To investigate the awareness of cognitive impairment disorders among residents of the Xizang Autonomous Region and its influencing factors, thereby providing a basis for targeted prevention and treatment efforts.

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.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe ^-/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Objective:To investigate the complement C3a receptor 1 (C3AR1) expression in glioma and its mechanism in progressing malignancy.Methods:(1) The C3AR1 mRNA expression data and clinical information were obtained in 607 glioma patients from The Cancer Genome Atlas (TCGA) database and 656 glioma patients from Chinese Glioma Genome Atlas (CGGA) database; the differences in C3AR1 mRNA expression were analyzed among gliomas with different World Health Organization (WHO) grading. The overall survival and disease-free survival were compared between high and low C3AR1 mRNA expression patients obtained from TCGA database by Gene expression profiling interactive analysis (GEPIA). Gene body (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of C3AR1 related differentially expressed genes were performed by DAVID database. Correlation of C3AR1 mRNA expression with immune cell infiltration was analyzed using TIMER online website. (2) The brain tissues from 3 non-tumor patients and 9 glioma patients surgically resected in Department of Neurosurgery, First Affiliated Hospital of Xinxiang Medical University from January 2019 to September 2021 were collected; the C3AR1 protein expression was detected by Western blotting. (3) The in vitro cultured U87 and U251 cells were divided into negative control group and C3AR1 knockdown group ( C3AR1 being knocked down by lentivirus transfection); and CCK-8 assay, plate cloning assay and Transwell assay were used to detect the proliferation rate, number of colony formation and number of membrane penetrating cells. Western blotting was used to detect the nuclear factor-κB (NF-κB) signaling pathway protein expressions. Results:(1) In TCGA database, the C3AR1 mRNA expression in gliomas of WHO grading II, grading III and grading IV increased sequentially, with significant differences ( P<0.05). In CGGA database, the C3AR1 mRNA expression in glioma of WHO grading IV was statistically higher than that in gliomas of WHO grading II and grading III ( P<0.05). GEPIA showed that the overall survival and disease-free survival in the low C3AR1 mRNA expression group were statistically higher than those in the high C3AR1 mRNA expression group ( P<0.05). GO function analysis and KEGG pathway enrichment analysis revealed that C3AR1 related differentially expressed genes were more enriched in such biological processes and signaling pathways as calcium homeostasis, membrane structural valves, proton transmembrane transporter protein activity, chemokine signaling pathway and NF-κB signaling pathway. TIMER showed that C3AR1 mRNA expression in glioblastoma and low-grade glioma was positively correlated with infiltration degrees of B cells, CD4 + T cells, neutrophils, macrophages and dendritic cells, and C3AR1 mRNA expression in glioblastoma was negatively correlated with infiltration degree of CD8 + T cells ( P<0.05). (2) C3AR1 protein expression in glioma tissues was significantly higher than that in non-tumor tissues. (3) Compared with the negative control group, the C3AR1 knockdown group group had significantly lower proliferation rate, smaller numbers of colony formation and membrane penetrating cells, and lower expressions of NF-κB, phosphorylated (p)-NF-κB, p-NF-κB inhibitory protein (IκB)α, p-I-κB kinase (IKK)α and N-cadherin, and significantly higher E-cadherin expression. Conclusion:C3AR1 is highly expressed in glioma and progresses malignancy through NF-κB signaling pathway.

Objective:To explore the role of intra-abdominal pressure (IAP) monitoring in evaluating the efficacy of early enteral nutrition (EN) in patients with acute pancreatitis (AP).Methods:The clinical data were collected from the AP patients in department of criticle care medicine of Baoshan Branch of Huashan Hospital Affiliated to Fudan University from July 2020 to June 2021. The patients were divided into three groups according to their treatments: no gastrointestinal decompression with fasting group, gastrointestinal decompression with fasting group, gastrointestinal decompression with indwelling jejunal tube within 24 hours group. The data of white blood cell (WBC), procalcitonin (PCT), serum amylase (AMY) and IAP were analyzed before and after treatment, the initiation time oral feeding were also analyzed.Results:The decrease of WBC, PCT, AMY, and IAP in gastrointestinal decompression with indwelling jejunal tube within 24 hours group were significantly greater than those in the other groups [WBC (×10 9/L): -1.72±0.74 vs. -0.68±0.36, -1.23±86.97; PCT (μg/L): -3.14±5.19 vs. 0.06±0.48, -1.57±0.78; AMY (U): -148.43±75.89 vs. -74.85±78.84, -93.78±1.17; IAP (cmH 2O, 1 cmH 2O≈0.098 kPa): -4.82±1.66 vs. 0.36±1.32, -3.22±4.36, all P < 0.05]. There were no correlation between the changes of IAP and the changes of WBC, PCT or AMY in the non-gastrointestinal decompression with fasting group and the gastrointestinal decompression with indwelling jejunal tube within 24 hours group (all P > 0.05). The decreasing trend of IAP in patients with gastrointestinal decompression with fasting group was positively correlated with the change of AMY ( r = 0.65, P < 0.001). The initiation time of oral feeding in gastrointestinal decompression with indwelling jejunal tube within 24 hours group was significantly shorter than that in the other groups (hours: 89.538 vs. 111.273, 109.714), the difference was statistically significant ( P < 0.05). Conclusions:IAP monitoring, as an emergency means of monitoring the efficacy of early EN in AP patients, has the advantages of simplicity, efficiency and rationality, which has a more objective basis than the previous empirical treatment and open oral feeding.

BACKGROUND: Porous silicon carbide has excellent physical and chemical properties and can be used to repair complex shapes and long weight-bearing bone defects, but it has no biological activity and cannot promote bone remodeling and integration. OBJECTIVE: A tantalum (Ta) coating was deposited on the surface of the porous silicon carbide scaffold to evaluate its biological activity. METHODS: The chemical vapor deposition method was used to deposit a Ta coating on the surface of the porous silicon carbide scaffold. The optimal experimental parameters were explored by setting different gas reaction flow rates and temperatures. The Ta coating was prepared with the best experimental parameters to test the mechanical properties of porous Ta. Human osteoblasts were co-cultured with the Ta coating specimens, and were observed by scanning electron microscopy after 3 and 7 days of cultivation. RESULTS AND CONCLUSION: (1) After the optimization of experimental parameters, the best experimental conditions were controlled as follows: deposition temperature of 1 050 °C, hydrogen flow rate of 180 mL/min and chlorine flow rate of 100 mL/min. (2) The compressive strength of the Ta coated specimen was (61.4±3.2) MPa; the yield strength was (45.8±2.9) MPa; and the elastic modulus was 4.8 GPa. (3) Scanning electron microscopy demonstrated that after 3 days of co-cultivation, a large number of cells adhered to the surface of the porous silicon carbide scaffold that is coated with Ta and the porous structure. Some of the cells protruded from the pseudopod and were connected to each other. After 7 days of co-cultivation, the cell protrusions fused to form a sheet covering the surface of the porous Ta. In the porous structure, the cells protruded from the pseudopods, cross-linked to each other across the pores, secreted in the matrix, and coated the microparticle structure, gradually spreading in the pores. (4) The results show that the Ta coating on the surface of porous silicon carbide scaffold has good mechanical properties and biological activity.

Objective:To summarize the experience of Bacillus Calmette-Guerin(BCG) in the treatment of bladder cancer secondary to renal transplantation.Methods:The clinical data of 5 patients who underwent BCG bladder irrigation after secondary bladder cancer after kidney transplantation in Tianjin First Central Hospital from January 2015 to December 2019 were analyzed. There were 1 male and 4 female cases. During the period of immunosuppression after transplantation, 1 case developed secondary high-level non-muscular invasive bladder cancer (NMIBC), 3 cases developed secondary low-grade NMIBC, and 1 case developed secondary glandular cystitis (4 cases). The mean age of the 5 patients with secondary bladder cancer was 59.7±4.0 years. Case one with high level NMIBC was treated with transurethral resection of bladder tumor (TURBT) and postoperative irrigation of epirubicin. Case 3 and 5 with low-level NMIBC accepted regular postoperative irrigation of gemcitabine. No irrigative therapy was performed in case 2. Bladder cancer recurred in case 1, 2, 3 and 5 after 20.1±9.7 months. TURBT was observed in all the 4 patients, among which 3 were of high grade NMIBC and 1 was of low grade NMIBC. Four patients were irrigated with BCG 2 weeks after operation. Postoperative pathology indicated low-level NMIBC in case 4, and BCG was irrigated 2 weeks after the operation. During perfusion therapy, immunosuppressive agents were continued.Results:During BCG perfusion, 4 of the 5 cases showed BCG related local inflammation, among which 2 cases presented symptoms of bladder irritation, 1 case presented hematuria, and 1 case presented hematuria with low fever. Patients with frequent urination, pain in urine, hematuria and other symptoms improved after drinking plenty of water, taking bed rest and taking levofloxacin (0.5g/ day ×7 days). Patients with low fever were treated with antipyretic treatment. No antituberculous agents were used prophylactically during BCG perfusion. There were no symptoms of tuberculosis infection or sepsis. The function of transplantated kidney was normal and no tendency of rejection. The 5 patients were followed up for 7-24 months, 1 patient was lost to follow-up after 7 months of BCG bladder perfusion, and no tumor recurrence or metastasis was found in 5 patients during the follow-up.Conclusions:The use of immunosuppressive agents does not reduce the biological activity of BCG, and BCG does not increase the risk of systemic toxicity or affect the function of transplanted kidneys in immunocompromised patients. BCG is a treatment option for bladder cancer secondary to renal transplantation.

The Delta variant of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a new global wave of the Coronavirus Disease 2019 (COVID-19) pandemic. COVID-19 vaccines currently available in China show high effectiveness against severe illness and death. However, transmission of the virus is not fully stopped by vaccination alone, therefore, integrated vaccination and non-pharmacological interventions is necessary to prevent and control the epidemic in the near future. Further expanded vaccine coverage of primary doses as well as booster shots in China's domestic population are needed to reduce severe illness and death. In order to provide evidence necessary for adjusting and optimizing immunization strategies and pandemic control measures, it is essential to conduct research on vaccine effectiveness against emerging variants, persistence of vaccine-induced protection, surveillance of adverse event following immunization with large-scale vaccine use, and modelling studies on strategic combinations of vaccination and non-pharmacological interventions.
COVID-19 ; COVID-19 Vaccines ; China ; Humans ; Immunization, Secondary ; SARS-CoV-2 ; Vaccination ; Vaccine Efficacy