Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Cognitive impairment is the main clinical manifestation of many nervous system diseases such as stroke,multiple sclerosis,and neurodegeneration,and neuroinflammation is one of the key mechanisms for the onset of cognitive disorders.Chemokines are a class of highly conserved small-molecule secretory proteins that bind to the corresponding chemokine receptors located on cell mem-brane,activating downstream signaling pathways and playing an important role in cell migration,proliferation,differentiation,and sur-vival.In the central nervous system,chemokines and their receptors are involved in immune response and can exert a certain regulatory effect on neuroinflammation.This article reviews the research advances in chemokines and their receptors in cognitive disorders,in or-der to provide new insights and targets for the early diagnosis and treatment of related diseases.

Objective To establish a human luminal breast cancer stem cell(BCSC)model and investigate the inhibitory effects of astragaloside Ⅳ(AS-Ⅳ)on BCSC growth.Methods MCF-7 breast cancer cells were cultured in stem cell-specific medium to induce BCSC formation.The BCSCs were then divided into a blank control group and an AS-Ⅳ treatment group,both groups were given PBS or AS-Ⅳ treatment.Morphological changes were observed after intervention.The therapeutic efficacy of AS-Ⅳ was evaluated using 3D spheroid formation and cell viability assays.Transcriptomic profiling and gene expression analysis were performed to elucidate the underlying mechanisms.Results Compared with the MCF7 breast cancer cells,MCF7 breast cancer stem cell mammospheres exhibited accelerated growth(P＜0.01)and significantly increased expression of the stemness marker ALDH1A1(P＜0.01).Further comparison with the blank control group revealed that astragaloside Ⅳ(AS-Ⅳ)treatment significantly inhibited MCF7 breast cancer stem cell proliferation(P＜0.001)and slowed mammosphere growth(P＜0.01).Transcriptomic analysis demonstrated that differentially expressed genes(DEGs)induced by stem cell modeling and AS-Ⅳ intervention were enriched in the cellular senescence signaling pathway.AS-Ⅳ intervention substantially increased the number of SA-β-gal-positive cells(P＜0.01).RT-PCR analysis confirmed that AS-Ⅳsignificantly upregulated mRNA expression of IL-1α(P＜0.01),P21(P＜0.001),and P53(P＜0.05)in MCF7 breast cancer stem cells.Conclusion Astragaloside Ⅳ suppresses the growth of human luminal breast cancer stem cells by inducing cellular senescence.

Objective: To investigate the epidemiological characteristics of human brucellosis in Jiande City, Zhejiang Province from 2005 to 2024, so as to provide the evidence for strengthening the prevention and control of brucellosis. Methods: Data on brucellosis cases and surveillance in Jiande City from 2005 to 2024 were collected through the Chinese Disease Prevention and Control Information System, the annual brucellosis surveillance reports from the Jiande Center for Disease Control and Prevention, and the annual summaries of brucellosis prevention and control efforts. The epidemiological characteristics of human brucellosis were analyzed using a descriptive epidemiological method. Results: A total of 1 125 individuals were monitored in Jiande City from 2005 to 2024, with 18 seropositive cases identified and the seropositivity rate of 1.60%. The average annual seropositivity rate from 2015 to 2024 was 3.35%, which was significantly higher than that of 0.57% from 2005 to 2014 (P<0.05). There were 10 confirmed brucellosis cases and 8 asymptomatic infections, with no reported deaths. The peak incidence occurred between March and August. Among the 16 towns (streets) in Jiande City, 8 reported brucellosis cases. Of the brucellosis cases, 14 were male and 4 were female, with a male-to-female ratio of 3.5∶1. The majority of cases (13 cases) were aged between 40 and 60 years. Occupational exposure was identified in 16 cases, all of whom were infected through direct hand contact with the excreta, secretions, or animal products of infected sheep or cattle. The primary source of infection was sheep, followed by cattle. Five strains of Brucella were isolated and cultured, all identified as Brucella melitensis biovar 3. Conclusions The brucellosis epidemic in Jiande City remained at a sporadic and low prevalence level from 2005 to 2024, with an increasing trend observed from 2015 to 2024. Male occupational groups aged 40 to 60 years were the key population for brucellosis prevention and control, and sheep were the primary source of infection.

Objective To understand the equity and influencing factors of maternal health service utilization in Changning District, Shanghai. Methods A convenience sampling method was used to conduct a questionnaire survey among mothers of children aged 1 to 1.5 years old who received health services from the child health care clinics and EPI clinics of 10 community health service centers in Changning District, Shanghai from March to April 2022. Count data was expressed by frequency and percentage. Chi-square analysis, binomial logistic regression analysis, and multivariate logistic regression analysis were used to analyze fairness-related factors. Rate difference, rate ratio and concentration index were used to represent fairness. Results A total of 696 subjects were investigated, with an average age of (33.35±4.76) years. There were statistically significant differences in service utilization among women with different household registrations only in early pregnancy registration (χ²=11.026, P=0.001) and postpartum visits (χ²=4.989, P=0.026). Women with a career showed differently in folic acid supplement (χ²=6.247, P=0.012), early pregnancy registration (χ²=12.989, P=0.002), physical examination in 42 days postpartum (χ²=4.446, P=0.035) and postpartum contraception (χ²=4.061, P=0.044), and the differences were statistically significant. Women with different monthly family income had a statistically significant difference in pre-pregnancy examination (χ²=8.977, P=0.030) and postpartum visit (χ²=16.114, P=0.001). There was a statistically significant difference between women with maternity insurance or not in the early pregnancy registration (χ²=10.576, P=0.001) and physical examination in 42 days postpartum (χ²=8.166, P=0.004). The results of the multivariate analysis showed that occupation (OR=2.616, 95% CI: 1.142-5.990) and maternity insurance (OR=4.490, 95% CI: 1.992~10.120) affected the utilization of service in early pregnancy registration. The monthly household income (OR=0.278, 95% CI: 0.124-0.625) affected the utilization of services in postpartum visit. At the same time, the monthly household income (10,000-19,999: OR=0.286, 95% CI: 0.090-0.907; ≥30,000: OR=0.180, 95% CI: 0.041-0.801) also affected the utilization of service in physical examination in 42 days postpartum. Conclusion The equity of maternal health care service utilization overall is good in central area in Shanghai, but there is still room for improvement. It is necessary to strengthen community mobilization, propagandize maternal health services, and expand the coverage of maternity insurance to improve the equity of maternal health service utilization and provide equal access to maternity health services.

Objective:To explore the personality latent profiles of university first-year students and examine their associations with demographic characteristics,psychological symptoms,and major satisfaction.Methods:A to-tal of 52 783 first-year university students were assessed with the Minnesota Multiphasic Personality Inventory(MMPI),Beck Depression Inventory,Beck Anxiety Inventory,self-developed major satisfaction item and demo-graphic checklist.Data were analyzed with potential profile model,chi-square test,multiple logistic regression,co-variance analysis and median test.Results:Five latent profiles of MMPI among university freshmen were found,namely gender conflict group(23.4％),real healthy group(27.9％),defensive healthy group(37.3％),borderline-psychosis risk group(6.7％)and neurosis risk group(4.8％).Gender,grade period,childhood up bringers,par-ents'marital status and family atmosphere predicted differences between profiles of MMPI.Different profiles showed statistically meaningful differences at depressive symptoms,anxiety symptoms and major satisfaction.Conclusion:The latent profiles of MMPI among first-year university students demonstrate distinct classification patterns,diffe-ring demographic characteristics and psychologically problematic levels.

A 30-year-old female patient with a benign tumor in the superficial lobe of the left parotid gland underwent tumor resection via a 5 cm intra-hairline incision, using the da Vinci Xi surgical robot combined with the NIM-Response 3.0 facial nerve monitoring system. During the operation, facial nerve branches were located and protected through facial nerve monitoring, and the robotic arms were used for precise tumor dissection. Postoperatively, the facial nerve function, incision healing, and tumor recurrence were observed. duration of the procedure was 120 minutes, and the tumor（2.0 cm×1.5 cm） was completely resected. Postoperative pathological examination indicated a pleomorphic adenoma. During the 3-month postoperative follow-up, the patient's facial nerve function remained normal, no salivary fistula occurred, the incision was hidden within the hairline, no tumor recurrence was found in the ultrasound reexamination, and the patient was highly satisfied with the appearance. The surgical approach of robot-assisted resection of benign parotid gland tumor via a hairline incision under facial nerve monitoring has significant advantages in facial nerve protection and cosmetic effect, and is suitable for patients with benign parotid gland tumors meeting specific conditions.
Humans ; Female ; Adult ; Parotid Neoplasms/surgery* ; Facial Nerve ; Robotic Surgical Procedures/methods* ; Adenoma, Pleomorphic/surgery* ; Parotid Gland/surgery* ; Monitoring, Intraoperative

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.