ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

OBJECTIVE: To investigate the whole-genome differential methylation profile of patients with high-altitude polycythemia (HAPC). METHODS: In this study, a total of 20 adult male patients with HAPC were included, including 10 Tibetan and 10 Han patients. The control group consisted of 20 healthy adult males, including 10 Tibetan and 10 Han patients. Peripheral blood was collected from each group for DNA extraction and quality inspection, and DNA libraries were constructed. The differential methylation regions (DMRs) between groups were detected using reduced representation bisulfite sequencing, with enriched regions compared to those of the control group. The differential enrichment regions were selected, and the intersection of the enriched regions was associated with genes. The methylation enrichment regions that differed significantly between groups were filtered based on the number of enriched samples in the enriched regions between the groups. GO, KEGG functional, and pathway analysis were performed on the differentially associated gene sets to reveal significant differences between the patients and control groups at the functional and pathway levels. RESULTS: In comparison with the control group, 17 152 sites with more than 25% difference and 15 558 sites with less than -25% difference were identified in Tibetan patients. The top 5 genes with the largest methylation differences between the two groups were MCCC2, RP3-399L15.3, ZNF621, RP11-394A14.2 and SLC39A10. The top significantly different pathways annotated in the differentially expressed genes pathway was serotonergic synapse. In comparison with the control group, 2 687 CpG sites with a greater than 25% difference and 2 602 CpG sites with a less than -25% difference were identified in Han patients. The top 5 genes with the largest methylation differences between the two groups were NAA25, CORO2B, PDC, ZNF853, and MLLT10. The top significantly different pathways annotated in the differentially expressed genes pathway were glutamatergic synapse, retrograde endocannabinoid signaling, Rap1 signaling pathway and cholinergic synapse. In comparison with the control group, 3 895 CpG sites with a greater than 25% difference and 3 969 CpG sites with a less than -25% difference were identified in HAPC patients. The maximum methylation difference between the two groups could reach 78.1%, while the minimum was -42.6%. The top 5 genes with the largest methylation differences between the two groups were MCCC2, ARSJ, CTNNA3, SLC39A10, and SWAP70. The top significantly different pathways annotated in the differentially expressed genes pathway was signaling pathways regulating pluripotency of stem cells. CONCLUSION The occurrence of HAPC may be related to abnormal changes in DNA methylation, and methylation sites may be helpful for the early diagnosis of HAPC.
Humans ; DNA Methylation ; Altitude ; Polycythemia/genetics* ; Male ; Adult ; CpG Islands

Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Objective:To explore the clinical efficacy of metoprolol combined with trimetazidine on elderly patients with coronary heart disease(CHD)and chronic heart failure(CHF).Methods:This randomized controlled trial enrolled 120 elderly CHD+CHF patients admitted to Army 73rd Group Military Hospital of Chinese PLA between June 2020 and June 2023.Patients were divided into control group(metoprolol based on routine treatment)and in-tervention group(additional trimetazidine therapy).Each group consisted of 60 patients,treated for 1 month.The clinical efficacy,left ventricular ejection fraction(LVEF),cardiac index(CI),left ventricular end-systolic diame-ter(LVESd),left ventricular end-diastolic diameter(LVEDd),serum levels of brain natriuretic peptide(BNP),high sensitive C-reactive protein(hsCRP),platelet a granule membrane protein-140(GMP-140),intercellular adhesion molecule-1(ICAM-1)and growth differentiation factor 15(GDF-15),and incidence of adverse reac-tions were compared between the two groups.Results:The total effective rate of the intervention group was significant-ly higher than that of the control group(95.00％vs.81.67％,P=0.023).Compared to patients in the control group,those in the intervention group had significant lower LVESd[(35.03±5.14)mm vs.(40.63±3.87)mm],LVEDd[(43.53±4.27)mm vs.(48.36±5.22)mm],levels of BNP[(94.35±7.55)pg/ml vs.(127.86±45.11)pg/ml],hsCRP[(0.91±0.28)mg/L vs.(1.47±0.52)mg/L],GMP-140[(7.14±1.06)μg/L vs.(9.37±1.59)μg/L],ICAM-1[(43.81±5.75)pg/ml vs.(52.74±5.83)pg/ml]andGDF-15[(891.46±62.51)pg/ml vs.(1025.57±110.08)pg/ml],and significant higher LVEF[(55.62±5.11)％vs.(47.35±8.61)％]and CI[(3.41±0.38)L·min-1·m-2 vs.(3.08±0.31)L·min-1·m-2](P＜0.001 all).There was no significant difference in the total inci-dence of adverse reactions between the intervention group and control group(8.33％vs.11.67％,P=0.543).Conclu-sion:Metoprolol combined trimetazidine may relieve myocardial inflammatory response and injury,and inhibit ventricular remodeling,thereby improve cardiac function in elderly patients with CHD and CHF.