Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

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.

Recent clinical trials have demonstrated a protective effect in using traditional Chinese medicine Tongxinluo (TXL) capsule to treat atherosclerosis. However, clinical evidence of the effects of TXL treatment on coronary plaque vulnerability is unavailable. In response, we developed this study to investigate the hypothesis that on the basis of statin therapy, treatment with TXL capsule may stabilize coronary lesions in patients with acute coronary syndrome (ACS). The TXL-CAP study was an investigator-initiated, randomized, double-blind clinical trial conducted across 18 medical centers in China. Patients with ACS aging from 18 to 80 years old who had a non-intervened coronary target lesion with a fibrous cap thickness (FCT) < 100 μm and lipid arc > 90° as defined by optical coherence tomography (OCT) were recruited. A total of 220 patients who met the selection criteria but did not meet the exclusion criteria will be finally recruited and randomized to receive treatment with TXL (n = 110) or placebo (n = 110) for a duration of 12 months. The primary endpoint was the difference in the minimum FCT of the coronary target lesion between TXL and placebo groups at the end of the 12-month follow-up. Secondary endpoints included: (1) changes of the maximum lipid arc and length of the target plaque, and the percentage of lipid, fibrous, and calcified plaques at the end of the 12-month period; (2) the incidence of composite cardiovascular events and coronary revascularization within the 12 months; (3) changes in the grade and scores of the angina pectoris as assessed using the Canadian Cardiovascular Society (CCS) grading system and Seattle angina questionnaire (SAQ) score, respectively; and (4) changes in hs-CRP serum levels. The results of the TXL-CAP trial will provide additional clinical data for revealing whether TXL capsules stabilizes coronary vulnerable plaques in Chinese ACS patients.

BACKGROUND: Spinal cord injury (SCI) survivors often experience constipation, which contributes to a reduced sense of well-being and a lower quality of life. Acupressure offers a non-pharmacological and non-invasive alternative therapy for treating constipation. OBJECTIVE: This study examined the effects of home-based acupressure on constipation and subjective well-being among SCI survivors. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This randomized controlled trial randomly assigned 80 adults from Hong Kong with SCI to two study groups. Using a video demonstration filmed by a registered traditional Chinese medicine practitioner, the intervention group performed home-based acupressure (self-administered or caregiver-assisted) twice daily, 15 min/session, for 10 consecutive days. The control group performed manual light touching of the abdomen with the same frequency and duration as the intervention group. Both groups received defecation education through a structured booklet. MAIN OUTCOMES MEASURES: The primary outcome was constipation severity. Secondary outcomes included bowel habits, psychological well-being, and quality of life. Focus group interviews were conducted after the intervention to collect subjective feedback from participants. RESULTS: Significant group-by-time interaction effects on constipation severity (P = 0.005) and quality of life (P = 0.001) revealed that home-based acupressure produced better results than the control. These treatment effects persisted at the one-month follow-up and continued to have a large effect size (Cohen's d > 0.8). Compared to the control group, the acupressure group also had improvements in anxiety (Cohen's d = 0.69) and depression (Cohen's d = 0.72) at the end of the intervention period. Three qualitative categories were identified from the focus group interviews: improvements in bowel function and management; reduced psychological distress following relief from constipation; and acceptability of home-based acupressure. CONCLUSION: Acupressure effectively relieves constipation, enhances psychological well-being, and improves quality of life in people with SCI. These data provide novel evidence supporting the use of home-based acupressure as an acceptable and effective therapy for treating constipation after SCI. TRIAL REGISTRATION ClinicalTrials.gov (NCT05558657). Please cite this article as: Li MQ, Li Y, Lam W, Yeung WF, Ho YS, Li JY, Sun TC, Yuen S, Hu YL, Yorke J. Home-based acupressure for managing constipation and subjective well-being in spinal cord injury survivors: A randomized controlled trial. J Integr Med. 2025; 23(6):660-669.
Humans ; Acupressure/methods* ; Constipation/psychology* ; Male ; Female ; Spinal Cord Injuries/complications* ; Middle Aged ; Adult ; Quality of Life ; Aged

Objective To explore the effect of PSMA gene on the biological behavior of prostate cancer cells and its molecular mechanism.Methods The expression of PSMA in prostate cancer and its relationship with prognosis were analyzed based on the GEPIA database.The mRNA and protein expression levels of PSMA in normal prostate epithelial cell RWPE-2 and prostate cancer cells DU145 and PC-3 were detected by RT-qPCR and Western blot,respectively.DU145 cells were used to construct knockdown cell lines,which were transfected with PSMA lentiviral knockdown plasmid and its negative control,serving as the sh PSMA group and the sh NC group,respectively;PC-3 cells were used to construct overexpression cell lines,which were transfected with PSMA lentiviral overexpression plasmid and its negative control,serving as the OE PSMA group and the OE NC group.CCK-8 assay and clone formation assay were used to detect the cell proliferation ability,wound healing assay and Transwell assay were used to detect the cell migration and invasion abilities,flow cytometry was used to detect the cell apoptosis,and Western blot was used to detect the expression of PI3K,Akt,BAX and Bcl-2 proteins.Prostate cancer cells of DU145 cell line were inoculated into the left armpit of BALB/c nude mice to form tumors,the tumor size was observed,and the tumor weight was measured;HE staining was used to evaluate the degree of damage;and the expression of PSMA was detected by immunohistochemistry.Results GEPIA database analysis showed that PSMA gene was highly expressed in prostate cancer and was related to the prognosis of prostate cancer.The results of RT-qPCR and Western blot showed that the mRNA and protein expression levels of PSMA in PC-3 and DU145 cells were higher than those in RWPE-2 cell(P<0.01).Compared with the sh NC group,the sh PSMA group showed decreased cell proliferation,migration and invasion abilities(P<0.05),and increased cell apoptosis rate(P<0.05).Compared with the OE NC group,the OE PSMA group demonstrated increased cell proliferation,migration and invasion abilities(P<0.05),and decreased apoptosis rate(P<0.05).Compared with the sh NC group,the protein expression of PI3K,Akt and Bcl-2 in the sh PSMA group decreased(P<0.05),and the protein expression of BAX increased(P<0.05).Compared with the OE NC group,the protein expression of PI3K,Akt and Bcl-2 in the OE PSMA group increased(P<0.05),and the protein expression of BAX decreased(P<0.05).Results of subcutaneous transplantation of prostate cancer in nude mice showed that the tumor weight of nude mice decreased(P<0.05),tumor cells exhibited irregular shapes,nuclei were deeply stained,and PSMA expression was weakly positive,after knocking down the PSMA.Conclusion PSMA gene may participate in regulating the proliferation,invasion,migration,and apoptosis of prostate cancer cells through the PI3K/Akt signaling pathway.

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

Objective:This study applies an integrated SWOT-CLPV framework combined with stakeholder analysis to systematically assess the strengths,weaknesses,opportunities,and threats of China's disease control inspector system,while identifying its control factors,leverage points,key problems,and vulnerabilities.Methods:Drawing on literature review,policy document analysis,and expert interviews with seven public health professionals,we extracted and categorized SWOT elements.A CLPV interaction analysis was conducted alongside stakeholder mapping to evaluate internal dynamics and systemic risks.Results:The inspector system demonstrates strengths in policy innovation and medical-public health integration,with external opportunities stemming from rising public health awareness and digital health advancements.However,the system faces weak endogenous momentum,limited leverage,and prominent control constraints and problem-prone areas,especially among grassroots institutions and inspectors themselves.Cross-sectoral coordination barriers and uneven local implementation contribute to significant institutional vulnerabilities.Conclusion:To enhance implementation and resilience,the system requires capacity building for key actors,improved governance structures,incentive and evaluation reforms,and strengthened coordination mechanisms to support the sustained and adaptive development of public health supervision.

Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.