Abstract Ischemic stroke is characterized by high morbidity, disability and mortality. At present, there is a lack of effective treatment for ischemic stroke, so it is of great significance to reduce the incidence risk of ischemic stroke. Studies show that vitamin C can prevent atherosclerosis, thus reduce the incidence risk of ischemic stroke. However, this point is controversial due to the differences of study population, inconsistent evaluation methods of vitamin C content and the influence of various confounding factors. This paper reviews the related animal experiments, clinical trials and cohort studies, in order to provide reference for subsequent studies on reducing the incidence risk of ischemic stroke.

BACKGROUND: The association of tumor necrosis factor alpha (TNF-α) gene polymorphisms with the onset and development of ankylosing spondylitis (AS) has been the focus of studies on AS in the field of genetics.OBJECTIVE: To explore the association of the polymophisms of TNF-α promoter gene at positions-308 and -238 with AS susceptibility and clinical pathological changes.DESIGN: A case-control study.SETTING:The Rheumatic Immunology Department of Changhai Hospital of the Second Military Medical University of Chinese PLA.PARTICIPANTS: Totally, 108 AS patients were recruited from Rheumatic Immunology Department of Changhai Hospital, Second Military Medical University of Chinese PLA from January 1999 to December 2003 ,they had no kinship. The ratio of men to women was 5.3: 1. They aged from 13 to 71 (30-± 12) years old, and AS was divided into Ⅰ- Ⅳ radiographic stages according to the sacro-iliac joint damage. A total of 100 healthy controls were randomly selected from the blood donators(Shanghai Hospital) who were aged from 19 -56 (33 ±9) years old, and the ratio of men to women was 4.9: 1. Informed consent was obtained from all the subjects.ti-coagulated with EDTA. Polymerase chain reaction amplification and purification of the TNF-α promoter region was made and the sequence of polymerase chain reaction products was examined and displayed by Chromas 1.62 softcorresponding radiographic stage of sacro-iliac joint damage was assessed to investigate the influence of gene polymorphisms on AS.MAIN OUTCOME MEASURES: DNA direct sequencing method was used to detect -238 and -308 allele phenotypes for investigating the association with clinical presentations.G and -238G/A allele was 98.1% (106 cases) and1. 9% (2 cases) respectively in AS group and 95.0% (95 cases) and 5.0% (5 cases) respecquency of TNF-α promoter gene at positions -308. 1.1(G/G) and - 308.1.2(G/A) alleles was 82.4% (89 cases) and 17.6% (192 cases) respectively in AS group, which was not significantly different compared respectively with 85.0% (85 cases) and 14.0% (14 cases) of the control of sacro-iliac joint damage and the frequency of TNF-α promoter gene at the position of - 308 (G/G) and (G/A): AS patients with(G/G) phenotype who were confirmed of radiographic stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ were observed in 3/35/40/11cases,compared with (G/A) phenotype of 1/12/6/0 cases.The difference was statistically significant (χ2GMH = 4.77, P ＜ 0.05 ).CONCLUSION: Our data suggest that the polymorphisms of TNF-α promoter gene at positions of - 238 and - 308 allele has no association with AS susceptibility, but the polymorphisms of TNF - α promoter gene at the position of -308 might exert great influence on AS according to the radiographic stage of sacro-iliac joint damage.

Objective:To evaluate the diagnostic value of hydrogen sulfide breath test(SBT) for small intestinal bacterial overgrowth (SIBO).Methods:College students were enrolled to complete gastrointestinal symptom scale, food frequency questionnaire, lactulose hydrogen- methane breath test (LHMBT) and SBT. Based on the correlation between hydrogen sulfide(H 2S) and hydrogen or methane gas,the receiver operating characteristic (ROC) curve of H 2S was drawn and diagnostic criteria of SBT was defined. Results:A total of 300 subjects including 84 males and 216 females with age 17-32 (21.6±2.4) years were enrolled from April 2019 to December 2019 and divided into two groups.Two hundred and three patients reported SIBO discomforts with 99 (48.8%) LHMBT positive, while 38 (39.2%) were LHMBT positive in 97 health controls. Rise of H 2S at 90 min was positively related with that of hydrogen ( r=0.516, P<0.01), and H 2S levels at 90 min were positively correlated with methane ( r=0.632, P<0.01). A rise in H 2S of ≥25.0 ppb or H 2S levels ≥62.5 ppb at 90 min during lactulose breath test was considered positive for SIBO, that sensitivity, specificity and accuracy were 66.4%,79.1% and 73.3% respectively. H 2S levels were significantly related to the amount of Vitamin B 12 intake ( P=0.011). H 2S-positive subjects exhibited a constipation-predominant pattern. Conclusion:SBT is consistent with LHMBT, especially in constipation-predominant patients, which may provide a reference to the diagnosis of SIBO.

Objective Through the detection of the levels of serum betatrophin,anthropometric and biochemical indices,to determine the alteration of betatrophin levels in patients with polycystic ovary syndrome (PCOS) and the relationship between betatrophin levels and metabolic indexes such as 25-hydroxy vitamin D3 [25 (OH) D3].Methods The study group was composed of 24 women with PCOS and 20 age-natched healthy women as controls.Following general physical examination of the subjects,anthropometrie measurements were performed (height,weight,waist circumference,hip circumference).Body mass index (BMI) and waist-hip ratio were calculated;25 (OH) D3,Ca2+,fasting blood glucose,fasting insulin,triglycerides,high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) were also measured and homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated in all subjects.Serum betatrophin levels were examined with an enzyme-linked immunosorbent assay (ELISA).Using independent sample T test to compare the differences between groups,the linear correlation analysis was performed to study the correlation of betatrophin with anthropometric and biochemical indices,the influencing factors of betatrophin were analyzed by multiple linear regression.Results Circulating betatrophin levels [(0.341±0.034) ng/ml vs.(0.810±0.162) ng/ml,t=4.271,P＜0.001] and HDL-C [(1.014±0.321) mmol/L vs.(1.419±0.287) mmol/L,t=2.218,P＜0.05] significantly decreased in women with PCOS compared with controls,and BMI [(27.691±4.392) kg/m2 vs.(23.310±4.781) kg/m2,t=-2.073,P＜0.05],fasting blood glucose [(5.950±0.411) mmol/L vs.(4.883±0.314) mmol/L,t=-2.142,P＜ 0.05],HOMA-IR [(4.946 ± 0.741) vs.(3.387± 0.397),t=-2.493,P＜0.05],triglycerides [(1.510± 0.848) mmol/L vs.(1.037±0.402) mmol/L,t=-2.223,P＜0.05],LDL-C [(3.431±0.479) mmol/L vs.(2.396±0.435) mmol/L,t=-2.433,P＜0.05] were obviously increased.Moreover,there was a postive correlation between betatrophin and HOMA-IR (r=0.425,P＜0.05) as well as 25(OH)D3 (r=0.577,P＜0.05) and Ca2+ (r=0.448,P＜0.05),while the betatrophin was negatively related to BMI (r=-0.451,P＜0.05),triglycerides (r=-0.454,P＜0.05),LDL-C (r=-0.551,P＜0.05).Circulating betatrophin levels were higher when 25 (OH) D3 levels were beyond 35 nmol/L in PCOS patients [(0.539±0.092) ng/ml vs.(0.199±0.031) ng/ml,t=3.072,P＜0.001],and the multiple linear regression analysis showed that the main factors affecting the levels of betatrophin were BMI (OR=-0.260),HOMA-IR (OR=0.218),25(OH)D3 (OR=0.238),and glycerol (OR=-0.162).Conclusion It is speculated that betatrophin may be a valuable predictive factor of PCOS because betatrophin is closely associated with insulin resistance,lipid metabolism disorders and the lack of 25-hydroxy vitamin D3 in PCOS patients.

OBJECTIVETo investigate the predictive factors of pathological complete response (pCR) in primary human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC).

METHODSTotally 101 patients of primary HER2-positive breast cancer treated with trastuzumab-based NAC and subsequent curative surgical therapy in the Breast Disease Center of Peking University First Hospital from September 2007 to December 2014 were retrospectively reviewed. All patients were female with a median age of 53 (range 23 to 70) years.All patients received a taxanes- and carboplatin-containing chemotherapy, and trastuzumab was administered concurrently.A pCR, defined as the absence of invasive tumor cells in the breast and axillary lymph nodes, was achieved in 37.6% of patients (38/101). For analysis of the associations between clinicopathological factors and pCR, the χ(2) test or Fisher's exact test was used for univariate analysis, and multivariate Logistic regression analysis was performed to estimate OR and 95% CI.

RESULTSTumor-infiltrating lymphocytes (χ(2)=14.981, P=0.000), hormone receptor (HR) status (χ(2)=9.513, P=0.002), and tumor grade (χ(2)=4.005, P=0.045) were significantly associated with pCR in univariate analysis. Tumor-infiltrating lymphocytes positive (OR=4.74, 95% CI: 1.87 to 12.01, P=0.001) and HR-negative (OR=3.28, 95% CI: 1.31 to 8.20, P=0.011) were independent predictive factors of pCR in multivariate analysis.

CONCLUSIONTumor-infiltrating lymphocytes-positive and HR-negative were independent predictive factors of pCR in primary HER2-positive breast cancer treated with trastuzumab-based NAC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Axilla ; Breast Neoplasms ; drug therapy ; metabolism ; Female ; Humans ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating ; cytology ; Middle Aged ; Neoadjuvant Therapy ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Trastuzumab ; therapeutic use ; Young Adult

Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.

Objective:To observe the therapeutic effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on insulin resistance, and to investigate the molecular mechanisms in T2DM rats.Methods:The T2DM rats were induced by a high fat and high glucose diet for 10 weeks combined with low-dose streptozocin. Four weeks after infusion of HUC-MSCs via tail vein of the rats, fasting blood glucose, triglycerides, cholesterol were measured. Intraperitoneal glucose tolerance test, intraperitoneal insulin tolerance test and hyperinsulinemic-euglycaemic clamp test were performed to evaluate the islet function and insulin resistance level of rats. The protein expression levels of lipid metabolism signal pathway adenine monophosphate activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC) in liver tissue were detected by western blot.Results:Compared with the T2DM group, HUC-MSCs treatment can significantly reduce fasting blood glucose, triglycerides, total cholesterol levels ( P<0.01), and the values of area under the curve of glucose tolerance and insulin tolerance ( P<0.05) in the T2DM+ HUC-MSCs group. Hyperinsulinemic-euglycaemic clamp test found that compared with the T2DM group, after HUC-MSCs treatment, the glucose infusion rate level was significantly higher in the T2DM+ HUC-MSCs group( P<0.01); Western blot showed that compared with the T2DM group, the ratio of p-AMPK to AMPK and p-ACC to ACC in liver tissues of T2DM+ HUC-MSCs group were significantly increased( P<0.01). Conclusion:Human umbilical cord mesenchymal stem cells treatment may improve lipid metabolism and insulin resistance by activating AMPK/ACC signaling pathways in type 2 diabetic rats.

Objective:To investigate the relationship between blood glucose fluctuation and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes mellitus (T2DM) and the predictive value of betatrophin.Methods:A total of 180 newly diagnosed T2DM patients in Taiyuan Central Hospital from June 2018 to December 2019 were included for the study. And they were divided into normal intima-media group (81 cases), intima-media thickening group (60 cases) and plaque formation group (39 cases) according to the results of carotid ultrasound. The body test indexes, glucose and lipid metabolism indexes, blood glucose fluctuation and betatrophin level were compared among the three groups, and the correlation of these indexes with CIMT and risk factors of CIMT were analyzed.Results:The mean and maximal amplitude of glycemic excursions (AGE) in the plaque formation group and intima-media thickening group were significantly higher than those in the normal intima-media group [(5.08±0.62), (4.06±0.54) vs (3.17±0.41) mmol/L and (5.20±0.72), (4.26±0.54) vs (3.34±0.59) mmol/L] (all P<0.05), and these indexes in the plaque formation group were significantly higher than the intima-media thickening group (all P<0.05). Betatrophin levels in intima-media thickening group and plaque formation group were significantly higher than those in normal intima-media group [(423.35±76.24) and (490.68±97.84) vs (358.29±92.27) ng/L] (both P<0.05). Hip circumference and triglyceride (TG) in plaque formation group were obviously higher than those of the normal intima-media group and intima-media thickening group [(103.5±6.3) vs (97.6±7.0), (99.5±7.4) cm and 2.99 (1.32, 3.92) vs 1.70 (1.21, 2.39), 1.84(1.43, 2.93) mmol/L] (all P<0.05), and waist circumference, systolic blood pressure, fasting blood glucose (FBG), total cholesterol (TC), insulin resistance of homeostasis model assessment (HOMA-IR) levels in plaque formation group were significantly higher than those in normal intima-media group [(94.0 (86.0, 102.0) vs 88.0 (82.5, 94.0) cm, (136.2±18.0) vs (125.9±15.3) mmHg, 10.16 (8.43, 13.23) vs 8.49 (6.98, 9.97) mmol/L, (6.31±0.90) vs (4.99±0.99) mmol/L, 4.90 (3.50, 7.13) vs 2.77 (1.32, 5.07)] (all P<0.05). CIMT was positively correlated with waist circumference, hip circumference, systolic blood pressure (SBP), FBG, TC, TG, HOMA-IR, betatrophin, the mean and maximal AGE, blood glucose fluctuation coefficient (BGFC) (all P<0.05), and it was negatively correlated with time in range (TIR) ( P<0.05). The mean and maximal AGE, TC, TG and betatrophin were independent risk factors of CIMT (all P<0.05). Conclusion:Blood glucose fluctuation is closely related to CIMT in patients with T2DM, and betatrophin is expected to be an early predictor of diabetic macroangiopathy.

Objective:Through meta-analysis, the association of three common adipokines (leptin, adiponectin, and chemerin) with bone nutrition of senile osteoporosis (SOP) in China was systematically evaluated.Methods:CNKI, CBM, VIP, Wanfang, PubMed, Web of Science, Embase, Cochrane Library, and other databases were searched for articles published from the establishment of the database to July 30, 2022. After literature screening, data extraction, and quality evaluation of the included studies were independently conducted by two researchers, a meta-analysis was performed using RevMan5.4 and Stata17.0 softwares.Results:A total of 13 studies in the Chinese population were included, including 897 patients with SOP and 673 elderly with normal bone mineral density . The results of the meta-analysis showed that compared with the control group, the serum leptin levels were significantly lower ( MD -2.64, 95% CI -4.04 to -1.23, P < 0.001), chemerin levels were significantly higher ( MD 25.23, 95% CI 14.57 to 35.90, P < 0.001), and adiponectin levels were not significantly different ( MD -0.55, 95% CI -2.26 to 1.17, P > 0.05) in SOP patients. After subgroup analysis according to the measurement method, leptin levels remained lower in SOP patients than in the control group. Conclusions:Compared with the control group, leptin levels were lower and chemerin levels were higher in SOP patients. Therefore, dysregulation of adipokines may play an important role in the occurrence and development of SOP, and regulation of adipokine levels and functions may play a role in the treatment of SOP and the improvement of bone nutrition as a nutritional intervention.

Objective:The purpose of this study is to explore the clinical characteristics of Coronavirus Disease 2019 (COVID-19) in patients with type 2 diabetes mellitus (T2DM), and analyze the risk factors for adverse outcomes.Methods:2 052 patients diagnosed with COVID-19 who were hospitalized in Shanxi Bethune Hospital between December 1, 2022 and March 20, 2023 were included. They were divided into diabetes group ( n=70) and non-diabetes group ( n=1 982) according to the presence or absence of comorbid T2DM. The two groups were matched at 1:1 via propensity score matching. Clinical characteristics and laboratory examination results of the two groups were compared. According to the outcomes during hospitalization, the two groups were further divided into two subgroups respectively. Univariate analysis and subsequent binary Logistic regression was used to analyze the risk factors of adverse outcomes in patients with COVID-19 and type 2 diabetes. Results:After the propensity score matching, the most common comorbid condition in diabetes group and non-diabetes group was hypertension. The proportion of patients with severe or critical disease in diabetes group was higher compared with non-diabetes group. The levels of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), blood urea, IL-4, IL-6, IL-10, IFN-γ and TNF-α were significantly higher in the diabetes group ( P<0.05). Logistic regression analysis within the diabetes group showed that hypertension ( OR=3.640, 95% CI: 3.156 to 4.290), FBG>11 mmol/L ( OR=3.283, 95% CI: 1.416 to 7.611), HbA1c>10% ( OR=2.718, 95% CI: 1.024 to 7.213) were independent risk factors for adverse outcomes in patients with COVID-19 and type 2 diabetes(all P<0.05). Conclusions:Compared with the non-diabetes group, patients with COVID-19 and T2DM have worse inflammatory response and higher levels of inflammatory cytokines. The elevated levels of FBG and HbA1c are related to the adverse outcome in patients with COVID-19 and T2DM.