OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

Objective: To explore the characteristics of the diversity and composition of oral microbial flora with age, and to provide a reference for understanding the succession of oral microecology at different ages. Methods: Oral rinse 16S rRNA (V4 region) sequencing data from 9 021 participants 14-69 years of age in the 2009-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Alpha diversity (Observed OTUs, Faith’s PD, Shannon Index), beta diversity (Bray-Curtis and UniFrac), and genus-level composition were examined using weighted generalized linear models (GLMs), including quadratic terms for age and adjusting for key covariates (gender, race/ethnicity, BMI, smoking status, and periodontitis severity). Results: Alpha diversity demonstrated a clear inverted U-shaped trajectory across age, peaking at 25-30 years old and declining thereafter. This trend remained consistent across sex, race, smoking, and periodontal health strata. Beta diversity analyses revealed a modest but steady age-related shift in community structure. Genus-level analyses revealed that Rothia, Prevotella_6, and Lactobacillus increased steadily with age, while Haemophilus, Porphyromonas, and Corynebacterium declined significantly. Notably, potential periodontopathogens, such as Fusobacterium and Treponema_2, peaked in early adulthood before declining with age. Conclusion Age is an important driver of oral microbial succession, and the oral microbiome exhibits dynamic changes across different life stages. Future longitudinal and multi-omic studies are warranted to elucidate the mechanisms underlying these age-related trajectories.

Ethical review represents the core of the scientific and technological ethical governance， and its quality depends on the participation of ethics. The absence of ethics and ethical experts will compromise the quality of the review. According to the spirit of the Guidelines on Strengthening the Governance over Ethics in Science and Technology， this paper analyzed the process of separating scientific and technological ethics from the field of scientific research morality， clarified the ethical attributes of ethical review， and argued that scientific research and technological innovation activities originated from ethics. On this basis， the fundamental principle of “ethics first” was proposed， aiming to proactively embed ethical considerations throughout the entire process of scientific and technological activities. This principle was the primary requirement for ensuring governance effectiveness and can also eliminate the risk of ethics being obscured in ethical governance. In practice， “ethics first” manifested specifically in dimensions such as prioritizing academic systems， prioritizing publicity， education， and training， as well as further advancing ethical considerations.

Drug clinical trials constitute a critical link in new drug development and an essential means to verify the safety and efficacy of pharmaceuticals. The protection of participants’ rights and interests and the prevention of risks directly affect the scientific ethics and social credibility of the trials. Vulnerable groups， due to restricted autonomous decision-making capacities or special social status， are more susceptible to safety risks. Children are a typical representative of vulnerable groups. Their physiological particularities， cognitive limitations， and dependence collectively epitomize the universal protection demands of vulnerable research participants. Taking children as an instance， this paper analyzes the current weak links in the protection of pediatric research participants. Integrating advanced international experience with domestic practical demands， it comprehensively identified protection risk points at every stage and constructed a multi-stakeholder collaborative mechanism for the full-process protection of pediatric research participants. This mechanism incorporated seven main entities， including drug regulatory authorities， sponsors， researchers， and ethics committees， covering the pre-trial， intra-trial， and post-trial phases to meet the requirements of full-chain and multi-dimensional protection. It provided references for the subsequent establishment of a systematic protection mechanism for vulnerable populations.

Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

Objective:To analyze the clinical characteristics and prognostic factors of patients with acute low-frequency hearing loss（ALHL） and explore the potential role of migraine in its pathogenesis. Methods:A total of 56 ALHL patients treated at our outpatient clinic from June 2024 to January 2025 were randomly divided into two groups: a standardized treatment group and an anti-migraine treatment group. The standardized group received oral/intravenous steroids + oral/intravenous Ginkgo biloba extract, while the anti-migraine group received postauricular steroid injection/oral steroids + oral flunarizine for 2 weeks. Audiological, clinical, and psychological characteristics were collected, and statistical analysis was performed to assess clinical features and treatment outcomes, exploring the potential mechanism of migraine in ALHL. Results:The anti-migraine treatment group showed a significantly higher recovery rate than the standardized treatment group（92.86% vs 71.43%, P=0.036）. Among the anti-migraine group, 6 patients（21.43%） had a history of ALHL, 13（46.43%） had a confirmed migraine history, 26（92.86%） had anxiety, 26（92.86%） had depression, 5（17.86%） had irritable bowel syndrome, 21（75.00%） had sleep disorders, and 1（3.57%） experienced recurrence within 6 months. Conclusion:Anti-migraine therapy significantly improves the recovery rate in ALHL patients, suggesting that migraine may have a certain correlation with the pathogenesis of acute low-frequency hearing loss.
Humans ; Migraine Disorders/complications* ; Ginkgo biloba ; Male ; Female ; Flunarizine/therapeutic use* ; Plant Extracts/therapeutic use* ; Adult ; Treatment Outcome ; Middle Aged ; Ginkgo Extract

In recent years,the incidence of childhood cancer has shown a steady upward trend.Due to the unique nature of this disease,the issue of affiliate stigma among primary caregivers of children with cancer has gradually drawn attention.Affiliate stigma not only directly affects caregivers' mental health and quality of life,but also leads to reduced social support and lower self-efficacy,thereby impacting their engagement in the caregiving process and affecting the treatment adherence and prognosis of children with cancer indirectly.This article provides a review covering 5 main areas:the conceptual definition of affiliate stigma,measurement tools,influencing factors,intervention strategies,and insights and recommendations,to provide a theoretical basis and guidance for subsequent research and the development of interventions.

Diabetic foot is one of the most common and serious chronic complications in diabetic patients.With the advancement of digital healthcare,digital therapy has been gradually implemented and promoted among diabetic foot patients as an emerging tool with the advantages of safety,efficiency,and intelligence that can make up for the shortcomings of traditional diabetic foot risk assessment,health education,and self-management.This study provides an overview of digital therapeutics,summarizes its application in patients with diabetic foot,and proposes relevant recommendations,aiming to provide a reference for improving the quality of life and satisfaction of patients with diabetic foot and reducing the recurrence of diabetic foot.

Objective To explore the predictive value of electroencephalograph(EEG)quantitative parameters combined with serum microRNAs(miR)-146a-5p in cognitive dysfunction in patients with Alzheimer's disease(AD).Methods A total of 96 AD patients diagnosed in Shaoxing Seventh People's Hospital from March 2022 to May 2024 were selected to assess whether the patients had cognitive impairment according to the Montreal cognitive scale(MoCA)score,and 40 patients with cognitive impairment were set as occurrence group(MoCA score＜26points).A total of 56 patients with normal cognitive function were set as non-developing group(MoCA score ≥ 26points).Quantitative electroencephalography(EEG)parameters and serum miR-146a-5p were compared between the two groups.The risk factors of cognitive dysfunction in AD patients were analyzed by Logistic regression,and receiver operating characteristic curve was used to predict efficacy of EEG quantitative parameters and serum miR-146a-5p on cognitive dysfunction in AD patients.Results The δ frequency band,θ frequency band,and serum miR-146a-5p levels were lower in occurrence group than those in non occurrence group,while β frequency band and α frequency band were higher in occurrence group than in those non occurrence group(P＜0.05).δ frequency band,θ frequency band,miR-146a-5p,age,and years of education were risk factors for cognitive dysfunction in AD patients(P＜0.05).The area under the curve(AUC)of predicting cognitive impairment in AD patients using the combination of δ frequency band,θ frequency band,βfrequency band,α frequency band,and miR-146a-5p was 0.908.The sensitivity of predicting cognitive impairment in AD patients using the combination of delta frequency band,δ frequency band,β frequency band,α frequency band,and miR-146a-5p was higher than that of individual detection(P＜0.05).Conclusion The decrease in δ frequency band,θ frequency band,serum miR-146a-5p,and the increase in β frequency band and α frequency are closely related to the occurrence of cognitive dysfunction in AD patients.Combined detection of EEG of electroencephalogram and serum miR-146a-5p can improve the predictive efficiency of cognitive dysfunction.