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 prognostic value of the combined use of central venous-arterial carbon dioxide partial pressure difference/arterial-central venous oxygen content difference ratio (Pv-aCO 2/Ca-vO 2) combined with peripheral perfusion index (PI) for prognosis in middle-aged and elderly patients with acute heart failure (AHF) complicated by hypoperfusion. Methods:A case-control study was conducted, enrolling middle-aged and elderly AHF patients with tissue hypoperfusion admitted to the Emergency Intensive Care Unit of Nanjing First Hospital from May 2022 to May 2024. The primary endpoint was 28-day all-cause mortality. Patients were divided into survival and death groups based on prognosis. Baseline characteristics and clinical data were compared between groups. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of risk factors. Stratified analysis based on optimal cutoff values was performed, and Kaplan-Meier survival curves were used to compare prognostic differences between subgroups.Results:A total of 70 patients with AHF and hypoperfusion were enrolled, with 36 deaths (28-day mortality rate: 51.43%). No significant differences were observed in baseline characteristics, N-terminal B-type natriuretic peptide precursor, creatine kinase, creatine kinase-myocardial band, cardiac troponin I,central venous pressure, or left ventricular ejection fraction between groups(all P>0.05). Compared with the survival group, the death group exhibited significantly higher APACHEⅡ scores, lactate levels, and Pv-aCO 2/Ca-vO 2 ratios, along with lower PI values (all P<0.05). The area under the ROC curve (AUCs) for PI, Pv-aCO 2/Ca-vO 2, and their combination in predicting 28-day mortality were 0.804 (95% CI: 0.701-0.908), 0.848 (95% CI: 0.758-0.938), and 0.922 (95% CI: 0.859-0.985), respectively. The optimal cutoff value for PI was 1.17 (sensitivity 83.3% and specificity 67.6%), and for Pv-aCO 2/Ca-vO 2 was 1.59 (sensitivity 77.8% and specificity 79.4%). Stratified analysis revealed that the PI≤1.17 group had a significantly higher 28-day mortality rate than the PI>1.17 group ( P<0.01), and the Pv-aCO 2/Ca-vO 2>1.59 group had a markedly higher mortality rate than the Pv-aCO 2/Ca-vO 2≤1.59 group ( P<0.01) ,consistent with Kaplan-Meier survival analysis. Conclusion:Early assessment of Pv-aCO 2/Ca-vO 2 combined with PI demonstrates superior predictive performance for prognosis in AHF patients with hypoperfusion.

Objective:To investigate the use of targeted next generation sequencing (tNGS) for the detection of drug resistance in mycoplasma pneumoniae pneumonia (MPP) and analyze the clinical characteristics of MPP.Methods:The clinical data of patients with MPP who underwent bronchoalveolar lavage fluid tNGS at the Department of Respiratory and Critical Care Medicine, The Third People's Hospital of Hubei Province, Jianghan University from February 2022 to February 2024 were collected. According to inclusion and exclusion criteria, 80 patients with MPP were included in this study. The clinical data of the patients were retrospectively analyzed. tNGS of bronchoalveolar lavage fluid was performed to assess drug resistance in MPP. These patients were divided into a drug resistance group ( n = 55) and a non-drug resistance group ( n = 25) based on the presence or absence of the 23SrRNA:A2063G drug resistance mutation. Patient's clinical characteristics were compared between the two groups. The significant indicators from the univariate analysis were introduced into a binary logistic regression model to analyze the independent predictors of drug resistance and their predictive values. Results:The median age of patients with MPP was 38 years, with 53.75% (43/80) being female. Among the patients, 62.50% (50/80) had no underlying diseases, and 68.75% (55/80) exhibited drug resistance, while 42.50% (34/80) had mixed infections. The three most common clinical symptoms were cough (92.50%, 74/80), fever (62.50%, 50/80), and dyspnea (31.25%, 25/80). The most common imaging findings in MPP included patchy shadows (48.75%, 39/80) and consolidation shadows (42.50%, 34/80). Nodular shadows (7.50%, 6/80), tree-in-bud signs (5.00%, 4/80), ground-glass opacities (11.25%, 9/80), bronchial wall thickening (3.75%, 3/80), and pleural effusions (5.00%, 4/80) were not common. Bilateral lesions were present in 40.00% (32/80) of cases. In laboratory examinations, the median levels of inflammatory markers C-reactive protein (39.45 mg/L), procalcitonin (0.08 g/L), and serum amyloid A (168.31 mg/L) were increased. The median or mean levels of other indicators were within the normal range. There were no significant differences between the drug resistance and non-drug resistance groups in terms of gender, age, underlying diseases, clinical symptoms, length of hospital stay, mixed infection rate, mycoplasma pneumoniae (MP)-IgG positivity, MP-IgM level > 300 AU/mL, MP-DNA positivity, percentage of lymphocytes, platelet count, number of lymphocytes, and procalcitonin, D-dimer, prealbumin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and albumin levels as well as imaging findings (all P > 0.05). In the drug resistance group, the number of fever days, sequence number, white blood cell count, percentage of neutrophils, C-reactive protein level, and serum amyloid A level were as follows: 4 (0, 7), 24464.00 (2754.00, 43457.00), 7.35 (6.09, 9.84), 73.70 (67.20, 73.70), 39.82 (20.82, 70.40), and 205.40 (81.08, 338.30), respectively. These values were significantly higher than those in the non-drug resistance group [2 (0, 4.50), 658.00 (323.00, 7593.00), 6.12 (5.04, 7.20), 64.45 (58.58, 76.33), 35.63 (4.94, 57.36), 81.30 (12.51, 243.76), Z = -2.43, -4.67, -2.72, -2.36, -2.04, -2.37]. The albumin level in the drug resistance group was 41.50 (38.10, 44.30), which was significantly lower than that in the non-drug resistance group [43.55 (40.03, 46.05), Z = -2.07, P < 0.05]. In the binary logistic regression analysis, the sequence number was identified as an independent predictor of drug resistance. When the sequence number exceeded 1001, the area under the curve value was 0.827, with a sensitivity of 94.5% and specificity of 68.0%. Conclusions:The clinical manifestations of MPP are similar in both the macrolide-resistant and the non-resistant groups. However, the drug-resistant group exhibits a greater number of fever days, higher sequence numbers, and more severe inflammatory responses. The sequence number of MPP can be used to predict drug resistance. When the sequence number exceeds 1001, its predictive value for drug resistance is significantly higher.

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 explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.

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

Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in controlling HBV infection; however, their function is impaired during chronic HBV infection, manifesting as a state of dysfunction. Recent studies have revealed that CD8⁺ T cell dysfunction in chronic HBV infection differs from the classical exhaustion observed in other viral infections or tumors. In 2024, several pivotal studies further elucidated novel mechanisms underlying CD8⁺ T cell dysfunction in chronic HBV infection and identified new therapeutic targets, including 4-1BB and transforming growth factor-beta (TGF-β). This review, while elucidating the dysfunction of CD8⁺ T cells in chronic HBV infection and its underlying mechanisms, focuses on summarizing the key findings from these latest studies and explores their translational value and clinical significance.
Humans ; Hepatitis B, Chronic/virology* ; CD8-Positive T-Lymphocytes/immunology* ; Hepatitis B virus/physiology* ; Animals ; Transforming Growth Factor beta/immunology*

Resectable non-small cell lung cancer (NSCLC) is prone to recurrence and metastasis after simple surgery. Although patients can benefit from preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy, the 5-year survival rate is not significantly improved. In recent years, with the rise of immunotherapy, NSCLC immunotherapy has gradually received attention. Many explorations have been made on resectable NSCLC immunotherapy, and satisfactory results have been obtained. With the release of multiple phase 3 research results, a new chapter in resectable NSCLC immunotherapy has officially opened. However, there are still many problems in the immunotherapy of resectable NSCLC. This article reviews the current relevant research and provides reference for clinical application.