BackgroundDementia seriously affects the quality of life and lifespan of elderly people， with Alzheimer's disease （AD） being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD， but the causal relationship between the two still requires further research. ObjectiveTo investigate the potential causal relationship between gout and AD through a two-sample Mendelian randomization （MR） analysis， so as to provide references for the prevention and treatment of AD. MethodsData from Genome-Wide Association Studies （GWAS） extracted in 2024 were analyzed， using pooled data on gout （6 810 cases in the case group and 477 788 cases in the control group） published by UK Biobank in 2021 as the exposure variable， and data on AD （3 899 cases in the case group and 214 893 cases in the control group） published by FinnGen in the same year as the outcome variable. The inverse-variance weighted， MR-Egger regression， weighted median estimation， simple model and weighted model were used to analyze the potential causal relationship between gout and AD. Pleiotropic effects were assessed using MR-Egger regression. Heterogeneity assessment was conducted using Cochran's Q test. The leave-one-out analysis was carried out for sensitivity analysis. And a funnel plot was drawn to detect potential publication bias. ResultsThe inverse-variance weighted analysis demonstrated a negative causal relationship between gout and AD （OR=0.004， 95% CI： 0~0.700， P<0.05）. The plot resembled a symmetrical inversed funnel， indicating the absence of publication bias. No heterogeneity was detected by Cochran's Q test. The MR-Egger regression indicated no significant horizontal pleiotropy. Concerning the reverse directions， no significant associations between AD and gout were noted. ConclusionThere is a negative causal relationship between gout and AD， with gout potentially reducing the risk of developing AD. ［Funded by The Third Batch of Social Welfare and Basic Research Projects （Medical and Health） of Zhongshan City in 2022 （number， 2022B3017）］

Objective: To investigate the effect of a free pit and fissure sealing program for caries prevention on first permanent molars (six-year molars) in Haizhu District, Guangzhou, three years after its implementation in 2019. The study aims to provide a reference for the future development of pit and fissure sealing programs for children’s first permanent molars and the effective prevention and treatment of permanent tooth caries in children. Methods: A random sampling method was used. In 2022 October, 270 sixth-grade primary-school students in Haizhu District, Guangzhou, who had participated in the free pit and fissure sealing program for their first permanent molars in 2019, were placed in the sealant group. Another 223 age-matched students from the same schools who met the criteria for the pit and fissure sealing but did not participate in the program were placed in the control group. The first permanent molars of students in both groups were examined. The retention status of the sealant and the caries status of the first permanent molars were recorded for the sealant group, and the caries status of the first permanent molars was recorded for the control group. The 2022 results were compared with the results of a prior pit and fissure sealing program implemented in Haizhu District in 2011, three years after its implementation. Results: Compared with the control group, the caries rate in the sealant group decreased (15.56% vs. 21.52%, P>0.05), the caries detection rate was significantly lower (6.12% vs. 9.00%, P<0.001), and the mean number of decayed teeth was significantly reduced (0.19 vs. 0.37, P<0.001). Compared with the results of the pit and fissure sealing program in Haizhu District in 2011 (in 2014, the retention rate of the first permanent molar sealant was 65.56%, the intact rate was 42.25%, and the protection rate was 38.34%), the results of the pit and fissure sealing program in Haizhu District in 2019 [in 2022, the retention rate of the first permanent molar sealant was 86.09% (P<0.001), the intact rate was 47.00% (P<0.001), and the protection rate was 51.97%] were improved. Conclusion The quality of the pit and fissure sealing program for the first permanent molars in Haizhu District, Guangzhou in 2019 was good. It reduced the caries detection rate, and the retention rate of the sealant was maintained at a high level. However, the intact rate was less than 50%; therefore, it is necessary to vigorously promote oral-health education and examinations in all age groups, and to be attentive to the re-examination and re-sealing of fissure sealants.

Objective: To investigate the trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

Objective: To explore the possibility of performing allogeneic platelet-rich plasma (PRP) treatment for patients who were not suitable for autologous PRP collection through case reports of two patients with refractory wounds treated with allogeneic PRP. Methods: The ABO-compatible allogeneic whole blood was centrifuged 3 times to obtain allogeneic PRP within 6 hours of blood collection. Then the qualified allogeneic PRP was applied to 2 cases of refractory wound on the same day. Results: The platelet concentration in allogeneic PRP was higher than 1 000×10 /L, and the test results of infectious diseases, as well as the mixing of red blood cells and white blood cells, met the standard of quality control. Both patients achieved satisfactory wound healing outcomes (3 d). Conclusions: For patients who were not suitable for autologous PRP treatment, allogeneic PRP might be a new option.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.