To investigate the impact of maternal hepatitis B virus (HBV) carrier state on twin pregnancy outcomes. Methods From January 2004 to December 2012, 569 women with twin pregnancy were hospitalized in Nanjing Drum Tower Hospital. Thirty-two women positive for hepatitis B surface antigen (HBsAg)(negative for hepatitis B e antigen, with normal liver function before conception)were included in the HBsAg-positive group and the other 537 women were included in the HBsAg-negative group. The pregnancy outcomes of the two groups were compared by t test and Chi-square test. The risk factors for neonatal birth weight were analyzed by multivariate regression analysis. Results Compared with the HBsAg-negative group, the HBsAg-positive women had a higher incidence of abnormal liver function (alanine aminotransferase≥50 U/L) [18.8% (6/32) vs 5.8% (31/537), χ2=6.367, P=0.012]. The incidence of gestational diabetes mellitus was 21.9% (7/32) in the HBsAg-positive group, which was higher than in the HBsAg-negative group [11.6% (62/537)], although the difference was not significant (χ2=2.132, P=0.144). The incidences of intrahepatic cholestasis of pregnancy,hypertensive disorders complicating pregnancy, premature rupture of membranes, placenta previa, fetal distress, postpartum hemorrhage, preterm birth, caesarean section, umbilical cord around the neck, meconium-staining amniotic fluid and neonatal asphyxia were no statistical difference between two groups (all P<0.05, respectively). Multivariate regression analysis showed that gestational diabetes mellitus (β=67.869, 95%CI: 0.494-135.244, P=0.048), maternal age (β=6.592, 95%CI: 2.020-11.880, P=0.006) and gestational age (β=164.069, 95%CI:154.426-173.712, P<0.01) were risk factors for neonatal birth weight, but not the maternal HBsAg-positive status (β=78.864, 95%CI: -16.950-174.678, P=0.107). Conclusion Twin pregnancy and HBV carrier state increase the risk of abnormal liver function, but not other adverse pregnancy outcomes and newborn diseases.

Granzyme exists in the cytotoxic granules and belongs to a highly homologous serine protease family. Granzyme is synthesized and released from natural killer cells and cytotoxic lymphocytes. It induces multiple programmed death with the participation of perforin and is an important medium for immune cells to exert anti-tumor effects. This article reviews the granzyme-mediated tumor cell death and the relationship between granzyme and kinds of ways of cell apoptosis, in order to provide new theoretical basis and therapeutic strategies for tumor therapy.

Objective:To evaluate the effect of surgical resection on the prognosis of patients with China Liver Cancer Staging (CNLC)-Ⅱ hepatocellular carcinoma.Methods:Patients with CNLC-Ⅱ hepatocellular carcinoma between 2004 and 2015 from the SEER database were included. A total of 3 764 patients were enrolled, with the age (64±11)(18-93) years, including 2 935 males and 829 females. Among them, 2 825 patients underwent non-surgery treatment (NST), 510 patients underwent liver resection (LR), and 429 patients underwent local ablation (LA). The effects of different treatment modalities on overall survival (OS) and cancer-specific survival (CSS) were evaluated by using Kaplan-Meier analysis, propensity score matching analysis, and subgroup analysis. Cox regression were used to analyze the prognosis.Results:The 1-, 3- and 5-year overall survival rates of LR group were 76.3%, 51.9% and 34.0% respectively, which were significantly higher than those in LA group (71.7%, 34.8% and 24.9%, χ 2=18.50, P<0.001), and those in NST group (46.8%, 16.1% and 8.4%, χ 2=276.00, P<0.001). Similarly, the 1-, 3-, and 5-year cancer-related survival rates of LR group were 80.2%, 58.9%, and 41.8% respectively, which were significantly higher than those in LA group (75.9%, 42.8%, and 32.6%, χ 2=15.20, P<0.001), and those in NST group (52.3%, 21.5% and 12.7%, χ 2=245.00, P<0.001). Cox regression analysis showed that age, tumor size, chemotherapy, pathological grade, AFP levels, and surgical modalities were independent prognostic factors (all P<0.05). Propensity score matching analysis further showed that the prognosis of LR patients was significantly better than NST group [median OS: 52 months (95% CI: 38-60) vs. 10 months (95% CI: 7-16), P<0.001; median CSS: 59 months (95% CI: 44-77) vs. 11 months (95% CI: 8-18), P<0.001]. However, subgroup analysis showed no clinical benefit from surgical resection when the tumor size exceeded 10.0 cm. Conclusions:It was suggested that surgical resection could improve the OS and CSS of patients with CNLC-Ⅱ hepatocellular carcinoma.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.
Animals ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Experimental ; immunology ; pathology ; therapy ; Receptor, ErbB-2 ; immunology ; Receptors, Antigen, T-Cell ; immunology ; Stomach Neoplasms ; immunology ; pathology ; therapy ; Tumor Cells, Cultured

ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg^-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.