Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Background Public places are important areas for daily human activities. Frequent contact with public items promotes their role as vehicles for microbial spread, creating a substantial risk for the transmission of pathogenic microorganisms. Objective To understand the hygiene status and influencing factors of public items in typical public places in Shanghai from 2010 to 2024, and to provide a scientific basis for optimizing the hygiene management of public items. Methods Based on the monitoring data of public items in public places in Shanghai from 2010 to 2024, the hygiene status was evaluated in three stages: 2010–2019, 2020–2022, and 2023–2024. Chi-square test and logistic regression were used to analyze the impact of factors such as monitoring stages, public place types, and public item categories on the hygiene status. Results The public items in 13807 public places were monitored. A total of 1 022 bed sheets and 9 271 towels were tested for pH value, with qualified rates of 77.66% and 87.81%, respectively. The OR (95%CI) for the pH compliance of towels relative to bed sheets was 1.77 (1.45, 2.15). Compared with bathing places, the ORs for pH compliance of towels in hair salons and beauty salons were 2.24 (1.75, 2.87) and 2.15 (1.57, 2.95), respectively. Additionally, a total of 221 650 samples from various public items were tested for microorganisms, yielding 215554 qualified samples, with an average qualified rate of 97.25%. The qualified rates for total bacterial count, total fungal count, coliforms, and Staphylococcus aureus were 92.66%, 94.63%, 98.85%, and 99.84%, respectively. The logistic regression analysis showed that, compared to the 2016–2019 baseline, no statistically significant differences were observed in the qualified rates of total fungal count across different stages; however, significantly higher qualified rates for total bacterial count, total fungal count, coliforms, and Staphylococcus aureus were recorded during 2020–2022, with ORs (95%CI) of 1.27 (1.16, 1.38), 23.20 (8.42, 63.94), and 12.08 (1.63, 89.92), respectively. Conclusion The pH compliance ranks among the top tier nationwide for cotton textile goods in Shanghai, suggesting minimal detergent retention. Furthermore, continuous improvement in cleaning and disinfection measurements has markedly enhanced the microbial hygiene of public items in public places.

ObjectiveThis study aimed to explore the effects of aerobic exercise on cognitive function in aging mice and to elucidate the underlying molecular mechanisms by which aerobic exercise ameliorates cognitive decline through the regulation of gut microbiota-metabolite network. By providing novel insights into the interplay between exercise, gut microbiota, and cognitive health, this research seeks to offer a robust theoretical foundation for developing anti-aging strategies and personalized exercise interventions targeting aging-related cognitive dysfunction. MethodsUsing naturally aged C57BL/6 mice as the experimental model, this study employed a multi-omics approach combining 16S rRNA sequencing and wide-targeted metabolomics analysis. A total of 18 mice were divided into 3 groups: young control (YC, 4-month-old), old control (OC, 21-month-old), and old+exercise (OE, 21-month-old with 12 weeks of moderate-intensity treadmill training) groups. Behavioral assessments, including the Morris water maze (MWM) test, were conducted to evaluate cognitive function. Histopathological examinations of brain tissue sections provided morphological evidence of neuronal changes. Fecal samples were collected for gut microbiota and metabolite profiling via 16S rRNA sequencing and ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS). Data were analyzed using a combination of statistical and bioinformatics tools to identify differentially abundant microbial taxa and metabolites and to construct interaction networks between them. ResultsBehavioral tests revealed that 12 weeks of aerobic exercise significantly improved spatial learning and memory capacity of aged mice, as evidenced by reduced escape latency and increased target area exploration and platform crossings in the MWM. Histopathological analysis demonstrated that exercise mitigated aging-related neuronal damage in the hippocampus, enhancing neuronal density and morphology. 16S rRNA sequencing indicated that exercise increased gut microbiota α‑diversity and enriched beneficial bacterial genera, including Bifidobacterium, Parabacteroides, and Rikenella. Metabolomics analysis identified 32 differentially regulated metabolites between OC and OE groups, with 94 up-regulated and 30 down-regulated in the OE group when compared with OC group. These metabolites were primarily involved in energy metabolism reprogramming (e.g., L-homocitrulline), antioxidant defense (e.g., L-carnosine), neuroprotection (e.g., lithocholic acid), and DNA repair (e.g., ADP-ribose). Network analysis further revealed strong positive correlations between specific bacteria and metabolites, such as Parabacteroides with ADP-ribose and Bifidobacterium with lithocholic acid, suggesting potential neuroprotective pathways mediated by the gut microbiota-metabolite axis. ConclusionThis study provides comprehensive evidence that aerobic exercise elicits cognitive benefits in aging mice by modulating the gut microbiota-metabolite network. These findings highlight three key mechanisms: (1) the proliferation of beneficial gut bacteria enhances metabolic reprogramming to boost DNA repair pathways; (2) elevated neuroinflammation-inhibiting factors reduce neurodegenerative changes; and (3) enhanced antioxidant defenses maintain neuronal homeostasis. These results underscore the critical role of the “microbiota-metabolite-brain” axis in mediating the cognitive benefits of aerobic exercise. This study not only advances our understanding of the gut-brain axis in aging but also offers a scientific basis for developing personalized exercise and probiotic-based interventions targeting aging-related cognitive decline. Future research should further validate these mechanisms in non-human primates and human clinical trials to establish the translational potential of exercise-induced gut microbiota-metabolite modulation for combating neurodegenerative diseases.

OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Flowers/chemistry* ; Humans ; Animals ; Quality Control ; Flavonoids/chemistry*