical characteristics at the time of the initial diagnosis of HCC and time-to-event information of the enrolled patients were retrospectively collected. After stratified by the Barcelona Clinic Liver Cancer (BCLC) staging and then balanced with the stabilized inverse probability of treatment weighting(IPTW) between NAFLD and non-NAFLD group, the Kaplan-Meier survival curve, log-rank test and Cox regression were used to compare the prognosis of patients with HBV-related HCC between NAFLD group and non-NAFLD group. The endpoint of this study was HCC-related death. Results A total of 833 patients were enrolled in the study. Among them, 465 patients in resectable group and 368 in non-resectable group. There were 161 (34.6%) patients with NAFLD in resectable group, and 76 (20.7%) patients with NAFLD in non-resectable group. After stabilized IPTW weighting, all indicators showed no statistical difference between two groups. Survival analyses showed that median survival time of NAFLD patients with HBV-related HCC was significantly longer than that of non-NAFLD patients. The 3-, 5-, and 8-year cumulative survival rates of NAFLD patients in resectable group were 96.9%, 82.1% and 41.2%, which were significantly higher than 91.1%, 60.4% and 13.7% of non-NAFLD patients (P<0.01). Cox analysis showed that NAFLD was the protective factor of survive (HR=0.473, 95%CI 0.356-0.627, P<0.01). Similarly, those of NAFLD patients in non-resectable group were 76.8%, 53.7% and 18.4%, which were significantly higher than those of non-NAFLD patients (53.0%, 25.7% and 2.5%, respectively, P<0.01). Cox analysis also showed that NAFLD was the protective factor of survive(HR=0.358, 95%CI 0.247-0.518, P<0.01). Conclusion The cumulative survival rate of HBV-related HCC patients with NAFLD is higher than that of patients without NAFLD.

  • Hang-Bin Zheng, Guang-Lan Xu, Guo-Sheng Li, Yuan-Ling Li, Yi-Hui Guo
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 231-236.

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by airway inflammation,lung tissue destruction and airflow limitation associated with airway remodeling. As an important form of cellular communication,extracellular vesicles (EVs) are capable of selectively transmitting signals to nearby or distant cells to regulate their function and phenotype, and thought to play an indispensable role in lung disease. EVs can be released by bronchial epithelial cells, lymphocytes,neutrophils, macrophages, vascular endothelial cells and mesenchymal stem cells upon activation or apoptosis under specific conditions. The role of EVs derived from these cells in the pathogenesis and progression of COPD is reviewed in present paper for contributing a more comprehensive and detailed understanding of the role of EVs in the complex pathophysiology of COPD.

  • Ke-Xin Feng, Wen-Yan Wang, Jia-Xiang Liu, Qing-Yao Shang, Chen-Xuan Yang, Fei Ren, Xin Wang, Xiang Wang
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 204-210.

    Objective To analyze the clinical and pathological features of primary breast lymphoma (PBL) and explore the value of appling rituximab for the prognosis of patients with PBL. Methods The clinicopathological characteristics and therapeutic effect of rituximab were retrospectively analyzed of 65 patients with PBL admitted in the Cancer Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences from January 1, 2000 to January 31, 2020. According to different treatment methods,they were divided into CHOP group [n=41, using CHOP regimen (cyclophosphamide + epirubicin + vincristine + prednisone)] and RCHOP group (n=24, using rituximab combined CHOP regimen treatment). Patients received telephone follow-up or outpatient review until January 31, 2022 or mortality. Univariate regression analysis and multivariate regression analysis were used to analyze the factors influencing the prognosis of patients with PBL. Results All the 65 patients were female, aged 57(23, 86) years old.The tumor size was 2.8(0.4, 5.3) cm, and the follow-up time was 4.3(0.7, 21.8) years. There was a statistically significant difference in Ki-67 expression between the two groups (P=0.043), and there was no significant difference in other clinicopathological features and treatment plans (P>0.05). The 5- and 10-year overall survival rate of the 65 PBL patients were 93.4% and 87.9%,and the 5- and 10-year progression-free survival rate were 88.2% and 79.6%, the central nervous system recurrence rate was 4.6%.The 5-year overall survival rate in CHOP group was 93.8% and in RCHOP group was 92.9% (P=0.733), and 5-year progression-free survival rate was 89.9% in CHOP group, and in RCHOP group was 92.9% (P=0.897). Multivariate logistic regression analysis showed the international prognostic index (IPI) score and the level of β2 microglobulin were the independent risk factors of overall survival (P<0.05). Conclusions There is no special clinical manifestation of PBL. The definite diagnosis mainly depends on histopathological examination and immunophenotype. Radical surgical resection can not improve the prognosis of patients, and comprehensive treatment based on full-term chemotherapy should be adopted; whether patients with PBL received rituximab was not associated with the survival benefits.

  • Ya-Meng Du, Ning Kang, Li-Li Zhao, Shuo-Wen Bai, Qian-Qian Li, Xiao-Xia Niu, Jia Li, Dong Ji, Chun-Yan Wang
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 151-156.

    Objective To analyze the risk factors of esophago-gastric fundal varices (EGV) in patients with hepatitis B virus (HBV)-related compensated cirrhosis, and to compare the clinical performance of multiple noninvasive prediction models for EGV evaluation. Methods A retrospective analysis was performed on the clinical data of patients with hepatitis B cirrhosis from two centers from January 2017 to December 2019. All patients underwent biochemical examination, gastroscopy, and liver stiffness measurement (LSM). AST-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4) and LSM-spleen diameter (SD)-to-platelet ratio score (LSPS) were calculated. According to the results of gastroscopy, they were divided into EGV and non-EGV group. The high-risk factors of EGV were explored by binary logistic regression. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to evaluate the clinical performance of each indicator in predicting EGV. Results A total of 470 patients were enrolled, including 292 in the non-EGV group and 178 in the EGV group. Logistic regression analysis showed low PLT (platelet)(OR=0.99, 95%CI 0.98-0.99), high SD (spleen diameter)(OR=1.02, 95%CI 1.01-1.03) and high LSM(OR=1.04, 95%CI 1.02-1.07) were high risk factors for EGV (all P<0.05). The AUC of LSPS in predicting EGV [0.75(95%CI 0.71-0.79)] was significantly higher than that of PLT [0.72(95%CI 0.67-0.76)], SD [0.69(95%CI 0.64-0.73)], LSM [0.67(95%CI 0.63-0.72)], APRI [0.69(95%CI 0.65-0.74)] and FIB-4 [0.66(95%CI 0.62-0.71)](P<0.05). The LSPS score in EGV group was significantly higher than that in non-EGV group [2.7(1.3, 5.0) vs. 1.0(0.5, 1.7), P<0.001]. With the aggravation of EGV, LSPS score showed an upward trend (r=0.426, P<0.001). The cutoff value of LSPS for high risk of EGV was >3.5, the corresponding specificity and positive predictive value (PPV) ratio were 93.6% and 79.8% respectively. The cutoff value of LSPS for low risk of EGV was<1.3, its sensitivity and negative predictive value were 75.5% and 81.1% respectively. Conclusions Incorporating three risk factors including low PLT, high LSM and SD, the LSPS in predicting EGV in patients with compensated hepatitis B cirrhosis is better than ARPI, FIB-4, or LSM, and can reduce the need for gastroscopy.

  • Liao Wan, Shuang Wang, Jin-Hong Yu, Jing-Ru Ding, Qing Zou, Xi-Yan Wang
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 198-203.

    Objective To investigate the effect of exposure to bisphenol A (BPA) on maturation and oxidative stress injury in mouse oocytes in vitro. Methods Oocytes from female ICR mice were randomly divided into control group, DMSO group,and BPA group. Mouse oocytes in control group was cultured normorly in vitro,while added 0.1% DMSO in DMSO group, and 45 μmol/L BPA in 0.1% DMSO in BPA group. MII oocytes and oocytes stagnated in the GV phase were obtained .The levels of ROS in MII and GV oocytes of each group was detected by kit. The expression level of antioxidant enzyme in MII and GV oocytes was detected by immunofluorescence and Western blotting. Results Compared with control group, exposure to 45 μmol/L BPA during in vitro maturation, resulted in a significant decrease in the maturation rate of mouse oocytes in BPA group (26.32%±1.12%vs. 98.22%±0.89%, P<0.05), the levels of ROS in GV and MII oocytes were significantly higher (P<0.05), the levels of antioxidant enzymes CAT and SOD2 in GV and MII oocytes were significantly decreased (P<0.05). Conclusion Exposure to 45 μmol/L BPA increased ROS production and inhibited antioxidant enzyme expression, leading to oxidative stress damage of mouse oocytes and thus inhibiting oocyte maturation in vitro.

  • Chun-Yan Wang, Dong Ji, Yan Chen, Guang-De Zhou, Zheng Dong, Jian-Jun Wang, Guo-Feng Chen, Yong-Ping Yang
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 143-150.

    Objective To identify the high-risk factors and establish a nomogram for evaluating significant histological response (SHR) in chronic hepatitis B (CHB) patients receiving entecavir treatment. Methods Treatment-naive CHB patients who were presented to 14 hospitals, from October 2013 to October 2014, were enrolled and treated with entecavir for 72 weeks,prospectively. All the patients who underwent paired biopsies at treatment baseline and week 72 were analyzed. According to whether SHR (Ishak fibrosis score F≤2 points and histology activity index HAI≤4 points) was obtained during treatment, they were assigned to response group (n=160) and non-response group (n=567). High-risk factors were identified by multivariate logistic regression, and then were incorporated into a nomogram model. The discrimination, calibration and clinical applicability of nomogram were assessed by concordance index (C-index), calibration curve and clinical decision curve (DCA). Results After 72 weeks of treatment, regression of fibrosis, improvement of inflammation, virologic response, alanine aminotransferase (ALT)normalization and HBeAg seroconversion were 51.2%, 74.4%, 86.0%, 83.5% and 13.3%, respectively, however, 49.0% (306/625) of patients with virological response and 43.4% (165/380) of patients with ALT normalization did not achieved regression of fibrosis.Logistic regression analysis showed that baseline age (OR=0.978, 95%CI 0.958-0.998, P=0.030), platelet (PLT) (OR=1.005, 95%CI 1.001-1.010, P=0.030), liver stiffness measurement (LSM) (OR=0.931, 95%CI 0.892-0.972, P=0.001) and 72-week ALT (OR=0.980,95%CI 0.964-0.996, P=0.016), 72-week LSM (OR=0.858, 95%CI 0.782-0.941, P=0.001) were independent high-risk factors associated with SHR. The C-index of the nomogram model based on the above factors was 0.784, which was significantly better than 72-week AST/PLT ratio (APRI) (0.643), fibrosis-4 (FIB-4) (0.691) and LSM (0.735) alone, and had well-fitted calibration curves and DCA. Conclusions Incorporating baseline age, PLT, LSM, 72-week ALT and 72-week LSM, the established individualized nomogram model for evaluating significant histological response in CHB patients receiving antiviral therapy has good predictive performance and can reduce the need of liver biopsy.

  • Dong Ji, Yong-Ping Yang
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 132-137.

    Chronic hepatitis B virus infection is prevalent worldwide, and can progress to liver cirrhosis and even hepatocellular carcinoma if left untreated. Over the past 20 years, due to the approval and upgrading of nucleoside/nucleotide analogues, a qualitative leap has been made in inhibiting HBV replication. Most chronic hepatitis B (CHB) patients can achieve relief of hepatocellular inflammation, regression of hepatic fibrosis, improvement of life quality and survival time. With the extension of treatment time and the enrichment of treatment experience, new hot clinical issues gradually emerge, including the clinical application of new serum markers, the expansion of indicators for CHB antiviral treatment, the formation of CHB treatment plan and the improvement of long-term prognosis, which derserve further clinical attention.

  • Jia-Lin Qu, Wei Zou, Ting-Ting Luo
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 218-223.

    Objective To investigate the effects of hepatitis B virus (HBV) and liver function status on the occurrence and development of gestational diabetes mellitus (GDM). Methods The medical data of 628 pregnant women, who underwent prenatal examination and delivery in Chongqing Health Center for Women and Children from January 2018 to October 2021, were collected and retrospectively analyzed. Depending on whether infected with HBV, the patients were divided into HBV positive group(n=389) and HBV negative group (n=239). Those in HBV positive group were then further divided into normal liver function group(n=301) and abnormal liver function group (n=88) according to the liver function status in the second trimester of pregnancy so as to analyze the influence of HBV infection and liver function status on the occurrence and development of GDM. A total of 137 pregnant women who met the diagnostic criteria of GDM were divided into HBV positive group (n=97) and HBV negative group(n=40) according to the different HBV infection status. Those in HBV positive group were then divided into normal liver function group (n=62) and abnormal liver function group (n=35) according to their liver function status in the second trimester, so as to analyze the influence of HBV infection on blood glucose and postpartum blood glucose in GDM patients and adverse pregnancy outcomes. Results The fluctuation of blood glucose levels of pregnancy OGTT 1 h and 2 h was more obvious in pregnant women with positive HBV infection than those in negative group of HBV infection (P<0.05). The incidence of GDM was increased (24.9%vs. 16.7%) and gestational age was shortened in the pregnant women with positive HBV infection (P<0.05). Among the pregnant women with positive HBV infection, the average age, fasting blood glucose in the second trimester, OGTT 1 h, 2 h blood glucose and the incidence of GDM were higher in those with abnormal liver function (39.8% vs. 20.1%) than in those with normal liver function (P<0.05). HBV-infected GDM pregnant women with abnormal liver function developed higher blood glucose level in the second trimester of pregnancy, fasting blood glucose level within 6-12 weeks postpartum and a higher risk of impaired glucose tolerance than those with normal liver function (P<0.05). The incidence of GDM in the second pregnancy of pregnant women with HBV infection was higher than those in the first pregnancy (P<0.05). The rate of cesarean section and postpartum hemorrhage was higher in GDM with HBV infection pregnant women than those GDM pregnant women with normal liver function (P<0.05). Conclusions HBV infection with liver function damage can increase the incidence of GDM. GDM patients with HBV infection and liver function damage have a higher risk of adverse pregnancy outcomes. HBV infection may prolong the recovery time of postpartum blood glucose metabolism in pregnant women.

  • Dian Lou, Li Liu, Wei-Wei Qin
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(2): 211-217.

    Objective By literature review to retrospectively study the diagnosis and treatment process of decitabine combined with ruxolitinib in treatment of elderly patient with atypical chronic myeloid leukemia (aCML) for improving the understanding of aCML. Methods To report a case data of elderly aCML patients with CSF3R T618I mutation and the clinical treatment process using decitabine combined with ruxolitinib. Search CNKI, Wanfang data knowledge service platform, PubMed database (as of December 2021). Combined with literature reports to summarize the clinical characteristics of aCML and the effectiveness and safety in treatment applying decitabine combined with ruxolitinib. Results A case of 72-year-old man, admitted to our hospital since fatigue and dizziness for more than 1 month, and diagnosed as aCML with obviously increased white blood cells, granulocytic proliferation and granulocytic dysplasia with primitive cells <20%, and CSF3R T618I mutation detected by next-generation sequencing (NGS) analysis. After targeted therapy with ruxolitinib and 4 courses of treatment with decitabine, the patient achieved complete remission (CR) on morphology and had a good response on molecular. The patient's primary disease remained stable by maintenance therapy with ruxolitinib. A total of 11 cases treated with hypomethylating agents such as decitabine and azacitidine in aCML were found in literature, including 8 cases treated with decitabine alone [the CR rate was 87.5%(7/8)],2 cases treated with azacitidine alone [the effective rate was 50.0%(1/2)], and 1 case treated with decitabine combined with CAG(recombinant human granulocyte colony-stimulating factor + cytarabine + aclacinomycin) chemotherapy and achieved CR. A total of 4 cases treated with ruxolitinib alone in CSF3R T618I mutant aCML were found in literature and the overall efficiency was 50.0%(2/4). No case treated with drug combination in treatment of decitabine and ruxolitinib were found by searching literature. Conclusion aCML is a kind of rare disease, the diagnosis is based on morphological grounds only. The drug combination of decitabine and ruxolitinib is effective and well tolerable in this elderly patient with aCML.

  • Yan-Rong Yang, Man-Man Xu, Yu Chen
    Medical Journal of Chinese People’s Liberation Army. 2023, 48(1): 7-12.

    Acute-on-chronic liver failure (ACLF) is an acute decompensated syndrome that occurs on the basis of chronic liver disease, with rapid disease progression and poor prognosis, thus being an important cause of death in patients with cirrhosis. Predisposing factors play an important role in the occurrence, progression and prognosis of ACLF, which are heterogeneous in different definitions and regions. With the development of medical and health services and changes in lifestyles, the composition of predisposing factors also changes. These factors cause damage to organ function in various ways, leading to different types of organ failure and prognosis. Early warning of the predisposing factors can prevent the occurrence of ACLF. Actively removing predisposing factors can improve the prognosis of ACLF. Reasonable management of precipitating factors is important for ACLF.