Prognostic value of targeted temperature management on outcomes of hanging-induced out-of-hospital cardiac arrest: A nationwide observational study

This study aimed to evaluate the prognostic significance of targeted temperature management (TTM) on hanging-induced out-of-hospital cardiac arrest (OHCA) patients using nationwide data of South Korea.Adult hanging-induced OHCA patients from 2008 to 2018 were included in this nationwide observational study. Patients who assigned into 2 groups based on whether they did (TTM group) or did not (non-TTM group) receive TTM. Outcome measures included survival to hospital discharge and a good neurological outcome at hospital discharge.Among the 293,852 OHCA patients, 3545 patients (non-TTM, n = 2762; TTM, n = 783) were investigated. After propensity score matching for all patients, 783 matched pairs were available for analysis. We observed no significant inter-group differences in the survival to hospital discharge (non-TTM, n = 27 [3.4%] vs TTM, n = 23 [2.9%], P = .666) or good neurological outcomes (non-TTM, n = 23 [2.9%] vs TTM, n = 14 [1.8%], P = .183). In the multivariate analysis, prehospital return of spontaneous circulation (odds ratio [OR], 22.849; 95% confidence interval [CI], 11.479–45.481, P < .001) was associated with an increase in survival to hospital discharge, and age (OR, 0.971; 95% CI, 0.944–0.998, P = .035), heart disease (OR, 16.875; 95% CI, 3.028–94.036, P = .001), and prehospital return of spontaneous circulation (OR, 133.251; 95% CI, 30.512–581.930, P < .001) were significant prognostic factors of good neurological outcome. However, TTM showed no significant association with either outcome.There were no significant differences in the survival to hospital discharge and good neurological outcomes between non-TTM and TTM groups of hanging-induced OHCA patients.     

16层螺旋CT在肝癌动门脉分流中的诊断价值探讨

目的 研究肝癌APS的16层螺旋CT和DSA表现,探讨16层螺旋CT对肝癌APS的诊断价值。方法 分析175例肝癌患者的16层螺旋CT扫描和DSA影像表现,比较两种检查方法在检出和显示肝癌APS影像学征象方面的差别并分析16层螺旋CT诊断肝癌APS的准确性、敏感性和特异性。结果 16层螺旋CT在显示肝癌APS的密度差异和解剖位置上优于DSA。以DSA作为金标准,16层螺旋CT诊断肝癌APS的准确性、敏感性、特异性分别为98．8％、98．4％、99．1％。结论 16层螺旋CT对肝癌APS的密度差异和解剖位置显示优于DSA。16层螺旋CT诊断肝癌APS有较高的准确性、敏感性和特异性。     

Loss of glucose 6-phosphate dehydrogenase function increases oxidative stress and glutaminolysis in metastasizing melanoma cells

The pentose phosphate pathway is a major source of NADPH for oxidative stress resistance in cancer cells but there is limited insight into its role in metastasis, when some cancer cells experience high levels of oxidative stress. To address this, we mutated the substrate binding site of glucose 6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway, in patient-derived melanomas. G6PD mutant melanomas had significantly decreased G6PD enzymatic activity and depletion of intermediates in the oxidative pentose phosphate pathway. Reduced G6PD function had little effect on the formation of primary subcutaneous tumors, but when these tumors spontaneously metastasized, the frequency of circulating melanoma cells in the blood and metastatic disease burden were significantly reduced. G6PD mutant melanomas exhibited increased levels of reactive oxygen species, decreased NADPH levels, and depleted glutathione as compared to control melanomas. G6PD mutant melanomas compensated for this increase in oxidative stress by increasing malic enzyme activity and glutamine consumption. This generated a new metabolic vulnerability as G6PD mutant melanomas were more dependent upon glutaminase than control melanomas, both for oxidative stress management and anaplerosis. The oxidative pentose phosphate pathway, malic enzyme, and glutaminolysis thus confer layered protection against oxidative stress during metastasis.

The pentose phosphate pathway is an important source of NADPH for oxidative stress resistance (1–5). The oxidative branch of the pentose phosphate pathway contains two enzymes that generate NADPH from NADP⁺, glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) (SI Appendix, Fig. S1). NADPH is an important source of reducing equivalents for oxidative stress resistance because it is used by cells to convert oxidized glutathione (GSSG) to glutathione (GSH), an abundant redox buffer. Complete deficiency for G6PD is embryonic-lethal in mice (2, 6, 7) but hypomorphic G6PD mutations are common in certain human populations, perhaps because they protect against malaria (8, 9). These partial loss-of-function G6PD mutations are well tolerated in adults, though they sensitize red blood cells to hemolysis from oxidative stress under certain circumstances (10).Several studies have reported a lower incidence and mortality for certain cancers in people with hypomorphic mutations in G6PD (11–14), suggesting that cancer cells depend upon G6PD to manage oxidative stress. Cells experience high levels of oxidative stress during certain phases of cancer development and progression, including during metastasis (15–17). Antioxidant mechanisms thus promote the survival of cells during oncogenic transformation (18, 19) as well as during metastasis (15, 16). For example, relative to primary cutaneous tumors, metastasizing melanoma cells exhibit increased dependence upon the folate pathway (15), monocarboxylate transporter-1 (MCT1) (20), and glutathione peroxidase-4 (GPX4) (21), each of which directly or indirectly attenuate oxidative stress. By better understanding the mechanisms that confer oxidative stress resistance in cancer cells, it may be possible to develop pro-oxidant therapies that inhibit cancer progression by exacerbating the oxidative stress experienced by cancer cells.G6PD (22) or PGD deficiency (23–25) reduce the growth of some cancers, including melanoma, but G6PD deficiency has little effect on primary tumor formation by K-Ras–driven epithelial cancers (26). This is at least partly because loss of G6PD in these cancers leads to compensatory increases in the function of other NADPH-generating enzymes, including malic enzyme and isocitrate dehydrogenase (1, 27). Nonetheless, pentose phosphate pathway function may increase during metastasis (20, 28–30) and higher G6PD expression is associated with worse outcomes in several cancers (31–33), raising the question of whether metastasizing cells are particularly dependent upon G6PD. G6PD is not essential for metastasis in a breast cancer cell line but it reduces their capacity to form metastatic tumors (26).Melanoma cells show little evidence of oxidative stress in established primary tumors but exhibit increased levels of reactive oxygen species (ROS) and dependence upon antioxidant mechanisms during metastasis (15, 20, 21). To test if these cells are more dependent upon the pentose phosphate pathway during metastasis, we generated three G6PD mutant melanomas, including two patient-derived xenografts and one human melanoma cell line. Reduced G6PD function had little effect on the formation or growth of primary subcutaneous tumors but significantly increased ROS levels and reduced spontaneous metastasis. G6PD mutant melanomas compensated by increasing malic enzyme activity and glutamine consumption, both to increase oxidative stress resistance and to replenish tricarboxylic acid (TCA) cycle intermediates through anaplerosis. Melanoma cells thus have redundant layers of protection against oxidative stress during metastasis, including the abilities to alter fuel consumption and antioxidant pathway utilization.     

鼻咽癌患者血清TGF-β1、IL-8水平和T淋巴细胞亚群水平测定的临床意义

目的：探讨了鼻咽癌患者血清TGF-β1、IL-8和T淋巴细胞亚群水平的变化及意义。方法：分别应用放免法、酶联免疫法和单克隆抗体测定对31例鼻咽癌患者进行了血清TGF-β1、IL-8水平和T淋巴细胞亚群的测定,并与35例正常健康人作比较。结果：鼻咽癌患者血清TGF-β1、IL-8和CD8水平非常显著高于正常人组（P〈0．01）,而CD3、CD4、CD4／CD8比值又非常显著低于正常人组（P〈0．01）。鼻咽癌患者血清TGF-β1水平和CD4细胞数量及与CD4／CD8比值呈负相关,与CD8细胞呈正相关。结论：观察鼻咽癌患者血清TGF-β1、IL-8水平和T淋巴细胞亚群水平的改变有助于鼻咽癌的诊断及对预后的评价。     

Clinical therapy of platelet-rich plasma vs hyaluronic acid injections in patients with knee osteoarthritis: A systematic review and meta-analysis of randomized double-blind controlled trials

Objective:Knee osteoarthritis (KOA) is the most common degenerative disease of the joints caused by articular cartilage injury, degeneration of joint edges and hyperplasia of subchondral bone. The purpose of this study is to investigate the efficacy and safety of clinical therapy of platelet-rich plasma vs hyaluronic acid injections in patients with KOA.Methods:We systematically investigated Pubmed, Embase, and the Cochrane Library for all related articles published through May 2020. Any study was included that compared the effect of platelet-rich plasma (PRP) and hyaluronic acid (HA) in patients with KOA. The search terms included “platelet-rich plasma,” “PRP,” “hyaluronic acid,” “HA,” “knee,” “osteoarthritis,” “arthritis,” “KOA”. Review Manager 5.3 was used to analyze and calculate data regarding these outcome indicators.Results:In this study,

• 1.Six randomized double-blind controlled trials were included, including 338 patients in the PRP group and 323 patients in the HA group.
• 2.Meta-analysis results showed that the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) Total Score was differed significantly between the PRP and HA groups at the 1, 6, 12 months follow-up (MD = 3.39, 95% CI: 2.85–3.92, P < .05). In a comparison of Physical function scores at the 12 months follow-up, PRP improved knee function scores more than HA (MD = 3.28; 95% CI: 2.13–4.43; P < .05). However, International Knee Documentation Committee (IKDC), Tegner Activity scores, EuroQol visual analogue scale (EQ-VAS), and Adverse Events (AEs) were all not significantly different (P > .05).
• 3.Results showed that compared with HA, PRP had significant advantages in relevant improving knee function and quality of life.

Conclusion:In improving knee function and quality of life, PRP showed superiority over HA in long-term follow-up from well-designed double-blind trials, but a large number of high-quality multi-center studies are still needed to provide more sufficient evidence.     

The risk assessment model of fracture nonunion after intramedullary nailing for subtrochanteric femur fracture

To investigate the influencing factors of fracture nonunion after intramedullary nailing for subtrochanteric fractures and to construct a risk assessment model.Based on the multicenter retrospective analysis of 251 patients, all patients were divided into modeling group and verification group. In the modeling group, postoperative fracture nonunion rate, general data, fracture-related factors, surgical reduction-related factors, mechanical and biological factors were calculated, and the influencing factors of fracture nonunion were screened by univariate analysis. Logistic regression model was used for multifactor analysis to construct the risk assessment model. Based on the logistic regression model, the risk prediction model was constructed by drawing the Nomogram diagram. Through the verification group, the influencing factors were evaluated again, and the differentiation and calibration of the model were evaluated. The calibration degree was evaluated by Hosmer-Lemeshow test, goodness of fit test, and calibration curve. The discriminant degree was evaluated by the receiver operating characteristic curve.Fracture nonunion occurred in 34 of 149 patients in the modeling group. Among the 14 potential influencing factors, univariate analysis and logistic regression analysis showed that postoperative hip varus, intramedullary nail fixation failure, and reduction of fracture with large incision were the risk factors of fracture nonunion. The medial cortex fracture was seen reduced on X-Ray was a protective factor for fracture nonunion, and a regression equation was established. Based on the logistic regression model, the Nomogram diagram is drawn. Twenty-four cases of fracture nonunion occurred in the verification group. The area under the receiver operating characteristic curve was area under curve =0.883 > 0.7, indicating that there was a moderate differentiation to evaluate the occurrence of fracture nonunion after operation. The goodness of fit test: the Hosmers-Lemeshow test (X² = 2.921, P = .712 > .05) showed that the model had a good calibration.After intramedullary nailing of subtrochanteric fracture, hip varus, failure of intramedullary nail fixation and wide surgical dissection are the risk factors of fracture nonunion, and the postoperative reduction of medial cortex fracture is protective factor.National key research and development projects: 2016YFC0105806     

The cancer-testis gene,MEIOB, sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency

Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.     

COVID‐19 lockdown consequences on body mass index and perceived fragility related to physical activity: A worldwide cohort study

BackgroundThis paper is a follow‐up study continuing the COVISTRESS network previous research regarding health‐related determinants.ObjectiveThe aim was to identify the main consequences of COVID‐19 lockdown on Body Mass Index and Perceived Fragility, related to Physical Activity (PA), for different categories of populations, worldwide.DesignThe study design included an online survey, during the first wave of COVID‐19 lockdown, across different world regions.Setting and participantsThe research was carried out on 10 121 participants from 67 countries. The recruitment of participants was achieved using snowball sampling techniques via social networks, with no exclusion criteria other than social media access.Main outcome measures Body Mass Index, Physical Activity, Perceived Fragility and risk of getting infected items were analysed. SPSS software, v20, was used. Significance was set at P < .05.Results Body Mass Index significantly increased during lockdown. For youth and young adults (18‐35 years), PA decreased by 31.25%, for adults (36‐65 years) by 26.05% and for the elderly (over 65 years) by 30.27%. There was a high level of Perceived Fragility and risk of getting infected for female participants and the elderly. Correlations between BMI, Perceived Fragility and PA were identified.Discussion and ConclusionsThe research results extend and confirm evidence that the elderly are more likely to be at risk, by experiencing weight gain, physical inactivity and enhanced Perceived Fragility. As a consequence, populations need to counteract the constraints imposed by the lockdown by being physically active.     

Synthesis of tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols

A facile and efficient route to tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative annulation reactions is described. This reaction proceeds through a cascade sequence of Friedel–Crafts-type alkylation followed by intramolecular “Click” reaction, involving the formation of multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.

The synthesis of tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative [4 + 2]-annulation reaction is described.     

Recent developments of a co-immobilized laccase–mediator system: a review

The laccase–mediator is a promising biocatalyst with many possible applications, including bioremediation, chemical synthesis, biobleaching of paper pulp, biosensing, textile finishing and wine stabilization. The immobilization of laccase and the mediator offers several improvements for laccase–mediator system applications because the storage and operational stabilities are frequently enhanced. Moreover, the reusability of the immobilized laccase and mediator represents a great advantage compared with the free laccase and mediator. In this work, we review the methods of co-immobilization of the laccase–mediator system for the first time systematically and comprehensively. In addition, we discuss the different methodologies of laccase and mediator immobilization that have been reported.

The laccase–mediator is a promising biocatalyst with many possible applications, including bioremediation, chemical synthesis, biobleaching of paper pulp, biosensing, textile finishing and wine stabilization.