[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。

Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

Objective To explore the predictive value of automated breast ultrasound(ABUS)features combined with Ki-67 in predicting pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC).Methods A retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital,Air Force Medical University from March 2019 to December 2023.All patients underwent NAC and surgical treatment after ABUS examination.Based on postoperative pathological results,patients were divided into pCR group(n=60)and non-pathological complete response(npCR)group(n=67).Differences in various parameters before NAC were compared between the two groups.LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients,and a predictive model was constructed using multivariate logistic regression.The prediction model was internally validated using the Bootstrap method(1000 resamples).The discriminative ability of the model was evaluated using receiver operating characteristic(ROC)curves,and the area under the curves(AUCs)of different prediction models were compared using De-long's test.The accuracy of the model was assessed using calibration curves,and the clinical benefit of the model was evaluated using clinical decision curve analysis(DCA).Results Significant differences were observed between two groups in terms of age,Ki-67,menopausal status,tumor type,posterior echo,coronal plane convergence sign,coronal plane skip sign,and coronal plane white wall sign before NAC(P<0.05).LASSO regression analysis showed that Ki-67,coronal plane convergence sign,and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients(P<0.05).The AUC of the multivariate logistic regression model based on Ki-67 was 0.733(95%CI 0.646-0.819),the AUC of ABUS model was 0.777(95%CI 0.695-0.858),and the AUC of ABUS combined with Ki-67 model was 0.816(95%CI 0.741-0.890).De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model,with statistically significant differences(P<0.05).There was no significant difference in the AUC between ABUS feature model and Ki-67 model(P=0.40).Hosmer-Lemeshow test indicated that the combined model had a good fit(P=0.304).Internal validation results showed that the combined model had a good stability with a consistency index(C-index)of 0.820(95%CI 0.726-0.879).The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model,and the DCA curve indicated that the model had favorable clinical benefit.Conclusion The combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients,providing a reference for the formulation of clinical treatment plans in TNBC patients.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective To investigate the effect of programmed death-1(PD-1)on cell infiltration in muscle tissue and immune response types in mice infected with Trichinella spiralis.Methods C57BL/6J wild-type(WT)and PD-1 deficient(PD-1-/-)mice were infected with T.spiralis(400 muscle larvae per mouse),and samples were collected on day 35 after infection.The proportions of infiltrating inflammatory cells and fibroblasts around encapsulated larvae were assessed by immunohistochemistry.The expression levels of interferon-γ(IFN-γ),interleukin(IL)-4,IL-5,IL-13,and eotaxin in muscle tissue were measured using enzyme-linked immunosorbent assay.Peripheral blood and spleen were collected at different time points after infection.The percentages of CD4+IFN-γ+Th1 and CD4+IL-4+Th2 within CD4+T cells population in peripheral blood and spleen of mice were analyzed using flow cytometry.Results The proportions of eosinophils and fibroblasts among total infiltrating cells around the encapsulated larvae in the muscle of PD-1-/-mice were significantly lower than those in WT mice after T.spiralis infection(P＜0.01).The infected PD-1-/-mice exhibited higher proportions of macrophages,T cells and B cells in total infiltrating cells than the infected WT mice(P＜0.01).The levels of IL-4,IL-5,IL-13,and eotaxin in the muscle tissue of infected PD-1-/-mice were significantly lower than those in infected WT mice(P＜0.05).However,IFN-γ levels were not significantly different between the infected WT and PD-1-/-mice.The proportions of Th2 cells in CD4+T cells from peripheral blood and spleen of infected PD-1-/-mice were significantly lower than those in infected WT mice,whereas the proportion of Th1 cells showed no difference among the infected groups.Conclusions PD-1 deletion results in decreased expression of key chemokines of eosinophils and key cytokines of fibroblast formation,and a corresponding decrease in inflammatory cells in muscle in T.spiralis-infected mice.This effect may be associated with a diminished Th2 immune response caused by PD-1 deletion.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6％ in trial group and 83.5％ in control group(P=0.657).The difference between the two groups was 2.11(95％CI-7.19-11.41).Given that the lower confidence limit of the 95％CI was greater than-12％,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5％ in trial group and 77.7％ in control group(P=0.970).The difference between the two groups was-0.21(95％CI-10.95-10.54),with the lower bound of the 95％CI exceeding-12％.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95％CI-10.0-0.1).As the lower limit of the 95％CI exceeded-12％,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7％,6.3％,2.7％and 69.4％in trial group,and 22.3％,4.1％,6.6％ and 66.9％ in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7％ in trial group and 7.1％ in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4％ vs.4.7％,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2％ vs.15.0％,P=0.144).There was no significant difference in the incidence of major bleeding(1.7％ vs.0.8％,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.