Objective: To assess the effect of 12-year-old children s pit and fissure sealants on the health of first permanent molars, so as to provide evidence for optimizing caries prevention strategies among children. Methods: In March 2025, a cluster random sampling method was used to conduct oral examinations on 965 students aged 12 from Chengdu s 2021 Comprehensive Intervention Program for Pediatric Oral Diseases. Data from the Comprehensive Intervention System for Children s Oral Diseases were referenced. Participants were divided into a sealed group ( n =755) and an unsealed group ( n =210) based on whether they had received sealants on their first permanent molars. Chi square test or analysis of variance were used to compare indicators such as caries incidence, new caries detection rate, and new caries mean (DMFT increment) between the two groups Results: The sealed group showed significantly lower caries incidence, new caries detection rate, and new caries mean (33.38%, 17.65%, 0.59±1.00) compared to the unsealed group (43.81%, 24.70%, 0.87±1.22)( χ 2/F =7.79, 18.26, 9.55, all P <0.05). However, no significant difference was found in the filled teeth ratio between the two groups (20.38% , 20.16%; χ 2=0.01, P =0.94). In girls, the sealed group exhibited significantly lower caries incidence, new caries detection rate, and new caries mean (36.78%, 20.99%, 0.69± 1.10 ) than the unsealed group (57.55%, 33.52%, 1.15±1.29) ( χ 2/F =14.42, 23.76, 10.92, all P <0.05), whereas no significant differences were observed between boys in the sealed (30.47%, 14.85%, 0.50±0.89) and unsealed groups (29.81%, 16.18%, 0.59± 1.08) ( χ 2/F =0.02, 0.41, 0.74, all P >0.05). Boys had significantly lower new caries detection rates and new caries means than girls in both groups ( χ 2/F =16.20, 6.94; 29.93, 11.84, all P <0.05). In urban areas, the sealed group had lower new caries detection rates and new caries means (19.37%, 0.68±1.04) than the unsealed group (24.66%, 0.90±1.20) ( χ 2/F =6.86, 3.94, both P <0.05). In suburban areas, all indicators for the sealed group (24.71%, 13.77%, 0.42±0.87) were significantly lower than those for the unsealed group (38.81%, 24.77%, 0.82±1.28) ( χ 2/F =5.28, 15.36, 6.00, all P <0.05). Indicators from specialized dental institutions (11.25%, 4.81%, 0.16±0.56) were significantly lower than those from county level or above general hospitals (33.33%, 19.11%, 0.38±1.00) and primary healthcare institutions (37.59%, 19.24%, 0.67±1.05) ( χ 2/F =20.99, 34.31, 21.08 , all P <0.01). Conclusions The 12-year-old children s pit and fissure sealants effectively reduce the caries incidence in first permanent molars, particularly showing significant effectiveness in girls and suburban children. Intervention strategies should be optimized according to gender.

Breast cancer is a malignant tumor that occurs in the glandular epithelium of the breast, and it is one of the most common tumors that seriously affect the physical and mental health of women. With the aggravation of population aging, the incidence of breast cancer in the elderly has increased year by year in recent years. Elderly patients with breast cancer often have a variety of underlying diseases, and their prognosis is usually related to many factors such as cancer staging, cancer classification, treatment status and health status, with a significant difference in survival rate among patients. Due to the unique clinical and pathological characteristics of elderly patients with breast cancer compared to young and middle-aged patients, there are many studies on the treatment of elderly breast cancer patients in the past, and there are few reviews on the influencing factors of prognosis in elderly patients. This paper reviews the research progress of influencing factors of prognosis in elderly patients with breast cancer from the aspects of clinicopathological factors, treatment options and prognosis factors, in order to provide a reference for clinical determination of treatment options for elderly patients with breast cancer in the future.

BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

OBJECTIVE:Although wearable electronic devices have demonstrated potential utility as intervention tools to enhance physical activity,comprehensive evaluations of their specific effects on the healthy adolescent population remain scarce.Consequently,this article aims to systematically explore and summarize the impact of interventions based on wearable electronic devices on the physical activity and sedentary behavior of healthy adolescents,thereby providing more precise and reliable evidence-based support for public health practices. METHODS:Randomized controlled trials assessing the effects of wearable electronic device-based interventions on the physical activity and sedentary behavior of healthy adolescents were retrieved from databases including Web of Science,PubMed,Scopus,The Cochrane Library,and EBSCO.Meta-analysis was conducted using Review Manager 5.4 and Stata 17,evaluating the effects of interventions on physical activity and sedentary behavior through the standardized mean difference.To ensure the robustness of the research findings,a Leave-One-Out sensitivity analysis was conducted,and subgroup analyses were carried out to explore the potential influence of different factors on the results.The review protocol was registered with the International Prospective Register of Systematic Reviews(CRD42023406645). RESULTS:(1)Twelve publications were ultimately included,consisting of three randomized controlled trials and nine cluster-randomized controlled trials,involving a total of 4 933 healthy adolescents.(2)Meta-analysis results revealed that interventions based on wearable electronic devices had a positive effect on moderate to vigorous physical activity[standardized mean difference(SMD)=0.10;95%confidence interval(CI):0.04 to 0.17;P<0.05).However,the interventions did not significantly improve low-intensity physical activity(SMD=-0.15;95%CI:-0.32 to 0.02;P>0.05),daily step count(SMD=0.13;95%CI:-0.65 to 0.91;P>0.05),and sedentary behavior(SMD=0.00;95%CI:-0.09 to 0.09;P>0.05).(3)Subgroup analyses indicated that short-term interventions(≤12 weeks)(SMD=0.11;95%CI:0.03 to 0.18;P=0.008),studies using pedometers worn at the waist or hip(SMD=0.10;95%CI:0.04 to 0.17;P=0.002),and experiments registered at clinical trial centers(SMD=0.11;95%CI:0.04 to 0.17;P=0.001)had a more significant effect on enhancing daily moderate to vigorous physical activity. CONCLUSION:The current evidence suggests that interventions based on wearable electronic devices possess certain advantages in enhancing the daily moderate-to-vigorous physical activity of healthy adolescents.It is recommended that interventions not exceeding 12 weeks and utilizing pedometers positioned at the waist or hip may yield more favorable results.However,the effects of these interventions on daily step count,low-intensity physical activity,and sedentary behavior exhibit some limitations.Consequently,future investigations necessitate higher-quality,larger-scale randomized controlled trials for further validation.

Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

OBJECTIVE To provide a reference for pharmaceutical care in patients with ulcerative colitis （UC） and ankylosing spondylitis （AS） who developed pustular psoriasis induced by infliximab. METHODS Clinical pharmacists participated in the pharmaceutical care process of a patient with UC and AS who developed pustular psoriasis after using infliximab. The clinical pharmacists determined， using Naranjo’s Scale， that the correlation between the patient’s pustular psoriasis and infliximab was “likely”. Regarding the patient’s development of pustular psoriasis after using infliximab， the clinical pharmacists recommended discontinuing infliximab and switching to Upadacitinib extended-release tablets. For the patient’s skin allergic reaction after using upadacitinib， the clinical pharmacists advised continuing the use of upadacitinib and closely monitoring any potential adverse reactions during the treatment period. RESULTS The clinicians adopted the clinical pharmacists’ recommendation. Following the treatment， the patient’s symptoms were significantly alleviated， and the patient was discharged with medication. The follow-up after discharge showed that the treatment was effective and well-tolerated. CONCLUSIONS The clinical pharmacists analyzed the causal relationship between infliximab and pustular psoriasis. Through pharmaceutical care measures such as dynamic monitoring of skin lesions， evaluation of treatment responses， and optimization of drug regimens， they assisted the physicians in formulating an individualized medication plan， ensuring the safety and efficacy of the patient’s medication use.

By exploring theories related to yin-yang， body and spirit， and the relationship between nature and human beings， this study proposed the holistic functional perspective in Traditional Chinese Medicine （TCM） rehabi-litation. This perspective emphasizes the influence of various internal and external factors on the body's function and health status， with the integration of form and spirit as its core concept. It integrates the principles of correspondence between nature and human beings， as well as the unity of individuals and society， positioning holistic function as the key focus in TCM rehabilitation practice. It guides the prevention， assessment， and rehabilitation treatment of functional disorders， ultimately achieving the goal of comprehensive recovery of health. Additionally， the study reviewed the current application status of the holistic functional perspective in clinical TCM rehabilitation， clarified its integration throughout the entire TCM rehabilitation process， with the goal of providing a theoretical and practical foundation for further research and application in TCM rehabilitation.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To explore the expression differences of the docking protein 1(DOK1)gene in multiple tissues of mice during the development stage from prediabetes to type 2 diabetes mellitus(T2DM),as well as its correlation with blood lipid levels.Methods The mice were divided into the 0 d group(control),the 20 d group,the 40 d group,the 60 d group,the 80 d group and the T2DM group.The 0 d group was fed with normal diet,while the other four groups were fed with high-fat diet to establish the prediabetes model.On this basis,the T2DM group was given low-dose multiple intraperitoneal injections of streptozotocin(STZ)to establish the T2DM model.The fasting and intraperitoneal glucose tolerance test(IPGTT)and insulin tol-erance test(IPITT)blood glucose of mice in each group were detected,and the expression of the DOK1 gene in nine tissues(heart,liver,kidney,skeletal muscle,pancreas,adipose,spleen,lung and colon tissues)was de-tected by qPCR.The level of DOK1 in serum was determined by ELISA,and the lipid level in serum was measured by an automatic biochemical analyzer.The correlations between serum DOK1 and TG,TC,HDL-C,LDL-C,lipoprotein A[LP(a)],and free fatty acids(FFA)were analyzed by Spearman correlation analysis.Re-sults The prediabetic and T2DM model mice were successfully established.Compared with the 0 d group,the blood glucose and lipid levels in the 80 d group and the T2DM group were significantly increased(P<0.001).Compared with the 0 d group,the expression level of DOK1 mRNA in the T2DM group was significantly de-creased in heart,liver,kidney,skeletal muscle,pancreas and adipose tissue(P<0.05).Compared with the 0 d group,the expression level of DOK1 mRNA in the 80 d group was significantly decreased in heart,liver,kid-ney and skeletal muscle tissue(P<0.05).Compared with the 0 d group,the expression levels of DOK1 mR-NA in the 40 d group and the 60 d group was significantly decreased in the liver tissues(P<0.05).Compared with group 0 d,there was no statistically significant difference in the expression level of DOK1 mRNA in the spleen,lung and colon tissues among each group(P>0.05).DOK1 in the 80 d group and the T2DM group was negatively correlated with TG,TC,LDL-C,LP(a),and FFA(r=-0.787 8,-0.727 2,-0.763 7,-0.764 2,-0.892 5,P<0.001),while positively correlated with HDL-C(r=0.961 3,P<0.001).Conclu-sion The reduction of DOK is related to the mechanism of insulin resistance and may play a key role in lipid metabolism disorders associated with diabetes.

Objective To investigate the expression of serum microRNA(miR)-494 and miR-155 in chil-dren with Enterovirus type 71 hand-foot-mouth disease(EV71-HFMD),and to analyze the clinical significance of serum miR-494 and miR-155 in EV71-HFMD.Methods A total of 145 children with EV71-HFMD treated in this hospital from May 2021 to May 2023 were selected.According to the severity of the disease,they were divided into mild group(n=81)and severe group(n=64).In addition,73 healthy and disease-free children in the hospital were included in the health group.Serum expression levels of miR-494 and miR-155 as well as helper T cell 17(Th17),regulatory T cell(Treg)and Th17/Treg in the three groups were detected and com-pared.Pearson correlation analysis was used to analyze the correlation between the expression levels of serum miR-494,miR-155,Th17 and Treg,as well as Th17/Treg.The clinical data of children with EV71-HFMD were collected,and the factors influencing the severity of EV71-HFMD were analyzed by multivariate Logistic regression model.Results Compared with healthy group,serum miR-494,miR-155,Th17 and Th17/Treg in mild and severe groups were increased,and Treg were decreased(P＜0.05).Compared with mild group,ser-um miR-494,miR-155,Th17 and Th17/Treg in severe group were increased,and Treg was decreased(P＜0.05).Pearson correlation analysis showed that Th17 and Th17/Treg were positively correlated with the ex-pression levels of serum miR-494 and miR-155,while Treg was negatively correlated with the expression lev-els of serum miR-494 and miR-155(P＜0.05).The peak temperature,duration of fever ≥3 d proportion and eruption of isthmus in severe group were higher than those in mild group(P＜0.05).Multivariate Logistic re-gression results showed that the duration of fever ≥3 d,eruption in the isthmus,the high expression level of miR-494 and the high expression level of miR-155 were risk factors for severe EV71-HFMD(P＜0.05).Conclusion Se-rum miR-494 and miR-155 are abnormally elevated in children with EV71-HFMD,and the changes in their levels are closely related to Th17/Treg imbalance.Increased expression levels of serum miR-494 and miR-155 are risk factors for severe EV71-HFMD.