Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) among children aged 0-9 years in Guangzhou, so as to provide reference basis for further exploring scientifically effective prevention and control measures. Methods: Reported cases of HFMD in children aged 0-9 years in Guangzhou City from 2013-2025 were selected from China disease prevention and control information system, and the incidence in different years was analyzed descriptively; the trends of the composition ratio and incidence in various age groups were analyzed by using the Joinpoint regression model, spatial autocorrelation analyses were performed at the district level, and the seasonal autoregressive integrated moving average model (SARIMA) was applied to predict annual incidence rate for 2026. Results: From 2013 to 2025, the average annual reported incidence rate of HFMD among children aged 0-9 years in Guangzhou was 2 513.98/100 000, showing a fluctuating trend. Peaks of incidence occurred from May to July and from September to October. The male to female ratio was 1.49∶1. The average annual incidence rate was 4 743.99/100 000 in the 0-1 years age group, 3 298.19/100 000 in the 2-5 years age group, and 544.22/ 100 000 in the 6-9 years age group. Joinpoint regression analysis showed a decreasing trend in the proportion of the 0-1 years age group (APC= -6.02 %, t =-3.77) and an increasing trend in the proportion of the 6-9 years age group (APC=16.39%, t =5.67) (both P < 0.05 ). No significant global spatial clustering was observed at the district level; however, local scattered clusters were identified in certain areas. Using the SARIMA(2,0,0)(2,0,0) 12 model, the predicted annual incidence rate of HFMD among children aged 0-9 years in Guangzhou in 2026 was 2 680.56/100 000. Conclusions From 2013 to 2025, the annual incidence rate of HFMD among children aged 0-9 years in Guangzhou exhibited a fluctuating trend; the highest incidence rate is observed in the 0-1 years age group, while the proportion of cases in the 6-9 years age group increase year by year;and local spatial clusters of abnormal distribution are identified. It is essential to enhance risk monitoring and health education in key populations and areas to mitigate the risk of infection in children.

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective To investigate the factors influencing pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC)and its correlation with prognosis in patients with human epidermal growth factor receptor 2(HER2)-low breast cancer.Methods A retrospective analysis was conducted on patients with HER2-low breast cancer who underwent NAC at the Second Affiliated Hospital of Jiujiang College from February 28,2018 to February 28,2021.Patients were divided into pCR group(achieved pCR,n=143)and non-pCR group(did not achieve pCR,n=300)based on pCR status.General clinicopathological data were collected and compared between the two groups,including age,surgical method,NAC regimen,postoperative radiotherapy,clinical tumor stage,tumor cT stage,tumor cN stage,pathological type,tumor Nottingham grade,hormone receptor(HR)status,Ki-67 status,menopausal status,and endocrine therapy.Binary logistic regression analysis was used to identify factors influencing pCR after NAC.Propensity score matching(1:1)was employed to balance baseline characteristics between the two groups.The matched groups'baseline data were compared.Kaplan-Meier method was used for survival analysis of the matched cohorts.Multivariate Cox proportional hazards regression models were used to analyze the independent influence of pCR on disease-free survival(DFS)and overall survival(OS)in HER2-low breast cancer after matching.Results A total of 443 patients with HER2-low breast cancer receiving NAC were included,with a mean age of(49.5±8.0)years.Binary logistic regression analysis identified clinical tumor stage(OR=0.498,95%CI 0.267-0.930),HR status(OR=0.513,95%CI 0.328-0.801),Ki-67 status(OR=2.580,95%CI 1.366-4.874),tumor Nottingham grade Ⅲ(OR=3.197,95%CI 1.147-8.910),and endocrine therapy(OR=0.513,95%CI 0.328-0.801)as independent factors influencing pCR after NAC(P<0.05).After propensity score matching,80 patients remained in each group(PCR and non-PCR).No significant differences were found in clinicopathological characteristics between the matched groups(P>0.05).The median follow-up time was 45.0 months(95%CI 43.1-46.9)for pCR group and 43.0 months(95%CI 41.0-45.0)for non-pCR group.The DFS rate was significantly higher in pCR group than that in non-pCR group(87.5%vs.70.0%,P=0.004),but there was no significant difference in OS rate(88.8%vs.85.0%,P=0.438).Multivariate Cox regression analysis showed that pCR was an independent factor influencing on DFS(HR=0.312,95%CI 0.142-0.688,P=0.004),but not OS in HER2-low breast cancer patients.Conclusions Patients with HER2-low breast cancer who have a lower clinical tumor stage,HR-negative status,high Ki-67 expression,high tumor Nottingham grade,and absence of endocrine therapy are more likely to achieve pCR.Achieving pCR prolongs DFS significantly but does not significantly improve OS in these patients.

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*

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.