Investigation of the causal relationship between inflammatory bowel disease and type 2 diabetes mellitus: a Mendelian randomization study.

Background: Type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) have been associated, according to various epidemiological research. This study uses Mendelian randomization (MR) to investigate the causal link between T2DM and IBD. Methods: To investigate the causal relationship between IBD and T2DM risk using European population data from the genome-wide association study (GWAS) summary datasets, we constructed a two-sample MR study to evaluate the genetically predicted impacts of liability towards IBD outcomes on T2DM risk. As instrumental variables (IVs), we chose 26 single nucleotide polymorphisms (SNPs) associated with IBD exposure data. The European T2DM GWAS data was obtained from the IEU OpenGWAS Project database, which contains 298,957 cases as the outcome data. The causal relationship between T2DM and IBD using a reverse MR analysis was also performed. Results: The two-sample MR analysis, with the Bonferroni adjustment for multiple testing, revealed that T2DM risk in Europeans is unaffected by their IBD liability (odds ratio (OR): 0.950-1.066, 95% confidence interval (CI): 0.885-1.019, p = 0.152-0.926). The effects of liability to T2DM on IBD were not supported by the reverse MR analysis either (OR: 0.739-1.131, 95% confidence interval (CI): 0.651-1.100, p = 0.058-0.832). MR analysis of IBS on T2DM also have no significant causal relationship (OR: 0.003-1.007, 95% confidence interval (CI): 1.013-5.791, p = 0.069-0.790). FUMA precisely mapped 22 protein-coding genes utilizing significant SNPs of T2DM acquired from GWAS. Conclusion: The MR study showed that the existing evidence did not support the significant causal effect of IBD on T2DM, nor did it support the causal impact of T2DM on IBD.

Glycemic dispersion: a new index for screening high glycemic variability.

OBJECTIVE: For patients with diabetes, high-frequency and -amplitude glycemic variability may be more harmful than continuous hyperglycemia; however, there is still a lack of screening indicators that can quickly and easily assess the level of glycemic variability. The aim of this study was to investigate whether the glycemic dispersion index is effective for screening high glycemic variability. METHODS: A total of 170 diabetes patients hospitalized in the Sixth Affiliated Hospital of Kunming Medical University were included in this study. After admission, the fasting plasma glucose, 2-hour postprandial plasma glucose, and glycosylated hemoglobin A1c were measured. The peripheral capillary blood glucose was measured seven times in 24 h, before and after each of three meals and before bedtime. The standard deviation of the seven peripheral blood glucose values was calculated, and a standard deviation of > 2.0 was used as the threshold of high glycemic variability. The glycemic dispersion index was calculated and its diagnostic efficacy for high glycemic variability was determined by the Mann-Whitney U test, receiver operating characteristic (ROC) curve and, Pearson correlation analysis. RESULTS: The glycemic dispersion index of patients with high glycemic variability was significantly higher than that of those with low glycemic variability (p < 0.01). The best cutoff value of the glycemic dispersion index for screening high glycemic variability was 4.21. The area under the curve (AUC) was 0.901 (95% CI: 0.856-0.945) and had a sensitivity of 0.781 and specificity of 0.905. It was correlated with the standard deviation of blood glucose values (r = 0.813, p < 0.01). CONCLUSIONS: The glycemic dispersion index had good sensitivity and specificity for screening high glycemic variability. It was significantly associated with the standard deviation of blood glucose concentration and is simple and easy to calculate. It was an effective screening indicator of high glycemic variability.

Application of robot-assisted radical prostatectomy in men over 75 years: an analysis of comparative outcomes.

OBJECTIVE: This study aimed to summarize the current evidence regarding the feasibility of robot-assisted radical prostatectomy (RARP) in men aged over 75 years. METHOD: A comprehensive search of four electronic databases (China National Knowledge Infrastructure, PubMed, Web of Science, and Cochrane Library) was performed to identify eligible comparative studies as of April 2022. Parameters, including perioperative results and oncological and functional outcomes, were evaluated. RESULTS: Seven articles with 7575 patients undergoing RARP were included in this study. Patients with prostate cancer were grouped by age ≥ 75 years versus < 75 years. Our results demonstrated that compared with the older group, the younger group had better potency (p < .00001). However, there were no significant differences in operation time (p = .29), estimated blood loss (p = .13), length of hospital stay (p = .48), complications (p = .22), continence (p = .21), positive surgical margin (p = .28), and biochemical recurrence (p = .74) between the groups. CONCLUSION: Our study revealed that the perioperative, oncological, and functional outcomes in men aged over 75 years undergoing RARP were not significantly different from those of their younger counterparts. RARP is feasible in men aged over 75 years.

Comparative study of type 2 diabetes mellitus-associated gut microbiota between the Dai and Han populations.

BACKGROUND: The global prevalence of type 2 diabetes mellitus (T2DM) is increasing. T2DM is associated with alterations of the gut microbiota, which can be affected by age, illness, and genetics. Previous studies revealed that there are discriminating microbiota compositions between the Dai and the Han populations. However, the specific gut microbiota differences between the two populations have not been elucidated. AIM: To compare the gut microbiota differences in subjects with and without T2DM in the Dai and Han populations. METHODS: A total of 35 subjects of the Han population (including 15 healthy children, 8 adult healthy controls, and 12 adult T2DM patients) and 32 subjects of the Dai population (including 10 healthy children, 10 adult healthy controls, and 12 adult T2DM patients) were enrolled in this study. Fasting venous blood samples were collected from all the subjects for biochemical analysis. Fecal samples were collected from all the subjects for DNA extraction and 16S rRNA sequencing, which was followed by analyses of the gut microbiota composition. RESULTS: No significant difference in alpha diversity was observed between healthy children and adults. The diversity of gut microbiota was decreased in T2DM patients compared to the healthy adults in both the Dai and Han populations. There was a significant difference in gut microbiota between healthy children and healthy adults in the Han population with an increased abundance of Bacteroidetes and decreased Firmicutes in children. However, this difference was less in the Dai population. Significant increases in Bacteroidetes in the Han population and Proteobacteria in the Dai population and decreases in Firmicutes in both the Han and Dai population were observed in T2DM patients compared to healthy adults. Linear discriminant analysis Effect Size analysis also showed that the gut microbiota was different between the Han and Dai populations in heathy children, adults, and T2DM patients. Four bacteria were consistently increased and two consistently decreased in the Han population compared to the Dai population. CONCLUSION: Differences in gut microbiota were found between the Han and Dai populations. A significant increase in Bacteroidetes was related to the occurrence of T2DM in the Han population, while a significant increase in Proteobacteria was related to the occurrence of T2DM in the Dai population.

Serum albumin to globulin ratio prior to treatment as a potential non-invasive prognostic indicator for urological cancers.

Background: Numerous clinical studies have reported an association between the pretreatment albumin to globulin ratio (AGR) and survival outcomes of urological cancers. However, these conclusions remain controversial. Therefore, we performed a meta-analysis to explore the prognostic value of the AGR in urinary system tumors. Methods: We retrieved eligible studies published up to June 2022 through a comprehensive search of multiple databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and biochemical recurrence-free survival (BRFS) were used to evaluated the predictive effect of the AGR before treatment in urinary system tumors. Heterogeneity test, random-effects models, fixed-effects models and sensitivity tests were used for analyses. Results: A total of 21 studies with 18,269 patients were enrolled in our meta-analysis. We found that patients with urinary system cancer with low AGR prior to treatment had poor OS [HR = 1.93, 95% CI (1.56-2.39), p < 0.001], CSS [HR = 2.22, 95% CI (1.67-2.96), p < 0.001], RFS [HR = 1.69, 95% CI (1.29-2.22), p < 0.001], and PFS [HR = 1.29, 95% CI (0.54-3.07), p < 0.001]. For prostate cancer (PCa), a low pretreatment AGR was associated with poor BRFS [HR = 1.46, 95% CI (1.28-1.67), p < 0.001]. Also, a subgroup analysis, stratified by ethnicity, cancer type, cutoff value, sample size and publication year, was conducted. The results showed that worse OS and CSS were significantly associated with these factors. Conclusion: Our meta-analysis revealed that the AGR before treatment could be used as a non-invasive predictive biomarker to evaluate the prognosis of urological cancer patients in clinical practice.

Prognostic value of pretreatment serum albumin-globulin ratio in urothelial carcinoma: A systematic review and meta-analysis.

Objective: To evaluate whether pretreatment albumin-globulin ratio (AGR) can be used as a biomarker for predicting the prognosis of patients with urothelial carcinoma (UC). Methods: We systematically searched PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Google Scholar and Cochrane Library; the search time was up to May 2022. Stata 16.0 was used for data processing and statistical analysis. Results: We identified 12 studies with 5,727 patients from 317 unique citations during the meta-analysis. Our results suggested that a low AGR before treatment was significantly associated with poor overall survival (OS) [hazard ratio (HR) = 1.99, 95% confidence interval (CI) = 1.45-2.75, P < 0.001], cancer-specific survival (CSS) [HR=2.01, 95% CI = 1.50-2.69, P < 0.001] and recurrence-free survival (RFS) [HR=1.39, 95% CI = 1.12-1.72, P = 0.002]. Furthermore, we defined different subgroups according to ethnicity, cancer type, cut-off value, sample size and stage. Similar prognostic outcomes for OS and CSS were observed in most subgroups. However, for subgroup of stage, the low pretreatment AGR only predicted the poor survival of patients with non-metastatic UC. Conclusion: Our meta-analysis revealed that the AGR before treatment could be used as a predictive biomarker to indicate the prognosis of UC patients during clinical practice, especially in patients with non-metastatic UC.

Co-Occurrence of the bla KPC-2 and Mcr-3.3 Gene in Aeromonas caviae SCAc2001 Isolated from Patients with Diarrheal Disease.

PURPOSE: To characterize the genetic feature of a multi-drug-resistant Aeromonas caviae strain isolated from the diarrhea sample of a 45-year-old male patient with acute diarrhea. MATERIALS AND METHODS: Whole-genome of the A. caviae strain SCAc2001 was sequenced via the Illumina system, followed by a series of bioinformatic analyses to describe the genetic feature. RESULTS: The genome sequence of A. caviae SCAc2001 was assembled into 340 scaffolds (305 of them were > 1000 bp in length and 4,487,370 bp in total) with an average G+C content of 61.09%. Phylogenetic analysis showed that the A. caviae SCAc2001 strain was highly similar to the A. caviae strain R25-2 and T25-39. Resistome analysis identified that A. caviae SCAc2001 carried 13 antimicrobial resistance genes, including ß-lactams (bla KPC, bla CTX-M-14, bla TEM-1, bla OXA-10, bla OXA-427, bla VEB-3 and bla MOX-6), aminoglycosides (aadA1), fluoroquinolones (aac(6')-Ib-cr), phenicol resistance (catB3), sulfonamide (sul1), trimethoprim (dfrA5) and colistin resistance (mcr-3.3).And also, A. caviae ScAc2001 carried 54 putative virulence genes including the type IV pilus, fimbria, flagellarthe, and hemolysin A encoding genes, and 12 pathogen-host interactions (PHI) genes. There were also four genomic islands and eight prophages in the genome of A. caviae ScAc2001. In addition, A. caviae SCAc2001 also carried three secondary metabolism products coding clusters including nonribosomal peptide synthetases (nrps), hserlactone and bacteriocin. CONCLUSION: A. caviae ScAc2001 carries many resistance genes, a variety of virulence factors, PHI genes and four genomic islands and eight prophages, which poses a severe threat to infectious diseases control strategies, diagnosis methods and clinical treatment.

Whole-Genome Analysis of Two Copies of bla NDM-1 Gene Carrying Acinetobacter johnsonii Strain Acsw19 Isolated from Sichuan, China.

PURPOSE: To characterize the genetic feature of the carbapenems resistant Acinetobacter johnsonii strain Acsw19 isolated from municipal sludge. This strain was found to carry two copies of bla NDM-1, cmlB1-like gene, and bla OXA-211-like gene along with other 8 antimicrobial resistance genes, 3 plasmids, 15 genomic islands and 8 prophages. METHODS: A carbapenem-resistant Acinetobacter johnsonii strain Acsw19 isolated from municipal sludge was subjected to whole-genome sequencing (WGS) via the PacBio and Illumina MiSeq platforms. Thereafter, the characteristic was analyzed by a series of bioinformatics software. RESULTS: The results showed that the genome of Acsw19 was consisted of a 3,433,749 bp circular chromosome and 3 circular plasmids, pAcsw19-1 (11,161 bp), pAcsw19-2 (351,885 bp) and pAcsw19-3 (38,391bp), respectively. Resistome analysis showed that Acsw19 carried 12 antimicrobial resistance genes, including 6 [cmlB1-like, bla NDM-1, bla OXA-58, aph (3')-VIa, msr(E) and mph(E)] in the plasmid pAcsw19-2 and 6 (bla OXA-211-like, bla NDM-1, aph(3")-Ib, aph(6)-Id, sul2, and floR) in the chromosome genome. Specifically, the cmlB1-like gene shared 86.33%, 71.7% and 71.9% similarities with the cmlB1, cmlA4 and cmlA8 gene, and the bla OXA-211-like gene shared 94.4%, 95.39% and 96.36% similarities with bla OXA-211, bla OXA-643 and bla OXA-652, at the nucleotide level, respectively. Phylogenetic analysis showed that the bla OXA-211-like gene and cmlB1-like gene had the closest evolutionary relationship with bla OXA-643 and cmlB1, respectively. These results indicated that the bla OXA-211-like and cmlB1-like genes identified in the current study should be the novel variant resistance genes. CONCLUSION: Carrying of two copies of bla NDM-1, cmlB1-like, bla OXA-211-like and along with other 8 antimicrobial resistance genes, 3 plasmids, 15 genomic islands and 8 prophages Acinetobacter johnsonii strain might increase the possibility of spreading of resistance genes.

Study on the prediction of the contamination symptoms in the fermentation process of Chlortetracycline based on soft sensor modeling method.

BACKGROUND: How to accurately predict the occurrence of contamination in the fermentation process of Chlortetracycline? How to prompt field operators to take effective measures in time? This is a difficult problem that the fermentation process of Chlortetracycline has not been solved well. OBJECTIVE: The aim of this paper is to effectively predict whether the fermentation process of Chlortetracycline is contaminated or not. METHODS: A Gaussian process regression soft sensor modeling method with real time integration learning is studied in depth by combining two local learning strategies, namely just-in-time learning (JITL) method and integrated learning method, and a multi-model weighted Gaussian process regression (MWGPR) soft sensor modeling method based on real-time integration learning is proposed in the paper. This soft sensing method was used to study the relationship between the viscosity of fermentation broth and the contamination in fermentation process. A soft-sensing model based on the viscosity of fermentation broth for predicting the signs of contamination is established. RESULTS: The validity of this method is verified by field data. The experimental results demonstrate that the soft sensing model proposed in this paper can effectively determine whether the fermentation broth is infected by hybrid bacteria. CONCLUSIONS: The method proposed in this paper is innovative and practical so that field operators can issue early warning and take effective measures.

Co-location of the blaKPC-2, blaCTX-M-65, rmtB and virulence relevant factors in an IncFII plasmid from a hypermucoviscous Klebsiella pneumoniae isolate.

Hypervirulent variants of klebsiella pneumoniae (hvKP), which cause serious infections not only healthy individuals, but also the immunocompromised patients, have been increasingly reported recently. One conjugation of a hypermucoviscous strian SWU01 co-carried the resistance gene blaKPC-2 and virulence gene iroN by the PCR detection from three carbapenem-resistance hvKP. To know the genetic context of this plasmid. The whole genome of this strain was sequenced. We got a 162,552-bp plasmid (pSWU01) which co-carried the resistance gene blaKPC-2 and virulence gene iroN. It is composed of a typical IncFII-type backbone, five resistance genes including blaCTX-M-65, blaKPC-2, blaSHV-12, blaTEM-1 and rmtB, and several virulence relevant factors including iroN, traT and toxin-antitoxin systems. The plasmid pSWU01 co-carrying the multidrug resistance determinants and virulence relevant factors from the hypermucoviscous K. pneumoniae represents a novel therapeutic challenge.