Mesenchymal Stem Cells Attenuates Hirschsprung Disease-Associated Enterocolitis by Reducing M1 Macrophages Infiltration via COX-2 Dependewhant Mechanism.

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.

The clinical and genetic characteristics of maternally inherited diabetes and deafness (MIDD) with mitochondrial m.3243A > G mutation: A 10-year follow-up observation study and literature review.

Maternally inherited diabetes and deafness (MIDD) is often caused by the m.3243A > G mutation in mitochondrial DNA. Unfortunately, the characteristics of MIDD, especially long-term outcomes and heteroplasmic changes, have not been well described previously. The purpose of this study was to describe the clinical and genetic features of a family with MIDD after 10 years of follow-up.A 33-year-old male patient with typical characteristics of MIDD, including early-onset diabetes, deafness, and low body mass index, was admitted to our department. Further investigation revealed that the vast majority of his maternal relatives suffered from diabetes with or without deafness. A detailed family history was then requested from the patient and a pedigree was constructed. The patient suspected of MIDD was screened for mutations using whole mitochondrial DNA sequencing. Candidate pathogenic variants were then validated in other family members through Sanger sequencing. The patient was diagnosed with MIDD, with inherited m.3243A > G mutation in the mitochondrially encoded tRNA leucine 1 (MT-TL1) gene, after 10 years of symptom onset. The patient was then treated with insulin and coenzyme Q10 to improve mitochondrial function. During the follow-up period, his fasting blood glucose and HbA1c levels were improved and the incidence of diabetic ketoacidosis was significantly reduced. Our findings indicate that whole mitochondrial DNA sequencing should be considered for patients suspected of MIDD to improve the efficiency of diagnosis and prognosis.

Clinical characteristics of 30 COVID-19 patients with epilepsy: A retrospective study in Wuhan.

OBJECTIVE: This study aims to present the clinical characteristics of 30 hospitalized cases with epileptic seizures and coronavirus disease 2019(COVID-19). METHODS: This is a retrospective observational research study. Clinical data were extracted from electronic medical records in 1550 patients with a laboratory-confirmed diagnosis of COVID-19, who were hospitalized in Wuhan Central Hospital, China, from 1 January to 31 April 2020. 30 COVID-19 patients with the diagnosis of epilepsy were enrolled. The clinical characteristics, complications, treatments, and clinical outcomes of 30 cases were collected and analyzed. RESULT: Of 30 patients with a diagnosis of epilepsy and COVID-19, 13 patients (43.4%) had new-onset epileptic seizures without an epilepsy history(new-onset seizure group, NS group), ten patients(33.3%) had an epilepsy history with a recurrent epileptic seizure (recurrent seizure group, RS group) and seven patients(23.3%) had an epilepsy history but no seizure during the course of COVID-19 (epilepsy history group, EH group). Patients in the RS group had a larger number of other-neurological-disease histories than those in the NS and EH groups (7/10[70%] VS 1/13 [7.7%] VS 1/7[14.3%]); the difference between the RS group and NS group is significant (P < 0.05). Patients in the NE and RS groups suffered more severe/critical COVID-19 infection than patients in the EH group (10/13[76.9%] VS 6/10[60%] VS 1/7[14.3%]); the difference between the NS group and EH group is significant (P < 0.05). 36.7% of patients had one to five neurological complications, and 46.4% of patients had 6-10 neurological complications. The complications in patients with seizures (in the RS and NS groups) seem to be more than those without seizures (in the EH group), but it did not reach statistical significance. The proportion of antiepileptic drugs (AEDs) treatment before admission was higher in the EH group than in the RE group(7/7 [100%] VS 2/10 [20%], P < 0.05). The mortality of 30 patients with epilepsy and COVID-19 was 36.67%. The mortality of the NS group(38.5%) and the RS group(50%) were a little higher than in the EH group(14.3%). None of the convalescent patients had a recurrent seizure, and there were no more deaths in the 3-month follow-up after discharge. CONCLUSIONS: COVID-19 patients with recurrent epileptic seizures had more underlying neurological diseases than patients who had an epilepsy history but without a seizure. Patients with new-onset and recurrent epileptic seizures suffered more severe/critical COVID-19, which may lead to a worse prognosis. If patients with epilepsy history continue using AEDs during COVID-19 pandemics, the risk of recurrent seizure may be reduced, and a good prognosis for patients with epilepsy history could be expected.

Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19.

Aim: We aimed to explore the biomarkers for disease progression or the risk of nonsurvivors. Materials & methods: This study included 134 hospitalized patients with confirmed COVID-19 infection. The outcome of moderate versus severe versus critically ill patients and survivors versus nonsurvivors were compared. Results: An increase in the severity of COVID-19 pneumonia was positively associated with lower levels of platelets and albumin (all p < 0.05). In the critical group, the plasma levels of albumin continued to have a significant association for the risk of nonsurvivors (p < 0.05), even after adjusting for confounding factors. Conclusion: Albumin levels could be used as an independent predictor of the risk of nonsurvivors in critically ill patients with COVID-19.

Inverse Association Between Serum Vitamin B12 Concentration and Obesity Among Adults in the United States.

Introduction: Several studies have suggested that vitamin B12 deficiency is more common in obese individuals. We evaluated the cross-sectional associations of serum vitamin B12 concentrations with obesity in a nationally representative sample of adults in the United States. Methods: We included 9,075 participants aged ≥20 years in the National Health and Nutrition Examination Survey 2011-2014. Serum vitamin B12 concentrations were measured by electrochemiluminescence immunoassay. Obesity was defined as BMI ≥30 kg/m2. We used logistic regression with sample weights to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results: Serum vitamin B12 concentrations were lower among obese adults compared with non-obese adults. After adjustment for age, gender, race/ethnicity, socioeconomic status, dietary and lifestyle factors, use of medications that could affect the serum vitamin B12 levels, dietary supplement use and fasting time, the multivariable-adjusted ORs (95% CIs) of obesity were 1.00 (reference), 0.95 (0.79, 1.14), 0.86 (0.74, 0.99), and 0.71 (0.60, 0.84) (p for trend <0.001) for increasing quartiles of serum vitamin B12 concentrations. Conclusions: In a large nationally representative sample of U.S. adults, higher serum vitamin B12 levels were inversely associated with obesity. Further investigation is needed to understand the underlying mechanisms.

Increased BMR in overweight and obese patients with type 2 diabetes may result from an increased fat-free mass.

The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI≤28 kg/m(2), n=99), or obese (BMI ≥28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (P<0.05) and patients with normal BMI did (P<0.05). The measured BMR was significantly lower than the predicted BMR (P<0.05) in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat-free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients (P<0.05). Fat-free mass was closely correlated with BMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.