[摘 要] 目的：探讨免疫检查点抑制剂（ICI）治疗非小细胞肺癌（NSCLC）患者发生免疫检查点抑制剂相关性肺炎（CIP）的发生情况和免疫治疗疗效的关系，分析接受ICI治疗的NSCLC患者的预后相关因素。方法：回顾性分析2020年3月至2023年3月在新疆医科大学附属肿瘤医院接受ICI治疗145例NSCLC患者的临床资料，将患者分为CIP组和非CIP组，随后将发生CIP的患者分为轻度（1、2级）CIP和重度（3、4级）CIP两个亚组，通过Kaplan-Meier法比较生存曲线，分析CIP的发生及严重程度对于患者PFS及OS的影响。通过单因素及多因素COX风险比例回归模型分析与PFS和OS相关的预后因素。结果：145例患者中有26例患者出现CIP，发生率为17.93％，重度CIP发生率为3.45%。CIP组患者PFS明显长于非CIP组患者（12.3 vs 7.6个月，P<0.05），CIP组与非CIP组的OS比较差异无统计学意义（16.2 vs 15.8个月，P>0.05)。亚组分析显示，轻度CIP和重度CIP相比，PFS（12.2 vs 12.9个月）及OS（16.1 vs 17.8个月）均无统计学意义（均P>0.05）。多因素COX回归分析显示，CIP[HR=0.55，95%CI（0.33, 0.90），P=0.02]、免疫疗程>6个[HR=0.51，95%CI（0.31, 0.85），P=0.01]是影响患者PFS的有利预后因素，免疫疗程>6个[HR=0.4，95%CI（0.18, 0.88），P=0.02]是影响OS的有利预后因素。结论：CIP的发生率为17.93％，CIP的发生与PFS的延长密切相关。免疫疗程>6个是影响NSCLC患者PFS、OS的有利预后因素。

Objective To understand how warfarin inhibition is hindered by the vitamin K epoxide reductase(VKORC1)resistant mutations.Methods An electrophoretic mobility assay was conducted based on the principle that binding with warfarin resulted in changes in VKORC1 electrophoretic mobility.The activity of VKORC1 and the half maximal inhibitory concentration(ICs0)of warfarin inhibiting VKORC1 were detected by ELISA.These experiments evaluated the binding ability of VKORC1 resistant mutants to warfarin.Results With warfarin bound,VKORC1 was protected from N-ethylmaleimide(NEM)modification and showed increased electrophoretic mobility,which was dependent on an unmodified cysteine on the flexible transmembrane helix 1(TM1)of VKORC1.In-creasing the warfarin concentration could shift more VKORC1 towards the species with the fast mobility.Compared to the wildtype VKORC1,the fast mobility fraction became less or disappeared in warfarin-resistant mutants,indi-cating weakened binding of warfarin.In addition,VKORC1 mutants with the weaker electrophoretic mobility shift indicated the stronger warfarin resistant.Conclusion Weakened warfarin binding is the primary cause of warfarin resistance.

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Objective:To evaluate the effect of hyperthermia on radiation pneumonitis (RP) in elderly patients with esophageal cancer undergoing intensity-modulated radiotherapy (IMRT).Methods:Clinical data of 177 elderly esophageal cancer patients (aged ≥60 years) receiving IMRT in the First Affiliated Hospital of Soochow University and Yixing Cancer Hospital from August 1, 2017 to February 6, 2023 were retrospectively analyzed. Patients were divided into the hyperthermia and non-hyperthermia groups based on whether they received hyperthermia treatment. Patients in two groups received IMRT with 6 MV X-rays. Patients in the hyperthermia group underwent high-frequency hyperthermia within 1 h before radiation using the external thermotherapy device HG-2000Ⅲ (heating temperature: 41-43 ℃ for 40 min, twice a week). After adjusting for confounding factors between two groups using propensity score matching (PSM), the short-term effective rates between two groups were compared using Chi-square test. Univariate analysis and logistic multivariate analysis were employed to compare the incidence of RP between two groups. Results:After applying PSM, 42 pairs were successfully matched, and the baseline data and radiotherapy parameters showed no statistically significant differences between two groups (all P>0.05). The objective response rate (ORR) in the hyperthermia group was significantly higher than that in the non-hyperthermia group (83.3% vs. 64.3%, P=0.047). Univariate analysis revealed that the incidence of RP and symptomatic RP (≥ grade 2) in the hyperthermia group was significantly lower than that in the non-hyperthermia group (61.9% vs. 85.7%, P=0.013; 21.4% vs. 47.6%, P=0.012). Logistic multivariate analysis indicated that hyperthermia was an independent protective factor for symptomatic RP ( P=0.011). Conclusions:The incidence and severity of RP in elderly esophageal cancer patients receiving IMRT can be reduced by hyperthermia. Hyperthermia, as a clinically beneficial green treatment, improves efficacy and reduces toxicity for patients with esophageal cancer.

Objective To explore the current status and potential subtypes of frailty among family caregivers of patients with dementia,and to analyze the related influencing factors of different subtypes.Methods Dementia patients and their family caregivers in 8 community health service centers in Shanghai from June to October 2023 were recruited by convenience sampling.General information questionnaire,Tilburg Frailty Indicator(TFI),Pittsburgh Sleep Quality Index(PSQI),Self-Rating Depression Scale(SDS),Zarit Caregiver Burden Interview(ZBI),and Connor-Davidson Resilience Scale(CD-RISC)were conducted for investigation.Latent profile analysis was used to explore the potential subtypes of frailty among family caregivers of patients with dementia.The influencing factors associated with the potential subtypes were identified by univariate analysis and multivariate Logistic regression analysis.Results A total of 470 family caregivers of patients with dementia were surveyed,and 46.17％of them suffered from frailty.Frailty among family caregivers of patients with dementia can be classified into 3 potential subtypes:comprehensive-low frailty subtype(70.64％),psychosocial-medium frailty subtype(19.57％),and physical-high frailty subtype(9.79％).Family caregivers of patients with dementia who had poor sleep quality and suffered from 2 or more chronic diseases were more likely to be classified into the physical-high frailty subtype(P＜0.05).Family caregivers of patients with dementia who had higher levels of depression,lower mastery levels of caregiving knowledge and skills and spousal caregivers were more likely to be classified into the psychosocial-medium frailty subtype(P＜0.05).Family caregivers of patients with dementia who had higher levels of resilience were more likely to be classified into the comprehensive-low frailty subtype(P＜0.05).Conclusion The incidence of frailty among family caregivers of patients with dementia is at a high level with significant heterogeneity.It is suggested that medical staff should pay attention to the frailty of family caregivers,with a focus on family caregivers in the psychosocial-medium frailty subtype or physical-high frailty subtype,and take timely and targeted interventions according to the characteristics and influencing factors of different subtypes,so as to prevent or delay the occurrence and development of frailty.

Objective:To discuss the effect of temperature-controlled shrinkage polytrimethylene carbonate(PTMC)/polyvinylpyrrolidone(PVP)nanofiber membrane on the biological behavior of mouse fibroblasts and the repairment effect on full-thickness skin defects in the rats,and to clarify the potential mechanism.Methods:The murine L929 fibroblast cells were used in the in vitro experiments and were divided into control group and experimental group(treated with PTMC/PVP nanofiber membranes).The proliferation activities of the cells in two groups were detected by CCK-8 assay;the numbers of live/dead cells in two groups were observed by live/dead cell staining;the morphology of the cells was observed by cytoskeletal staining.A total of 12 six-week-old male SD rats were selected in the in vivo experiment,and were randomly divided into control group and experimental group,and there were six rats in each group.The full-thickness skin defect model was established,and the rats in experimental group were treated with PTMC/PVP nanofiber membranes.The photographs were taken after operation,and the wound healing rates of the cells in two groups were calculated on the 0,3rd,6th,and 12th days.On the 6th and 12th days after operation,the skin samples around the wound of the rats in two groups were taken,and the histopathology of the would skin and adjacent tissue was detected by HE staining;the collagen deposition in wound skin tissue of the rats in two groups was observed by Masson trichrome staining;the numbers of angiogenesis in wound skin tissue of the rats were detected by CD31 immunohistochemical staining.Results:The CCK-8 assay results showed that the proliferation activity of the cells in experimental group showed an increasing trend on the 1st,3st,and 5st days,and there was no significant difference in the proliferation activities of the cells bewteen experimental group and control group(P＞0.05).The live/dead cell staining experiment results showed that compared with control group,the cell density and number of the cells in experimental group had no significant changes,and were predominantly live cells.The cytoskeletal staining results showed that the cells in experimental and control groups appeared spindle-shaped and well-spread.In the in vivo experiments,on the 3rd,6th,and 12th days,compared with control group,the wound healing rates of the cells in experimental group were increased(P＜0.01),and the wound healing rate of the cells was 95.45％on the 12th day,indicating nearly complete healing of the wound.The HE staining showed that on the 12th day,the wound skin structure of the cells in experimental group was more similar to the normal skin,and there was abundant granulation tissue,regular epidermal structure,and new blood vessel formation.The Masson trichrome staining results showed that compared with control group,the collagen deposition in wound tissue of the rats in experimental group was increased.The immunohistochemical staining results showed that the expression of CD31 in wound tissue of the rats in experimental group was increased,indicating the increasing of the number of angiogenesis.Conclusion:The PTMC/PVP thermoresponsive nanofiber membranes exhibit good biocompatibility and can promote the repairment of full-thickness skin defects in the rats;its mechanism may be related to the enhancement of proliferation activity of the basal cells.

Objective:To investigate the correlation between serum miR-122-5p and FOXO3 levels and osteoporosis (OP) in postmenopausal women with non-alcoholic fatty liver disease (NAFLD) .Methods:The clinical data and serum of 30 postmenopausal women with NAFLD and 48 postmenopausal women with no-NAFLD were collected. The levels of miR-122-5p and FOXO3 in serum were detected by qRT-PCR. Triglycerides, high-density lipoproteins, and low-density lipoproteins were detected by biochemical autoanalyzer. The bone mineral density of lumbar vertebrae 1-4, Wards triangular bone, femoral neck, greater trochanter and total hip was detected by bone mineral density analyzer. The correlation between the above clinical indicators and OP was analyzed.Results:The expression of miR-122-5p in postmenopausal female NAFLD patients (0.76±0.28) was lower than that in non-NAFLD patients (1±0.31) ( t=3.43, P=0.001) . The downstream target gene FOXO3 of miR-122-5p was identified by bioinformatics website analysis. The expression of FOXO3 in postmenopausal female NAFLD patients (1.31±0.30) was higher than that in non-NAFLD patients (1±0.27) ( t=4.73, P<0.001) . Student’ s t test and Logistic regression analysis showed that triglyceride, miR-122-5p and FOXO3 levels were risk factors for NAFLD (all P<0.05) . Pearson correlation coefficient showed that miR-122-5p level was significantly positively correlated with BMD of femoral neck ( r=0.488, P=0.006) , greater trochanter ( r=0.367, P=0.046) and whole hip ( r=0.404, P=0.027) . FOXO3 level was negatively correlated with bone mineral density of femoral neck ( r=-0.445, P=0.014) and whole hip ( r=-0.507, P=0.004) , while other indexes were not significantly correlated (all P>0.05) . Conclusion:Decreased serum miR-122-5p level and increased FOXO3 level in postmenopausal women with NAFLD may increase the risk of OP.

Objective:To investigate the risk factors of non-alcoholic fatty liver disease (NAFLD) in patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (HR+/HER2-BC) and the impact of NAFLD on the survival of patients.Methods:54 HR+BC patients were enrolled in this study. The liver fat accumulation was examined by magnetic resonance imaging (MRI). The patients were divided into two groups: non-NAFLD and NAFLD. Student's t test or Fisher's test was used to analyze the clinical indicators of the two groups. Logistic univariate and multivariate tests were used to analyze the clinical risk factors related to NAFLD. Receiver operating characteristic curve (ROC curve) was used to further analyze the sensitivity of clinical risk factors to predict the diagnosis of NAFLD. The Disease-free survival (DFS) and Overall survival (OS) of the two groups were analyzed by Log-rank (Mantel-Cox) test. Results:There were 22 NAFLD patients and 32 non-NAFLD patients diagnosed by MRI. Student's t test or Fisher's test showed that BMI, waist circumference, AST, ALT, GGT, TG, LDL and HDL were statistically different between the two groups (all P<0.05). Logistic univariate and multivariate analysis showed that AST ( OR=1.05, 95% CI: 1.02-1.10, P=0.007), GGT ( OR=1.04, 95% CI: 1.01-1.09, P=0.038), TG ( OR=1.03, 95% CI: 1.01-1.06, P=0.011) and HDL ( OR=1.06, 95% CI: 1.01-1.12, P=0.037) were the risk factors associated with NAFLD. ROC curve analysis showed that the combination of AST, GGT, TG and HDL had high sensitivity in predicting NAFLD (AUC=0.869, P<0.05). There was no difference in DFS ( HR=1.830, 95% CI: 0.983-3.409, P=0.057) or OS ( HR=2.482, 95% CI: 0.761-8.093, P=0.132) between the two groups. Conclusion:AST, GGT, TG and HDL are the independent risk factors for NAFLD in HR+BC patients during treatment, but concurrent NAFLD has no significant effect on DFS or OS.

"Double-driven" teacher professional development is a transformation from a novice teacher to an expert teacher through both internal and external driving pathway based on education ecology and teacher encouragement theory. The internal driving pathway of teacher professional development includes socialist belief, professional conscience, and professional consciousness, while the external driving pathway includes standardized management system, school-based teaching and research activities, medicine-education cooperation, and campus positive culture.

【Objective】 To investigate the impact of long non-coding RNA (lncRNA) FGD5-AS1 on the malignant biolo-goical behavior of bladder cancer (BC) cells by regulating micro RNA (miR)-129-5p/cyclin dependent kinase 6 (CDK6) axis. 【Methods】 Human BC cell line T24 was cultured from tumor tissue and paracancerous tissue of 105 patients with confirmed BC. The expressions of FGD5-AS1, miR-129-5p and CDK6 mRNA in tissue samples and T24 cells were detected with RT-qPCR. T24 cells were randomly divided into control group, si-NC group, si-FGD5-AS1 group, si-FGD5-AS1+inhibitor NC group and si-FGD5-AS1+miR-129-5p inhibitor group. The cell viability, migration, invasion andapoptosis were detected with CCK-8, Wound healing test, Transwell assay and flow cytometry, respectively. The expressions of Bax, Bcl-2, Caspase3 and CDK6 were detected with Western blot. The relationship between FGD5-AS1 and miR-129-5p, between miR-129-5p and CDK6 were verified with double luciferase reporter gene experiment. 【Results】 FGD5-AS1 and CDK6 mRNA were highly expressed in BC tissue, while miR-129-5p was lowly expressed (P<0.05). After FGD5-AS1 silencing, the expression of FGD5-AS1,A450 value, cell scratch healing rate, cell invasion number, and expressions of Bcl-2 and CDK6 were significantly lower, while the apoptosis rate and expressions of miR-129-5p, Bax and Caspase3 were significantly higher (P<0.05). Inhibition of miR-129-5p expression reversed the effects of FGD5-AS1 silencing on various indexes of BC cells (P<0.05). FGD5-AS1 negatively regulated the expression of miR-129-5p, and miR-129-5p negatively regulated the expression of CDK6. 【Conclusion】 Silencing FGD5-AS1 may inhibit the expression of CDK6 protein by up-regulating miR-129-5p, thus inhibiting the proliferation, migration and invasion of BC cells and promoting cell apoptosis.