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.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Aim To investigate the therapeutic effects of cinnamaldehyde on synovial lesions in mice with knee osteoarthritis(KOA)and its regulatory mecha-nism in the phagocytic function of synovial macropha-ges.Methods In the animal experiments,mouse ser-um and synovial tissue were extracted.HE staining was used to evaluate the inflammatory cell infiltration in the synovial tissue.ELISA was employed to detect the lev-els of inflammatory factors such as interleukins in the serum.Western blot was used to detect the expression of Ras homolog family member A(RhoA),Rho-associ-ated protein kinase 1(ROCK1),myosin light chain(MLC),and p-MLC proteins in the synovial tissue.RT-qPCR was utilized to detect the expression of in-flammatory factors and pathway-related mRNA in the synovial tissue.TUNEL staining was used to detect ap-optosis in the synovial tissue.In the cellular experi-ments,after the intervention,RAW267.4 cells were subjected to Western blot and RT-qPCR for the detec-tion of the aforementioned indicators,and confocal mi-croscopy was used to assess phagocytic function.Re-sults After cinnamaldehyde intervention,the synovial inflammatory infiltration was significantly reduced,the protein and mRNA expression of the RhoA/ROCK1/MLC signaling pathway was markedly downregulated,the fluorescence intensity of TUNEL staining signifi-cantly decreased,and the phagocytic function of macro-phages was enhanced.Conclusion Cinnamaldehyde can inhibit RhoA/Rock1/MLC signaling pathway,en-hance macrophage burial,improve synovial inflamma-tion,and delay the progression of KO A mice.

Aim To verify the mechanism of action of Carthami Flos-Lycopodii Herba in treating KOA carti-lage inflammation based on network pharmacology and in vitro and in vivo experiments.Methods The effec-tive ingredients of Carthami Flos-Lycopodii Herba were screened through the database,the core targets of"drug disease"were analyzed,and pathway enrichment analy-sis and molecular docking verification were conducted.Experimental verification:Primary chondrocytes were extracted from mice and divided into the control group,IL-1β group,treatment group,and treatment+TLR4 agonist group.CCK-8 method was used to screen the optimal intervention concentration of Carthami Flos-Ly-copodii Herba.ELISA was used to detect the content of inflammatory factors in chondrocytes.Western blot was employed to detect the protein expression related to cellular pathways.Subsequently,a KOA mouse model was constructed using the DMM method.After admin-istration,the knee joint injury of mice was evaluated u-sing safranin O-green staining.ELISA was used to de-tect the levels of inflammatory factors in serum.West-ern blot was employed to detect collagen Ⅱ,MMP13,Aggrecan,and apoptosis related protein expression in cartilage tissue.TUNEL staining was used to detect the apoptosis rate of cells.Results A total of 26 active ingredients of Carthami Flos-Lycopodii Herba were screened,as well as 123 potential targets for treating KOA.The enrichment analysis results indicated that it mainly involved mechanisms such as Toll like receptors and cell apoptosis.The experimental results showed that Carthami Flos-Lycopodii Herba alleviated the in-flammatory response of chondrocytes and affected the expression of pathway related proteins.Compared with KOA mice,safflower stretched muscle grass could im-prove cartilage damage and reduce the concentration of serum inflammatory factors,regulate the expression of collagen Ⅱ,MMP13,Aggrecan,and apoptosis related proteins in cartilage tissue,and reduce the fluorescence intensity of TUNEL staining in the tissue.Conclusions Carthami Flos-Lycopodii Herba can improve KOA cartilage inflammation,and its mechanism may be relat-ed to the TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.

Objective To investigate the effects of indirect moxibustion on the expressions of DNA methyltransferases(DNMT)and methylation of the brain-derived neurotrophic factor(BDNF)promoter region in uterine tissues of rats with primary dysmenorrhea(PD);To explore the mechanism of epigenetic regulation of indirect moxibustion on PD model rats.Methods A total of 32 female SD rats were randomly divided into blank group,model group,indirect moxibustion group and Western medicine group,with 8 rats in each group.The PD model with cold dampness stagnation syndrome was established using ice-water baths combined with estradiol benzoate and oxytocin.Starting from the first day of modeling,the indirect moxibustion group received salt-partitioned moxibustion at"Shenque"and ginger-partitioned moxibustion at"Guanyuan"for 20 min,while the Western medicine group was gavaged ibuprofen solution.Both interventions were given once a day for 10 days.On day 11,writhing responses were observed and scored after oxytocin injection,Western blot and RT-qPCR were used to detect protein and mRNA expression of BDNF,DNMT3A and DNMT3B in uterine tissue,immunohistochemical staining was used to detect the positive expressions of DNMT3A and DNMT3B in uterine tissue.The DNA methylation of BDNF promoter region in uterine tissue was detected by sulfite sequencing.Results Compared with the blank group,the writhing latency was shortened and the writhing score increased in the model group(P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue increased(P<0.01),the positive expressions of DNMT3A and DNMT3B increased(P<0.01),and the DNA methylation rate in BDNF promoter region decreased(P<0.01).Compared with the model group,the writhing latency was lengthened and the writhing score decreased in the indirect moxibustion group and Western medicine group(P<0.05,P<0.01);the protein and mRNA expressions of BDNF,DNMT3A and DNMT3B in uterine tissue decreased(P<0.05,P<0.01),the positive expressions of DNMT3A and DNMT3B decreased(P<0.01),and the DNA methylation rate in BDNF promoter region increased(P<0.01).Conclusion Indirect moxibustion at"Shenque"and"Guanyuan"may inhibit the transcription of BDNF by increasing the DNA methylation level of BDNF promoter region,and reduce the expression of BDNF,so as to relieve the pain of PD rats.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

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*