Background: Recurrent pregnancy loss undermines the physical and mental health of women. Recent randomized controlled trials have reported some effects of traditional Chinese medicine (TCM); however, whether various TCM methods have different effectiveness remains unclear. Objective: To comprehensively evaluate the efficacy and adverse events of TCM for patients with RPL and to explore whether various TCM methods have different effectiveness. Methods: Ten databases were searched up to May 27, 2024. The risk of bias was assessed using the RoB2 tool. The certainty of the evidence was evaluated using the grading of Recommendations, Assessment, Development, and Evaluation tool. Pairwise and network analyses were conducted using Stata 18.0. Results: A total of 47 randomized controlled trials enrolling 6678 women with RPL were included. Pairwise analysis showed that use of TCM had a significantly lower miscarriage rate (RR 0.50 [95% CI 0.45, 0.55]), lower preterm birth rate (RR 0.81 [95% CI 0.67, 0.98), and lower adverse event rate (RR 0.46 [95% CI 0.37, 0.58]). Moreover, use of TCM was associated with a higher alive-fetus rate (RR 1.21 [95% CI 1.15, 1.26]), live-birth rate (RR 1.20 [95% CI 1.15, 1.25]), and full-term rate (RR 1.37 [95% CI 1.23, 1.53]) compared with nonuse of TCM. Network analysis demonstrated that Bushenshugan combined with conventional Western medicine was ranked the best for the reduction of miscarriage rate. Discussion: Use of TCM is more likely to improve pregnancy outcomes and reduce adverse events compared with nonuse of TCM in patients with RPL. Different TCM methods have differences in reducing the miscarriage rate. The Bushenshugan method might be a potential optimal TCM therapy, but more high-quality evidence is needed to further validate and evaluate the efficacy and safety.

ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B （CHB） comorbid with metabolically associated fatty liver disease （MAFLD） and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed， and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information， traditional Chinese medicine syndromes information， laboratory indicators， and imaging examination results were collected using case report forms （CRF）. Tongue images of patients were acquired using a tongue diagnosis instrument， and tongue feature parameters were extracted using computer image processing technology. Frequency analysis， factor analysis， and cluster analysis， and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome， liver stagnation and spleen deficiency syndrome， and phlegm-blood stasis syndrome， with damp-heat accumulation syndrome accounting for the highest proportion （41.89%）. Compared with those without damp-heat accumulation syndrome， patients with damp-heat accumulation syndrome had significantly lower tongue proper H value， tongue coating H value， and tongue coating a^* value （P<0.05）， significantly higher tongue coating b^* value （P<0.05）， significantly increased levels of white blood cell （WBC）， red blood cell （RBC）， hemoglobin （HGB）， and glucose （GLU）， increased CAP values （P<0.05）， a higher proportion of males （P<0.05）， and a younger age （P<0.05）. Univariate and multivariate logistic regression analyses show that age， hepatitis B surface antigen （HBsAg）， diabetes， and damp-heat accumulation syndrome are independent risk factors for liver fibrosis （P<0.05）， and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD， which is significantly associated with enhanced inflammatory response， metabolic disorders， and early liver fibrosis， and is a key link in disease progression. Clinical attention and early intervention are needed.

The purpose of this paper is to explore the decoction and dosing methods of rhubarb root and rhizome in classical prescriptions and to provide a reference basis for the clinical use of rhubarb root and rhizome. By collating the relevant classical prescriptions of rhubarb root and rhizome in Shanghan Lun and Jingui Yaolüe, the relationship between its decoction and dosing methods and the syndrome was analyzed. The decoction of rhubarb root and rhizome in classical prescriptions can be divided into three categories: simultaneous decoction, decoction later, and other methods (impregnation in Mafei decoction, decoction with water from the well spring first taken in the morning, and pills). If it enters the blood level or wants to slow down, rhubarb root and rhizome should be decocted at the same time with other drugs. If it enters the qi level and wants to speed up, rhubarb root and rhizome should be decocted later. If it wants to upwardly move, rhubarb root and rhizome should be immersed in Mafei decoction. If it wants to suppress liver yang, rhubarb root and rhizome should be decocted with water from the well spring first taken in the morning. If the disease is prolonged, rhubarb root and rhizome should be taken in pill form. The dosing methods of rhubarb root and rhizome can be divided into five categories: draught, twice, three times, before meals, and unspecified. For acute and serious illnesses with excess of pathogenic qi and adequate vital qi, we choose draught. For gastrointestinal diseases, we choose to take the medicine twice. For achieving a moderate and long-lasting effect, we choose to take the medicine three times. If the disease is located in the lower part of the heart and abdomen, we choose to take it before meals. The use of rhubarb root and rhizome in clinical practice requires the selection of the appropriate decoction and dosing methods according to the location of the disease, the severity of the disease, the patient′s constitution, and the condition after taking the medicine.

BACKGROUND:During healing process of chronic wounds,excessive production of reactive oxygen species can impair the function of L929 fibroblasts,thereby delaying wound repair.Therefore,protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE:To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma(CMC-OCS/PRP)hydrogel on L929 cells under H2O2 stimulation. METHODS:CMC-OCS/PRP hydrogels were prepared,and the micromorphology,degradation performance,scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized.L929 cells with good growth state were taken and cultured in five groups.The control group was cultured conventionally.H2O2 was added to the H2O2 group.Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract+H2O2 was added to the CMC-OCS group.Platelet-rich plasma gel extract+H2O2 was added to the PRP group.The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract+H2O2.Each group was treated with hydrogel extract for 6 hours,and then H2O2 for 24 hours.After culture,the levels of active oxygen and malondialdehyde,apoptosis and expression of collagen fiber I protein were detected.In the presence of H2O2,the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours,respectively.Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION:(1)CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability,could effectively remove H2O2 and hydroxyl radicals in vitro,and had good biocompatibility.(2)Compared with the control group,the apoptosis rate,reactive oxygen species,and malondialdehyde levels were increased(P<0.05);the spread area of cells was decreased(P<0.05),and the expression of collagen fiber I protein had no significant changes(P>0.05)in the H2O2 group.Compared with the H2O2 group,reactive oxygen species level was decreased in the CMC-OCS group(P<0.05),malondialdehyde level was decreased(P<0.05),and cell spread area was increased(P<0.05)in the PRP group,CMC-OCS group,and CMC-OCS/PRP group;apoptosis rate was decreased in the CMC-OCS/PRP group(P<0.05),and collagen fiber I protein expression was increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05).(3)Compared with the control group,the number of cell migration was decreased(P<0.05),and the migration area had no significant change(P>0.05)in the H2O2 group.Compared with the H2O2 group,the number and area of cell migration were increased in the PRP group,CMC-OCS group,and CMC-OCS/PRP group(P<0.05),and the increase was most significant in the CMC-OCS/PRP group.(4)Under oxidative stress,CMC-OCS/PRP hydrogel can improve the migration ability of fibroblasts,resist cell apoptosis,and preserve cell extension function.

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective:To explore the progress and trend in research of target trial emulation (TTE) and provide reference for research in this field.Methods:A literature retrival of research papers in this field published as of November 30, 2024 was conducted based on three databases (i.e. PubMed, Web of Science, and Scopus). The papers which were highly cited were analyzed by Bibliometrix package in R 4.3.2. The co-occurrence network of keywords were analyzed by using software VOSviewer. The keyword burst test was carried out with software CiteSpace.Results:A total of 685 papers from 314 journals were included. The annual number of the papers published showed a significant growth in recent three years. JAMA Network Open had the highest publication mumber related to TTE (34 papers), Annals of Internal Medicine had the highest H-index and American Journal of Epidemiology had the highest total citations. In the 2 997 authors, Hernán MA made a greatest contribution. In the 2 046 institutions, Harvard Medical School was at leading position. The analysis on highly cited papers and keyword co-occurrence showed that TTE was mainly used in the studies of COVID-19 vaccine, cancer and the treatment efficacy and safety of chronic diseases. The analysis on the co-occurence of keyword burst test showed that keywords frequently used until 2024 were COVID-19 vaccine, cardiovascular disease and breast cancer. Conclusions:TTE is mainly used in the studies of public health emergency (such as COVID-19), patients with cancer and chronic diseases. TTE will play a crucial role when randomized controlled trial is difficult to conduct or current evidence requirement can not be met.

Objective To investigate the influencing factors of antibiotic-associated diarrhea(AAD)following congenital heart disease(CHD)surgery in pediatric patients,develop a nomogram-based predictive model,and validate its efficacy.Methods A retrospective analysis was conducted on the clinical data of pediatric patients who underwent CHD surgery in the Pediatric Intensive Care Unit(PICU)of a tertiary hospital in Guang-dong Province from July 2022 to July 2024.Patients were categorized into an AAD group and a non-AAD group.Univariate and multivariate logistic regression analyses were performed to identify risk factors for AAD occurrence following CHD surgery.A risk prediction model was developed,and a nomogram was constructed.The predictive performance of the model was evaluated using the Receiver Operating Characteristic(ROC)curve to calculate the area under the curve(AUC),the Hosmer-Lemeshow goodness-of-fit test,calibration curves,and clinical decision curve analysis.External validation of the model was conducted using data from patients in the Surgical Intensive Care Unit(SICU).Results The incidence of AAD following CHD surgery was 48.52%(229 out of 472 cases).Risk factors for AAD included the combined use of antibiotics,mechanical ventilation,elevated C-reactive protein levels,prolonged surgical duration,and extended antibiotic usage time(all with OR>1,P<0.05).Conversely,probiotic administration was identified as a protective factor(OR<1,P<0.05).The predictive model demon-strated excellent discrimination,as evidenced by the ROC curve areas:0.922(95%CI:0.894～0.951)in the modeling group,0.886(95%CI:0.838～0.915)in the internal validation group,and 0.862(95%CI:0.784～0.941)in the external validation group.Additionally,the model exhibited satisfactory calibration,as indicated by the Hosmer-Lemeshow test results:χ2=7.96,P=0.538 in the modeling group;χ2=4.24,P=0.895 in the inter-nal validation group;and χ2=9.923,P=0.270 in the external validation group.Furthermore,the model provided significant clinical utility.Conclusions Combined antibiotic use,duration of antibiotic therapy,mechanical ventilation,surgical duration,C-reactive protein(CRP)levels,and probiotic administration are key factors influ-encing the occurrence of AAD.The risk prediction model developed based on these variables demonstrates robust predictive performance and can serve as a valuable reference for the development and implementation of preventive and therapeutic strategies in clinical practice.

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective To explore the efficacy of Ludangshen oral liquid combined with piperacillin tazobactam in the treatment of severe pneumonia and its influence on inflammatory factors and immune function.Methods A total of 80 patients with severe pneumonia who were treated in Jiangxi Chest Hospital from January 2024 to March 2025 were selected and randomly divided into control group and observation group,with 40 cases in each group.The control group was treated with intravenous infusion of piperacillin tazobactam,while the observation group was additionally given Ludangshen oral liquid on the basis of the treatment given to control group.The therapeutic effects,inflammatory indicators[interleukin-6(IL-6),procalcitonin(PCT),C-reactive protein(CRP)],immune function indicators[immunoglobulin(Ig)G,IgA,IgM],blood gas indicators[arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),pH,fraction of inspired oxygen(FiO2)],pulmonary function indicators[forced expiratory volume in one second(FEV1),forced vital capacity(FVC),FEV1/FVC]and the occurrence of drug-related adverse events of two groups of patients were compared.Results The total effective rate of treatment in observation group was significantly higher than that in control group(P＜0.05).After treatment,IL-6,PCT,CRP,PaCO2 and FiO2 in both groups of patients were significantly lower than those before treatment,while IgG,IgA,IgM,PaO2,pH,FEV1,FVC and FEV1/FVC were significantly higher than those before treatment(P＜0.05).The IL-6,PCT,CRP,PaCO2 and FiO2 in observation group were significantly lower than those in control group,while IgG,IgA,IgM,PaO2,pH,FEV1,FVC and FEV1/FVC were significantly higher than those in control group(P＜0.05).During the treatment period,there was no statistically significant difference in the incidence of drug-related adverse events between two groups of patients(P＞0.05).Conclusion The combination of Ludangshen oral liquid and piperacillin tazobactam for the treatment of severe pneumonia has a good efficacy,can enhance pulmonary function,and has a good safety.