ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Objective To determine the risk factors related to the occurrence of colorectal adenomatous polyps and provide a basis for early screening, diagnosis, and treatment of colorectal cancer. Methods A total of 1 527 cases of colorectal polyps detected by colonoscopy were selected as the research subjects. Data on sociodemographic information, lifestyle and dietary habits, clinical history, laboratory tests, and endoscopic characteristics were collected. The patients were divided into adenoma and non-adenoma groups based on the pathological type. Multivariate logistic regression analysis was conducted to explore the influence of the above factors on the occurrence of colorectal adenoma. Results Old age (OR: 1.024, 95%CI: 1.001-1.048, P=0.044), high body mass index (OR: 1.046, 95%CI: 1.008-1.087, P=0.020), and a history of smoking (OR: 1.493, 95%CI: 1.035-2.158, P=0.032) were independent risk factors for the occurrence of colorectal adenoma. Patients with better cognitive function had a lower risk of developing colorectal adenoma than those with poorer cognitive function (OR: 0.929, 95%CI: 0.871-0.984, P=0.017). Polyps located in the rectum (OR: 0.396, 95%CI: 0.229-0.677, P=0.001) and those of flat type (OR: 0.531, 95%CI: 0.342-0.810, P=0.004) or laterally spreading type (OR: 0.306, 95%CI: 0.135-0.698, P=0.005) were more likely to be non-adenomatous polyps. The possibility of adenomatous pathological changes increased significantly with an increase in polyp size (OR: 1.063, 95%CI: 1.035-1.095, P<0.001). Conclusion Old age, high body mass index, smoking history, and large polyp diameters are related with a high risk of adenoma in the patients with colorectal polyps. Patients who have satisfactory cognitive function, polyps located in the rectum and polyps of flat type or laterally spreading type are likely to have non-adenoma.

Objective: To systematically evaluate the influencing factors for autism spectrum disorder (ASD) in Chinese children, so as to provide the evidence for risk prediction and intervention of ASD. Methods: The publications pertaining to the influencing factors for ASD in Chinese children were retrieved from CNKI, Wanfang Data, VIP, PubMed and Embase database from inception to August 2024. A meta-analysis was performed using R package version 4.4.1. Sensitivity analysis was performed using the "leave-one-out" evaluation procedure. Publication bias was assessed using Egger regression test. Results: A total of 38 high-quality articles out of 9 015 articles were finally included, covering 149 607 individuals, with 5 974 cases of ASD. The meta-analysis showed that demographic factors including family history of related diseases (OR=14.958), maternal age of ≥35 years (OR=2.287) and parental history of hazardous occupations (OR=3.511); pregnancy-related factors including history of abortion (OR=5.832), no folate supplementation before and during pregnancy (OR=4.566), tobacco exposure before and during pregnancy (OR=2.596), history of other adverse exposures before and during pregnancy (OR=3.533), history of infectious diseases during pregnancy (OR=3.753), history of non-infectious diseases during pregnancy (OR=2.563), psychological problems during pregnancy (OR=3.864), history of medication during pregnancy (OR=6.651), adverse environmental exposures during pregnancy (OR=3.754), severe pregnancy reactions (OR=5.082), abnormal perinatal period (OR=2.987), cesarean delivery (OR=1.659), other perinatal adverse factors (OR=3.856), history of neonatal asphyxia (OR=2.792) and neonatal jaundice (OR=3.687); parenting factors including non-exclusive breastfeeding (OR=2.510), early/excessive screen exposure (OR=3.589) and feeding problems (OR=3.113); and individual factors including being male (OR=3.333) and history of convulsions/epilepsy (OR=7.035) were influencing factors for ASD in Chinese children. Conclusions The prevalence of ASD in Chinese children is primarily associated with 23 influencing factors, including family history of related diseases, history of abortion, no folate supplementation before and during pregnancy, medication during pregnancy, early/excessive screen exposure and history of convulsions/epilepsy.

Objective:To evaluate the clinical efficacy of left ventricular assist device(LVAD) in the treatment of end-stage heart failure.Methods:This is a retrospective case series study. Data were retrospectively analyzed from 48 patients treated at eight domestic cardiac surgery centers in China between March 2022 and September 2024, who underwent LVAD implantation due to end-stage heart failure. All surgeries were led by the cardiovascular surgery team from Nanjing First Hospital. The study included 42 male and 6 female patients, aged (59.1±12.3) years (range:28 to 73 years). All patients had a preoperative New York Heart Association(NYHA) functional class of Ⅳ. General preoperative data, intraoperative extracorporeal circulation time, cross-clamp time, postoperative ICU stay, hospital stay, pump parameters at discharge, intraoperative and postoperative left ventricular end-diastolic diameter, left ventricular ejection fraction, and follow-up results post-discharge were collected. The generalized estimation equation was used to compare the difference of cardiac function indexes in patients with different follow-up time points. The Tukey′s Honestly Significant Difference test was used for pairwise comparison within the group.Results:The surgery was successfully completed for 47 patients, and 1 perioperative death. The extracorporeal circulation time was (122.4±21.6) minutes (range: 101 to 200 minutes), the cross-clamp time was (70.1±18.3) minutes (range: 101 to 200 minutes), the postoperative ICU length of stay was (6.9±3.2) days (range: 2 to 23 days), and the hospital length of stay was (28.1±4.2) days (range: 23 to 42 days). At discharge, the blood bump flow rate was (3.4±0.6) L/min(range: 3.1 to 3.6 L/min), and speed was (2 791.3±142.0) r/min(range: 2 680 to 3 250 r/min). The follow-up period was (12.2±0.78) months (range:2 to 24 months) of 47 patients. One case underwent heart transplantation during the follow-up period, and 3 cases died, with no major device malfunction events. Three months post-surgery, the patients showed a significant reduction in left ventricular end-diastolic diameter compared to pre-surgery ((69.1±8.3) mm vs. (77.3±8.3) mm, q=6.73, P<0.01); the left ventricular ejection fraction significantly increased ((29.6±8.0)% vs. (23.2±5.8)%, q=6.49, P<0.01); and the 6-minute walk distance significantly improved ((382.0±12.8)metres vs. (114.8±18.4)metres, q=116.56, P<0.01). Six months postoperatively, all patients′ cardiac function had recovered to NYHA class Ⅰor Ⅱ. Conclusions:Preliminary research findings indicate that left ventricular assist device therapy yields favorable outcomes in the treatment of end-stage heart failure. serving as a bridge to transplantation, recovery, or a destination therapy.

Objective To explore the effects of aberrant O-glycosylation modifications induced by the knockout of Cosmc or T-synthase genes on the expression profiles of miRNAs in exosomes derived from colorectal cancer cells and to reveal the molecular mechanisms of O-glycosylation in the development of colorectal cancer and identify potential biomarkers for early diagnosis and treatment.Methods This research specifically targets the Cosmc or T-synthase genes in the human colorectal cancer cell line HCT116 to create stable cell lines exhibiting abnormal O-glycosylation with CRISPR/Cas-9 gene editing technology.Exosomes originating from these colorectal cancer cells were isolated and authenticated.A microarray chip equipped with primer sequences for 16 miRNAs closely associated with colorectal cancer was employed to assess the differential expression of miRNAs within these exosomes with fluorescent quantitative polymerase chain reaction(PCR).And then,a cohort of miRNAs that exhibited significant and consistent changes in expression levels across the exosomes from both cell lines was selected.These miRNAs were further validated independently with traditional fluorescent quantitative PCR.Subsequently,data from The Cancer Genome Atlas Program(TCGA)database containing patient information on colorectal cancer was harnessed.Employing R programming language,Gene Set Enrichment Analysis(GSEA)was conducted on the upregulated miRNA to investigate the downstream pathways significantly impacted and the malignant biological behaviors they may influence.Results The absence of either Cosmc or T-synthase genes results in the dysregulation of O-glycosylation in colorectal cancer cells,leading to the exposure of Tn antigens.This,in turn,affects the expression levels of specific miRNAs in exosomes derived from these cells.Specifically,the expression of hsa-miR-125b-1-3p was downregulated,while that of hsa-miR-218-5p was upregulated.Notably,hsa-miR-218-5p were found to be closely associated with the epithelial-mesenchymal transition(EMT)process in tumor cells,which is a key mechanism in cancer progression.Conclusion It elucidates that the aberrant O-glycosylation mediated by the knockout of Cosmc or T-synthase genes significantly influences the expression of certain miRNAs in exosomes from colorectal cancer cells,potentially affect the EMT process in colorectal cancer and thereby promoting distant metastasis.Given the inherent stability and detectability advantages of colorectal cancer-derived exosomes,the altered expression levels of miRNAs within these exosomes may serve as indicators of the stated of abnormal O-glycosylation in colorectal cancer.These findings suggest that exosomal miRNAs have potential as biomarkers for monitoring disease progression and therapeutic efficacy.Consequently,this could pave the way for more personalized diagnostic and treatment strategies tailored to individual colorectal cancer patients,enhancing the precision and effectiveness of clinical management.

In line with the rising global incidence of cancer,tumor metastasis has become the leading cause of mortality among cancer patients.Formation of the pre-metastatic niche(PMN)creates an optimal microenvironment for tumor cell colonization and metastasis,thus facilitating tumor dissemination.In this context,cancer-associated fibroblasts(CAFs)have garnered significant attention as a result of their multifaceted roles in tumor progression.CAFs enhance the formation of the PMN and promote the invasive behavior of tumor cells by remodeling the extracellular matrix,inducing epithelial-mesenchymal transition,stimulating angiogenesis and modulating the tumor immune microenvironment.These processes not only expedite metastasis but also enable tumor immune evasion.This paper reviews the fundamental mechanisms and functions of CAFs in tumor metastasis,examines their potential applications in cancer research and therapy,and offers new perspectives and directions for the development of anti-tumor metastasis strategies.

Objective:To explore the diagnostic key points, treatment strategies, and prognosis of graft-versus-host disease (GVHD) after liver transplantation.Methods:The clinical data of 5 recipients diagnosed with GVHD after liver transplantation at the Liver Transplantation Center of the First Affiliated Hospital of Army Medical University from May 1999 to October 2024 were retrospectively analyzed. The causes, onset, diagnosis, treatment, and prognosis of GVHD after liver transplantation were summarized and analyzed. Literature was searched in CNKI, Wanfang, VIP, Chinese Medical Journal Full-text Database, PubMed, Web of Science, and Google Scholar using the Chinese keywords "移植物抗宿主病+肝移植", and the English keywords "graft versus host disease + liver transplantation". The search time ranged from January 1988 to January 2025. Inclusion criteria for the literature: (1) meeting the clinical or pathological diagnostic criteria of GVHD after liver transplantation; (2) recipient age >18 years; (3) case number ≥2. Exclusion criteria: incomplete clinical data such as incidence, mortality, and clinical manifestations of GVHD after liver transplantation. The retrieved literature was reviewed.Results:All 5 recipients were male. Among them, 4 cases underwent liver transplantation at this center. The incidence of GVHD after liver transplantation in this center was 0.46% (4/872). All 5 cases developed symptoms such as fever, rash, diarrhea, oral ulcers, and pancytopenia on the 19th (5-21) day after liver transplantation. One case had gastrointestinal bleeding. Two cases were diagnosed by skin pathological biopsy, and three cases were diagnosed based on clinical manifestations such as fever, rash, diarrhea, and bone marrow suppression. One case discontinued immunosuppressants, and four cases reduced the dosage of immunosuppressants. Four cases were treated with high-dose glucocorticoids, four with intravenous immunoglobulin (IVIG), three with ruxolitinib, and three with hematopoietic factors. All five cases received protective isolation, anti-infection, and symptomatic supportive treatment. Among the three recipients treated with ruxolitinib, body temperature returned to normal, rash gradually faded, oral ulcers gradually healed, blood cells returned to normal, and they were eventually discharged after recovery. The remaining two cases showed no symptom improvement and died of severe lung infection and multiple organ failure. Literature review A total of 34 articles were included. The incidence of GVHD after liver transplantation was 1.03% (279/27 018), and the onset time ranged from 7 to 1,865 days post-transplantation; 272 cases (97.49%) occurred within 1-8 weeks. The main clinical manifestations included fever (195 cases, 69.89%), rash (267 cases, 95.70%), diarrhea (173 cases, 62.01%), and bone marrow suppression (214 cases, 76.70%). Treatment mainly involved adjustment of immunosuppressants (201 cases, 72.04%), high-dose corticosteroids (215 cases, 77.06%), and IVIG pulse therapy (146 cases, 52.33%). In the end, 83 cases (29.75%) recovered and were discharged, while the mortality rate was 70.25% (196/279), with causes of death including infection, gastrointestinal bleeding, and multiple organ failure.Conclusions:GVHD after liver transplantation has a low incidence, high mortality, and poor prognosis. Diagnosis mainly relies on typical clinical manifestations and pathological results of tissue biopsy. Early administration of high-dose corticosteroids combined with IVIG pulse therapy, timely reduction or discontinuation of immunosuppressants, use of ruxolitinib, active infection management, and enhanced symptomatic and supportive care are effective strategies for treating GVHD after liver transplantation.

Objective To establish an animal model of anterior displacement of the temporomandibular joint disc in rabbits and ob-serve the pathological changes of condylar cartilage under stress by using HE staining,immunohistochemical staining and immunofluo-rescence staining.Methods Thirty adult New Zealand white rabbits were randomly divided into a Sham operation group and four ex-perimental groups,with six rabbits in each group.The Sham operation group underwent a sham operation,while the experimental groups were used to establish an animal model of anterior displacement of the temporomandibular joint disc.The experimental groups were further divided into a model group(no postoperative treatment),a 2-APB(TRPM7 inhibitor)group,a PDTC(NF-κB specific inhibitor)group,and a Diclofenac group.Two weeks after the operation,the experimental animals were sacrificed,and pathological sections of the condylar cartilage were made.HE staining was used to observe the pathological changes of the condylar cartilage,and immunohistochemical staining and immunofluorescence staining were used to observe the expression of NF-κB and its inflammatory fac-tors.Results ① HE staining showed that the pathological changes of the condylar cartilage were obvious at the 2nd week.Compared with the 2-APB group,PDTC group,and Diclofenac group,the pathological changes in the model group were more obvious.② Immu-nohistochemical staining showed that the expression of TRPM7,NF-κB,IL-1,IL-6,TNF-α and MMP-3 in the model group was higher than that in the sham operation group.After treatment with 2-APB,PDTC or diclofenac,the expression of TRPM7,NF-κB,IL-1,IL-6,TNF-α and MMP-3 decreased.③ Immunofluorescence staining showed that the expression of NF-κB in the model group was higher than that in the sham operation group.After treatment with 2-APB,PDTC or diclofenac,the expression of NF-κB decreased.Conclu-sion ① Under stress,the condylar bone undergoes early remodeling,and the apoptosis of condylar chondrocytes increases with the extension of loading time within a certain period.② Diclofenac,2-APB and PDTC can all reduce the apoptosis of condylar cells,and inflammatory factors also play an important role in the apoptosis of condylar chondrocytes.