Cryptogenic stroke (CS) is a type of stroke that can not find the exact cause after using the standard clinical examination procedure of stroke. In recent years, many studies have shown that patent foramen ovale (PFO) is closely associated with CS, and its main pathogenesis is paradoxical embolism. In clinical practice, ultrasound is often used for PFO screening. In the context of PFO, the secondary prevention of CS includes drug therapy and PFO closure, but the choice of treatment is still controversial. Screening and evaluation of possible PFO will help to develop secondary prevention strategies for patients with CS, especially those who can benefit from PFO closure.

Objective:To investigate the potential risk factors for cryptogenic stroke (CS) in patients with patent foramen ovale (PFO).Methods:Patients underwent PFO closure in the Department of Cardiovascular Surgery, the Second Hospital of Hebei Medical University from June 2018 to December 2021 were enrolled retrospectively. Transesophageal echocardiography was used to evaluate the morphological characteristics of foramen ovale and right-to-left shunt (RLS). Multivariate logistic regression analysis was used to determine the independent risk factors for CS in patients with PFO. Results:A total of 203 patients with PFO were enrolled. Their age was 41.9±14.3, and 116 patients (57.1%) were male. There were 102 patients in CS group and 101 patients in non-stroke group. The age, body mass index, systolic blood pressure and diastolic blood pressure, and the constituent ratios of male, hypertension, diabetes, hyperlipidemia and smoking of the CS group were significant higher than those of the non-stroke group (all P<0.05). The PFO channel of the CS group was longer, wider and more combined with resting RLS (all P<0.05). Multivariate logistic regression analysis showed that systolic blood pressure (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.022-1.111; P=0.003), PFO length ( OR 1.124, 95% CI 1.004-1.258; P=0.043) and resting RLS ( OR 5.449, 95% CI 2.283-13.004; P<0.001) were the independent risk factors for CS in patients with PFO. Conclusion:Systolic blood pressure, PFO length and the presence of resting RLS are the independent risk factors for CS in patients with PFO.

Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from

Objective:To analyze the clinical features of type 2 diabetic patients with insulin autoimmune syndrome after treatment with exogenous insulin.Methods:A total of 106 patients with type 2 diabetes diagnosed with exogenous insulin-related insulin autoimmune syndrome (EIAS) were included from September 2017 to March 2019 in the Department of Endocrinology, Zhongshan Hospital, Fudan University. The clinical data, physical examination, and laboratory examination results of patients were collected.Results:Of the 106 patients, 84 (79.24%) used premixed human insulin or premixed insulin analogs, and 18 patients (16.98%) presented recurrent hypoglycemia. The arginine stimulation test showed that the median value of the baseline insulin was 73.40 (23.07-146.75) μU/ml, and the median ratio of 4 minute insulin to 0 minute insulin was 1.27 (1.03-1.85), with the mean of the ratio 1.72±1.47. The ratio of baseline insulin (μU/ml) to C-peptide (ng/ml) was 44.60 (14.92-87.93), with an average of 81.92±130.93. Taking the two-fold upper limit of fasting insulin reference value (49.8 μU/ml) as the cut-off point, the subjects were divided into insulin accumulation group (baseline insulin≥49.8 μU/ml) and insulin non-accumulation group (baseline insulin <49.8 μU/ml). Among the 66 patients in the insulin accumulation group, 14 patients had hypoglycemia (21.21%) and 4 patients in the insulin non-accumulation group presented hypoglycemia (10%). The ratio of 4 minute insulin to baseline insulin, ratio of baseline insulin to C-peptide, blood glucose level standard deviation (SDBG) and maximum blood glucose fluctuation amplitude (LAGE) in the insulin accumulation group were significantly higher than those in the insulin non-accumulation group (all P<0.05). Among 66 patients in the insulin accumulation group, 36 patients changed the type of insulin preparafion (insulin treatment group), 30 patients were changed from insulin to oral hypoglycemic agents (oral medication group). After treatment, both SDBG and LAGE in the two groups were significantly lower than before treatment ( P<0.05). Conclusions:With the aggravation of exogenous insulin accumulation, the fluctuation of blood glucose and the proportion of hypoglycemia were significantly increased. There was a characteristic change in islet function in patients with insulin autoimmune syndrome. After arginine stimulation, there was no significant peak of insulin secretion, showing a " high-level" curve. The baseline insulin/C-peptide ratio was significantly increased. The prognosis of EIAS patients is good after timely diagnosis and adjustment of treatment.

This paper analyzed the necessity of due diligence in hospital mergers and acquisitions from the perspective of two trading parties,and summarized such roadblocks in hospital due diligence,as lack of awareness,information asymmetry and lack of co-ordination of the investigated.Going through the five main aspects of due diligence in hospital mergers and acquisitions,including business due diligence,financial due diligence,human resource due diligence,legal due diligence and hospital environmental and occupational safety due diligence,the authors put forward pertinent suggestions and countermeasures on efficient due diligence work.

Objective:To compare different non‐invasive hepatic fibrosis evaluation criteria for the evaluation of hepatic fibrosis in patients with type 2 diabetes mellitus(T2DM ) combined with non‐alcoholic fatty liver disease(NAFLD) .Methods:A total of 996 patients(male 578 ,female 418) definitely diagnosed with T2DM ,who were simultaneously identified as NAFLD by ultrasonography ,were involved in the analysis .The venous fasting blood was collected from patients ,and blood routine and hepatic enzymes were evaluated .Aspartate aminotransferase(AST)/alanine aminotransferase(ALT) ratio ,FIB‐4 index ,BARD score ,AST to platelet ratio index (APRI) and NAFLD fibrosis scores(NFS) were calculated .NFS was set as the evaluation criterium for hepatic fibrosis .The correlations between the other indexes and the NFS were compared with correlation analysis . As the next step ,consistency of these indexes was evaluated by Bland‐Altman method .Results:AST/ALT ratio ,FIB‐4 index , BARD score and APRI ratio had linear positive correlation with NFS among male and female patients with T2DM combined with NAFLD .Furthermore ,the most significant correlation was observed between FIB‐4 index and NFS(r=0 .619 ,P<0 .01) . Bland‐Altman analysis indicated that AST/ALT ratio and FIB‐4 index were highly consistent with NFS ,and the FIB‐4 index was the best among the indexes .Conclusions:AST/ALT ratio and FIB‐4 index can be used to identify whether there is hepatic fibrosis in patients with T2DM combined with NAFLD .

Microsomal triglyceride transfer protein (MTP) is a key transfer protein in lipid metabolism and is mainly expressed in the hepatocytes and enterocytes.It plays an important role in transferring triglyceride as well as in assembly and secretion of very low density lipoprotein.Recent studies have shown that MTP is closely related to the onset and development of non-alcoholic fatty liver disease.

Objective To investigate the effects of diabetic duration on liver fat content (LFC) in patients with type 2 diabetes,and to explore its relationship with the outcome of liver disease.Methods A total of 435hospitalized patients with type 2 diabetes were recruited.The history data,results of laboratory tests,and hepatic 1 H-MRS were collected,and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) was calculated.Results The prevalence of NAFLD in newly-diagnosed type 2 diabetes mellitus (NT2DM) group was higher than that in predousb-diagnosed type 2 diabetes mellitus (PT2DM) group (92.7％ vs 82.2％,P＜0.05),with higher LFC [(27.97 ± 16.88 vs 19.44± 15.54) ％,P＜0.01].The LFC was reduced with prolonged duration of diabetes.Partial correlation analysis showed that LFC was negatively correlated with duration of diabetes (rs =-0.233,P＜0.01) after adjustment for gender,age,body mass index (BMI),oral anti-diabetic drugs,lipid-lowering drugs,and insulin treatment.Multiple linear regression analysis showed that LFC was positively correlated with BMI,albumin,and alanine aminotransferase while negatively correlated with duration of diabetes.The proportion of patients without advanced fibrosis (NFS＜-1.455) was significantly higher in NT2DM group than that in PT2DM group (26.3％ vs 15.5％,P＜0.05),and the proportion of PT2DM in patients with advanced fibrosis (NFS＞0.676) was significantly higher than that of NT2DM (79.2％ vs 20.8％,P＜0.05).NFS was positively correlated with the duration of diabetes (rs =0.236,P＜0.01).The liver fat content in patients with advanced liver fibrosis decreased significantly,and the LFC was negatively correlated with NFS (rs =-0.164,P＜0.01).Conclusions The duration of diabetes is an independent influencing factor of LFC.With the extension of the duration of diabetes,the decreased LFC in type 2diabetic patients with NAFLD is related to the development of advanced fibrosis.The decrease in LFC in type 2diabetic patient is associated with poor outcome of NAFLD.

Objective To analyze the association of fat content,enzymes,and fibrosis in liver with iron overload in patients with type 2 diabetes,and to explore the relationship between iron overload and severity of nonalcoholic fatty liver disease (NAFLD) in these patients.Methods Five hundred and thirty hospitalized patients with type 2 diabetes and 18 patients with abnormal glucose metabolism undergoing liver biopsy were recruited.History data,results of laboratory tests,liver ultrasound,hepatic 1 H-MRS were collected and serum ferritin level was determined.Results The serum ferritin level was significantly higher in patients with NAFLD than that without NAFLD [(328.7±252.2 vs 239.9 ± 171.8) μg/L,P＜0.01].Serum ferritin was an independent risk factor for NAFLD (P＜0.05).Multiple linear regression analysis showed that serum ferritin was positively correlated with liver fat content after adjustment for sex,age,and duration of diabetes.The serum ferritin level in NAFLD with elevated liver enzymes was significantly higher than that in simple steatosis [(429.9 ± 287.4 vs 293.4 ± 233.3) μg/L,P＜0.01].Serum ferritin was an independent risk factor for elevated liver enzymes in patients with NAFLD (P ＜0.05).Serum ferritin level in patients with advanced fibrosis was significantly lower than that in patients without advanced fibrosis [(246.8 ± 191.2 vs 382.5 ± 253.7) μg/L,P＜0.01].In 18 patients with NAFLD proven by biopsy,serum ferritin level was slightly higher in NASH group than that in simple steatosis group,but there was no statistically significant difference.Serum ferritin levels were comparable between patients with and without advanced fibrosis.Conclusion The iron overload in type 2 diabetic patients seems to be an independent risk factor for the development of NAFLD and elevated liver enzymes.Iron load in patients with advanced fibrosis is significantly decreased.

Objective To evaluate the severity of non-alcoholic fatty liver disease(NAFLD) and progressive liver fibrosis(stage＞2)in hospitalized patients with type 2 diabetes mellitus(T2DM) by using NAFLD fibrosis score (NFS).The risk factors associated with progressive fibrosis were also analyzed.Methods A total of 721 hospitalized patients with T2DM and uhrasound verified NAFLD were involved.The history information and laboratory examinations were collected,NFS was calculated.The low cutoff score (-1.455) of NFS was used to exclude,and high cutoff score (0.676) to further accurately diagnose progressive fibrosis.Results (1) A total of 721 subjects (male/female 371/350) were diagnosed as NAFLD by ultrasound.In those subjects,173 patients were with progressive fibrosis (24.0％),111 patients without progressive fibrosis (15.4％),and 437 patients (60.6％) with NFS ranged from-1.455 to 0.676.(2) Aging,raised body mass index,aspartate amino transferase/alanine aminotransferase (AST/ALT) ratio,lowered albumin,and platelet were risk factors for progressive fibrosis of NAFLD.In addition,NFS was positively correlated with duration of diabetes,waist circumference,SBP,glycated albumin (GA),and GA/HbA1c(all P＜0.01),and negatively with red blood cell count,hemoglobin,white blood cell count (WBC),total cholesterol (TC),triglyceride,apolipoprotein-B,ALT,γ-glutamyltranspeptidase (all P＜0.01),AST,low-density lipoprotein cholesterol (all P＜0.05).(3) Logistic stepwise regression analysis showed diabetes duration,waist circunference,and GA were positively correlated with progressive liver fibrosis(OR =1.182,1.076,1.074,all P＜0.01),and negatively with WBC and TC (OR =0.613,0.703,all P＜0.01).Conclusions The detection rate of progressive fibrosis in patients with NAFLD and T2DM was approximately 24.0％ by applying NFS.Only 15.4％ of those subjects could be excluded from progressive fibrosis.It suggests that we should be alert to the risk of liver fibrosis in patients with type 2 diabetes.