[Survey on Toxoplasma gondii Infection in Depressed Patients and Genotype Identification in Guizhou Province].

Objective: To survey on Toxoplasma gondii infection in depressed patients in Guizhou Province and identify the genotype of T. gondii. Methods: Enzyme-linked immunosorbent assay (ELISA) was applied to detect the T. gondii-specific antibodies IgG, IgM and circulating antigens (CAg) of T. gondii in 141 patients and 150 healthy subjects. The specific repeated DNA fragment (529 bp) of T. gondii was amplified by PCR. The genotype of T. gondii was determined by multiplex multilocus nested polymerase chain reaction-restriction fragment length polymorphism (Mn-PCR-RFLP). Results: ELISA showed that the positive rate of anti-T. gondii antibody in depressed patients and healthy subjects was 21.3%（30/141） and 7.3%（11/150）, respectively. The positive rate of IgG in depressed patients was 18.4% （26/141）, significantly higher than that in healthy subjects （7.3%, 11/150）（P<0.05）. The positive rate of IgM and CAg in depressed patients was both 1.4% （2/141）, while these were not found in healthy subjects. PCR revealed one patient positive for T. gondii, whose genotype was further identified to be Toxo DB #9（Chinese 1 type） by Mn-PCR-RFLP. Conclusion: The positive rate of T. gondii is higher in depressed patients than in the healthy subjects in Guizhou Province. The genotype of T. gondii detected in one depressed patient is the Chinese 1 type.

[Effect of perinatal factors on postnatal development of lymphocyte subsets in early preterm infants].

OBJECTIVE: To study the postnatal changes in lymphocyte subsets in early preterm infants and the effect of perinatal factors on lymphocyte subsets. METHODS: A total of 61 early preterm infants were enrolled. Flow cytometry was used to measure the absolute counts of lymphocytes and lymphocyte subsets at 1, 7, 14, and 28 days after birth, as well as at 6 months after birth for 17 of these early preterm infants. The effects of perinatal factors, such as antepartum use of hormone, intrauterine infection, gestational age at birth, and Ureaplasma urealyticum (UU) colonization, on lymphocyte subsets were analyzed. RESULTS: The absolute counts of lymphocyte subsets except natural killer (NK) cells were lowest at birth, increased rapidly at 1 week after birth, and reached the levels in healthy infants at 6 months; the count of NK cells remained at a low level and increased significantly at 6 months after birth. Compared with those with a gestational age of <28 weeks, the early preterm infants with a gestational age of ≥28 weeks had significantly higher absolute counts of T cells, T helper (Th) cells, and NK cells at 7 days after birth, a significantly higher absolute count of T cells at 14 days after birth, and significantly higher absolute counts of lymphocytes and Th cells at 28 days after birth (P<0.05). Compared with the group not using hormone, the group using hormone showed a significantly higher absolute count of T cells at 7 days after birth and significantly higher absolute counts of lymphocytes and all subsets at 14 days after birth (P<0.05). There was no significant difference in lymphocyte subsets at 1 day after birth between the intrauterine infection and non-infection groups (P>0.05); the intrauterine infection group had significantly higher absolute counts of B cells at 7 and 14 days after birth than the non-infection group. Compared those without UU colonization, the infants with UU colonization had significantly higher absolute counts of lymphocytes, T cells, Th cells, and Ts cells at 1 day after birth and a significantly higher absolute count of B cells at 14 days after birth. CONCLUSIONS: Early preterm infants have deficiencies in innate immune cells at birth and normal levels at about 6 months after birth. Various perinatal factors including antepartum use of hormone, gestational age at birth, intrauterine infection, and UU colonization have long-term effects on lymphocyte subsets in early preterm infants.

[Toxoplasma gondi Antibody Profile in Patients with Leukemia or Lymphoma].

Blood samples were collected from patients with leukemia (n = 150) or lymphoma (n = 150) in the Cancer Hospital from March to September 2014. The specific antibodies (IgG, IgM) to, and circulating antigens (CAg) of Toxoplasma gondii were determined by ELISA. A 529 bp specific sequence was amplified by PCR from the genomic DNA of T. gondii. T. gondii-specific IgG positive rate in patients with leukemia and lymphoma were 16.0% (24/150) and 20.0% (30/150), respectively, which were significantly higher than that of healthy persons (6.4%, 7/110) (P < 0.05). IgM positive rate of the leukemia patients, lymphoma patients, and healthy persons was 2.7% (4/150), 1.3% (2/150), and 0.9% (1/110) (P > 0.05), respectively. No significant difference was found in IgM and CAg positive rate among leukemia patients, lymphoma patients, and healthy persons (P > 0.05). No specific band (529 bp) was detected in all samples.

Follow-up study to explore the relationship between Neutrophil to lymphocyte ratio and impaired fasting glucose-using the group-based trajectory modeling.

Previous studies have indicated a link between neutrophil to lymphocyte ratio (NLR) and impaired fasting glucose (IFG), but the findings have been disputed. By conducting a real-world follow-up study, we can monitor the development of diseases and confirm the connection between NLR and IFG. A total of 1168 patients without IFG or T2DM were followed up for six years. At baseline, participants' NLR levels, fasting plasma glucose and other clinical characteristics were recorded. During the follow-up period, NLR levels and the prevalence of IFG were recorded. Ultimately, 45 individuals were lost to follow-up, leaving 1,123 participants for analysis. Using Group-Based Trajectory Modeling (GBTM), the sample was divided into three groups. The prevalence of IFG in the three groups was 12.1%, 19.4%, and 20.85%, respectively. Compared with the low-level NLR group, the hazard ratio of IFG in the moderate-level NLR group and high-level NLR group were 1.628 (1.109-2.390) and 1.575 (1.001-2.497), respectively. There was a significant interaction effect of BMI and NLR on the risk of IFG (P < 0.001). In this real-world follow-up study, we observed a positive association between NLR and the risk of IFG, with this relationship being exacerbated by obesity status.

Comparative efficacy of diabetes medications on liver enzymes and fat fraction in patients with nonalcoholic fatty liver disease: A network meta-analysis,.

OBJECTIVES: This network meta-analysis (NMA) aimed to evaluate the relative rank-order of existing diabetes medications in patients with nonalcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM). METHODS: A systematic literature search was conducted using the Medline, Embase and Cochrane databases. Clinical trials comparing the efficacy of diabetes medications with other interventions, including lifestyle modification and placebo, in patients with NAFLD were included. The results from the NMA are presented as the weighted mean difference (WMD) of the continuous results and the corresponding 95% confidence intervals (95% CIs). RESULTS: The articles presented the results of 49 trials involving 3,836 subjects published between 2013 and 2021. According to our results, thiazolidinedione (TZD) was ranked as the best diabetes medication in the reduction of alanine aminotransferase (ALT) (WMD = -10.10, 95% CI: -15.18, -5.01), followed by dipeptidyl peptidase-4 inhibitor (DPP4i) (WMD = -8.90, 95% CI: -14.41, -3.40). DPP4i also resulted in the greatest reduction in aspartate aminotransferase (AST) (WMD = -6.89, 95% CI: -11.72, -2.07). γ-Glutamyl transferase (γ-GT) reduction was highest in patients treated with glucagon-like peptide 1 receptor agonists (GLP1RAs) (WMD = -15.48, 95% CI: -30.93, -0.02). Ultimately, SGLT2is and GLP1RAs were superior to other diabetes medications or placebo in reducing liver fat fraction (LFF) (WMD = -6.09, 95% CI: -10.50, -1.68; WMD = -5.55, 95% CI: -10.40, -0.69, respectively). CONCLUSION: Diabetes medications, including TZD, DPP4i and GLP1RAs, were found to be suitable alternatives for liver enzyme reduction in the treatment of NAFLD patients. SGLT2is are considered the most effective therapies for lipid modulation in these patients.

MALDI-TOF MS Based Bacterial Antibiotics Resistance Finger Print for Diabetic Pedopathy.

Diabetes mellitus has become a major global health issue. Currently, the use of antibiotics remains the best foundational strategy in the control of diabetic foot infections. However, the lack of accurate identification of pathogens and the empirical use of antibiotics at early stages of infection represents a non-targeted treatment approach with a poor curative effect that may increase the of bacterial drug resistance. Therefore, the timely identification of drug resistant bacteria is the key to increasing the efficacy of treatments for diabetic foot infections. The traditional identification method is based on bacterial morphology, cell physiology, and biochemistry. Despite the simplicity and low costs associated with this method, it is time-consuming and has limited clinical value, which delays early diagnosis and treatment. In the recent years, MALDI-TOF MS has emerged as a promising new technology in the field of clinical microbial identification. In this study, we developed a strategy for the identification of drug resistance in the diagnosis of diabetic foot infections using a combination of macro-proteomics and MALDI MS analysis. The macro-proteomics result was utilized to determine the differential proteins in the resistance group and the corresponding peptide fragments were used as the finger print in a MALDI MS analysis. This strategy was successfully used in the research of drug resistance in patients with diabetic foot infections and achieved several biomarkers that could be used as a finger print for 4 different drugs, including ceftazidime, piperacillin, levofloxacin, and tetracycline. This method can quickly confirm the drug resistance of clinical diabetic foot infections, which can help aid in the early treatment of patients.

[Serum uric acid and prehypertension among Chinese adults].

OBJECTIVE: The aim of this article is to discuss the relation between serum uric acid and prehypertension, and to evaluate the influence of age, obesity, fasting plasma glucose (FPG) and lipids in Chinese adults. METHODS: All the 14 451 non-hypertensive samples were analyzed for blood pressure, body mass index (BMI), FPG, lipids and serum uric acid. RESULTS: The serum uric acid levels were stratified by quintiles, after adjustment for relevant factors, OR values of prehypertension increased with the elevated uric acid levels. Serum uric acid level was 200 - 380 µmol/L, it had a linear relationship with the risk of prehypertension, 200 µmol/L as a turning point for this linear relationship, FPG could affect their correlation (P < 0.0001). CONCLUSIONS: Serum uric acid was associated with prehypertension, independent of metabolic risk factors. The associations were not significant in old individuals. FPG may modify the associations.

Effects of SGLT2 inhibitors on cardiovascular outcomes and mortality in type 2 diabetes: A meta-analysis.

BACKGROUND: Optimal glycemic control is required to restrain the increase of cardiovascular events in patients with type 2 diabetes. The effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular events and mortality in those patients are not well established. This meta-analysis was conducted to assess the effects of SGLT2 inhibitors on cardiovascular events and mortality in patients with type 2 diabetes. METHODS: We conducted a systematic literature search of Medline, Embase and Cochrane Library and included randomized controlled trials (RCTs) of 3 different SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin) that evaluated the effects on cardiovascular outcomes and mortality in the final meta-analysis. The intervention arm was defined either as SGLT2 inhibitor monotherapy or as SGLT2 inhibitor add-on to other non-SGLT2 inhibitor antidiabetic agents (ADAs). RESULTS: Forty-two trials with a total of 61,076 patients with type 2 diabetes were included in the meta-analysis. Compared with the control, SGLT2 inhibitor treatment was associated with a reduction in the incidence of major adverse cardiovascular events (MACEs) (OR = 0.86, 95% CI 0.80-0.93, P < .0001), myocardial infarction (OR = 0.86, 95% CI 0.79-0.94, P = .001), cardiovascular mortality (OR = 0.74, 95% CI 0.67-0.81, P < .0001) and all cause mortality (OR = 0.85, 95% CI 0.79-0.92, P < .0001). However, the risk of ischemic stroke was not reduced after SGLT2 inhibitor treatment in patients with type 2 diabetes (OR = 0.95, 95% CI 0.85-1.07, P = .42). CONCLUSION: These data suggest a decreased risk of harm with SGLT2 inhibitor as a class with respect to cardiovascular events and mortality.

[Effect of integrin alpha2beta1 on invasion and migration of neuroblastoma cells].

OBJECTIVE: To study the effect of integrin alpha2beta1 on invasion and migration of SK-N-SH neuroblastoma cells. METHODS: Neuroblastoma SK-N-SH cell line was cultured in the modified eagle's medium. The effects of monoclonal antibodies to integrin alpha2 and integrin beta1 on migration and invasion were measured by inclined test and polycarbonate filters incorporated in modified Transwell chambers respectively. The migration and invasion cells were stained with Gimsa staining and counted under a 200 multiplied microscope. The blocking rate of migration and invasion of cells was calculated. RESULTS: The number of migrated SK-N-SH cells in the anti-alpha2 and anti-beta1 treatment groups (50.9+/-10.5 and 54.3+/-9.0 respectively) was significantly less than that in the control group without monoclonal antibody treatment (98.1+/-7.4) (P<0.01), with a blocking rate of cell migration of 48.1% and 44.5% respectively. The invasion to matrigel of SK-N-SH cells exposed monoclonal antibodies to integrin alpha2 and integrin beta1 was significantly blocked compared with the control SK-N-SH cells, with the number of invasion cells in the anti-alpha2 and anti-beta1 treatment groups of 25.3 +/- 4.4 and 18.8 +/- 3.9 respectively vs 41.5 +/- 4.8 in the control group (P<0.01). The blocking rate of cell invasion in the anti-alpha2 and anti-beta1 treatment groups was 39.0% and 54.7% respectively. CONCLUSIONS: Integrin alpha2beta1 may promote migration and invasion of neuroblastoma cells.

Regulation of hepatic carbohydrate metabolism by Selenium during diabetes.

In the present study, we have tried to unravel the role of Selenium supplementation in containing hyperglycemia by regulating enzymes activities involved in carbohydrate metabolism in liver of diabetic animals. Male wistar rats were divided into four groups: normal control, diabetic, Selenium treated control and Selenium treated diabetic group. Diabetes was induced in the animals by injecting alloxan intraperitoneally at a dose level of 150 mg/kg body weight. Selenium in the form of sodium selenite was supplemented to rats at a dose level of 1 PPM in drinking water, ad libitum for two time durations of 2 and 4 weeks. Animals were sacrificed and livers were excised for the analyses of enzymes involved in carbohydrate metabolism as well as the levels of glycogen. In-vitro (14)C-d glucose uptake and its turnover were also assessed in liver slices of all the treatment groups using radiorespirometry. Selenium supplementation to the diabetic rats normalized the enzyme activities of glucose-6-phosphatase, lactate dehydrogenase and glycogen phosphorylase as well as restored the glycogen levels to within the normal limits which were altered during diabetes. Interestingly, when Selenium was supplemented to diabetic rats, (14)C-d glucose uptake and its turnover showed a statistically significant increase in their values which however, were decreased in diabetic rats. In conclusion, Selenium mediates insulin-like role during diabetes by tending to normalize the altered activities of glucose metabolizing enzymes and also improves the glucose uptake and its metabolism by the liver.

Adiponectin Genotype, Blood Pressures, and Arterial Stiffness: The Cardiometabolic Risk in Chinese (CRC) Study.

The authors examined whether the adiponectin gene (ADIPOQ) variant was associated with blood pressure and arterial stiffness in Chinese adults. A genome-wide association study of the adiponectin variant rs864265 in the ADIPOQ gene was genotyped in a total of 2364 participants. After adjustment for sex, age, body mass index (BMI), fasting glucose, and lipids, participants carrying the T allele of rs864265 showed a greater increase in carotid-femoral pulse wave velocity (cfPWV) and systolic blood pressure (SBP). Further adjustment for blood pressure did not appreciably change the association with cfPWV. The authors found significant interactions between rs864265 and BMI, waist circumference, body fat percentage, and SBP in relation to cfPWV (P for interaction = .035, .001, .003, .013, respectively). The T allele of rs864265 was associated with high blood pressure and arterial stiffness. BMI, body fat percentage, waist circumference, and SBP might modify the effects of genetic polymorphism on arterial stiffness.

Synergistic effects of neck circumference and metabolic risk factors on insulin resistance: the Cardiometabolic Risk in Chinese (CRC) study.

OBJECTIVES: Recent studies have associated neck circumference (NC) with insulin resistance (IR). We examined whether such relation was modified by other metabolic risk factors. METHODS: The study samples were from a community-based health examination survey in central China. A total of 2588 apparently healthy Chinese men and women were included. RESULTS: Plasma levels of total cholesterol (TC), HDL-C, uric acid (UA) and diastolic blood pressure (DBP) were independently associated with NC after adjusted for age, sex, body mass index (BMI), waist circumference (WC) and hip circumference (HC) (P = 0.009, 0.001, 0.015 and 0.015, respectively). We observed significant interactions of NC with triglyceride (TG) and UA (all the p for interaction = 0.001) in relation to HOMA-IR. It appeared that the associations between NC and HOMA-IR were more evident in those with higher UA or TG level. CONCLUSIONS: Our data indicate that in apparently healthy Chinese adults, there were synergistic effects of UA, TG and neck circumference on insulin resistance.

Serum gamma-glutamyltransferase is associated with impaired fasting glucose in Chinese adults: the Cardiometabolic Risk in Chinese (CRC) study.

Recently, several studies found raised serum γ-glutamyltransferase (GGT), and traditional marker of liver damage was associated with the risk of type 2 diabetes. The purpose of this study was to investigate the relationship between GGT and impaired fasting glucose (IFG), and evaluate the modification effects of age, BMI, prehypertension, and lipids in a large sample of Chinese adults. The study samples are from a community-based health examination survey in China. The sample for our analysis included 7,309 participants. IFG was defined as FBG from 6.1 to 7.0 mmol/L. Serum GGT, lipids, blood pressure, and glucose were measured. The odds ratios (ORs, 95 % CI) of IFG across increasing quintiles of GGT were 1.00, 0.91 (0.49-1.72), 1.27 (0.68-2.38), 2.31 (1.29-4.15), and 2.42 (1.32-4.42) (P for trend < 0.0001), adjusting for age, sex, BMI, blood pressure, glucose, and lipids. We found significant interactions between age, BMI, and GGT on IFG risk. When the joint effects were examined, we found an additional effect of triglycerides (TG) and GGT levels on IFG. Our data indicate that serum GGT concentration was associated with the risk of IFG, and the association was modified by TG level.

Synergistic effects of serum uric acid and cardiometabolic risk factors on early stage atherosclerosis: the cardiometabolic risk in Chinese study.

OBJECTIVE: To comprehensively examine the associations of serum uric acid (SUA) with central and peripheral arterial stiffness in Chinese adults, and particularly assess the interactions between SUA and other cardiometabolic risk factors. METHODS: The study included 3,772 Chinese men and women with carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and SUA measured. RESULTS: After adjustment for age, sex, and BMI, the levels of SUA were significantly associated with increasing trend of cfPWV, crPWV and cdPWV (P for trend <0.0001). Further adjustment for heart rate (HR), blood pressure (BP) and lipids attenuated the associations with crPWV and cdPWV to be non-significant (P = 0.1, P = 0.099 respectively), but the association between SUV and cfPWV remained significant (P = 0.004). We found significant interactions between SUA and HR or BP in relation to cfPWV (P for interaction = 0.03, 0.003 respectively). The associations between SUA and cfPWV were more evident among individuals with higher HR or normal BP than those with lower HR or hypertension. CONCLUSIONS: SUA was associated with elevated aortic arterial stiffness in Chinese adults, independent of conventional cardiovascular risk factors. BP and HR might modify the deleterious effects of SUA.

Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in Chinese (CRC) study.

OBJECTIVE: The American Diabetes Association (ADA) recently published new clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT). RESEARCH DESIGN AND METHODS: The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV) and HbA1c were measured in 5,098 men and women. RESULTS: After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend <0.0001). The associations remained significant after further adjustment for blood pressure, heart rate, and lipids (P = 0.004), and the difference in cfPWV between the highest and the lowest quintiles of HbA1c was 0.31 m/s. Fasting glucose and 2 h OGTT were not associated with cfPWV in the multivariate analyses. HbA1c showed additive effects with fasting glucose or 2 h OGTT on cfPWV. In addition, age and blood pressure significantly modified the associations between HbA1c and cfPWV (P for interactions <0.0001 for age; and  = 0.019 for blood pressure). The associations were stronger in subjects who were older (≥60 y; P for trend = 0.004) and had higher blood pressure (≥120 [systolic blood pressure]/80 mmHg [diastolic blood pressure]; P for trend = 0.028) than those who were younger and had lower blood pressure (P for trend >0.05). CONCLUSIONS: HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.

A genome-wide association study identifies two new risk loci for Graves' disease.

Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.

Serum uric acid and prehypertension among Chinese adults.

BACKGROUND: Raised blood pressure is emerging as an independent risk factor for cardiovascular diseases and diabetes. We examined the relation between serum uric acid and prehypertension and the modification effects of age, obesity, fasting glucose, and lipids in Chinese adults. METHODS: The study samples are from a community-based health examination survey in China. A total of 14 451 patients with normal range of blood pressure were included. RESULTS: The odds ratios [ORs, 95% confidence interval (CI)] of prehypertension across increasing quintiles of serum uric acid were 1.00, 1.04 (0.92-1.18), 1.21 (1.06-1.38), 1.26 (1.09-1.45), and 1.36 (1.17-1.58) (P for trend < 0.0001), adjusting for age, sex, body mass index, glucose, and lipids. The regression splines suggested a possible threshold effect for serum uric acid of approximately 200 micromol/l on prehypertension risk. The associations were significant in both men and women, but was not significant in older individuals aged above 60 years. In addition, fasting glucose significantly interacted with uric acid (P for interaction < 0.0001). The associations were more evident in patients with low (P = 0.0005) and median glucose levels (P = 0.002) than in those with high glucose levels. CONCLUSIONS: Serum uric acid was associated with prehypertension, independent of metabolic risk factors. The associations were not significant in old individuals. Fasting glucose may modify the associations.