Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.

ObjectiveTo address the challenges of unstructured classical Chinese expressions， nested entity relationships， and limited annotated data in famous traditional Chinese medicine（TCM） case records， this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping， aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction（CasRel） model for TCM semantics was designed， integrating a pre-trained bidirectional encoder representations from transformers（BERT） layer for classical TCM texts to enhance semantic representation， and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model， combining data augmentation and entity mapping， outperformed the pipeline-based Bert-Radical-Lexicon（BRL）-bidirectional long short-term memory（BiLSTM）-Attention model. The overall precision， recall， and F₁-score across 12 relation types reached 65.73%， 64.03%， and 64.87%， which represent improvements of 14.26%， 7.98%， and 11.21% compared to the BRL-BiLSTM-Attention model， respectively. Notably， the F₁-score for tongue syndrome relations increased by 22.68%（69.32%）， and the prescription-syndrome relations performed the best with the F₁-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts， offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation， prescription optimization， and drug compatibility， providing a methodological reference for TCM artificial intelligence research.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Objective To construct prostate cancer(PCa)prediction models based on machine learning algorithms, so as to improve the accuracy of early diagnosis of PCa. Methods A retrospective analysis was performed on the clinical data of 504 patients who underwent prostate biopsy at our hospital during Jan. 2020 and Nov. 2024. Patients' age, body mass index(BMI), history of hypertension, diabetes and smoking, total prostate-specific antigen(tPSA), free prostate-specific antigen(fPSA), f/tPSA, prostate volume(PV), neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio(NLR), Prostate Imaging Reporting and Data System(PI-RADS)score, digital rectal examination(DRE)results, and pathological findings were collected. The patients were divided into the training and testing sets at a ratio of 7:3. Ten early diagnosis prediction models of PCa were constructed using 10 supervised machine learning algorithms. Model performance was evaluated and validated using metrics including area under the receiver operating characteristic curve(AUC), accuracy, sensitivity, specificity, calibration curves, and decision curve analysis(DCA). SHAP analysis was used to interpret the models, and to clarify the importance of each feature and the basis for model decisions. Results All models showed good predictive value, with the gradient boosting machine(GBM)model performing the best(AUC=0.905, accuracy=84.1%, sensitivity=90.2%, specificity=80.0%). Calibration curves indicated good calibration and fitting of the GBM model, while DCA demonstrated favorable clinical net benefits. SHAP analysis identified the most significant features affecting PCa occurrence in descending order:tPSA, f/tPSA, PIRADS score, PV, age, and DRE. Conclusion The GBM model exhibits the optimal performance among the 10 models. The importance of features for predicting the occurrence of PCa, from the highest to the lowest, is as follows:tPSA, f/tPSA, PIRADS score, PV, age, and DRE.

ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

BACKGROUND:Adipose-derived stem cells have anti-aging effects,but whether adipose-derived stem cells from donors of different ages are different needs further study. OBJECTIVE:To compare the biological properties of adipose-derived stem cells in old and young mice. METHODS:Adipose-derived stem cells were extracted from adipose tissue of C57BL mice aged 8 and 14 weeks,respectively.The differences of cell cycle,apoptosis,and proliferation of adipose-derived stem cells in old and young mice were compared.The expression levels of aging-related P21 and P27 genes and proteins of adipose-derived stem cells in old and young mice were detected by quantitative PCR and western blot assay. RESULTS AND CONCLUSION:Compared with old mouse adipose-derived stem cells,young mouse adipose-derived stem cells were more active,more regular in morphology,less apoptosis,faster proliferation,and lower in expression of age-related P21 and P27 genes and proteins.It has been proven that adipose-derived stem cells from young mice have better anti-aging effects.

Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.

Objective:To explore the predictive factors for ureteral stone impaction preoperatively and to construct a nomogram prediction model for impacted ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 209 patients with ureteral stones treated at The Second Affiliated Hospital of Zhengzhou University from July 2023 to June 2024. There were 164 males（78.5%）and 45 females（21.5%）. The age was 49（47，57）years，and the body mass index（BMI）was 25.10（23.55，27.24）kg/m2. Of the patients，85（40.7%）had comorbid hypertension and 85（40.7%）had comorbid diabetes. Stones were located on the left side in 124 patients（59.3%）and on the right side in 85 patients（40.7%）. Hydronephrosis was present in 169 patients（80.9%），and urine culture was positive in 29 patients（13.9%）. Patients were divided into impacted and non-impacted groups based on the presence or absence of ureteral stone impaction. Univariate and multivariate logistic regression analyses were performed to determine independent predictive factors for impacted ureteral stones. A nomogram model was constructed based on these results. The performance of the predictive model was evaluated using receiver operating characteristic（ROC）curves，calibration plots，and decision curve analysis（DCA）.Results:Among the 209 patients in this study，85（40.7%）experienced ureteral stone impaction. The impacted group had a significantly higher neutrophil-to-lymphocyte ratio（NLR）than the non-impacted group（3.91 ± 2.05 vs. 3.25 ± 2.10， P = 0.024），a higher rate of hydronephrosis［81.2%（69/85）vs. 80.6%（100/124）， P = 0.002］，larger stone surface area［（64.96 ± 39.96）mm2 vs.（51.86 ± 39.80）mm2， P = 0.021］，greater ureteral wall thickness（UWT）［（3.96 ± 1.37）mm vs.（3.06 ± 1.33）mm， P < 0.001］，and a higher ratio of the upper ureter diameter（D1）to the lower ureter diameter（D2）（DDR）（2.87 ± 1.58 vs. 2.00 ± 0.99， P < 0.001）. Univariate analysis showed that NLR，hydronephrosis，stone length，stone surface area，UWT，D1，D2，and DDR were statistically significant（ P < 0.05）. After multivariate logistic regression analysis，the following items were identified as independent predictors of impacted ureteral stones：NLR（ OR = 1.205，95% CI 1.026 - 1.415， P = 0.023），hydronephrosis（ OR = 1.840，95% CI 1.236 - 2.740， P = 0.003），stone length（ OR = 1.587，95% CI 1.142 - 2.206， P = 0.006），ureteral wall thickness（UWT）（ OR = 1.643，95% CI 1.263 - 2.136， P < 0.001），and DDR（ OR = 2.907，95% CI 1.040 - 8.130， P = 0.042）.Based on these independent predictive factors，a nomogram prediction model for impacted ureteral stones was constructed. The area under the ROC curve was 0.797（95% CI 0.737 - 0.858），and the calibration curve showed good consistency. The decision curve suggested that the model had good clinical net benefit. Conclusions:NLR，hydronephrosis，stone length，UWT，and DDR are all independent predictors for impacted ureteral stones. The nomogram model constructed based on these factors has good predictive performance.

Xiaoyao Powder has pharmacological action such as neuroprotection, anti-tumor, anti-depression, liver protection, regulation of intestinal flora, anti-fatigue and so on. Based on the five aspects of quality transfer and traceability, component measurability, component effectiveness, component specificity and compound compatibility environment, the quality marker (Q-marker) of Xiaoyao Powder was predicted and analyzed. It was considered that paeoniflorin, atractylenolide Ⅰ, atractylenolid Ⅱ, atractylenolide Ⅲ, liquiritin,glycyrrhizic acid, Saikosaponin A, Saikosaponin D, ferulic acid, Z-ligustilide, pachymic acid, Menthol,6-gingerol 8-gingerol and 10-gingerol have strong measurability and can be used as Q-marker of Xiaoyao Powder.