Objective To investigate the ameliorative effects of 4-hydroxybenzyl alcohol(4HBA)on energy metabolism in ischemic astrocytes(ASC).Methods Primary ASC were isolated from rat cortical tissue,and then randomly divided into control,oxygen-glucose deprivation/reoxygenation(OGD/R)group,low-,medium-and high-dose 4HBA groups(50,100 and 200 μmol/L),and edaravone group.Except for the control group,OGD/R injury models were established in a tri-gas incubator.The following parameters were measured:cell mortality,adenosine triphosphate(ATP)content,activities of mitochondrial ATP enzymes(Na+/K+-ATPase and Ca2+/Mg2+-ATPase),activities of mitochondrial complexes Ⅰ-Ⅴ,and expression of energy metabolism-related genes.Results Compared with the control group,the OGD/R group showed significantly higher cell mortality[(9.49±0.85)％vs(0.00±0.00)％,P＜0.01],along with obviously decreased ATP content,Na+/K+-ATPase activity,Ca2+/Mg2+-ATPase activity,and mitochondrial complex Ⅰ-V activities(P＜0.01).Compared with the OGD/R group,three 4HBA groups as well as the edaravone group exhibited significantly reduced cell mortality and elevated ATP content,Na+/K+-ATPase activity,and complex Ⅰ,Ⅲ,and V activities.The high-and medium-dose 4HBA groups and the edaravone group demonstrated increased Ca2+/Mg2+-ATPase activity,and the high-dose 4HBA group and edaravone group exhibited more enhanced complexⅡ activity,and the three 4HBA groups had elevated complex Ⅳ activity(P＜0.05,P＜0.01).Conclusion 4HBA exerts protective effect against ischemic injury in ASC by mitigating energy metabolism dysfunction and reducing cell death.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective:To investigate whether intermittent fasting alleviates insulin resistance in a polycystic ovary syndrome(PCOS) mouse model through the regulation of autophagy.Methods:Fifty 3-week-old female C57BL/6J mice were randomly assigned into the following groups using a random number table: normal control(NC) group( n=10), maintained on a standard chow diet; high-fat diet(HFD) group( n=10) fed a diet with 60% of calories derived from fat; and PCOS model group( n=30), established by combining a HFD with dehydroepiandrosterone(DHEA) administration. Successful modeling was confirmed by disrupted estrous cycles, hyperandrogenism, and polycystic ovarian morphology. The PCOS model mice were further divided into three groups: PCOS group( n=9), PCOS with intermittent fasting group(PCOS+ IF, n=9), and PCOS with intermittent fasting plus the autophagy inhibitor 3-methyladenine(3-MA) group(PCOS+ IF+ 3-MA, n=9). Autophagy levels were assessed by detecting markers LC3 and p62 and observing autophagosomes via transmission electron microscopy. Glucose tolerance test(GTT) and insulin tolerance test(ITT) were performed, and the area under the curve(AUC) was calculated to evaluate insulin resistance. Western blotting was used to detect phosphorylation levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), and p70S6 kiase(p70S6K). Results:Compared with the NC group, the PCOS model group showed absent estrous cycles, significantly elevated serum testosterone, sex hormone binding globulin, and luteinizing hormone(LH) levels( P<0.001), and polycystic ovarian changes on hematoxylin-eosin staining, confirming successful model establishment. Immunohistochemistry, transmission electron microscopy, and Western blotting demonstrated that autophagy levels were increased in the PCOS+ IF group compared with the PCOS group, while 3-MA administration reduced the intermittent fasting - induced autophagy. The AUC values for both GTT and ITT were significantly lower in the PCOS+ IF group than those in the PCOS group( P<0.001, P=0.003), but increased in the PCOS+ IF+ 3-MA group compared to the PCOS+ IF group( P<0.001, P=0.020). Western blotting analysis showed that phosphorylation levels of PI3K, Akt, mTOR, and p70S6K were significantly decreased in the PCOS+ IF group compared with the PCOS group( P=0.002, P=0.001, P=0.001, and P<0.001, respectively), and increased in the PCOS+ IF+ 3-MA group compared with the PCOS+ IF group( P=0.021, P=0.041, P=0.047, and P=0.024, respectively). Conclusions:Intermittent fasting alleviates insulin resistance in a PCOS mouse model through inhibitiing PI3K/Akt/mTOR signaling pathway and promoting autophagy.

Objective To investigate the ameliorative effects of 4-hydroxybenzyl alcohol(4HBA)on energy metabolism in ischemic astrocytes(ASC).Methods Primary ASC were isolated from rat cortical tissue,and then randomly divided into control,oxygen-glucose deprivation/reoxygenation(OGD/R)group,low-,medium-and high-dose 4HBA groups(50,100 and 200 μmol/L),and edaravone group.Except for the control group,OGD/R injury models were established in a tri-gas incubator.The following parameters were measured:cell mortality,adenosine triphosphate(ATP)content,activities of mitochondrial ATP enzymes(Na+/K+-ATPase and Ca2+/Mg2+-ATPase),activities of mitochondrial complexes Ⅰ-Ⅴ,and expression of energy metabolism-related genes.Results Compared with the control group,the OGD/R group showed significantly higher cell mortality[(9.49±0.85)％vs(0.00±0.00)％,P＜0.01],along with obviously decreased ATP content,Na+/K+-ATPase activity,Ca2+/Mg2+-ATPase activity,and mitochondrial complex Ⅰ-V activities(P＜0.01).Compared with the OGD/R group,three 4HBA groups as well as the edaravone group exhibited significantly reduced cell mortality and elevated ATP content,Na+/K+-ATPase activity,and complex Ⅰ,Ⅲ,and V activities.The high-and medium-dose 4HBA groups and the edaravone group demonstrated increased Ca2+/Mg2+-ATPase activity,and the high-dose 4HBA group and edaravone group exhibited more enhanced complexⅡ activity,and the three 4HBA groups had elevated complex Ⅳ activity(P＜0.05,P＜0.01).Conclusion 4HBA exerts protective effect against ischemic injury in ASC by mitigating energy metabolism dysfunction and reducing cell death.

Objective:To investigate whether intermittent fasting alleviates insulin resistance in a polycystic ovary syndrome(PCOS) mouse model through the regulation of autophagy.Methods:Fifty 3-week-old female C57BL/6J mice were randomly assigned into the following groups using a random number table: normal control(NC) group( n=10), maintained on a standard chow diet; high-fat diet(HFD) group( n=10) fed a diet with 60% of calories derived from fat; and PCOS model group( n=30), established by combining a HFD with dehydroepiandrosterone(DHEA) administration. Successful modeling was confirmed by disrupted estrous cycles, hyperandrogenism, and polycystic ovarian morphology. The PCOS model mice were further divided into three groups: PCOS group( n=9), PCOS with intermittent fasting group(PCOS+ IF, n=9), and PCOS with intermittent fasting plus the autophagy inhibitor 3-methyladenine(3-MA) group(PCOS+ IF+ 3-MA, n=9). Autophagy levels were assessed by detecting markers LC3 and p62 and observing autophagosomes via transmission electron microscopy. Glucose tolerance test(GTT) and insulin tolerance test(ITT) were performed, and the area under the curve(AUC) was calculated to evaluate insulin resistance. Western blotting was used to detect phosphorylation levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), and p70S6 kiase(p70S6K). Results:Compared with the NC group, the PCOS model group showed absent estrous cycles, significantly elevated serum testosterone, sex hormone binding globulin, and luteinizing hormone(LH) levels( P<0.001), and polycystic ovarian changes on hematoxylin-eosin staining, confirming successful model establishment. Immunohistochemistry, transmission electron microscopy, and Western blotting demonstrated that autophagy levels were increased in the PCOS+ IF group compared with the PCOS group, while 3-MA administration reduced the intermittent fasting - induced autophagy. The AUC values for both GTT and ITT were significantly lower in the PCOS+ IF group than those in the PCOS group( P<0.001, P=0.003), but increased in the PCOS+ IF+ 3-MA group compared to the PCOS+ IF group( P<0.001, P=0.020). Western blotting analysis showed that phosphorylation levels of PI3K, Akt, mTOR, and p70S6K were significantly decreased in the PCOS+ IF group compared with the PCOS group( P=0.002, P=0.001, P=0.001, and P<0.001, respectively), and increased in the PCOS+ IF+ 3-MA group compared with the PCOS+ IF group( P=0.021, P=0.041, P=0.047, and P=0.024, respectively). Conclusions:Intermittent fasting alleviates insulin resistance in a PCOS mouse model through inhibitiing PI3K/Akt/mTOR signaling pathway and promoting autophagy.

Objective:To summarize the clinical features of developmental epileptic encephalopathy children with DNM1 gene variants. Methods:The genotypes and clinical features of 15 children with DNM1 variants related epilepsy in the Department of Pediatrics, Peking University First Hospital from June 2017 to October 2021 were retrospectively analyzed. Results:A total of 8 male and 7 female epilepsy patients with DNM1 gene variants with the age of seizure onset ranging from 15 days to 22 months were recruited, median age was 8 months.All cases belonged to de novo heterozygous variants of the DNM1 gene, including 13 cases of missense variants, 1 case of frame shift variant and 1 case of nonsense variant, 8 cases of ectopic sites have not been reported.Multiple seizure types were observed, including epileptic spasms in 15 patients, focal seizure in 9 patients, atypical absence seizure in 2 patients and tonic seizure in 2 patients.There were various types of seizures in 7 children.Nine cases occurred as infantile spasm for the first time.All 15 patients showed varied degrees of development delay, among them, 11 cases had developmental retardation before epilepsy.Three patients had slow rhythm of electroencephalogram background activity, the electroencephalography showed hypsarrhythmia in 13 patients; clinical seizures were detected in 8 cases, among them, epileptic spasms were captured in 7 patients, tonic seizure was captured in 1 patient.Widened frontotemporal subarachnoid space, cerebral atrophy, and corpus callosum dysplasia were examined in 6, 2 and 3 patients by cranial magnetic resonance imaging, respectively.All 15 cases were diagnosed as developmental epileptic encephalopathy, of which 13 cases were consistent with infantile spasms.The age of the last follow-up ranged from 1 year old to 7 years old.After multi-antiepileptic drug treatment, 2 patients were remission, 1 patient(small size of identical twins) died of severe pneumonia at the age of 2 years, and 12 patients still had intermittent seizures, of which 1 patient was transformed from infantile spasms to Lennox-Gastaut syndrome. Conclusions:The onset age of developmental epileptic encephalopathy caused by the DNM1 gene variant usually begins in the infantile period, the peak onset age was 8 months.The main types of seizures include epileptic spasms and focal seizures, developmental retardation can occur before seizures.The clinical manifestations are mostly infantile spasms syndrome, and some children can be transformed into Lennox-Gastaut syndrome.