Application and development of stabilizers in coronary artery bypass grafting / 中国医师杂志

The first robotic heart surgery was performed more than two decades ago. Less invasive cardiac surgical techniques have become increasingly popular in recent years. The integration of emerging materials, computers and engineering technologies has provided the conditions for the application of robotic surgery in various cardiac procedures. Coronary artery bypass grafting (CABG), mitral valvuloplasty/valvuloplasty and radiofrequency/cryoablation for atrial fibrillation are some of the most common surgical procedures. Currently, only a few international cardiac centers have teams specializing in total endoscopic coronary artery bypass grafting. Although some studies have shown good results in robot-assisted heart surgery, questions remain about its safety, cost-benefit ratio, and long-term clinical outcomes. Robotic heart surgery poses higher challenges to myocardial protection and precise anastomosis. The role of stabilizers is to provide a relatively stable field of vision for heart surgery, which is the basis of all non-stop heart surgery. Because of their importance, researchers around the world are constantly exploring how to develop new, more sophisticated stabilizers. This review focuses on the research and development status and development trend of the stabilizer, summarizes the advantages and disadvantages of the current commonly used stabilizer, closely follows the clinic, makes in-depth analysis, and puts forward the key points of the future development of the stabilizer in coronary artery bypass surgery.

Performance of exhaled carbon monoxide measurement in smoking cessation clinics and its influence on patients' willingness and behavior for smoking cessation / 中华流行病学杂志

Objective: To evaluate the performance of exhaled carbon monoxide measurement in smoking cessation clinics and its influence on patients' willingness and behavior for smoking cessation in China. Methods: Data of 41 566 patients who visited 257 smoking cessation clinics equipped with exhaled carbon monoxide detectors from 2019 to 2021 were selected to study the relationship between exhaled carbon monoxide measurement and patients' willingness to quit smoking as well as smoking cessation rate in those who completed follow up. Results: Only 21 470 (51.7%) of the patients received exhaled carbon monoxide measurement in the first visit. Patients who had exhaled carbon monoxide measurement were 1.87 (95%CI: 1.78-1.96) times more likely to have stronger willingness to quit smoking. The follow up results indicated that the patients with exhaled carbon monoxide measurement in the first visit were 1.10 (95%CI: 1.05-1.16) times more likely to quit smoking one month later than those without the measurement, and 1.22 (95%CI: 1.17-1.29) times more likely to quit smoking three months later than those without measurement. Conclusions: Exhaled carbon monoxide measurement can improve patients' willingness to quit smoking and increase smoking cessation rate. However, the testing rate is low in smoking cessation clinics at present. It's important to promote the equipment and utilization of exhaled carbon monoxide detector in smoking cessation clinics.

Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021 / 中华预防医学杂志

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

Influencing factors of the adverse outcome of pulmonary tuberculosis among adolescents in Hangzhou City between 2005 and 2020: a school-based retrospective cohort study / 中华预防医学杂志

Objective: To explore the influencing factors of the adverse outcome of pulmonary tuberculosis (PTB) among adolescents in Hangzhou City between 2005 and 2020. Methods: A retrospective cohort study was used to collect the information of adolescent PTB patients with the onset of PTB occurring from January 1, 2005 to December 31 in 12 designated tuberculosis hospitals in Hangzhou, mainly including demographic, epidemiological, clinical manifestations, bacteriological characteristics and other data, through the China Management Information System for Infectious Disease Surveillance and Reporting and the follow-up survey. All patients were followed up and the end time was December 31, 2021. Multivariate Cox regression model was used to analyze the factors affecting the adverse outcome of these patients. Results: The mean age of 4 921 adolescent PTB patients was (18.9±3.6) years old, and the number of male and female patients were 3 074 and 1 847 respectively. The adverse outcome accounted for 14.7% (725) of all patients. Multivariate Cox regression model showed that eight risk factors, including management model from patients themselves or family members (HR=5.87, 95%CI: 4.55-7.64), molecular biology examination positive for PTB (HR=4.62, 95%CI: 2.98-7.19), the number of sputum smears-positive≥1 (HR=3.72, 95%CI: 2.87-4.83), non-standardized therapy regimens of PTB (HR=3.69, 95%CI: 2.95-4.64), history of retreated PTB (HR=2.22, 95%CI: 1.46-3.36), migrant adolescents (HR=1.89, 95%CI: 1.54-2.34), the number of chest X-ray scan (HR=1.83, 95%CI: 1.65-2.04), and severe PTB (HR=1.38, 95%CI: 1.02-2.05), were associated with the adverse outcome of adolescent PTB patients. Age (HR=0.94, 95%CI: 0.92-0.96), as the only protective factor, was associated with the adverse outcome of these patients. Conclusion: The management mode, molecular biological examination, chemotherapy program, history of tuberculosis, sputum smear examination, severity of tuberculosis, household residence, chest X-ray examination and age are associated with the adverse outcomes of adolescent PTB patients in Hangzhou.

Qualitative and quantitative study of constituents in Lysionoti Herba based on UHPLC-Q-Exactive Orbitrap HRMS and HPLC-UV / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HRMS) was employed to systematically analyze the chemical constituents in Lysionoti Herba, and high perfor-mance liquid chromatography-ultraviolet(HPLC-UV) to determine the content of main compounds. A Synergi~(TM) Hydro-RP 100 Å colu-mn(2 mm×100 mm, 2.5 μm) was used for gradient elution with acetonitrile-0.1% aqueous formic acid as the mobile phase at a flow rate of 0.2 mL·min~(-1) and a column temperature of 40 ℃. MS and MS/MS were conducted with electrospray ionization(ESI) in both positive and negative modes. The chemical components in Lysionoti Herba were identified by comparison with the retention time and mass spectra of reference compounds and the relevant mass spectral data reported in MS databases and relevant literature. Furthermore, the content of five constituents(neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin) in different Lysiono-ti Herba samples was simultaneously determined by HPLC-UV at the wavelength of 330 nm. A total of 84 compounds were identified in Lysionoti Herba, including 27 flavonoids, 20 phenylethanoid glycosides, 5 amino acids, 18 organic acids, 1 alkaloid, 6 nucleosides, and 7 others. The content of neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin showed good linear relationship(r>0.999) with the peak area within certain concentration ranges, which were 3.22-102.90, 12.84-410.82, 31.63-1 012.01, 25.00-800.11, and 4.08-130.51 μg·mL~(-1), respectively. The instrument precision, method repeatability, and solution stability all met requirement, and the average recovery rate was 97.31%-100.2%, with RSD ranging from 0.95% to 2.4%. The content of the five components varied among different Lysionoti Herba samples collected from different regions of Guizhou, and the average content of forsythoside B was the highest. The established qualitative method can rapidly and efficiently identify the chemical components of Lysionoti Herba, and the developed HPLC-UV method can simultaneously determine the content of five components in a simple, ra-pid, and accurate manner, providing a scientific basis for the quality evaluation of Lysionoti Herba.

Analysis on the industry characteristics of newly diagnosed occupational pneumoconiosis in Foshan City， 2007-2021 / 中国职业医学

@#Abstract: Objective To analyze the industry characteristics of new occupational pneumoconiosis in Foshan from 2007 to Methods 2021. The data of new cases of occupational pneumoconiosis in Foshan City from 2007 to 2021 were obtained from “ ” ， “ the China Disease Prevention and Control Information System subsystem the Occupational Disease and Health Hazardous ”， Results Factors Monitoring Information System and the industry characteristics of the cases were analyzed. From 2007 to ， ， （ ） 2021 there were 886 new cases of occupational pneumoconiosis in Foshan mainly include silicosis 68.3% in males （ ）， （ ） 94.2% and stage Ⅰ pneumoconiosis cases 75.9% . The median age of cases at the time of diagnosed disease was 47 years ， old and the median working age of dust exposure was 11.2 years. The enterprises where all cases are located involve eight top ， ； ， - industry categories of which manufacturing industry accounted for 97.6% and 30 major industry categories of which non （ ） ， metallic mineral products industry was the highest 60.5% . There were 554 sporadic cases and 332 cluster cases and the ， ， Conclusion industries were mainly non-metallic mineral products accounting for 55.0% and 69.6% respectively. ， - Occupational pneumoconiosis in Foshan is dominated by silicosis and the key industries are non metallic mineral products.

Effects of learning and lifestyle behaviors during home confinement on depressive and anxiety symptoms among primary school students / 中国学校卫生

Objective@#To examine the changes of depressive and anxiety symptoms in school aged children during home confinement and to identify possible influence of learning and lifestyle behaviors on mental health changes.@*Methods@#The population of this study were obtained from the "Tongji Mental Health Cohort". Two primary schools in Wuhan were selected through cluster sampling and students in grade 2-5 were surveyed. This study was divided into two stages. In the first stage (T1=during home learning), a total of 2 588 valid questionnaires were collected. In the second phase (T2=during school learning), 2 424 children were followed up successfully. Combining the results of the depression and anxiety symptoms of the two surveys of children respectively to classify the children s psychological outcomes. Association between home learning and lifestyle behaviors with the change of psychological symptoms in school aged children were estimated by disordered multi classification Logistic regression.@*Results@#The prevalence of depressive and anxiety symptoms were 28.9% and 21.0% in school aged children at T1, 35.6% and 30.6% at T2, respectively. The aggravation and persistence of depressive and anxiety symptoms in children were partly related to their home learning and lifestyle behaviors. Concentration in class（ OR=0.63，95%CI =0.45-0.89）, frequent interaction with teachers ( OR =0.74, 95% CI = 0.57- 0.95 ), participation in physical exercise at home ( OR =0.60, 95% CI =0.41-0.87) was negatively associated with depressive symptoms in children. Time spent on playing video games ( OR =1.15, 95% CI =1.06-1.24) and fear of infection with coronavirus disease 2019 ( OR =1.83, 95% CI =1.39-2.42) were positively associated with anxiety in children. Boys（ OR=0.70， 0.63 ） were more likely to suffer from depression and anxiety symptoms than girls.@*Conclusion@#The prevalence of depressive and anxiety symptoms among school aged children increased when they went back to school after home confinement, suggesting more attention are needed for mental health intervention among school aged children.

The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.

Hand-sewn expanded polytetrafluoroethylene valved conduit for right ventricular outflow tract reconstruction / 中南大学学报(医学版)

OBJECTIVES@#Due to the lack of large-sized pulmonary valved conduit products in clinical practice, hand-sewn expanded polytetrafluoroethylene (ePTFE) valved conduit has been used for right ventricular outflow tract (RVOT) reconstruction in many heart centers around the world. This study aims to summarize the early results of the ePTFE valved conduit and the sewing technology of the conduit in combination with the latest progress, and to provide a reference for the application of ePTFE valved conduit.@*METHODS@#A total of 21 patients using ePTFE valved conduit for RVOT reconstruction in the Second Xiangya Hospital, Central South University from October 2018 to October 2020 were prospectively enrolled in this study. The age at the implantation of the conduit was 4.3 to 43.8 (median 15.1) years old, with weight of (38.9±4.1) kg. In this cohort, 14 patients underwent re-reconstruction of RVOT, including 12 patients with pulmonary regurgitation at 6.3 to 31.0 (median 13.8) years after tetralogy of Fallot (TOF) repair, and 2 patients with failed bovine jugular vein conduit (BJVC). Seven patients underwent Ross operations. Among them, 3 were for aortic valve stenosis, 2 were for aortic regurgitation, and 2 were for both stenosis and regurgitation. The ePTFE valved conduits were standard hand-sewn during the surgery. The 3 leaflets were equal in size with arc-shaped lower edge of the valve sinus. The free edge of the valve leaflets was straight with the length of about 1 mm longer than the diameter. The height of the valve sinus was 4/5 of the diameter. The junction of the valve leaflet was 3/4 of the height of the sinus. The designed leaflets were then continuous non-penetrating sutured into the inner surface of Gore-Tex vessel to make a valved conduit. Valved conduits with diameter of 18, 20, and 22 mm were used in 2, 9, and 10 cases, respectively. The surgical results, postoperative recovery time, and serious complications were summarized, and the changes of postoperative cardiac function status and hemodynamic status of the conduits were investigated.@*RESULTS@#During the implantation of ePTFE valved conduit for RVOT reconstruction, 2 patients underwent mechanical mitral valve replacement with Ross operation, 2 patients with pulmonary regurgitation with repaired TOF underwent left and right pulmonary artery angioplasty, and 1 patient with failed BJVC underwent tricuspid valvuloplasty. The cardiopulmonary bypassing time for patients underwent re-reconstruction of RVOT was (130.9±16.9) min, with aorta clamping for 1 patient to repair the residual defect of the ventricular septum. The cardiopulmonary bypassing and aorta clamping time for Ross operation were (242.7±20.6) min and (145.6±10.5) min, respectively. The duration of postoperative ventilator assistance, intensive care unit stay, and hospital stay were 3.5 h to 7.7 d (median 17.1 h),11.2 h to 29.5 d (median 1.9 d), and 6.0 to 56.0 (median 13.0) d, respectively. All patients survived after discharge from hospital. The follow-up rate after discharge was 100% with median time at 15.0 (13.0 to 39.0) months. No death happened during the follow-up. One patient underwent stent implantation due to right coronary stenosis 2 months after Ross operation. One patient underwent balloon dilation due to right pulmonary artery ostium stenosis 1 year after re-reconstruction of RVOT. The cardiac function of all patients recovered to NYHA class I 6 months after operation. The peak pressure gradient across the valve measured by transthoracic echocardiography before discharge was (9.4±2.6) mmHg (1 mmHg=0.133 kPa), and (18.3±6.1) mmHg at the last follow-up. There was no significant increase in the gradient during the follow-up (P=0.134). No patient suffered from mild or more pulmonary regurgitation.@*CONCLUSIONS@#Hand-sewn ePTFE valved conduit is feasible for RVOT reconstruction. It is a promising material for RVOT reconstruction which can effectively meet clinical need. In our experience, the ePTFE valved conduit is simple to manufacture with satisfactory early outcomes.In the application of ePTFE valved conduit, attention should be paid to implantation indications and postoperative anticoagulation management, especially to the preparation details of the valved conduit, to obtain better function and durability of the conduit after implantation.

Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Establishment of EGFR-T790M mutation detection method for non-small cell lung cancer based on droplet digital PCR / 中华检验医学杂志

Objective:Use the droplet digital PCR (ddRCR) technology to establish, optimize and evaluate the method of EGFR-T790M mutation detection.Methods:The relevant probes and primers were designed for EGFR-T790M mutations. The ddPCR reaction system was established, the optimal annealing temperature was set and the basic performance of the method was tested. On this basis, from January 2019 to October 2019, 72 cell-free DNA (cfDNA) samples from NSCLC patients were collected from Shandong Cancer Hospital Affiliated to Shandong First Medical University, and clinically verified. The consistency of the gene mutation detections with Bole ddPCR products was analyzed using Kappa test.Results:The ddPCR reaction system was established and optimized. Linear evaluation showed the R2 value was greater than 0.99. Using ddPCR, the blank detection limit was determined to be the numbers of mutant droplets≥2, with excellent specificity. For the sensitivity analysis, the lower limit of mutation detection was determined to be at least 0.05%. In the repeatability and inter-assay precision tests, the results had a coefficient of variation( CV)<20%. The relative deviation of the results was within the range of±10% for the accuracy analysis. Using the established T790M mutation detection method, 72 samples from the NSCLC patients were tested for genetic mutation in cfDNA, and the overall agreement with the Bole ddPCR products was 91.67% (66/72, Kappa=0.749; P<0.001). Conclusion:Using ddPCR, the method of EGFR-T790M mutation detection for NSCLC was successfully established.

Enlarged perivascular space and post-stroke cognitive impairment / 国际脑血管病杂志

Post-stroke cognitive impairment (PSCI) directly affects the outcome of patients with stroke. Enlarged perivascular spaces (EPVS) suggest the impairment of brain clearance mechanism and may affect cognitive function. More and more studies have confirmed that the presence of EPVS will aggravate PSCI. This article reviews the relationship between EPVS and PSCI.

Lipoprotein (a) and ischemic stroke / 国际脑血管病杂志

A large number of studies have shown that the elevated lipoprotein (a) is a risk factor for ischemic stroke, but the specific mechanism is still unclear. Therefore, this article reviews the role of elevated lipoprotein (a) in ischemic stroke, its mechanism, and intervention measures.

Selection of enteral nutrition regimens for children with abdominal Henoch-Schönlein purpura / 中国当代儿科杂志

OBJECTIVE@#To explore the reasonable and effective enteral nutrition regimen for children with abdominal Henoch-Schönlein purpura (HSP).@*METHODS@#A retrospective analysis was performed on the medical data of children with abdominal HSP who were hospitalized from August 2013 to August 2018. According to the starting time of enteral nutrition after abdominal pain relief, the children were divided into three groups: < 24 hours (@*RESULTS@#The retrospective analysis showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had a lower recurrence rate of clinical symptoms and the highest degree of satisfaction among their family members (@*CONCLUSIONS@#It is reasonable and effective to start the feeding with extensively hydrolyzed lactoprotein formula at 24-48 hours after abdominal pain relief in children with abdominal HSP.

A nomogram for predicting the risk of multidrug-resistant tuberculosis / 中华传染病杂志

Objective:To construct a simple, precise and personalized comprehensive nomogram for prediction the risk of multidrug-resistant tuberculosis (MDR-TB) and to evaluate its prediction value among individuals with previous tuberculosis history (PTBH).Methods:A matched case-control study (1∶2 ratios) was performed in 1 881 patients with PTBH treated in 12 designated tuberculosis hospitals in Hangzhou City between January 1, 2005 and December 31, 2019, and there were 1 719 patients in training set, and 162 in validation set. A multivariable Cox regression analysis was used to evaluate independent predictors for the incident of MDR-TB in individuals with PTBH. A comprehensive nomogram was developed based on the multivariable Cox model. The accuracy of the prediction was assessed using concordance index (C-index), calibration curve and area under the receiver operator characteristic (ROC) curve.Results:The nomogram constructed based on the multivariable Cox regression model incorporated 10 independent predictors of the risk of MDR-TB. A history of direct contact (grade 1, 0-100.0 points) ranked on the top of all risk factors, followed by duration of positive sputum culture (grade 2, 0-84.5 points), unfavorable treatment outcome (grade 3, 0-52.0 points), human immunodeficiency virus infection (grade 4, 0-48.5 points), retreated tuberculosis history (grade 5, 0-40.0 points), non-standardized treatment regimens of retreated tuberculosis (grade 6, 0-32.5 points), duration of pulmonary cavities (grade 7, 0-31.0 points), passive mode of tuberculosis case finding (grade 8, 0-25.0 points), age<60 years (grade 9, 0-17.5 points), and standard frequencies of chest X-ray examination (grade 10, 0-14.0 points). The C-indexes of this nomogram for the training and validation sets were 0.833 (95% confidence interval ( CI) 0.807-0.859) and 0.871 (95% CI 0.773-0.969), respectively, indicating that the nomogram had good fitting effect. The calibration curves for the risk of incident MDR-TB showed an optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively.The areas under ROC curve of the 1-year, 5-year, and 10-year MDR-TB risk probability of the training set were 0.904, 0.921, and 0.908, respectively, and those of the validation set were 0.954, 0.970, and 0.919, respectively. Conclusion:Through this nomogram model, clinicians could precisely predict the risk of incident MDR-TB among individuals with PTBH in the clinical practice.

Bushen Huoxue Prescription Replenishes Diminished Ovarian Reserve in Rats Through PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the mechanism of Bushen Huoxue prescription in regulating the related factors in phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt）/ mammalian target of rapamycin （mTOR） pathway and improving ovarian reserve function of rats with diminished ovarian reserve （DOR）. Method:Sixty DOR model rats were duplicated by Ataya method （intraperitoneal injection of cyclophosphamide） and then randomized into the model group， estradiol valerate （0.000 9 g·kg^-1） group， and high- （33 g·kg^-1）， middle- （16.5 g·kg^-1） and low-dose （8.25 g·kg^-1） Bushen Huoxue prescription groups， with 12 rats in each group. Another 12 healthy rats were classified into the blank control group. The rats in each group were given the corresponding drugs by gavage， while those in the blank control group and model group received the same volume of normal saline， once per day， for 14 successive days. After treatment， the ovarian tissue was stained with hematoxylin-eosin （HE） for observing the changes in quantities of primary follicles， mature follicles， and total follicles under a light microscope， followed by the detection of vascular endothelial growth factor （VEGF） expression in the ovarian tissue by immunohistochemistry. The protein expression levels of PI3K， Akt， mTOR， and cysteine-dependent aspartate-directed protease-3 （Caspase-3） in the ovarian tissue were assayed by Western blot， whereas the mRNA expression levels of PI3K， Akt， and mTOR were measured by Real-time polymerase chain reaction （Real-time PCR）. Result:As revealed by comparison with the blank control group， the quantities of mature follicles and total follicles in the ovarian tissue of model group were significantly reduced （<italic>P</italic><0.05， <italic>P</italic><0.01）. The protein expression levels of VEGF and Caspase-3 in the ovarian tissue were increased （<italic>P</italic><0.05）， while the protein and mRNA expression levels of PI3K， Akt， and mTOR were decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， Bushen Huoxue prescription at the high and middle doses elevated the quantities of mature follicles and total follicles to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）， and VEGF increased most significantly in the middle-dose Bushen Huoxue prescription group （<italic>P</italic><0.05）. Caspase-3 in the low-， middle-， and high-dose Bushen Huoxue prescription groups and the western medicine group declined. The protein and mRNA expression levels of PI3K， Akt， and mTOR were up-regulated in the middle- and high-dose Bushen Huoxue prescription groups （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the levels in the middle-dose Bushen Huoxue prescription group were closer to those in the blank control group. Conclusion:Bushen Huoxue prescription effectively improves the ovarian reserve function of rats with DOR and increases the number of follicles possibly by up-regulating VEGF expression in the ovarian tissue， activating the PI3K/Akt/mTOR signaling pathway， and regulating the content of Caspase-3.

Classification and reconstruction of complex defects after lateral facial tumor surgery / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the classification and reconstruction strategy of defects in lateral face region after operation of malignant tumors. Methods: Eighteen cases with the reconstruction of complicated defects after resection of tumors in the region of lateral face from January 2015 to January 2018 in Hunan Cancer Hospital were retrospectively reviewed. There were 14 males and 4 females, aged from 32 to 68 years. According to the presence or absence of bony scaffold, complicated defects were divided into two main categories: soft tissue perforating defects and soft tissue defects combined with bony scaffold defects. All soft tissue perforating defects in 5 cases were repaired with free anterolateral femoral flaps. Among 13 cases with soft tissue plus bony scaffold defects, 3 were repaired with free fibular flaps, 6 with free fibular flaps combined with free anterolateral femoral flaps, and 4 with chimeric deep circumflex iliac artery perforator flaps combined with anterolateral femoral flaps. Results: All flaps survived well. Two patients complicated with fistula in floor of mouth, but the wound healed after dressing change. Transoral feeding was resumed within 2 weeks after surgery in all patients. One year follow-up evaluation showed that 14 cases had symmetrical face and 10 cases had mouth opening more than 3 transverse fingers. After 36-50 months of follow-up, 6 patients died, with an overall 3-year survival rate of 66.7%. Conclusion: The classification of defects with or without bony stent loss is conducive to the overall repair design, the recovery of facial contour stent, the effective fill of dead space and the maintain of residual occlusal relationship. Good reconstruction results require a multi flap combination of osteocutaneous and soft tissue flaps.

Reconstruction of complex tissue defects in temporal region: report of 3 cases / 中华耳鼻咽喉头颈外科杂志

Objective: To discuss the techniques and repairing methods of various degree of compound tissue defects in the auriculotemporal region. Methods: Retrospective analysis was conducted on three cases of different repairing methods for huge compound tissue defects in different degrees in the auriculotemporal region after the resection of the malignant tumor or sinus tract due to repeated infection in our hospital. Results: Following total removal of the tumors or sinus tract in all patients, we applied retroauricular lingual flap transfer repairing, latissimus dorsi flap free transfer repairing and vascular anastomosis, scalp tissue expansion in stage Ⅰ, then repairing the lesion with expanded scalp and filling the huge mastoid cavity with abdominal fat in stage Ⅱ, respectively, according to the characteristics of compound tissue defects in the auriculotemporal region. All free flaps survived well. Conclusions: The anatomy of the auricular-temporal area is complex and involves important vascular and neural structures of head and neck and lateral skull base. The huge composite tissue defect following auriculotemporal region surgery, which is composed of skin, muscle and bone tissue, needs to be repaired in one stage. Therefore, flexible repairing methods should be chosen based on different situations, for attaining the goal of completely removing tumor and lesions, and then, covering the operation cavity.

Establishment of a cell-based screening assay for inhibitors of SARS-CoV-2 3CL protease / 药学学报

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that caused the global COVID-19 outbreak. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a key role in virus replication and has become an ideal target for antiviral drug design. In this paper, we report the validation and use of bioluminescence resonance energy transfer (BRET) technology to establish a cell-based assay for screening for SARS-CoV-2 virus 3CL protease inhibitors. The results show that the method is able to monitor the cleavage efficiency of 3CL protease with good reproducibility (Z' factor is 0.59), and is consistent with antiviral activity analysis in cell culture. This work demonstrates that this method can be applied to the screening and evaluation of 3CL protease inhibitors, providing a powerful tool for the development of new drugs.

Overexpressed GATA-4 bone marrow-derived mesenchymal stem cell exosomes improve myocardial infarction via miRNA-673-5p/Tsc-1 molecular axis / 医学研究生学报

ObjectiveExosomes secreted by BMSC overexpressing GATA-4 gene (BMSCGATA-4-exosome) can promote the differentiation of BMSC into cardiomyocyte-like cells, thereby improve cardiac function after myocardial infarction. However, the molecular mechanism of BMSCGATA-4-exosome in cardiomyocyte-like cell differentiation is unknown. The effect of the secretion of BMSCGATA-4 exosome from bone marrow mesenchymal stem cells (BMSC) in the differentiation of stem cells into cardiomyocytes was determined in miRNA-673-5p/Tsc-1 axis dependent manner.MethodsMouse models of myocardial infarction were established and divided into seven groups. Simulation group (BMSCmiR-673-5p-mimic exosome), inhibition group (BMSCmiR-673-5p-inhibitor exosome), GATA-4 group (BMSCGATA-4 exosome), empty vector group (BMSCempty vector exosome）, and BMSC group (BMSC exosome) were injected into the tail vein for 48 h, and the untreated and normal mice were used as the control group. Cardiac ultrasound was used to detect cardiac function in each group. miRNA-673-5p expression in myocardial infarction was detected using real-time polymerase chain reaction (RT-PCR). The myocardial tissues were extracted from the same myocardial infarction site. Myocardial-specific molecules, such as α-actin, Desmin, cTnT, and Cx43, were detected using RT-PCR. Western blot was used to determine the expression of the corresponding target gene of miRNA-673-5p, Tsc-1, Erk1/2, and Mef2c proteins.ResultsThe simulation group wan shown the most significantly improved myocardial function (P<0.05) with an expression peak of miRNA-673-5p in cardiomyocytes (P<0.05). The highest content of myocardial-specific molecules including α-actin, Desmin, cTnT, and Cx43 was found in the simulation group. The simulation group had the lowest expression of Tsc-1 in cardiomyocytes (P<0.05).ConclusionOverexpressed BMSCGATA-4 exosomes inhibit Tsc-1 expression through miRNA-673-5p to improve cardiac function during myocardial infarction.