ObjectiveTo investigate the expression level of HBV cccDNA in patients in the convalescence stage of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） and its correlation with HBV markers and liver histopathological changes. MethodsA total of 30 patients in the convalescence stage of HBV-ACL who were hospitalized in The Ninth Hospital of Nanchang from January 2015 to October 2023 were enrolled as liver failure group， and 9 patients with chronic hepatitis B （CHB）， matched for sex and age， were enrolled as control group. The content of HBV cccDNA in liver tissue was measured， and its correlation with clinical data and laboratory markers was analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and a one-way analysis of variance or the Kruskal-Wallis H test was used for comparison between multiple groups； the Fisher’s exact test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed. ResultsThe liver failure group had a significantly lower content of HBV cccDNA in liver tissue than the control group （-0.92±0.70 log₁₀ copies/cell vs -0.13±0.91 log₁₀ copies/cell， t=2.761， P=0.009）. In the liver failure group， there was no significant difference in the content of HBV cccDNA in liver tissue between the HBeAg-positive patients and the HBeAg-negative patients （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different grades （G0-G2， G3， and G4） of liver inflammatory activity （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with different stages （S0-S2， S3， and S4） of liver fibrosis （P>0.05）； there was no significant difference in the content of HBV cccDNA in liver tissue between the patients with negative HBV DNA and those with positive HBV DNA （P>0.05）. For the liver failure group， the content of HBV cccDNA in liver tissue was positively correlated with the content of HBV DNA in liver tissue （r=0.426， P=0.043） and was not significantly correlated with the content of HBV DNA in serum （P>0.05）. ConclusionThere is a significant reduction in the content of HBV cccDNA in liver tissue in the convalescence stage of HBV-ACLF. HBV cccDNA exists continuously and stably in liver tissue and can better reflect the persistent infection and replication of HBV than HBV DNA in serum and liver tissue.

Objective To explore the risk factors associated with the development of acute respir-atory distress syndrome(ARDS)in patients with severe traumatic brain injury(sTBI)and to construct and validate a risk prediction model for ARDS in these patients.Methods Clinical data from 371 sTBI patients admitted to Yangzhou Affiliated Hospital of Yangzhou University between January 2017 and December 2023 were retrospectively collected.Patients were randomly divided into modeling group(n=259)and validation group(n=112)at a 7-to-3 ratio.A nomogram model was constructed after screening for risk factors using the Least Absolute Shrinkage and Selection Operator(LASSO)and multivariate Logistic regression analysis.Model performance was evaluated using the receiver operating characteristic(ROC)curve,area under the curve(AUC),Hosmer-Lemeshow test,calibration curve,and deci-sion curve analysis(DCA).Results Statistically significant differences were observed in heart rate,respiratory rate,pupil size,percutaneous oxygen saturation(SpO2),Glasgow Coma Scale(GCS)score,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,head Ab-breviated Injury Scale(AIS)score,chest AIS score,emergency intubation,pulmonary infection,associated chest trauma,midline shift,blood transfusion within 12 hours of admission,fluid intake within 24 hours of admission,shock,mechanical ventilation,hemoglobin level,hematocrit,white blood cell count,prothrombin time,international normalized ratio,total protein,albumin,serum calcium,oxygenation index,and base excess between the two groups(P＜0.05).Multivariate Lo-gistic regression analysis revealed that SpO2,pulmonary infection,and fluid intake within 24 hours of admission were predictors of ARDS in sTBI patients.The Hosmer-Lemeshow test results for the modeling and validation groups showed good fit(x2=10.373,P=0.240;x2=13.21,P=0.105).DCA results for both groups indicated net benefit at threshold probabilities ranging from 0％to 72％and 0％to 50％,respectively.Conclusion SpO2,pulmonary infection,and fluid in-take within 24 hours of admission are risk factors for ARDS in sTBI patients.The model constructed using these factors demonstrates good performance and provides a reliable tool for clinical screening of high-risk ARDS populations among sTBI patients.

Objective:To systematically evaluate the current status of research on the development of indicators for entrustable professional activities (EPAs) of residents in China.Methods:We searched the China National Knowledge Infrastructure, Wanfang Data, Airiti Library, PubMed, Embase, and Web of Science databases for literature on the development of EPA indicators for residents in China published between January 1, 2005 and February 28, 2025. Two researchers independently screened the literature and extracted data, followed by descriptive analysis. The quality of the studies was assessed using the Joanna Briggs Institute critical appraisal tool for expert opinion. Quantitative data were presented as medians (ranges) and qualitative data were presented as frequencies (percentages).Results:A total of eight articles were included, in which two general EPA indicator systems and six specialty-specific EPA indicator systems were developed for residents. The overall quality of the research was high, with the main shortcomings related to the methods used in the process of constructing the consensus indicators. The number of experts recruited ranged from 22 to 45, with 100.00% response rate, high authority coefficients (0.820-0.914), and high coordination coefficients (0.157-0.741). Most of the studies used literature reviews as one source for the indicator pool (8 studies, 100.00%), employed the Delphi method to reach consensus (6 studies, 75.00%), and provided inclusion criteria for the indicators (7 studies, 87.50%). However, only one study (12.50%) explored the practical application of the developed indicators, and none of the studies set indicator weights or conducted quality assessments. The number of EPA indicators developed ranged from 10 to 38 per study. The reporting of EPA indicators was included in most studies regarding titles (8 studies, 100.00%) and the expected levels of entrustment at various stages of training (6 studies, 75.00%), but the reporting on other aspects was lacking. Among the specialty-specific EPA indicators, 38.39% overlapped with the general EPAs indicators.Conclusions:The research on the development of EPA indicators for residents in China is still in its early stages, and there is room for improvement in methodological quality and reporting coverage. There is partial overlap between specialty-specific and general EPA indicators, failing to fully reflect the unique characteristics of different specialties.

Objective:To investigate the current status of Chinese-foreign cooperative education programs for medical majors, and to discuss the potential problems and development trends of this field.Methods:Related data were collected from the information platform of Chinese-Foreign Cooperation in Running Schools by Ministry of Education of the People's Republic of China, and the characteristics of Chinese-foreign cooperative education programs for medical majors were extracted for analysis. Categorical data were expressed as frequency (percentage), and continuous data were expressed as mean±standard deviation.Results:A total of 83 Chinese-foreign cooperative education programs for medical majors were included in the study, accounting for only 3.45% (83/2 406) of all programs. Chinese partners in these cooperative programs were mainly from East China (41 programs, 49.40%), while foreign partners were mainly from Europe (39 programs, 46.99%). The mean duration of these programs was (3.61±0.88) years, with an enrollment of (87.08±35.52) students. Most of the students were included in National General Higher Education Enrollment Plan (79 programs, 95.18%), and the main majors included nursing (39 programs, 46.99%), medical technology (19 programs, 22.89%), and clinical medicine (11 programs, 13.25%), with the main enrollment level of junior college (45 programs, 54.22%). Chinese partners in the cooperative programs mainly issued academic certificate (45 programs, 54.22%) or academic certificate plus degree certificate (36 programs, 43.37%), while most foreign partners did not issue such certificates (44 programs, 53.01%).Conclusions:There are several problems in Chinese-foreign cooperative education programs for medical majors, such as a limited number of programs, a significant regional difference, an imbalanced distribution of specialties, a low level of education, and inconsistency in issuance of certificates, which still requires further improvement and standardization. However, there are also high-level and high-quality programs for reference.

Objective To investigate the feasibility of magnetic tracer technique for locating pulmonary nodules.Methods A tracer magnet and a matching puncture instrument were designed by ourselves for locating pulmonary nodules.After preliminarily verifying the feasibility of the operation in the isolated lung,four beagle dogs were used as animal models to perform puncture localization of the assumed lesions in the upper lobe of the right lung under the guidance of X-ray by using self-designed tracer magnets and puncture instruments,and the positioning effect was observed and evaluated after thorax opening.The operation time required for the tracer magnet implantation,whether there is bleeding at the puncture site,whether the tracer magnet is displaced,and the positioning time of pulmonary nodules after thorax opening were recorded.Results Two tracer magnets were successfully inserted into the upper lobe of the right lung under X-ray guidance in four beagle dogs,and the magnets were successfully attracted and fixed.The median insertion time of the tracer magnet was 5 minutes(4 to 7 minutes),and the insertion process was smooth without bleeding at the puncture site.After thorax opening,oval forceps were used to conveniently locate the location of the tracer magnet,achieving accurate positioning of pulmonary nodules with a median positioning time of 13 seconds(10 to 17 seconds),and the tracer magnet did not shift during the whole process.Conclusion The magnetic tracer technique is simple to operate and pricise for localization of pulmonary nodules.With further optimization of the operation process,this technique is expected to be applied in clinic.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.