Pulmonary tuberculosis and diabetes mellitus: Epidemiology, pathogenesis and therapeutic management (Review).

The dual burden of pulmonary tuberculosis (PTB) and diabetes mellitus (DM) is a major global public health concern. There is increasing evidence to indicate an association between PTB and DM. DM is associated with immune dysfunction and altered immune components. Hyperglycemia weakens the innate immune response by affecting the function of macrophages, dendritic cells, neutrophils, and natural killer cells, and also disrupts the adaptive immune response, thus promoting the susceptibility of PTB in patients with DM. Antituberculosis drugs often cause the impairment of liver and kidney function in patients with PTB, and the infection with Mycobacterium tuberculosis weaken pancreatic endocrine function by causing islet cell amyloidosis, which disrupts glucose metabolism and thus increases the risk of developing DM in patients with PTB. The present review discusses the association between PTB and DM from the perspective of epidemiology, pathogenesis, and treatment management. The present review aims to provide information for the rational formulation of treatment strategies for patients with PTB-DM.

The association between blood lipids and cognitive impairment in type 2 diabetes mellitus.

OBJECTIVE: The study was performed to explore the association between blood lipids and cognitive impairment in patients with type 2 diabetes mellitus (T2DM). METHODS: This study included 336 patients with T2DM. Relevant clinical data including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A1, apolipoprotein B were collected, and the Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score were used to assess the cognitive function in patients with T2DM. RESULTS: Serum apolipoprotein A1 levels were significantly increased in T2DM patients with cognitive impairment compared with T2DM patients without cognitive impairment (p = 0.017). Serum apolipoprotein A1 levels were significantly negatively correlated with MoCA score (r = - 0.143, p = 0.009) and MMSE score (r = - 0.132, p = 0.016) in patients with T2DM. In multivariable-adjusted regression model, serum apolipoprotein A1 was independently associated with cognitive impairment in patients with T2DM (OR = 5.201, p = 0.024). CONCLUSION: Serum apolipoprotein A1 is associated with cognitive impairment in patients with T2DM, but not TC, TG, HDL-C, LDL-C, and apolipoprotein B, indicating that increased serum apolipoprotein A1 may be a risk factor of cognitive impairment in patients with T2DM.

Serum bilirubin levels in primary Sjögren's syndrome: an association with interstitial lung disease.

OBJECTIVE: We aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: The retrospectively analysis included 89 consecutive patients with pSS, we collected the clinical materials of pSS patients from the electronic medical records, and all pSS patients were divide into pSS with ILD group and pSS without ILD group. RESULTS: Serum bilirubin levels were significantly lower in pSS patients with ILD than those without ILD (p = 0.010). Serum bilirubin levels showed a significant negative correlation with erythrocyte sedimentation rate (ESR) (r = -0.321, p = 0.002) in patients with pSS. A multivariable logistic regression analysis confirmed that serum bilirubin presented an independent association with ILD in patients with pSS (OR = 0.841, 95%CI:0.728-0.972, p = 0.019). CONCLUSION: Serum bilirubin is independently associated with ILD and therefore may be a promising marker of ILD in patients with pSS.

The Clinical Usefulness of Mean Corpuscular Hemoglobin Concentration in Patients with Pneumoconiosis.

Aim: We investigated the clinical usefulness of mean corpuscular hemoglobin concentration (MCHC) in patients with pneumoconiosis. Methods: We retrospectively investigated the medical records from 52 patients with pneumoconiosis, and erythrocyte parameters were analyzed in pneumoconiosis patients with different stages. Results: Here, we found that the values of MCHC were significantly lower in III stage pneumoconiosis than those with I/II stage (p = 0.024), and there was no significantly difference in MCHC between smoking pneumoconiosis patients and non-smoking pneumoconiosis patients. A negatively correlation between MCHC and disease stage was observed in patients with pneumoconiosis (r = -0.298, p = 0.032). In multiple linear regression analysis, the MCHC was found to be independently associated with advanced pneumoconiosis in patients with pneumoconiosis (p=0.011). The results of logistic regression analysis indicated that decreased MCHC was an independent risk factor of advanced pneumoconiosis in patients with pneumoconiosis (OR: 0.936, CI95%: 0.877-0.999, p = 0.046). Receiver operating characteristic curve analysis showed that the optimal cutoff value of MCHC was 330 g/L to identify advanced pneumoconiosis with the area under the curve of 0.694 (CI95%:0.550-0.839, p = 0.018). Conclusion: The decreased MCHC is associated with advanced pneumoconiosis, and MCHC may be used as a monitoring marker for follow-up of pneumoconiosis patients.

Serum Bilirubin Levels and Disease Severity in Patients with Pneumoconiosis.

Aim: To investigate the association between serum bilirubin and disease severity in patients with pneumoconiosis. Methods: The study comprised 45 patients with pneumoconiosis retrospectively; all pneumoconiosis patients were classified into I, II, and III stage according to the radiological severity. Results: Serum direct bilirubin levels were significantly lower in III stage pneumoconiosis patients than those in I/II stage (p = 0.012) but not serum indirect bilirubin. Serum direct bilirubin was negatively correlated with radiological severity in patients with pneumoconiosis (r = -0.320; p = 0.032); by multiple linear-regression analysis, we observed that serum direct bilirubin levels had independent association with radiological severity in patients with pneumoconiosis (beta = -0.459; p = 0.005). Conclusions: Serum direct bilirubin levels are negatively associated with disease severity in patients with pneumoconiosis.

Advances in microfluidic chips based on islet hormone-sensing techniques.

Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance. The mechanisms of islet dysfunction are still under investigation. Islet hormone secretion is the main function of islets, and serves an important role in the homeostasis of blood glucose. Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes. Therefore, it is crucial to develop accurate, real-time, labor-saving, high-throughput, automated, and cost-effective techniques for the sensing of islet secretome. Microfluidic chips, an elegant platform that combines biology, engineering, computer science, and biomaterials, have attracted tremendous interest from scientists in the field of diabetes worldwide. These tiny devices are miniatures of traditional experimental systems with more advantages of time-saving, reagent-minimization, automation, high-throughput, and online detection. These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years. In this review, we present a brief introduction of microfluidic chips, and three microfluidic chips-based islet hormone sensing techniques. We focus mainly on the theory of these techniques, and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.

Elevated monocyte to high-density lipoprotein cholesterol ratio correlates with clinical severity in acute inflammatory demyelinating polyradiculoneuropathy patients.

While monocyte to high-density lipoprotein cholesterol ratio (MHR) has been reported to be associated with nervous system lesions, the role of MHR has not been determined in patients with Guillain-Barré Syndrome (GBS). The purpose of our study was to explore the role of MHR in patients with GBS. A total of 52 GBS patients were involved in the study retrospectively, including patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor sensory axonal neuropathy (AMSAN). We used Hughes Functional Grading Scale (HFGS) score to evaluate functional status in GBS patients. Among patients with different subtypes of GBS, MHR was significantly elevated in those with demyelination compared to patients without demyelination (p < 0.001); AIDP patients had an increased MHR compared with AMAN or AMSAN patients (p = 0.001; p = 0.013). There was a positive correlation between MHR and HFGS score (r = 0.463, p = 0.006) in AIDP patients, but not in AMAN or AMSAN. Multiple linear regression analysis revealed that MHR was independently associated with HFGS score (beta = 0.405, p = 0.013) in AIDP patients. Our study suggests that MHR as an inflammatory marker is elevated in patients with AIDP compared to AMAN or AMSAN patients, while MHR has a positive correlation with clinical severity in AIDP patients, suggesting that MHR may provide an additional information to reflect the pathophysiology of AIDP.

Serum vitamin B12 levels and glycemic fluctuation in patients with type 2 diabetes mellitus.

Purpose: The aim of the study was to explore the correlation between serum vitamin B12 levels and glycemic fluctuation in patients with type 2 diabetes mellitus (T2DM). Methods: This study included 202 T2DM patients in whom blood glucose levels were recorded using a continuous glucose monitoring system retrospectively. Glycemic fluctuation was determined using the average daily risk range (ADRR), a diabetes-specific measure of the risk for hyper- and hypoglycemia. Results: Serum vitamin B12 levels were higher in T2DM patients with wider glycemic fluctuations than in those with minor glycemic fluctuations (p < 0.001). We observed a positive correlation between serum vitamin B12 levels and ADRR in both T2DM patients who received and did not receive metformin therapy (r = 0.388, p < 0.001 and r = 0.280, p = 0.004, respectively). Multiple linear regression analysis showed that serum vitamin B12 levels were independently correlated with ADRR in T2DM patients who received and did not receive metformin therapy (beta = 0.367, p < 0.001 and beta = 0.410, p < 0.001, respectively). Conclusions: Serum vitamin B12 levels are correlated with glycemic fluctuation in patients with T2DM and may serve as an underlying useful biomarker of glycemic fluctuation in T2DM patients, treated with or without metformin therapy.

Heat shock protein 90 inhibitor ameliorates pancreatic fibrosis by degradation of transforming growth factor-ß receptor.

BACKGROUND AND AIM: Pancreatic fibrosis increases pancreatic cancer risk in chronic pancreatitis (CP). Pancreatic stellate cells (PSCs) play a critical role in pancreatic fibrosis by transforming growth factor-ß (TGFß) has been shown to inhibit transforming growth factor-ß receptor (TGFßR)-mediated Smad and no-Smad signaling pathways. Thus, the effects of Hsp90 inhibitor on pancreatic fibrosis are evaluated in CP mice, and the association between Hsp90 and biological functions of PSCs is further investigated in vitro. METHODS: The effects of Hsp90 inhibitor 17AAG on pancreatic fibrosis were assessed in caerulein-induced CP mice, and primary PSCs were used to determine the role of Hsp90 inhibitor 17AAG in vitro. RESULTS: We observed increased expression of Hsp90 in pancreatic tissues of caerulein-induced CP mice. Hsp90 inhibitor 17AAG ameliorated pancreatic inflammation and fibrosis in caerulein-induced CP mice. In vitro, Hsp90 inhibitor 17AAG inhibited TGFß1-induced activation and extracellular matrix accumulation of PSCs by blocking TGFßR-mediated Smad2/3 and PI3K /Akt/GSK-3ß signaling pathways.Hsp90 inhibitor 17AAG degraded TGFßRII by a ubiquitin-proteasome pathway, co-immunoprecipitation showed an interaction between Hsp90 and TGFßRII in PSCs. CONCLUSIONS: The study suggests that an Hsp90 inhibitor 17AAG remarkable prevents the development of pancreatic fibrosis in caerulein-induced CP mice, and suppresses activation and extracellular matrix accumulation of PSCs in vitro. The current results provide a potential treatment strategy based on Hsp90 inhibition for pancreatic fibrosis in CP.

Renal Impairment Increases Serum Cancer Antigen 125 Levels in Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: Poor glycemic control increases the risk of diabetes complications. Serum cancer antigen 125 (CA125) has been associated with diabetes status in patients with type 2 diabetes mellitus (T2DM). Our aim was to focus on the association between serum CA125 and renal impairment in patients with T2DM. METHODS: Retrospective study included 151 patients with T2DM, with review of clinical and laboratory data. RESULTS: Serum CA125 levels were positively correlated with urinary microalbumin and 24-hours urinary protein (r=0.170, p=0.037; r=0.186, p=0.022) in T2DM patients. Patients with 24-hours urinary protein positive maintained higher serum CA125 levels than those with 24-hours urinary protein negative (p=0.047). Multiple linear regression analysis indicated that serum CA125 was independently correlated with urinary microalbumin and 24-hours urinary protein in T2DM patients (beta=0.192, p=0.042; beta=0.203, p=0.025). CONCLUSIONS: Serum CA125 levels are positively correlated with urinary microalbumin and 24-hours urinary protein in T2DM patients; renal impairment may increase serum CA125 levels in T2DM patients.

First-Trimester Platelet Count as a Predictive Biomarker for Neonatal Birth Weight Among Pregnant Women at Advanced Maternal Age.

The aim of this study was to investigate the association between first-trimester platelet count and neonatal birth weight in pregnant woman at advanced maternal age. Our study included 148 pregnancy women of advanced maternal age, the clinical and laboratory materials were retrospective obtained from medical record system. The neonatal birth weight was positively correlated with maternal body mass index and fetus gestational age (r = 0.332, P < .001; r = 0.469, P < .001), even more interestingly, the neonatal birth weight was positively correlated with first-trimester platelet count in pregnant women of advanced maternal age (r = 0.203, P = .013). Multiple linear regression analysis revealed that neonatal birth weight had an independently association with first-trimester platelet count in pregnant women of advanced maternal age (multiple-adjusted r values 0.167, P = .013). First-trimester platelet count is positively associated with neonatal birth weight, suggesting that first-trimester platelet count may be a predictive biomarker for neonatal birth weight in pregnant women of advanced maternal age.

Is testing of aspartate aminotransferase necessary along with every alanine aminotransferase for health check in elderly individuals?

OBJECTIVE: This study is to evaluate whether Aspartate Aminotransferase (AST) is necessary to screen for liver function in apparently healthy elderly individuals. METHODS: We derived the proportions of elevated ASTs that would not be measured based on 2018-year of paired Chinese elderly (Age ≥ 65 years old) check-up. Defined as AST > 40U/L is elevated. The relationship between alanine aminotransferase (ALT) and AST was analyzed by using Pearson's approach. Receiver operating characteristics curve analysis was used to evaluate the predictive accuracy of ALT for abnormal AST. RESULTS: 52,857 pairs of ALT and AST were analyzed. Serum AST was found to be positively correlated with serum ALT, r = 0.81, p < 0.01 for the entire cohort. The receiver operating characteristics (ROC) curve of ALT for predicting positive AST is 0.918. The optimal threshold for ALT is 28 U/L with the sensitivity of 82.6%, and specificity of 86.8%. At the threshold, below 0.7% of subjects with positive AST were missed, but approximately 83% of the AST tests were eliminated. CONCLUSION: Our study showed that tests of AST were not necessary along with every ALT test for health check in elderly individuals. An estimated 84.5% of subjects were not needed for AST tests which could have saved about CN¥ 815 million (USD$115 million or EURO$100 million) every year.

The alterations of gut microbiota in mice with chronic pancreatitis.

BACKGROUND: The changes of intestinal microbiome are associated with inflammatory, metabolic, and malignant disorders, and there are no studies assessing the intestinal microbiota of mice with chronic pancreatitis (CP). Thus, we aim to investigate the variations in diversity, composition and function of intestinal microbiota in CP mice. METHODS: Sixteen male C57BL/6 mice were randomly selected, and divided into two groups, treated intraperitoneally with saline (normal control group, CT group) or ethanol + cerulein (experimental group, CP group) for 6 weeks. Body weight as measured in entire processes. Histopathological examination of CP index was conducted to verify the CP induction. Extracted DNA from colon samples was used for Illumina HiSeq sequencing of the bacterial V4 region of 16S rRNA gene and analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Functional profiling of microbial communities was predicted with BugBase. RESULTS: Significant alterations of the gut microbiota were found in the CP mice compared to CT groups, as revealed by significant decrease in bacterial richness and diversity, declined the relative abundance of Lachnospiraceae_NK4A136, Ruminiclostridium and Roseburia, and increased the relative abundances of Bacteroides and Alloprevotella genera. Analysis of microbial community-level phenotypes revealed significant differences in nine phenotypes (aerobic, anaerobic, containing mobile elements, facultatively anaerobic, biofilm forming, gram-negative, gram-positive, potentially pathogenic, and stress tolerant) between CP group and CT group. CONCLUSIONS: This study indicated that mice with CP had a distinct microbiota profile.

Vitamin B6 Intake and Pancreatic Carcinoma Risk: A Meta-Analysis.

Objectives: There are conflicting results for the association between vitamin B6 intake with reduced pancreatic carcinoma risk. Thus, a meta-analysis was performed to summarize the evidences from epidemiological studies. Methods: We searched documents from PubMed-Medline, Web of Science, and Cochrane Library. The results were analyzed by using Stata software. Results: A total of nine studies were included. The multivariate-adjusted results found that the total RR values of pancreatic carcinoma was 0.65 (95% CI: 0.53-0.80) for the highest vitamin B6 intake vs the lowest vitamin B6 intake, and there was no significant heterogeneity among studies (I2 = 42.0%, P = 0.087). Sensitivity analysis indicated that no single study leaded to an excessive change for the relation between vitamin B6 intake and pancreatic carcinoma risk. Conclusions: This meta-analysis suggested that vitamin B6 intake could significantly decrease pancreatic carcinoma risk. However, further study is needed based on the limitations of the current analysis.

Probiotics improve glucose and lipid metabolism in pregnant women: a meta-analysis.

BACKGROUND: This study aims to assess the effects of probiotic supplementation on the maternal metabolism and the risk of development of gestational diabetes mellitus (GDM) in the pregnant women by a meta-analysis of relevant randomized controlled trials (RCTs). METHODS: The medical literature was searched from PubMed, Web of Science and the Cochrane Library since inception to October 2017. Two investigators independently performed the data extraction and quality assessment. The mean differences (MD) or standardized mean differences (SMD) or relative risk (RR) with 95% confidence intervals (CIs) were calculated with the random-effects model. RESULTS: From 648 citations, a total of ten RCTs published in 13 articles with 1,139 participants met the inclusion criteria. The meta-analysis showed that probiotics supplementation effectively reduced the fasting blood glucose (FBG) levels (MD -0.11 mmol/L, P=0.0003), serum insulin levels (MD -2.06 µU/mL, P<0.00001), insulin resistance (HOMA-IR) (MD -0.38, P<0.00001). The study found a significant effect of probiotics on decreasing the risk of GDM [risk ratio (RR) 0.52, P=0.003) in early pregnancy. Additionally, there were statistically significant reductions in the total cholesterol and triglycerides levels after probiotic interventions (SMD -0.56, P=0.03; SMD -0.66, P=0.04), respectively. CONCLUSIONS: Our study shows that the probiotic use was associated with improved glucose and lipid metabolism in the pregnant women, and might also contribute to the reduced risk of GDM.

Serum amylase activity altered by the ABO blood group system in Chinese subjects.

OBJECTIVE: The underlying interactions between ABO blood group antigens and pancreatic exocrine tissue have been demonstrated, and serum amylase was synthesized by pancreatic ductal cells. Thus, we investigated the link between ABO blood type and serum amylase activity in Chinese subjects. METHODS: Our study included 343 relatively healthy Chinese individuals, and the data were retrieved from electronic medical record database. RESULTS: A increased trend was observed for serum amylase activity in ABO blood type distribution, and we found that serum amylase activity was remarkable increased in subjects with O blood type compared to those with non-O blood type (P = 0.013). Logistic regression analysis indicated that serum amylase was independently associated with individuals with O blood group (adjusted odds ratio 1.574; 95% CI, 1.022-2.425, P = 0.039). CONCLUSIONS: The present evidence suggests a significant link between serum amylase activity and ABO blood type in the study population, indicating ABO blood type may be associated with the susceptibility of pancreatic disease.

Serum carbohydrate antigen 153 and renal function in patients with type 2 diabetes mellitus.

OBJECTIVE: The aim of our study was to investigate the correlation between serum carbohydrate antigen 153 (CA153) and renal function in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 184 patients with T2DM were included, and renal function was assessed by the modification of diet in renal disease (MDRD) formula adjusted coefficient of the Chinese people. RESULTS: Serum CA153 concentrations were positively correlated with blood glucose (BG) and glycated hemoglobin (HbA1c) (r = .204, P = .005; r = .165, P = .025) in patients with T2DM. There was a negative correlation between serum CA153 and estimated glomerular filtration rate (GFR) (r = -.229, P = .002) in whole patients with T2DM; similarly, the correlations were observed in both women and men (r = -.228, P = .028 for women, r = -.231, P = .028 for men). Multiple linear regression analysis suggested that serum CA153 was still significantly correlated with estimated GFR (beta = -0.286, P < .001). CONCLUSIONS: Serum CA153 is negatively correlated with estimated GFR in patients with T2DM, and serum CA153 may be a potentially useful clinical biomarker to assess renal function in the study population.

Serum uric acid and high-risk pregnancy: an intriguing correlation in advanced pregnant women.

BACKGROUND: The aim of our study is to explore the relationship between serum uric acid (UA) and high-risk pregnancy (HRP) in advanced pregnant women. METHODS: The study included 226 advanced pregnant women (≥35 years), and the HRP score were assessed according to China HRP score standards. RESULTS: All data were separated into the three groups according to HRP score, we observed significant increases of serum UA concentrations between the three groups (207.51±42.45; 226.65±45.42 and 228.27±49.70 µmol/L, P=0.017). Notably, serum UA concentrations were found to be positive correlated with HRP score (r=0.165, P=0.013) in advanced pregnant women. Serum UA was independent correlated with HRP score (beta =0.164, P=0.009) in multiple linear regression analysis. CONCLUSIONS: We conclude that serum UA is correlated with HRP score, and increased serum UA levels may herald HRP in advanced pregnant women.

Association of miR-21, miR-126 and miR-605 gene polymorphisms with ischemic stroke risk.

We investigated whether three common microRNA polymorphisms (miR-21T>C [rs1292037], miR-126G>A [rs4636297] and miR-605T>C [rs2043556]) were associated with ischemic stroke (IS) risk in a Chinese population. The study population comprised 592 ischemic stroke patients and 456 normal controls. The polymorphisms were measured using Snapshot SNP genotyping assays and confirmed by sequencing. Relative expressions of miR-21, miR-126 and miR-605 were measured by quantitative real-time PCR. We found that miR-126 gene rs4636297 polymorphism was associated with decreased ischemic stroke risk (GA vs. GG: AOR=0.64, adjust P=0.025; AA vs. GG: AOR=0.32, adjust P=0.007; dominant model: AOR=0.58, adjust P=0.004). MiR-21 gene rs1292037 and miR-605 gene rs2043556 polymorphisms were not associated with ischemic stroke risk. In addition, compared with normal controls, serum miR-126 level was significantly decreased in ischemic stroke patients, while the miR-21 level was significantly increased. Importantly, patients carrying rs4636297 GA/AA genotypes had higher serum miR-126 level (P<0.05). MiR-126 gene rs4636297 polymorphism and serum miR-126/-21 levels are associated with ischemic stroke risk. Our data indicates that miR-126 and miR-21 play roles in the development of ischemic stroke.