There are practical and cost-effective opportunities for the prevention and early intervention of periodontal disease, a common oral condition. Depression and anxiety represent major global mental health challenges, and they are characterized by high prevalence rates and an elevated suicide risk. Their clinical management is complicated by extended treatment timelines and substantial healthcare costs. Accumulating evidence demonstrates a statistically significant bidirectional association between periodontal disease and depression/anxiety disorders. However, established clinical pathways integrating these conditions remain lacking. This review presents a comprehensive analysis of current research examining the relationship between periodontal disease and mood disorders, specifically depression and anxiety. This study explored the bidirectional mechanisms within the microbiota-oral-brain axis, which includes both periodontal disease inducing neuroinflammation through pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) activating the TLR-4/NF-κB signaling pathway, and depression and anxiety leading to “glucocorticoid resistance” through hypothalamic-pituitary-adrenal (HPA) axis dysregulation, thus causing dual immune dysfunction that exacerbates periodontal tissue destruction, as well as the mechanisms by which biological, psychological, and social factors contribute to the bidirectional association between periodontal disease and depression/anxiety. We propose implementing bidirectional referral protocols between dental and psychiatric services in clinical practice, incorporating mental health screening tools, such as Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7(GAD-7), for patients with moderate-to-severe periodontal disease, and incorporating periodontal examination into routine assessment during psychiatric services. This multidisciplinary approach aims to break the vicious circle between these conditions and provide clinicians with pragmatic intervention strategies.

Objective To explore the predictive value of peripheral blood cells in the efficacy of neoadjuvant immunotherapy combined with chemotherapy for esophageal squamous cell carcinoma. Methods A retrospective study was conducted on patients with esophageal squamous cell carcinoma (clinical stages Ⅱ-Ⅳa) who underwent neoadjuvant immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College from April 2020 to November 2023. According to whether the pathology was completely relieved after treatment, patients were divided into a pathological complete remission group and a pathological incomplete remission group. The College of American Pathologists criteria were used to evaluate the tumor pathological regression grade (TRG) after neoadjuvant therapy (TRG=0, 1 defined as a good efficacy group, TRG=2, 3 defined as a poor efficacy group). Results A total of 92 patients with esophageal squamous cell carcinoma were collected, including 72 males and 20 females. The average age was (65.86±7.66) years. The complete remission of pathology was closely related to the number of lymphocytes in the blood before treatment (P=0.019). The area under the curve (AUC) for predicting complete remission of esophageal squamous cell carcinoma after neoadjuvant immunotherapy combined with chemotherapy was 0.678, the maximum Youden index was 0.328, and the optimal cutoff value was 1.845. The incidence of postoperative pulmonary infection in the pathological incomplete remission group was higher than that in the pathological complete remission group (25.0% vs. 5.6%, P=0.030). Using the optimal cutoff value, there were statistically significant differences in pathological N stage and pathological TNM stage between patients with lymphocyte counts <1.845×109/L and ≥1.845×109/L (P<0.05). Treatment response (by TRG) was significantly associated with the pretreatment red blood cell count (P=0.009). The AUC for predicting a good TRG response was 0.669, with a maximum Youden index of 0.385 and an optimal cutoff value of 4.235. Between the good and poor response groups, there were statistically significant differences in postoperative pathological T stage (P<0.001), N stage (P=0.041), and TNM stage (P＜0.001). When stratified by the optimal cutoff value, there were statistically significant differences in age (P＜0.001) and the prevalence of hypertension (P=0.022) between patients with red blood cell counts <4.235×1012/L and ≥4.235×1012/L. Conclusion A pretreatment absolute lymphocyte count ≥1.845×109/L and a red blood cell count <4.235×1012/L are good predictors for pathological complete response and a good pathological response, respectively, following neoadjuvant immunotherapy combined with chemotherapy in patients with esophageal squamous cell carcinoma.

Objective: To investigate the awareness of core tuberculosis (TB) knowledge and the willingness to TB preventive intervention among secondary school students in Lanzhou City, so as to provide a reference basis for the prevention and control of TB in schools. Methods: From April to June 2024, a total of 1 127 secondary school students from 8 schools in 4 districts (counties) of Lanzhou City were recruited by stratified cluster sampling method to conduct a questionnaire survey on the awareness of core TB knowledge and the willingness for preventive intervention against latent tuberculosis infection. Data were analysed using χ 2 test and binary Logistic regression model. Results: The overall awareness rate of core TB knowledge among secondary school students in Lanzhou City was 74.48%, while only 25.91% demonstrated awareness of all core knowledge items. The lowest awareness was observed for the item "tuberculosis is a chronic infectious disease" (61.84%). About 94.85% of the students reported willingness to receive preventive interventions after a diagnosis of latent tuberculosis infection. Multifactorial Logistic regression analysis showed that students whose father s education was junior high school ( OR=3.14, 95%CI =1.22-8.08), senior high school or secondary vocational school ( OR=3.55，95%CI =1.16-10.86) had a higher willingness to receive preventive interventions than those whose father s education was primary school or below (both P <0.05). In addition, students who recognized "suspected tuberculosis" were also more likely to express willingness to receive preventive interventions ( OR=1.96, 95%CI =1.01-3.80, P <0.05). Conclusions The total awareness rate of core TB knowledge among secondary school students in Lanzhou City is low; willingness to receive preventive interventions for latent tuberculosis infection is high and it is related to father s literacy and core TB knowledge level.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

OBJECTIVES: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). METHODS: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. RESULTS: Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. CONCLUSIONS In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Sjogren's Syndrome/pathology* ; Epithelial Cells/cytology* ; Submandibular Gland/cytology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Class Ia Phosphatidylinositol 3-Kinase ; Cells, Cultured

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective:To discuss the causal association between sterol esters and intrahepatic duct,biliary tract,and gallbladder malignancies using two-sample Mendelian randomization(MR)analysis,and to clarify the biological mechanisms of sterol esters,and to provide the a basis for early prevention and treatment of these malignancies.Methods:The instrumental variable data for 15 different types of sterol ester traits were obtained from the Finnish database(FinnGen).The genome-wide association study(GWAS)data for intrahepatic duct,biliary tract,and gallbladder malignancies were retrieved from the GWAS database using the keywords"sterol ester"and"intrahepatic duct,biliary tract,and gallbladder malignancies"(accession numbers:ICD-O-3 and GCST90277238-GCST9027725).The inverse-variance weighted(IVW)method,MR-Egger regression,and weighted median(WM)method were used to assess the causal association between sterol esters and the risk of these malignancies.Pleiotropy was tested using the MR-Egger intercept method;heterogeneity was evaluated using Cochran's Q test;and sensitivity analysis was performed using the leave-one-out approach to comprehensively assess the reliability and robustness of the results.Results:The IVW analysis results showed that Sterol ester(27:1/14:0)odds ratio(OR)=2.349,95%confidence interval(CI)=1.371-4.025,P=0.002),Sterol ester(27:1/16:0)(OR=1.248,95%CI=1.018-1.523,P=0.033),Sterol ester(27:1/18:2)(OR=1.361,95%CI=1.078-1.718,P=0.009),and Sterol ester(27:1/22:6)(OR=1.339,95%CI=1.001-1.791,P=0.049)were associated with an increased risk of intrahepatic duct,biliary tract,and gallbladder malignancies.The MR-Egger regression analysis results indicated that Sterol ester(27:1/18:2)(OR=2.038,95%CI=1.337-3.105,P=0.011)was a risk factor for these malignancies.The WM analysis results revealed that Sterol ester(27:1/14:0)(OR=2.786,95%CI=1.419-5.468,P=0.003)and Sterol ester(27:1/18:2)(OR=1.548,95%CI=1.148-2.088,P=0.004)were also risk factors.The MR-Egger intercept analysis and Cochran's Q test results indicated no significant horizontal pleiotropy or heterogeneity.The leave-one-out sensitivity analysis did not identify any influential outlier single nucleotide polymorphism(SNPs),confirming the reliability of the study.Conclusion:Sterol ester(27:1/14:0),Sterol ester(27:1/16:0),Sterol ester(27:1/18:2),and Sterol ester(27:1/22:6)exhibit causal associations with intrahepatic duct,biliary tract,and gallbladder malignancies and may promote their development.

Objective:To explore the learning curve of primary urologists mastering Holmium laser enucleation of the prostate for the treatment of large volume benign prostatic hyperplasia (BPH).Methods:The clinical data of 92 patients with larger volume BPH who received HoLEP performed by a urologist in Beijing Friendship Hospital Pinggu Campus, Capital Medical University were retrospectively reviewed. 92 patients were divided into group A (1-23 cases, n=23), group B (24-46 cases, n=23), group C (47-69 cases, n=23), and group D (70-92 cases, n=23) based on the sequence of surgery. The clinical characteristics, including prostate volume, operation time, enucleation efficiency, indwelling catheter time, decrease value of hemoglobin, intraoperative blood transfusion, perioperative complications, and international prostate symptom score (IPSS), quality of life (QOL) score, Qmax, and postvoid residual urine (PVR) at 3 months postoperatively were compared between the four groups. Measurement data were expressed as mean ± standard deviation ( ± s), one-way analysis of variance was used for comparisons among multiple groups, and t-test was used for comparisons between two groups. Count data were expressed as the cases and percentage, and the Chi-square test was used for comparison between groups. Results:There were significant differences among the four groups in terms of operation time [(94.43±8.26) min, (86.39±5.89) min, (70.70±5.64) min, (64.70±4.23) min, P=0.001], enucleation efficiency [(0.90±0.08) mL/min, (1.01±0.07) mL/min, (1.23±0.12) mL/min, (1.34±0.12) mL/min, P=0.001], decrease value of hemoglobin [(25.98±1.39) g/L, (23.27±1.49) g/L, (20.03±1.07) g/L, (18.49±0.96) g/L, P=0.001] and indwelling catheter time [(5.91±1.54) d, (5.35±1.27) d, (3.39±0.72) d, (3.04±0.64) d, P=0.001]. Compared with group C and group D, the operation time was longer, the enucleation efficiency was lower, the decrease value of hemoglobin before and after the operation was higher, and the indwelling catheter time was longer, the above differences were all statistically significant ( P<0.05). However, there was no statistically significant difference between group A and group B, or group C and group D ( P>0.05). Among the 92 patients, only 3 patients received blood transfusion during operation, including 2 patients in group A and 1 patient in group B. 2 patients underwent surgical complications during the perioperative period. Among them, 1 patient suffered bladder wall injury due to improper operation of the tissue pulverizer in group A, and 1 patient developed prostatic capsule perforation in group B. Furthermore, after 56 cases of operation, a primary urologist can perform HoLEP surgery quickly and safely. Conclusion:The learning curve of a primary urologist mastering HoLEP for larger volume (≥ 80 mL) BPH was 56 procedures, and the operation efficiency and safety were significantly improved.

Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.

Objective:To evaluate the effectiveness of an integrated management model involving the Centers for Disease Control and Prevention (CDC), general hospitals, and community health service centers in improving outcomes for community-dwelling patients with chronic obstructive pulmonary disease (COPD), with the aim of optimizing existing COPD management strategies.Methods:This study was a cluster randomized controlled trial. From January to March 2022, a total of 236 patients with COPD were recruited from four communities in Chibi City, Hubei Province. Ultimately, 223 patients completed follow-up and participated in the intervention evaluation. The participants were cluster-randomized into an intervention group ( n=121) and a control group ( n=102). The intervention group received a one-year "trinity" integrated community management model, while the control group received only basic follow-up. Face-to-face questionnaires were administered before and after the intervention to collect data on demographics, disease awareness, risk factors, respiratory symptoms, medication use, and disease management. Quality of life scores and pulmonary function tests were also assessed. Pre-and post-intervention outcomes were compared using t-tests or chi-square tests. Results:The intervention group demonstrated significantly higher rates of COPD awareness and disease-related knowledge compared to the control group (94.12% vs 77.78% and 78.15% vs 49.49%; both P<0.05), along with lower overall smoking rate and current smoking rate (57.14% vs 70.71% and 29.41% vs 47.47%; both P<0.05). The intervention group showed reduced household polluting fuel use for heating (17.65% vs 28.93%; P<0.05), while the control group exhibited no significant change. Significant improvements were observed in the intervention group for inhaler medication usage (14.05% vs 2.94%), exercise training, and respiratory muscle training (22.31% vs 2.94% and 26.45% vs 0.98%)(all P<0.05). Additionally, the intervention group reported lower prevalence of chronic sputum production, wheezing, and dyspnea (12.40%, 0.83%, 27.27% vs 24.51%, 9.80%, 41.18%; all P<0.05) compared to controls. Pulmonary function tests revealed that the percentage of forced expiratory volume in one second (FEV 1%predicted) was significantly higher in the intervention group than in the control group [(69.53±18.01)% vs (54.90±12.39)%; both P<0.05]. Conclusions:The "trinity" integrated management model effectively enhances health literacy, self-management capabilities, and quality of life among COPD patients, while reducing behavioral risk factors. This model aligns with the long-term and individualized management needs of COPD patients.