Gut microbiota influence acute pancreatitis through inflammatory proteins: a Mendelian randomization analysis.

Background/Aim: We employed Mendelian randomization (MR) analysis to investigate the causal relationship between the gut microbiota, acute pancreatitis, and potential inflammatory proteins. Methods: The data for gut microbiota, acute pancreatitis, and inflammatory proteins are sourced from public databases. We conducted a bidirectional MR analysis to explore the causal relationship between gut microbiota and acute pancreatitis, and employed a two-step MR analysis to identify potential mediating inflammatory proteins. IVW is the primary analysis method, heterogeneity, pleiotropy, and sensitivity analyses were also conducted simultaneously. Results: We identified five bacterial genera associated with the risk of acute pancreatitis, namely genus.Coprococcus3, genus.Eubacterium fissicatena group, genus.Erysipelotrichaceae UCG-003, genus.Fusicatenibacter, and genus.Ruminiclostridium6. Additionally, we have discovered three inflammatory proteins that are also associated with the occurrence of acute pancreatitis, namely interleukin-15 receptor subunit alpha (IL-15RA), monocyte chemoattractant protein-4 (CCL13), and tumor necrosis factor receptor superfamily member 9 (TNFRSF9). Following a two-step MR analysis, we ultimately identified IL-15RA as a potential intermediate factor, with a mediated effect of 0.018 (95% CI: 0.005 - 0.032). Conclusion: Our results support the idea that genus.Coprococcus3 promotes the occurrence of acute pancreatitis through IL-15RA. Furthermore, there is a potential causal relationship between the gut microbiota, inflammatory proteins, and acute pancreatitis. These findings provide new insights for subsequent acute pancreatitis prevention.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

The efficacy of Da Chaihu decoction combined with metformin tablets for type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone. METHODS: This systematic review and meta-analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3. RESULTS: Six randomized controlled trials comprising 516 participants were included. The meta-analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (-0.66 mmol/L; 95 % CI (confidence intervals) [- 1.28, - 0.04]), plasma glucose 2 h after meal (2-h PG) (-1.18 mmol/L; 95 % CI [-1.94, -0.42]) in six RCTs, body mass index (BMI) (-3.07 mmol/L; 95 % CI [-6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (-0.36 mmol/L; 95 % CI [-1.04, 0.31]) in three RCTs, and triglycerides (TG) (-0.76 mmol/L; 95 % CI [-1.37, -0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (-0.97 mmol/L; 95 % CI [-1.18, -0.76]). CONCLUSIONS: Very low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.

Mediating effects of insulin resistance on the development of hypertension associated with elevated serum uric acid: a prospective cohort study.

Many studies have demonstrated that elevated serum uric acid independently increases the risk of developing hypertension. However, the role of insulin resistance in the relationship between serum uric acid and hypertension is still unelucidated. Based on a prospective cohort study, we aimed to examine the longitudinal link between serum uric acid and hypertension and whether this relationship was mediated by insulin resistance. Overall, 21,999 participants without hypertension or gout at baseline with a mean age of 46 ± 13 years in the Jinchang Cohort were included in our study. Adjusted Cox-regression analyses and mediation analyses were performed to assess the risk of hypertension by serum uric acid quartile distribution and whether insulin resistance mediated the association between serum uric acid and hypertension. During the first follow-up period, 3080 participants developed hypertension. After controlling for covariates, compared with the lowest quartile of serum uric acid, the risk of hypertension in the highest quartile was 1.21 (1.06, 1.38) in the overall population. The risks for males and females were 1.14 (1.00-1.29) and 1.30 (1.08-1.56), respectively. The correlation between serum uric acid and hypertension was especially observed in younger people (<30 years). The mediating effects of insulin resistance were 0.058 (0.051, 0.065), 0.030 (0.025, 0.036) and 0.056 (0.047, 0.065), and the proportions mediated were 39.73, 36.59 and 38.62% in the overall, male and female populations, respectively. Elevated serum uric acid levels are associated with an increased risk of incident hypertension, and insulin resistance may play a mediating role in the relationship between serum uric acid and hypertension.

PandaX-4T cryogenic distillation system for removing krypton from xenon.

An efficient cryogenic distillation system was designed and constructed for the PandaX-4T dark matter detector based on the McCabe-Thiele method and the conservation of mass and energy. This distillation system is designed to reduce the concentration of krypton in commercial xenon from 5 × 10-7 to ∼10-14 mol/mol with 99% xenon collection efficiency at a maximum flow rate of 10 kg/h. The offline distillation operation has been completed and 5.75 tons of ultra-high purity xenon was produced, which is used as the detection medium in the PandaX-4T detector. The krypton concentration of the product xenon is measured with an upper limit of 8.0 ppt. The construction, operation, and stable purification performance of the cryogenic distillation system are studied with the experimental data, which is important for theoretical research and distillation operation optimization.

Sex-specific associations of blood and urinary manganese levels with glucose levels, insulin resistance and kidney function in US adults: National health and nutrition examination survey 2011-2016.

Exposures to heavy metals play a role in the etiopathogenesis of diabetes. Epidemiological studies investigating a potential sex-specific linkage between manganese (Mn) exposures and glucose homeostasis are rare. We comprehensively estimated the associations of blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) among 1417 adults in the US National Health and Nutrition Examination Survey (NHANES) 2011-2016. We further examined the potential heterogeneities by sex and joint-effects of multiple metal exposures by the Bayesian kernel machine regression (BKMR). Among women, we found positive linear relationships between urinary Mn with FPG (Poverall = 0.003, Pnonlinear = 0.817) and HbA1c (Poverall = 0.023, Pnonlinear = 0.854). Among men, J-shaped relationships were observed between blood Mn with HOMA-IR (Pnonlinear = 0.042) and insulin (Pnonlinear = 0.014). For eGFR, positive linear relationships were obserned among women for blood Mn (Pnonlinear = 0.549) and among both men and women for urinary Mn levels. The joint-effects of urinary Mn with molybdenum (Mo) on FPG and HbA1c, urinary Mn with cadmium (Cd) and cesium (Cs) on eGFR, and blood Mn with Cd and lead (Pb) on eGFR were detected. In summary, blood and urinary Mn levels were independently associated with glucose levels, insulin resistance and kidney function with potential sex-dependent heterogeneities. These findings emphasize the probable role of Mn in the regulation of glucose metabolism and kidney function, and confirm the need for more studies on sex-specific risk of diabetes.

Assessing different anthropometric indices and their optimal cutoffs for prediction of type 2 diabetes and impaired fasting glucose in Asians: The Jinchang Cohort Study.

BACKGROUND: To study the association between anthropometric measurements and the risk of diabetes and impaired fasting glucose (IFG) and compare body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) to determine the best indicator and its optimal cutoffs for predicting type 2 diabetes and IFG. METHODS: A Chinese prospective (2011-2019) cohort named the Jingchang cohort that included 48 001 participants was studied. Using Cox proportional hazard models, hazard ratios (HRs) for incident type 2 diabetes or IFG per 1 SD change in BMI, WC, and WHtR were calculated. Area under the curve (AUC) was compared to identify the best anthropometric variable and its optimal cutoff for predicting diabetes. RESULTS: The association of BMI, WC, and WHtR with type 2 diabetes or IFG risk was positive in the univariate and multivariable-adjusted Cox proportional hazard models. Of all three indexes, the AUC of BMI was largest and that of WC was smallest. The derived cutoff values for BMI, WC, and WHtR were 24.6 kg/m2 , 89.5 cm, and 0.52 in men and 23.4 kg/m2 , 76.5 cm, and 0.47 in women for predicting diabetes, respectively. The derived cutoff values for BMI, WC, and WHtR were 23.4 kg/m2 , 87.5 cm, and 0.50 in men and 22.5 kg/m2 , 76.5 cm, and 0.47 in women for predicting IFG, respectively. [Correction added on 14 April 2020, after first online publication: '0' has been deleted from 'WC,0' in the first sentence.]. CONCLUSIONS: Our derived cutoff points were lower than the values specified in the most current Asian diabetes guidelines. We recommend a cutoff point for BMI in Asians of 23 kg/m2 and for WC a cutoff point of 89 cm in men and 77 cm in women to define high-risk groups for type 2 diabetes; screening should be considered for these populations.

Risk factors for the development of early-onset delirium and the subsequent clinical outcome in mechanically ventilated patients.

OBJECTIVES: The aim of the study was to investigate the risk factors of developing early-onset delirium in mechanically ventilated patients and determine the subsequent clinical outcomes. METHODS: Confusion assessment method for the intensive care unit (ICU) was used to assess the enrolled mechanically ventilated patients for delirium. The risk factors of developing delirium and clinical outcomes were determined in these subjects. RESULTS: Delirium was present in 31 (21.7%) of 143 patients in the first 5 days. In multivariable analysis, hypoalbuminemia (odds ratio, 5.94; 95% confidence interval, 1.23-28.77) and sepsis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9) increased the risk of developing delirium in mechanically ventilated patients. The patients with delirium had a higher in-hospital mortality (67.7% vs 33.9%, respectively; P = .001) and longer duration of mechanical ventilation (19.5 +/- 15.8 vs 9.3 +/- 8.8 days, respectively; P = .003) than patients without delirium. The incidence of nosocomial pneumonia was increased in delirious patients (64.5% vs 38.4%, P = .01) compared with nondelirious patients, whereas the lengths of ICU or hospital stay were similar between both groups. CONCLUSIONS: Mechanically ventilated patients with sepsis or hypoalbuminemia were more vulnerable to develop delirium in their early stay in the ICU. Early-onset delirium is associated with prolonged duration of mechanical ventilation and higher incidence of nosocomial pneumonia, leading to a higher mortality.

The impact of delirium on the survival of mechanically ventilated patients.

OBJECTIVES: To revalidate a means of assessing delirium in intensive care unit patients and to investigate the independent effect of delirium on the mortality of mechanically ventilated patients. DESIGN: A prospective cohort study. SETTING: A 37-bed medical intensive care unit of a tertiary care hospital. PATIENTS: Subjects were 102 of 131 consecutive mechanically ventilated patients. MEASUREMENTS: All the enrolled patients were assessed for delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Mortality rate were compared between patients with or without delirium, and the predictors of death were investigated. RESULTS: The two CAM-ICU assessors' sensitivities in diagnosing delirium compared with reference standard were 91% and 95%, whereas their specificities were both 98%. They also demonstrated high interrater reliability with kappa statistics of 0.91. Delirium was present in 22 of 102 (22%) patients in the first 5 days. The delirious patients had higher intensive care unit mortality rate than nondelirious patients (63.6% vs. 32.5%, respectively), with a hazard ratio of 2.57 (95% confidence interval, 1.56-8.15). In multivariate analysis, delirium (odds ratio, 13.0; 95% confidence interval, 2.69-62.91), shock (odds ratio, 12.91; 95% confidence interval, 2.93-56.92), and illness severity (odds ratio, 9.61; 95% confidence interval, 2.24-41.18) were independent predictors of mortality. CONCLUSIONS: This study confirms previous work showing that delirium is an independent predictor for increased mortality among mechanically ventilated patients.