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Hypertriglyceridemia is a common cause of acute pancreatitis. Pregnant women are at risk of developing hypertriglyceridemia-induced acute pancreatitis (HTG-AP); however, whether pregnancy increases the risk of infected pancreatic necrosis (IPN) is unknown. We aimed to assess the association between pregnancy and IPN. This 10-year retrospective cohort study was conducted at Jinling Hospital. Adult female patients of childbearing age with HTG-AP between January 2013 and September 2022 were screened. Logistic regression analyses were performed to assess the risk factors for IPN. Patients admitted within 7 days were assigned to the training and validation sets to develop a dynamic nomogram for IPN prediction. 489 patients were included, and 144 developed IPN. Logistic regression analyses revealed pregnancy (OR: 2.578 95% CI: 1.474–4.510) as an independent risk factor for IPN. Gestation weeks, ARDS, albumin level, and serum creatinine level were selected as the predictors of the dynamic nomogram for IPN prediction, with good discrimination in the training set (AUC 0.867 95% CI: 0.794–0.940) and validation set (AUC 0.957 95% CI: 0.885–1.000). Pregnancy increases the risk of IPN in adult patients of childbearing age with HTG-AP, and the dynamic nomogram may help risk stratification for IPN. [ABSTRACT FROM AUTHOR]

To examine the associations of parental obesity prior to pregnancy with offspring overweight before two years of age among children of Chinese women with gestational diabetes mellitus (GDM). Offspring of women with GDM (n = 774) who were diagnosed in 2010–2012 were followed up to two years of age in Tianjin, China. Multinomial logistic regression was used to obtain odds ratios (ORs) and 95% confidence interval (CI) of maternal and paternal prepregnancy obesity with offspring overweight at < 1, 1–1.5, and 1.5–2 years of age. Among 774 offspring of women with GDM, 457 (59.0%) of the offspring developed overweight before two years of age. Maternal prepregnancy obesity was associated with increased risk of offspring overweight at 1–1.5 years of age and 1.5–2 years of age (ORs: 1.98, 95%CI: 1.09–3.59 & 2.14, 1.10–4.15, respectively). Paternal prepregnancy obesity was only associated with elevated risk of offspring overweight at 1.5–2 years of age (1.82, 1.08–3.06). Furthermore, copresence of both maternal and paternal obesity prior to pregnancy had an additive effect on the risk of offspring overweight at 1.5–2 years of age (3.73, 1.50–9.27). Parental prepregnancy obesity predicted offspring overweight before two years of age among children of Chinese women with GDM. • Among Chinese women with gestational diabetes mellitus, we found: • Maternal prepregnancy obesity predicted offspring overweight before 2 years of age. • Paternal prepregnancy obesity predicted offspring overweight before 2 years of age. • Maternal and paternal obesity had an additive effect on the offspring overweight. • Risk of overweight increased with age in the offspring of parents with obesity. [ABSTRACT FROM AUTHOR]

Timely and accurate microbial diagnosis is important in managing patients with infected pancreatic necrosis (IPN). To evaluate the diagnostic performance of Metagenomic next-generation sequencing (mNGS) in patients with suspected IPN. The clinical data of 40 patients with suspected IPN who underwent CT-guided pancreatic fluid aspiration were retrospectively analyzed. Microbial culture and mNGS were simultaneously applied to identify the potential pathogens. The diagnostic performance of the mNGS was assessed by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The mNGS report can be obtained significantly earlier than culture methods (42 (36–62 h) vs. 60 (42–124 h), P = 0.032). Across all the study samples, seven species of bacteria and two species of fungi were reported accordingly to the culture results, while 22 species of bacteria and two species of fungi were detected by mNGS. The sensitivity, specificity, NPV, and PPV of mNGS were 88.0%, 100%, 83.33%, and 100%, respectively. The diagnostic accuracy of mNGS in patients with suspected IPN is satisfactory. Moreover, mNGS may broaden the range of identifiable infectious pathogens and provide a more timely diagnosis. [ABSTRACT FROM AUTHOR]

• HTG-AP patients had a higher rate of GPIHBP1 autoantibody than reported HTG patients. • The GPIHBP1 autoantibody-positive group had a high recurrence rate of HTG-AP. • The GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence. GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP. [ABSTRACT FROM AUTHOR]

The optimal protein intake approach during the early phase of critical illness remains controversial. This study aimed to evaluate the association between different trajectories of protein intake and 28-day mortality in a cohort of critically ill patients. The NEED trial is a multicenter, cluster-randomized controlled trial assessing the impact of an actively implemented evidence-based nutrition guideline on mortality in critically ill patients. This secondary analysis included the patients who stayed in ICU for at least seven days. Group-based trajectory modeling was applied to identify subgroups with similar protein intake trajectories in this cohort. Cox proportional hazards models were used to analyze the impact of different trajectories on 28-day mortality. Overall, 2191 patients were included for analysis. A distinct triple-group trajectory of protein intake was identified, with 919 patients categorized into the low-level protein intake group, 1146 the medium-level group, and 126 the high-level group. The mean daily protein intake from the low-to high-level protein intake group during the first week of enrollment were 0.38 ± 0.14, 0.8 ± 0.18, and 1.68 ± 0.39 g/kg/d, respectively. Compared with the medium-level protein intake group, the low-level or high-level protein intake group was associated with significantly increased 28-day mortality (hazard ratio [HR] = 1.348, 95% confidence interval [CI]: 1.067–1.704; HR = 2.291, 95% CI: 1.533–3.423, respectively). After controlling for potential confounders, the adjusted HRs were 1.365 (95% CI: 1.032–1.807) for the low-level group and 1.921 (95% CI: 1.274–2.896) for the high-level group. However, when taking energy intake into account, low-level protein intake was no longer related to mortality. In contrast, the detrimental effects of high-level protein intake remain tenable (Adjusted HR = 2.324, 95% CI: 1.524–3.543, P < 0.001). Low-level or high-level protein intake in the early phase of critical illness was associated with increased 28-day mortality than medium-level protein intake. However, when adjusted for energy intake, low-level protein intake in the early phase was no longer associated with increased 28-day mortality. [ABSTRACT FROM AUTHOR]

Background Interactions between genetic and nutritional factors can contribute to the risk of gestational diabetes mellitus (GDM). Objectives We aimed to explore the associations of cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) single-nucleotide polymorphism (SNP) rs7747752 and serum concentrations of SFAs with the risk of GDM in Chinese women. Methods We conducted a 1:1 case–control study in a prospective cohort of pregnant women in Tianjin, China. Serum SFA data were collected from a total of 243 women with GDM and their controls matched by maternal age (±1 y). Among them, 207 case–control pairs had high-quality sequencing data. P/L and S/P ratios were defined as palmitic acid (16:0)/lauric acid (12:0) and stearic acid (18:0)/palmitic acid, respectively. Conditional logistic regression analysis was performed to estimate associations of CDKAL1 SNP rs7747752 and serum concentrations of SFAs with the risk of GDM. An additive interaction between rs7747752 and palmitic acid was analyzed to test the contribution of their interaction to the risk of GDM. Results Among the 5 tested SFAs, palmitic acid was positively whereas lauric acid was negatively associated with the risk of GDM. A P/L ratio ≥12.2 and an S/P ratio ≤0.71 were independently and synergistically associated with an increased risk of GDM. The CDKAL1 rs7747752 G > C variant was significantly associated with an increased risk of GDM (P  < 0.05). Furthermore, the presence of the rs7747752 G > C variant increased the OR (95% CI) of high palmitic acid concentration from 1.55 (0.61, 3.97) to 4.34 (2.04, 9.23), with a significant additive interaction. Conclusions The interaction between high serum palmitic acid concentration and the CDKAL1 rs7747752 G > C variant played a critical role in GDM. Given that a hypocaloric low-carbohydrate diet can lower palmitic acid concentrations, it is worthwhile to test whether such a diet is effective in reducing the risk of GDM, especially among women who have both risk factors. [ABSTRACT FROM AUTHOR]

Women with prior gestational diabetes mellitus (GDM) or high genetic susceptibility are prone to development of type 2 diabetes. We examined whether a lifestyle intervention modified the genetic effect on changes in glycemic markers among women with prior GDM. This study included 560 women with prior GDM from a randomized controlled trial, the Tianjin Gestational Diabetes Mellitus Prevention Program, who were assigned into an intervention arm (improved physical activity and healthy dietary intakes) or a control arm. We assessed associations of GDM related genetic variants in/near the CDKAL1 (rs7754840) and MTNR1B (rs10830962) genes with changes in fasting levels of glucose and insulin, β-cell function (HOMA-B) and insulin resistance (HOMA-IR) at 1 year and 2 years after the baseline. We found significant interactions between CDKAL1 variant rs7754840 and lifestyle intervention on changes in fasting insulin and HOMA-IR at 1 year (P for interactions = 0.008 and 0.006, respectively). The GDM-increasing C allele was associated with a 0.07-unit greater increase in fasting insulin (P = 0.048) and HOMA-IR (P = 0.045) in the control group, while opposite-directional associations were observed in the intervention group; women with the C allele seemed to decrease more in these glycemic markers than the non-C-carriers (both P ≤ 0.06). The interactions between the CDKAL1 genetic variant and lifestyle intervention on changes in fasting insulin (P = 0.035) and HOMA-IR (P = 0.024) remained significant over the 2-year period, even though the effects of lifestyle intervention were attenuated at 2-year. The MTNR1B variant rs10830962 did not show interaction with lifestyle intervention on changes in the glycemic markers. Healthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance. ClinicalTrials.gov NCT01554358. https://clinicaltrials.gov/ct2/show/NCT01554358. [ABSTRACT FROM AUTHOR]

Background Maternal metabolic abnormalities have been related to offspring obesity especially during childhood. Objectives We analyzed whether the gestational diabetes mellitus (GDM)-associated melatonin receptor 1B (MTNR1B) genotype of mothers modified the relation between maternal gestational weight gain and childhood obesity. Methods A total of 1114 Chinese mother-child pairs (mothers with or without prior GDM) were included. Mothers' MTNR1B rs10830962 genotype and gestational weight gain were assessed. Indicators of childhood obesity included BMI-for-age z -score, weight-for-age z -score, waist circumference, and body fat. Childhood overweight and obesity were also analyzed. Results We found that the maternal MTNR1B genotype significantly interacted with gestational weight gain on indicators of offspring's obesity (all P for interaction < 0.05). After multivariable adjustment, BMI-for-age z -scores associated with 1-kg gestational weight gain were 0.009 (SE 0.018), 0.026 (SE 0.010), and 0.061 (SE 0.010) in children with the maternal MTNR1B genotype CC, CG, and GG, respectively (P -interaction = 0.012). Similar interactions were observed for weight-for-age z -score, waist circumference, and body fat (P -interaction = 0.001, 0.003, and 0.012, respectively). The associations remained consistently significant in women with and without GDM. We also found significant interactions between the maternal MTNR1B genotype and gestational weight gain on the offspring's childhood overweight and obesity (P -interaction = 0.005 and 0.026, respectively). Conclusions The maternal MTNR1B genotype might interact with gestational weight gain on offspring's obesity risk during childhood. [ABSTRACT FROM AUTHOR]

Background A history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM. Objective The objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM. Methods We genotyped MC4R rs6567160 and measured glucose and insulin in fasting plasma samples at baseline and during the first 2 follow-up visits in 1128 women with prior GDM. They were randomly assigned to either a 4-y lifestyle intervention involving both diet and physical activity or a control group from a randomized clinical trial, the Tianjin Gestational Diabetes Mellitus Prevention Program. We analyzed the interaction between the MC4R genotype and lifestyle intervention on changes in insulin resistance. Results From baseline to 1.28 y, the MC4R genotype was related to changes in fasting insulin, HOMA-IR, and homeostasis model assessment of β cell function (HOMA-B) in the intervention group. Each risk allele (C) of rs6567160 was associated with a 0.08-unit greater decrease in log(insulin), log(HOMA-IR), and log(HOMA-B) (P  = 0.02, 0.04, and 0.04, respectively), whereas in the control group, each C allele tended to be associated with a greater increase in HOMA-IR (P  = 0.09). We found significant interactions between the MC4R genotype and lifestyle intervention on 1.28-y changes in fasting insulin and HOMA-IR (P  = 0.006 and 0.008, respectively), and such interaction remained significant when we analyzed the trajectory of changes in insulin and HOMA-IR from baseline to 2.55 y (both P  = 0.03). Conclusions The exploratory results from the first 2 follow-up visits indicate that women with prior GDM carrying a diabetes-increasing MC4R genotype (CC or TC) may obtain better improvement than the TT genotype in insulin resistance through lifestyle intervention. This trial was registered at clinicaltrials.gov as NCT01554358. [ABSTRACT FROM AUTHOR]

The flourishing development of the asymmetric supercapacitor (ASC) device has improved the energy density of supercapacitor in some extent. However, the energy density of the present ASC device is too low to meet the requirement of daily life. The two principal factors determining the energy density are the specific capacitance and the voltage window of the ASC device, which are closely related with the kinds of the electrode materials and the electrolytes. In this work, a new MnO 2 @C branch-dendrite (MnO 2 @C-BD) nanoarchitectures as a whole have been triumphantly in-situ prepared and acted as the cathode materials of the ASC device. Moreover, the MnO 2 @C-BD materials are assembled by innumerable MnO 2 nanoparticles coated by the thin carbon layer which provides porous texture and benefits the transportation of ions and electrons. The electrochemical performances of the MnO 2 @C-BD electrode were assessed in 5 M lithium bistrifluoromethanesulfonimide (LiTFSI) electrolyte with the purpose of broaden voltage window aqueous electrolyte. Subsequently, the nanoporous carbon (NPC) materials have been acted as the anode for the MnO 2 @C-BD//NPC ASC device. As we expected that the MnO 2 @C-BD//NPC ASC device can offer 3 V voltage window and exhibit the maximum energy density of 88.7 Wh kg −1 at 103 W kg −1 power density. [ABSTRACT FROM AUTHOR]

Background The recommended goal for blood pressure (BP) control has recently been adjusted for people with diabetes, but the optimal BP control range for the diabetic population is still uncertain. Methods We performed a prospective cohort study of 35,261 patients with type 2 diabetes. Cox proportional hazard regression models were used to estimate the association of BP with all-cause mortality. Results During a mean follow-up period of 8.7 years, 4199 deaths were identified. The multivariable-adjusted hazard ratios of all-cause mortality associated with different levels of systolic/diastolic BP (< 110/65, 110–119/65–69, 120–129/70–80, 130–139/80–90 [reference group], 140–159/90–100, and ≥ 160/100 mm Hg) were 1.70 (95% confidence interval [CI] 1.42–2.04), 1.26 (95% CI 1.07–1.50), 0.99 (95% CI 0.86–1.12), 1.00, 0.92 (95% CI 0.82–1.03), and 1.10 (95% CI 0.98–1.23) using baseline BP measurements, and 2.62 (95% CI 2.00–3.44), 1.77 (95% CI 1.51–2.09), 1.22 (95% CI 1.09–1.36), 1.00, 0.90 (95% CI 0.82–1.00), and 0.98 (95% CI 0.86–1.12) using an updated mean value of BP during follow-up, respectively. The U-shaped associations were confirmed in both African American and white patients, in both men and women, in those who were or were not taking antihypertensive drugs, and in patients aged 30–49 years and 50–59 years. Conclusions The current study found a U-shaped association between BP at baseline and during follow-up and the risk of all-cause mortality among patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Several prospective studies have evaluated the association between glycosylated hemoglobin (HbA 1c ) and death risk among diabetic patients. However, the results have been inconsistent. Methods We performed a prospective study which included 13,334 men and 21,927 women with type 2 diabetes. Cox proportional hazards regression models were used to estimate the association of different levels of HbA 1c with all-cause mortality. Results During a mean follow up of 8.7 years, 4199 (2082 men and 2117 women) patients died. The multivariable-adjusted hazard ratios (HRs) of all-cause mortality associated with different levels of HbA 1c at baseline (< 6.0%, 6.0–6.9% [reference], 7.0–7.9, 8.0–8.9%, 9.0–9.9%, 10.0–10.9%, and ≥ 11.0%) were 1.06, 1.00, 1.10, 0.93, 1.26, 1.18 and 1.31 (P non-linear = 0.008) for men, and 1.21, 1.00, 1.01, 1.08, 1.30, 1.30 and 1.74 (P non-linear < 0.001) for women, respectively. The J-shaped association of HbA 1c with all-cause mortality was confirmed among African American and white diabetic patients, patients who were more than 50 years old, never smoked or used insulin. When we used an updated mean value of HbA 1c , the J-shaped association of HbA 1c with the risk of all-cause mortality did not change. Conclusions Our study demonstrated a J-shaped association between HbA 1c and the risk of all-cause mortality among men and women with type 2 diabetes. Both high and low levels of HbA 1c were associated with an increased risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

ApoC2 is an important activator for lipoprotein lipase-mediated hydrolysis of triglyceride-rich plasma lipoproteins. ApoC2-deficient patients display severe hypertriglyceridemia (sHTG) and recurrent acute pancreatitis. However, due to embryonic lethality in ApoC2 deleted mouse extensive understanding of ApoC2 function is limited in mammalian species. We sought to generate an animal model with ApoC2 deficiency in a rodent with some human-like features and then study the precise effects of ApoC2 on lipid and glucose homeostasis. Using CRISPR/Cas9, we deleted Apoc2 gene from golden Syrian hamster and the homozygous (−/−) pups can be born in matured term but exhibited neonatal lethality. By continuous iv administration of normal hamster serum the ApoC2−/− pups could survive till weaning and displayed severe HTG in adulthood on chow diet. A single iv injection of AAV-hApoC2 at birth can also rescue the neonatal death of ApoC2−/− pups. Adult ApoC2−/−hamsters exhibited a unique phenotype of sHTG with hypoglycemia, hypoinsulinemia and spontaneous atherosclerosis. The sHTG in ApoC2−/− adult hamsters could not be corrected by various lipid-lowering medications, but partially ameliorated by medium chain triglyceride diet and completely corrected by AAV-hApoC2. Our study provides a novel ApoC2-deleted mammalian model with severe hypertriglyceridemia that was fully characterized and highlights a potential therapeutic approach for the treatment of ApoC2 deficient patients. • The first small rodent human-like hamster model with ApoC2 deficiency is created by CRISPR/Cas9 in the present study. • ApoC2-deficient hamsters show neonatal death, which can be rescued by an administration of normal hamster serum or AAV-hApoC2. • Rescued ApoC2-deficient hamsters from normal serum show severe hypertriglyceridemia and spontaneous atherosclerosis. • AAV-hApoC2 completely abolishes severe hypertriglyceridemia and reverses atherosclerotic development in ApoC2-deficient hamsters. [ABSTRACT FROM AUTHOR]