BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Objective The aim of this study was to investigate the prospective association between physical activity (PA),independently or in conjunction with other contributing factors,and osteoporosis (OP) outcomes. Methods The Physical Activity in Osteoporosis Outcomes (PAOPO) study was a community-based cohort investigation. A structured questionnaire was used to gather the participants' sociodemographic characteristics. Bone mineral density (BMD) measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort. Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China's Jidong community. Based on their PA level,participants were categorized as inactive,moderately active,or very active. Men showed higher physical exercise levels than women across the activity groups. BMD was significantly higher in the very active group than in the moderately active and inactive groups. Individuals aged>50 years are at a higher risk of developing OP and osteopenia. Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.

Objective To investigate the value of intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)in quantitatively evaluating the involved muscle in idiopathic inflammatory myopathies(IIM).Methods Totally,50 patients with clinically diagnosed IIM(IIM group)and 15 healthy controls(control group)were selected for bilateral thigh MRI examination,including IVIM-DWI sequences.The right quadriceps(vastus lateralis,vastus intermedius,vastus medialis,and rectus femoris)of all subjects were selected as region of interest(ROI).Single-exponential and double-exponential analysis were employed to quantitatively measure IVIM-DWI parameters,including apparent diffusion coefficient(ADC),D,f,and D*.Based on T1WI and T2WI fat-suppressed images of the right quadriceps,these muscles were divided into affected and unaffected groups.One-way analysis of variance was used to compare IVIM-DWI parameters between affected group,unaffected group,and control group.Receiver operating characteristic(ROC)curve was performed to analyze the differences in IVIM-DWI parameters among the above groups.Results The D and ADC values were significantly higher in the affected group compared to the unaffected group and the control group(P＜0.001).ROC curve analysis revealed that D and ADC values had moderate diagnostic significance with area under the curve(AUC)of 0.794 and 0.882,respec-tively.The cutoff values for D values and ADC values were 1.63×10-3 mm2/s and 1.44×10-3 mm2/s,respectively.Additionally,MRI follow-up performed one year after treatment in three patients with IIM showed significant resolution of inflammatory edema in thigh muscles,accompanied by a marked decrease in IVIM-DWI parameter values,particularly D values and ADC values.Conclusion The affected muscle in IIM show distinctive diffusion characteristics,and IVIM-DWI parameters,especially D values and ADC val-ues,show a higher diagnostic value for assessing muscle status in IIM.In addition,IVIM-DWI parameters also demonstrate a promis-ing value in the follow-up of IIM,which requires further confirmation in larger cohorts.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective:To learn about the employment situation of community-dwelling spinal cord injury (SCI ) survivors in Jiangsu Province and the factors which influence it, aiming to put forward suggestions which can help them return to work.Methods:This cross-sectional observational study was based on a International Spinal Cord Injury (InSCI) community survey in Jiangsu Province using a questionnaire (InSCI questionnaire) devloped with the International Classification of Functioning, Disability and Health as the framework. Data were collected using the InSCI questionnaire. Data on sociodemographics, diseases, body functions, activities and participation, environmental factors, general health, well-being and so on were collected. Descriptive statistics were computed to analyze the respondents′ employment-related information. Correlation analysis and multiple linear regression were used to analyze factors influencing the employment of these community-dwelling SCI survivors.Results:From January to December of 2018, 726 completed questionnaires were collected-541 through telephone interviews, 152 via Internet links and 33 via face-to-face interviews. Logistic regression showed that residential patterns (odds ratio, OR=0.472), whether there was someone to take care of them at home or going out ( OR=0.405), age at the onset of injury ( OR=0.949), personal factors ( OR=1.068), activity and participation ( OR=1.034), and environmental factors ( OR=1.043) all influenced the respondents′ engaging in paid work. Conclusion:The employment rate of patients with spinal cord injury living in the community is low (22.8%). Comprehensive rehabilitation programs and adequate family and social support should be implemented to help them return to work.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integra-tion of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation,and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, hap-lotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Objective To investigate the clinical characteristics of patients with acute myocardial infarction (AMI) complicated with cardiac rupture (CR) and to explore the risk factors for the survival time of AMI combined with CR. Methods A retrospective study was conducted. The clinical data of 75 hospitalized patients with the confirmed diagnosis of AMI combined with free wall rupture (FWR) or ventricular septal rupture (VSR) admitted to Guangdong General Hospital from April 2009 to March 2015 were collected. They were divided into a survival < 30-day group (42 cases) and a survival ≥ 30-day (33 cases) group, and their clinical characteristics were analyzed. Receiver operating characteristic curve (ROC curve) was drawn, and the predictive value of each indicator for the patient's 30-day survival time was analyzed. Results The number of female patients (25 cases vs. 0 case) and the number of patients without diabetes (36 cases vs. 21 cases) in the survival < 30-day group were significantly higher than those in survival ≥ 30-day group (all P < 0.05). Therefore, both female and without diabetes were risk factors for the recent death of AMI complicated with CR. In the survival ≥ 30-day group, the number of patients with right coronary artery (RCA) lesions and immediately undergoing early percutaneous coronary intervention therapy (PCI) was significantly higher than that in survival < 30-day group (11 cases vs. 4 cases, P < 0.05). Therefore, the RCA lesion and immediately undergoing early PCI therapy was a recent survival protective factor. ROC curve analysis showed that AMI female and combined with diabetes and lesions in RCA had a certain predictive value for survival time of the patients, the area under ROC curve (AUC) and 95% confidence interval (95%CI) were 0.798 (0.696-0.899), 0.592 (0.542-0.743) and 0.647 (0.500-0.794) respectively, sensitivity and specificity were 34.6%, 16.1% and 42.3% and 12.9% respectively, all P < 0.05. Conclusions Women and without diabetes are the risk factors of recent death of AMI complicated by CR, and in patients with AMI complicated with CR and the involved lesion being RCA, PCI therapy should be performed as early as possible that may elevate the 30-day survival rate for the patients.

Objective To investigate the influence of acupuncture on learning and memorial function and the expression of BDNF in prefrontal cortex of rats with sleep deprivation (SD), for providing theoretical evidence for treating sleep deprivation with acupuncture.Method Sixty Wistar rats were randomly divided into a control group, a model group, and an acupuncture group, 20 rats in each group. SD models were established by the modified multiple platform methods; the acupuncture group was intervened by acupuncture at Shenmen (HT 7); while the control group was left intact. Respectively after SD for 24 h and 72 h, the learning and memorial function was tested by using Morris water maze. Ten the rats were sacrificed to collect brain for detecting the expression of BDNF in prefrontal cortex via immunohistochemical method.Result The body weight, learning and memorial function, and the expression of BDNF in prefrontal cortex of the acupuncture group and model group were significantly different from those of the control group after SD for 24 h and 72 h (P<0.05). The learning and memorial function of the acupuncture group was significantly different from that of the model group after SD for 24 h and 72 h (P<0.05). The body weight and expression of BDNF in prefrontal cortex of the acupuncture group were significantly different from those of the model group after SD for 72 h (P<0.05).Conclusion Acupuncture can obviously improve the decline of the function of learning and memory of the SD rats, and also up-regulate the declined expression of BDNF in prefrontal cortex caused by SD.

Objective To study the impact of setup error caused by computed tomography ( CT) images with different resolutions in the Sentinel system on clinical treatment. Methods A phantom was scanned by large?aperture positioning CT with two different resolutions ( CT1:0. 5 mm × 0. 5 mm × 1. 0 mm, FOV 256 mm, Matrix 512, thickness 1 mm;CT3:1. 0 mm×1. 0 mm×3. 0 mm, FOV 500 mm, Matrix 512, thickness 3 mm) . The CT images were transferred to the planning system. The radiation fields were designed and transferred to MOSAIQ and Sentinel systems. Ten fixed setup errors were applied to a six degree of freedom couch. The Sentinel system was used to position the two groups of CT images and generate the setup errors. The comparison of two datasets was made by paired t?test. Cone?beam CT was used for independent verification. Results The setup errors in x?, y?, and z?directions were significantly smaller on CT1 than on CT3(0.19±0. 11 vs. 0.33±0. 16 mm, P=0. 061;0.59±0. 79 vs. 1.07±1. 09 mm, P=0. 008;0.67±0. 75 vs. 1.16±1. 30 mm, P=0. 043). There were no significant differences in rotational errors in x?, y?, or z?directions between the two datasets ( P=0. 494;P=0. 182;P=0. 298) . Conclusions The Sentinel system has a higher setup accuracy in the 0. 5 mm×0. 5 mm×1. 0 mm mode than in the 1. 0 mm×1. 0 mm×3. 0 mm mode. However, the later mode is still an acceptable choice in clinical treatment.