Phytoestrogens refer to a class of compounds in plants that can bind to and activate estrogen receptors in mammalian organisms,exerting varying degrees of protective and improvement effects on the body.Modern pharmacological studies have found that phytoestrogens have therapeutic effects on the cardiovascular system,nervous system,endocrine system,immune system,and so on.It is worth noting that the binding of phytoestrogens to estrogen receptors in the brain can produce central neuroprotective effects and improve learning and cognitive impairment in Alzheimer's pectients through multiple targeted pathways.This paper describes the research progress and related mechanisms of phytoestrogen-like monomers,Chinese herbal medicine,and compound formulations in Alzheimer's disease.The aim is to provide new drug design ideas and solutions for the effective treatment of senile dementia with traditional Chinese medicine.

Objective:The aMAP score is a hepatocellular carcinoma (HCC) risk prediction model based on an international cooperative cohort, which can be applied to various liver diseases. The aim of this study is to use the aMAP score to stratify the risk of HCC in patients with chronic liver disease (combined or non-combined metabolic diseases) admitted to People's Hospital of Yudu County, Ganzhou City, Jiangxi Province, in order to guide personalized HCC screening.Methods:The demographic information, laboratory test results (platelets, albumin, and total bilirubin) and combined disease information of patients with chronic liver disease who were admitted to People's Hospital of Yudu from January 2016 to December 2020 were collected, and the aMAP score was calculated to stratify HCC risk in this population.Results:A total of 3629 cases with chronic liver disease were included in the analysis, including 3 452 (95.1%) cases with hepatitis B virus (HBV) infection, 177 (4.9%) cases with fatty liver, and 22 (0.6%) cases with HBV infection and fatty liver. There were 2 679 (73.8%) male and the median age was 44 (35, 54). In the overall population, low, medium and high risk of HCC accounted for 52.6%, 29.0%, and 18.4% respectively. In the HBV-infected population, the proportion of high risk of HCC was significantly higher than that of fatty liver (18.9% vs. 9.6%, P = 0.001). The proportion of chronic liver disease patients with combined hypertension or diabetes was significantly higher than that of those with non-combined metabolic diseases (combined hypertension: 32.3% vs. 17.9%, P < 0.001; combined diabetes: 36.5% vs. 18.1%, P < 0.001). Moreover, the proportion of high-risk population with two metabolic diseases was significantly higher than that with one and no metabolic diseases (40.9% vs. 31.8% vs. 17.7%, P < 0.001). Conclusion:The aMAP score can be used as a simple tool for HCC screening and management of chronic liver disease in primary hospitals, and it is helpful to improve the personalized follow-up management system of chronic liver disease population. Chronic liver disease patients with metabolic diseases have a higher risk of HCC, and people with high risk of HCC should be given special priority in follow-up visits, so as to improve the rate of HCC early diagnosis and reduce the mortality rate.

Objective: To investigate the genotype and genetic characteristics of the pathogens associated with the epidemic outbreak of acute gastroenteritis(AGE) in Guangyuan city, Sichuan province. Methods: Eighteen stool samples and 15 anal swab samples from 4 AGE outbreaks were collected from Feb 2017 to May 2017. Norovirus (NoV) nucleic acid was detected by Real-time PCR method , and the positive samples were amplified by conventional reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing. Results: Four AGE outbreaks were all caused by NoV. And 20 (60.6%) samples were positive for NoV GⅡ. Gene sequence comparison and phylogenetic analysis showed that 4 AGE outbreaks were all caused by GⅡ.P16/GⅡ.2 NoV. All the strains of GⅡ.P16/GⅡ.2 NoV shared high homology in nucleotides. One of the outbreaks was caused by GⅡ.P16/GⅡ.2 and GⅡ.P7/GⅡ.14 NoV co-infection. Conclusions The 4 outbreaks of AGE in Guangyuan city, Sichuan province were major caused by GⅡ.P16/GⅡ.2 NoV, meanwhile GⅡ.P16/GⅡ.2 and GⅡ.P7/GⅡ.14 NoV co-infection existed.

Objective Childhood asthma is closely related to MP infection.This study was to investigate the distribution of ORMDL3 and HLA-DQ gene SNP in children with MP-associated asthma and gene-gene interactions.Methods One hundred and ninety-four patients with MP infection were enrolled.Extraction of whole blood genomic DNA was carried out.The genotype was collected by Flnidigm Juno 96.96 Genotyping integrated fluid pathway system.The patients were divided into MP-asthma group and MP-non-asthma group.Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction.Results MP-asthma group included 63 cases (32.5％),MP-non asthma group included 131 cases (67.5％).ORMDL3 gene rs4794820 had three genotypes of AG,GG,AA.,MP-asthma group GG genotype and G allele frequency was higher than that in MP-non-asthma group.The frequency of AA genotype was the lowest among the two groups,but in the MP-non-asthma group were higher than that in the MP-asthma group.The rs7216389 had three genotypes of TT、TC、CC,the frequency of TT genotype and T allele in MP-asthma group was significantly higher than that in MP-non-asthma group.The frequency of CC genotype was the lowest among the two groups,but CC genotype in MP-non-asthma group was significantly higher than that in MP-asthma group.The rs794820 GG genotype and rs7216389 TT genotype were found to be risk factors.ORMDL3、HLA-DQA1 and HLA-DQA2 have gene-gene interaction.Conclusion MP infection is an important external cause of asthma in children.The genotype of rs7794820 GG genotype and rs7216389 TT genotype are an important internal cause of asthma after childhood MP infection.ORMDL3 rs4794820,rs7216389 and HLA-DQA1 rs9272346,HLADQA2 rs7773955 have gene-gene interaction,synergistically enhance the risk of asthma associated with asthma in children with MP.

α-Amino acid ester acyltransferase (Aet) catalyzes the L-alanyl-L-glutamine forming reaction from L-alaine methylester hydrochloride and L-glutamine. In this study, the recombinant Escherichia coli saet-QC01 was used to express the α-amino acid acyltransferase, and its expression conditions were optimized. The recombinant protein was separated and purified by Ni-NTA affinity chromatography, and its enzymatic properties and catalytic applications were studied. The induction conditions suitable for enzyme production optimized were as follows: The temperature was 20 ℃, the induction stage (OD₆₀₀=2.0-2.5), IPTG concentration was 0.6 mmol/L, induction time was 12 h. The optimal reaction conditions of α-amino acid acyltransferase were 27 ℃, pH 8.5, it was most stable between pH 7.0 and 8.0 and relatively stable in an acidic environment, and low concentration of Co²⁺ or EDTA could promote the enzyme activity. Under optimal reaction conditions, 600 mmol/L of L-alaine methylester hydrochloride and 480 mmol/L of L-glutamine, the yield of L-alanyl-L-glutamine reached 78.2 g/L and productivity of 1.955 g/L/min, the conversion rate reached 75.0%. α-Amino acid ester acyltransferase has excellent acid-basei resistance, high catalytic efficiency. These characteristics suggest its application prospects in the industrial production.

OBJECTIVETo summarize clinical features and diagnosis of Chinese infantile patients with glycogen storage disease type II (GSD II).

METHODSix infant patients with GSD II diagnosed from January 2012 to June 2014 in the Department of Pediatrics, Peking University First Hospital were enrolled into this study. Clinical information of the 6 patients, including clinical manifestation, blood biochemistry, chest X-ray, echocardiogram, electrocardiogram, acid alpha-glucosidase (GAA) activity and GAA gene mutation analysis by direct sequencing of polymerase chain reaction (PCR) product were reviewed.

RESULTOf the 6 patients, five were female and one was male, five of whom were classic infantile type while the other one was atypical. The age of onset ranged from birth to 3-month-old. All patients had varying degrees of generalized muscle weakness, hypotonia and development retardation or retrogression. Other common findings were feeding difficulties in two patients, tongue weakness in two patients, respiratory distress in four patients, macroglossia in one patient, and hepatomegaly in two patients. Left ventricular hypertrophy and cardiomegaly were obvious in all the six patients. All six patients were found to have a enlarged heart in physical examination, and three patients who underwent a chest X-ray examination had an enlarged heart shadow. Four patients who had an echocardiography were found to have myocardial hypertrophy. The electrocardiogram in three patients showed short PR intervals and high voltage. The creatine kinase (CK) levels were three to seven times elevated. The mildest elevated CK was 441 IU/L, and the highest CK level was 1 238 U/L. Assay of GAA enzyme activity in whole blood showed significantly reduced activity (1.3 nmol/ (spot·d) to 2 nmol/(spot·d)) in the patients tested. Gene sequencing in 4 patients showed 8 pathogenic mutations, including 6 missense mutations, one nonsense mutation and one frameshift mutation. The missense mutations were c.998C > A (p.Thr333Lys), c.1280T > C (p.Met427Thr), c.1760T > C (p.Leu587Pro), c.1924G > T (p.Val642Phe), c.2012T > A (p.Met671Lys) and c.2105G > A (p.Arg702His). The nonsense mutation was c2662G > T (p.Glu888X), and the frameshift mutation was c2812_2813delTG (p.Cys938fs). The 5 classic infantile patients died at the age of 7 to 22 months. The atypical infantile patient was 2 years and five months old according to our latest follow up.

CONCLUSIONInfantile GSD II had similar motor manifestations and cardiac involvements, blood biochemical test, imaging findings, enzyme assays, though there were slight differences. The probability of GSD II should be taken into consideration if an infant has both muscular disease and cardiac involvement.

Asian Continental Ancestry Group ; Female ; Glycogen Storage Disease Type II ; diagnosis ; pathology ; Humans ; Infant ; Infant, Newborn ; Macroglossia ; congenital ; Male ; Muscle Weakness ; Mutation ; Mutation, Missense ; Polymerase Chain Reaction ; alpha-Glucosidases ; genetics ; metabolism

PurposeAs a main method to detect thyroid nodules, ultrasonography seems to have a rather low accuracy in differentiating benign and malignant ones. The present study aims to explore the diagnostic value of thyroid imaging reporting and data system (TI-RADS) in identifying benign and malignant thyroid nodules.Materials and Methods A total of 168 patients with thyroid nodules conifrmed pathologically (with 251 suspicious nodules) underwent ultrasonography and were further grouped into category 3-5 according to TI-RADS classiifcation standard. The results were retrospectively compared with histopathological ifndings. The sensitivity, speciifcity, accuracy, positive predictive value and negative predictive value of TI-RADS classiifcation in the diagnosis of benign and malignant thyroid nodules were calculated, and the differences in ultrasonic features between benign and malignant thyroid nodules were also compared.Results The surgical and pathological findings showed that 94 nodules were benign and 157 were sinister; TI-RADS regarded 93 nodules were benign and 185 were malignant. The difference of the two means of identification was significant (χ2=149.6,P<0.01). The sensitivity, speciifcity, accuracy, positive predictive value and negative predictive value of TI-RADS were 91.2% (144/157), 85.1% (80/94), 89.3% (224/251), 91.2% (144/158) and 86.0% (80/93), respectively. The ultrasonic manifestations of benign and malignant nodules were signiifcantly different with regard to aspect ratio, echogenicity, shape, calciifcation inside the nodule (χ2=8.7-121.4,P<0.01).Conclusion TI-RADS classiifcation standards have a high accuracy in the differentiation of benign and malignant thyroid nodules as a means of ultrasound examination, and thus can serve as an important guiding method in clinical diagnosis and treatment.

Objective To acquire normative values of anorectal manometry and sensation in population of our country with different gender and age.Methods Healthy individuals from four medical centers were collected and divided into three group according to their age,group Ⅰ 18 - 39 years old, group Ⅱ 40-59 years old and group Ⅲ ≥60 years old.The parameters of anal of subjects at resting status was examined by pneumohydraulic capillary perfusion system and high resolution PC Polygraf HR desktop gastrointestinal dynamic monitoring system.Subjects were asked to simulate defecation and then the defecation related indexes were recorded.In the end rectoanal inhibitory reflexes (RAIR)and rectal sensation were assessed by aired balloon.One-way analysis of variance and independent sample test were performed to compare indexes among three groups with different age and between different genders. Results A total of 166 healthy subjects were enrolled,79 in group Ⅰ with 40 male,68 in group Ⅱ with 29 male and 19 in group Ⅲ with 11 male.There was no significant difference in anal sphincter length (ASL),valid anal sphincter length (VASL),resting anal sphincter pressure (RASP),squeeze anal sphincter pressure (SASP)and duration of valid squeeze anal sphincter pressure (VSASP)among three groups with different age (all P > 0.05 ).Compared between male and female,only SASP of male ((180.13±8.10)mmHg,1 mmHg=0.133 kPa)was significantly higher than that of female ((143.93± 6.59)mmHg,t = -3.489,P <0.001 ),no difference in other parameters was found (all P >0.05 ). There was no significant difference in rectal pressure (RP),rectoanal pressure gradient (RAPG),anal sphincter relaxation rate (ASRR),and rectoanal coordination (RAC)among three groups (all P >0.05). During simulated defecation,RP and RAPG of men ((61 .23±3.46)mmHg and (40.04±4.08)mmHg) were significantly higher than those of women ((44.47 ± 2.32)mmHg and (24.00 ± 2.59 )mmHg, t=-4.075 ,-3.367,both P <0.01 ).There was no significant difference in other parameters between men and women (all P >0.05).All participants had RAIR,and there was no significant difference neither among three groups nor between men and women (both P >0.05).There was no significant difference in first rectal sensation (FRS)and constant rectal sensation (CRS)among three groups with different age (all P >0.05).However,the maximum rectal tolerable sensation (MRTS)of group Ⅱ and group Ⅲ was significantly higher than that of group Ⅰ ((194.41 ±6.32)mL and (200.00±12.75)mL vs (167.80 ± 5 .00)mL,F = 6.698,P = 0.002).There was no significant difference in rectal sensation between different gender (all P >0.05 ).Conclusions In our country,SASP,RP and RAPG during simulated defecation of male are higher than those of female.The value of MRTS increases along with the age.

Objective To discuss a optimal culture method of primary hippocampal neurons and a more suitable method of mor-phological observation ,and provide basis to the study of synapse in Alzheimer′s Disease .Methods Postnatal 0 -1 days (P0 -1 ) C57BL/6J mice were decollated and bilateral hippocampus were separated .Low level concentration of trypsin and mechanical disso-ciation were adopted .And culture medium without serum was used to culture neurons .After 17 days culturing ,transfected neurons with Green Fluorescent Protein(GFP) by calcium phosphate precipitation ,and then observed neurons and spines by fluorescence mi-croscope .Results The neurons looked good and healthy by using this method .And the axons ,dendrites and spines which were typ-ical structure of neurons were observed clearly after transfected with GFP .Conclusion The cultured hippocampal neurons look good by this method .And the morphological characteristics of neurons and spines are observed much more clearly after transfected GFP by calcium phosphate precipitation .

ObjectiveTo establish normative values of esophageal manometry in different age groups and standard test method.Methods The values of esophageal manometry were tested in healthy subjects of 3 different age groups (Group Ⅰ: 18-39 years,Group Ⅱ: 40-59 years,Group Ⅲ:≥60 years) with pneumohydraulic capillary perfusion system.The repeatability and stability of this method in lower esophageal sphincter (LES) testing were observed. Results There were no significant differences of LES length (LESL),LES pressure (LESP) at the end of expiration,average LESP,residual pressure of LES and LES relaxation rate (LESRR) in three groups (P＞0.05).The LESP at the end of inspiration in Group Ⅰ (28.98± 1.11 ) mm Hg was significantly lower than that of Group Ⅲ (34.35±1.96) mm Hg (P＜0.05).Trandiaphragmatic pressure (Pdi) in Group Ⅰ (9.55±0.62) mm Hg was significantly lower than that of Group Ⅱ (13.05±0.76) mm Hg (P＜0.05).There were no significant differences in contraction amplitude and duration of proximal and distant esophagus in 3 groups (P＞0.05).UES pressure (UESP) of Group Ⅲ was significantly lower than that of Group Ⅰ and Ⅱ (P＜0.05).As for repeatability,the second recording of LESP in Group Ⅰ and Ⅱ were significantly higher than first recording (P＜0.05).Amplitude of distant esophageal peristaltic contraction (DEPC) of female was significantly higher than of male (P＜0.05).However,there was no significant difference in amplitude of proximal esophageal peristaltic contraction (PEPC)between femal and male (P＞0.05).ConclusionsThe normative values of esophageal manometry in different age groups have been obtained.The dynamic parameters of LES do not change with age.Between age 40 to 59 years old,the contraction of esophageal body is strongest.UESP decreases significantly in old people.If the subjects have enough time to adapt before test,it will help to get accurate and reliable dynamic parameters of LES.