Objective To investigates the inhibitory and cytotoxic effects of chimeric antigen receptor-engineered natural killer(CAR-NK)cells targeting cellular-mesenchymal epithelial transition factor(c-Met)against gastric cancer(GC)cells in vitro.Methods c-Met expression at protein and mRNA levels was evaluated in GC cell lines(MKN-45,GTL-16,NCI-N87)and gastric mucosal epithelial cells(GES-1)by using flow cytometry(FCM),Western blot,and reverse transcription quantitative polymerase chain reaction.Immunofluorescence assays were conducted to confirm c-Met CAR-mediated specificity toward c-Met-overexpressing GTL-16 cells.Lentiviral vectors were utilized to construct c-Met-targeting CAR-NK cells,with transduction efficiency and phenotypic integrity verified by FCM.Cytotoxic activity against GC cells and normal epithelial cells was quantified via lactate dehydrogenase(LDH)release assays and cytokine secretion measured by enzyme-linked immunosorbent assay.Results c-Met exhibited significantly higher expression in GTL-16 and MKN-45 cells at both transcriptional and protein levels compared to NCI-N87 and GES-1 cells(P＜0.05).CAR-NK cells demonstrated a transduction efficiency of(14.97±0.25)％ without altering NK-92 cell phenotypes.Immunofluorescence confirmed specific binding of c-Met CAR-expressing Lenti-X-293T cells to GTL-16 targets.LDH assays revealed enhanced cytotoxicity of c-Met CAR-NK cells against c-Met-high GC cells(GTL-16,MKN-45)versus untransduced NK-92 controls(P＜0.05).At a 10∶1 effector-to-target ratio,c-Met CAR-NK cells co-cultured with c-Met-high GC cells secreted significantly elevated tumor necrosis factor(TNF-α)and interferon(IFN)-γ(P＜0.05).Conclusion The c-Met CAR-NK cells constructed in this study have the ability to specifically recognize and target to kill gastric cancer cells with high expression of c-Met,and have a strong killing effect function,which can release more TNF-α and IFN-γ.

Objective To investigate the impact of linked color imaging(LCI)combined with a transparent cap on the detection rate of colorectal sessile serrated lesion(SSL).Methods A total of 492 patients who underwent colonoscopy the First People's Hospital of Huzhou from February 2024 to January 2025 were randomly assigned to three groups:White light imaging(WLI)group,LCI group,and LCI combined with transparent cap group,with 164 cases in each group.The general clinical data,cecal intubation time(CIT),withdrawal time,SSL detection rate,small(≤5mm)SSL detection rate,and proximal colon SSL detection rate were analyzed and compared among three groups.Results There were no significant differences in general clinical data,CIT,or withdrawal time among three groups(P>0.05).Statistical analysis revealed that the SSL detection rates for WLI group,LCI group,and LCI combined with transparent cap group were 6.10％,12.20％,and 18.90％,respectively;In the proximal colon,the SSL detection rates for WLI group,LCI group,and LCI combined with transparent cap group were 3.66％,9.15％,and 16.46％,respectively;For small(≤5mm)SSL,the detection rates were 1.22％,2.44％,and 7.32％in WLI group,LCI group,and LCI combined with transparent cap group,respectively also showing statistically significant differences(P<0.001).Conclusion Colonoscopy using LCI combined with a transparent cap significantly improves the detection rate of SSL,particularly for small SSL.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigates the inhibitory and cytotoxic effects of chimeric antigen receptor-engineered natural killer(CAR-NK)cells targeting cellular-mesenchymal epithelial transition factor(c-Met)against gastric cancer(GC)cells in vitro.Methods c-Met expression at protein and mRNA levels was evaluated in GC cell lines(MKN-45,GTL-16,NCI-N87)and gastric mucosal epithelial cells(GES-1)by using flow cytometry(FCM),Western blot,and reverse transcription quantitative polymerase chain reaction.Immunofluorescence assays were conducted to confirm c-Met CAR-mediated specificity toward c-Met-overexpressing GTL-16 cells.Lentiviral vectors were utilized to construct c-Met-targeting CAR-NK cells,with transduction efficiency and phenotypic integrity verified by FCM.Cytotoxic activity against GC cells and normal epithelial cells was quantified via lactate dehydrogenase(LDH)release assays and cytokine secretion measured by enzyme-linked immunosorbent assay.Results c-Met exhibited significantly higher expression in GTL-16 and MKN-45 cells at both transcriptional and protein levels compared to NCI-N87 and GES-1 cells(P＜0.05).CAR-NK cells demonstrated a transduction efficiency of(14.97±0.25)％ without altering NK-92 cell phenotypes.Immunofluorescence confirmed specific binding of c-Met CAR-expressing Lenti-X-293T cells to GTL-16 targets.LDH assays revealed enhanced cytotoxicity of c-Met CAR-NK cells against c-Met-high GC cells(GTL-16,MKN-45)versus untransduced NK-92 controls(P＜0.05).At a 10∶1 effector-to-target ratio,c-Met CAR-NK cells co-cultured with c-Met-high GC cells secreted significantly elevated tumor necrosis factor(TNF-α)and interferon(IFN)-γ(P＜0.05).Conclusion The c-Met CAR-NK cells constructed in this study have the ability to specifically recognize and target to kill gastric cancer cells with high expression of c-Met,and have a strong killing effect function,which can release more TNF-α and IFN-γ.

Objective To investigate the impact of linked color imaging(LCI)combined with a transparent cap on the detection rate of colorectal sessile serrated lesion(SSL).Methods A total of 492 patients who underwent colonoscopy the First People's Hospital of Huzhou from February 2024 to January 2025 were randomly assigned to three groups:White light imaging(WLI)group,LCI group,and LCI combined with transparent cap group,with 164 cases in each group.The general clinical data,cecal intubation time(CIT),withdrawal time,SSL detection rate,small(≤5mm)SSL detection rate,and proximal colon SSL detection rate were analyzed and compared among three groups.Results There were no significant differences in general clinical data,CIT,or withdrawal time among three groups(P>0.05).Statistical analysis revealed that the SSL detection rates for WLI group,LCI group,and LCI combined with transparent cap group were 6.10％,12.20％,and 18.90％,respectively;In the proximal colon,the SSL detection rates for WLI group,LCI group,and LCI combined with transparent cap group were 3.66％,9.15％,and 16.46％,respectively;For small(≤5mm)SSL,the detection rates were 1.22％,2.44％,and 7.32％in WLI group,LCI group,and LCI combined with transparent cap group,respectively also showing statistically significant differences(P<0.001).Conclusion Colonoscopy using LCI combined with a transparent cap significantly improves the detection rate of SSL,particularly for small SSL.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Due to the difference of cultural background, the psychological, social and spiritual needs of dying people are very different, so there are great differences in the care and nursing concept of dying people in different countries and nationalities. In order to construct the modern hospice care, we should actively learn from the western experience, but more important is to dig the local ideological resources from the traditional culture, build a set of caring care theory and practice rooted in China and originated from the concept of a good end of Chinese traditional culture, with the characteristics of the times and the cultural confidence of the Chinese nation, serving the Chinese people, and with Chinese characteristics.

Objective:To observe the effects of continuous light exposure on skeletal muscle fiber type transformation and lipid metabolism, and to explore its internal relationship.Methods:Mice were randomly divided into normal light group and 24-hour continuous light group by random number table. The serum and skeletal muscle lipid content and urine 6-sulfatoxymelatonin(6-SML)level were detected by ELISA. The expression of circadian clock and lipid metabolism related genes mRNA were observed by realtime PCR. The muscle fiber type and lipid deposition were evaluated by tissue immunofluorescence as well as oil red O staining.Results:Compared with the normal light group, the level of 6-SML in urine at night decreased( P<0.05), and the expression level and rhythm of brain and muscle ARNT-like protein 1(Bmal1), circadian locomotor output cycles protein kaput(Clock), and period 2(Per2)mRNA in the skeletal muscle changed in continuous light group. In addition, the body weight, blood lipid, free fatty acid, and triglyceride contents of skeletal muscle in continuous light group increased significantly( P<0.05 or P<0.01), the expression of carnitine palmitoyltransferase 1b (Cpt1b)mRNA, the key enzyme of fatty acid oxidation, decreased significantly( P<0.05), while the expression of stearoyl-CoA desaturase(Scd1)mRNA, a lipid synthesis related gene, increased significantly( P<0.01). Further immunofluorescence analysis showed that the proportion of slow muscle fibers decreased and that of fast muscle fibers increased in continuous light group(both P<0.05). Conclusion:The process of ectopic deposition of lipid in skeletal muscle in mice induced by continuous light exposure may be related to the remodeling of skeletal muscle fibers.

Objective:To identify anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibody in patients with encephalitis of unknown etiology and describe the clinical features of anti-DPPX antibody-associated encephalitis in Chinese patients.Methods:For patients registered in the Peking Union Medical College Hospital Encephalitis and Paraneoplastic Syndrome Registration Project from 2016 to 2019 with negative findings in autoimmune encephalitis routine antibody profile and paraneoplastic antibody profile, but with positive tissue-based assay (TBA) results, further tests for rare antibodies, including cell-based assay (CBA) of anti-DPPX antibody, were performed. Patients positive for anti-DPPX antibody were enrolled and the clinical data were collected.Results:Two patients with anti-DPPX antibody-associated encephalitis were found from 2016 to 2019 among about 15 000 patients. Both were females, aged 46 and 75 years. One patient had diarrhea, cachexia, cognitive dysfunction, agitation, myoclonus, tremor, and seizures. The other had cognitive impairment, restlessness, memory loss, disorientation, and sleep disturbance. The second patient had medical history of systemic lupus erythematosus and secondary Sj?gren′s syndrome.Conclusions:TBA should be combined with CBA in identification of anti-DPPX antibody to confirm the diagnosis. Anti-DPPX antibody-associated encephalitis has clinical manifestations of encephalopathy with diarrhea and cachexia, and can coexist with systemic lupus erythematosus.