Increasing evidence shows that alterations in gut microbiome (GM) contribute to the development of type 2 diabetes mellitus (T2DM), and fecal microbiota transplantation (FMT) successfully treats ...various human diseases. However, the benefits of FMT therapy to T2DM patients remain unknown.
We enrolled 17 patients with T2DM for nonblinded, one-armed intervention trial of FMT. A total of 20 healthy individuals were recruited as the baseline control. HbA1c% and metabolic parameter change were evaluated in 17 T2DM patients 12 weeks after they received FMT from healthy donors. The GM composition was characterized by 16S rRNA gene amplicon sequencing from fecal samples prior to and 12 weeks after FMT treatment.
We found that the GM of T2DM patients was reconstituted by FMT. We observed a statistically significant decrease in HbA1c% (from 7.565 ± 0.148 to 7.190 ± 0.210, p<0.01), blood glucose (from 8.483 ± 0.497 to 7.286 ± 0.454 mmol/L, p<0.01), and uric acid (from 309.4 ± 21.5 to 259.1 ± 15.8 µmol/L, p<0.01) while a significant increase in postprandial C-peptide (from 4.503 ± 0.600 to 5.471 ± 0.728 ng/ml, p<0.01) at 12 weeks after FMT. Closely evaluating the changes in these assays, we found individual variability in response to FMT treatment. Out of 17 T2DM patients, 11 were found to significantly improve T2DM symptoms. The FMT responders have significantly higher levels of the family
and the genus
(family
) in their pretreated fecal in comparison to nonresponders, which could predict the clinical response with an area under the curve of 0.83.
Our findings suggest that certain T2DM patients can potentially benefit from FMT, and the pretreated abundance of
and
in the fecal of patients may serve as potential biomarkers for selecting T2DM patients to receive FMT.
Alpha-fetoprotein (AFP)-producing pancreatic neuroendocrine tumors (pNETs) are rare, and the few reported cases usually coexisted with other malignant components such as adenocarcinoma or hepatoid ...carcinoma. We present here the first case of pure AFP-producing pNET.
A 56-year-old male patient underwent resection of the pancreatic tail and body because of elevated serum AFP levels and pancreatic mass. Microscopy showed that the tumor tissue consisted of large and small solid nests of polygonal cells. The tumor cells were positive for chromogranin A, synaptophysin, CD99, cytokeratin 19, pan-cytokeratin and β-catenin, and also showed diffuse immunoreactivity for AFP and human chorionic gonadotrophin. The mitotic rate was nearly 30 per 10 high-power fields and the Ki-67 index was nearly 25%. The histopathologic findings supported the diagnosis of an AFP-producing pNET. Other malignant components were not found. Serum AFP levels decreased to near-normal after operation and gradually increased to >1000 ng/ml at 5 months post-surgery. Recurrence and hepatic metastases were revealed by computed tomography. The patient died 21 months after surgery.
This was the first case of pure AFP-producing pNET to be reported in the English literature. Serum AFP levels may provide useful information for monitoring the therapeutic effectiveness, early recurrence or metastases.
Context * Diabetes mellitus (DM) represents an emerging epidemic, poses serious threats to human health, and can seriously compromise patients' quality of life (QoL). Currently, no cure exists for ...DM. Some studies have found that both liraglutide and dapagliflozin have great therapeutic potential in preventing and treating DM and its complications. Objective * The study aimed to examine the impact of liraglutide plus dapagliflozin on high uric acid (UA) and microalbuminuria (MAU) in patients with diabetes mellitus (DM) complicated with metabolic syndrome (MS). Design * The research team designed a randomized controlled trial. Setting * The study took place at the Second Affiliated Hospital of Nanjing Medical University in Nanjing, Jiangsu, China. Participants * Participants were 125 patients with DM complicated with MS who were treated in the outpatient clinic of the endocrinology department at the hospital between January 1, 2020 and December 31, 2021, with 68 in the intervention group and 57 in the control group. Intervention * The intervention and control groups both received 0.6 mg of liraglutide. The intervention group also received 5 mg of dapagliflozin once a day. The dosages were increased at one week after baseline based on the participant's condition. Outcome Measures * Therapeutic effects, glycolipid metabolism, inflammation, uric acid (UA), microalbuminuria (MAU), cardiac function, and quality of life (QoL) were compared between the two groups. Results * Postintervention, the clinical efficacy was significantly higher in the intervention group than in the control group. The intervention group had significantly lower glycolipid metabolism and inflammatory-factor levels than the control group UA and MAU had declined in both groups but were significantly lower in the intervention group. The left ventricular ejection fraction (LVEF) increased and the left ventricular end diastolic diameter (LVEDd) decreased in both groups, but the intervention group had significantly greater changes as compared with those in the control group. The intervention group was also superior to the control group in patients' QoL. Conclusions * Liraglutide plus dapagliflozin has highly therapeutic effect for patients with DM complicated with MS and can effectively reduce UA and MAU levels. The current research team will launch a more comprehensive analysis as soon as possible to obtain the most accurate results.
Podocyte apoptosis is a typical early feature of diabetic nephropathy (DN), with loss of nephrin integrity contributing to increased proteinuria in patients with DN. Emerging evidence shows that ...microRNAs (miRNAs) play vital roles in the pathogenesis of DN. Thus, we aimed to further elucidate the role of miRNAs in podocyte apoptosis in DN. We used db/db and db/m mice maintained under a continuous feeding regime for 12 weeks. Using microarray analysis, we found several miRNAs potentially related to podocyte apoptosis. In addition, we cultured a conditionally immortalized human podocyte cell line in 30 mM D-glucose and found that miR-134-5p was upregulated in both db/db mice and high-glucose (HG)-treated podocytes. Upregulation of miR-134-5p was accompanied by podocyte apoptosis and downregulation of nephrin. Inhibition of miR-134-5p produced the opposite effect. Dual-luciferase reporter assays showed that miR-134-5p directly targeted the 3'-untranslated region of the B-cell lymphoma-2 gene (BCL2), and further study confirmed an increase in bcl-2 protein level in HG-treated podocytes transfected with anti-miR-134-5p. Knockdown of BCL2 impeded the antiapoptotic effect of anti-miR-134-5p. Finally, we found that miR-134-5p might regulate apoptosis in db/db mice and podocytes by targeting BCL2. Taken together, our findings suggest that miR-134-5p promotes podocyte apoptosis under HG conditions by targeting BCL2. Our study provides a meaningful approach to interpret the mechanisms of action of miRNAs involved in DN.
Objectives The Novel approaches for preventing or limiting events (NAPLIES) and The Atorvastatin for Reduction of Myocardial Damage during Angioplasty (ARMYDA) studies demonstrated a beneficial ...effect of statin loading in preventing major adverse cardiac events (MACE) after elective percutaneous coronary intervention (PCI) for stable angina, unstable angina, non-ST-segment-elevation myocardial infarction (NSTEMI). The so called ‘pleiotropic effects’ of statins include modulation of endothelial function, inhibition of inflammation, and attenuation of thrombosis, all of which could provide clinical benefits in the setting of elective PCI by reducing postprocedural incidence of myocardial and MACE. So far, the efficacy of atorvastatin loading in patients with acute ST-segment-elevation myocardial infarction (STEMI) undergoing primary PCI has not been confirmed. Also, whether the ‘pleiotropic effects’ of statins could explain the possible mechanism(s) needs to be discussed. This study sought to explore potential protective effects of statin loading before primary PCI on coronary endothelial function, inflammation, and MACE. Methods A total 60 patients with STEMI were randomised into loading dose group (80 mg atorvastatin before PCI, n=20), regular dose group (20 mg atorvastatin before PCI, n=20), and control group (without atorvastatin before PCI, n=20). All patients received primary PCI and routine treatment. The plasma samples were collected before, immediately after, 6 h after and 24 h after PCI in all the patients. Plasma concentrations of endothelial nitric oxide synthase (eNOS), Nitric Oxide (NO), interleukin-6 (IL-6), tumour necrosis factor (TNF-а), intercellular adhesion molecule-1 (ICAM-1) were tested by ELISA. The results of coronarography, electrocardiogram, myocardial enzyme, high-sensitivity C-reactive protein (hs-CRP), amino terminal-pro brain natriuretic peptide (NT-proBNP), echocardiography, MACE, and the safety of statin loading were also collected. Results Plasma eNOS immediately and 24 h after PCI were higher in the regular dose group (p<0.05). Plasma eNOS before and 24 h after PCI, along with plasma NO at any time point did not show significant differences among the 3 groups. Plasma IL-6 before PCI were lower in the loading dose group (90.773±7.646 pg/ml vs 95.592±4.269 pg/ml vs 94.324±3.692 pg/ml, p=0.023). Plasma IL-6 after PCI, plasma TNF-a and ICAM-1 at any time point did not show significant differences among the 3 groups. MACE occurred in 2 (10.0%) patients in the loading dose group, 2 (10.0%) patients in the regular dose group, 3 (15.0%) patients in the control group, respectively (p=0.855). Conclusions Atorvastatin loading in patients with STEMI undergoing primary PCI may not have protective effects on coronary endothelial function, inflammation, and MACE.
Coronary heart disease (CHD) is characterized by inflammatory process and endothelial dysfunction. To investigate angiopoietin-2 (Ang-2) profiles, we evaluated serum Ang-2 levels in different types ...of CHD in 166 subjects. Ang-2 was measured by enzyme-linked immunosorbent assay. Serum Ang-2 levels were significantly elevated in patients with CHD and gradually increased with advance of CHD. Ang-2 was positively correlated with Gensini scores and hs-CRP. Ang-2 might have potential implication in detecting and monitoring the progression of CHD.
Previous studies have demonstrated the beneficial effect of statin loading prior to elective and early percutaneous coronary intervention (PCI), in which the 'pleiotropic effects' of statins may ...contribute to these clinical benefits. The aim of the present study was to examine the potential effects of atorvastatin loading prior to primary PCI on coronary endothelial function and inflammatory factors in patients with acute ST-segment elevation myocardial infarction (STEMI). A total of 60 patients with STEMI were randomized into three groups: Loading dose (80 mg atorvastatin prior to PCI; n=20), regular dose (20 mg atorvastatin prior to PCI; n=20) and control (without atorvastatin prior to PCI; n=20). The plasma samples were collected prior to, and immediately, 6 and 24 h after PCI in all the patients. The plasma concentrations of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) were examined using ELISA. The plasma eNOS levels immediately and 24 h after PCI were significantly higher in the regular dose group compared with the other groups. However, there were no significant differences in the plasma eNOS concentration prior to and 6 h after PCI, or in the plasma NO concentration at any of the time-points among the three groups. The plasma IL-6 levels prior to PCI were significantly lower in the loading dose group compared with the other groups; however, there were no significant differences in the plasma concentration of IL-6 following PCI or in the concentrations of TNF-α and ICAM-1 at any of the time-points among the three groups. In conclusion, atorvastatin loading in patients with STEMI undergoing primary PCI may not have protective effects on endothelial function and the inflammatory reaction.
Background Elderly multiple organ dysfunction syndrome （MODS） patients receiving invasive mechanical ventilation have poor prognosis in intensive care units （ICUs）.We studied the usefulness of four ...commonly used severity scores and extrapulmonary factors that affected weaning to predict outcome of such patients.Methods Clinical data of 197 patients on admission to ICUs （from January 2009 to June 2012） were used retrospectively.The Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱ,APACHE Ⅲ,Sample Acute Physiological Score （SAPS） Ⅱ and MODS scores were calculated.All the patients were grouped into survivors and nonsurvivors according to the prognosis.Patients,who weaned from ventilator （n=154）,were subdivided into a successful weaning group and a failed weaning group.The receiver operating characteristic （ROC） curves and Logistic regression was used for prognostic and weaning assessment.Results Based on the outcomes,the areas under the ROC of APACHE Ⅱ,APACHE Ⅲ,SAPS Ⅱ,and MODS were 0.837,0.833,0.824,and 0.837,respectively.The Logistic regression analysis revealed that the odds ratio （OR） of underlying lung diseases,serum albumin and creatinine,and the number of organ failures was 2.374,0.920,1.003,and 1.547.APACHE Ⅱ scores on admission performed excellent （ROC：0.921） on the weaning assessments.Conclusions APACHE Ⅱ and MODS systems were marginally better for evaluating the prognosis of elderly MODS patients who received invasive mechanical ventilation.Underlying lung diseases,serum albumin,serum creatinine and the number of organ failures were independent prognostic factors.Using the APACHE Ⅱ scores on admission before weaning may increase the likelihood of successful weaning.（ClinicalTrial.gov identifier NCT01802983）.
Syntheses and optical properties of cyclic arylethynylsilanes containing one or two trialkyne pockets were described. Optical properties such as UV-vis spectra, photoluminescence and quantum yield ...based on these conjugated structural features were compared with each other. The photoactivated insecticidal activities against the 4th-instar larvae of Aedes albopictus （Skuse） were evaluated.
This paper proposes a unified semiparametric method for the additive risk model under general biased sampling. By using the estimating equation approach, we propose both estimators of the regression ...parameters and nonparametric function. An advantage is that our approach is still suitable for the length- biased data even without the information of the truncation variable. Meanwhile, large sample properties of the proposed estimators are established, including consistency and asymptotic normality. In addition, the finite sample behavior of the proposed methods and the analysis of three groups of real data are given.
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