Non-Obese Type 2 Diabetic Rat Models-GK Rat and SDT Rat

The number of diabetic patients has recently been increasing all over the world together with lifestyle changes including sedentary life and high-calorie diet intake, and as a result the increase in these suffering from diabetes mellitus has become a global issue. Diabetic animal models play a key role in bettering our understanding of the pathophysiology of diabetes and in developing new therapies for the disease. Diabetes is classified into two types, type 1 and type 2, and type 2 diabetes is chiefly caused by a depletion of insulin secretion in the pancreas and insulin resistance in peripheral tissues. The Goto-Kakizaki (GK) rat and the Spontaneously Diabetic Torii (SDT) rat are genetic non-obese type 2 diabetic models, and the both rats are considered to be suitable models for investigating the etiology of the depletion of insulin secretion and impaired glucose tolerance. In this review, we overviewed the outline of pathophysiological features in GK rats and SDT rats, including biological parameters and pharmacological responses.

From non-obese diabetic to Network for the Pancreatic Organ Donor with Diabetes: New heights in type 1 diabetes research

Since the discovery of therapeutic insulin in 1922 and the development of the non-obese diabetic spontaneous mouse model in 1980,the establishment of Network for Pancreatic Organ Donor with Diabetes(n POD) in 2007 is arguably the most important milestone step in advancing type 1 diabetes(T1D) research. In this perspective,we briefly describe how n POD is transforming T1 D research via procuring and coordinating analysis of disease pathogenesis directly in human organs donated by deceased diabetic and control subjects. The successful precedent set up by n POD is likely to spread far beyond the confines of research in T1 D to revolutionize biomedical research of other disease using high quality procured human cells and tissues.

Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.

Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Ileal transposition rapidly improves glucose tolerance and gradually improves insulin resistance in non-obese type 2 diabetic rats

Background:Many studies have confirmed that ileal transposition can improve type 2 diabetes mellitus(T2DM),accompanied by increased glucagon-like peptide-1(GLP-1).We performed the experiment on diabetic rats to evaluate the effects and mechanisms of ileal transposition on the glycemic metabolism.Methods:Twenty Goto-Kakizaki(GK)rats were randomly divided into the ileal transposition group(IT group)and the sham operation group(Shamgroup).Weight,food intake,fasting plasma glucose(FPG),fasting insulin(F-ins),oral glucose tolerance test(OGTT)and GLP-1 were determined at baseline and 1,4,8,16 and 24weeks post-operatively.The homeostasis model assessment-insulin resistance(HOMA-IR)index and the area under the curve(AUC)during OGTT were measured.Histological determination of the GLP-1 receptor(GLP-1R)was performed on the pancreas and ileum24weeks post-operatively.Results:In comparison with the Sham group,the IT group showed a higher GLP-1 level and lower AUC at 4,8,16 and 24 weeks post-operatively(all P<0.05)and a lower FPG,F-ins levels and HOMA-IR at 8,16 and 24 weeks post-operatively(all P<0.05).Compared with baseline levels,the plasma GLP-1,AUC and FPG levels decreased significantly at each postoperative time point in the IT group(all P<0.05),but not in the Sham group(all P>0.05);F-ins and HOMA-IR significantly decreased at 8,16 and 24 weeks post-operatively in the IT group(all P<0.05).GLP-1R expression in the IT group was significantly higher than that of the Sham group in both the pancreas and the ileum at 24 weeks post-operatively(P<0.05).Conclusions:Ileal transposition ameliorated glucose metabolism without reduction in weight or food intake in GK rats,which may be induced by the increased GLP-1 expression.However,the delayed improvement of insulin resistance,accompanied by decreased plasma insulin levels,might not directly result from the increased GLP-1.

Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Evaluation of Lipid Profile in Obese and Non-Obese Hypertensive Adult Patients Attended in Medicine Department of a Medical College Hospital of Bangladesh

Background: By the dawn of this modern era of science, the prime challenge of physician is cardiovascular disease (CVD). The most important modifiable risk factors of CVDs are unhealthy diet, physical inactivity and tobacco use. The effects of unhealthy diet and physical inactivity include abnormal blood lipid, obesity and hypertension. We tried to evaluate and correlate the pattern of lipid profile in obese and non-obese hypertensive patients. Objectives: This study was conducted at medicine department of Cumilla Medical College Hospital. The principal aim was to evaluate the lipid profile in obese and non-obese adult hypertensive patients. Methodology: During this cross sectional analytical study, a total of 100 adult hypertensive patients were taken by purposive sampling. Among them 50 (group 1) patients were taken those were obese and 50 (group 2) patients taken those were non-obese according to BMI measurement on operational definition. Diagnosis of hypertension would be established with the help of ambulatory BP measurements two occasions few minutes apart. The staging of hypertension was done according to JNC7 Criteria. Morning blood samples were taken after 8 - 12 hours of fasting and lipid profiles were done on authentic laboratories. The laboratory values were interpreted according to the operational definition of dyslipidaemia. The ethical research and review committee approved the study protocol and signed informed consent was obtained from the participants. The statistics was analyzed using the IBM SPSS software of version 19.0. Statistical significance was set at p < 0.05. Results: Among the two groups, there were 56 (56%) males and 44 (44%) females. The mean age of group 1 (46.10 ± 11.09) was compared to that of group 2 (45.5 ± 10.6). Lipid profile abnormalities were significantly higher in the stage 2 hypertension (59.62%) and stage 3 hypertension (66.66%), higher in class 2 obese (100%) and class 3 obese subjects (100%), female hypertensive patients had significantly higher BMI than their male counterparts (27.24 ± 3.63 kg/m2 versus 29.29 ± 3.99 kg/m2), lipid profiles were higher in the female than male hypertensive patients (63.33% vs 55.35%) but only TC was statistically significant (4.45 ± 1.19 mmol/l versus 4.86 ± 1.29 mmol/l, p < 0.05). Those who were obese had significant high TG (p < 0.001), high TC (p < 0.001) and high LDL-C (p < 0.001). 38 (76%) of the obese hypertensive patients had dyslipidaemia whereas 21 (42%) of non-obese hypertensive patients had dyslipidaemia. In multivariate regression, TG was significantly and directly associated with BMI of subjects. Dyslipidaemia was more prevalent in the age group 30 - 59 of adult hypertensive patients. It showed that obese hypertensive patients had significantly higher SBP (p < 0.001), DBP (p < 0.001) than non-obese subjects. The mean TC (4.83 ± 0.95 mmol/l versus 4.15 ± 0.57 mmol/l, t = -9.70, p < 0.001), TG (2.64 ± 0.67 mmol/l versus 2.10 ± 0.45 mmol/l, t = -5.37, p < 0.001) and LDL-C (3.00 ± 0.82 mmol/l versus 2.44 ± 0.53 mmol/l, t = -9.11, p < 0.001) were also significantly higher among the hypertensive obese subjects. The mean HDL-C was however comparable in the two groups (1.25 ± 0.27 mmol/l versus 1.24 ± 0.57 mmol/l, t = -0.25, p = 0.08)...

Metabolic syndrome in metabolic obese, non-obese elderly in northern Taiwan

Background: The prevalence of metabolic syndrome is high in non-obese adult individuals, but less research focusing on elderly group. We aimed to assess the prevalence rates of metabolic syndrome (MetS) and its individual components in metabolic obese, non-obese elderly population in northern Taiwan (body mass index [BMI] 2). Methods: A cross-sectional survey was conducted among elderly people (≥65 y/o) who received a senior citizen health examination from March to November 2009. A total of 1180 participants (433 men, 36.7%;748 women, 63.3%) were investigated. The prevalence and odds ratios of metabolic syndrome, as defined by the modified Adult Treatment Panel III (ATP III), were analyzed in the following BMI groups: 2, 18.5 - 24 kg/m2, 24 - 27 kg/m2, and ≥27 kg/m2. Results: The prevalence of metabolic syndrome increased with BMI in both women and men (P 2, and 1.09 (1.02 - 1.17) for men with BMI 24 - 27 kg/m2. Conclusions: Elderly individuals in the BMI belong to normal and overweight groups have a relatively high prevalence and increased risk of developing MetS. Therefore, physicians should perform screening examinations for MetS and its risk factors not only in obese patients but also in non-obese elderly patients to prevent Mets. This electronic document is a “live” template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

Correlation of periodontal inflamed surface area with glycated hemoglobin,interleukin-6 and lipoprotein(a)in type 2 diabetes with retinopathy

BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic complications.An inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the literature.AIM To determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in T2DM subjects with retinopathy.METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR.All subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5%and 27.5%respectively.Severity of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in T2DM with DR group compared to T2DM without DR group.Significant difference was observed in the mean percentage of sites with BOP between T2DM with DR(69%)and T2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,P<0.0001);PISA and Lp(a)(r=0.59,P<0.001);CAL and IL-6(r=0.527,P<0.0001)and CAL and Lp(a)(r=0.631,P<0.001)among study subjects.CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to T2DM without DR.Since a bidirectional link exists between periodontitis and DM,the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

Intestinal glucagon-like peptide-1:A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice

BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions.However,the pathogenesis of hypoglycaemic counterregulation is still unclear.Glucagon-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been reported.AIM To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice.METHODS T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)secretion.The GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice.RESULTS The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 mice.Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during hypoglycaemia.DH5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels decreased.Furthermore,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group.Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway.CONCLUSION Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia,leading to reduced appetite and compromised secretion of adrenaline,noradrenaline,and GCG during hypoglycaemia.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Mechanism underlying the effects of exercise against type 2 diabetes:A review on research progress

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes(T2D)in certain nations.The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D.The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D,in addition to identify the limitations of the existing literature,thereby provide direction for future research in this field.

Evaluation of the efficacy and safety of endoscopic band ligation in the treatment of bleeding from mild to moderate gastric varices type 1

BACKGROUND According to practice guidelines,endoscopic band ligation(EBL)and endoscopic tissue adhesive injection(TAI)are recommended for treating bleeding from esophagogastric varices.However,EBL and TAI are known to cause serious complications,such as hemorrhage from dislodged ligature rings caused by EBL and hemorrhage from operation-related ulcers resulting from TAI.However,the optimal therapy for mild to moderate type 1 gastric variceal hemorrhage(GOV1)has not been determined.Therefore,the aim of this study was to discover an individualized treatment for mild to moderate GOV1.AIM To compare the efficacy,safety and costs of EBL and TAI for the treatment of mild and moderate GOV1.METHODS A clinical analysis of the data retrieved from patients with mild or moderate GOV1 gastric varices who were treated under endoscopy was also conducted.Patients were allocated to an EBL group or an endoscopic TAI group.The differences in the incidence of varicose relief,operative time,operation success rate,mortality rate within 6 wk,rebleeding rate,6-wk operation-related ulcer healing rate,complication rate and average operation cost were compared between the two groups of patients.RESULTS The total effective rate of the two treatments was similar,but the efficacy of EBL(66.7%)was markedly better than that of TAI(39.2%)(P<0.05).The operation success rate in both groups was 100%,and the 6-wk mortality rate in both groups was 0%.The average operative time(26 min)in the EBL group was significantly shorter than that in the TAI group(46 min)(P<0.01).The rate of delayed postoperative rebleeding in the EBL group was significantly lower than that in the TAI group(11.8%vs 45.1%)(P<0.01).At 6 wk after the operation,the healing rate of operation-related ulcers in the EBL group was 80.4%,which was significantly greater than that in the TAI group(35.3%)(P<0.01).The incidence of postoperative complications in the two groups was similar.The average cost and other related economic factors were greater for the EBL than for the TAI(P<0.01).CONCLUSION For mild to moderate GOV1,patients with EBL had a greater one-time varix eradication rate,a greater 6-wk operation-related ulcer healing rate,a lower delayed rebleeding rate and a lower cost than patients with TAI.

Quantitative effect of kerogen type on the hydrocarbon generation potential of Paleogene lacustrine source rocks,Liaohe Western Depression,China

Kerogen types exert a decisive effect on the onset and capacity of hydrocarbon generation of source rocks.Lacustrine source rocks in the Liaohe Western Depression are characterized by thick deposition,high total organic carbon(TOC)content,various kerogen types,and a wide range of thermal maturity.Consequently,their hydrocarbon generation potential and resource estimation can be misinterpreted.In this study,geochemical tests,numerical analysis,hydrocarbon generation kinetics,and basin modeling were integrated to investigate the differential effects of kerogen types on the hydrocarbon generation potential of lacustrine source rocks.Optimized hydrocarbon generation and expulsion(HGE)models of different kerogen types were established quantitatively upon abundant Rock-Eval/TOC/vitrinite reflectance(R_(o))datasets.Three sets of good-excellent source rocks deposited in the fourth(Es4),third(Es3),and first(Es1)members of Paleogene Shahejie Formation,are predominantly types I-II_(1),II_(1)-II_(2),and II-III,respectively.The activation energy of types I-II_(2)kerogen is concentrated(180-230 kcal/mol),whereas that of type III kerogen is widely distributed(150-280 kcal/mol).The original hydrocarbon generation potentials of types I,II_(1),II_(2),and III kerogens are 790,510,270,and 85 mg/g TOC,respectively.The Ro values of the hydrocarbon generation threshold for type I-III source rocks gradually increase from 0.42%to 0.74%,and Ro values of the hydrocarbon expulsion threshold increase from 0.49%to 0.87%.Types I and II_(1)source rocks are characterized by earlier hydrocarbon generation,more rapid hydrocarbon expulsion,and narrower hydrocarbon generation windows than types II_(2)and III source rocks.The kerogen types also affect the HGE history and resource potential.Three types(conventional,tight,and shale oil/gas)and three levels(realistic,expected,and prospective)of hydrocarbon resources of different members in the Liaohe Western Depression are evaluated.Findings suggest that the Es3 member has considerable conventional and unconventional hydrocarbon resources.This study can quantitatively characterize the hydrocarbon generation potential of source rocks with different kerogen types,and facilitate a quick and accurate assessment of hydrocarbon resources,providing strategies for future oil and gas exploration.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathwaye

Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.

Early detection of multiple endocrine neoplasia type 1: A case report

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is low.MEN type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical diagnosis.CASE SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hos-pital.Blood tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid lesion.Gastroscopy findings suggested a duodenal bulge and ulceration.Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb.Further blood tests revealed elevated levels of serum gastrin.Surgery was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy.The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year.CONCLUSION For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.