Objective To investigate the inhibitory effect of Zheng Gan Decoction(ZGF)on tumor progression in a rat model of diethylnitrosamine(DEN)-induced hepatocellular carcinoma(HCC)and explore the possible mechanism.Methods Seventy SD rats were subjected to regular intraperitoneal injections of DEN(50 mg/kg)for 12 weeks to induce HCC tumorigenesis,with another 10 rats receiving saline injections as the normal control.After successful modeling,the rats were randomized into 5 groups(n=10)for daily treatment with distilled water(model group),Huaier Granules(4 g/kg;positive control group),or ZGF at low,medium,and high doses(2,4,and 8 g/kg,respectively)via gavage for 17 weeks.Body weight changes of the rats were monitored,and after completion of the treatments,the rats were euthanized for measurement of liver,spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining.The expressions of YAP,p-YAP,MST1,LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting.Results Compared with the normal control rats,the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate,increased body weight and liver and spleen indices,and a lowered thymus index.ZGF treatment obviously reduced liver and spleen indices,increased the thymus index,and improved pathologies of the liver tissues of the rat models.Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats,which also exhibited significantly upregulated hepatic expressions of MST1,LATS1 and p-LATS1.Conclusion ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression,which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.

OBJECTIVE: To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 (CYP19A1) gene with risk of Breast cancer. METHODS: Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No. 2021-182). RESULTS: No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups (P > 0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group (P < 0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages III-IV were significantly higher than those at stage I-II (P < 0.05). CONCLUSION Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.
Humans ; Female ; Breast Neoplasms/genetics* ; Aromatase/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Middle Aged ; Genetic Predisposition to Disease ; Adult ; Genotype ; Case-Control Studies ; Alleles ; Gene Frequency ; Risk Factors ; Aged

Malignant tumors (commonly referred to as cancer) represent a major global public health challenge and contribute significantly to the worldwide disease burden. Early screening plays a critical role in improving detection rates, enabling timely intervention, and enhancing patient survival rates. However, current cancer screening guidelines primarily focus on site-specific screening, which may not fully address the need for comprehensive early detection. A scientifically rational, multi-cancer screening approach offers several advantages: it optimizes the use of biological samples, reduces time costs for participants, enhances the efficiency and comprehensiveness of screening, and minimizes overall expenses. Such an approach also facilitates the rational allocation of healthcare resources, ultimately helping to reduce the societal burden of cancer. To address this need, the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China. This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and international researches on cancer screening, early detection, and treatment for prevalent malignancies. Drawing upon China's unique demographic and healthcare context, as well as practical screening experiences, the consensus provides evidence-based recommendations on target populations, screening technologies, and procedural workflows for multi-cancer screening. These guidelines align with the principles and methodologies established by the World Health Organization (WHO), aiming to enhance the effectiveness of combined cancer screening in China, improve early detection rates, and provide a scientific foundation for national cancer prevention and control strategies.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To assess the association of single nucleotide polymorphisms of rs700519 and rs4646 loci of cytochrome P450 19A1 ( CYP19A1) gene with risk of breast cancer. Methods:Two hundred patients with breast cancer treated at Xinxiang Central Hospital between January 2019 and January 2024 and 100 healthy individuals were enrolled as the study group and control group, respectively. The genotypes of the CYP19A1 gene at the rs700519 and rs4646 loci were determined by direct sequencing. The general data, distribution of CYP19A1 genotypes and alleles were compared between the two groups. This study has been approved by the Medical Ethics Committee of Xinxiang Central Hospital (Ethics No.2021-182). Results:No significant difference was found in age, body mass index, times of conception and proportion of menopause between the two groups ( P>0.05). The frequencies of AA genotype and A allele at the rs700519 locus, and the CC genotype and C allele at the rs4646 locus in the study group were significantly higher than those of the control group ( P<0.05). The frequencies of AA genotype at the rs700519 locus and CC genotype at the rs4646 locus in patients with breast cancer at stages Ⅲ-Ⅳ were significantly higher than those at stage Ⅰ-Ⅱ ( P<0.05). Conclusion:Polymorphisms of CYP19A1 gene at the rs700519 and rs4646 loci are associated with susceptibility of breast cancer. The AA and CC genotypes at the two loci may increase the risk for breast cancer.

Objective:To evaluate the impact of implementing a regional hierarchical medical management model based on the medical internet of things (medical IoT) on the frequency of emergency department visits and hospitalizations, as well as related medical expenses, in patients with chronic obstructive pulmonary disease (COPD).Methods:This retrospective study included COPD patients enrolled in the regional hierarchical medical management system based on Medical IoT across 21 community health service centers in Songjiang District, Shanghai, between July 2017 and May 2018. Utilizing patient data from the year prior to enrollment as the baseline, changes in the number of emergency visits, hospitalizations, and associated medical costs during the first and second years of management were compared. Changes for patients receiving drug treatment were also analyzed.Results:A total of 973 COPD patients were enrolled. The mean age was 75.2±17.0 years, and 64.34% (626/973) were male. Compared to baseline, all COPD patients in the first year of management showed significant reductions: emergency visits decreased by 33.67%, total emergency costs by 45.60%, hospitalizations by 27.15%, and total hospitalization costs by 25.42%. In the second year, reductions were: emergency visits by 28.08%, total emergency costs by 36.10%, hospitalizations by 35.26%, and total hospitalization costs by 18.13% (all P<0.05). Among patients receiving drug therapy, reductions in the first year were: emergency visits by 39.66%, total emergency costs by 47.54%, hospitalizations by 25.19%, and total hospitalization costs by 28.40%. In the second year, reductions were: emergency visits by 46.98%, total emergency costs by 45.99%, hospitalizations by 41.98%, and total hospitalization costs by 24.94% (all P<0.05). No significant differences were observed before and after management for patients without drug treatment. Conclusion:The implementation of the regional hierarchical medical management model based on Medical IoT significantly reduced the frequency of emergency visits and hospitalizations, as well as related costs, for COPD patients.

OBJECTIVES: To investigate the inhibitory effect of Zheng GanDecoction (ZGF) on tumor progression in a rat model of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and explore the possible mechanism. METHODS: Seventy SD rats were subjected to regular intraperitoneal injections of DEN (50 mg/kg) for 12 weeks to induce HCC tumorigenesis, with another 10 rats receiving saline injections as the normal control. After successful modeling, the rats were randomized into 5 groups (n=10) for daily treatment with distilled water ( model group), Huaier Granules (4 g/kg; positive control group), or ZGF at low, medium, and high doses (2, 4, and 8 g/kg, respectively) via gavage for 17 weeks. Body weight changes of the rats were monitored, and after completion of the treatments, the rats were euthanized for measurement of liver, spleen and thymus indices and morphological and histopathological examinations of the liver tissues using HE staining. The expressions of YAP, p-YAP, MST1, LATS1 and p-LATS1 in the liver tissues were detected using immunohistochemistry and Western blotting. RESULTS: Compared with the normal control rats, the rat models with DEN-induced HCC exhibited much poorer general condition with a significantly reduced survival rate, increased body weight and liver and spleen indices, and a lowered thymus index. ZGF treatment obviously reduced liver and spleen indices, increased the thymus index, and improved pathologies of the liver tissues of the rat models. Immunohistochemistry and Western blotting showed a dose-dependent reduction of YAP expression and an increment of p-YAP expression in ZGF-treated rats, which also exhibited significantly upregulated hepatic expressions of MST1, LATS1 and p-LATS1. CONCLUSIONS ZGF inhibits DEN-induced HCC in rats by activating the Hippo/YAP pathway via upregulating MST1 and LATS1 expression, which promotes YAP phosphorylation and degradation to suppress proliferation and induce apoptosis of the tumor cells.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Diethylnitrosamine ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Protein Serine-Threonine Kinases/metabolism* ; Carcinoma, Hepatocellular/drug therapy* ; YAP-Signaling Proteins ; Liver Neoplasms/drug therapy* ; Hippo Signaling Pathway ; Male ; Liver Neoplasms, Experimental/metabolism* ; Transcription Factors/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism*

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*