[摘 要] 目的：探讨环指蛋白8（RNF8）对子宫内膜癌（EC）细胞顺铂（CDDP）敏感性的影响及可能机制。方法：基于在线数据库分析RNF8在EC组织中的表达及拷贝数变异；采用慢病毒介导shRNA稳定敲低Ishikawa细胞中RNF8表达并进行CDDP处理，按sh-NC+溶剂对照、sh-RNF8+溶剂对照、sh-NC + CDDP、sh-RNF8 + CDDP分组处理，并设置sh-RNF8 + CDDP + KU60019抑制实验。采用CCK-8、克隆形成、Annexin V-FITC/PI流式细胞术、Hoechst 33258/PI染色、WB及γ-H2AX免疫荧光检测细胞活力、克隆形成、凋亡、DNA损伤累积及ATM/CHK2通路相关蛋白表达。结果：RNF8在EC组织和细胞中表达升高。RNF8敲低降低细胞存活率和IC50，抑制克隆形成，并进一步增强CDDP诱导的凋亡；同时BAX、Cleaved-Caspase-3和γ-H2AX表达升高，BCL-2、p-ATM、p-CHK2和RAD21表达降低。KU60019处理进一步促进DNA损伤累积和细胞凋亡，并降低细胞活力。结论：RNF8可能通过ATM/CHK2轴促进DNA损伤应答并降低EC细胞对CDDP的敏感性；敲低RNF8可增加DNA损伤累积并增强CDDP敏感性。

Objective To investigate the relationship between the expression of platelet autophagy related factors and peritoneal metastasis of gastric cancer.Methods The data of 360 patients with gastric cancer who underwent surgery in Hunan Provincial People's Hospital from January 2021 to May 2023 were reviewed.Patients were divided into non-peritoneal metastasis group(n=322)and peritoneal metastasis group(n=38)according to whether peritoneal metastasis occurred or not.The following information was collected:patient's personal information(i.e.age,sex,body mass index)and tumor characteristics(i.e.location,size,pathological type,histopathological differentiation,lymphatic infiltration).Platelets were collected from all subjects,and the levels of autophagy-associated protein 7(ATG7),benzalkonium chloride 1(BECN1),microtubule-associated protein 1 light chain 3(LC3)and sequestosome 1(p62)were measured by enzyme-linked immunosorbent assay(ELISA).Results Among the 360 patients included,peritoneal metastasis was detected in 38 cases.Compared with the non-peritoneal metastasis group,the peritoneal metastasis group exhibited decreased BMI(P<0.05),while the tumor size,non-ulcerative tumor,number of lymph node metastasis,infiltration depth,number of cases of lymphatic invasion,platelet count,platelet LC3-Ⅱ level,platelet ATG7 level and CEA level were increased(P<0.05).Multivariate logistic regression analysis showed that BMI(OR=1.094),lymphatic invasion(OR=2.658),and LC3-Ⅱ(OR=3.793)and ATG7(OR=2.010)were independent influencing factors for peritoneal metastasis in patients with gastric cancer(P<0.05).LC3-Ⅱ>2.59ng/ml had the highest ability to predict peritoneal metastasis in patients with gastric cancer(AUC=0.932),followed by ATG7(AUC=0.916).Conclusions Elevated levels of platelet LC3-Ⅱ and ATG7 are independently related to peritoneal metastasis in patients with gastric cancer,and can be used to predict the occurrence of peritoneal metastasis,which is helpful to guide individualized treatment.

Ischemic obstruction is a dangerous condition with a high mortality rate.Professor Jin Shi proposed that vascular intesti-nal obstruction disease is based on the intestinal tract while the structure of mesenteric vascular structure in modern medicine is highly similar to the morphological description of"intestinal collateral"in traditional Chinese medicine.The"hypercoagulable state"of blood is highly consistent with the core of the pathogenesis of"intestinal stasis"in traditional Chinese medicine.Blood stasis is a key patho-logical product and pathogenic factor of vascular intestinal obstruction and it is necessary to pay attention to the combination of disease identification,clarification of urgency,and phased treatment.This study provides a theoretical basis and practical example for the treatment of vascular intestinal obstruction in traditional Chinese medicine.

Objective:To investigate improvement effect of osthol(OST)on inflammatory response in gestational diabetes mel-litus(GDM)rats by regulating cGAS-STING signaling pathway.Methods:GDM rat model was established by intraperitoneal injection of 35 mg/kg streptozotocin on the fifth day of pregnancy,and randomly grouped into GDM group,OST-L group(1 mg/kg),OST-M group(10 mg/kg),OST-H group(50 mg/kg),OST-H+DMXAA group(50 mg/kg OST solution+25 mg/kg DMXAA),positive control group(200 mg/kg metformin hydrochloride),with 10 rats in each group,another 10 rats with 5-day pregnancy were regarded as con-trol group.After intervention,glucose meter was applied to detect fasting blood sugar;ELISA was applied to detect insulin and TNF-α,IL-6,IL-1β levels;automatic biochemical analyzer was applied to detect contents of total cholesterol(TC),triglyceride(TG)and high-density lipoprotein(HDL);pancreatic tissues were separated and Western blot was applied to detect cGAS and STING proteins expressions in pancreatic tissue;HE staining was applied to detect pathological changes in pancreatic tissue.Results:Compared with control group,pathological damage in GDM group was severe,cGAS and STING protein expressions,pathological score,TNF-α,IL-6,IL-1β,TC,TG,insulin and fasting blood sugar levels were increased obviously,HDL level was decreased obviously(P<0.05);compared with GDM group,pathological damage in OST-L group,OST-M group and OST-H group was improved,cGAS and STING protein expressions,pathological score,TNF-α,IL-6,IL-1β,TC,TG,insulin and fasting blood sugar levels were decreased obviously,HDL level was increased obviously(P<0.05);compared with OST-H group,pathological damage in OST-H+DMXAA group was aggravated,cGAS and STING protein expressions,pathological score,TNF-α,IL-6,IL-1β,TC,TG,insulin and fasting blood sugar levels were increased obviously,HDL level was decreased obviously(P<0.05),however,there was no difference in posi-tive control group(P>0.05).Conclusion:OST can alleviate inflammatory response in GDM rats by inhibiting cGAS-STING signaling pathway.

Ischemic obstruction is a dangerous condition with a high mortality rate.Professor Jin Shi proposed that vascular intesti-nal obstruction disease is based on the intestinal tract while the structure of mesenteric vascular structure in modern medicine is highly similar to the morphological description of"intestinal collateral"in traditional Chinese medicine.The"hypercoagulable state"of blood is highly consistent with the core of the pathogenesis of"intestinal stasis"in traditional Chinese medicine.Blood stasis is a key patho-logical product and pathogenic factor of vascular intestinal obstruction and it is necessary to pay attention to the combination of disease identification,clarification of urgency,and phased treatment.This study provides a theoretical basis and practical example for the treatment of vascular intestinal obstruction in traditional Chinese medicine.

Objective:To investigate improvement effect of osthol(OST)on inflammatory response in gestational diabetes mel-litus(GDM)rats by regulating cGAS-STING signaling pathway.Methods:GDM rat model was established by intraperitoneal injection of 35 mg/kg streptozotocin on the fifth day of pregnancy,and randomly grouped into GDM group,OST-L group(1 mg/kg),OST-M group(10 mg/kg),OST-H group(50 mg/kg),OST-H+DMXAA group(50 mg/kg OST solution+25 mg/kg DMXAA),positive control group(200 mg/kg metformin hydrochloride),with 10 rats in each group,another 10 rats with 5-day pregnancy were regarded as con-trol group.After intervention,glucose meter was applied to detect fasting blood sugar;ELISA was applied to detect insulin and TNF-α,IL-6,IL-1β levels;automatic biochemical analyzer was applied to detect contents of total cholesterol(TC),triglyceride(TG)and high-density lipoprotein(HDL);pancreatic tissues were separated and Western blot was applied to detect cGAS and STING proteins expressions in pancreatic tissue;HE staining was applied to detect pathological changes in pancreatic tissue.Results:Compared with control group,pathological damage in GDM group was severe,cGAS and STING protein expressions,pathological score,TNF-α,IL-6,IL-1β,TC,TG,insulin and fasting blood sugar levels were increased obviously,HDL level was decreased obviously(P<0.05);compared with GDM group,pathological damage in OST-L group,OST-M group and OST-H group was improved,cGAS and STING protein expressions,pathological score,TNF-α,IL-6,IL-1β,TC,TG,insulin and fasting blood sugar levels were decreased obviously,HDL level was increased obviously(P<0.05);compared with OST-H group,pathological damage in OST-H+DMXAA group was aggravated,cGAS and STING protein expressions,pathological score,TNF-α,IL-6,IL-1β,TC,TG,insulin and fasting blood sugar levels were increased obviously,HDL level was decreased obviously(P<0.05),however,there was no difference in posi-tive control group(P>0.05).Conclusion:OST can alleviate inflammatory response in GDM rats by inhibiting cGAS-STING signaling pathway.

Objective:To analyze the value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly hip fracture patients.Methods:In this retrospective study, clinical data were collected of hip fracture patients aged 60 years and above surgically treated at Beijing Luhe Hospital affiliated to Capital Medical University between January 2015 and December 2019.Patients' group assignment was based on whether the modified frailty index score was ≤1 or ≥2, and a post-surgery follow-up was conducted for survival at 30 days, 1 year, 2 years, and 4 years, which was analyzed by the Kaplan-Meier method.Multivariate Cox regression analysis was used to identify factors affecting death in elderly patients.Results:A total of 1 208 patients were included, with 890 in the group with the index score ≤1 and 318 in the group with the index score ≥2.There was no difference in mortality at 30 days(1.6% or 14/890 vs.1.9% or 6/318, P=0.707), 1-year(11.3% or 99/874 vs.11.6% or 36/310, P=0.917), 2-years(19.7% or 168/852 vs.24.3% or 73/300, P=0.099)and 4-years(44.0% or 238/541 vs.51.5% or 106/206, P=0.071). The incidence of postoperative complications in the group with the score ≥2 was higher(14.8% or 47/318 vs.9.7% or 86/890, P=0.012), including the incidence of stroke(6.3% or 20/318 vs.1.8% or 16/890, P<0.001)and the incidence of postoperative pneumonia(6.0% or 19/318 vs.3.1% or 28/890, P=0.029), and the differences were statistically significant.Multivariate Cox regression analysis showed that age, being female, the Charlson comorbidity index score and low hemoglobin at admission were risk factors for 1-year, 2-year and 4-year mortality post-surgery(all P<0.05), while the modified frailty index score had no correlation with postoperative mortality. Conclusions:A modified frailty index ≥2 is predictive of increased risk of postoperative pneumonia and stroke in patients with hip fractures, but is not correlated with the risk of postoperative mortality.

Objective To explore clinical effect of Jiawei Sangju decoction combined with oseltamivir in the treatment of influenza B complicated with benign acute childhood myositis(BACM).Methods Sixty children with influenza B complicated with BACM hospitalized in the Department of Pediatrics,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2021 to January 2024 were selected and divided into control group and study group according to random number table method,with 30 cases in each group.The control group was treated with oseltamivir,and the study group was treated with Jiawei Sangju decoction combined with oseltamivir.The clinical efficacy,symptom improvement time and aspartate transaminase(AST),alanine transaminase(ALT),creatine kinase(CK),creatine kinase isozyme(CK-MB),lactate dehydrogenase(LDH)and myoglobin(Mb)before and after treatment were compared between two groups.Results After treatment,the total effective rate of study group was significantly higher than that of control group(χ2=5.455,P=0.020).The duration of fever and leg pain relief in study group were significantly shorter than those in control group(P<0.05).After 5 days of treatment,the levels of AST,CK,CK-MB,LDH and Mb in two groups were significantly lower than before treatment(P<0.05),and the levels of AST,CK,CK-MB,LDH and Mb in study group were significantly lower than those in control group(P<0.05).Conclusion Jiawei Sangju decoction combined with oseltamivir can improve the symptoms of influenza B with BACM,reduce the levels of muscle enzyme and Mb,and have a positive effect on the prognosis of children.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To discussed the regulation role of calcium/calmodulin dependent protein kinase(CaMK4)on γδT cells in the pathogenesis of lupus nephritis.Methods:The proportion of γδT cells in peripheral blood of LN patients and healthy con-trols were compared by flow cytometry.Magnetic bead was used to separation LN patients and healthy controls of gamma delta T cells in peripheral blood.RNA-SEQ analysis were performed in γδT cells of peripheral blood from LN patients and healthy controls.Real-time PCR and western blot were used to verify the expression level of differential gene CaMK4.The expression levels of CD80,CD86 and CD40L on γδT cells treated with CaMK4 inhibitor were detected by flow cytometry.ELISA was used to measure the level of IL-17 secreted by γδT cells after CaMK4 inhibitor treatment.Results:The proportion of γδT cells in the peripheral blood of LN patients was lower than that of healthy control group.A total of 28 differential genes related to LN were screened by RNA-SEQ sequencing,among which CaMK4 had significant by differences at molecular level and protein level.After γδT cells from LN patients were treated with CaMK4 inhibitor,KN-93,the expressions of surface costimulatory molecules CD80,CD86 and CD40L was decreased,and the level of IL-17 also was decreased.Conclusion:CaMK4 regulates γδT cells to participate in the pathogenesis of LN by IL-17 secretion and the expression of costimulatory molecules.Inhibition of CaMK4 may become a new target for the treatment of LN.