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*

AIM To investigate the mechanism of Shaoyao Gancao Decoction in preventing meglumine diatrizoate-induced post-ERCP pancreatitis in rats through autophagy regulation.METHODS The rats were randomized into the normal group,the model group,the low-dose and high-dose Shaoyao Gancao Decoction(1.5,3.0 g/kg),and the indomethacin suppository group.A rat model of post-ERCP pancreatitis was induced by meglumine diatrizoate injection into the pancreatic duct under continuous pressure.The rats had their pancreatic tissues stained with HE to observe the pathological alterations,inflammatory cell infiltration,hemorrhage and necrosis;their serum levels of IL-1β,IL-6,IL-8,TNF-α,AMS,and IL-10 identified by ELISA;their autophagic vacuoles in pancreatic acinar cells observed by transmission electron microscopy;their pancreatic protein expressions of Beclin1,LC3B,p62,TRAF2 and p-JNK detected by IHC and Western blot;and their pancreatic mRNA expressions of Beclin1 and TRAF2 detected by RT-qPCR.RESULTS Compared with the model group,the high-dose Shaoyao Gancao Decoction group displayed no obvious hemorrhage;improvement in edema of acinar and interstitial cells;obviously less cellular inflammatory infiltration;substantially decreased serum levels of IL-1β,IL-6,TNF-α and AMS(P＜0.05,P＜0.01);drastically reduced amount of autophagosomes in acinar cells;and down-regulated expressions of autophagy-related proteins Beclin1,LC3,p62,TRAF2 and p-JNK(P＜0.05,P＜0.01).CONCLUSION Shaoyao Gancao Decoction can prevent post-ERCP pancreatitis by ameliorating pancreatic tissue injury,decreasing serum inflammatory response level,and interfering with abnormal autophagy of pancreatic acinar cells.Its molecular mechanism may involve inhibition of TRAF2 protein expression and modulation of p-JNK activation.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Objective:To investigate the relationship between dietary behavior and sarcopenia in older adults aged ≥65 years in longevity areas of China based on latent class analysis.Methods:A total of 4 358 older adults aged ≥65 years were selected from the 2021 Healthy Aging and Biomarkers Cohort Study. The information about their demographic characteristics, lifestyles, and chronic disease histories were collected. A simplified food frequency questionnaire was used to collect information about their dietary intake in the last month. The food intake frequency and food category score were calculated, and the higher the food category score, the richer the dietary intake. Latent class analysis was used to identify the latent classes of the dietary behavior. Sarcopenia was diagnosed using the SARC-CalF. Multivariate logistic regression model was used to analyze the association of food category scores and different latent classes of the dietary behavior with the risk for sarcopenia.Results:In 4 358 older adults, 1 841 (42.24%) had sarcopenia. The frequencies of intakes of cereals and potatoes, vegetable and fruit, meat and bean products were lower in the sarcopenia group than in the non-sarcopenia group. The risk for sarcopenia decreased with the increase of food category score in older adults ( OR=0.850, 95% CI: 0.796-0.907). Latent class analysis identified 4 latent classes of the dietary behavior. Compared with those with class 1 (frequency of intake of all 5 food species was higher probability in T3 group), those with class 2 (frequency of intake of vegetables and fruits and energy-only foods were less likely to be in the T3 group) and class 3 (frequency of intake of all 5 food species was lower probability in T3 group) had significantly increased risk for sarcopenia ( OR=1.377, 95% CI: 1.131-1.676) and ( OR=1.354, 95% CI: 1.091-1.680), 37.7% and 35.4% increased risk for sarcopenia, respectively. Conclusion:Increasing dietary intake category and sufficient intake of various foods for a balanced dietary pattern can reduce the risk of sarcopenia in older adults.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Objective:To compare the clinical characteristics of monogenic and non-monogenic early-onset inflammatory bowel disease (EO-IBD) in children and to explore the necessity of genetic analysis in EO-IBD research.Methods:A retrospective analysis of clinical data was conducted on 73 children diagnosed with EO-IBD at the Children's Hospital affiliated with Capital Institute of Pediatrics between January 2017 and December 2023. Genetic analysis was performed utilizing next-generation sequencing technology, with patients stratified into monogenic and non-monogenic groups based on the presence or absence of pathogenic mutations. Subsequently, a comparative analysis of clinical characteristics was conducted between these two cohorts of EO-IBD patients.Results:Among the 73 EO-IBD cases, 27 (37%) were diagnosed as monogenic IBD, and 46 (63%) as non-monogenic IBD. Compared to the non-monogenic group, the monogenic group had an earlier age of onset [1 (0.2, 3.0) months vs. 15 (4.1, 51.3) months, P < 0.001], with a higher incidence within the first month of life (70.4% vs. 13.0%, P < 0.001). Monogenic IBD cases were more likely to present with Crohn's disease (CD) phenotypes (88.9% vs. 52.2%, P = 0.003) and colonic involvement (L2) (91.7% vs. 62.5%, P < 0.001), but were less likely to present with non-penetrating, non-stricturing (B1) disease (87.5% vs. 95.8%, P = 0.019). Children in the monogenic group were more prone to severe malnutrition (74.1% vs. 21.3%, P < 0.001), perianal abscesses (40.7% vs. 8.7%, P < 0.001), perianal tags (22.2% vs. 0%, P = 0.004), fever (74.1% vs. 23.9%, P < 0.001), oral ulcers (44.4% vs. 6.5%, P < 0.001), and skin lesions (33.3% vs. 2.2%, P < 0.001). Regarding treatment, the monogenic group had higher usage of thalidomide (88.9% vs. 54.3%, P = 0.002) and hematopoietic stem cell transplantation (HSCT) (37.0% vs. 0, P < 0.001) and a higher mortality rate (22.2% vs. 2.2%, P = 0.017) . Conclusions:For children with IBD presenting at an early age, especially within the first month of life, and showing symptoms like fever, oral ulcers, skin lesions, severe malnutrition, and perianal disease, monogenic IBD should be considered. Genetic testing results can aid in guiding treatment decisions.

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

Objective:To explore the impact of plant and animal dietary behaviors on type 2 diabetes mellitus (T2DM) in older adults aged ≥65 in 18 longevity areas of China.Methods:The subjects were 5 223 older adults over 65 years old from the Healthy Ageing and Biomarkers Cohort Study (HABCS) in 18 longevity areas in China. Through a questionnaire survey and physical examination, information about their demographic characteristics, lifestyles, daily activities, self-health status, current diseases, and fasting venous blood were collected. Food Frequency and Questionnaire (FFQ) was used to collect data on food intake frequency. Based on the prior method, the plant-based diet index (PDI) and animal-based diet index (ADI) of 5 223 older adults were calculated. Subjects were divided into three groups (low-level group: PDI<39 or ADI<31, middle-level group: 39≤PDI≤42 or 31≤ADI≤34, high-level group: PDI>42 or ADI>34) by tertiles of PDI and ADI. Multivariate logistic regression was used to analyze the association between PDI and ADI and the risk of T2DM.Results:The average age of 5 223 subjects was (84.8±11.5) years, with the median ( Q1, Q3) of PDI about 41(38, 43) and the median ( Q1, Q3) of ADI about 33 (30, 35). The prevalence rate of T2DM was 16.41% (857/5 223). After adjusting for covariates, multivariate logistic regression showed that PDI was negatively associated with T2DM. Compared with the low-level group, the OR (95% CI) for T2DM in the high-level group was 0.83 (0.69-0.99). ADI was positively associated with T2DM, and compared with the low-level group, the OR (95% CI) for T2DM in the high-level group was 1.28 (1.06-1.55). For every one-point increase in PDI and ADI, the risk of T2DM decreased by 2% and increased by 3%, respectively, with the OR (95% CI) of 0.98 (0.96-1.00) and 1.03 (1.01-1.06), respectively. Conclusion:In Chinese older adults ≥65 years in 18 longevity areas, higher adherence to the plant-based behavior may be negatively associated with the risk of T2DM, while higher adherence to the animal-based behavior may be positively associated with the risk of T2DM.