This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

BACKGROUND: There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region. OBJECTIVE: This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis. MAIN OUTCOME MEASURES: The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention. RESULTS: Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively. CONCLUSION: Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions. TRIAL REGISTRATION ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult ; Female ; Humans ; Male ; Young Adult ; Acupuncture Points ; Acupuncture Therapy ; Body Temperature ; Healthy Volunteers ; Lumbosacral Region/physiology* ; Moxibustion ; Adolescent

Background::The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods::We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results::We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions::REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.
Humans ; SARS-CoV-2 ; COVID-19/pathology* ; Cause of Death ; Lung/pathology* ; Autopsy

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis

Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G

Tomato (Solarium lycopersicum) is one of the most popular vegetables worldwide and is a classic model plant for studying fruit development and ripening due to its short growth cycle, clear genetic background and ease of molecular manipulation. This paper used virus-induced gene silencing (VIGS) to construct SlWRKY53b gene-silenced tomato fruits and analyzed the effect of SIWRKY531) gene silencing in the tomato fruit ripening process. We found that transient silencing of SIWRKY531) resulted indelayed in-broken color, higher chlorophyll contents (P<0.05) and reduced carotenoid contents (P<0.05) in tomato fruits, and color difference results indicated that the differences in L *, a * and b * values were consistent with fruit color changes. Further studies showed that genes significantly down-regulated (P<0.01) in SIWRKY531) gene-silenced tomato fruits include the chlorophyll degradation-related genes (AFCl, PAO, PPH, SGR1), carotenoid synthesis-related genes (PSYl, PDS, ZDS), ethylene synthesis pathway-related genes (ACOl, ACS2, NOR, AC03, EA, RIN), and cell wall degradation-related genes (PG, EXP, CELT.). Correlation analysis showed that the expression of SlWRKY53b was negatively correlated with chlorophyll contents and positively correlated with carotenoid contents and the expression of maturation-related genes. These results suggest that inhibition of SIWRKY531) expression at the transcrip-tional level can achieve the effect of delaying tomato fruit ripening, indicating that S1WRKY531) plays arole as a facilitator in the tomato fruit ripening process.

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans ; Female ; Lymphatic Metastasis ; B7-H1 Antigen/metabolism* ; Triple Negative Breast Neoplasms/pathology* ; Breast Neoplasms ; Osteonectin/therapeutic use* ; Prognosis