Objective : To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA) by network pharmacology and animal experiments. Methods : Traditional Chinese Medicine Systems Pharmcolog Database(TCMSP) and SwissTargetPrediction database were used to collect puerarin targets, and the targets of RA were obtained from GeneCards database and OMIM database. The PPI network was established by Cytoscape 3.7.2 software. Gene ontology(GO) function and Kyotoencyclopedia of genes(KEGG) enrichment analysis were performed through the Metascape database. RA rat-collagen-induced arthritis(CIA) model was reproduced using type Ⅱ collagen emulsion, 49 Wistar rats were randomly assigned to seven groups: control group, CIA model group, low-dose, medium-dose and high-dose puerarin group, methotrexate group, Tripterysium Glycosides Tablets group. Except for the control group, the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared. The redness and swelling of the joints and ankle joint pathological changes were observed in each group. Western blot was used to detect the expression of Glycogen synthase kinase3β(GSK-3β), beta-catenin(β-catenin) proteins in the synovium. Real-time quantitative polymerase chain reaction(qPCR) was used to detect the expression of GSK-3β, β-catenin and c-Myc mRNA in the synovium. Results : Puerarin had 134 targets genes, RA had 5 821 target genes, and there were 102 overlapping target genes of puerarin and RA. It involved 184 signaling pathways, including JAK-STAT signaling pathway, NF-κB signaling pathway, Wnt signaling pathway, et al. The results of animal experiments showed that after the intervention of M-puerarin and MTX, the symptoms of redness and swelling of the hind foot were alleviated, the inflammatory cell infiltration in the synovium of the joint was significantly reduced, and the damage of cartilage and bone tissue was reduced. Compared with CIA group, the expressions of GSK-3β, β-catenin protein and GSK-3β, β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P<0.05). Conclusion Puerarin has the characteristic of multi-components, multi-targets and multi-pathway intervention in RA. Puerarin may alleviate synovial hyperplasia, reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

The study employed network Meta-analysis to evaluate the efficacy and safety of Chinese patent medicines combined with recombinant human interferon α-2b(interferon) in the treatment of cervical human papillomavirus(HPV) infections. The relevant randomized controlled trial(RCT) published from inception to May 8, 2024 were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science. The modified Jadad scale and the Cochrane risk of bias tool were used to evaluate the quality of the included studies, and RevMan 5.4, R 4.3.3, and Stata 17 were used for data analysis. A total of 105 RCTs were included, involving 12 732 participants and 7 Chinese patent medicines: Baofukang Suppository, Compound Seabuckthorn Seed Oil Suppository, Huangqi Shengmai Decoction, Kangfu Gel, Kangfuyan Capsules, Kushen Gel, and Puling Penyankang Granules. Network Meta-analysis yielded the following results:(1)For improving the negative conversion rate of HPV, SUCRA top-ranked intervention was Puling Penyankang Granules + interferon.(2) For shortening vaginal discharge time, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(3) For reducing the serum level of hypersensitive C-reactive protein(hs-CRP), SUCRA top-ranked intervention was Baofukang Suppository + interferon.(4) For elevating the serum level of CD~+_4 T cells, SUCRA top-ranked intervention was Baofukang Suppository + interferon.(5) For elevating the serum level of CD~+_8 T cells, SUCRA top-ranked intervention was Kangfuyan Capsules + interferon.(6) For improving the CD~+_4/CD~+_8 ratio, SUCRA top-ranked intervention was Compound Seabuckthorn Seed Oil Suppository + interferon.(7)In terms of reducing serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), recurrence rate at 6 months after treatment, and incidence of adverse events, there were no significant differences between the interventions when compared pairwise. The cluster analysis revealed that Puling Penyankang Granules + interferon, Baofukang Suppository + interferon, Kangfu Gel + interferon, and Huangqi Shengmai Decoction + interferon simultaneously improved the negative conversion rate of HPV and reduced the incidence of adverse events. The findings suggested that Chinese patent medicines combined with interferon were effective in treating cervical HPV infection by enhancing the negative conversion rate, shortening the vaginal discharge time, and improving the levels of hs-CRP and T lymphocyte subsets. However, due to the limitations of sample size and quality of the included studies, these conclusions require further validation by studies with larger sample sizes and higher quality.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Papillomavirus Infections/virology* ; Interferon alpha-2/administration & dosage* ; Recombinant Proteins ; Drug Therapy, Combination ; Randomized Controlled Trials as Topic ; Antiviral Agents/administration & dosage* ; Interferon-alpha ; Papillomaviridae/physiology*

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.
Animals ; Antimalarials/pharmacology* ; Antiviral Agents ; Artemether ; Artemisinins ; Mammals

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Self Efficacy ; Self-Management ; Blood Glucose Self-Monitoring ; Blood Glucose ; Self Care

Objective: To explore the value of vector angle of Lorenz plots(LPs) and the role of combining B-line slope in improving the diagnostic efficiency of arrhythmia． Methods: LPs of 119 cases with ventricular premature contraction (VPC group ) ，97 cases with supraventricular premature contraction(SPC group) ，52 cases with type II°I atrioventricular block ( Ⅱ ° Ⅰ group) and 54 cases with type Ⅱ ° Ⅱ atrioventricular / sinoatrial block ( Ⅱ ° Ⅱ group) were retrospectively analyzed．The B-line slope and vector angle were measured，and the differences between groups were compared. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of B-line slope，vector angle and their combination between groups ，and MedCalc software was used for statistical comparison．The consistency of intra-observer and inter-observer measurements of B-line slope and vector angle was evaluated using Intra group correlation coefficient (ICC) and Bland-Altman plot. Results: There were significant differences between VPC group and SPC group，and between Ⅱ ° Ⅰ group and II°II group (P＜0. 05) ．The area under the curve (AUC) of B-line slope，vector angle，and the combination of the two in distinguishing ventricular and supraventricular premature contraction were 0. 81，0. 84 and 0. 87 respectively，and the AUC in distinguishing type Ⅱ ° Ⅰ and type Ⅱ ° Ⅱ atrioventricular / sinoatrial block were 0. 76，0. 78 and 0. 80 respectively．The ICC of vector angle was better than B-line slope (Intra-observer 0. 99 vs 0. 98，Inter-observer 0. 97 vs 0. 96) ． Conclusion Vector angle can be used to identify the type of arrhythmia，and has good intraobserver and interobserver consistency．Its combination with B-line slope has the highest accuracy in diagnosing arrhythmia，providing a new reference for clinical diagnosis and treatment.

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.