Survey and analysis on the cognition and attitude towards hospice care among medical staff in Liaocheng / 中国医学伦理学

ObjectiveTo investigate the current status of cognition and attitude towards hospice care among medical staff in Liaocheng，analyze the related influencing factors，and to provide reference for further development of hospice care services. MethodsUsing the method of convenient sampling，404 medical staff from all levels of hospitals in Liaocheng were selected as the research subjects from January to June 2022 to conduct a questionnaire survey on the cognition and attitude towards hospice care.Statistical methods were used to analyze the related influencing factors. ResultsThe knowledge score of hospice care among medical staff in Liaocheng was （13.02 ± 4.10），with an average score rate of 65.10%.The score of attitude was （38.67 ± 5.64），with an average score rate of 64.50%.Age （41~50 years old），having received education and training，treated or cared for patients in the middle and late stages，and understanding ethics and morality，as well as cultural customs were significantly positively correlated with knowledge scores.Age （> 50 years old），professional title （deputy senior professional title），position （medical treatment），and experience in treating or caring for patients in the middle and late stages were positively related to attitude scores. ConclusionThe cognition and attitude towards hospice care among medical staff in Liaocheng were at a moderate level.Strengthening the construction of a standardized hospice care system is helpful to improve the cognition and attitude level towards hospice care among medical staff.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

Pseudomonas aeruginosa-induced mitochondrial dysfunction inhibits proinflammatory cytokine secretion and enhances cytotoxicity in mouse macrophages in a reactive oxygen species (ROS)-dependent way / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

随着铜绿假单胞菌（铜绿）的耐药性逐年增强，铜绿感染已经成为公共医疗卫生的重点关注问题。线粒体自噬及其介导的线粒体功能障碍在多种细菌感染中已被报道，但线粒体功能障碍在宿主调控铜绿感染中的作用尚不明确。因此，本研究建立铜绿刺激小鼠巨噬细胞感染模型和小鼠急性铜绿感染模型，探讨铜绿是否通过诱导线粒体自噬改变线粒体功能，进而影响宿主免疫炎症反应和细胞毒性，并通过监测生存率和肺组织病理学变化进一步确定线粒体自噬在小鼠铜绿体内感染模型中的作用。结果表明，铜绿引起小鼠腹腔巨噬细胞线粒体功能障碍，并通过线粒体自噬途径清除铜绿刺激引起的活性氧（ROS）累积，从而抑制铜绿引起的促炎性细胞因子分泌并增强细胞毒性。体内实验进一步确认线粒体自噬在铜绿体内感染中的作用。

Detection methods for polyethylene terephthalate degrading enzymes: a review / 生物工程学报

Polyethylene terephthalate (PET) is one of the most widely used synthetic polyester. It poses serious threat to terrestrial, aquatic ecosystems and human health since it is difficult to be broken down and deposited in the environment. The biodegradation based on enzymatic catalysis offers a sustainable method for recycling PET. A number of PET hydrolases have been discovered in the last 20 years, and protein engineering has increased their degradation capabilities. However, no PET hydrolases that are practical for widespread industrial use have been identified. Screening of PET hydrolase using conventional detection techniques is laborious and inefficient process. Effective detection techniques are required to promote the commercialization of PET hydrolases. Using efficient detection techniques to screen potent industrial enzymes is essential for supporting the widespread industrial implementation of PET hydrolases. To define PET hydrolase, scientists have created a number of analytical techniques recently. The detection techniques that can be used to screen PET hydrolase, including high performance liquid chromatography, ultraviolet absorption spectrometric, and fluorescence activated droplet sorting method, are summarized in this study along with their potential applications.

The effect of ADSC on the activity of EPC under co-culture and its related mechanism / 安徽医科大学学报

Objective@#To investigate the effect of co-culture of adipose-derived stem cells(ADSC) and endothelial progenitor cells(EPC) on the activity of EPC and its related mechanism．@*Methods@#Rat ADSC and EPC were isolated，cultured，expanded and identified in vitro ．The experiment was divided into three groups : EPC group，EPC + ADSC co-culture group，and EPC + ADSC + PI3K-inhibitor group．After 48 hours of co-culture，the cells of the three groups were treated with Transwell．The effects of ADSC and EPC co-culture and PI3K / AKT pathway on EPC activity were evaluated by CCK-8 assay，scratch assay and angiogenesis assay，respectively．Western blot was used to detect vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) ，vascular endothelial-cadherin ( VE-cadherin) ，CD133 ，phospho-phosphatidylinositol 3-kinase ( phospho-phosphatidylinositol 3-kinase(p-PI3K) and phospho-protein Kinase B (p-AKT) expression levels in EPC to detect the effects of ADSC and EPC co-culture and PI3K / AKT pathway on the differentiation ability of EPC into mature endothelial cells. @*Results@#CCK-8 results showed that the absorbance at 450 nm of EPC in EPC + ADSC co-culture group was higher than that in EPC group and EPC + ADSC + PI3K-inhibitor group at different time points，and the difference was statistically significant (P＜0. 01) ．The scratch test showed that the relative scratch distance of EPC + ADSC co-culture group was smaller than that of EPC group and EPC + ADSC + PI3K-inhibitor group after 24 hours ，and the difference was statistically significant (P＜0. 01) ．Tube formation assay showed that the average number of tubelike structures formed in EPC + ADSC co-culture group was higher than that in EPC group and EPC + ADSC + PI3K-inhibitor group，and the difference was statistically significant (P＜0. 01) ．Western blot showed that the expression levels of VEGFA，eNOS，VE-cadherin，p-PI3K and p-AKT of EPC in EPC + ADSC co-culture group were higher than those in EPC group and EPC + ADSC + PI3K-inhibitor group．The expression level of CD133 in EPC group was lower than that in EPC + ADSC + PI3K-inhibitor group，and the difference was statistically significant (P ＜0. 01) ．@*Conclusion @#Co-culture of ADSC and EPC can improve the proliferation，migration，differentiation and vasogenic activity of EPC through the regulation of PI3K / AKT pathway.

Strategic Exploration of Targeted Therapy for BRAF Non-V600E Mutant Lung Cancer / 中国肺癌杂志

BACKGROUND@#Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment.@*METHODS@#Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature.@*RESULTS@#There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib.@*CONCLUSIONS@#At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.

Exploration of the online and offline mixed teaching mode of Medical Imaging / 中华医学教育探索杂志

Based on the online course of Medical Imaging, the online and offline mixed teaching mode is an important reform against the traditional teaching mode. Combining the teaching reform experience of Chongqing Medical University, this paper introduces the resource construction of the online teaching platform of Medical Imaging, the construction of the online and offline mixed teaching mode (including the overall reconstruction design of the online and offline teaching content, and the organic integration of the online and offline teaching content before, during and after class), the details of teaching implementation (taking ischemic cerebral infarction as an example), the teaching efficiency, the existing problems and related improvement measures. The preliminary practice shows that it has great significance in enhancing the teaching quality since it can break through time and space constraints, expand teaching space, effectively stimulate students' learning autonomy, enhance their practical skills, increase the communication and interaction between teachers and students, and improve the teaching effect.

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M

The effect of hyperlipidemia on perioperative outcomes of rectal cancer patients / 中华老年医学杂志

Objective:To examine the influence of hyperlipidemia on perioperative outcomes of rectal cancer patients.Methods:From June 2016 to June 2019, 86 patients who had received laparotomy or laparoscopic radical resection of rectal cancer at the Department of General Surgery of Nanjing Jiangbei People's Hospital were selected as research subjects.Preoperative blood lipids were measured.Based on lipid levels, patients were divided into the hyperlipidemia group(46 cases)and the normal blood lipid group(40 cases). Operative time, intraoperative blood loss, postoperative recovery outcomes, incidence of anastomotic fistula, and incidences of incision fat liquefaction and incision infections were compared between the two groups.SPSS21.0 was used for data analysis.Results:Compared with the normal lipid group, the operative time of the hyperlipidemia group was significantly longer and the amount of intraoperative blood loss was higher in the hyperlipidemia group, and the differences were statistically significant.Compared with the normal lipid group, the hyperlipidemia group showed a longer time to first postoperative flatus and to first postoperative oral intake, delayed drainage tube removal and ambulation, and longer hospital stays, with statistically significant differences.There were 17 cases of postoperative complications in the hyperlipidemia group(37.0%)and 4 cases in the normal lipid group(10.0%), and the difference was statistically significant( χ2=7.027, P=0.008). Conclusions:Hyperlipidemia has adverse effects on surgical outcomes and postoperative recovery for rectal cancer patients.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB-AcpM

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

Effect of endocrine gland-derived vascular endothelial growth factor on the proliferation and apoptosis of pancreatic cancer cells / 中华肝胆外科杂志

Objective To investigate the effect of endocrine gland-derived vascular endothelial growth factor(EG-VEGF) on the proliferation and apoptosis of pancreatic cancer cells and on the regulation of PI3K/AKT signaling pathway.Methords The expression of EG-VEGF and its receptor-VEGFR-2 in pancreatic cancer tissues and adjacent normal tissues was detected by PCR.The effect of EG-VEGF on proliferation of human pancreatic cancer cells was detected by MTT assay.The effect of EG-VEGF on the apoptosis of human pancreatic cancer cells was detected by flow cytometry.Western lot was used to detect the changes of related proteins expression in PI3K/AKT signaling pathway after EG-VEGF treatment.Results The expression (3.08±0.30,2.17±0.16 respectively) of EG-VEGF and VEGFR-2 in pancreatic cancer tissues was significantly higher than those (1.55±0.73,0.54±0.34 respectively) in adjacent tissues (both P＜ 0.05).MTT and flow cytometry data showed that EG-VEGF could promote the proliferation of pancreatic cancer cells and inhibit cell apoptosis.Western blot showed that EG-VEGF promoted AKT phosphorylation and activated PI3K/AKT signaling pathway.Conclusion EG-VEGF is highly expressed in pancreatic cancer tissue,and can activate PI3K/AKT signaling pathway to promote cell proliferation and inhibit cell apoptosis.

Clinical significance of neutrophil-to-lymphocyte ratio in assessing response to cardiac resynchronization therapy in elderly patients / 中华老年医学杂志

Objective To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR)in assessing response to cardiac resynchronization therapy(CRT)in elderly patients.Methods Clinical data of 105 elderly patients with chronic heart failure(CHF)who had received CRT at our hospital from January 2006 to January 2017 were retrospectively analyzed,and patients were divided into a no-response group(n=42)and a response group(n=63)according to CRT outcomes after 6 months.General clinical data were compared between the two groups.Factors influencing response to CRT were analyzed by logistic regression model analysis.The receiver-operating characteristic(ROC)curve was used to assess the predictive value of NLR in response to CRT.Results Compared with the response group,the no-response group had increased baseline levels of initial QRS width,serum creatinine(Scr) and uric acid(UA)(P ＜0.05).There was no significant difference in left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter (LVESD),the New York Heart Association (NYHA) functional classification,neutrophil count,lymphocyte count and NLR between the two groups before CRT(P＞0.05).After 6 months of CRT,the LVEDD,NYHA functional class,neutrophil count and NLR were higher,and LVEF and lymphocyte count were lower in the no-response group than in the response group(P ＜0.05).The difference in NLR between 6 months after CRT and before CRT(△NLR)was higher in the no-response group than in the response group(P ＜0.05).Multi-factor Cox regression analysis showed that NLR (OR =1.895,95％CI:1.538～5.284,P =0.031)and △NLR(OR =2.579,95％CI:2.110～8.329,P =0.005) were independent risk factors for CRT (HR =1.590,95 ％ CI:1.215 ～ 2.146,P =0.013).ROC curve analysis showed that ROCAUC of △NLR in the no-response group was 0.891,95％CI:0.832～0.937,which was higher than that at 6 months after CRT(0.813,95 ％ CI:0.765～0.864)(Z=2.712,P＜0.05).Conclusions The increase in NLR after CRT may be an early sign for noresponse to CRT,and dynamic monitoring of NLR should be promoted to assess the prognosis of patients undergoing CRT.

Effect of a noise-optimized virtual monoenergetic reconstruction technique on dual-energy CT for image quality of inflammatory bowel disease / 中南大学学报(医学版)

To assess the value of noise-optimized virtual monoenergetic imaging (VMI+) reconstruction technique on objective and subjective image quality in patients with inflammatory bowel disease (IBD) undergoing abdominal dual-energy computed tomography (DECT).
 Methods: Datasets from 32 patients (22 men, 10 women) with IBD, who underwent abdominal DECT, were reconstructed by using the standard linearly blended (M_0.6), traditional monoenergetic (VMI) and VMI+ algorithms in 10-keV intervals from 40-100 keV. Attenuation in IBD lesions was measured to perform objective evaluation using signal-to-noise (SNR) and contrast-to-noise ratios (CNR). Subjective evaluation was performed by 3 independent blinded radiologists using 5-point Likert scales. The overall image quality, image sharpness, lesion delineation, and image noise were analyzed. 
 Results: Mean SNR and CNR peaked at 40 keV VMI+ series (SNR 8.28±2.34, CNR 5.10±2.10) and they were significantly higher than those in linearly blended (SNR 5.82±1.44, CNR 1.53±0.86) and all VMI series (all P<0.01). Subjective image parameter was the highest for the 50 keV VMI+ series regarding overall image quality (mean 4.80, all P<0.01). The highest image sharpness scores were observed at 40 and 50 keV VMI+ reconstructions (mean 4.14 and 4.25, respectively; P=0.415). VMI+ series at 40 keV provided the highest lesion delineation (mean 4.52, all P<0.01). Image noise was low at the 100 keV VMI+ and VMI series (mean 4.58 and 4.40, respectively; P≥0.11).
 Conclusion: Low-keV VMI+ reconstructions improves SNR, CNR, and subjective image quality significantly in patients with IBD.

Drug resistance mutations and its associated factors among 579 HIV/AIDS patients experiencing failure of antiretroviral therapy in Jiangsu Province, China / 中华预防医学杂志

Objective@#To understand the incidence and related factors of HIV-1 drug resistance among HIV/AIDS patients experiencing treatment failure in Jiangsu province, China.@*Methods@#The HIV/AIDS integrated prevention and control data information management system of China were used to collect the basic data of patients, blood specimens were collected from patients who had antiretroviral therapy (ART) failure with ≥12 months and older than 18 years in 2016 in Jiangsu, excluding cases with missing information, 713 cases were enrolled in this study. HIV-1 RNA was extracted, and then pol gene region was amplified and sequenced. The obtain sequences were submitted to Stanford University HIV Drug Resistance Database to interpret and analyse HIV-1 drug resistance and sub-types. Multivariate logistic regression model was used to explore the related factors of drug resistance.@*Results@#A total of 579 subjects were amplified successfully, male accounted for 85.66% (496 cases), and the median age was 39 years old. The main route of infection was sexual transmission (553 cases, 95.51%). A total of 331 patients with drug resistance gene mutation were detected, drug resistance mutation rate was 57.18%. Compared with patients with baseline CD4+T cell count >500 cells/μl, patients with CD4+T cell count in 201-500 cells/mm3 and ≤200 cells/μl had a higher incidence of genetic drug resistance, the odds ratio was 3.33 and 6.87, respectively. Compared with patients with treatment less than 24 months, patients treated for 25-48 months had a higher incidence of drug resistance, the odds ratio was 1.88. Compared with patients infected by CRF07_BC strains, patients infected by CRF01_AE strains were associated with higher incidence of drug resistance, the odds ratio was 2.22 and 3.32, respectively. Protease inhibitor (PI) resistance mutations, nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) were found in 3.80%, 33.16% and 53.37% of patients, respectively. 31.95% of patients harbored NRTI and NNRTI resistance mutations simultaneously. M184V/I and K103N/Q were the highest frequency of NRTI and NNRTI resistance mutation, the prevalence of M184V/I and K103N/Q were 28.15% and 22.28%, respectively.@*Conclusion@#The status of HIV-1 drug resistance mutations are complex and diverse among patients experiencing failure of ART in Jiangsu. Patients with lower baseline CD4+T cell count, longer treatment time and HIV-1 CRF01_AE and B strains infection were associated with higher incidence of drug resistance mutation.

The advance of detection technology of HIV self-testing / 中华预防医学杂志

At present, China's AIDS testing increased rapidly, but there are still many people living with HIV do not recognize their status, thus postponing the antiviral treatment time. HIV self-testing (HST) is an effective method to expand the testing, not only simple operation, easy to get a result, effectively protect the detection privacy, expand the selection of testers, suit to the entire population, but also the premise and basis of other AIDS comprehensive prevention measures, all over the world are promoting it. Because the HST has controversies in the window period, price and before and after controversial, and our country is in the initial stage of HST, so it is not to develop related policies, but more and more countries are in accordance with their own situations are modified or developed to allow to use rapid detection of AIDS policy to regulate the field. This paper analyzed and summarized the advantage and influence factors of HST promotion, HST believes that in the long term, the advantages outweigh the disadvantages, we need to formulate relevant policies, and improve the sensitivity of the kit, shorten the window period of time, production and promotion of operation standard of video, specification and testing the operating practices, preventing and reporting the possible social harm, investigation and understanding of the needs of the people of the crowd, to maximize the advantages of HST, find more infection, so as to curb the epidemic of AIDS.

Study on improving the standardized training resident radiologists' comprehensive ability in medi-cal teaching and research based on PACS retrospective case report presentation / 中华医学教育探索杂志

Picture archiving and communication system (PACS) was used to perform archiving and retrospective cases report presentation in resident radiologist standardized training, and the current conven-tional article reviewing case report presentation form was compared. The results showed the scores of quiz and questionnaire of using archiving and retrospective cases report based on PACS were higher than using the current conventional form (P<0.05). This type of case report presentation can improve overall capability of resident radiologist standardized training including imaging diagnose,research and educational skill.

Correlation between marrow edema and related MRI and clinical manifestations in patients with knee osteoarthritis / 实用放射学杂志

Objective To investigate the relationship between the marrow edema and general clinical index,quadriceps muscle area,and the meniscus grade of knee osteoarthritis(OA).Methods 72 patients were collected with knee OA in our hospital, underwent X-ray and routine MRI examination of knee, and the same X-ray and MRI were reviewed at 12 months later in different time point.The K-L grading, bone marrow edema score, meniscal grading and VAS score of each knee joint were evaluated.The t-test and Rank-sum test were used to compare the two groups of general data, Spearman was used to perform bivariate correlation analysis.Results The age and VAS score of bone marrow edema group at the initial follow-up were significantly lower than those without edema group(P<0.05),the degree of marrow edema was moderately correlated with age and VAS score, and was not significantly correlated with other indexes.12 months later, BMI and the area of quadriceps femoris in the group with marrow edema were different from those in the group without bone marrow edema(P<0.05), the degree of marrow edema was moderately correlated with age, quadriceps area and VAS.Conclusion The range of marrow edema was related to age, quadriceps area, BMI index and VAS score in MRI.The MRI measurement could reflect the progression of knee OA more than that of X-ray.It also revealed some factors related to the progression of knee OA.

Structural basis of Zika virus helicase in recognizing its substrates

The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn(2+) and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn(2+). The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV) apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.