Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis.

BACKGROUND: The incidence of chronic kidney disease among patients with diabetes mellitus (DM) remains a global concern. Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus. However, no previous meta-analysis has assessed the effects of body mass index (BMI) on adverse kidney events in patients with DM. AIM: To determine the impact of BMI on adverse kidney events in patients with DM. METHODS: A systematic literature search was performed on the PubMed, ISI Web of Science, Scopus, Ovid, Google Scholar, EMBASE, and BMJ databases. We included trials with the following characteristics: (1) Type of study: Prospective, retrospective, randomized, and non-randomized in design; (2) participants: Restricted to patients with DM aged ≥ 18 years; (3) intervention: No intervention; and (4) kidney adverse events: Onset of diabetic kidney disease [estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 and/or microalbuminuria value of ≥ 30 mg/g Cr], serum creatinine increase of more than double the baseline or end-stage renal disease (eGFR < 15 mL/min/1.73 m2 or dialysis), or death. RESULTS: Overall, 11 studies involving 801 patients with DM were included. High BMI (≥ 25 kg/m2) was significantly associated with higher blood pressure (BP) [systolic BP by 0.20, 95% confidence interval (CI): 0.15-0.25, P < 0.00001; diastolic BP by 0.21 mmHg, 95%CI: 0.04-0.37, P = 0.010], serum albumin, triglycerides [standard mean difference (SMD) = 0.35, 95%CI: 0.29-0.41, P < 0.00001], low-density lipoprotein (SMD = 0.12, 95%CI: 0.04-0.20, P = 0.030), and lower high-density lipoprotein (SMD = -0.36, 95%CI: -0.51 to -0.21, P < 0.00001) in patients with DM compared with those with low BMIs (< 25 kg/m2). Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI (RR: 1.22, 95%CI: 1.01-1.43, P = 0.036). CONCLUSION: The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

Combined use of the neutrophil-to-lymphocyte ratio and CRP to predict 7-day disease severity in 84 hospitalized patients with COVID-19 pneumonia: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide from Wuhan. An easy-to-use index capable of the early identification of inpatients who are at risk of becoming critically ill is urgently needed in clinical practice. Hence, the aim of this study was to explore an easy-to-use nomogram and a model to triage patients into risk categories to determine the likelihood of developing a critical illness. METHODS: A retrospective cohort study was conducted. We extracted data from 84 patients with laboratory-confirmed COVID-19 from one designated hospital. The primary endpoint was the development of severe/critical illness within 7 days after admission. Predictive factors of this endpoint were selected by LASSO Cox regression model. A nomogram was developed based on selected variables. The predictive performance of the derived nomogram was evaluated by calibration curves and decision curves. Additionally, the predictive performances of individual and combined variables under study were evaluated by receiver operating characteristic curves. The developed model was also tested in a separate validation set with 71 laboratory-confirmed COVID-19 patients. RESULTS: None of the 84 inpatients were lost to follow-up in this retrospective study. The primary endpoint occurred in 23 inpatients (27.4%). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were selected as the final prognostic factors. A nomogram was developed based on the NLR and CRP. The calibration curve and decision curve indicated that the constructed nomogram model was clinically useful. The AUCs for the NLR, CRP and Combined Index in both training set and validation sets were 0.685 (95% CI: 0.574-0.783), 0.764 (95% CI: 0.659-0.850), 0.804 (95% CI: 0.702-0.883), and 0.881 (95% CI: 0.782-0.946), respectively. CONCLUSIONS: Our results demonstrated that the nomogram and Combined Index calculated from the NLR and CRP are potential and reliable predictors of COVID-19 prognosis and can triage patients at the time of admission.

Multi-gate memristive synapses realized with the lateral heterostructure of 2D WSe2 and WO3.

The development of novel synaptic device architectures with a high order of synaptic plasticity can provide a breakthrough toward neuromorphic computing. Herein, through the thermal oxidation of two-dimensional (2D) WSe2, unique memristive synapses based on the lateral heterostructure of 2D WSe2 and WO3, with multi-gate modulation characteristics, are firstly demonstrated. An intermediate transition layer in the heterostructure is observed through transmission electron microscopy. Raman spectroscopy and detailed electrical measurements provide insights into the mechanism of memristive behavior, revealing that the protons injected into/removed from the intermediate transition layer account for the memristive behavior. This novel memristive synapse can be used to emulate two neuron-based synaptic functions, like post-synaptic current, short-term plasticity and long-term plasticity, with remarkable linearity, symmetry, and an ultralow energy consumption of ∼2.7 pJ per spike. More importantly, the synaptic plasticity between the drain and source electrodes can be effectively modulated by the gate voltage and visible light in a four-terminal configuration. Such multi-gate tuning of the synaptic plasticity cannot be accomplished by any previously reported multi-gate synaptic devices that only mimic two neuron-based synapses. This new synaptic architecture with electrical and optical modulation enables a realistic emulation of biological synapses whose synaptic plasticity can be additionally regulated by the surrounding astrocytes, greatly improving the recognition accuracy and processing capacity of artificial neuristors, and paving a new way for highly efficient neuromorphic computation devices.

Development and Preliminary Validation of a Depression Assessment Tool for Maintenance Hemodialysis Patients.

Patients undergoing maintenance hemodialysis (MHD) are subject to a higher-than-usual prevalence of depressive disorders. However, the lack of consensus regarding the best assessment method remains an important problem. Thus, there is a clear need for more effective screening tools and an easily administered, disease-specific self-report measure of depression in MHD patients. After we developed and administered an initial depression inventory for MHD patients (I-DI-MHD), we created the DI-MHD and administered the DI-MHD and the Beck Depression Inventory (BDI) to 354 patients from four hospitals. Reliability, construct validity and receiver operator characteristic curves were assessed. The 17-item DI-MHD instrument displayed good internal consistency (Cronbach's alpha =0.893), provided excellent convergent validity, and correlated with the BDI scale (kappa =0.785, P <0.001). A factor analysis pattern matrix analysis showed that a four-factor model provided the best account of the data. Finally, the DI-MHD cutoff yielded a sensitivity of 0.97 and a specificity of 0.86, which were slightly better than the corresponding values for the BDI. The DI-MHD scale shows reasonable validity and reliability for assessing depression in MHD patients.

BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.

Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.

Hierarchically clustering to 1,033 genes differentially expressed in mouse superior colliculus in the courses of optic nerve development and injury.

Tempo spatially specific expression of many development-related genes is the molecular basis for the formation of the central nervous system (CNS), especially those genes regulating the proliferation, differentiation, migration, axon growth, and orientation of nerve cells. The development-related genes are usually prominent during the embryonic and newborn stages, but rarely express during the adulthood. These genes are believed to be suitable target genes for promoting CNS regeneration, despite majority of which remains unknown. Hence, the aim of this study was to screen development-related genes which might contribute to CNS regeneration. In this study, 1,033 differentially-expressed genes of superior colliculus in the courses of mouse optic nerve development and injury, as previously identified by cDNA microarrays, were hierarchically clustered to display expression pattern of each gene and reveal the relationships among these genes, and infer the functions of some unknown genes based on function-identified genes with the similar expression patterns. Consequently, the expression patterns of 1,033 candidate genes were revealed at eight time points during optic nerve development or injury. According to the similarity among gene expression patterns, 1,033 genes were divided into seven groups. The potential function of genes in each group was inferred on the basis of the dynamic trend for mean gene expression values. Moreover, the expression patterns of six function-unidentified genes were extremely similar to that of the ptn gene which could promote and guide axonal extension. Therefore, these six genes are temporally regarded as candidate genes related to axon growth and guidance. The results may help to better understand the roles of function-identified genes in the stages of CNS development and injury, and offer useful clues to evaluate the functions of hundreds of unidentified genes.

Relation between proteinuria and acute kidney injury in patients with severe burns.

INTRODUCTION: Proteinuria in burn patients is common, and may be associated with acute kidney injury (AKI) and adverse outcomes. We evaluated the incidences, outcomes, characteristics and determinants of proteinuria and its influence on AKI and outcomes in burn patients. METHODS: This retrospective study was carried out in a hospital's burn department. The study population consisted of patients with burn injuries admitted during a five-year period. Positive urine dipstick readings were defined as mild (± or 1+) or heavy (≥ 2+) proteinuria, and AKI was diagnosed and staged according to the Risk, Injury, Failure, Loss, End Stage (RIFLE) classification system. Patient characteristics, management and outcomes were evaluated for associations with proteinuria using nonparametric tests, chi-square (χ(2)) tests and binary logistic regression. RESULTS: Of the patients admitted to the burn unit during the study period (n = 2,497), 865 (34.64%) were classified as having proteinuria. In the patients whose total burn surface areas (TBSA) were > 30% (n = 396), 271 patients (68.43%) had proteinuria and 152 of these patients (56.09%) met AKI criteria. No patients without proteinuria developed AKI. Intensive care unit (ICU) mortality rates were 0.8%, 16.67% and 30.77% (P < 0.001) in the groups with no, mild and heavy proteinuria, respectively. Logistic regression analysis identified proteinuria (OR 4.48; 95% CI, 2.824 to 7.108; P < 0.001) and sequential organ failure assessment (OR 1.383; 95% CI, 1.267 to 1.509; P < 0.001) as risk factors for AKI. CONCLUSIONS: We observed a high prevalence of proteinuria in patients with severe burns (> 30% TBSA). Severely burned patients with proteinuria had a high risk of developing AKI and a poor prognosis for survival. This suggests that proteinuria should be used for identifying burn patients at risk of developing AKI.

Application of Crossover Analysis-logistic Regression in the Assessment of Gene- environmental Interactions for Colorectal Cancer.

BACKGROUND: Analysis of gene-gene and gene-environment interactions for complex multifactorial human disease faces challenges regarding statistical methodology. One major difficulty is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes or environmental exposures. Based on our previous case-control study in Chongqing of China, we have found increased risk of colorectal cancer exists in individuals carrying a novel homozygous TT at locus rs1329149 and known homozygous AA at locus rs671. METHODS: In this study, we proposed statistical method- crossover analysis in combination with logistic regression model, to further analyze our data and focus on assessing gene-environmental interactions for colorectal cancer. RESULTS: The results of the crossover analysis showed that there are possible multiplicative interactions between loci rs671 and rs1329149 with alcohol consumption. Multi- factorial logistic regression analysis also validated that loci rs671 and rs1329149 both exhibited a multiplicative interaction with alcohol consumption. Moreover, we also found additive interactions between any pair of two factors (among the four risk factors: gene loci rs671, rs1329149, age and alcohol consumption) through the crossover analysis, which was not evident on logistic regression. CONCLUSIONS: In conclusion, the method based on crossover analysis-logistic regression is successful in assessing additive and multiplicative gene-environment interactions, and in revealing synergistic effects of gene loci rs671 and rs1329149 with alcohol consumption in the pathogenesis and development of colorectal cancer.

An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris.

Psoriasis vulgaris (PV) is a common autoimmune disease that involves the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key transcription factor in the development and function of CD4+CD25+ regulatory T cells. Previous studies have demonstrated a genetic association between the FOXP3 gene and some autoimmune diseases. To elucidate the association between the FOXP3 gene and the risk of PV, 408 patients diagnosed with PV and 363 age and sex-matched healthy controls from a cohort of the Chinese majority Han population were recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547, rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the polymerase chain reaction and ligase detection reaction. The major allele of three single nucleotide polymorphisms (SNPs - rs2232365 A, rs3761547 A and rs3761549 C) were associated with an increased risk of PV in a clinical subgroup of female patients, who were less than 40 yrs of age, had a family history of the disease and did not have disease complications (p < 0.05 for all parameters). The haplotype was structured between rs3761547 and rs3761549. An increased risk of PV was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188; 95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288; 95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic effect was found among the three SNPs. Subjects with the rs2232365AA- rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR = 2.90; 95% CI = 1.05-7.97). No correlation was found between rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms appear to contribute to the risk of psoriasis among the Chinese majority Han population. These findings may aid in our understanding of the pathogenesis of psoriasis.

[Analysis and quantitative assessment on the risks of diabetes at the community level in Chongqing].

OBJECTIVE: To investigate the correlation risk factors of diabetes over 16-year-olds at the community level in Chongqing and to set a quantitative criteria for determining risk for diabetes and to identify persons having potential risk. METHODS: 1981 cases with 1:2 matched controls were chosen from five communities in Chongqing including Shapingba, Xiaolongkan, Tianxingqiao, Yubei Road, Ciqikou, which were interviewed with a uniformed questionnaire. The risk factors of diabetes mellitus were analyzed with logistic regression, and to calculate the odds ratios of risk factors for diabetes. Different levels of risk exposure factors were converted into a risk scores, using statistical models. RESULTS: An individual health risk appraisal model of diabetes was established, applicable to individuals of different sex, age, health behavior,disease,and family history, for men, 13 risk factors including hyperlipidemia (14.995), coronary heart disease (6.689), family history of hypertension (4.005), smoking (3.111 ) etc. while for women, hyperlipidemia (12.426), family history of hypertension (3.986), stroke (2.714), liking sweets (1.244), about 15 risk factors, were entering the main effect model. The related risk scores were added to obtain a combined risk score to predict the individual's risk of diabetes in the future. CONCLUSION: The incidence of diabetes could be effectively reduced by changing the unhealthy lifestyle and curing the patient with the disease. Evidence was provided to persuade people change their unhealthy lifestyles and behaviors through health education. The results could also be used in community to improve their health services.

[Gene expression profiles in early stage of BALB/c 3T3 cells' transformation promoted with 12-O-tetradecanoylphorbol-13-acetate].

OBJECTIVE: To elucidate the potential molecular mechanism responsible for the early time of tumor promotion, gene expression profile was studied in the transformed BALB/c 3T3 cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS: The two-stage cell transformation model was established by using the initiator of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoter of TPA. Cell proliferation was measured by trypan blue staining and cell cycle analysis was carried out by flow cytometry assay. A cDNA microarray representing 1 152 genes was used to investigate the gene expression profiles of BALB/c 3T3 cells exposed to TPA at 4 h and 24 h respectively. RESULTS: TPA could effectively inhibit cell proliferation and induce the G1 and S cell cycle arrested in the early time. Moreover 19 genes were found differentially expressed at least twofold in the TPA treated cells as compared with the control cells, 9 of them were upregulated and 10 downregulated. Most of the differentially expressed genes were involved in cell proliferation, differentiation or apoptosis, and related to ras or p53 signal transduction pathway. CONCLUSION: TPA could influence the transcriptional expression of some genes related to cell cycle modulation and ultimately result in the cell growth arrest.