Objective To construct hepatocyte-specific silence information regulator 3(Sirt3)gene knockout(Sirt3 Δhep)mice by Cre-loxP technique,and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases.Methods LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous(Alb-Cre+/+)mice,and the F1 generation Sirt3flox/-/Alb-Cre+/-mice were then mated with Sirt3flox/flox mice,and the F2 genotype of Sirt3flox/flox/Alb-Cre+/-mice were the Sirt3 Δhep mice constructed in this ex-periment.Sirt3flox/flox/Alb-Cre-/-(Sirt3flox/flox)mice were the control mice.Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice.Immunofluorescence was used to detect Sirt3 ex-pression in mouse hepatocytes.Primary hepatocytes and tissue proteins of Sirt3 Δhep mice were extracted,and the ex-pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot.HE staining was used to ob-serve mice's liver,heart,spleen,and lung tissue structure.Results Sirt3 Δhep mice were successfully identified.Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group(P<0.01).At the same time,there was no significant difference in the expression of Sirt3 in the heart,spleen,kidney,and lung tissues of Sirt3 Δhep mice compared with the control group(P>0.05).The results of HE staining showed that the histological characteristics of the liver,heart,spleen,lungs,kidneys,and other major organs of Sirt3 Δhep mice were not significantly different from those of the control group mice.Conclusion Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed,which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases.

Objective:To investigate the agreement of ultrasound derived fat fraction (UDFF) with magnetic resonance imaging proton density fat fraction (MRI PDFF) on evaluating hepatic steatosis, and the performance of UDFF on diagnosing metabolic dysfunction associated steatotic liver disease (MASLD).Methods:One hundred and twenty-five volunteers and one hundred and seven inpatients who underwent abdominal ultrasound examination in Zhongda Hospital Southeast University from November 2023 to February 2024 were prospectively enrolled.UDFF and MRI PDFF were applied to evaluate hepatic steatosis. Spearman correlation test and Bland-Altman plot were applied to analyze the agreement of UDFF and MRI PDFF. Receiver operating characteristic curve (ROC) was applied to calculate the performance of UDFF on diagnosing MASLD.Results:In our participants, compared to individuals without hepatic steatosis, patients with MASLD had higher body mass index (BMI), waist-to-hip ratio, prevalence of diabetes mellitus, levels of alanine transaminase (ALT), aspertate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), triglyceride, and UDFF (all P<0.05). The percentage of hepatic steatosis measured by UDFF and MRI PDFF was strongly correlated[ρ=0.873(95% CI=0.837-0.901), P<0.001]. UDFF performed excellent for diagnosing MASLD with an area under the curve (AUC) of 0.983(95% CI=0.956-0.995, P<0.001), and was better than semi-quantitative assessment based on two-dimensional ultrasound as well as ultrasound attenuation parameter. The optimal cut off value of UDFF to diagnose MASLD was ≥6%. Conclusions:The percentage of hepatic steatosis measured by UDFF and MRI PDFF agrees with each other, and UDFF obtains an excellent performance on diagnosing MASLD, so that UDFF should be considered a reliable imaging technique for quantitively evaluating hepatic steatosis and diagnosing MASLD.

Objective:To retrieve, evaluate and summarize the best evidence of exercise reversal intervention in the elderly with cognitive frailty, and to provide evidence for guiding exercise in elderly patients.Methods:This study was a summary of evidence-based nursing evidence. Based on the PIPOST (P: Population; I: Intervention; P: Professional; O: Outcome; S: Setting; T: Type of evidence) mode, the evidence of exercise reversal intervention in the elderly with cognitive frailty in 25 relevant guideline network and association websites, Chinese and foreign language comprehensive databases such as PubMed, CINAHL, Web of Science, Embase, Chinese Biomedical Database, China National Knowledge Internet and others were searched, extracted and integrated. The retrieval time was from January 1, 2013 to February 14, 2022.Results:A total of 22 articles were included, including 3 guidelines, 2 expert consensuses, 1 clinical decision-making, 1 evidence summary, 9 Meta analysis, and 6 randomized controlled trials. Finally, 28 pieces of the best evidence including 7 dimensions were namely formulate principles,overall assessment, exercise mode, exercise intensity, exercise time and frequency, exercise management, health guidance.Conclusions:This study summarized the best evidence of exercise intervention in the elderly with cognitive frailty, which are systematic, comprehensive, rigorous, and reliable. It can provide references for healthcare administrators to dynamically evaluate patients′cognitive frailty status, formulate personalized exercise programs, and standardize exercise guidance for patients, so as to delay or even reverse cognitive frailty.

Objective:To analyze the clinical manifestations, gene mutation characteristics and treatment effects of patients with GATOR1 complex-related epilepsy, and to explore the diagnosis and treatment of this disease.Methods:The medical history, electroencephalogram, brain imaging, genetic test results, treatment and follow-up data of patients with GATOR1 complex-related epilepsy who attended the Children′s Hospital Affiliated to Capital Institute of Pediatrics, Beijing Tsinghua Changgung Hospital, and Shanghai Deji Hospital from May 2017 to July 2022 were retrospectively analyzed.Results:A total of 16 patients with GATOR1 complex-related epilepsy were collected, including 7 males and 9 females. The age of onset of epilepsy was from 2 months to 14 years. Ten cases had focal seizures only, 2 cases had generalized seizures only, and 4 cases had coexistence of focal seizures and generalized seizures, of which generalized seizures included generalized tonic-clonic seizure, spastic seizure, and myoclonic seizure. Among the 16 patients, 2 had infantile spasms, 3 had familial focal epilepsy with variable focus, and 1 had sleep related hyperkinetic epilepsy. Electroencephalogram intervals suggested multiple brain areas discharge or diffuse discharge. A total of 13 DEPDC5 gene mutation sites, 1 NPRL2 gene mutation site, and 2 NPRL3 gene mutation sites were found; 4 sites of DEPDC5 gene were reported sites, the rest were unreported; all mutations had pathogenic significance; 8 cases had nonsense mutation, 1 case had large fragment deletion, 4 cases had frameshift mutation, 1 case had integer mutation, 2 cases had splicing mutation; 13 cases′ mutation was inherited from parents, 2 cases had new mutation, and 1 case had unverified mutation. Magnetic resonance imaging (MRI) showed 5 of the 16 patients were normal, and 11 had abnormal cerebral cortex structure, manifested as bottom-of-sulcus focal cortical dysplasia (FCD), abnormal formation of sulci and (or) gyri with or without ill-defined gray-white matter and malformation of cortical dysplasia of the bilateral brain. Seven patients underwent stereotactic electroencephalogram (SEEG) monitoring, and the SEEG showed low-amplitude fast rhythm at the beginning in 6 patients, of whom 5 cases started from the frontal lobe, and 1 case started from the parietal lobe. Eight patients were only treated with drugs, 1 with single-drug therapy and the rest with multi-drug combination therapy. Eight patients underwent surgery. Among them, 5 patients with DEPDC5 gene mutation underwent epileptogenic cortex excising after SEEG monitoring, and postoperative pathological examinations showed FCDⅡ, FCDⅢ or non-specific changes; 1 patient was waiting for surgery. One patient with NPRL3 gene mutation underwent epileptogenic foci resection and postoperative pathological examinations showed FCDⅡa; the other patient with NPRL3 gene mutation underwent radiofrequency thermocoagulation after SEEG monitoring. Follow-up showed that 3 patients were seizure-free with drug treatment, and 4 patients had fewer seizures after drug treatment. Six cases underwent epileptic foci resection. Five of them were assisted by SEEG to locate the epileptic foci before surgery and were seizure-free after the operation, but the range of surgical resection was wider than the abnormal range shown by MRI; whereas 1 case who was not assisted by SEEG showed no improvement. There was still 1 case who underwent SEEG-guided radiofrequency thermocoagulation and had no improvement after operation. Conclusions:GATOR1 complex-related epilepsy mostly manifests as focal seizures. SEEG shows that seizures originate from the frontal lobe more often, and cortical developmental abnormalities are often found. DEPDC5 gene mutations are the most common ones, mostly inherited from parents, with high incomplete penetrance rate. Therefore, genetic testing is recommended for non-acquired brain structural abnormalities. For those who are refractory to drugs, a radical cure can be obtained by resection of the epileptogenic foci after preoperative evaluation.

Ischemic stroke in young adults has attracted more and more attention due to the diversity of its etiology. Although atherosclerosis is the most common cause of stroke in young adults, other or unknown causes are not uncommon . To improve clinicians′ understanding of the etiological diagnosis of stroke in young adults, this article reports a case of ischemic stroke in the First Affiliated Hospital of Jinan University. The patient was a 22-year-old male with acute onset who was diagnosed with acute ischemic stroke based on clinical presentation, physical examination, and magnetic resonance imaging of the brain. After actively searching for the cause, laboratory and genetic tests revealed that the patient had inherited thrombophilia (protein C and protein S deficiency), and cardiac magnetic resonance imaging examination found that the patient had noncompaction of the ventricular myocardium.

Objective To analyze the clinical and electroencephalogram(EEG)characteristics of nonepileptic seizures in low aged children younger than 6 years.Methods The case data of low-aged children younger than 6 years who were admitted to the Affiliated Children's Hospital of Capital Institute of Pediatrics from July 2019 to July 2021 with episodic symptoms as the main complaint and under-went video EEG monitoring were retrospectively analyzed.According to the patient's clinical symptoms and signs,combined with the video EEG monitoring results,the diagnosis was made by two neurologists.To summarize the clinical characteristics of nonepileptic seizures,and analyze the characteristics of video EEG.Results A total of 433 cases of nonepileptic seizures were recorded by video EEG,inclu-ding 398 cases(91.9％)of physiological nonepileptic seizures and 35 cases(8.1％)of psychogenic nonepileptic seizures.Interparoxys-mal epileptic discharges were detected in 24 cases(5.5％,24/433),and 15 cases(3.5％)in Rolandic region were the most common.The motor seizures were most common(392 cases,90.5％).There were 41 cases(9.5％)of non-motor seizures.Nonepileptic my-oclonic seizures were the most common in nonepileptic seizures.The number of men with physiological nonepileptic seizures was more than that of women,and the number of women with psychogenic nonepileptic seizures was more than that of men.There was significant differ-ence in gender composition between the groups(x2=12.513,P＜0.001).The proportion of psychogenic nonepileptic seizures in the 1-3 years group was significantly higher than that in the 0-1 year group(x2=8.713,P=0.003),but there was no statistical difference compared with the 3-6 years group(x2=5.253,P=0.022).Conclusion The EEG of nonepileptic seizures in low-aged children younger than 6 years is mostly normal,the epileptic discharge rate is low in the interictal period,and there is no characteristic EEG change in the interseizure period,the interictal background EEG can be used as a diagnostic reference.The clinical characteristics of non-epileptic seizures in low-aged children younger than 6 years are complex and diverse,mainly physiological nonepileptic seizures,and nonepileptic myoclonic seizures are the most common.Psychogenic nonepileptic seizures are relatively common in children aged 1-3 years.

Objective:To investigate the incidence of social isolationin community elderly patients with knee osteoarthritis and analyze its influencing factors.Methods:From January to April 2021, 240 community elderly with knee osteoarthritis in three community health service centers in Taiyuan (Yingbin community, Dawang community and Pingyang second community) were selected as research objects by convenient sampling method. They were investigated by general data questionnaire, Lubben Social Network Scale-6(Lubben-6), Geriatric Depression Scale-15, Perceived Social Support Scale, Numerical Rating Scale. Single factor analysis and binary Logistic regression analysis were used to explore the influencing factors of social isolation in elderly patients with knee osteoarthritis.Results:The prevalence of social isolation among community elderly patients with knee osteoarthritis was 43.33% (104/240) . The results of binary logistic regression analysis showed that age ( OR = 2.228, 95% CI 1.436-3.457), complicated diseases ( OR = 1.733, 95% CI 1.028-2.919), exercise ( OR = 0.560, 95% CI 0.360-0.869), depression ( OR = 3.603, 95% CI 1.768-7.339), comprehension of social support ( OR = 0.424, 95% CI 0.253-0.710) and pain ( OR = 1.792, 95% CI 1.147-2.799) were the influencing factors of social isolation in elderly patients with knee osteoarthritis ( P<0.05). Conclusions:The degree of social isolation in community elderly patients with knee osteoarthritis is relatively high, and is affected by many factors. Community medical staff should formulate targeted nursing intervention plans based on their influencing factors to reduce the occurrence of social isolation.

Objective:To evaluate the role of Tg in diagnosis of lateral cervical lymph node recurrence in papillary thyoid cancer(PTC)after radioactive iodine(RAI) therapy.Methods:From Jan 2012 to Aug 2018, 22 PTC patients who received RAI therapy after operation were reoperated for lateral cervical lymph node recurrence. The clinical data was retrospectively analyzed.Results:The median recurrence time was 30.5 (5-86) months. All 22 patients received RAI therapy after the first operation, and the median dose of RAI was 250mCi(100-700 mCi) and the episode of RAI therapy ranged from 1 to 4. All 22 PTC patients underwent neck reoperation, among which 20 cases were identified to have lymph node metastasis. The median number of lymph nodes dissected was 31 (8-83) and median number of metastatic lymph nodes was 4 (1-19) . The diagnostic accuracy of ultrasonography in detecting lymph node metastasis was 90.9%. Before reoperation, the median Tg was 1.305 (0.10-99.51) μg/L, with the cutoff value of Tg being 0.2 μg/L, and its sensitivity and specificity were 80.0% and 100%, respectively. The median stimulated Tg was 5.89 (0.14-255.80) μg/L in the 10 patients, with the cutoff value of stimulated Tg of 2 μg/L, and its sensitivity and specificity were 88.9% and 100%, respectively.Conclusions:The serum Tg level is helpful for monitoring the recurence of PTC, but recurrence cannot be completely ruled out for those with low Tg.

Objective:To report the clinical features of KCNQ2-associated epilepsy and the novel mutations and unreported clinical phenotype of KCNQ2 gene, so as to provide help for treatment selection and prognosis evaluation.Methods:Among 979 patients with epilepsy and developmental delay who were admitted to the Department of Neurology,Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2015 to October 2019, a total of 13 patients were selected from 12 families with KCNQ2 gene mutation by whole exome sequencing technology. Suspected mutations were verified by Sanger sequencing on the probands and their parents to identify the source. The clinical phenotype and genotype were analyzed according to these results.Results:Among the 13 patients with epilepsy, the onset age of four cases were older than six months [two cases in infancy (epilepsy encephalopathy), one case in early childhood (epilepsy encephalopathy) and one case in adolescence (benign epilepsy)]. Eight cases were treated with oxcarbazepine, of whom five cases were seizure free, and two cases showed partial response (>50%). Two cases treated with topiramate were seizure free. Five novel mutations were found in this research, including c.379T>G(p.Y127D), c.1A>C(initial codon mutation), c.708G>C(p.W236C), c.1027G>T(p.A343S) and c.1649T>G(p.V550G).Conclusions:Although it was rare in clinical work, the variation of KCNQ2 gene existed in patients with childhood-onset epilepsy and adolescent-onset epilepsy. Meanwhile, five novel mutations of KCNQ2 gene were reported, which further expanded its gene spectrum. This research supported that oxcarbazepine was the efficient medicine for the KCNQ2-associated epilepsy. Genetic testing showed great help to the treatment of epilepsy.

Objective:To explore the changes of corneal neuropathy and ocular surface flora in patients with type 2 diabetes, and the correlation between corneal neuropathy and ocular surface flora changes.Methods:According to the results of fundus fluorescein angiography, 65 patients with type 2 diabetes (130 eyes in total) who were treated with insulin alone and without comorbid retinopathy in the Department of Endocrinology, Henan People′s Hospital from March to June 2019 were selected. Sixty-five age-matched normal glucose tolerance subjects (130 eyes in total) were also enrolled. Confocal microscopy was performed and conjunctival sac secretions were collected. Through 16S rRNA analysis and sequencing and PICRUSt bacterial gene function prediction, the relationship between patients with type 2 diabetes and the difference in the degree of corneal neuropathy and the composition of ocular surface flora and function prediction in healthy people were explored, and the correlation between corneal neuropathy and ocular surface flora was analyzed as well.Results:Compared with healthy people, patients with type 2 diabetes have more severe corneal neuropathy, and it was related to the changes in ocular surface flora. Brevibacillus and paenibacillus were significantly positively correlated with the degree of corneal neuropathy ( P<0.05), and enhydrobacter and proteobacteria were significantly negatively correlated with the degree of corneal neuropathy ( P<0.05). PICRUSt analysis showed that the degree of enrichment of metabolism-related genes in the ocular surface flora of patients with type 2 diabetes was significantly changed compared with healthy people. Conclusion:Patients with type 2 diabetes present with more severe corneal neuropathy. The diversity of ocular surface flora and metabolic function have significant changes. The degree of severity corneal neuropathy is related to brevibacillus, paenibacillus, enhydrobacter, and proteobacteria.