Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

OBJECTIVE: Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS: This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS: This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; 23(3): 282-288.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Retrospective Studies ; Aged ; Neutrophils ; COVID-19 Drug Treatment ; COVID-19/blood* ; Middle Aged ; Prognosis ; Lymphocytes ; Blood Platelets ; Platelet Count ; SARS-CoV-2 ; Aged, 80 and over ; Adult

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To analyze the association between eye-related behaviors and myopia among preschool chil-dren in Ningxia Hui Autonomous Region,and to develop a predictive nomogram model.Methods Using stratified cluster random sampling,36 062 preschool children from 400 randomly selected kindergartens in Ningxia Hui Autonomous Region were enrolled between October and December 2023.Primary caregivers of participants completed structured question-naires.Data were randomly split into a training set(n=25 243,70％)and a validation set(n=10 819,30％)in a ratio of 7∶3.The training set was used for model construction,and the validation set for external validation.Calibration plots and the Hosmer-Lemeshow(H-L)goodness-of-fit test assessed agreement between predicted and observed risks.Decision curve analysis(DCA)and clinical impact curve analysis(CICA)evaluated clinical utility.Results The myopia preva-lence among preschool children in Ningxia Hui Autonomous Region was 3.8％.A nomogram model based on binary Logistic regression showed area under the curve(AUC)values of 0.88(95％CI:0.87-0.89)for the training set and 0.89(95％CI:0.87-0.90)for the validation set,indicating strong discriminative ability.Calibration curves and H-L tests revealed good model fit(training set:x2=4.92,P=0.766;validation set:x2=5.52,P=0.961),with all P＞0.05.DCA and CICA confirmed clinical utility.The nomogram identified parental myopia,academic pressure,frequency of eye fatigue,daily screen time,and regular vision checks as the top five predictors of myopia.Conclusion The nomogram demonstrates promising potential for predicting myopia risk in preschool children in Ningxia Hui Autonomous Region,serving as a robust tool for clinical and educational myopia risk assessment.

Objective:To explore the evaluation value of blood routine derived indicators[derived neutrophil to lymphocyte ratio(dNLR),red blood cell distribution width to platelet ratio(RPR)]combine with serum C-reactive protein(CRP)and procalcitonin(PCT)detection for the clinical outcomes of children with Mycoplasma pneumoniae pneumonia(MPP).Methods:149 children with MPP who were admitted to our hospital from April 2022 to August 2024 were included,they were divided into good prognosis and poor prognosis groups based on their clinical outcomes 28 d after admission.The blood routine derived indicators,serum CRP,and PCT levels between the good prognosis group and the poor prognosis group were compared.The influencing factors of clinical outcomes in children with MPP were analyzed by Multiple logistic regression analysis,the value of blood routine derived indicators,serum CRP,and PCT testing alone and in combination to evaluate the clinical outcomes of children with MPP were analyzed by receiver operating characteristic(ROC)curves.Results:Among 149 children with MPP,113 had good prognosis and 36 had poor prognosis 28 d after admission,with a poor prognosis incidence rate of 24.16％(36/149).dNLR,RPR,CRP,and PCT levels in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).Univariate analysis showed that,the clinical outcome of children with MPP was related to pleural thickening,pleural effusion,severity disease and peak body temperature(P＜0.05).Multivariate Logistic regression analysis showed:Pleural thickening,pleural effusion,severity disease was severe,elevated dNLR,elevated RPR,elevated CRP and elevated PCT were risk factors for poor prognosis in children with MPP(P＜0.05).The area under the Curve(AUC)of dNLR,RPR,CRP and PCT combined to predict the prognosis of children with MPP was higher than that evaluated by the four indicators alone.Conclusion:Pleural thickening,pleural effusion,severe disease severity,elevated dNLR,elevated RPR,elevated CRP and elevated PCT are risk factors for poor prognosis in children with MPP.Moreover,the combined evaluate value of dNLR,RPR,CRP,and PCT is relatively high.

Objective To investigate the effects of sufentanil on proliferation,invasion,migration,and apoptosis of thyroid cancer cells,and analyze whether its mechanism is related to the AMP-activated protein kinase(AMPK)-silent information regulator 1(SIRT1)-peroxisome proliferat or activator receptor gamma coactivator 1α(PGC-1α)signaling pathway.Methods The human thyroid cancer cell line(TPC-1)was separated into a control group,L,M,H-sufentanil groups,and H-sufentanil+AICAR group.TPC-1 cell activity,apoptosis,invasion,migration,and expression of proteins were detected using CCK-8 assay,flow cytometry,Transwell assay,scratch assay,and Western blot,respectively.Results Compared with the control group,the absorbance value,invasion number,scratch healing rate,cleaved-Caspase-3,programmed cell death 1 ligand 1,B lymphoblastoma-2,p-AMPK/AMPK,SIRT1,and PGC-1αprotein levels in L,M,and H-sufentanil groups were reduced;the apoptosis rate and Bax protein level were increased(P＜0.05).AICAR treatment reversed the effect of H-sufentanil on the above indicators(P＜0.05).Conclusion Sufentanil may inhibit the AMPK-SIRT1-PGC-1α signaling pathway,thereby inhibiting the proliferation and invasion migration of thyroid cancer cells,and promoting cell apoptosis.