Cage-Confinement Induced Emission Enhancement.

As a proof-of-concept study, Imi-cage and Phos-cage organic molecular cages (OMCs) containing the triphenylphosphine (TPP) moiety, a nonclassic AIE luminogen (AIEgen), have been designed to demonstrate the cage-confinement induced emission enhancement (CCIEE). Thanks to the confinement effect of OMCs, the rigid Imi-cage exhibits much higher photoluminescence (PL) quantum yield (ΦPL) than the open-shell Semicage and small molecule TPP in both solution and amorphous solid states. The emission of Phos-cage could be further enhanced in crystalline solid state with a remarkably high ΦPL of 97.6% (vs 3.47% of crystalline TPP) benefiting from AIE enabled by the highly ordered molecular packing. The novel strategy of CCIEE via confining an AIEgen into an OMC to achieve a significant emission enhancement will shed light on the development of solid-state highly fluorescent materials. The fluorescent nature of Imi-cage was further exploited for the ultrahighly sensitive detection of the explosive picric acid.

Expert consensus on personalized initiation of glucose-lowering therapy in adults with newly diagnosed type 2 diabetes without clinical cardiovascular disease or chronic kidney disease.

Since it is difficult for clinicians to make a decision among the various types of antidiabetic medications due to their great discrepancy in mechanisms, pharmacological properties, and cardiovascular/renal protection, a relatively "precision" or personalized hypoglycemic treatment suggestion is practical for type 2 diabetes (T2D) management in adults. This expert consensus makes some recommendations based on the characteristics of adult T2D patients without clinical cardiovascular disease (CVD) or chronic kidney disease (CKD) by evidence from large-scale clinical trials. The main consideration for initiating antidiabetic medications is the safety and benefits for prevention of target organ damage, such as CVD and CKD. The choice of personalized glucose-lowering therapy regarding target organ protection is based on the various effects of antidiabetic medications, patients' clinical characteristics and their key risks, as well as the sociological factors. According to the effects on glucose reduction, cardiovascular protection, renal benefit, body weight change, hypoglycemic risk, and liver function impact, the antidiabetic medications are recategorized in this consensus. Combined with the glucose control target and the different effects of hypoglycemic agents, a significant body of recommendations have been developed for optimal T2D management according to the risk factors for atherosclerotic CVD, heart failure, CKD, primary fatty liver, and hypoglycemia. This consensus gives detailed guidance on personalized antidiabetic therapy initiation in newly diagnosed T2D adults, which attaches great importance to both glucose control and target organ protection.

Recycling silicon kerf waste: Use cryolite to digest the surface oxide layer and intensify the removal of impurity boron.

The surface oxide layer (SiO2 layer) is still one of the main limitations of the recovery and purification of silicon kerf waste (SKW). Herein, to recycle SKW as the low-boron silicon ingot, an effective combination strategy that digests the surface oxide layer by pretreatment and then removes impurity boron by slag treatment is proposed. In the pretreatment part, the surface oxide layer of SKW was successfully digested into a liquid phase after mixing 10.5 wt% cryolite and sintering at 1400 °C, and the obtained SKW-ceramic has a dense structure. Moreover, when holding at 1400 °C for 2 h, the boron concentration in SKW-ceramic was decreased to 5.75 ppmw, and the removal rate reaches 14.18%. In the slag treatment part, CaO and SiO2 are selected as slag agents. The CaO/SiO2 mass ratio and reaction temperature were determined to be 2 and 1600 °C based on thermodynamic simulation. Besides, Na2O formed due to the dissociation of cryolite, which can enhance the oxygen ion activity and boron-absorbing capacity of the slag. The experimental result exhibited that the boron removal efficiency reached 86.56%. The simplicity and scalability of this strategy provide a better alternative for the recovery of SKW.

Synergy between vitamin E and D-sorbitol in enhancing oxidation stability of highly crosslinked ultrahigh molecular weight polyethylene.

Oxidative stability of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) artificial joints is significantly improved by vitamin E (VE), but there is a dilemma that VE hinders crosslinking and thus jeopardizes the wear of UHMWPE. In this effort, we proposed an efficient strategy to stabilize UHMWPE under limited antioxidant contents, where VE and D-sorbitol (DS) were used as the primary antioxidant and the secondary antioxidant respectively. For non-irradiated blends with fixed antioxidant contents, oxidative stability accessed by oxidation induction time (OIT) of VE/DS/UHMWPE blends was superior to that of VE/UHMWPE blends, while DS/UHMWPE blends showed no increase in OIT. The cooperation between DS and VE exhibited a synergistic effect on enhancing the oxidative stability of UHMWPE. Interestingly, the irradiated VE/DS/UHMWPE blends showed comparable OIT but a significantly higher crosslink density than the irradiated VE/UHMWPE blends. The crystallinity, melting point, and in vitro biocompatibility of the blends were not affected by VE and DS. The quantitative relationships of mechanical properties, oxidation stability, crystallinity and crosslink density were established to unveil the correlation of these key factors. The overall properties of VE/UHMWPE and VE/DS/UHMWPE blends were compared to elucidate the superiority of the antioxidant compounding strategy. These findings provide a paradigm to break the trade-off between oxidative stability, crosslink density and mechanical properties, which is constructive to develop UHMWPE bearings with upgraded performance for total joint replacements. STATEMENT OF SIGNIFICANCE: VE-stabilized UHMWPE is the most commonly used material in total joint replacements at present. However, oxidation and wear resistance of VE/UHMWPE implants cannot be unified since VE reduces the efficiency of radiation crosslinking. It limits the use of VE. Herein, we proposed a compounding stabilization by the synergy between VE and DS. The antioxidation capability of VE was revived by DS, thus enhancing the oxidation stability of unirradiated UHMWPE. The irradiated VE/DS/UHMWPE exhibited similar oxidation stability but higher crosslink density than irradiated VE/UHMWPE, which is beneficial to combat wear of UHMWPE and to inhibit the occurrence of osteolysis. This synergistic antioxidation strategy endows the UHMWPE joint material with good overall performance, which is of clinical significance.

Environmental regulation and the growth of the total-factor carbon productivity of China's industries: Evidence from the implementation of action plan of air pollution prevention and control.

To abate the severe air pollution, the Chinese government released the Action Plan of Air Pollution Prevention and Control (APAPPC) in 2013. This paper regards the APAPPC as a quasi-experiment and uses the DID method to investigate the impact of environmental regulation on the growth of green total-factor productivity of China's industries. This article employs the non-radial directional distance function (NDDF) and the global Malmquist index to measure the total-factor carbon productivity of China's industries. Further regressions suggest that the implementation of the APAPPC has significantly promoted the growth of the total-factor carbon productivity in the air pollution-intensive industries, and its marginal effect has steadily increased with time. This result is still valid after using a series of counterfactual tests and robustness tests. The further mechanism study shows that the APAPPC has significantly promoted R&D investment, especially in instruments and equipment, which has effectively promoted technical efficiency and technological advancement. It indicates that stringent and well-designed environmental regulations should lead to a "win-win" situation of environmental improvement and economic development by encouraging enterprises to upgrade their technology and equipment.

Comparison Between Pioglitazone/Metformin Combination Therapy and Sitagliptin/Metformin Combination Therapy on the Efficacy in Chinese Type 2 Diabetic Adults Insufficiently Controlled with Metformin: Study Protocol of an Open-Label, Multicenter, Non-Inferiority Parallel-Group Randomized Controlled Trial.

INTRODUCTION: The prevalence of type 2 diabetes (T2D) has risen substantially in China, where its pathophysiology is primarily characterized by insulin resistance (IR). Alleviating IR may help with the management of T2D in the Chinese population. Pioglitazone and sitagliptin are two hypoglycemic medications with different pharmacological actions, both of which are optimal choices for use in combination with metformin. Previous studies have yielded mixed findings regarding the differences in hypoglycemic effects between the two agents. Though pioglitazone is associated with weight gain, both drugs have been shown to decrease visceral adipose tissue (VAT) and improve IR in individuals with T2D. There is a lack of direct comparisons between pioglitazone and sitagliptin among Chinese individuals with T2D. Therefore, this paper describes a protocol for a randomized controlled trial (RCT) that investigates the differences in hypoglycemic efficacy, IR improvement, and safety profiles between these drugs. METHODS AND ANALYSIS: This is a 24-week, open-label, multicenter, non-inferiority parallel-group RCT with a 1:1 allocation ratio. It compares pioglitazone/metformin (15 mg/500 mg) combination therapy with sitagliptin/metformin (50 mg/500 mg) combination therapy in Chinese adults with T2D insufficiently controlled with metformin. The primary outcomes are HbA1c reduction, insulin level increase, and IR index change. The secondary outcomes are body weight and abdominal VAT decreases, lipid profiles, and inflammatory indicators. Tolerability and safety data will also be collected. CONCLUSION: It is believed that the direct comparisons of the hypoglycemic effects, VAT reductions, and safety profiles between pioglitazone and sitagliptin will help to optimize treatments for Chinese adults with T2D who are primarily characterized by IR. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900021861).

Thermal transport properties of graphite carbon nitride.

Graphite carbon nitride (GCN), which can be regarded as a nitrogen heteroatom-substituted graphite framework, has attracted great attention as a new 2D layered structure material with semiconductor electronic characteristics. Using molecular dynamics simulations, the in-plane thermal conductivity and cross-plane thermal resistance of two GCN structures (i.e., triazine-based and heptazine-based) are investigated. Our results show that the in-plane thermal conductivities of the triazine-based and heptazine-based GCN monolayers along the armchair direction are 55.39 and 17.81 W m-1 K-1, respectively. The cross-plane thermal resistance decreases with increasing layer number and reaches asymptotic values of 3.6 × 10-10 and 9.3 × 10-10 m2 K W-1 at 40 layers for triazine-based and heptazine-based GCN, respectively. The in-plane thermal conductivity can be effectively manipulated by changing the temperature and applying strain, while it is insensitive to the number of layers, which is in sharp contrast to that of graphene. Moreover, the cross-plane thermal resistance decreases monotonically with temperature and coupling strength, and can be modulated by external strain. Surprisingly, the cross-plane tensile strain can reduce the thermal resistance of the heptazine-based GCN. Our study serves as a guide to groups interested in the physical properties of GCN.

Acarbose With Comparable Glucose-Lowering but Superior Weight-Loss Efficacy to Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Acarbose and dipeptidyl peptidase-4 inhibitors (DPP-4is) have several similarities regarding their efficacy. Assessing the hypoglycemic and weight-loss effects, as well as the tolerability between them at their optimal dosages, could provide a better management of adult type 2 diabetics. Methods: We performed a systematic review and network meta-analysis (NMA) on randomized controlled trials that were identified from the databases of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Conference Proceedings Citation Index, ClinicalTrials.gov, China National Knowledge Infrastructure, Wan Fang, and SinoMed. The trials with 300 mg/day of acarbose or the recommended doses of DPP-4is were the most optimal for our NMA. The mean differences (MD) and relative risk (RR) derived from eligible studies were used. Results: Among the 15,411 obtained potential studies, 13 pair-wise trials and 48 monotherapy studies were included in the meta-analysis and NMA, respectively. DPP-4is had a greater glucose-lowering effect, but a weaker weight-loss effect than acarbose in pair-wise meta-analysis (p < 0.05). However, NMA with 11,877 participants showed that, at their optimal doses, acarbose and DPP-4is had similar glucose-lowering effects on the 2-h postprandial glucose (MD 0.96 mmol/L, 95% credible interval -0.56 to 2.54), HbA1c (0.05%, -0.25 to 0.33), fasting plasma glucose reductions (-0.27 mmol/L, -0.76 to 0.24), and HbA1c < 7.0% target goal achievement (RR 1.33, 0.51 to 3.64). Acarbose was superior to DPP-4is regarding weight loss (MD -1.23 kg, -2.08 to -0.33). Acarbose had more withdrawal, gastrointestinal, and overall adverse events than DPP-4is (p < 0.05), but the differences disappeared after longer treatment (p > 0.05). Conclusions: Acarbose and DPP-4is have similar glucose-lowering effects, but the weight-loss effects of acarbose are superior. Therefore, in the use of the most optimal dosages, overweight/obese type 2 diabetics might benefit more from a treatment with acarbose than DPP-4is.

Systemic Delivery of siRNA Specific for Silencing TLR4 Gene Expression Reduces Diabetic Cardiomyopathy in a Mouse Model of Streptozotocin-Induced Type 1 Diabetes.

INTRODUCTION: Diabetic cardiomyopathy is a cardiac dysfunction in patients with diabetes which may lead to overt heart failure and death. Toll-like receptor (TLR) signaling triggers diabetic cardiomyopathy through various mechanisms, one of which is the upregulation of TLR4 expression. The aim of this study was to delineate the role of TLR4 in diabetic cardiomyopathy. METHODS: C57BL/6 mice were injected with streptozotocin to induce diabetes. The experimental and control groups were treated with 5 µg of TLR4 small interfering RNA (siRNA) or scrambled siRNA. Cardiac histopathology was evaluated by hematoxylin and eosin, Sirius red, and immunofluorescence staining after treatment with TLR4 siRNA. The myocardial fibrosis and inflammatory factors were detected by quantitative real-time polymerase chain reaction after treatment with TLR4 siRNA. The myocardial function was evaluated by echocardiography after treatment with TLR4 siRNA. RESULTS: Compared with non-diabetic mouse hearts, hypertrophy, fibrosis, inflammation of cardiomyocytes, and myocardial dysfunction were significantly increased in diabetic mice (p < 0.05). Knockdown of TLR4 decreased hypertrophy, fibrosis, inflammation of cardiomyocytes, and myocardial dysfunction (p < 0.05). Cardiomyocytic cross-sectional areas in hearts of TLR4 siRNA-treated diabetic mice were similar to those of the sham-treated mice (p > 0.05). The induction of expression of cardiac fetal genes, beta-myosin heavy chain (ß-MHC) and atrial natriuretic peptide (ANP), which are two markers of cardiac hypertrophy, was significantly reduced in TLR4 siRNA-treated hearts compared with controls (p < 0.05). Moreover, siRNA-mediated silencing of TLR4 reduced diabetes-induced collagen deposition (p < 0.05). Paralleled with changes in collagen deposition and the expression of collagen I and collagen III, knockdown of TLR4 also reduced the expression of transforming growth factor-ß1 (TGFß1) mRNA (p < 0.05). The increased expression of intercellular cell adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was significantly attenuated by TLR4 siRNA treatment in the hearts of diabetic mice (p < 0.05). Furthermore, both fractional shortening (FS) and ejection fraction (EF) values were preserved in TLR4 siRNA-treated diabetic mice compared with control siRNA-treated mice (31.80% ± 2.82% vs. 28.50% ± 5.83% for FS, p < 0.05) (57.95% ± 6.48% vs. 45.34% ± 4.25% for EF, p < 0.05). CONCLUSION: Our study used siRNA to specifically silence TLR4 gene expression in the diabetic mouse heart in vivo and to investigate the role that TLR4 plays in diabetic cardiomyopathy. It is likely that silencing of the TLR4 gene through siRNA could prevent the development of diabetic cardiomyopathy.

Exploration Of The Seated Saline Suppression Test For The Diagnosis Of Primary Aldosteronism In The Chinese Population.

OBJECTIVE: We prospectively investigated the accuracy of the seated saline suppression test (SSST) in 113 patients with hypertension (including 93 primary aldosteronism [PA] and 20 essential hypertension patients) in the Department of Endocrinology and Metabolism. METHODS: Each patient underwent a recumbent saline suppression test (RSST) and SSST. The accuracy of the SSST for a confirmative PA diagnosis and subtype classification was evaluated and compared with the RSST. RESULTS: The area under the receiver operating characteristic (ROC) curve of plasma aldosterone concentration (PAC) for the SSST was significantly greater than that for the RSST (0.945±0.0199 vs. 0.828 ± 0.0404; P<.05). The ROC analysis showed that the optimal PAC cut-off values were 12.94 ng/dL for the SSST (sensitivity 86.02%, specificity 95%; Youden index [YI] 0.810) and 12.04 ng/dL for the RSST (sensitivity 83.15%, specificity 57%; YI 0.401). The optimal PAC cut-off value for classifying aldosterone-producing adenoma and idiopathic hyperaldosteronism was 18.12 ng/dL for the SSST (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSST. CONCLUSION: The SSST is safe and convenient for PA diagnosis. The accuracy of the SSST for a confirmatory diagnosis of PA was better than that of the RSST. The SSST is a reliable alternative for PA confirmation in Chinese individuals. ABBREVIATIONS: APA = aldosterone-producing adenoma; ARR = aldosterone to renin ratio; AVS = adrenal vein sampling; CT = computed tomography; EH = essential hypertension; IHA = idiopathic hyperaldosteronism; MRI = magnetic resonance imaging; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; ROC = receiver operating characteristic; RSST = recumbent saline suppression test; SSST = seated saline suppression test; YI = Youden index.

The association of circulating irisin with metabolic risk factors in Chinese adults: a cross-sectional community-based study.

BACKGROUND: Irisin is a myokine that leads to increased energy expenditure by stimulating the browning of white adipose tissue. We aimed to investigate the association of serum irisin levels with metabolic parameters in middle aged Chinese population. METHODS: The study was based on a cross-sectional analysis of data from 524 nondiabetic subjects aged 40~65. All participants were recruited from a screening survey for Metabolic Syndrome in a community in Southwest China, including 294 subjects categorized as overweight (defined as BMI≧25 kg/m2) and 230 subjects as normal control (defined as 18.5≦BMI < 25 kg/m2). Serum irisin concentration was quantified by enzyme linked immunosorbent assay (ELISA). The relationship of irisin with metabolic factors was determined by Pearson correlation. Multivariate linear regression was used to analyze the association of irisin with insulin resistance. Logistic regression was performed to assess the association of irisin with odds of overweight. RESULTS: Serum irisin levels were significantly lower in nondiabetic overweight subjects compared with control (11.46 ± 4.11vs14.78 ± 7.03 µg/mL, p = 0.02). Circulating irisin was positively correlated with quantitative insulin sensitivity check index (QUICKI, r = 0.178, p = 0.045) and triglycerides (r = 0.149, p = 0.022); while irisin was negatively correlated with waist circumference (WC, r = - 0.185, p = 0.037), waist-to-hip ratio (WHR, r = - 0.176, p = 0.047), fasting insulin (r = - 0.2, p = 0.024), serum creatinine (r = - 0.243, p = 0.006), homeostasis model assessment for insulin resistance (HOMA-IR, r = - 0.189, p = 0.033). Multiple linear regression showed that irisin was inversely associated with HOMA-IR (ß = - 0.342 ± 0.154, p = 0.029). Higher irisin was associated with decreased odds of being overweight (OR = 0.281, ß = - 1.271, p = 0.024). CONCLUSIONS: We found that serum irisin levels were lower in overweight subjects. Moreover, serum irisin levels were inversely correlated with adverse metabolic parameters including WC, WHR, creatinine, HOMA-IR and fasting insulin, suggesting that irisin may play a role in obesity related insulin resistance.

Bisphosphonates as a therapeutic choice for multifocal epithelioid hemangioma of bone: A case report.

RATIONALE: Epithelioid hemangioma (EH) of bone is an intermediate vascular tumor that can be locally aggressive. The optimum management of multifocal EH of bone is not well delineated. We described our experience treating one patient with multifocal EH of bone in an effort to document the effect of bisphosphonates in bone EH. PATIENT CONCERNS: In this report, a 53-year old male patient presented with back pain which was initially been diagnosed of multiple bone metastatic carcinoma by 18F-FDG PET/CT scan and bone scintigraphy. DIAGNOSIS: CT-guided bone biopsy of ilium indicated that puncture tissue had irregular hyperplasia of thick and thin-walled blood vessels, immunohistochemistry revealed positive staining for CD31 and CD34, negative for CAMTA-1, PCK and EMA, which confirmed the diagnosis of multiple EH. INTERVENTIONS: The patient was treated with 4 times of intravenous Zometa (zoledronate, 4 mg each time) with average three-month interval. Bone metabolic markers including serum bone specific alkaline phosphatase (BALP) and type I collagen cross-linked C-terminal telopeptide (CTX) levels were closely monitored before and after use of bisphosphonates each time. OUTCOME: BALP and CTX were significantly lowered following intravenous Zometa and the back pain improved with integrated therapy including bone graft fusion internal fixation surgery and vertebroplasty. CONCLUSIONS: EH of multiple bones responded favorably to intravenous Zometa with improvement of bone metabolic markers. After 1 year on follow-up, the patient was doing well with no significant pain. We suggest that bisphosphonates should be considered in the treatment of multifocal osteolytic EH of bone.

Visceral fat is associated with elevation of serum alanine aminotransferase and gamma glutamyltransferase in middle-aged Chinese adults.

BACKGROUND : Elevation of hepatic enzymes is associated with insulin resistance, dyslipidaemia and obesity. However, the factors behind elevation of liver enzymes remain unclear. The aim of this study was to compare the role of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in relation with serum alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) in middle-aged Chinese adults. METHODS : We performed a cross-sectional study on 959 adults aged 40-65 without hepatitis. VAT and SAT were measured at the level of L4-L5 by MRI. Pearson correlation and linear regression were performed to assess the association of VAT/SAT with serum ALT and GGT. Logistic regression was used to evaluate the association of VAT and SAT with high ALT (≥40 U/L) and high GGT (≥35 U/L). RESULTS: VAT had higher correlation coefficient r with ALT and GGT than SAT. VAT, but not SAT, was associated with ALT (males: ß=0.15, p=0.01; females: ß=0.17, p=0.02) and GGT (males: ß=0.39, p<0.0001) in linear regression. VAT remained to be associated with GGT in males (ß=0.33, p=0.0001) when was further adjusted. Logistic regression showed that VAT was associated with elevated GGT (OR=2.218, p=0.043) in males but not in females and no such association was observed for SAT. CONCLUSIONS: Increased VAT, but not SAT, was associated with elevation of hepatic enzymes including ALT and GGT. Moreover, VAT was associated with elevated GGT independent of insulin resistance and subcutaneous fat in males.

Evaluation of the HbA1c Reduction Cut Point for a Nonglycemic Effect on Cardiovascular Benefit of Hypoglycemic Agents in Patients with Type 2 Diabetes Based on Endpoint Events.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death among patients with diabetes but can be improved by certain hypoglycemic agents. However, adjudicating criteria on whether improvements are a glycemic or nonglycemic effect of these agents remain unclear. METHODS: Hypoglycemic agents that produce a cardiovascular benefit in nondiabetic patients are considered to do so via a nonglycemic effect. We performed a subgroup analysis for primary and secondary prevention or very high risk of ASCVD in patients with type 2 diabetes (T2DM). Where glycosylated hemoglobin (HbA1c) was reduced to the same extent in a head-to-head comparison, cardiovascular benefits were judged as a nonglycemic effect. Furthermore, by analyzing the endpoints of four important randomized controlled intensive glucose control studies, UKPDS33, ADVANCE, ACCORD, and VADT, we calculated the cut point of HbA1c reduction for a nonglycemic effect on cardiovascular benefit by hypoglycemic agents in ASCVD groups of different severities. RESULTS: For the ASCVD primary prevention group of T2DM, UKPDS33 indicated a reduction in HbA1c < 0.9%, and a cardiovascular benefit within 10 years was considered a nonglycemic effect. For ASCVD secondary prevention or in the very high-risk group, pioglitazone exerted a nonglycemic effect on cardiovascular benefit in nondiabetic patients with insulin resistance; metformin may exert a similar effect in T2DM patients in a head-to-head study. Analysis of T2DM intensive glucose control studies showed a reduction in HbA1c of <1.0%, and a cardiovascular benefit after approximately 5 years was deemed a nonglycemic effect. CONCLUSIONS: For ASCVD primary prevention in T2DM, a reduction in HbA1c < 0.9% and a cardiovascular benefit within 10 years were considered a nonglycemic effect. For ASCVD secondary prevention or in a very high-risk population, a reduction in HbA1c < 1.0% and a cardiovascular benefit within about 5 years were also considered a nonglycemic effect.

Pheochromocytoma crisis presenting with hypotension, hemoptysis, and abnormal liver function: A case report.

RATIONALE: Pheochromocytomas are rare catecholamine-secreting tumors arising from adrenomedullary chromaffin cells, usually causing hypertension, palpitation and headache. However, pheochromocytoma crisis, on the contrary, might present with hypotension, multiple organ dysfunction or even mimicking other diseases, leaving physician with diagnostic difficulties. In this study, we present a case featured hypotension, shock and multiple organ dysfunction syndrome on admission, which nearly lead us to miss the diagnosis of pheochromocytoma. PATIENT CONCERNS: A 14-year-old female student presented with cough, hemoptysis and dyspnea for one week was reported. DIAGNOSES: The laboratory test showed significantly increase in plasma norepinephrine and 24-hour urine norepinephrine, the enhanced CT of bilateral adrenal gland showed two round-like masses (left: 4 × 5 × 3 cm; right: 6 × 4 × 3 cm) with soft tissue density in each adrenal gland. The post-surgical pathology confirmed the diagnosis of pheochromocytoma. INTERVENTIONS: The resection of bilateral adrenal tumors was conducted after the preoperative medical treatment of phenoxybenzamine for two weeks. OUTCOMES: The patient underwent follow-up for a year and a half and showed no signs of recurrence. LESSONS: The diagnosis and treatment process of the patient in this study indicates us that when we meet a patient with hypotension and multiple organ dysfunctions in a relatively short time, the suspicion of pheochromocytoma should not be missed.

Identical anthropometric characteristics of impaired fasting glucose combined with impaired glucose tolerance and newly diagnosed type 2 diabetes: anthropometric indicators to predict hyperglycaemia in a community-based prospective cohort study in southwest China.

OBJECTIVES: To assess the anthropometric characteristics of normoglycaemic individuals who subsequently developed hyperglycaemia, and to evaluate the validity of these measures to predict prediabetes and diabetes. DESIGN: A community-based prospective cohort study. PARTICIPANTS: In total, 1885 residents with euglycaemia at baseline from six communities were enrolled. SETTING: Sichuan, southwest China. PRIMARY OUTCOME MEASURES: The incidences of prediabetes and diabetes were the primary outcomes. METHODS: The waist-to-height ratio (WHtR), body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) of all participants were measured at baseline and during follow-up. A 75 g glucose oral glucose tolerance test was conducted at each survey. RESULTS: During a median of 3.00 (IQR: 2.92-4.17) years follow-up, the cumulative incidence of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined with IGT (IFG+IGT), and newly diagnosed diabetes mellitus (NDDM) were 8.44%, 18.14%, 8.06% and 13.79%, respectively. WHtR, BMI, WC and WHR were significantly different among subjects who subsequently progressed to isolated IFG or IGT, IFG+IGT or NDDM (p<0.05). The anthropometric characteristics of IFG+IGT subjects were similar to those of the NDDM population (p>0.005). All the baseline anthropometric measurements were useful for the prediction of future prediabetes and NDDM (p<0.05). The optimal thresholds for the four measurements were calculated for the prediction of hyperglycaemia, with a WHtR value of 0.52 performing best to identify isolated IFG or IGT, IFG+IGT and NDDM. CONCLUSIONS: Anthropometric measures, especially WHtR, could be used to predict hyperglycaemia 3 years in advance. Distinct from isolated IFG and IGT, the individuals who developed combined IFG+IGT had identical anthropometric profiles to those who progressed to NDDM.

Consideration of the diagnosis of hypertension accompanied with hypokalaemia: monism or dualism?

This case report describes a 53-year-old male patient with persistent hypertension and hypokalaemia. Laboratory tests showed that the patient had hypokalaemia, hypocalcaemia and reduced urine calcium/creatinine. Levels of aldosterone and renin activity were increased significantly. Serum levels of adrenocorticotropic hormone, plasma total cortisol level, 24-h urinary-free cortisol, catecholamines, thyroid stimulating hormone and free tetraiodothyronine were normal. A novel single heterozygous mutation (c.836T> G [E6]) was found after full sequencing of the solute carrier family 12 member 3 ( SLC12A3) gene exons. The patient was diagnosed as having primary hypertension with Gitelman syndrome (GS). These findings triggered the careful consideration of whether a monistic or dualist approach to the diagnosis of this patient was the most appropriate. Monism may not always be the most appropriate approach for the diagnosis of coexistent hypertension and hypokalaemia. Consideration should be given to the possibility of the independent existence of distinct diseases (i.e. dualism) when secondary hypertension cannot be confirmed by conventional examinations and when a genetic diagnosis is crucial. As a common cause of hypokalaemia with a high level of clinical phenotypic variation, GS does not conform to the usual diagnostic criteria. It should also be noted that single heterozygous SLC12A3 gene mutations can cause disease symptoms and other genetic mutations might be involved in the pathogenesis of GS.

Evaluation of brain targeting in rats of Salvianolic acid B nasal delivery by the microdialysis technique.

The purpose of this study was to investigate the biodistribution of Salvianolic acid B in rats blood and brain after intranasal administration and explore its feasibility and evaluate its brain targeting effect. The concentration of Salvianolic acid B in blood and brain following nasal administration (32 mgckg-1) was measured combining with microdialysis sampling and liquid chromatograph-mass spectrometer/MS detection technology. After the microdialysis samples were corrected with in vivo recoveries, the pharmacokinetic parameters were obtained by using non-compartment model and the brain targeting evaluated by the value of drug targeting index (DTI). The Cmax in blood and brain by intravenous injection were higher than intranasal administration, but the intranasal administration of MRT0-∞ significantly prolonged and increased by nearly 2.03 and 1.86 times, respectively. The DTI value of Salvianolic acid B was 5.54 and bioavailability (F) was 43.98%. After nasal administration of Salvianolic acid B, it has a certain brain targeting, which could become a new drug system for the treatment of brain diseases.

Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with and without overweight/obesity: meta-analysis of randomized controlled trials.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI. Among 3190 searched studies, 20 trials were included in the meta-analysis. The standardized mean differences in HbA1c change, fasting glucose change, and postprandial glucose change were equivalent between normal BMI and overweight/obese studies (p > 0.05). The relative risk of HbA1c < 6.5% target achievement in normal BMI trials (7.93; 95% confidence interval: 3.27, 19.20) was superior to that in overweight/obesity trials (2.23; 1.67, 2.97), with a significant difference (p = 0.020). Body weight loss (p = 0.572) and hypoglycemic risk(p = 0.920) were similar in the two groups. The glucose-lowering effects of GLP-1RAs were equivalent among Asian T2D patients. With their advantages for weight-loss or weight-maintenance, GLP-1RAs are optimal medicines for Asian T2D patients with and without overweight/obesity.

Cardiovascular effects of dipeptidyl peptidase-4 inhibitor in diabetic patients with and without established cardiovascular disease: a meta-analysis and systematic review.

OBJECTIVES: We aim to conduct a meta-analysis, by stratifying diabetic patients with or without clinical cardiovascular diseases (CVD), to explore whether there are different cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) on these two different classes of diabetic patients. METHODS: We searchedMedline,Embase, theCochrane Libraryand ClinicalTrials.gov for relevant randomized controlled trials (RCTs). The included trials are divided into CVD (+) trials (subjects with established CVD), and CVD (-) trials (subjects with no CVD). We use all-cause mortality and cardiovascular outcomes as primary endpoints. RESULTS: (1) Three CVD (+) trials were included and 36,895 subjects were enrolled with a mean follow-up duration of 127.1 weeks. The pooled results showed that DPP-4is treatment, compared with the placebo, did not significantly affect all-cause mortality (RR, 1.03; 95% CI, 0.95 to 1.11), cardiovascular death (1.01, 0.91 to 1.12), myocardial infarction (0.98, 0.88 to 1.08) or stroke (1.02, 0.88 to 1.18) in diabetic patients with coexisting CVD history; however, it significantly increased the risk of heart failure (1.14, 1.01 to 1.27) in this population. 2) Thirty-five CVD (-) trials were included, and 29,600 patients were enrolled with a mean follow-up duration of 77.8 weeks. The analysis comparing DPP-4is with the placebo control showed that DPP-4is treatment did not significantly affect the risk of all-cause mortality or cardiovascular outcomes in diabetic patients free of CVD history. However, when compared with the active control, the pooling data showed that DPP-4is had a significant reduction on the risk of stroke (0.58, 0.34 to 0.99) but did not significantly affect the risk of all-cause mortality and other cardiovascular outcomes. CONCLUSION: DPP-4is may have no cardiovascular protective effects in diabetic patients with coexisting CVD, while there is a lack of definitive evidence supporting the cardiovascular benefits of DPP-4is treatment among diabetic patients free of CVD history.