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.

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 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.

[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.

[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.

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].

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.

[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.