This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

PURPOSE: Bone cement-reinforced fenestrated pedicle screws (FPSs) have been widely used in the internal fixation and repair of the spine with osteoporosis in recent years and show significant improvement in fixation strength and stability. However, compared with conventional reinforcement methods, the advantages of bone cement-reinforced FPSs remain undetermined. This article compares the effects of fenestrated and conventional pedicle screws (CPSs) combined with bone cement in the treatment of osteoporosis. METHODS: A clinical control study of FPSs and CPSs combined with bone cement reinforcement in osteoporotic vertebral internal fixation was performed using the database PubMed, Embase, Cochrane Library, CNKI, the Wanfang, and the China Biomedical Literature Service System. Two evaluators screened the relevant literature in strict accordance with the inclusion criteria (diagnosis of participants, type of clinical study, treatment with FPS and CPS, and outcome indicators) and exclusion criteria (duplicate literature and missing or incorrect data) and independently conducted data extraction and quality evaluation. Clinical control studies of direct comparison between FPS and CPS combined with bone cement reinforcement in patients who were definitively diagnosed with thoracolumbar fractures or spinal degenerative diseases were included. Quality evaluation was conducted using the Cochrane risk bias evaluation tool for randomized controlled studies and using the Newcastle-Ottawa scale for retrospective case-control studies. RevMan software (version 5.3) was used for the meta-analysis to compare the clinical efficacy, radiological results, and related complications of the 2 methods. RESULTS: A total of 13 articles were included, including 7 randomized controlled studies and 6 retrospective case-control studies. There were 909 patients in these studies, 451 in the FPS and polymethyl methacrylate (FPS & PMMA) group and 458 in the CPS and polymethyl methacrylate (CPS & PMMA) group. The results of the meta-analysis showed that there was no significant difference between the 2 groups in operation time, hospital stay, visual analogue score, Japanese orthopaedic association score, Oswestry disability index score, Cobb angle, vertebral body deformation index and fusion rate (p > 0.05). The mean difference of intraoperative bleeding volume was -10.45, (95% confidence intervals (CI) (-16.92, -3.98), p = 0.002), the mean difference of loss height of the anterior edge of the vertebral body after surgery was -0.69 (95% CI (-0.93, -0.44), p < 0.001), and the relative risk (RR) of overall complication rate was 0.43 (95% CI (0.27, 0.68), p < 0.001), including the RR of bone cement leakage rate was 0.57 (95% CI (0.39, 0.85), p = 0.005). The screw loosening rate (RR = 0.26, 95% CI (0.13, 0.54), p < 0.001) of the FPS group was significantly lower than that of the CPS group. CONCLUSION The existing clinical evidence shows that compared with the CPS combined with bone cement, the use of FPS repair in the internal fixation of an osteoporotic vertebral body can reduce the amount of intraoperative bleeding, be more conducive to maintaining the height of the vertebral body, and significantly reduce the incidence of postoperative complications such as bone cement leakage and screw loosening.
Humans ; Pedicle Screws ; Bone Cements ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Fracture Fixation, Internal/instrumentation*

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective Taking a tertiary Traditional Chinese Medicine(TCM)hospital in Beijing as an example,it explores the differences in service quality perception among medical providers in Internet-based diagnostic services,aiming to provide robust support for the digital transformation of TCM medical services.Methods A questionnaire survey was conducted among 145 doctors who had diagnostic privileges on the Internet hospital platform of a certain hospital in September 2024.The survey focused on doctors'perceptions and satisfaction differences between online and offline medical service quality.Data processing and analysis were performed using EXCEL and SPSS 26.0 software,including descriptive analysis,reliability and validity tests,and rank-sum tests.Results 66.34%of the doctors recognized the Internet hospital platform established by the hospital,but the average satisfaction score(3.86)was still lower than that of offline outpatient service platforms,which was 4.59.Especially in the three dimensions of diagnosis and treatment,quality assurance,and psychosocial care,the perception of online service quality was significantly lower than that of offline services(P＜0.001).Despite this,82.76%of doctors were still inclined to recommend the internet-based diagnostic model to suitable patients.Conclusion Internet hospitals should establish a refined and intelligent platform system and rigorous service quality control standards to optimize doctors'online consultation processes.Comprehensive training for online consulting doctors should be strengthened.By improving the service quality of medical providers,the integration of online and offline services can be promoted to meet patients'demands for high-quality medical services.

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

Objective Taking a tertiary Traditional Chinese Medicine(TCM)hospital in Beijing as an example,it explores the differences in service quality perception among medical providers in Internet-based diagnostic services,aiming to provide robust support for the digital transformation of TCM medical services.Methods A questionnaire survey was conducted among 145 doctors who had diagnostic privileges on the Internet hospital platform of a certain hospital in September 2024.The survey focused on doctors'perceptions and satisfaction differences between online and offline medical service quality.Data processing and analysis were performed using EXCEL and SPSS 26.0 software,including descriptive analysis,reliability and validity tests,and rank-sum tests.Results 66.34%of the doctors recognized the Internet hospital platform established by the hospital,but the average satisfaction score(3.86)was still lower than that of offline outpatient service platforms,which was 4.59.Especially in the three dimensions of diagnosis and treatment,quality assurance,and psychosocial care,the perception of online service quality was significantly lower than that of offline services(P＜0.001).Despite this,82.76%of doctors were still inclined to recommend the internet-based diagnostic model to suitable patients.Conclusion Internet hospitals should establish a refined and intelligent platform system and rigorous service quality control standards to optimize doctors'online consultation processes.Comprehensive training for online consulting doctors should be strengthened.By improving the service quality of medical providers,the integration of online and offline services can be promoted to meet patients'demands for high-quality medical services.

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

Objective:To investigate the relationship between different states of cardiac function and their changes during the course of diabetic foot ulcers(DFU), and to evaluate their impact on patient prognosis.Methods:A retrospective analysis was conducted on 194 DFU patients who were rehospitalized at approximately 3-month intervals. Basic clinical data and cardiac function-related indicators were collected at baseline and follow-up. Patients were followed until death or until November 10, 2024. Outcomes including ulcer healing, recurrence, minor amputation, and death were recorded. Logistic regression models were used to analyze the effects of cardiac function status and its changes on these four outcomes. Results:After treatment, the proportion of patients with NYHA class Ⅱ-Ⅲ decreased significantly from 33.5% at baseline to 21.6%( P=0.009). Serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) level also decreased after treatment compared with baseline [635.85(59.83, 453.28) pg/mL vs 728.67(81.48, 696.15) pg/mL, P=0.055]. Serum NT-proBNP level was significantly higher in the death group compared to the survival group( P=0.002). The proportion of DFU patients with baseline NYHA class Ⅱ-Ⅲ was significantly higher than that in those with class Ⅰ( P=0.012). Regression analysis showed that an improvement in NT-proBNP levels was associated with a lower risk of DFU recurrence( OR=0.378, 95% CI 0.183-0.779, P=0.008), and improvement in NYHA class was associated with a lower mortality risk( OR=0.074, 95% CI 0.020-0.275, P<0.001). Conclusion:Cardiac function status and its changes during the treatment of DFU patients have strong prognostic implications, particularly in predicting the risk of recurrence and death outcomes.