Objective To analyze the clinicopathological characteristics and survival prognosis of young female patients with gastric adenocarcinoma. Methods A retrospective analysis was conducted on female patients who underwent radical gastrectomy at Zhongshan Hospital, Fudan University between January 2014 and December 2020, with postoperative pathological confirmation of gastric adenocarcinoma. Those aged ≤45 years were defined as the young group (n＝287), and were matched in a 1∶2 ratio by pTNM stage with female patients aged ≥60 years (elderly group, n＝574). Clinicopathological characteristics were compared between the two groups. Survival curves were plotted using the Kaplan-Meier method, and overall survival (OS) rates were assessed by log-rank test. Prognostic factors in the young group were analyzed using Cox regression models. Results Compared to elderly patients, young female gastric cancer patients exhibited a higher prevalence of tumors in the middle third of the stomach and a lower proportion in the upper third of the stomach. Molecular profiling revealed a higher frequency of HER2-low expression and elevated Ki-67 index. Pathologically, these patients were more frequently diagnosed with poorly differentiated or undifferentiated adenocarcinoma and signet ring cell carcinoma, while Lauren classification showed a predominance of the diffuse type with a lower proportion of the intestinal type (P＜0.05). Stratified analysis showed no significant difference in OS rates between the two groups for stage Ⅱ and Ⅲ patients; however, among stage Ⅰ patients, the young group had significantly better OS rates than the elderly group (P＝0.037). Multivariate Cox analysis and log-rank test confirmed that pN₃ stage (HR＝3.576, 95%CI 1.652–7.740), stage Ⅲ (HR＝3.581, 95%CI 1.059–12.106), and diffuse type (HR＝2.711, 95%CI 1.316–5.585) were risk factors for poor prognosis in young female gastric cancer patients. Conclusions Young female patients with gastric adenocarcinoma typically present with clinicopathological features such as the diffuse type, poor differentiation, and high proliferation. Moreover, pN₃ stage, stage Ⅲ cancer, and the diffuse type histology are correlated with a poor prognosis in this demographic.

Objective To evaluate the value of molecular markers of thrombine-antithrombin complex(TAT),soluble thrombomodulin(sTM),tissue-plasminogen activator-inhibitor complex(t-PAIC)in the early diagnosis of disseminated intravascular coagulation(DIC)in sepsis patients.Methods Thirty patients diagnosed with DIC secondary to hemoinfect-induced sepsis were selected as the DIC group in the intensive care unit(ICU)of the First Hospital of Lanzhou University from July to September 2023.Thirty patients with sepsis caused by bloodstream infection without DIC were randomly selected as the sepsis group.General data and procalcitonin(PCT),platelet count(PLT),white blood cell count(WBC),the levels of traditional clotting indexes activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(Fib),D-dimer and new clotting indexes(TM,TAT,t-PAIC)were collected.The indicators with statistical significance in univariate analysis were included in multivariate Logistic regression analysis to screen the independent risk factors for DIC in sepsis patients.Receiver operator characteristic curve(ROC curve)was drawn to analyze the diagnostic value of TM,TAT,t-PAIC and their combination in the occurrence of DIC in sepsis patients.Results A total of 60 patients with sepsis were included.There was no significant difference in gender,age,PCT,PLT and WBC between the DIC group and the sepsis group.In terms of traditional coagulation indexes,the PT level in sepsis DIC group was significantly lower than that in sepsis group,and the Fib level was significantly higher than that in sepsis group(both P<0.05).There were no statistically significant differences in APTT and D-dimer levels between the two groups.In terms of new coagulation indexes,TAT,sTM and t-PAIC levels in sepsis DIC group were significantly higher than those in sepsis group(all P<0.05).Multivariate Logistic regression analysis showed that TAT,sTM were independent risk factors for DIC in sepsis patients(both P<0.05).ROC curve analysis showed that TAT,sTM,t-PAIC combined detection had certain value in diagnosis of DIC in sepsis patients,area under the curve(AUC)was 0.735;when the cut-off value was 0.73,the sensitivity was 100.0%and specificity was 43.3%.Conclusion TAT,sTM and t-PAIC could help to predict DIC in sepsis.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To explore the clinical efficacy of different ligation methods in laparoscopic radi-cal resection of rectal cancer and sigmoid colon cancer and the influencing factors of anastomotic leakage.Methods A total of 82 patients who underwent laparoscopic radical resection of rectal cancer and sigmoid co-lon cancer in this hospital from December 2022 to December 2023 were selected and divided into the low-liga-tion group(n=42)and the high-ligation group(n=40)according to different surgical methods.The inferior mesenteric artery(IMA)classification,IMA length,operation time,intraoperative blood loss,total number of lymph node dissections,number of lymph node dissections in group 253,postoperative hospital stay,exhaust time,incidence of urinary retention,incidence of anastomotic leakage,and incidence of preventive stoma were compared between the two groups.Univariate and multivariate logistic regression analyses were conducted to analyze the influencing factors of anastomotic leakage in patients undergoing radical resection of rectal cancer and sigmoid colon cancer.Results There was no statistically significant difference in IMA length,IMA classi-fication proportion,operation time,intraoperative blood loss,the total number of lymph node dissections,the number of lymph node dissections in group 253,and the postoperative hospital stay between the two groups(P>0.05).Compared with the high-ligation group,the low-ligation group had a shorter exhaust time,lower incidence of anastomotic leakage and preventive ostomy,the differences were statistically significant(P<0.05).Anastomotic leakage occurred in 7 patients.Univariate analysis showed that whether left colic artery(LCA)was preserved,tumor location,presence of underlying diseases,and preventive stoma were associated with anastomotic leakage in patients undergoing radical resection of rectal cancer and sigmoid colon cancer(P<0.05).Multivariate logistics analysis showed that whether LCA was preserved,tumor location,presence of underlying diseases,and presence of preventive stoma were not influencing factors for anastomotic leakage in patients undergoing radical resection of rectal cancer or sigmoid colon cancer(P>0.05).Conclusion In laparoscopic radical resection of rectal and sigmoid colon cancer,the clinical efficacy of preserving LCA is com-parable to that of not preserving LCA,and it can reduce the risk of anastomotic leakage and the probability of preventive stoma,promoting the early recovery of intestinal function.

Objective To determine whether an intelligerct cloud platform follow-up model demonstrates superiority over conventional methods in enhancing follow-up quality,reducing costs,and improving functional recovery following total knee arthroplasty(TKA).Methods A retrospective cohort study was conducted on 260 patients undergoing TKA at our hospital from October 2022 to September 2023.According to the different postoperative follow-up methods,they were divided int a cloud platform group(n=130)and a traditional group(n=130).The baseline data,pre-and postoperative knee function scores,and follow-up costs were collected and compared between the 2 groups.Results The cloud platform group exhibited significantly higher rate of follow-up satisfaction,reduced resource utilization,shorter per-follow-up duration,fewer accompanying persons per visit,lower total follow-up expenditures,and decreased cumulative follow-up time when compared with the traditional group(P<0.05).At 6 weeks,3,6,and 12 months postoperatively,better range of motion(ROM)was observed in the cloud-based group than the traditional group(P<0.05),but no intergroup differences were seen in other knee function scores.Conclusion Cloud platform follow-up enhances early postoperative ROM(6 weeks to 12 months)and demonstrates marked cost-effectiveness when compared to the conventional mode.It represents a viable alternative for post-TKA rehabilitation surveillance.

Objective To explore the enzymatic reaction kinetics of metoprolol tartrate in an in vitro human liver microsome incubation experiment and to explore the effect of famotidine on the metabolism of metoprolol tartrate.Methods An LC-MS/MS method was developed to accurately measure the concentration of metoprolol tartrate in a human liver microsomal incubation system.A human liver microsome incubation system was established to determine the optimal incubation time and protein concentration;using the substrate depletion method,the enzymatic reaction kinetics parameters of metoprolol tartrate(such as Vmax and Km).Series concentrations of famotidine were co-incubated with metoprolol tartrate,and the concentration of metoprolol tartrate was measured to evaluate the effect of famotidine on its metabolism.Results The optimal incubation time for metoprolol tartrate in human liver microsomes was found to be 60 minutes,with an optimal protein concentration of 1.0 mg/mL.The enzymatic reaction kinetics parameters were Vmax=0.07 μmol/min/mg protein and Km=7.84 μmol/L.Conclusion The results indicated that famotidine did not produce a significant inhibitory effect on the metabolism of metoprolol tartrate in human liver microsome incubation system,suggesting that the combination of these two drugs may be relatively safe.

Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740～0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722～0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.

Silver nanoparticles(AgNPs)are employed as disinfectants due to their extensive antimi-crobial properties,but their biosafety in the livestock industry has not been comprehensively as-sessed.In this study,16 Black-skin Red-crowned chickens aged 32 weeks were randomly divided in-to four groups and sprayed with AgNP solution at the concentration of 0,0.064,0.128 or 0.256 g/L,respectively,every 72 h in their coops for 30 d.The effects of AgNPs as the disinfectant on lung tissue in chicken were investigated through calculation of organ coefficients,observation of lung tissue sections,analysis of bronchoalveolar lavage fluid,measurement of inflammatory factors,de-tection of silver residue in lung tissue,and exploration of signaling pathways in pulmonary fibrosis.The results indicated that chickens in the 0.128 and 0.256 g/L AgNPs treatment groups showed the blurred pulmonary lobule boundaries,the destroyed alveolar structure,and the significant in-crease in pulmonary fibrosis.These pathological changes were accompanied by the decrease in lung organ coefficient,the reduced SP-C content,the increased total protein concentration in lavage flu-id,and the elevated LDH and silver content in lung tissue.The levels of IL-6 and TNF-α in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than the control group,which suggested that AgNPs exposure could induce the pulmonary inflammatory responses.High concentrations of AgNPs can trigger pulmonary tissue fibrosis,damaging the structure and func-tions of lungs.The relative mRNA expression levels of NF-κB in all AgNPs treatment groups,TGF-β in the 0.128 g/L AgNPs treatment group,and Smad3 in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than these in the control group,respectively.Spraying chickens with 0.128 or 0.256 g/L AgNPs for disinfection led to pulmonary deposition of AgNPs,causing direct structural and functional damages to the lungs.It could also induce the chronic pul-monary inflammation through the NF-κB pathway and promote the TGF-β/Smad3 pathway to in-crease collagen synthesis,leading to pulmonary fibrosis.Therefore,the application of high concen-trations of AgNPs in livestock farming requires careful consideration of their potential biological safety issues.

Objective:This study analyzes the clinicopathological features and prognostic factors of early-stage gastric mixed adenoneuroendocrine carcinoma (G-MANEC), which is an exceedingly rare malignancy, in an effort to provide evidence-based insights for clinical decision-making.Methods:A retrospective observational study was conducted using the clinical data of 36 patients with early-stage G-MANEC who underwent surgical resection at Zhongshan Hospital, Fudan University, from July 2014 to May 2022. The observed indicators included clinicopathological data and follow-up information on recurrence, metastasis, and overall survival (OS).Results:Among the 36 patients there were 21 males and 15 females, aged 32-84 (65±11) years. The most common initial symptoms were abdominal pain and distension (19/36, 52.8%), followed by incidental findings during physical examinations (7/36, 19.4%). Tumors were located in the proximal stomach in 13 cases (36.1%), the middle stomach in 4 cases (11.1%), and the distal stomach in 19 cases (52.8%). Average tumor diameter was (2.48±1.18) cm. Gross morphology included elevated type in 12 cases (33.3%), flat type in 20 cases (55.6%), and depressed type in 4 cases (11.1%). Ulceration was present in 12 cases (33.3%). There were 11 cases (30.6%) at T1a stage and 25 cases (69.4%) at T1b stage. Lymph node metastasis was positive in 10 cases (27.8%), and the differentiation grades of the adenocarcinoma component were Grade I, II, and III in 3 (8.3%), 10 (27.8%), and 23 (63.9%) cases, respectively. Furthermore, the proportion of neuroendocrine carcinoma component was ≥50% in 18 cases (50.0%) and <50% in 18 cases (50.0%). Lymphovascular or perineural invasion was present in 18 cases (50.0%). Lauren classification included mixed type in 10 cases (27.8%), intestinal type in 19 cases (52.8%), and diffuse type in 7 cases (19.4%), and chromogranin A (CgA) positivity was found in 20 cases (55.6%). Additionally, the Ki-67 index positivity was found in 26 cases (72.2%). Total gastrectomy was performed in 12 cases (33.3%) and partial gastrectomy in 24 cases (66.7%), with a median follow-up duration of 77.5 months. The 3-year and 5-year OS rates were 88.89% and 79.67%, respectively. Univariate analysis revealed that age, gross morphology, ulceration, proportion of neuroendocrine carcinoma component, lymphovascular or perineural invasion, and chromogranin A (CgA) positivity showed statistical significance in their association with OS ( P<0.10). Multivariate Cox regression analysis further identified ulceration (HR=7.74, 95%CI: 1.24-48.30, P=0.028) and CgA positivity (HR=21.76, 95%CI: 1.86-53.97, P=0.014) as independent risk factors of OS. Conclusions:Patients with early-stage G-MANEC are typically asymptomatic, and those with ulceration or positive CgA immunohistochemical staining tend to have a poor prognosis.