Gastric cancer(GC)is one of the most common malignant tumors,and most GC patients in China are diagnosed as progressive GC at their first visit and late stage patients fail to have surgical treatment.The effects of conventional treatments,including chemotherapy,radiotherapy and targeted therapy,are limited and may induce poor prognosis.As a new treatment in hematological malignancy,chimeric antigen receptor(CAR)-T cell(CAR-T)immunotherapy is indicated as a promising treatment for advanced GC,which paves a new way for the GC immunotherapy.However,there are still some obstacles to overcome,such as the heterogeneity of GC,immunosuppression of tumor microenvironment,tumor target antigen escape and off-target toxicity.In this review,the CAR structure,therapeutic principle of CAR-T,and the main targets and treatment status of CAR-T immunotherapy for advanced GC are reviewed;the challenges faced by CAR-T immunotherapy in GC are discussed,so as to provide new ideas for the clinical immunotherapy of advanced GC.

Objective To use network pharmacology to mine and predict the targets and related signaling pathways of Miaoyao Yiai Tang(Miao-Yi-Ai-Tang,MYAT)in the treatment of small cell lung cancer(SCLC).And animal experiments to verify its mechanism of action,to provide a theoretical basis for basic experiments and clinical applications.Methods The active ingredients of MYAT were obtained from the TCMSP database,combined with PubMed data,Swiss Target Prediction database and Uniprot database to obtain potential targets;SCLC-related genes were collected through the DrugBank database,Genecards database,OMIM database and TTD database,and the Venny 2.1 platform After obtaining the intersection genes of MYAT and SCLC,import them into the STRING database,construct a protein-protein interaction(PPI)network,use Cytoscape 3.9.1 software for visual analysis,and use Metascape database for GO enrichment analysis and KEGG pathway analysis,to predict the direct action target and signaling pathway of MYAT in the treatment of SCLC.Using AutoDock Tools 1.5.7 software for molecular docking to verify the close relationship between the two.For cytological experiment verification,the cultured cells were treated with MYAT and the expression of β-catenin,AXIN,c-myc was detected by qPCR,and the expression of β-catenin in the cells was detected by Western blot;animal experiments were established to establish a subcutaneous xenograft tumor model of lung cancer NCI-H446,to observe the effect of MYAT on tumor growth.Results A total of 65 effective components of MYAT,1368 SCLC genes,and 260 MYAT-SCLC intersection genes were obtained.Enrichment analysis showed that they were related to cancer pathways,PD-L1/PD-1 pathways,NF-κB pathways,Wnt and other signaling pathways.The results of molecular docking validation showed that the binding energies of active components and core target proteins were all<0 kJ·mol-1,which indicated that the protein could spontaneously bind to active components and be stable.Cell experiments showed that the expression levels of β-catenin,c-myc and AXIN mRNA were significantly down-regulated in the MYAT group(P<0.05).Animal experiments show that:MYAT can significantly inhibit the growth of tumors in vivo.Conclusion Miao-Yi-Ai-Tang can inhibit the proliferation of small cell lung cancer through Wnt/β-catenin signaling pathway.

Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.
Animals ; Mice ; Tacrolimus ; Liver ; Cholesterol, LDL ; Autophagy ; Disease Models, Animal

Objective To investigate the risk factors for short-term prognosis in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods A retrospective analysis was performed for the clinical data of 119 patients with HBV-related ACLF who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2019 to October 2020, and according to their survival status on day 90, they were divided into death group and survival group. The patients were given antiviral therapy with entecavir or tenofovir. Related clinical data were collected, including alanine aminotransferase (ALT), aspartate aminotransferase, cholinesterase (ChE), albumin (Alb), cholesterol, alpha-fetoprotein, and HBV DNA at baseline, as well as the incidence rate of important complications. Model for End-Stage Liver Disease (MELD) score was also calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-squared test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for the 90-day prognosis of patients with HBV-related ACLF and establish a new predictive model; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the new model in predicting the prognosis of HBV-related ACLF. Results Of all patients, 33 died within 90 days, resulting in a mortality rate of 27.7%. There were significant differences between the survival group and the death group in age, ALT, Alb, ChE, MELD score, and incidence rates of hepatic encephalopathy, primary peritonitis, and hepatorenal syndrome (all P < 0.05). The logistic regression analysis showed that baseline hepatic encephalopathy (odds ratio [ OR ]=10.404, 95% confidence interval [ CI ]: 2.522-42.926, P =0.001), serum Alb at baseline ( OR =0.853, 95% CI : 0.764-0.952, P =0.005), and MELD score at baseline ( OR =1.143, 95% CI : 1.036-1.261, P =0.008) were independent predictive factors for the short-term prognosis of patients with HBV-related ACLF. A new predictive model was established based on the combination of these three indices, and the ROC curve analysis showed that this new model had an area under the curve of 0.833, while MELD score had an area under the ROC curve of 0.672. Conclusion As for the evaluation of the 90-day prognosis of patients with HBV-related ACLF, the new prognostic model established based on hepatic encephalopathy, Alb, and MELD score has a better predictive value than MELD score alone.

Objective:To investigate the correlation between RNF213 gene p. R4810K polymorphism and posterior cerebral artery involvement in Chinese children with familial moyamoya disease.Methods:Children with familial moyamoya disease admitted to the Department of Neurosurgery, the Fifth Medical Center of PLA General Hospital from August 2004 to June 2018 were enrolled, and they were divided into posterior cerebral artery involved group and posterior cerebral artery uninvolved group. RNF213 gene p. R4810K single nucleotide polymorphism was detected. Multivariate logistic regression analysis was used to determine the independent risk factors for posterior cerebral artery involvement. Results:A total of 65 children with familial moyamoya disease were enrolled. Their age was 6.98±4.46 years and 37 (56.9%) were male. The first symptom of 55 children (84.6%) was cerebral ischemia, and 37 (56.9%) involved posterior cerebral artery. There were 3 (4.6%) children with p. R4810K AA genotype, 26 (40.0%) with GA genotype, and 36 (55.4%) with GG genotype. The p. R4810K genotype distribution in the posterior cerebral artery involved group was statistically different from that in the uninvolved group (GA+ AA genotype: 56.8% vs. 28.6%; χ2=5.124, P=0.024), and there were no statistical difference in gender, age, first symptom, and genetic pattern. Multivariate logistic regression analysis showed that after adjusting the first onset age and gender, p. R4810K G>A mutation was the only independent risk factor for posterior cerebral artery involvement (odds ratio 3.240, 95% confidence interval 1.082-9.705; P=0.020). Conclusion:The p. R4810K polymorphism of RNF213 gene is associated with posterior cerebral artery involvement in Chinese children with familial moyamoya disease.

Objective To investigate the clinical efficacy of percutaneous minimally invasive anchorage in the treatment of acute closed rupture of Achilles tendon. Methods A retrospective casecontrol study was conducted on the clinical data of 32 patients (16 cases on the left side and 16 cases on the right side) with acute closed Achilles tendon rupture treated from January 2015 to January 2017. There were 27 males and five females, aged 24-67 years (mean, 40.8 years). The patients were divided into treatment group which adopted percutaneous minimally invasive combined with anchor suture and control group which used simple minimally invasive suture, with 16 cases in each group. The operation time, hospitalization time, sural nerve injury, single foot heel raise at 3 months and 6 months, difference of calf circumference on the rupture surface between the affected side and healthy side at 6 months, ankle back foot score scale (AOFAS), and infection at 6 months were recorded. Results All patients were followed up for average 8.9 months (range, 6-12 months). In treatment group, the operation time was (35.75 ±3.10) minutes and hospitalization time was (8.38±1.62) days. The AOFAS score was(92.12 ±5.86)points. The result of single foot heel raise was positive in one case at 3 months and in 0 case at 6 months. The difference of calf circumference on the rupture surface between the affected side and healthy side at 6 months was (2.23 ±0.97)cm. In the control group, the operation time was (33.43± 3.89)minutes and hospitalization time was (8.50±1.75)days. The AOFAS score was (91.00 ±7.15) points at 6 months. The result of single foot heel raise was positive in eight cases at 3 months and in 0 case at 6 months. The difference of calf circumference on the rupture surface between the affected side and healthy side at 6 months was (1.64 ±2.34) cm. There were no significant differences between the two groups in operation time, hospitalization time, the AOFAS score at 6 months, and the results of single foot heel raise at 6 months(P ＞0.05). Treatment group had better results than control group in terms of the difference of calf circumference on the rupture surface between the affected side and healthy side at 6 months as well as the result of single foot heel raise at 3 months (P ＜ 0.05). No infection and sural nerve injury were found in either group. Conclusion The repair of Achilles tendon rupture by percutaneous minimally invasive anchor technique can help patients achieve heel raise early, obtain better muscle capacity, and return to work earlier.

Obiective To explore the risk factors of endometriosis-associated ovarian cancer (EAOC) in women with ovarian endometriosis aged 45 years and older in China. Methods The medical records of total 1038 women aged 45 years and older with a surgicopathological diagnosis of ovarian endometriosis treated at Peking Union Medical College Hospital from December 1994 to December 2014 were reviewed. Histology evaluation determined ovarian endometriosis with (n=30) or without (n=1008) ovarian cancer. Results (1) There were 30 (2.9%, 30/1018) cases confirmed as having EAOC. Clear cell carcinoma (63.3%, 17/30) and endometrioid adenocarcinoma (23.3%, 7/30) were commonly observed subtypes and 70.0%of EAOC patients were at stageⅠ. (2) Compared women with ovarian endometriosis in the same age group,patients with EAOC were older (50.8 vs 48.5 years, P=0.002). There were more in postmenopausal status at diagnosis of EAOC (P＜0.01). There were more found with a mass ≥8 cm (P＜0.01). Women with EAOC had higher prevalence of coexisting endometrial disorders (P=0.003). No differences were found in preoperative CA125 value and infertile or nulliparous women (P＞0.05). Conclusions For women with ovarian endometriosis aged 45 years and older, the subgroup of patients characterized by postmenopausal status and ovarian endometrioma (≥8 cm) have a higher risk of EAOC. Active intervention or intensive follow-up should be considered for this population group, especially for those concurrent with endometrial disorders.

Exocyst complex is known to function in the exocytosis network, however, the molecular mechanism is unclear yet. Using UV/trimethylpsoralen mutagenesis, the sec-10 (one component of the exocyst complex) knockout mutant of C. elegans was obtained for the first time. The drug sensitive assays revealed clearly that the sec-10 gene affected the neural signal transmission, however, the electrophysiological assay showed the function of the ionotropic receptors in the neuromuscular junctions (NMJs) were unaltered compared with the wild type (WT). Thus it was assumed that the sec-10 gene might not influence the known ionotropic receptors in the NMJs, but some other pathways instead.