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Background. Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective. A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods. We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results. A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and P = 0.006 ) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and P < 0.0001 ). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and P = 0.002 ) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and P < 0.0001 ). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and P < 0.00001 ) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and P = 0.0005 ). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions. TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.

Yu-fan Yang,1,* Hui Wang,1,2,* Nan Song,1,* Ya-hui Jiang,1 Jun Zhang,1 Xiao-wen Meng,1 Xiao-mei Feng,3,4 Hong Liu,5 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, University of Utah Health, Salt Lake City, UT, USA; 4Transitional Residency Program, Intermountain Medical Center, Murray, UT, USA; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comBackground: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury.Methods: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α 2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment.Results: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α 2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312.Conclusion: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.Keywords: myocardial ischemia/reperfusion injury, dexmedetomidine, endoplasmic reticulum stress, inflammation, apoptosis, GRP78/PERK/CHOP

Background:Older hypertensive adults are at increased risk for postoperative morbidity and mortality. As first line antihypertensive drug therapy, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have many beneficial effects. However, the use of ACEIs/ARBs in the perioperative period remains controversial. This study aims to determine the effects of withholding vs. continuing ACEIs/ARBs before non-cardiac surgery on perioperative hypotension and postoperative outcomes in older patients.Methods:In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 2036 patients aged 60–80 years undergoing non-cardiac surgical procedures will be randomly assigned, in a 1:1 ratio, to receive oral ACEIs/ARBs (the ACEIs/ARBs continued group) or inactive placebos (the ACEIs/ARBs withheld group) on the morning of surgery. For both groups, the ACEIs/ARBs will be continued from the first postoperative day. The primary outcome measure is the incidence of perioperative hypotensive events, defined as mean blood pressure (MBP) < 65 mmHg or ≥30% reduction in MBP from baseline during surgery and in a post-anesthesia care unit. The secondary outcomes include duration of perioperative hypotension, intraoperative use of fluids and vasopressors, hypotensive events within postoperative 3 days, and perioperative neurocognitive disorders, major adverse cardiocerebral events (a composite outcome of stroke, coma, myocardial infarction, heart block, and cardiac arrest), and mortality within 30 days after surgery.Discussion:The results of this trial will offer an evidence-based perioperative ACEIs/ARBs therapy for older hypertensive adults undergoing non-cardiac surgery.Study Registration:This study is approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (Approval No. 2020-077-1) and by the institutional ethics review board of each participating center. This protocol is registered at the Chinese Clinical Trials Registry (ChiCTR2000039376).

© 2016 John Wiley & Sons Australia, Ltd Pharmacological preconditioning reduces myocardial infarct size in ischaemia-reperfusion (I-R) injury. Dexmedetomidine, a selective α2-adrenoceptor agonist, has a proven cardioprotective effect when administered prior to I-R, although the underlying mechanisms for this effect are not fully understood. We evaluated whether dexmedetomidine preconditioning could induce a myocardio-protective effect against I-R injury by inhibiting associated inflammatory processes through downregulation of the high mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4)-nuclear factor κB (NF-κB) signalling pathway. Seventy rats were randomly assigned to seven groups: a control and six test groups, involving I-R for 30 and 120 minutes, respectively, in isolated rat hearts and different pretreatment protocols with dexmedetomidine (10 nmol/L) as well as yohimbine (1 μmol/L) and recombinant HMGB1 peptide (rHMGB1; 20 μg/L), alone or in combination with dexmedetomidine. Cardiac function was recorded; myocardial HMGB1, TLR4, and NF-κB activities and levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured as were lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary outflow. Dexmedetomidine preconditioning significantly improved cardiac function (P