OBJECTIVE To investigate the effects and mechanism of Yigan huayu formula in alleviating liver fibrosis in mice. METHODS Mice were randomly divided into blank group （normal saline）， model group （normal saline）， Yigan huayu formula low- and high-dose groups （28.98， 57.96 g/kg， calculated by crude drug）， with 8 mice in each group. Except for the blank group， the liver fibrosis model was induced by intraperitoneal injection of 15%CCl 4 -olive oil solution. From the third week， the mice received the medicine/normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， liver indexes were calculated， the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， as well as the hydroxyproline （HYP） content in liver tissue， were measured. Liver histopathology was evaluated. Differentially expressed proteins （DEPs） in liver tissue were analyzed based on proteomics， followed by bioinfo rmatics analysis. The expressions of core DEPs were validated using Western blot （WB） and immunohistochemistry （IHC） methods. RESULTS Compared with the blank group， the model group showed significantly elevated liver indexes， serum activities of ALT and AST， and hepatic HYP content （ P ＜0.05）， along with obvious pathological damage and collagen deposition. Compared with the model group， the above indexes of mice in the Yigan huayu formula high-dose group were decreased significantly （ P ＜0.05）， with marked improvement in liver pathological damage and collagen deposition. Proteomics identified 210 DEPs between the model group and Yigan huayu formula high-dose group. DEPs were significantly enriched in extracellular matrix （ECM）-receptor interaction and lipid metabolism pathways. WB and IHC confirmed that Yigan huayu formula could significantly inhibit the abnormally elevated expressions of collagen type Ⅳ alpha1 chain （COL4A1）， secreted protein acidic and rich in cysteine （SPARC）， vitronectin （VTN） and laminin subunit alpha5 （LAMA5） in liver tissue of mice （ P ＜0.05）. CONCLUSIONS Yigan huayu formula may exert anti-hepatic fibrosis effects by inhibiting the expressions of proteins such as COL4A1， LAMA5， SPARC， and VTN， thereby blocking the ECM-receptor interaction signaling pathway， and subsequently suppressing excessive ECM deposition and basement membrane remodeling.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To investigate the effects of backward walking observational training combined with Soundsory cognitive training based on PASS (P: planning; A: attention; S: simultaneous; S:successive) theory on cognitive function, balance function and self-efficacy in elderly patients with post-stroke mild cognitive impairment (MCI).Methods:A randomized controlled trial was conducted. Elderly patients with post-stroke MCI admitted to the Department of Neurology, Affiliated Hospital of Jiangnan University from December 2022 to November 2023 were selected as the study objects by convenience sampling method. The patients were divided into control group and observation group by random number table. The patients in the control group implemented routine care and rehabilitation training, while the observation group were implemented backward walking observational training combined with Soundsory cognitive training based on the PASS theory. The Montreal Cognitive Assessment (MoCA), the Brunel Balance, and the Stroke Self-Efficacy Questionnaire (SSEQ) were used to evaluate the intervention effect before intervention, 2 weeks and 4 weeks of intervention, respectively.Results:A total of 116 elderly patients with post-stroke MCI were included, comprising 58 patients in the observation group (32 males and 26 females), aged (73.47 ± 7.10) years, and 58 patients in the control group (33 males and 25 females), aged (72.72 ± 8.37) years. Before intervention, there were no significant differences in the total scores of MoCA, SSEQ and Brunel Balance Scale between the 2 groups (all P>0.05). At 2 and 4 weeks of intervention, the total score of MoCA in the observation group were (20.10 ± 2.73), (22.98 ± 2.98) points, which were higher than those of the control group (18.24 ± 2.84), (20.47 ± 3.29) points, the differences were statistically significant ( t=3.61, 4.32, both P<0.05). The total score of SSEQ in the observation group were (49.97 ± 7.73), (54.98 ± 7.88) points, which were higher than those in the control group (46.50 ± 8.69), (51.59 ± 6.10) points, the differences were statistically significant ( t=2.27, 2.60, both P<0.05). At 4 weeks of intervention, the Brunel Balance Scale score in the observation group was 11(9, 11) points, which was higher than 10(8, 11) points in the control group, the difference was statistically significant ( Z=-2.00, P<0.05). Conclusions:Backward walking observational training combined with Soundsory cognitive training based on PASS theory can effectively improve cognitive and balance functions, and enhance self-efficacy in elderly patients with post-stroke MCI.

Objective:To investigate the influence of serum C-X-C motif chemokine ligand 9 (CXCL9) and C-X3-C motif chemokine ligand 1 (CX3CL1) on the development of preeclampsia in patients with gestational diabetes mellitus (GDM).Methods:A retrospective analysis was conducted on the clinical data of 398 GDM patients admitted to Huangshi Aikang Hospital from January 2021 to August 2024. Based on the occurrence of preeclampsia, patients were divided into the GDM-preeclampsia group (51 cases) and the simple GDM group (347 cases). The baseline data, blood glucose indicators, four lipid items, platelet count (PLT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, serum creatinine, and 24-hour urinary protein quantification were compared between the two groups. The influencing factors for GDM complicated by preeclampsia were analyzed, and the predictive value of serum CXCL9 and CX3CL1 for the onset of preeclampsia in GDM patients was assessed. Measurement data with a normal distribution were expressed as Mean ± SD, and the t'-test was used for intergroup comparisons when variances were unequal; measurement data with a skewed distribution were expressed as M ( Q1, Q3), and the Wilcoxon rank-sum test was used for intergroup comparisons; counting data were expressed as case (%), and the χ2 test was used for intergroup comparisons. Unconditional logistic regression models were used to analyze the risk factors for preeclampsia in GDM patients. The predictive value of serum CXCL9 and CX3CL1 levels for preeclampsia in GDM patients was analyzed using the receiver operator characteristic (ROC) curve. Results:Pre-pregnancy body mass index, glycated hemoglobin, and 24-hour urinary protein quantification in the GDM-preeclampsia group [(24.50±3.74) kg/m 2, (5.68±0.52)%, 0.42 (0.17, 0.69) g] were all higher than those in the simple GDM group [(22.70±2.97) kg/m 2, (5.42±0.44)%, 0.30 (0.10, 0.44) g], with statistically significant differences between groups (statistic values: t'=3.90, t'=3.85, U=2.70; P values: <0.001, <0.001, 0.007, respectively). Serum CXCL9 levels in the GDM-preeclampsia group [(111.69±36.65) ng/L] were lower than those in the simple GDM group [(200.16±85.57) ng/L], while CX3CL1 levels [(2.22±0.29) μg/L] were higher than those in the simple GDM group [(1.83±0.35) μg/L], with statistically significant differences ( t' values: 7.28 and 7.58, respectively; both P<0.001). Multivariate logistic regression analysis showed that increased CX3CL1 ( OR=1.562, 95% CI: 1.237-1.972), decreased CXCL9 ( OR=0.979, 95% CI: 0.970-0.989), increased pre-pregnancy body mass index ( OR=1.226, 95% CI: 1.060-1.417), and increased glycated hemoglobin ( OR=3.474, 95% CI: 1.192-10.122) were associated with an increased risk of developing preeclampsia in GDM patients ( P values: <0.001, <0.001, 0.006, 0.023, respectively). The ROC curve showed that the area under the curve for serum CXCL9 (sensitivity: 88.24%, specificity: 70.89%) and CX3CL1 (sensitivity: 78.43%, specificity: 69.16%) in predicting preeclampsia in GDM patients were both >0.50 ( P values: 0.015, 0.034, respectively), indicating that both have high predictive efficacy, with CXCL9 being slightly superior to CX3CL1. Conclusion:Decreased serum CXCL9 and increased CX3CL1 are associated with an increased risk of preeclampsia in GDM patients. Both can serve as auxiliary predictive indicators for preeclampsia in GDM patients.

Objective:To investigate the incidence of hypomineralized second primary molars (HSPM) and deciduous teeth caries in school-aged children of Kaifeng City, and to discuss the association between HSPM and deciduous teeth caries, providing scientific guidance for clinical prevention and treatment.Methods:A cross-sectional study was carried out on first-grade children aged 6-7 years in five primary schools chosen from the eastern, western, southern, northern, and central areas of Kaifeng City by cluster random sampling method. The European Academy of Pediatric Dentistry criteria was used for scoring HSPM. The International Caries Detection and Assessment System (ICDAS-Ⅱ) was used to evaluate caries status.Results:This cross-sectional study was with a sample of 913 children. The prevalence of HSPM was 8.76% (80/913), with 39 boys and 41 girls, the most common type of which was atypical caries [35.00% (28/80)]. Regarding the distribution of HSPM, the incidence in maxilla [6.13% (56/913)] showed no statistically significant difference with that in the mandible [5.70% (52/913)] (χ2=0.16, P=0.692). In terms of severity, 56 cases were severe and 24 cases were mild. The association between HSPM and deciduous teeth caries was analyzed. The results showed that 56 had caries on their second primary molars among the 80 HSPM children. Children with HSPM had an increased risk of second deciduous molar decay compared to non-HSPM children ( OR=1.94, 95 %CI: 1.18-3.19, P<0.05); meanwhile, the deciduous teeth of HSPM children were more prone to suffer caries than those of non-HSPM children ( OR=2.33, 95 %CI: 1.26-4.29, P<0.05). Conclusions:The HSPM prevalence in school-aged children of Kaifeng City was 8.76%. Child with HSPM was more likely to have deciduous teeth caries than non-HSPM child. Special attention should be paid to children with HSPM after the eruption of affected molars.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals

Objective:To analyze the effects of electrophysiological combined therapy on pelvic floor function and electrophysiological indexes of pelvic floor in elderly patients with pelvic prolapse.Methods:A total of 46 elderly patients with pelvic prolapse admitted to Noncommissioned Officer School Hospital, Army Medical University from Jan. 2022 to Jul. 2023 were selected as subjects. All patients were divided into control group and study group by random number table method, with 23 cases in each group. The control group was treated with conventional operation, and the study group was treated with electrophysiological combination. The therapeutic effect, psychological state, pelvic floor electrophysiology and pelvic floor muscle function before and after treatment were compared between the two groups.Results:The treatment efficacy rate in the observation group was 95.65%, while that in the control group was 73.91%, with the observation group showing a significantly higher rate than the control group ( P<0.05). There were no statistically significant differences between the two groups in terms of psychological state scores, pelvic floor electrophysiological indicators, or pelvic floor muscle function before treatment ( P>0.05). After treatment, the SAS score, SDS score, fatigue degree of Type I muscle fibers, fatigue degree of Type II muscle fibers, and absolute values of gh scores in the observation group were lower than those in the control group ( P<0.05) ; The observation group had higher Type I muscle fiber strength, Type II muscle fiber strength, Ba point, Bp point, pb point, TVL point, pelvic floor contraction pressure, rapid contraction pressure, resting pressure, and number of contractions than the control group ( P<0.05) . Conclusion:Electrophysiological combined therapy is helpful to improve the therapeutic effect of elderly patients with pelvic prolapse, improve their psychological state, pelvic floor electrophysiological indexes and pelvic floor muscle function.

Estimating an individual's age based on biological evidence found at a scene can provide valuable information for crime investigations and aid in identifying the identities of disaster victims.Developing novel age prediction methods remains a key focus in forensic medicine research.Traditional forensic age estimation,reliant on skeletal and dental morphological examinations,necessitates high sample integrity and is impractical for challenging samples.Currently,molecular methods for age estimation have begun to show effectiveness,especially the age inference method based on DNA methylation,which yields relatively accurate results.MicroRNAs and circRNAs in the transcriptome molecules,due to their short lengths and high stability,may hold greater potential for detecting challenging samples.This review provides an overview of the current state of predicting forensic age using transcriptome molecules,with particular emphasis on the research advancements involving microRNAs and circRNAs in age inference applications for challenging samples.