Predicted lean body mass, fat mass, and heart failure in patients with type 2 diabetes mellitus.

BACKGROUND: High body mass index (BMI) is associated with a higher risk of heart failure (HF) in patients with new-onset type 2 diabetes mellitus (T2DM). However, limited studies have investigated the independent association between fat mass or lean body mass and HF risk among T2DM patients with cardiovascular disease (CVD) or high CVD risk. OBJECTIVES: To investigate the association between fat mass index (FMI, kg/m2) or lean BMI (LBMI, kg/m2) and HF risk. METHODS: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional-hazards models were applied to evaluate the association of FMI, LBMI, and BMI with HF risk. Discordant analysis was performed to compare the magnitude of this associations. RESULTS: HF occurred in 356 participants (3.7%). After adjusting for confounding factors, higher FMI values were independently associated with HF risk (HR: 1.72, 95% CI: 1.15-2.57, each 1 SD increase in FMI); LBMI was a protective risk factor for HF (HR: 0.58, 95% CI: 0.38-0.87,). After further adjusting for FMI, the association between BMI and HF risk (HR, 0.97; 95% CI, 0.67-1.42) disappeared. Compared with concordant values below the medians, discordant FMI above the median with BMI below yielded an HR of 1.78 (95% CI: 1.14-2.78) for HF. In contrast, BMI above the median with FMI below was not associated with HF risk (HR: 1.09, 95% CI: 0.57-2.09). CONCLUSIONS: The risk of HF conferred by higher BMI was primarily driven by the association between FMI and HF. After adjusting for BMI, LBMI played a protective role.

Efficacy and safety of zimberelimab (GLS-010) monotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, single-arm, phase II study.

OBJECTIVE: There is an unmet need to improve clinical outcomes for patients with recurrent/metastatic cervical cancer. Checkpoint inhibitors represent a promising treatment strategy. We evaluated the safety and anti-tumor activity of zimberelimab, an anti-programmed cell death protein-1 antibody, in patients with previously treated, recurrent, metastatic cervical cancer. METHODS: This phase II, single-arm, open-label study used a Simon two-stage minimax design. Eligible patients were women aged 18-75 years with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line chemotherapy (Eastern Cooperative Oncology Group (ECOG) performance status 0-1). Patients received intravenous zimberelimab (240 mg every 2 weeks) for 2 years until disease progression, intolerable adverse effects, or withdrawal from the study. The primary endpoint was objective response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, by an independent review committee. RESULTS: A total of 105 patients were enrolled. Median age was 51 (range, 31-75) years; 63.8% had an ECOG performance status of 1. The median number of previous treatment lines was 1 (range, 1-4). Median follow-up was 16.9 (range, 16.3-18.4) months. The objective response rate was 27.6%, and the disease control rate was 55.2%. Median duration of response was not reached. Median overall survival was 16.8 months, and median progression-free survival was 3.7 months. The incidence of treatment-related adverse events of any grade was 78.1%, of which the most common were hypothyroidism (26.7%) and anemia (19.0%). CONCLUSION: Zimberelimab monotherapy demonstrated durable anti-tumor activity and an acceptable safety profile in patients with cervical cancer. CLINICAL TRIAL REGISTRATION: NCT03972722.

Serum brain-derived neurotrophic factor in coronary heart disease: Correlation with the T helper (Th)1/Th2 ratio, Th17/regulatory T (Treg) ratio, and major adverse cardiovascular events.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts protective roles against dyslipidemia, atherosclerosis, and inflammation in cardiovascular diseases; meanwhile, it retards CD4+ T cell differentiation into T helper (Th)1 and Th17 cells. Hence, this study aimed to investigate the linkage of serum BDNF with Th1/Th2 ratio, Th17/regulatory T (Treg) ratio, and major adverse cardiovascular events (MACE) risk in the coronary heart disease (CHD) patients. METHODS: This prospective study detected serum BDNF in 210 CHD patients, 50 disease controls (DCs), and 50 healthy controls (HCs) using an enzyme-linked immunosorbent assay. For CHD patients only, the proportion of Th1, Th2, Th17, and Treg cells in blood CD4+ T cells was calculated by flow cytometry. RESULTS: The BDNF varied among CHD patients, DC, and HC (p < 0.001). Specifically, BDNF was declined in CHD patients compared with DCs (p < 0.001) and HCs (p < 0.001). In CHD patients, BDNF was negatively related to Th1 cells (p = 0.031), Th1/Th2 ratio (p = 0.026), Th17 cells (p = 0.001), and Th17/Treg ratio (p = 0.002). Concerning the prognosis, BDNF was reduced in patients with MACE occurrence compared to patients without MACE occurrence (p = 0.006). Furthermore, BDNF showed a trend (lacked statistical significance) to relate to longer MACE-free survival (p = 0.059). Besides, BDNF was related to the absence of obesity (p = 0.019), decreased total cholesterol (p = 0.043), low-density lipoprotein cholesterol (p = 0.019), C-reactive protein (p = 0.012), and Gensini score (p = 0.005). CONCLUSION: Serum BDNF negatively correlates with Th1/Th2 ratio, Th17/Treg ratio, and estimates lower MACE risk in CHD patients.

Clinical value of long non-coding RNA KCNQ1OT1 in estimating the stenosis, lipid level, inflammation status, and prognostication in coronary heart disease patients.

OBJECTIVE: Long non-coding RNA KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) could regulate lipid metabolism, vascular smooth muscle cell function, inflammation, and atherosclerosis. This study aimed to evaluate whether lncRNA KCNQ1OT1 could serve as a biomarker for reflecting coronary heart disease (CHD) patients' disease situation and prognosis. METHODS: LncRNA KCNQ1OT1 expression was determined in peripheral blood mononuclear cells from 267 CHD patients, 50 disease controls (DCs) (unexplained chest pain), and 50 healthy controls (HCs) by the RT-qPCR method. TNF-α, IL-17A, VCAM-1, and ICAM-1 were determined by the ELISA procedure in serum from CHD patients only. The mean (95% confidential interval) follow-up duration was 16.0 (15.3-16.8) months. RESULTS: LncRNA KCNQ1OT1 was highest in CHD patients, followed by DCs, and lowest in HCs (p < 0.001). LncRNA KCNQ1OT1 could distinguish the CHD patients from DCs (area under the curve [AUC]: 0.757) and from the HCs (AUC: 0.880). LncRNA KCNQ1OT1 was positively associated with triglyceride (p = 0.026), low-density lipoprotein cholesterol (p = 0.023), cardiac troponin I (p = 0.023), and C-reactive protein (p = 0.001). Besides, lncRNA KCNQ1OT1 was also positively linked with the Gensini score (p = 0.008). Furthermore, lncRNA KCNQ1OT1 was positively related to the TNF-α (p < 0.001), IL-17A (p = 0.008), and VCAM-1 (p = 0.003). LncRNA KCNQ1OT1 was elevated in CHD patients with MACE compared to those without MACE (p = 0.006); moreover, lncRNA KCNQ1OT1 high was associated with shorter MACE-free survival (p = 0.018). CONCLUSION: Circulating lncRNA KCNQ1OT1 expression not only reflects the stenosis degree, blood lipid level, and inflammation status but also predicts the MACE risk, while a large-scale study is needed for verification.

Effect of Multimodal Preemptive Analgesia of Flurbiprofen Axetil, Nalbuphine, and Retrobulbar Block on Postoperative Pain and Enhanced Recovery in Patients Undergoing Oculoplastic Day Surgery: A Prospective, Randomized, Double-Blinded Study.

PURPOSE: To evaluate the effect of either flurbiprofen axetil or nalbuphine combined with retrobulbar block (RB) before surgery on postoperative pain control and enhanced recovery in day-care patients undergoing orbital implantation. METHODS: A total of 45 patients undergoing orbital implantation with general anesthesia were randomly divided into three groups: flurbiprofen axetil (1 mg/kg) combined with RB (group F), nalbuphine (0.1 mg/kg) combined with RB (group N), and placebo as normal saline with RB (group C). The primary outcome was the average pain score (numeric rating scale: 0-10) within the first 24 hours. Other outcomes including the peak pain score, paracetamol requirement, quality of recovery (QoR)-15, and adverse effects (AEs) were assessed. RESULTS: The average and peak pain scores within 24 hours after surgery in group F were significantly lower than in other groups ( p < 0.0167). Compared with group C, the NRS scores were significantly decreased at 2 and 4 hours in group F, and 2 hours in group N after surgery ( p < 0.0167), but without significant differences at other measured time points. The time to first paracetamol oral intake displayed a significant difference among the three groups ( p < 0.0167). CONCLUSION: Preemptive use of flurbiprofen axetil 1 mg/kg combined with RB is an optimal choice for multimodal analgesia for day-care patients undergoing orbital implantation in terms of efficient acute pain control, without impeding patient-enhanced recovery.

MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-κB pathways by targeting CCAR2.

OBJECTIVES: Ischemic stroke causes high morbidity, mortality and health burden in the world. MiR-342-5p was associated with Alzheimer's disease and cardio-protection. Herein, we aimed to reveal effects of miR-342-5p on cerebral ischemia injury as well as novel targets for stroke. MATERIALS AND METHODS: AgomiR-342-5p was intracerebroventricularly injected into the middle cerebral artery occlusion (MCAO) mouse models to evaluate functions of miR-342-5p on cerebral ischemia. RT-qPCR and western blot assays were used to evaluate genes expression. Oxygen-glucose deprivation (OGD) was used as an in vitro model for ischemia. Viability and apoptosis ratio of neurons was evaluated by CCK-8, LDH release detection, and flow cytometry. The potential targets of miR-342-5p were predicted by Targetscan, and their interaction was confirmed by luciferase assay. RESULTS: The intervention of miR-342-5p effectively attenuated ischemic injury in MCAO mice. MiR-342-5p overexpression could protect neurons against OGD-induced injury, as revealed by increased cell viability and BCL2 expression, and decreased LDH release, apoptosis ratio, and BAX expression in OGD-induced neurons. Mechanically, miR-342-5p could directly bound with CCAR2 to inhibit its expression. Overexpressing CARR2 aggravated the OGD-induced injury of neurons, which was partly restrained by overexpressing miR-342-5p reversed. Furthermore, miR-342-5p/CARR2 axis regulates Akt/NF-κB signaling pathway in vitro as well as in vivo cerebral ischemia models. CONCLUSIONS: MiR-342-5p inhibited neuron apoptosis by regulating Akt/NF-kB signaling pathway via CCAR2 suppression. Our findings revealed the neuroprotection of miR-342-5p in cerebral ischemia.

The efficiency of quick response code versus telephone contact for post-discharge follow-up after ophthalmic day surgery: a randomized controlled trial.

PURPOSE: To assess and compare the efficiency of quick response (QR) code versus telephone contact for post-discharge follow-up in patients receiving low-risk ophthalmic day surgery. METHODS: One hundred and sixty patients undergoing strabismus day-care surgery with general anesthesia were randomly allocated to either the intervention group using QR code (QR group) or the control group receiving telephone call (TEL group) for post-discharge follow-up. The primary outcome was the follow-up overall attendance rate on the second postoperative day. Secondary outcomes included attendance rate at the first scheduled follow-up, number of text message reminders, elapsed time and estimated cost for follow-up, omission rate of follow-up responses, and patient satisfaction. RESULTS: The overall attendance rate of follow-up was significantly higher in the QR group than that in the TEL group (97.5% vs. 87.5%, p = 0.016). As compared with the TEL group, the QR group significantly reduced the number of text message reminders with higher attendances at the first scheduled follow-up (p < 0.001, p = 0.001). Besides, the TEL group cost a median time of 258 s and a median cost of RMB 5.8 yuan to complete a follow-up consultant, but was associated with a significantly high omission rate of follow-up responses comparing to the QR group (p = 0.002). Patient satisfaction was comparable between two groups. CONCLUSION: QR code follow-up can be more efficient than traditional telephone contact in assessing the post-discharge recovery after strabismus day surgery, which provides a safe and intuitively alternative follow-up pathway for identifying issues that may necessitate further clinical care for more low-risk ophthalmic day surgeries.

Preparation, Characterization, and Mechanism of Antifreeze Peptides from Defatted Antarctic Krill (Euphausia superba) on Lactobacillus rhamnosus.

Defatted Antarctic krill powder is the main by-product in the manufacturing of krill oil. Exploring a high value-added approach for utilizing this protein-rich material has received much attention in research and industry. Given this, the preparation and primary characterization of antifreeze peptides from defatted Antarctic krill (AKAPs) were carried out in this study. The cryoprotective effect of AKAPs on Lactobacillus rhamnosus ATCC7469 was also investigated. The results showed that Protamex was the optimum protease for AKAP preparation from defatted Antarctic krill. AKAPs were found to be rich in short peptides, with the MW ranging from 600 to 2000 Da (69.2%). An amino acid composition analysis showed that AKAPs were rich in glutamic acid (18.71%), aspartic acid (12.19%), leucine (7.87%), and lysine (7.61%). After freezing, the relative survival rate of Lactobacillus rhamnosus in the 1.0 mg/mL AKAP-treated group (96.83%) was significantly higher than in the saline group (24.12%) (p < 0.05). AKAPs also retarded the loss of acidifying activity of L. rhamnosus after freezing. AKAPs showed even better cryoprotective activity than three commercial cryoprotectants (sucrose, skim milk, and glycerol). In addition, AKAPs significantly alleviated the decrease in ß-galactosidase and lactic dehydrogenase activities of L. rhamnosus (p < 0.05). Furthermore, AKAPs effectively protected the integrity of L. rhamnosus cell membranes from freezing damage and alleviated the leakage of intracellular substances. These findings demonstrate that AKAPs can be a potential cryoprotectant for preserving L. rhamnosus, providing a new way to use defatted Antarctic krill.

Stem cell-like memory T cells: A perspective from the dark side.

Much attention has been paid to a newly discovered subset of memory T (TM) cells-stem cell-like memory T (TSCM) cells for their high self-renewal ability, multi-differentiation potential and long-term effector function in adoptive therapy against tumors. Despite their application in cancer therapy, an excess of TSCM cells also contributes to the persistence of autoimmune diseases for their immune memory and HIV infection as a long-lived HIV reservoir. Signaling pathways Wnt, AMPK/mTOR and NF-κB are key determinants for TM cell generation, maintenance and proinflammatory effect. In this review, we focus on the phenotypic and functional characteristics of TSCM cells and discuss their role in autoimmune diseases and HIV-1 chronic infection. Also, we explore the potential mechanism and signaling pathways involved in immune memory and look into the future therapy strategies of targeting long-lived TM cells to suppress pathogenic immune memory.

Incidence and Risk Factors of Moderate to Severe Postoperative Pain Following the Placement of Primary and Secondary Orbital Implants: A Prospective Observational Study.

PURPOSE: To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. METHODS: One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. RESULTS: Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. CONCLUSIONS: Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.

Vitamin C-dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition.

Hematopoietic stem cells (HSCs)/progenitor cells (HPCs) are generated from hemogenic endothelial cells (HECs) during the endothelial-to-hematopoietic transition (EHT); however, the underlying mechanism remains poorly understood. Here, using an array of approaches, including CRSPR/Cas9 gene knockouts, RNA-Seq, ChIP-Seq, ATAC-Seq etc., we report that vitamin C (Vc) is essential in HPC generation during human pluripotent stem cell (hPSC) differentiation in defined culture conditions. Mechanistically, we found that the endothelial cells generated in the absence of Vc fail to undergo the EHT because of an apparent failure in opening up genomic loci essential for hematopoiesis. Under Vc deficiency, these loci exhibited abnormal accumulation of histone H3 trimethylation at Lys-27 (H3K27me3), a repressive histone modification that arose because of lower activities of demethylases that target H3K27me3. Consistently, deletion of the two H3K27me3 demethylases, Jumonji domain-containing 3 (JMJD3 or KDM6B) and histone demethylase UTX (UTX or KDM6A), impaired HPC generation even in the presence of Vc. Furthermore, we noted that Vc and jmjd3 are also important for HSC generation during zebrafish development. Together, our findings reveal an essential role for Vc in the EHT for hematopoiesis, and identify KDM6-mediated chromatin demethylation as an important regulatory mechanism in hematopoietic cell differentiation.

Knockdown of SNHG1 inhibits cervical cancer growth through sponging miR-194 to regulate HCCR.

AIM: To investigate the mechanism of small nucleolar RNA host gene 1 (SNHG1) in cervical cancer (CC). Methods: The expression of SNHG1, miR-194 and human cervical cancer oncogene (HCCR) in CC tissues and cells was detected using qRT-PCR and western blot. The interaction among the three molecules was measured using dual-luciferase reporter assay and RNA immunoprecipitation assay. The function of SNHG1 in CC cells was detected by CKK-8 assay and flow cytometry analysis. Results: SNHG1 was highly expressed in CC tissues and CC cell lines. Knockdown of SNHG1 inhibited CC cell proliferation and enhanced the ability of cell apoptosis. Mechanism investigation revealed that SNHG1 modulated HCCR expression via acting as a competing endogenous RNA of miR-194. Moreover, miR-194 inhibitor changed the effects of si-SNHG1 on CC cells growth. In vivo experiment, silencing of SNHG1 suppressed CC tumor growth by modulating miR-194/HCCR axis. Conclusion: Knockdown of SNHG1 inhibited CC progression by targeting HCCR via sponging with miR-194.

Using Clinical-Based Discharge Criteria to Discharge Patients After Ophthalmic Ambulatory Surgery Under General Anesthesia: An Observational Study.

PURPOSE: To verify the feasibility of the clinical-based discharge (CBD) criteria and identify the reasons of long postanesthesia care unit length of stay (PACU-LOS) for ophthalmic ambulatory surgical patients under general anesthesia. DESIGN: A prospectively observational study conducted at a tertiary eye center in China. METHODS: Medical records were collected from patients admitted for strabismus ambulatory surgery under general anesthesia from September 2018 to March 2019. The patients were discharged home once met the CBD criteria based on a combination of the modified Aldrete's scoring system and Chung's Post-Anesthetic Discharge Scoring System. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate logistic regression was applied to identify the factors relating to late discharges. FINDINGS: All patients (N = 400) were safely and successfully same-day discharged home as none of the patients informed severe emergency events or unanticipated readmission. Nine displayed discharge delays mainly because of mild postoperative nausea and vomiting (PONV) although met the discharge criteria. About 85.5% of patients were discharged within a PACU-LOS of 150 minutes, 379 (94.8%) were within 180 minutes, and the cutoff time in PACU-LOS was 150 minutes. Multivariable analysis indicated that sevoflurane anesthesia and the presence of PONV were related to late discharges (PACU-LOS of greater than 150 minutes, all P < .05). CONCLUSIONS: The CBD criteria can efficiently and safely guide the ophthalmic ambulatory surgical patients to discharge home on the same-surgery day, whereas sevoflurane anesthesia and the presence of PONV are associated with a relatively long PACU-LOS.

LncRNA TUSC8 inhibits the invasion and migration of cervical cancer cells via miR-641/PTEN axis.

Cervical cancer (CC) is the fourth leading cause of cancer-related death in women worldwide. There is an urgent need to find novel targets for the treatment of CC. Recently, microRNA have emerged as critical factors in tumorigenesis. In this study, we aimed to investigate the mechanism of miR-641 on the migration and invasion of CC cells. In silico analysis revealed putative interaction between miR-641 and phosphatase and tensin homolog (PTEN) RNA/lncRNA tumor suppressor candidate 8 (TUSC8). Hence we evaluated the expression of TUSC8, miR-641, and PTEN. We found that the expressions of TUSC8 and PTEN were decreased in CC tissues, whereas miR-641 expression was increased. Inhibition of miR-641 suppressed the migration and invasion of Hela cells. In addition, TUSC8 and PTEN were upstream and downstream target molecule of miR-641, respectively. Overexpression of TUSC8 promoted PTEN expression, and suppressed the invasion and migration of Hela cells, whereas miR-641 mimic treatment changed the effects. These results demonstrated that overexpression of TUSC8 could inhibit the invasion and migration of CC cells by upregulating PTEN via miR-641.

Cricoid-mental distance-based versus weight-based criteria for size selection of classic laryngeal mask airway in adults: a randomized controlled study.

The optimal size selection of laryngeal mask airway (LMA) based on body weight is not always applicable. This study was prospectively conducted to evaluate the efficacy of cricoid-mental distance-based method versus weight-based method in optimal size selection of LMA in adults. Seventy-four patients (aged from 18 to 65) undergoing ophthalmic surgery were randomly assigned into cricoid-mental (CM) distance-based group or weight-based group to select appropriate size of LMA. The primary outcome was oropharyngeal leak pressure (OLP). Secondary outcomes included overall insertion success rate, number of insertion attempts, time to successful insertion, ease of insertion, score of fiber-optic view, peak inspiratory pressure during mechanical ventilation and postoperative pharyngolaryngeal morbidity. The OLP was significantly higher in CM distance-based group than that in weight-based group (19.38 ± 3.52 vs. 17.50 ± 3.18, P = 0.022). The successful placement at the first attempt in CM distance-based group was dramatically increased as compared with weight-based group (89.2% vs. 62.2%, P = 0.005). The overall success rate of LMA insertion in CM distance-based group was slightly increased in comparison with the weight-based group (100% vs. 91.9%, P = 0.240). There were no significant differences in score of fiber-optic view and postoperative pharyngolaryngeal morbidity between both groups (all P > 0.05). CM distance-based criteria is an alternative choice for optimizing size selection of classic LMA in adults.

MiR-125b-2 Knockout in Testis Is Associated with Targeting to the PAP Gene, Mitochondrial Copy Number, and Impaired Sperm Quality.

It has been reported that the miR-125 family plays an important role in regulating embryo development. However, the function of miR-125b-2 in spermatogenesis remains unknown. In this study, we used a model of miR-125b knockout (KO) mice to study the relationship between miR-125b-2 and spermatogenesis. Among the KO mice, the progeny test showed that the litter size decreased significantly (p = 0.0002) and the rate of non-parous females increased significantly from 10% to 38%. At the same time, the testosterone concentration increased significantly (p = 0.007), with a remarkable decrease for estradiol (p = 0.02). Moreover, the sperm count decreased obviously (p = 0.011) and the percentage of abnormal sperm increased significantly (p = 0.0002). The testicular transcriptome sequencing revealed that there were 173 up-regulated genes, including Papolb (PAP), and 151 down-regulated genes in KO mice compared with wild type (WT). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis showed that many of these genes were involved in sperm mitochondrial metabolism and other cellular biological processes. Meanwhile, the sperm mitochondria DNA (mtDNA) copy number increased significantly in the KO mice, but there were no changes observed in the mtDNA integrity and mutations of mt-Cytb, as well as the mt-ATP6 between the WT mice and KO mice. In the top 10 up-regulated genes, PAP, as a testis specific expressing gene, affect the process of spermatogenesis. Western blotting and the Luciferase assay validated that PAP was the target of miR-125b-5p. Intriguingly, we also found that both miR-125b and PAP were only highly expressed in the germ cells (GC) instead of in the Leydig cells (LC) and Sertoli cells (SC). Additionally, miR-125b-5p down regulated the secretion of testosterone in the TM3 cell by targeting PAP (p = 0.021). Our study firstly demonstrated that miR-125b-2 regulated testosterone secretion by directly targeting PAP, and increased the sperm mtDNA copy number to affect semen quality. The study indicated that miR-125b-2 had a positive influence on the reproductive performance of animals by regulating the expression of the PAP gene, and could be a potential drugs and diagnostic target for male infertility.

The first case of ischemia-free organ transplantation in humans: A proof of concept.

Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man. The recipient was a 51-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved, and implanted under continuous normothermic machine perfusion. The recipient did not suffer post-reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post-transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, or vascular or biliary complications occurred. The patient was discharged on day 18 post-transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization.

Suppressing P16Ink4a and P14ARF pathways overcomes apoptosis in individualized human embryonic stem cells.

Dissociation-induced apoptosis is a striking phenomenon in human embryonic stem cells (hESCs), but not in naive mouse ESCs. Rho-associated kinase-dependent actin-myosin hyperactivation is an underlying mechanism that triggers apoptosis in dissociated hESCs; however, in this study, we show that the Ink4A-ARF-mediated senescence pathway is another mechanism to cause apoptosis in individualized hESCs. We show that P16INK4A and P14ARF are immediately induced in hESCs upon dissociation, but not in mouse ESCs. Overexpression of BMI1, a suppressor for Ink4A-ARF, greatly promotes survival and cloning efficiency of individualized hESCs mechanistically via direct binding the H3K27me3-marked Ink4A-ARF locus. Forced expression of BMI1 in hESCs does not reduce the actin-myosin activation that is triggered by dissociation, which indicates it is an independent pathway for hESC survival. Furthermore, dual inhibition of both Ink4A-ARF and actin-myosin hyperactivation enables successful passaging of hESCs via gelatin, a nonbioactive matrix. In sum, we provide an additional mechanism that underlies cell death in individualized hESCs that might help to fully understand the differential cell characteristics between naive and primed ESCs.-Wang, W., Zhu, Y., Huang, K., Shan, Y., Du, J., Dong, X., Ma, P., Wu, P., Zhang, J., Huang, W., Zhang, T., Liao, B., Yao, D., Pan, G., Liu, J. Suppressing P16Ink4a and P14ARF pathways overcomes apoptosis in individualized human embryonic stem cells.

miR-146b Inhibits Glucose Consumption by Targeting IRS1 Gene in Porcine Primary Adipocytes.

Adipose tissue plays an important role in energy metabolism. Adipose dysfunction is closely related to obesity and type II diabetes. Glucose uptake is the key step for fat synthesis in adipocyte. miRNAs have been proven to play a crucial role in adipocyte differentiation, adipogenesis and glucose homeostasis. In this paper, we firstly reported that miR-146b decreased glucose consumption by up-regulating miR-146b in a porcine primary adipocyte model, while the inhibitor of endogenous miR-146b rescued the reduction. Then, miR-146b was predicated to target IRS1 by bioinformatics analysis, and a dual-luciferase reporter assay validated this predication. Western blot analyses indicated both IRS1 and glucose transporter type 4 (GLUT4) were down-regulated by miR-146b overexpression. Our study demonstrated that miR-146b regulated glucose homeostasis in porcine primary pre-adipocyte by targeting IRS1, and provided new understandings on regulations of lipogenesis by miRNAs.

Remote Ischemic Preconditioning and Clinical Outcomes in On-Pump Coronary Artery Bypass Grafting: A Meta-Analysis of 14 Randomized Controlled Trials.

The purpose of this article is to perform the first pooled analysis on remote ischemic preconditioning (RIPC) used for the improvement of clinical outcomes of patients only undergoing on-pump coronary artery bypass grafting (CABG) in randomized controlled trials (RCTs). A systematic search was performed using PubMed, the Cochrane Library, and the Web of Science to identify studies that described the effect of RIPC on postoperative mortality in patients only undergoing on-pump CABG. The outcomes included postoperative mortality, postoperative morbidity (including incidence of myocardial infarction, atrial fibrillation, stroke, acute kidney injury, and renal replacement therapy), mechanical ventilation (MV), intensive care unit length of stay (ICU LOS), and hospital length of stay (HLOS). A total of 14 RCTs (2830 participants) were included. Our meta-analysis found that RIPC failed to reduce the postoperative mortality in patients only undergoing on-pump CABG compared with control individuals (odds ratio, 0.81; 95% confidence interval, [0.40, 1.64]; P = 0.55; I2 = 25%). Moreover, there were no differences in postoperative morbidity, ICU LOS, and HLOS between the two groups. However, MV in the RIPC group was shorter than that in control individuals (standard mean difference, -0.41; 95% confidence interval, [-0.80, -0.01]; P = 0.04; I2 = 73%). The present meta-analysis found that RIPC failed to improve most of clinical outcomes in patients only undergoing on-pump CABG; however, MV was reduced. Adequately powered trials are warranted to provide more evidence in the future.