Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective:To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment.Methods:This retrospective, multicenter, single-arm, pre–post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m2, and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups.Results:In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923–0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions:FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.

Deep brain stimulation(DBS)has witnessed rapid advancement as a neurosurgical intervention over the past four decades,addressing movement disorders and a spectrum of neuropsychiatric conditions.Notably,subthalamic nucleus deep brain stimulation(STN-DBS)is widely implemented in the management of Parkinson's disease(PD)patients experiencing refractory motor fluctuations and complications,and has shown promise in ameliorating non-motor symptoms(NMS).However,the long-term efficacy of STN-DBS on NMS remains a subject of scholarly discourse.This review endeavors to synthesize current knowledge regarding the long-term impacts,underlying mechanisms,and future research directions of STN-DBS in the context of NMS in Parkinson's disease.

Deep brain stimulation(DBS)has witnessed rapid advancement as a neurosurgical intervention over the past four decades,addressing movement disorders and a spectrum of neuropsychiatric conditions.Notably,subthalamic nucleus deep brain stimulation(STN-DBS)is widely implemented in the management of Parkinson's disease(PD)patients experiencing refractory motor fluctuations and complications,and has shown promise in ameliorating non-motor symptoms(NMS).However,the long-term efficacy of STN-DBS on NMS remains a subject of scholarly discourse.This review endeavors to synthesize current knowledge regarding the long-term impacts,underlying mechanisms,and future research directions of STN-DBS in the context of NMS in Parkinson's disease.

Objective:To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment.Methods:This retrospective, multicenter, single-arm, pre–post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m2, and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups.Results:In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923–0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions:FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.

Background: Total knee arthroplasty (TKA) is a common surgical procedure for patients with knee osteoarthritis. The patellar component plays a crucial role in knee biomechanics and can influence postoperative outcomes. This study aimed to investigate the relationship between radiological indices of patellar height and patient outcomes following TKA. Methods: A retrospective analysis was conducted on patients who underwent TKA for osteoarthritis. Radiographic measurements of patellar height, including the Insall-Salvati (IS) ratio, modified Blackburne-Peel (mBP) ratio, Caton-Deschamps ratio, and plateaupatellar angle (PPA), were obtained. Clinical outcomes were assessed using the Knee Society Score (KSS) and the Forgotten Joint Score-12 (FJS-12). Patient satisfaction and postoperative complications were also evaluated. Statistical analyses, including correlation analysis and multiple regression models, were performed to determine the association between radiological indices and patient outcomes. Results: The study included 330 cases that met the inclusion criteria. The analysis revealed significant correlations between different radiological indices of patellar height and patient outcomes. Lower postoperative PPA was correlated with worse KSS and range of motion scores. A decreased mBP ratio was associated with poorer FJS-12 responses and higher risks of dissatisfaction and patellar clunk or crepitus. Increased IS ratio was linked to a lower likelihood of incidental giving way of the knee. Advanced age was associated with reduced dissatisfaction and incidental giving way probabilities. Conclusions The findings of this study demonstrate that radiological indices of patellar height can predict patient outcomes following TKA. Assessing patellar height using various radiographic measurements provides valuable information for surgical planning and prognostic evaluation. Understanding the impact of patellar height on clinical outcomes can aid in optimizing TKA procedures and improving patient satisfaction. These findings emphasize the importance of considering patellar height as a predictive factor in TKA and highlight its potential role in guiding postoperative management and rehabilitation strategies.

[摘 要] 目的：探讨含SET结构域蛋白5（SETD5）对结肠癌细胞增殖、迁移和对5-氟尿嘧啶（5-FU）药物敏感性的影响及机制。方法：常规培养结肠癌细胞，用Lipofectamine 2000将siSETD5-NC、si-SETD5-1~3质粒转染至HT-29细胞中，将其分为对照组（未处理）、si-SETD5-NC组、si-SETD5组和si-SETD5+SC79组，si-SETD5+SC79组HT-29细胞转染质粒的同时用10 µmol/L SC79处理。qPCR法检测NCM460、HT-29和LoVo细胞中SETD5 mRNA表达，流式细胞术、细胞划痕法、WB法和CCK-8法分别检测各组HT-29细胞的凋亡情况、迁移能力、相关蛋白的表达，以及对5-FU的敏感性。结果：SETD5 mRNA在HT-29、LoVo细胞中均呈高表达（均P<0.01）。在HT-29细胞中成功地敲减了SETD5 mRNA（P<0.01）。敲减SETD5 mRNA可明显抑制HT-29细胞的增殖活性（P<0.01）、迁移能力（P<0.01）、相关蛋白（SETD5、p-PI3K、p-AKT1、p-mTOR蛋白）的表达（均P<0.01）、促进细胞凋亡（P<0.01），且提高其对5-FU的敏感性（P<0.01），这些作用均可被AKT激活剂SC79部分阻挡（P<0.05或P<0.01）。结论：SETD5在HT-29、LoVo细胞中高表达，SETD5通过PI3K/AKT1通路促进结肠癌HT-29细胞的增殖、迁移，且降低其对5-FU的敏感性，SETD5是结肠癌临床诊断、治疗的潜在靶点。

Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.

OBJECTIVE To establish fingerprints and multi-components determination of Jieze lotion, and use chemometrics methods for quality evaluation. METHODS The HPLC-DAD fingerprints was established and 10 components were recognized by comparison with references. Meanwhile, their contents were determined. The data were evaluated by the methods of chemometrics such as similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. RESULTS The similarity of 11 batches of Jieze lotion were all >0.95. The linearity was good(r≥0. 999 1) and the average recoveries were between 89.70% and 106.0% with the RSD of 1.52%−3.41%. Instrument precision, stability and reproducibility of the method were all great. The contents of the common ten components(gallic acid, protocatechuic acid, neochlorogenic acid, caftaricacid, 5-O-feruloylquinicacid, chlorogenic acid, phellodendrine chloride, magnoflorine, 4-O-feruloylquinic acid, berberinehydrochloride) were 40.103−55.841, 2.347−6.179, 8.336−23.810, 7.084−21.956, 33.098−53.833, 24.597−49.610, 21.587−31.188, 5.915−13.162, 115.381−189.702, 31.378−112.686 μg·mL−1, respectively. The results of chemometrics showed that the 11 batches of samples could be divided into 4 categories, and the strong characteristic peaks used to distinguish each batch of samples were berberine hydrochloride, 4-O-feruloylquinic acid, chlorogenic acid, neochlorogenic acid and 5-O-feruloylquinic acid. CONCLUSION The method is accurate and reliable, and it can be used for the quality control and comprehensive evaluation of Jieze lotion.