Association of Long-term Ambient Fine Particulate Matter (PM2.5) and Incident CKD: A Prospective Cohort Study in China.

RATIONALE & OBJECTIVE: Increasing evidence has linked ambient fine particulate matter (ie, particulate matter no larger than 2.5 µm [PM2.5]) to chronic kidney disease (CKD), but their association has not been fully elucidated, especially in regions with high levels of PM2.5 pollution. This study aimed to investigate the long-term association of high PM2.5 exposure with incident CKD in mainland China. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 72,425 participants (age ≥18 years) without CKD were recruited from 121 counties in Hunan Province, China. EXPOSURE: Annual mean PM2.5 concentration at the residence of each participant derived from a long-term, full-coverage, high-resolution (1 × 1 km2), high-quality dataset of ground-level air pollutants in China. OUTCOMES: Incident CKD during the interval between the baseline examination of each participant (2005-2017) and the end of follow-up through 2018. ANALYTICAL APPROACH: Cox proportional hazards models were used to estimate the independent association of PM2.5 with incident CKD and the joint association of PM2.5 with temperature or humidity on the development of PM2.5-related CKD. Restricted cubic splines were used to model exposure-response relationships. RESULTS: Over a median follow-up of 3.79 (IQR, 2.03-5.48) years, a total of 2,188 participants with incident CKD were identified. PM2.5 exposure was associated with incident CKD with an adjusted hazard ratio of 1.71 (95% CI, 1.58-1.85) per 10-µg/m3 greater long-term exposure. Multiplicative interactions between PM2.5 and humidity or temperature on incident CKD were detected (all P < 0.001 for interaction), whereas an additive interaction was detected only for humidity (relative risk due to interaction, 3.59 [95% CI, 0.97-6.21]). LIMITATIONS: Lack of information on participants' activity patterns such as time spent outdoors. CONCLUSIONS: Greater long-term ambient PM2.5 pollution is associated with incident CKD in environments with high PM2.5 exposure. Ambient humidity has a potentially synergetic effect on the association of PM2.5 with the development of CKD. PLAIN-LANGUAGE SUMMARY: Exposure to a form of air pollution known as fine particulate matter (ie, particulate matter ≤2.5 µm [PM2.5]) has been linked to an increased risk of chronic kidney disease (CKD), but little is known about how PM2.5 affects CKD in regions with extremely high levels of PM2.5 pollution. This longitudinal cohort study in China investigates the effect of PM2.5 on the incidence of CKD and whether temperature or humidity interact with PM2.5. Our findings suggest that long-term exposure to high levels of ambient PM2.5 significantly increased the risk of CKD in mainland China, especially in terms of cumulative average PM2.5. The associations of PM2.5 and incident CKD were greater in high-humidity environments. These findings support the recommendation that reducing PM2.5 pollution should be a priority to decrease the burden of associated health risks, including CKD.

Association Between Lipid Profiles and Left Ventricular Hypertrophy: New Evidence from a Retrospective Study.

Objective To explore the association between lipid profiles and left ventricular hypertrophy in a Chinese general population. Methods We conducted a retrospective observational study to investigate the relationship between lipid markers [including triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL-cholesterol, apolipoprotein A-I, apolipoprotein B, lipoprotein[a], and composite lipid profiles] and left ventricular hypertrophy. A total of 309,400 participants of two populations (one from Beijing and another from nationwide) who underwent physical examinations at different health management centers between 2009 and 2018 in China were included in the cross-sectional study. 7,475 participants who had multiple physical examinations and initially did not have left ventricular hypertrophy constituted a longitudinal cohort to analyze the association between lipid markers and the new-onset of left ventricular hypertrophy. Left ventricular hypertrophy was measured by echocardiography and defined as an end-diastolic thickness of the interventricular septum or left ventricle posterior wall > 11 mm. The Logistic regression model was used in the cross-sectional study. Coxmodel and Coxmodel with restricted cubic splines were used in the longitudinal cohort. Results In the cross-sectional study, for participants in the highest tertile of each lipid marker compared to the respective lowest, triglycerides [odds ratio (OR): 1.250, 95%CI: 1.060 to 1.474], HDL-cholesterol (OR: 0.780, 95%CI: 0.662 to 0.918), and lipoprotein(a) (OR: 1.311, 95%CI: 1.115 to 1.541) had an association with left ventricular hypertrophy. In the longitudinal cohort, for participants in the highest tertile of each lipid marker at the baseline compared to the respective lowest, triglycerides [hazard ratio (HR): 3.277, 95%CI: 1.720 to 6.244], HDL-cholesterol (HR: 0.516, 95%CI: 0.283 to 0.940), non-HDL-cholesterol (HR: 2.309, 95%CI: 1.296 to 4.112), apolipoprotein B (HR: 2.244, 95%CI: 1.251 to 4.032) showed an association with new-onset left ventricular hypertrophy. In the Coxmodel with forward stepwise selection, triglycerides were the only lipid markers entered into the final model. Conclusion Lipids levels, especially triglycerides, are associated with left ventricular hypertrophy. Controlling triglycerides level potentiate to be a strategy in harnessing cardiac remodeling but deserve to be further investigated.

Regulator of G protein signalling 14 attenuates cardiac remodelling through the MEK-ERK1/2 signalling pathway.

In the past 10 years, several publications have highlighted the role of the regulator of G protein signalling (RGS) family in multiple diseases, including cardiovascular diseases. As one of the multifunctional family members, RGS14 is involved in various biological processes, such as synaptic plasticity, cell division, and phagocytosis. However, the role of RGS14 in cardiovascular diseases remains unclear. In the present study, we used a genetic approach to examine the role of RGS14 in pathological cardiac remodelling in vivo and in vitro. We observed that RGS14 was down-regulated in human failing hearts, murine hypertrophic hearts, and isolated hypertrophic cardiomyocytes. Moreover, the extent of aortic banding-induced cardiac hypertrophy and fibrosis was exacerbated in RGS14 knockout mice, whereas RGS14 transgenic mice exhibited a significantly alleviated response to pressure overload. Furthermore, research of the underlying mechanism revealed that the RGS14-dependent rescue of cardiac remodelling was attributed to the abrogation of mitogen-activated protein kinase (MEK)-extracellular signal-regulated protein kinase (ERK) 1/2 signalling. The results showed that constitutive activation of MEK1 nullified the cardiac protection in RGS14 transgenic mice, and inhibition of MEK-ERK1/2 by U0126 reversed RGS14 deletion-related hypertrophic aggravation. These results demonstrated that RGS14 attenuated the development of cardiac remodelling through MEK-ERK1/2 signalling. RGS14 exhibited great potential as a target for the treatment of pathological cardiac remodelling.

MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus.

OBJECTIVE: Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. APPROACH AND RESULTS: BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. CONCLUSIONS: miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.

Tacrolimus decreases insulin sensitivity without reducing fasting insulin concentration: a 2-year follow-up study in kidney transplant recipients.

New Onset Diabetes after Transplantation (NODAT) is defined as sustained hyperglycemia developing in patients without diabetes history before transplantation. A cohort study was performed to access the effects of tacrolimus on insulin secretion and insulin sensitivity and consequently in the development of NODAT in kidney transplant recipients. Then, we further investigated the association between NODAT and single-nucleotide polymorphisms of IRS-1 and IRS-2 in renal allograft recipients. One hundred and fifty-eight kidney transplant patients, receiving tacrolimus as the base immunosuppressant, were divided into two groups: with or without NODAT. Plasma levels of fasting insulin concentration (FINS) and C-peptide were determined by enhanced chemiluminescence immunoassay and ADVIA Centaur C peptide assay, respectively. The genotypes of Gly1057Asp in IRS-2 and Gly972Arg in IRS-1 were detected through polymerase chain reaction fragment length polymorphism in NODAT and non-NODAT patients. It was found that the concentrations of fasting plasma insulin and C-peptide in NODAT and non-NODAT patients treated with tacrolimus were higher than that in healthy volunteers (p < 0.05). Fasting plasma insulin concentration in NODAT was significantly elevated compared with than that in non-NODAT group (p < 0.05). But there are no statistical differences in fasting plasma C-peptide concentrations between NODAT and non-NODAT groups. The allele and genotype frequencies of IRS-2 Gly1057Asp and IRS-1 Gly972Arg in NODAT patients were not significantly different from non-NODAT patients (p > 0.05). In conclusion, insulin resistance is the primary cause of tacrolimus-induced NODAT. The IRS-2 Gly1057Asp and IRS-1 Gly972Arg genotypes are not related to NODAT.

Comprehensive, comparative evaluation of 25 automated SARS-CoV-2 serology assays.

IMPORTANCE: We have previously highlighted the fact that hundreds of SARS-CoV-2 serology tests were released months after the onset of the COVID-19 pandemic. Of the hundreds of studies investigating the test kits' performance, few were comparative reports, using the same comprehensive sample set across multiple tests. Recently, we reported a comparative assessment of 35 rapid diagnostic tests (RDTs) or microtiter plate enzyme immunoassays (EIA) for use in low- and middle-income countries, using a large sample set from individuals with a history of COVID-19. Only a few tests meet WHO Target Product Profile performance requirements. This study reports on the performance of a further 25 automated SARS-CoV-2 immunoassays using the same panel of samples. The results highlight the better analytical and clinical performance of automated serology test kits compared with RDTs, and the importance of independent comparative assessments to inform the use and procurement of these tests for both diagnostic and epidemiological investigations.

Enzymatic synthesis of glutathione using engineered Saccharomyces cerevisiae.

Two single gene cassettes, each containing one of the individual gene (γ-glutamylcysteine synthetase gene GSH1 or glutathione synthetase gene GSH2), were constructed under the control of alcohol dehydrogenase (ADH1) promoter and their respective native terminators. The recombinant plasmids constructed with Kan (r) or Hyg (r) as the selective markers and were transformed into Saccharomyces cerevisiae separately and jointly. Three engineered strains, GSH1-enhanced strain S.TS013/GSH1, GSH2-enhanced strain S.TS013/GSH2 and GSH1+GSH2 double-enhanced strain S.TS013/GSH1+GSH2, were constructed. Glutathione production using the recombinant strains to improve was then determined. By the cell dosage proportions of two engineered strains (S.TS013/GSH1, S.TS013/GSH2) and a two-stage reaction, GSH productivity increased by 84 and 59 % over that of the host strain and the S.TS013/GSH1+GSH2 strain, respectively.

NRS2002 assesses nutritional status of leukemia patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: To discuss whether nutritional risk screening 2002 (NRS2002) is appropriate for nutritional risk screening for leukemia patients before and after hematopoietic stem cell transplantation (HSCT), and whether there are risk differences in other conditions, such as age, gender and matching degree; to find the methods and indicators of nutritional risk screening for these patients before and after HSCT, in order to give timely intervention to guarantee the successful completion of the entire transplantation process. METHODS: Nutritional risk of 99 leukemia patients was screened with NRS2002 before and after HSCT. The (χ) (2) test was applied to compare the risk differences between groups such as age, gender and matching degree, while the differences of other enumeration data, such as recent (1-3 months) weight loss, reduced food intake within one week and BMI, were compared by continuity correction. RESULTS: Of the 99 leukemia patients, 22 cases (22.2%) had nutritional risk before HSCT, while all patients had nutritional risk after HSCT; there is no significant difference in nutritional risk between male and female, and patients of less than 30 years old, not-full matched, recent (1-3 months) weight loss, reduced food intake within a week or BMI <18.5 were more likely to have nutritional risk; and 77 cases (77.8%) had weight loss, among which 49 patients (63.6%) had more than 5% weight loss within one month. CONCLUSIONS: This study showed that leukemia patients should receive the nutritional risk screening conventionally before and after HSCT, and NRS2002 was only appropriate for nutritional risk screening before HSCT. More attention should be paid to the patients less than 30 years old or not-full matched. Weight change was one of the important nutritional indicators for patients after HSCT.

Lactobacillus levels and prognosis of patients with acute myocardial infarction.

OBJECTIVE: To explore the relationship between Lactobacillus and prognosis of acute myocardial infarction (AMI) patients treated by percutaneous coronary intervention (PCI) and its correlation with clinical parameters. METHODS: Consecutive patients with AMI in the coronary care unit of Tianjin Chest Hospital in China who received emergency PCI between July 2017 and December 2018 were enrolled. Subjects' fecal 16S rDNA gene sequencing data were analyzed and subjects were categorized into low, medium and high level groups according to stool Lactobacillus measurements. The primary endpoints were major adverse cardiac events. Cox regression analysis was used to analyze the relationship between Lactobacillus and prognosis. Spearman correlation analysis and trend tests were used to assess the relationship between Lactobacillus and the clinical indicators. RESULTS: The data of 254 patients were included in the analysis. Mean age was 65.90 ± 11.56 years, and 152 patients (59.84%) were male. Follow-up time was 652 (548.25-753.00) days. Multivariate Cox regression analysis showed a significantly lower risk of major adverse cardiac events in patients with Lactobacillus > 7.1 copies/g [adjusted hazard ratio (HR) = 0.216, 95% CI: 0.094-0.493,P < 0.001] compared to patients with Lactobacillus ≤ 3.6 copies/g. Statistically significant differences were shown in ST-segment elevation myocardial infarction (STEMI) (HR = 0.217, 95% CI: 0.085-0.551, P = 0.001). Lactobacillus was a protective factor for male smokers aged over 60 years whose brain natriuretic peptide was over 1,000 pg/mL. Spearman correlation analysis showed that Lactobacillus correlated negatively with white blood cells, neutrophils, high-sensitivity C-reactive protein, TroponinT, creatine kinase, creatine kinase-MB and brain natriuretic peptide (downward trend), and correlated positively with left ventricular ejection fraction (upward trend). CONCLUSIONS: This study is the first to reveal the correlation between Lactobacillus and inflammation and myocardial damage after STEMI. STEMI patients, especially male smokers aged over 60 years with severe impairment of cardiac function, have better outcomes with high levels of Lactobacillus, suggesting new therapeutic strategies for improving the prognosis and quality of life of AMI patients.

Soluble expression and purification of a crab antimicrobial peptide scygonadin in different expression plasmids and analysis of its antimicrobial activity.

Scygonadin is an anionic antimicrobial peptide recently identified from the seminal plasma of Scylla serrata. To gain more detailed information on its antimicrobial activity, scygonadin mature peptide was expressed in Escherichia coli in order to obtain a large quantity of biologically active product. An approximately 43 kDa fusion protein CKS-scygonadin was obtained in a highly stable and soluble form. The soluble component of the fusion CKS-scygonadin was purified by immobilized metal affinity chromatography (IMAC). A single 11 kDa recombinant scygonadin was cleaved from CKS-scygonadin and purified from the cleavage mixture using an affinity chromatography column with a yield of 10.6 mg/L. Alternatively, a recombinant scygonadin was purified from pET28-scygonadin by one-step Ni(2+) affinity chromatography and 65.9 mg/L pure recombinant scygonadin was obtained which was higher than that purified from pTrc-CKS/scygonadin in bacteria culture. The recombinant scygonadin was confirmed using SDS-PAGE analysis and MS-fingerprinting. Both recombinant products of scygonadin from different expressed plasmids showed the activity against both Gram-positive and Gram-negative bacteria, but no activity against yeast and fungi tested. The kinetic studies showed that the recombinant scygonadin was strong active against Staphylococcus aureus and the killing of S. aureus appeared time and dose dependent. Considering the quantity of recombinant product and the applicability of purification, the pET28-scygonadin expression system is a better choice to produce large quantities of recombinant scygonadin for commercial use in future. This is the first report on the heterologous expression of antimicrobial peptide scygonadin in E. coli.

[Evaluation of tumor angiogenesis using microbubbles conjugated with RGD peptides and contrast enhanced ultrasound].

OBJECTIVE: To assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis. METHODS: Lipid microbubbles (MB) were prepared, and the RGD peptides were covalently conjugated to the lipid shell of MB (MB(RGD)). Six nude mice with tumor created by dorsal inoculation of HepG2 tumor cells were used as the test group. Six nude mice without tumor were served as the control group. 10 minutes after bolus injection of MB and MB(RGD) randomly (30 min interval) via a tail vein catheter, CEU was performed on the tumors of the test group and the thigh skeletal muscles of control group. The video intensity (VI) of tumors and the skeletal muscles were measured. The tumors and the skeletal muscles were harvested for immunohistochemical examination. RESULTS: Only a slight contrast enhancement of the tumor was seen with MB, and the VI was 5.33 ± 1.71. While a remarkable enhancement of the tumor was observed after injection of MB(RGD). The VI was up to 17.03 ± 3.58, 3.18 folds higher as compared with that obtained by injection of MB (P < 0.05). As expected, there were no obvious contrast enhancement of the skeletal muscles with both MB(RGD) and MB. There was a high expression of αvß3-integrin in tumor neovascular endothelium, however, no apparent expression of αvß3-integrin was observed in the skeletal muscle vascular endothelium. CONCLUSION: CEU with MB(RGD) can be used to effectively evaluate the angiogenesis of tumors, and it may greatly contribute to the early judgement of the nature of tumor.

[Clinical Efficacy of ALL-2005 and ALL-2009 Regimen and Factors Influencing Prognosis of Newly Diagnosed ALL Patients Aged between 10-18 Years Old].

OBJECTIVE: To investigate the clinical efficacy of ALL-2005 and ALL-2009 regimen and factors influencing prognosis of newly diagnosed ALL patients aged between 10-18 years old to provide some reference for clinical diagnosis and treatment. METHODS: The clinical data including baseline clinical characteristics, induction chemotherapy effect, long-term clinical efficacy, recurrence rate and mortality of induction therapy of 119 newly diagnosed ALL patients aged between 10-18 years old from January 2008 to December 2015 were analyzed retrospectively, and the influencing factors of clinical prognosis were evaluated by univariate and multivariate analysis. RESULTS: The complete remission rate at the 5th week after induction therapy was not significantly different between ALL-2005 and ALL-2009 regimen groups (P＞0.05). The cumulative event-free survival rate and overall survival rate of 119 cases after 5-year follow-up were (63.41±3.65)% and (68.95±4.01)% respectively, and after 7-year follow-up were (61.86±3.72)% and (67.22±3.59)% respectively. The cumulative event-free survival rate and overall survival rate were not significantly different between ALL-2005 and ALL-2009 regimen groups (P＞0.05). The total recurrence rate, extramedullary recurrence rate, recurrence time and survival rate were not significantly different between ALL-2005 and ALL-2009 regimen groups (P＞0.05). The survival rate of extramedullary recurrence group was significantly higher than bone marrow recurrence group (P＜0.05). The survival rate in late term recurrence group was significantly higher than in early term recurrence group (P＜0.05). The mortality of ALL-2005 regimens was not significantly different from that of ALL-2009 regimen group (P＞0.05). Univariate analysis showed that age, sex, induction therapy, risk and fusion gene all were the factors influencing clinical prognosis (P＜0.05). Multivariate analysis by Cox regression model showed that male, non-remission after induction therapy and high risk were the independent risk factors for poor prognosis in patients (P＜0.05). The survival rate of patients with BCR-ABL+ treated with ALL-2009 regimen was significantly higher than that of patients treated with ALL-2005 regimen (P＜0.05). The event-free survival rate after 5-year follow-up of middle-risk patients treated with ALL-2005 and ALL-2009 regimens was significantly higher than that of high-risk patients (P＜0.05). The event-free survival rate after 5-year follow-up of patients with B-line ALL treated with ALL-2009 regimen was significantly higher than that of T-line ALL patients (P＜0.05). CONCLUSION: The survival rate of newly diagnosed ALL patients aged between 10-18 years old treated with ALL-2009 regimen was slightly higher than that of ALL-2005 regimen, it is more suitable for the ALL patients with BCR-ABL+, but can not reduce the recurrence rate. And the sex, the effect of induction therapy and risk closely relate with the clinical prognosis of above mentioned patients.

The association between fibroblast growth factor receptor 1 gene amplification and lung cancer: a meta-analysis.

INTRODUCTION: Identifying target oncogenic alterations in lung cancer represents a major development in disease management. We examined the association of fibroblast growth factor receptor 1 (FGFR1) gene amplification with pathological characteristics and geographic region. MATERIAL AND METHODS: We conducted a meta-analysis of studies published between January 2010 and October 2016. Relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated regarding the rate of FGFR1 amplification in different lung cancer types and geographic region. RESULTS: Twenty-three studies (5252 patients) were included. There was heterogeneity between studies. However, in subgroup analyses for squamous cell carcinoma (SCC), small cell lung cancer (SCLC), studies using the same definition of FGFR1 amplification, and those from Australia, no significant heterogeneity was detected. The prevalence of FGFR1 amplification in these studies ranged from 4.9% to 49.2% in non-small cell lung cancer (NSCLC), 5.1% to 41.5% in SCC, 0% to 14.7% in adenocarcinoma, and 0% to 7.8% in SCLC. The prevalence of FGFR1 amplification was significantly higher in SCC than in adenocarcinoma (RR = 5.2) and SCLC (RR = 4.2). The prevalence of FGFR1 amplification ranged from 5.6% to 22.2% in Europe, 4.1% to 18.2% in the United States, 7.8% to 49.2% in Asia, and 14.2% to 18.6% in Australia. The rate of FGFR1 amplification was higher in Asians than in non-Asians (RR = 1.9) in NSCLC. CONCLUSIONS: These results suggest that FGFR1 amplification occurs more frequently in SCC and in Asians. FGFR1 amplification may be a potential new therapeutic target for specific patients and lung cancer subtypes.

No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19.

BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes. AIM: To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19. METHODS: We conducted a multicenter, retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province, China. After excluding ineligible individuals, 142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis. We performed a strict propensity score matching (PSM) analysis where age, sex, comorbidities, number of oral hypoglycemic agents, heart rate, blood pressure, pulse oxygen saturation (SpO2) < 95%, CT diagnosed bilateral lung lesions, laboratory indicators, and proportion of insulin usage were matched. Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19. RESULTS: After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model, we found that there was no significant association between in-hospital DPP4i use (DPP4i group) and 28-d all-cause mortality (adjusted hazard ratio = 0.44, 95%CI: 0.09-2.11, P = 0.31). Likewise, the incidences and risks of secondary outcomes, including septic shock, acute respiratory distress syndrome, or acute organ (kidney, liver, and cardiac) injuries, were also comparable between the DPP4i and non-DPP4i groups. The performance of DPP4i agents in achieving glucose control (e.g., the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort. CONCLUSION: Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.

Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice.

With the increasing number of individuals with diabetes and obesity, nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent, affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden, and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD, including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice.

Current and Emerging Approaches for Nonalcoholic Steatohepatitis Treatment.

Nonalcoholic steatohepatitis (NASH) is the second leading cause of liver transplantation in the US with a high risk of liver-related morbidities and mortality. Given the global burden of NASH, development of appropriate therapeutic strategies is an important clinical need. Where applicable, lifestyle modification remains the primary recommendation for the treatment of NASH, even though such changes are difficult to sustain and even insufficient to cure NASH. Bariatric surgery resolves NASH in such patients where lifestyle modifications have failed, and is recommended for morbidly obese patients with NASH. Thus, pharmacotherapies are of high value for NASH treatment. Though no drug has been approved by the US Food and Drug Administration for treatment of NASH, substantial progress in pharmacological development has been made in the last few years. Agents such as vitamin E and pioglitazone are recommended in patients with NASH, and yet concerns about their side effects remain. Many agents targeting various vital molecules and pathways, including those impacting metabolic perturbations, inflammatory cascades, and oxidative stress, are in clinical trials for the treatment of NASH. Some agents have shown promising results in phase II or III clinical trials, but more studies are required to assess their long-term effects. Herein, we review the potential strategies and challenges in therapeutic approaches to treating NASH.

Nonalcoholic Fatty Liver Disease: An Update on the Diagnosis.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease and a major cause of related complications such as cirrhosis and hepatocellular carcinoma (HCC). NAFLD progresses through the stages of simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and HCC. However, NAFLD usually cannot be diagnosed in a timely manner, which is largely attributed to the asymptomatic features of NAFLD patients and the lack of an effective and accurate noninvasive screening approach. Although liver biopsy has been recognized as a gold standard for diagnosing NAFLD, this approach is not suitable for screening and monitoring NAFLD because of its high cost and invasiveness. Several noninvasive screening and diagnostic systemic assessments have been developed in recent years for NAFLD evaluation. Here we summarize the current status and methods for NAFLD diagnosis, including both noninvasive (imaging, biomarkers) and invasive (liver biopsy) assessments. We further discuss the advantages and disadvantages of these developed diagnostic approaches for NAFLD.

Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent: systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Relevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu. REVIEW METHODS: Randomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events. RESULTS: 17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results. CONCLUSIONS: In patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099519.

Analysis of the Clinicopathological Characteristics and Risk Factors in Patients with Lung Cancer and Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To investigate the clinicopathological characteristics and risk factors in patients with lung cancer and COPD. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 282 patients with lung cancer, including 174 and 108 patients with and without COPD, respectively. Information on age, sex, smoking status, and histologic type was obtained from medical records. RESULTS: Lung cancer patients with COPD and those with the chronic bronchitis (CB) phenotype had higher smoking indices compared to those without COPD (723.95 ± 631.48 and 920.95 ± 712.93 versus 418.40 ± 506.84; P = 0.010; P = 0.001, resp.), and current smokers accounted for significantly higher proportions of lung cancer patients with COPD and the CB phenotype versus without COPD (51.15% and 63.74% versus 35.19%; P = 0.009; P = 0.001, resp.). Adenocarcinoma was significantly more common in lung cancer patients without versus with COPD (48.15% versus 35.63%; P = 0.037), whereas small cell lung cancer was more common in patients with COPD (23.56% versus 13.89%). Among patients with COPD, male sex (odds ratio [OR], 19.946; P < 0.001), current smokers (OR: 6.588; P = 0.001), and age ≥ 75 years (OR: 2.670; P = 0.008) were identified as high-risk factors. CONCLUSION: The risk factors for COPD among lung cancer patients were age ≥ 75 years, current smokers with the CB phenotype, and male sex.