Objective To investigate the effect of basic helix-loop-helix family member E40 (BHLHE40) on the invasion and migration of osteosarcoma (OS) cells, and to explore the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the biological behavior of OS mediated by BHLHE40, providing a scientific basis for targeted therapy of OS. Methods On the basis of clinical OS samples and OS cell lines, the expression differences of BHLHE40 between OS and adjacent tissues, as well as those between OS cells and normal osteoblast cell lines, were analyzed. BHLHE40 knockdown OS cells were obtained through shRNA transfection. The effects of BHLHE40 on OS cell proliferation, migration, and invasion were examined using CCK-8, EdU staining, wound healing, and Transwell assays. The involvement of the PI3K/AKT signaling pathway was assessed by Western blotting. Further validation was conducted in vivo experiments. Results The expression of BHLHE40 was significantly higher in OS tissues compared to adjacent tissues. In OS cell lines, BHLHE40 protein expression levels were increased compared to normal osteoblasts, and the cell line with the highest BHLHE40 expression was selected for subsequent knockdown experiments. Compared with the knockdown control group, the BHLHE40 knockdown group exhibited reduced cell viability, EdU-positive cell count, colony number, cell migration, and invasion abilities, along with downregulation of phosphorylated PI3K(p-PI3K)/PI3K and p-AKT/AKT protein expression. The aforementioned functions of BHLHE40 were also reproduced in in vivo experiments. Conclusion BHLHE40 is highly expressed in OS tissues, and its knockdown can significantly inhibit OS cell proliferation, migration, and invasion, while reducing PI3K/AKT signaling pathway activity. This suggests that BHLHE40 could serve as a novel therapeutic target for OS.
Osteosarcoma/metabolism* ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Signal Transduction/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Animals ; Neoplasm Invasiveness ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Bone Neoplasms/metabolism* ; Mice ; Gene Knockdown Techniques ; Male ; Female ; Mice, Nude

Objective:To investigate the epidemic characteristics of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020, and provide a reliable scientific basis for formulating brucellosis prevention and control strategies in Inner Mongolia Autonomous Region.Methods:A retrospective study was carried out to collect data of human brucellosis in Inner Mongolia Autonomous Region from 2018 to 2020 from the "China Disease Control and Prevention Information System", and the monitoring data and information of confirmed cases were collected from the annual summary data reported by the leagues (cities) of the Inner Mongolia Autonomous Region. Using descriptive epidemiological methods, the epidemic situation, three distributions (time, region and population distributions) of brucellosis, and the serological and pathogenic test results of active monitoring population were analyzed.Results:From 2018 to 2020, a total of 40 665 cases of brucellosis were reported in Inner Mongolia Autonomous Region, with an annual average incidence rate of 53.47/100 000. The number of annual incidence had increased from 10 111 in 2018 to 16 406 in 2020, and the annual incidence rate had increased from 39.99/100 000 in 2018 to 64.60/100 000 in 2020. The spring and summer was the peak incidence, mainly in March to August, accounting for 64.90% (26 390/40 665) . There were reports of brucellosis cases in 12 leagues (cities) of Inner Mongolia Autonomous Region, and the top 3 regions with the number of reported cases were Tongliao City (9 896 cases), Xing'an League (6 136 cases) and Chifeng City (4 934 cases). The age of onset of brucellosis cases was mainly 30 - < 65 years old(33 539 cases), and the sex ratio between men and women was 2.18 ∶ 1.00 (27 890 ∶ 12 775); the occupational distribution was mainly farmers, accounting for 79.23% (32 221/40 665). From 2018 to 2020, 704 085 people were actively monitored in the region, of which 391 941 were serologically tested, and the infection rate was 4.57% (17 920/391 941); and there were 9 539 new cases in the active monitoring population. In 3 years, 19 strains of Brucella sheep type 3 and 11 strains of Brucella sheep type 1 were isolated. Conclusions:From 2018 to 2020, the incidence rate of brucellosis in Inner Mongolia Autonomous Region is increasing year by year. There are many new cases in the active monitoring population, and more underreporting cases. It is recommended to expand the scope of monitoring, strengthen pathogen monitoring among humans and animals, and joint prevention and control of various departments to improve the self-protection awareness of the masses.

【Objective】 To investigate the clinical characteristics， treatment and outcome of elderly patients with COVID-19. 【Methods】 We made a retrospective analysis of the clinical data of elderly patients with COVID-19 admitted by the National Anti-epidemic Medical Team of The First Affiliated Hospital of Xi’an Jiaotong University in Department of the seventh ward of Renmin Hospital of Wuhan University between February 9 and March 15， 2020. We fully extracted the patients’ demographics， epidemiological characteristics， clinical manifestations， laboratory examination， imaging performance， treatment and outcomes. 【Results】 In this study we included a total of 30 patients（18 males and 12 females）， with an average age of（71.1±14.4） years. Their underlying diseases included cardiovascular and cerebrovascular diseases（23 patients）， chronic pulmonary disease（3 patients）， digestive disease（2 patients）， diabetes mellitus（3 patients）， and chronic kidney disease（1 patients）. Before admission， 22 patients received oral medication. The initial symptoms were fever and cough. The peak body temperature averaged（38.4±0.6）℃ The mean time from symptom onset to hospitalization was 15.0±7.7 days. The clinical classification was mainly severe type in 26 patients（87%）. Laboratory examination revealed lower lymphocyte count（0.7±0.2）×10⁹/L， and higher blood D-D dimer lever（6.9±13）μg/L. Serum lactate dehydrogenase（LDH） significantly increased（310±136）U/L. Serum C-reactive protein（61±52）mg/L and erythrocyte sedimentation rate（ESR）（66±38）mmol/L slightly increased. Imaging performance revealed that diffuse lesions were located in bilateral pulmonary parenchyma（22 patients） and in single pulmonary parenchyma（7 patients）. Ground-glass opacity was found in all the patients， and the average number of CT examination during hospitalization was 3.5±1.3. Viral load revealed that nucleic acid in nasopharyngeal swabs of 30 patients was all positive， nucleic acid in the feces of 6 patients was positive， and nucleic acid in nasopharyngeal swab of 1 patient was positive， whose nucleic acid in alveolar lavage fluid was negative. Serum IgG antibody level was（157.5±29.2）AU/mL and IgM antibody level was（69.0±148.7）AU/mL. Complications included ARDS in 5 patients， AKI in 5 patients， cardiac injury in 3 patients， shock in 2 patients， nosocomial infection in 3 patients， coagulation disorder in 3 patients， and gastrointestinal bleeding in 3 patients. Finally， 5 patients received non-invasive mechanical ventilation and 2 patients received invasive mechanical ventilation. Another 2 patients underwent CRRT and 1 patient received CRRT plus ECMO. Of the 3 patients with critical type， 2 died and 1 survived. There were 25 patients who turned from severe type into normal type/light type， and 1 patient finally died（turned from severe type into critical type）. In the end， 15 patients were cured and discharged. The average time of viral nucleic acid from positive to negative was 12.4±5.6 and the average time of lesion absorption in computer tomography was 16.9±5.8 days. The total hospital stay was 22.9±8.1 days， and the 28-day mortality rate was 6.7%. 【Conclusion】 COVID-19 in elderly patients is mostly severe and its initial symptoms are still fever and cough. Patients should be immediately hospitalized when symptoms develop. The time of viral nucleic acid transformation and imaging improvement is longer than that of others. The mortality in critically ill patients is higher than that of others. Clinicians should pay more attention to the elderly people.

In order to improve the cure rate of critically ill patients in Wuhan epidemic area and reduce the fatality rate, the state have dispatched medical staffs from the whole country to support Wuhan and treat critically ill patients in dedicated facilities. A medical team from the First Affiliated Hospital of Xi’an Jiaotong University, consisting of 133 medical staffs major in critical care medicine, respiralogy, infection, cardiology, and general surgery, entirely took over the critical care unit of the East Hospital of the Renmin Hospital of Wuhan University, and formed a multidisciplinary collaboration team with local medical staffs to treat patients together. Up to March 13th in 2020, the author′s medical team has admitted a total of 109 patients, of which 48 had been discharged up on recovery. Critically ill patients with Corona Virus Disease 2019 mainly have elder age, comorbidities, complicated conditions, and difficult diagnosis and treatment. The author and the author′s team combined with clinical practice, share experience and strategies of general surgery related issues in the treatment of critically ill patients, providing reference for collegues in general surgery.

Objective To understand the epidemiological characteristics of recent brucellosis in Hohhot.Methods Clinical data of patients with brucellosis in Hohhot City were retrospectively analyzed,and the patients were diagnosed in the outpatient clinic of Comprehensive Center for Disease Prevention and Control of Inner Mongolia Autonomous Region from 2014 to 2017.To analyze the patient's area,age,gender,occupation and time distribution of the disease.Results A total of 1 940 patients with brucellosis were diagnosed in Hohhot from 2014 to 2017,with an average age of 50.8 years old.There were 1 464 males with an average age of 50.4 years old and 476 females with an average age of 51.9 years old;the male-female ratio was 3:1.The number of cases of brucellosis in 2014-2017 was 612,649,402,and 277,respectively.Brucellosis was mainly distributed in three districts including Horinger County (937 cases),Tumd Left Banner (236 cases) and Tuoketuo County (191 cases),accounting for 70.31％ (1 364/1 940) of the total number of cases in the city.The age of onset was at least 1 year old,the oldest age was 86 years old,and most cases were in the 45-＜ 65 age group,the total number of cases was 1 046,accounting for 53.92％ (1 046/1 940) of the total number of cases in the city;the occupational distribution was mainly farmers (1 795 cases),herders (13 cases) and veterinarians (17 cases),with a total of 1 825 cases,accounting for 94.07％ (1 825/1 940).The time distribution was mainly concentrated in March-July,and the number of cases was 1 157 cases.Conclusions The number of brucellosis cases in Hohhot area of Inner Mongolia is mainly from Horinger County,Tumd Left Banner and Tuoketuo County;the cases occur frequently in Spring and Summer;the age of onset is mainly between 45-＜ 65 years old,they are mainly male farmers.

Objective To investigate the predictive value of HIT-antibodies(HIT-Ab) detection for new thrombus in suspected Heparin-Induced thrombocytopenia (HIT). Methods Retrospective cohort study. 472 suspected HIT patients were collected from July 2016 to November 2018, and all subjects under-went a 4Ts score and were sent for HIT-Ab tests. According to the results of HIT-Ab, there were four groups:412 cases of negative HIT-Ab (0-0.9 U/ml), 45 cases of weak-positive HIT-Ab (1.0-4.9 U/ml), 12 cases of moderate-positive HIT-Ab (5.0-15.9 U/ml), and 3 cases of strong-positive HIT-Ab (≥16.0 U/ml) respective-ly. Ultrasound or CT examination was used to confirm new thrombosis as a standard to evaluate the value of HIT-Ab for predicting new thrombus. The diagnostic efficacy of HIT-Ab for HIT was evaluated in clinically confirmed HIT. Results The incidence rates of new thrombus in each group were: 15.8％ in Negative HIT-Ab group (62/412), 48.9％in Weak-positiveHIT-Ab group (22/45), 75.0％in Moderate-positive HIT-Ab group (9/12), and100％in Strong-positive HIT-Ab group (3/3)(P<0.00). When HIT-Ab≥1.0 U/ml, the speci-ficity for diagnosing new thrombus was 93.0％, the sensitivity was 34.2％, the negative predictive value (NPV) was 84.2％, and the positive predictive value (PPV) was 56.5％. The diagnostic rates of HIT in each group were:negative 0％(0/412), weak-positive 62.2％(28/45), moderate-positive (12/12) and strong-positive (3/3) were 100％. When HIT-Ab≥ 1.0 U/ml, the specificity for HIT diagnosis was 96.0％, the sensitivity was 100％, NPV was 100％, and PPV was 71.5％. Conclusions In suspected HIT patients, the incidence of new thrombosis increases with the elevated HIT-Ab level. HIT-Ab detection can be used as a crucial tool for new thrombosis prediction and HIT diagnosis in suspected HIT patients. Clinicians can develop treatment strategies based on HIT-Ab levels.

Objective To modify the existing preparation instrument for medical patch material to realize its scale and automatic production.Methods The instrument had its shaking table improved and a cylindrical processing system added with comprehensive analysis on raw materials and kinds of process flows.A spreading and fixation mechanism for animal materials was placed in the cylindrical processing system,which had the holes for liquid inlet and outlet respectively on its top and bottom.The cylindrical processing system was fixed to the base of the shaking table.Results The instrument enhanced preparation efficiency significantly,and had the raw material utilization rate increased by 20％,product qualification rate raised by 35％,preparation cycle reduced by 33％ and total cost saved by 40％.Conclusion The instrument behaves well in adaptability to multi animals,preparation process,inter-assay difference,raw material utilization rate,product qualification rate and cost reduction,which is of great significance to promote the clinical application of medical biological patch.

Objective To discuss the diagnostic value of HIT-antibodies in suspected HIT patients with heart diseases.Methods A single center study.We collected 242 blood samples of suspected HIT patients whose platelet count decreased after heparin application during July 1 st ,2012 to June 30th ,2016 in Wuhan Asia Heart Hospital and detected the concentration of HIT antibodies , meanwhile the 4T′s score were calculated.Among the study objects , there are 206 patients received cardiac surgery , 28 received cardiac interventional therapy and 8 received drug therapy.And we divided them into HIT group (44, median age 57.5, 23 females ) and non-HIT group ( 198, median age 63.5, 87 females ) according to clinical diagnosis.Quantitative data was analyzed by independent t-test or Mann-Whitney U test.Qualitative data was analyzed by Fisher′s exact test.We drew ROC curve according to the statistical analysis to determine the optimal threshold value of antibodies in diagnosis of HIT andsensitivity , specificity, negative likelihood ratio, positive likelihood ratio of the HIT antibody detection .Therefore, we can assess the value of HIT antibody detection in HIT clinical diagnosis and treatment .Moreover, we used the optimal threshold value of antibodies to testify the suspected HIT patients .Results The HIT antibody concentration of HIT group (44) and non-HIT group ( 198 ) are 3.2 ( 95% CI:1.8 -5.5 ) U/ml and 0.4 ( 95% CI:0.3 -0.4 ) U/ml, respectively.The concentration of HIT group is much higher than the non-HIT group(P<0.000).When the cut-off value of HIT-Ab is set at 0.9 U/ml, sensitivity and specificity are 93.2%and 91.9%, respectively. And negative likelihood ratio and positive likelihood ratio are 0.07 and 11.53, respectively.When the cut-off value of HIT-Ab is set at 0.6 U/ml, sensitivity and specificity are 100.0%and 73.7%.HIT-Ab and 4T′s score of ROC-AUC are 0.971 and 0.745, respectively.The diagnosis value of HIT-Ab in HIT is significantly higher than the 4T′s score ( P<0.000).Conclusions HIT antibody detection is a simple and effective auxiliary diagnostic method in HIT exclusion .And HIT antibody detection is more optimal than the 4T′s score in HIT diagnosis and treatment .

Objective: To investigate the association between D-dimer levels and clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy. Methods: This prospective study included 640 consecutive patients underwent mechanical heart valve replacement in Wuhan Asia Heart Hospital between January 2013 and June 2014.Patients were assigned to abnormal D-dimer group (D-dimer level>cut off value, n=88) and normal D-dimer group (D-dimer level≤cut off value, n=552) according to D-dimer levels measured at 3 months after the initiation of oral anticoagulation therapy.All patients were followed up for 24 months or until the observation of the end points, which included thrombotic events, bleeding events and all-cause deaths.The anticoagulation therapy was monitored once per 1-2 months by the international normalized ratio (INR), and the target value was 1.8-3.0. Results: During a follow-up period of 24 months, rates of total clinical events (19.30%(17/88) vs. 5.8%(32/552), P<0.01), thrombotic events (11.4%(10/88) vs. 2.3%(13/552), P<0.01), and all-cause deaths (8.0%(7/88) vs. 2.0%(11/552), P<0.01) were all significantly higher in abnormal D-dimer group than in normal D-dimer group.There were no significant difference in bleeding events between the two groups (2.3%(2/88) vs. 3.1%(17/552), P=0.77). Multivariate Cox regression analysis showed that high D-dimer level was an independent risk factor of total clinical events (HR=3.86, 95%CI 1.92-7.76, P<0.01), thrombotic events(HR=5.29, 95%CI 2.12-13.10, P<0.01), and all-cause deaths(HR=5.32, 95%CI 1.71-16.60, P<0.01), but which was not correlated with bleeding events(HR=1.36, 95%CI 0.27-6.84, P=0.71). Conclusion Elevated D-dimer levels are linked with clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy.

Objective To investigate the relationship between the prevalence of isolated systolic hypertension (ISH) and the stages of chronic kidney disease (CKD) in chronic kidney disease outpatient clinic.Methods CKD patients of stages 1,2,3,4 and 5 were recruited (n=626).Based on office systolic pressure (SBP) and diastolic pressure (DBP),they were classified into four subtypes:normotension (＜ 140/90 mmHg),isolated diastolic hypertension (IDH,SBP ＜ 140 mmHg and DBP ≥ 90 mmHg),ISH (SBP≥ 140 mmHg and DBP ＜ 90 mmHg) and systolic-diastolic hypertension (SDH,SBP≥140 mmHg and DBP≥90 mmHg).Results The control rate of blood pressure was 86.4％,75.6％,65.3％,51.0％ and 37.0％ at CKD stage 1,2,3,4 and 5,respectively,which decreased with the advancement of CKD.There was a stepwise increase in the prevalence of ISH (0,9.2％,23.9％,28.6％ and 37.0％ at CKD stage 1,2,3,4 and 5,respectively) and SDH (4.5％,8.4％,8.0％,17.3％,21.9％ at CKD stage 1,2,3,4 and 5,respectively).Logistic regression analysis showed that age,diabetes and CKD stages were independent predictors of ISH.Compared with CKD stage 1-2,CKD stage 3,4 and 5 showed 2.388,2.697 and 5.980 folds risk in developing ISH.Conclusion The prevalence of ISH increases correspondingly with the advancement of stages of CKD,which may partially contribute to the increased cardiovascular mortality during the progress of CKD.