Plant polyphenols are a group of naturally occurring phytochemicals which are present in high amounts in plants and are the most abundant dietary antioxidants. Epidemiological and animal model researches have indicated that polyphenols can improve cognitive function. The mechanism for polyphenols to improve cognitive function has been extensively studied and may be owing to antioxidant, anti-imflammatory, neuroprotective, cerebrovascular blood flow increasing activities, and etc. Nowadays, the plant polyphenols and its benefits to cognitive function have become a hot research topic. In this article, we reviewed the latest progress from the structure and origin of phenolic compound, as well as its effect and action mechanism on cognitive function.

Objective To analyze the blood flow velocities in middle cerebral artery with Rasmussen encephalitis. Methods8 patients with Rasmussen encephalitis were detected bilateral middle cerebral artery in both period of onset and intermission during simple partial seizures with Transcranial Doppler. ResultsThe mean velocity variance between focus side and non-focus side was minimums among the 3 indexes observed. The mean velocity of MCA displayed uneven increase during seizures. ConclusionThe mean velocity was the most stable index for judging.

ObjectiveTo discuss clinical significance of changes in cerebral blood flow velocities with Rasmussen encephalitis. Methods8 cases diagnosed as Rasmussen encephalitis were measured the blood flow velocities in middle cerebral artery (MCA) with transcranial Doppler in ictal and interictal seizures. ResultsIctal mean flow velocity in the ipsilateral MCA to the epileptogenic foci increased 14.02%～48.14% to interictal one, while it was -0.74%～22.63% in the contralateral MCA. ConclusionAn increased flow velocity has been found in the ipsilateral MCA to the epileptogenic foci during seizure in Rasmussen encephalitis patients.

BACKGROUND:The formation of postoperative abdominal adhesions is a complicated process,and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE:To analyze the mechanism of adhesion at cellular and molecular levels,and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS:"Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cells,stem cell exosomes,mesenchymal stem cell exosomes"were selected as Chinese and English search terms.We searched PubMed,CNKI,and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023.After systematic analysis,54 articles were finally included for the review. RESULTS AND CONCLUSION:(1)Any pathological factors such as peritoneal inflammation,mechanical injury,tissue ischemia,and foreign body implantation cause peritoneal surface injury,resulting in postoperative abdominal adhesion.The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair,inflammatory response,fibrinolytic system,coagulation pathway and other processes,involving a variety of cytokines and signaling pathways.Wnt/β-catenin pathway can induce fibrosis and angiogenesis,and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis.Meanwhile,nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors,promotes fibroblast proliferation,and plays a key role in the process of tissue fibrosis.(2)The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine.It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions.(3)Compared with traditional methods for treating abdominal adhesions,mesenchymal stem cell exosome has biological activity and is safe to use.Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity,longer stability and other advantages,can guide a normal repair and healing through a variety of ways.(4)Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies,showing potential application prospects in clinical studies.However,further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation.

Background and objective It has been proven that the lung cancer mortality rate in Xuanwei County, China was among the highest in the country and has been associated with exposure to indoor smoky coal emissions that con-tain high levels of polycyclic aromatic hydrocarbons. Tis risk may be modified by variation in genetic polymorphisms and coal subtypes. Our objective was to use molecular epidemiological techniques to investigate the relationship among genetic polymorphisms, coal subtype and lung cancer risk in Xuanwei County. Methods On the basis of two population-based case-control studies in residents of Xuanwei County, China, questionnaires covering demographic information, smoking his-tory, family and personal medical history, and information on other variables were administered and buccal cells and sputum samples were collected separately from each subject enrolled to extract DNA. GST superfamily, AKR1C3 superfamily, OGG1 superfamily and other genotype were scanned by useing PCR method. ORs and 95%CIs were used to estimate the associa-tion between genotypes, coal subtypes and lung cancer risk factors by conditional Logistic regression using Statistical Analysis Sofware. Results Compared with subjects who using smokeless coal or wood, smoky coal use was statistically significantly associated with lung cancer risk (OR=7.7, 95%CI: 4.5-13.3). Tere was marked heterogeneity in risk estimates for specific sub-types of smoky coal. Estimates were highest for coal from the Laibin (OR=24.8), Longtan (OR=11.6) and Baoshan (OR=6.0) coal types, and lower for coal from other types; the risk within the same subtype of coal in male and female were similar. Te GSTM1-null genotype, the AKR1C3 (Ex1-70C>G), OGG1 (Ex6-315C>G) genotypes were closely associated with increased risk of lung cancer in Xuanwei County, and their odds ratios (95%CI) were 2.3 (1.3-4.2), 1.8 (1.0-3.5) and 1.9 (1.1-3.3), re-spectively. Compared to subjects who with GSTM1-positive and used less than 130 tons of smoky coal during their lifetime, higher risks were closely associated with GSTM1-null and heavier users (≥130 tons), with the OR was 4.9 (95%CI: 1.3-18.2) and 2.7 (95%CI: 1.0-7.4) for female and male, respectively. However, higher risks were only found within female for AKR1C3 (Ex1-70C>G) and OGG1 (Ex6-315C>G), with OR (95%CI)=12.9 (2.2-107.8) and 5.7 (1.1-34.2), respectively. Conclusion Lung cancer risks varied among coal subtypes; however, risks were similar between men and women exposed to the same type of coal. Te GSTM1-null genotype may enhance susceptibility to air pollution from indoor smoky coal combustion emissions. AKR1C3 and OGG1 genotypes were significantly associated with higher risk of lung cancer, especially among heavily exposed women.

OBJECTIVETo explore the clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy (DRPLA).

METHODSDNA analysis for DRPLA gene was performed in two patients. Clinical features and genetic testing of Chinese DRPLA patients reported in the literature were reviewed in terms of initial symptoms, CAG repeat and age of onset.

RESULTSBoth families were confirmed by genetic analysis. In family 1, the number of CAG repeat in the proband, his brother and his mother was determined respectively as 8/65, 8/53 and 8/18. In family 2, the number of CAG repeat was respectively 13/63, 13/18, 18/52 and 13/13 in the proband, his brother, his father and his mother. The size of the expanded CAG repeats has inversely correlated with the age at onset (P<0.05, r=- 0.555). The age at onset of epilepsy was 10 and that for the onset of ataxia is forty years in initial symptom.

CONCLUSIONThe clinical characteristics of DRPLA include epilepsy, ataxia and cognitive impairment. The initial symptoms are epilepsy in adolescence and ataxia in adults. The size of expanded CAG repeats inversely correlates with the age at onset. The initial symptoms are different with different age of onset. It is difficult to diagnose DRPLA at an early stage.

Adolescent ; Adult ; Aged ; Atrophy ; genetics ; Basal Ganglia Diseases ; diagnosis ; genetics ; DNA Mutational Analysis ; Dentate Gyrus ; pathology ; Family Health ; Female ; Globus Pallidus ; pathology ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins ; genetics ; Pedigree ; Trinucleotide Repeat Expansion ; genetics ; Young Adult

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.

Objective:To explore the relationship between body mass index (BMI) and clinicopathological features and prognosis of gallbladder cancer.Methods:The clinical and follow-up data of three hundred and eighty-six patients of gallbladder carcinoma were retrospectively, who were treated from January 2008 to December 2013 in the Department of Hepatobiliary Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University. According to the guidelines for prevention and control of overweight and obesity in Chinese adults, the patients were divided into three groups: normal weight group(BMI<23.5 kg/m 2, 239 cases, accounting for 61.9%), overweight group (23.5 kg/m 2≤BMI<27.5 kg/m 2, 127 cases, accounting for 32.9%) and obesity group(BMI≥27.5 kg/m 2, 20 cases, accounting for 5.18%). The clinicopathological factors(gender, age, diabetes mellitus, hypertension, gallbladder related diseases, jaundice, tumor location, TMN, postoperative days, tissue differentiation, liver invasion, intraoperative blood transfusion, complications) of the three groups were compared, and the relationship between BMI and 5-year survival rate was analyzed. Measurement data with normal distribution were indicated as mean±standard deviation( Mean± SD), measurement data with skewed distribution were represented as M( P25, P75). Nonparametric rank sum test was used for measurement data. Categorical variables were compared by the chi-square test or Fisher probability method. The survival curve was drawn by the Kaplan-Meier method. The univariate analysis and multivariate analysis of prognosis were respectively done using the Log-rank test and COX regression model. Results:The median survival time of 386 patients with gallbladder cancer was 12.1 months. The overall survival rates of 1, 3 and 5 years were 51.8%, 25.2% and 16.8%, respectively. Univariate survival analysis showed that age, jaundice, accidental gallbladder cancer, tumor location, TMN, surgical method, tissue differentiation, liver invasion, intraoperative blood transfusion, and complications affected the 5-year survival rate ( χ2=12.24, 30.87, 37.01, 7.92, 104.23, 118.76, 12.05, 49.12, 6.85, 12.24, P<0.05). BMI was related to hypertension, but it had no significant effect on the 5-year survival rate. However, with the increase of BMI, the 5-year survival rate increased (16.3% vs 16.7% vs 23.3%, P=0.774). Multivariate survival analysis showed that surgical method( OR=1.441, 95% CI: 1.219-1.705), liver invasion( OR=1.625, 95% CI: 1.264-2.091), M stage( OR=1.664, 95% CI: 1.070-2.587), and N stage( OR=1.511, 95% CI: 1.218-1.875) were independent risk factors for prognosis in this group of patients ( P<0.05), and BMI was not an independent risk factor ( P=0.901). Conclusions:BMI has no significant effect on the prognosis of patients with gallbladder cancer. Obese patients with gallbladder cancer do not need to wait for weight loss before surgery.

OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.