BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear. OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

Objective To summarize the clinical experience of the treatment for complex aortic coarctation with extra anatomic bypass and anatomic correction techniques. Methods The clinical data of patients with complex aortic coarctation treated in the First Affiliated Hospital of Nanjing Medical University and Friendship Hospital of Ili Kazakh Autonomous Prefecture between April 2012 and November 2020 were retrospectively reviewed. Results A total of 12 patients were enrolled, including 5 males and 7 females aged 11-54 (34.3±16.2) years. Extra anatomic bypass grafting was performed in 8 patients and anatomic correction was performed in 4 patients. The operations were successful in all patients. There was no perioperative death. The average cardiopulmonary bypass time was 203.0±46.0 min (7 median incision patients), and the average intraoperative blood loss was 665.0±102.0 mL. The average postoperative ventilator support time was 32.3±7.5 h, and the average postoperative hospital stay time was 10.2±4.3 d. The mean drainage volume of median incision was 1 580.0±360.0 mL, and the mean drainage time was 9.3±2.7 d. The mean drainage volume of left thoracotomy was 890.0±235.0 mL, and the mean drainage time was 4.8±2.5 d. One patient had a transient hoarse after operation and recovered 6 months later. The follow-up period ranged from 2 to 10 years with an average time of 81.0±27.0 months. All patients had a recovery of hypertension, cardiac afterload after 2 years postoperatively. One patient who received an artificial blood vessel replacement in situ was examined stenosis recurrence at the third year after discharge. Others were asymptomatic during the follow-up period. There were no death or other complications. Conclusion The treatment strategy for complex aortic coarctation should be individualized according to the anatomical features and concomitant heart diseases. Extra anatomic bypass technique is a safe and feasible choice.

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.

Electroencephalography can continuously record the spontaneous and rhythmic electrical activity of local neurons in the brain region in real time and evaluate the functional state of the brain,which is a tool for monitoring brain activity.It has been widely used in the research fields of psychology,cognitive function and consciousness,which provides a new approach to study the mechanism of action of general an-esthetic drugs.Propofol is widely used in clinical practice,and its molecular mechanism has been deeply studied.The neural network mechanism of loss of consciousness induced by propofol is still unclear.This ar-ticle reviews the changes of electroencephalogram characteristics(including power spectrum,complexity,microstate,the functional connectivity,and brain network topology characteristics change)and corres-ponding brain functional changes of loss of conscionsness induced by propofol,the common general anesthet-ic,to provide a new idea for further research on the mechanism of action of anesthetic drugs and the depth of anesthesia monitoring.

Objective To explore the effect of circFAT1 on myocardial injury in rats with diabetic cardiomyopathy(DCM)and the regu-latory mechanism of circFAT1 on the miR-211-5p/CCND2 axis.Methods A DCM rat model was established by injecting rats with high glucose and high fat feed combined with STZ.The rats were randomly separated into DCM,circ-NC,circFAT1,circFAT1+agomir-NC,and circFAT1+miR-211-5p agomir groups,with 20 rats in each group;rats fed regular feed were used as control.Real-time PCR was used to detect the levels of circFAT1,miR-211-5p,and CCND2in myocardial tissue and Western blotting was used to detect CCND2 expression in myocardial tissue.The levels of fasting blood glucose(FBG),total cholesterol(TC),and triglycerides(TG)of rats were recorded.Car-diac ultrasound was used to detect the cardiac function of rats.Furthermore,HE and Masson staining were used to observe the pathological morphology of myocardial tissue and TUNEL staining was used to detect myocardial apoptosis.Additionally,ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Double luciferase reporter gene assay was used to verify the targeting relationship among circFAT1,miR-211-5p,and CCND2.Results Compared with the control group,the expression of circFAT1 and CCND2mRNA and protein and the levels of LVEF and LVFS decreased in the DCM group(P<0.05)whereas,the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-αincreased(P<0.05).Compared with the DCM group,the levels of circFAT1,CCND2mRNA and protein,LVEF,and LVFS increased in the circFAT1 group(P<0.05),whereas the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-α decreased(P<0.05).Furthermore,miR-211-5p agomir reversed the protective effect of circFAT1 on DCM myocardial injury,and the expression of CCND2mRNA and protein decreased(P<0.05).Conclu-sion circFAT1 alleviates myocardial tissue damage in rats with DCM by regulating the miR-211-5p/CCND2 axis.

PET (polyethylene terephthalate) is one of the most important petrochemicals that is widely used in mineral water bottles, food and beverage packaging and textile industry. Because of its stability under environmental conditions, the massive amount of PET wastes caused serious environmental pollution. The use of enzymes to depolymerize PET wastes and upcycling is one of the important directions for plastics pollution control, among which the key is the depolymerization efficiency of PET by PET hydrolase. BHET (bis(hydroxyethyl) terephthalate) is the main intermediate of PET hydrolysis, its accumulation can hinder the degradation efficiency of PET hydrolase significantly, and the synergistic use of PET hydrolase and BHET hydrolase can improve the PET hydrolysis efficiency. In this study, a dienolactone hydrolase from Hydrogenobacter thermophilus which can degrade BHET (HtBHETase) was identified. After heterologous expression in Escherichia coli and purification, the enzymatic properties of HtBHETase were studied. HtBHETase shows higher catalytic activity towards esters with short carbon chains such as p-nitrophenol acetate. The optimal pH and temperature of the reaction with BHET were 5.0 and 55 ℃, respectively. HtBHETase exhibited excellent thermostability, and retained over 80% residual activity after treatment at 80 ℃ for 1 hour. These results indicate that HtBHETase has potential in biological PET depolymerization, which may facilitate the enzymatic degradation of PET.
Hydrolases/metabolism* ; Bacteria/metabolism* ; Hydrolysis ; Polyethylene Terephthalates/metabolism*

Petrochemical-derived polyester plastics such as polyethylene terephthalate (PET) and polybutylene adipate terephthalate (PBAT) have been widely used. However, the difficulty to be degraded in nature (PET) or the long biodegradation cycle (PBAT) resulted in serious environmental pollution. In this connection, treating these plastic wastes properly becomes one of the challenges of environment protection. From the perspective of circular economy, biologically depolymerizing the waste of polyester plastics and reusing the depolymerized products is one of the most promising directions. Recent years have seen many reports on polyester plastics degrading organisms and enzymes. Highly efficient degrading enzymes, especially those with better thermal stability, will be conducive to their application. The mesophilic plastic-degrading enzyme Ple629 from the marine microbial metagenome is capable of degrading PET and PBAT at room temperature, but it cannot tolerate high temperature, which hampers its potential application. On the basis of the three-dimensional structure of Ple629 obtained from our previous study, we identified some sites which might be important for its thermal stability by structural comparison and mutation energy analysis. We carried out transformation design, and performed expression, purification and thermal stability determination of the mutants. The melting temperature (T_m) values of mutants V80C and D226C/S281C were increased by 5.2 ℃ and 6.9 ℃, respectively, and the activity of mutant D226C/S281C was also increased by 1.5 times compared with that of the wild-type enzyme. These results provide useful information for future engineering and application of Ple629 in polyester plastic degradation.
Plastics/metabolism* ; Polyethylene Terephthalates/metabolism* ; Biodegradation, Environmental ; Metagenome

Cancer is one of the major fatal diseases that seriously threaten human health， and its burden needs to be solved urgently. Health technology assessment （HTA） can provide scientific evidence-based basis for cancer diagnosis， treatment， prevention and related policy formulation. Cost-utility analysis is the gold standard for economic evaluation in HTA， and the accurate measurement of its health utility is one of the key elements to determine the accuracy of its results. This article focuses on systematic introduction of direct measures， multi-attribute health utility scales， and mapping methods in the field of cancer measurement and reviews their applications in cancer patients. Among them， direct measures are complex， costly， and require a high level of subject knowledge； multi-attribute health utility measures are currently the preferred method for measuring health utility in cancer patients； with the continuous development and refinement of disease-specific utility measures in multi-attribute health utility instruments， the mapping method may gradually decrease in future applications. This paper can provide a reference for the selection of health utility measurement tools for HTA in the field of cancer， and provide evidence-based basis for optimizing resource allocation and policy formulation in the field of cancer.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China. Radiotherapy is the first-line treatment. After appropriate radiotherapy, about 5%-15% patients experience recurrence. In view of the poor efficacy and high incidence of severe late toxicities associated with re-irradiation, salvage surgery by the transnasal endoscopic approach is recommended for recurrent NPC (rNPC). Compared with re-irradiation, endoscopic surgery can better prolong survival, improve the quality of life, and reduce complications and medical expenses of patients with rNPC. However, the complexity of the nasopharyngeal skull base enhances the difficulty and risk of surgery. Expanding the boundary of surgical resection remains a clinical challenge for otolaryngologists. In this regard, to help more advanced patients with rNPC, the surgical innovative system of NPC needs to be established by multi-disciplinary cooperation, involving skull base anatomy-based investigation, appropriate administration of the internal carotid artery (ICA), repair of skull base defect, and establishment of various types of endoscopic endonasal nasopharyngectomy.

Objective:To investigate the correlation between the high-resolution magnetic resonance imaging (MRI) vessel wall characteristics and risk of ischemic stroke in patients with middle cerebral artery (MCA) atherosclerotic stenosis.Methods:Patients with ischemic cerebrovascular disease treated in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University from January 2016 to January 2020 were enrolled prospectively. The patients presented with transient ischemic attack or acute ischemic stroke (AIS). Magnetic resonance angiography showed that the ipsilateral MCA had stenosis of 50%-99%, and it was identified as the responsible lesion. Routine MRI and the vessel wall imaging at the narrowest part of MCA were performed. The characteristics of vessels and plaques at MCA stenosis were compared between the AIS group and the non-AIS group. Multivariate logistic regression analysis was used to determine the independent risk factors for AIS. Receiver operating characteristic (ROC) curve was used to determine the predictive value of vessel wall characteristics for AIS. Results:A total of 65 patients with ischemic cerebrovascular disease and MCA stenosis were enrolled. The age of patients was 68±14 years, 50 were males (76.9%). There were 30 patients (46.2%) in the AIS group and 35 (53.8%) in the non-AIS group. There were no significant differences in demographic data, vascular risk factors and routine laboratory tests between the two groups. Compared with the non-AIS group, the narrowest lumen area in the AIS group (2.36±1.09 mm 2vs. 2.96±1.01 mm 2; t=2.274, P=0.027) was smaller, the plaque area (4.46 ±2.08 mm 2vs. 2.62±1.32 mm 2; t=4.315, P<0.001) was larger, the remodeling index (1.08±0.11 vs. 0.94±0.10; t=5.573, P<0.001) was higher, and the proportion of obvious enhanced plaque (63.3% vs. 11.4%; χ2=19.034, P<0.001) and positive remodeling plaque (80.0% vs. 20.0%; χ2=23.311, P<0.001) were higher. Multivariate logistic regression analysis showed that plaque area (odds ratio [ OR] 2.01, 95% confidence interval[ CI] 1.35-2.98; P=0.001), remodeling pattern ( OR 16.00, 95% CI 4.73-54.15; P=0.001), the narrowest lumen area ( OR 0.568, 95% CI 0.34-0.96; P=0.033) and degree of enhancement ( OR 21.85, 95% CI 5.13-93.00; P<0.001) were the independent risk factors for AIS. ROC curve analysis showed that the combination of plaque area, the narrowest lumen area and the degree of enhancement had the best prediction effect (area under the curve 0.927, 95% CI 0.84-0.96). Conclusion:AIS is more likely to occur when the plaque area at the narrowest part of the MCA is larger, the lumen area is smaller, and there is obvious plaque enhancement.