Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

OBJECTIVE: To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients. METHODS: The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively. RESULTS: A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival. CONCLUSION In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.
Humans ; East Asian People ; Hematologic Neoplasms/complications* ; Lymphoma/complications* ; Multiple Myeloma/complications* ; Neoplasms, Second Primary ; Retrospective Studies ; Survival Analysis

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q₁, Q₃) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q₁, Q₃) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q₁, Q₃) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ²=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.
Male ; Humans ; Female ; SARS-CoV-2 ; COVID-19/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.
Female ; Humans ; Uterine Cervical Neoplasms/pathology* ; HeLa Cells ; Fibronectins/metabolism* ; Culture Media, Conditioned ; Carcinoma, Squamous Cell/metabolism* ; Adenocarcinoma ; Cadherins/metabolism* ; RNA, Messenger/metabolism* ; Cell Movement ; Epithelial-Mesenchymal Transition/genetics* ; Cell Line, Tumor ; Cell Proliferation ; S100 Calcium Binding Protein A7/metabolism*

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ²=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ²<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ²<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ²=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ²=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.
Male ; Humans ; Female ; Young Adult ; Adult ; Helicobacter Infections ; Helicobacter pylori ; Bismuth ; Anti-Bacterial Agents/therapeutic use* ; Amoxicillin/adverse effects* ; Drug Therapy, Combination ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

ObjectiveTo investigate the feasibility of multiparametric MRI （mpMRI） combined with histogram analysis of apparent diffusion coefficient （ADC） in the assessment of patients with variant histology （VH） of urothelial carcinoma （UC）. MethodWe retrospectively analyzed the data of patients pathologically diagnosed with UC who underwent mpMRI in the First Affiliated Hospital of Sun Yat-sen University between March 2015 and March 2023. The patients were divided into VH group （urothelial carcinoma mixed with other histologies） and non-VH group （pure urothelial carcinoma） according to pathological results. We performed propensity score 1：1 nearest-neighbor matching on the two groups based on age and gender and 49 patients were included in each group. The regions of interest （ROIs） of the whole tumor were delineated manually by using ITK-SNAP software and Pyradiomics was applied to extract ADC histogram parameters. We compared the clinicopathological data， MRI morphological features and ADC histogram parameters between the groups. Multivariate logistic regression was used to identify independent risk factors and construct the prediction model. Receiver operating characteristic （ROC） curve analyses were performed to evaluate the diagnostic performance of these parameters for determining VH of UC. ResultsMRI morphological features including the lesion shape， vesical imaging-reporting and data system （Ⅵ-RADS）score， enhancement pattern and suspicious lymph node metastasis were markedly different between the two groups （all P < 0.05）. ADC _mean， ADC _median， ADC_25th， ADC_75th， ADC_10th and ADC_90th were significantly lower in patients with VH than those in non-VH group （all P<0.05）. Multivariate logistic regression analysis showed enhancement pattern， ADC_25th， ADC_75th and ADC mean were independent predictors （P < 0.05）. The combined model yielded the best predictive performance， with an area under the ROC curve （AUC） of 0.91 （95% CI： 0.83-0.96）. ConclusionsMpMRI combined with whole-tumor histogram analysis of ADC can serve as a reliable method for evaluating the presence of VH in UC， further to assist the clinical decision making.