Bile-processed Coptidis Rhizoma（B-pCR）， first documented in Shengji Zonglu， is a unique processed products of Coptidis Rhizoma（CR） characterized by "mutual enhancement processing" and "enhancing the cold property of cold-natured herbs". Pig bile can enhance the bitter and cold properties of CR， yielding potent effects in purging excess fire from the liver and gallbladder. The processing increases the dissolution of alkaloids such as berberine， coptisine， and palmatine， while introducing bile acids from pig bile， including taurine-type and glycine-type cholic acids. This enhances its pharmacological effects， such as antipyretic activity， regulation of glucose and lipid metabolism disorders， and intestinal absorption. Traditional processing techniques and quality standards for B-pCR are outlined in the Shanghai Traditional Chinese Medicine（TCM） Decoction Pieces Processing Standard and the Gansu TCM Processing Standard. However， incomplete specifications for critical process parameters and quality criteria significantly impact its production and clinical application. A review of research over the past two decades on the processing history， process optimization， quality evaluation， material basis， and changes in pharmacological effects and properties of B-pCR reveals that the pretreatment method and dosage of pig bile， and processing temperature are key factors influencing its quality. Furthermore， current quality standards lack specific indicators. Additionally， the enhancement of the cold property and medicinal efficacy direction of B-pCR is not only associated with changes in alkaloid groups but also depend on the synergistic effects of bile acids. This review can provide insights for improving the quality evaluation system of B-pCR.

ObjectiveTo observe the changes in the levels of different subtypes of epidermal growth factor receptor （ErbB）， namely ErbB1， ErbB2， ErbB3， and ErbB4， in the spinal dorsal horn of inflammatory pain model rats， and to explore their mechanism of mediating hyperalgesia as well as the intervention mechanism of electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）". MethodsThe study was divided into five parts. In experiment 1， 14 Sprague Dawley （SD） rats were randomly divided into control and inflammatory pain group （7 rats each group） to observe the pain behavior and the protein expression of different ErbB receptor subtypes in the spinal dorsal horn. In experiment 2， 30 rats were randomly divided into control group 1， inflammatory pain group 1， and low-， medium-， and high-concentration TX1-85-1 groups， with 6 rats in each group， to observe the effect of inhibiting spinal ErbB3 on inflammatory pain. In experiment 3， 12 rats were randomly divided into control virus group and ErbB3 knockdown virus group， with 6 rats in each group， to observe the effect of knocking down ErbB3 in the spinal dorsal horn on inflammatory pain. In experiment 4， 44 rats were randomly divided into control group 2， inflammatory pain group 2， electroacupuncture group， and sham electroacupuncture group， with 11 rats in each group， to observe the effect of electroacupuncture. In experiment 5， 40 rats were randomly divided into control group 3， inflammatory pain group 3， electroacupuncture group 1， and electroacupuncture + NRG1 group， with 10 rats in each group， to observe the effect of activating ErbB3 on electroacupuncture. A rat model of inflammatory pain was established by subcutaneous injection of 100 μl of complete Freund's adjuvant into the sole of the unilateral hind foot of SD rats. Rats in the low-， medium-， and high-concentration TX1-85-1 groups were intrathecally injected with ErbB3 inhibitor TX1-85-1 on day 5 to day 7 after modeling. Rats in the ErbB3 knockdown virus group were injected with ErbB3 knockdown virus packaged with adenovirus vector-based short hairpin RNA （shRNA） into the spinal dorsal horn in situ 3 weeks before modeling. Rats in each electroacupuncture group received electroacupuncture at bilateral "Zusanli （ST 36）" and "Kunlun （BL 60）" from day 1 to day 7 after modeling， with dense-sparse waves at a frequency of 2 Hz/100 Hz and a current of 0.5-1.5 mA for 30 minutes once a day. Rats in the electroacupuncture + NRG1 group were intrathecally injected with ErbB3 ligand recombinant human neuregulin-1 （NRG1） after electroacupuncture intervention from day 5 to day 7 after modeling. The mechanical withdrawal threshold and thermal withdrawal latency of rats were measured on day 1， 3， 5， and 7 after modeling to evaluate behavior， and Western Blot was used to detect the protein and phosphorylation levels of each ErbB subtype in the spinal dorsal horn. ResultsCompared with the control group， rats in the inflammatory pain group showed decreased mechanical withdrawal threshold and thermal withdrawal latency of rats， and increased expression of phosphorylated ErbB3 （p-ErbB3） protein in the spinal dorsal horn on days 1， 3， 5， and 7 after modeling （P＜0.01）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 1， the mecha-nical withdrawal threshold and thermal withdrawal latency of rats in the medium- and high-concentration TX1-85-1 groups increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 1， 3， 5， and 7 after modeling， compared with the control virus group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the ErbB3 knockdown virus group increased （P＜0.05）. On day 5 and day 7 after modeling， compared with the inflammatory pain group 2 and the sham electroacupuncture group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group increased， and the expression of p-ErbB3 protein decreased （P＜0.05）. On day 5 and day 7 after modeling， compared with the electroacupuncture + NRG1 group， the mechanical withdrawal threshold and thermal withdrawal latency of rats in the electroacupuncture group 1 increased （P＜0.05）. ConclusionThe p-ErbB3 in the spinal dorsal horn involved in hyperalgesia in rats with inflammatory pain， and electroacupuncture at "Zusanli （ST 36）" and "Kunlun （BL 60）" can alleviate inflammatory pain by inhibiting the expression of p-ErbB3 protein in the spinal dorsal horn of rats.

Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.

Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

Diabetes mellitus, characterized by glucose metabolism disorders and marked by insulin deficiency or insulin resistance, has seen a continuous rise in prevalence. In recent years, islet transplantation has matured as a therapeutic approach for diabetes, becoming an important method for glycemic control and the reduction of diabetes-related complications. Donor selection directly influences transplant outcomes, and various research institutions worldwide have proposed multiple scoring systems to optimize donor assessment, such as the University of Alberta scoring system and the North American Islet Donor Score. This article explores the impact of key factors such as donor age, body mass index and ischemia time on islet transplantation. Combining practical experience in pancreatic donor selection from Shanghai Changzheng Hospital, it proposes screening criteria for pancreatic donors suitable for China, aiming to provide new evidence for improving the success rate of islet transplantation.

OBJECTIVE To investigate the effects of Mitoxantrone liposomes （Lipo-MIT） on the proliferation， migration and cancer stem cell （CSCs） stemness of ovarian cancer cells， as well as to explore its mechanism of action based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （AKT） pathway. METHODS The effects of Lipo-MIT on cell proliferation， migration and the stemness characteristics of CSCs were investigated through in vitro experiments. A human ovarian cancer A2780 cells xenograft tumor model of nude mouse was established to explore the effects of Lipo-MIT at doses of 2 and 5 mg/kg on the safety of tumor-bearing mice， as well as in vivo tumor growth and the pathological characteristics of tumor tissues. The influence of Lipo-MIT on the expression levels of PI3K/AKT pathway-related proteins， epithelial-mesenchymal transition related proteins， and stemness related proteins in both cells and tumor tissues was also investigated. RESULTS The half maximal inhibitory concentrations of Lipo-MIT against A2780， SK-OV3， and OV-CAR5 cells were 0.72， 5.41， and 2.77 μmol/L， respectively. Compared with solvent control （0.1% dimethyl sulfoxide）， 0.5-2.5 μmol/L Lipo-MIT significantly reduced the cell colony formation rate， shortened the cell migration distance， decreased the number of migrated cells， down-regulated the protein expression of N-cadherin， up-regulated the protein expression of E-cadherin （P＜0.05）， and also decreased the stem cell sphere formation frequency and down-regulated the protein expression of aldehyde dehydrogenase 1A1 （ALDH1A1） （P＜0.05）. Additionally， 1.0 and 2.5 μmol/L Lipo-MIT significantly reduced the stem cell sphere formation probability and down-regulated the protein expression of sex determining region Y box protein 2 in cells （P＜0.05）. In vivo experimental results demonstrated that 2， 5 mg/kg Lipo-MIT had no significant effects on the body weight， food intake， water intake， and organ （heart， liver， spleen， lung， and kidney） indices of tumor-bearing nude mice （P＞0.05）， but could significantly improve the pathological changes of tumor tissues and remarkably inhibit the protein expressions of N-cadherin， CD133 and ALDH1A1（ only at 5 mg/kg Lipo-MIT）， up-regulate the expression of E- cadherin （only at 5 mg/kg Lipo-MIT） in tumor tissues （P＜0.05）. Lipo-MIT at different concentrations/doses significantly reduced the phosphorylation levels of PI3K and AKT proteins in cells/tumor tissues （P＜0.05）. CONCLUSIONS Lipo-MIT can inhibit the proliferation and migration of ovarian cancer cells and the stemness by suppressing the activity of the PI3K/AKT pathway.

Objective To screen for potential targets of the anti-tuberculosis lead compound M6 using antibody microarray,express Mycobacterium smegmatis(Ms) target protein 2-C-methy1-D-erythriol 4-phosphate cytidylyl-transferase(IspD) in E.coli, and prepare its polyclonal antibodies, in order to provide experimental basis for in-depth study of the protein function and the development of new anti-tuberculosis drugs.Methods The minimum inhibitory concentration(MIC) of M6 against Ms and Corynebacterium glutamicum(Cg) was determined. The protein samples of Cg treated with M6 were captured and analyzed by antibody microarray, and the differential targets were identified and screened by mass spectrometry. The ispD gene of Ms was amplified by PCR and cloned into vector pET28a(+) to construct recombinant plasmid pET28a-ispD. The recombinant plasmid was transformed into E.coli BL21(DE3), and the optimal conditions for protein expression were determined by optimizing the induction temperature(16, 25, 33, 37 ℃) and IPTG concentration(0-1. 5 mmol/L). The recombinant IspD protein was purified by nickel column affinity chromatography. The purified recombinant IspD protein was used as immunogen combined with Freund's incomplete adjuvant to immunize 11 female BALB/c mice to prepare polyclonal antibodies. The titer of antiserum was determined by indirect ELISA, and the antibody specificity was detected by Western blot.Using the prepared polyclonal antibodies, the effect of M6 treatment on the expression level of Ms IspD protein was analyzed by Western blot.Results The MIC of M6 against Cg and Ms was 0. 5 and 32 μg/mL, respectively. IspD protein was one of the primary target proteins of M6. The recombinant expression plasmid pET28a-ispD was constructed correctly as identified by double enzyme digestion, and the IspD protein was expressed in E.coli. The optimal induction conditions were determined to be 1. 0 mmol/L IPTG, 16 ℃ for 14 h. After purification, the purity of recombinant IspD protein reached, and it could specifically bind to mouse anti-His tag monoclonal antibodies. The polyclonal antibodies against IspD protein achieved a high titer of 1∶102 400, which could specifically recognize IspD protein in recombinant bacterial lysate. The expression level of Ms IspD protein did not change significantly after M6 treatment.Conclusion In this study, the potential target IspD protein of M6 was successfully screened by antibody microarray screening, and Ms IspD protein was expressed in E.coli. The polyclonal antibodies against IspD were prepared by immunizing mice, providing essential experimental basic for further functional studies of this protein and the development of novel anti-tuberculosis drugs.

Childhood obesity has become a global public health issue. Current research indicates that early life obesogen exposure has emerged as a significant risk factor for childhood obesity. While obesogens have been confirmed to influence the development and progression of childhood obesity through mechanisms such as endocrine disruption and epigenetic programming, controversies remain regarding the establishment of causal relationships, assessment of combined exposures, and validation of transgenerational effects in humans. In recent years, novel approaches including multi-omics technologies, exposome-based analysis, and multigenerational cohort studies have integrated dynamic biomarker monitoring with analyses of social-environmental interactions, offering new perspectives and methodologies for constructing a systematic "exposure-mechanism-outcome" research framework. This article reviews literature from PubMed and Web of Science up to August 2025 on the association between early life obesogen exposure and childhood obesity, summarizing evidence on the health effects of early life obesogen exposure, major exposure pathways and internal exposure assessment, interactions and amplifying effects of social and environmental factors, as well as the biological mechanisms underlying obesogen action. It further examines current research frontiers and challenges, aiming to provide a theoretical foundation for early prevention and precision intervention of childhood obesity.

ObjectiveTo investigate the liver histopathological features of HBeAg-negative patients in the indeterminate phase of low-viral-load chronic hepatitis B virus （HBV） infection. MethodsA total of 271 patients with low-viral-load HBeAg-negative chronic HBV infection who underwent liver biopsy in Department of Infectious Diseases， Affiliated Hospital of Yan’an University， from September 2013 to June 2021 were enrolled as subjects， and the degree of liver injury was compared between patients based on age， sex， presence or absence of the family history of hepatitis B， HBsAg， and alanine aminotransferase （ALT） level. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 271 patients with HBeAg-negative chronic HBV infection， 86 patients （31.73%） grade≥A2 liver inflammatory activity， 72 （26.57%） had a liver fibrosis stage of ive， and 112 （41.33%） had moderate or severe liver histological injury. The proportion of patients with grade≥A2 liver inflammatory activity in the patients with ALT>20 U/L was significantly higher than that in the patients with ALT≤20 U/L （χ²=3.938， P=0.047）. There were no significant differences in the proportion of patients with grade≥A2 liver inflammatory activity between the patients with different ages， sexes， family history of hepatitis B， HBsAg levels （all P>0.05），there were no significant differences in the proportion of patients with a liver fibrosis stage of ≥F2 between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）， and the stratified analysis of patients aged≤30 years and patients without the family history of hepatitis B showed no statistical significance between groups （all P>0.05）. There was no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels （all P>0.05）. ConclusionSignificant liver injury is observed in more than 40% of the patients with low-viral-load HBeAg-negative chronic HBV infection， and there is no significant difference in the degree of liver histological injury between the patients with different ages， sexes， family history of hepatitis B， HBsAg， and ALT levels. Even for the patients aged≤30 years who deny the family history of hepatitis B， there is still a considerable proportion of patients with liver injury， which should be taken seriously by clinicians.

ObjectiveTo investigate the effect of sorafenib and donafenib on the pharmacokinetics of ertugliflozin in rats， and to provide a theoretical basis for drug combination in clinical practice. MethodsA total of 24 male Sprague-Dawley rats were randomly divided into groups A， B， C， and D， with 6 rats in each group. The rats in groups A and B were given sorafenib control solvent and sorafenib （100 mg/kg）， respectively， by gavage for 7 consecutive days， followed by ertugliflozin （1.5 mg/kg） by gavage on day 7. Blood samples were collected from the angular vein plexus at different time points， and ultra-performance liquid chromatography-tandem mass spectrometry was used to determine the mass concentration of ertugliflozin and plot the plasma concentration-time curves， while the non-compartment model in DAS 2.1.1 software was used to calculate related pharmacokinetic parameters. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with group A， group B had significant increases in the AUC_0-t and AUC_0-∞ of the plasma concentration-time curve of ertugliflozin （both P<0.05）， significant prolongation of t_1/2， MRT_0-t， and MRT_0-∞ （all P<0.05）， and a significant reduction in CL_Z/F （P<0.05）. Compared with group C， group D had significant increases in the AUC_0-t and AUC_0-∞ of ertugliflozin （both P<0.05）， significant prolongation of T_max， t_1/2， MRT_0-t， and MRT_0-∞ （all P<0.01）， and significant reductions in V_Z/F and CL_Z/F （both P<0.05）. ConclusionBoth sorafenib and donafenib can affect the pharmacokinetics of ertugliflozin in rats and significantly increase the plasma exposure of ertugliflozin. The efficacy and adverse drug reactions of ertugliflozin should be closely monitored during combined use in clinical practice and the dose should be adjusted when necessary to avoid the potential risk of drug interaction.