COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

Abstract: Objective　To investigate the clustered regularly interspaced short palindromic repeats (CRISPR) genotypes and regional distribution of Yersinia pestis strains in the natural plague foci of Hainan Tibetan Autonomous Prefecture of Qinghai Province (referred to as "Hainan prefecture") and provide a scientific basis for plague prevention and control in this area. Methods　A total of 36 representative Yersinia pestis strains, which were isolated from different host animals and insect vectors from 1954 to 2009 in Hainan Prefecture, were selected as experimental subjects. The DNAs were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. Three pairs of CRISPR primers (YPa, Ypb, YPc) were used for PCR amplification, sequencing and analysis of the DNA of the tested strains, respectively, as a means to identify the CRISPR genotypes of Yersinia pestis in Hainan Prefecture. Results　A total of 17 spacers were observed among 36 strains of Yersinia pestis, including 9 of YPa, 5 of YPb and 3 of YPc. All strains were divided into 5 CRISPR gene clusters (Cb2, Cb4 ', Ca7, Ca7 ', Ca35 ') and 6 genotypes (G1, G9, G22, G22-A1 ', G26-A1 ', G26-A1 'A4 -). The G26-a1 ' was the main genotype, which was distributed in Gonghe, Guide and Xinghai County, and the G22 is the second type, which was distributed in Gonghe and Guide County. Conclusions　The genetic polymorphism of CRISPR loci of Yersinia pestis strains in Hainan was high, and the regional distribution characteristics of Yersinia pestis strains with different genotypes were significant.

Objective: To analyze the clinical features of patients with acute pulmonary embolism (APE) living in high altitude area of Yunnan province. Methods: This was a cross-sectional retrospective study. APE patients, hospitalized in our hospital between January 2017 and December 2019, were included. The selected patients were divided into low-risk group, medium-risk group and high-risk group according to risk stratification. The clinical data of patients, including demographic data, the main symptoms, risk factors of APE, heart rate and systolic blood pressure and laboratory testing results (D-dimer, cardiac troponin I (cTNI), N terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography and electrocardiogram examination results, were obtained through the electronic medical record system. The clinical characteristics of selected patients were analyzed. Results: A total of 392 patients, aged (63.5±15.7) years, 224 males (57.14%), were included in this study and there were 59 low-risk, 304 medium-risk and 29 high-risk patients in this cohort. The main clinical manifestations were chest pain (157(40.05%)), dyspnea (107(27.30%)), hemoptysis (55(14.03%)), syncope as the first symptom (20(5.10%)), and only 6 cases (1.53%) presented with the typical "Virchow's triad". Most of the patients were accompanied by atypical chest tightness (223(56.89%)) and cough (208(53.06%)). The main risk factors were venous thrombosis of lower limbs (179(45.66%)), hypertension (138(35.20%)), surgery (63(16.07%)), and chronic obstructive pulmonary disease (COPD) (62(15.82%)). There were 57 cases (14.54%) of coronary heart disease, 57 cases (14.54%) of diabetes, 51 cases (13.01%) of cerebral infarction, 47 cases (12.00%) of advanced age, 15 cases (3.83%) of tumor, 7 cases (1.79%) of activity restriction, 6 cases (1.53%) of pregnancy and 4 cases (1.02%) of hormone use in this cohort. The proportion of lower extremity venous thrombosis was significantly higher in low-risk group than in medium-risk group (P<0.01), COPD was more common in high-risk and medium-risk groups than in low-risk group (P<0.01), hypertension was more common in high-risk group than in medium-and low-risk groups (P<0.01). The proportion of advanced age was significantly higher in medium-risk group than in low-risk group (P<0.01). There were no significant differences in RBC and hemoglobin level between low-, medium-and high-risk groups (P>0.05). The level of D-dimer was significantly higher in high-risk group than in medium-and low-risk groups (P<0.05). Levels of NT-proBNP and cTNI were significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). Increased proportion of cTNI and NT-proBNP was significantly higher in high-risk group than in medium- and low-risk groups (P<0.05). There were 105 (26.79%) patients with pulmonary hypertension (PAH). The incidence of PAH was significantly higher in high-risk group than in low-risk group (P<0.01). There were 104 patients (26.53%) with right ventricular enlargement, and the incidence of right ventricular enlargement was significantly higher in high-risk group than in medium-and low-risk groups (P<0.01). Characteristic changes of electrocardiogram in patient with APE were T-wave inversion of limb leads (98(25.00%)), followed by S_ⅠQ_ⅢT_Ⅲ (83(21.17%)). Conclusions: The main clinical manifestations of APE in Yunnan high altitude area are chest pain and dyspnea, and syncope is the first symptom in some patients, but the typical "Virchow's triad" is rare. The most common risk factors are lower extremity venous thrombosis, hypertension, and COPD. Clinical symptoms, risk factors and laboratory examination results differ among patients with different risk stratification.
Adolescent ; Altitude ; Biomarkers ; China/epidemiology* ; Cross-Sectional Studies ; Humans ; Male ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Pulmonary Embolism/epidemiology* ; Retrospective Studies

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.
Abdomen ; surgery ; China ; Drainage ; methods ; Evidence-Based Medicine ; Humans ; Practice Guidelines as Topic ; Societies, Medical ; organization & administration ; Surgical Wound Infection ; prevention & control ; Traumatology ; organization & administration ; Vacuum

Objective To analyze the rates of occurrence,presentations and treatment of coronary intramural hematomas(IMH)after coronary artery stent implantation.Methods Retrospective analysis was carried out in non-chronic total occlusion patients who developed coronary intramural hematomas after coronary artery stent implantation between January 1,2011 to December 31,2016.Statistical analysis was made in the fields clinical data,coronary angiography features,treatment provided,and postoperative follow-up date of the patients.Results Among the 26 IMH patients,the male gender(15/26,57.7％)and existiing hypertension(17/26,65.4％)were more common risk factors for IMH after coronary artery stent implantation.Fourteen patients developed coronary dissection.The coronary intramural hematomas presented as new non-spasm and non-thrombus coronary stenosis.The coronary intramural hematomas were found to have involved the distal segment to the stents in 16 patients.Two patients received balloon dilation,five patients had stents implantation after balloon dilation,13 patients(50.0％)were treated with direct stent implantation and the other 6 patients did not have further intervention.The follow up period after hospital discharge was(2.39±1.68)years.No adverse cardiovascular event occurred.Five patients received follow-up angiography examination.Two patients and another one patient were found to have coronary intramural hematomas fully resolved at three months and one year with coronary angiographic follow up,respectively.Two patients had IMH on angiography at 1 year follow up.Conclusions Coronary intramural hematomas after coronary artery stent implantation often involved the distal segment to the stent in hypertensive patients presenting as new non-spasm and non-thrombus coronary stenosis.Patients at low risk of acute coronary occlusion could receive conservative treatment.Patients with extentsive length of intramural hematomas should consider stent implantation for treatment.

Objective: To describe the incidence,clinical characteristics,therapy strategy and outcomes of spontaneous coronary artery dissection based on single-center experience in China.Methods:We performed retrospective case-identification study in 16 526 patients underwent coronary angiography in Zhongshan Hospital of Fudan University between March 2015 to December 2016,and identified 17 patients with spontaneous coronary artery dissection.Risk factors,clinical features,angiographic features,therapy strategy,and clinical outcomes were analyzed.Results:The incidence of SCAD was 17 of 16 526(1.03/1 000).The mean age was(49.06 ± 10.73)years old(range:26-67 years old).In these 17 cases,4 cases were males,and others were females.Females constituted 13 of 17(76.5%).All SCAD patients presented with acute coronary syndrome,including 10 patients with acute ST-elevated myocardial infarction,3 patients with acute non-ST-elevated myocardial infarction and 4 patients with unstable angina.Twenty dissection sites were identified in 17 SCAD patients. Dissection was predominantly located at the left descending artery(50%)and the right coronary artery(35%).All lesions fell into three types:type Ⅰ(n=5),type Ⅱ A(n= 7),type ⅡB(n= 6),and type Ⅲ(n= 2).The TIMI flow in the distal segment of the coronary dissection was classified as follows:class 0(n=4),class 1(n=2),class 3(n=14).Conservative medical treatment was adopted by 7 of 17(41.1%)patients,and percutaneous transluminal coronary angioplasty(PTCA)in 1 of 17(5.9%)patients.No recurrent angina and other cardiovascular events was observed during clinical follow up. Percutaneous coronary intervention(PCI)was performed in 9 of 17(52.9%)patients,and the mean number of deployed stent was(2.44 ± 1.13).Intramural hematoma was extended during PCI in 5 of 9(55.6%)patients,resulting in new-onset nonfatal myocardial infarction in one patient and cardiac death in another patient.Conclusions:SCAD should be considered in young and middle-aged female patients presented with acute coronary syndrome,especially in those with few coronary risk factors. Interventional cardiologist should be familiar with the angiographic characteristics of SCAD,and turn to intravascular ultrasound if necessary.Conservative treatment should be the first choice in most patients with SCAD,while PCI intervention could be considered in high risk patients.Be caution to prevent interventional complications such as dissection expansion in the patients with high-risk.

Objective:To evaluate the safety and efficacy of balloon-assisted tracking (BAT) technique in guiding the catheter through the spastic radial artery via percutaneous coronary intervention.Methods:The data of patients who received coronary intervention through the transradial approach in Department of Cardiology of Zhongshan Hospital Affiliated to Fudan University from June 2014 to September 2016 were retrospectively analyzed.69 cases of radial artery and / or brachial artery spasm were selected, of which 24 cases were treated with BAT technique (group BAT), and 45 cases were treated by the conventional method (conventional group).The success rate of the catheter through the spastic segment and the incidence of related complications were compared between the two methods.Results:In the BAT group, the guide catheter was successfully negotiated across the spastic segment or dissecting vessels in all 24 cases (100%), while in only 14 cases (31.1%) in the conventional group (P=0.000).Guide catheter traversing the spastic segment within 5min, between 5min and 15min, and more than 15min was seen in 20 (83.3%), 3 (12.5%) and 1 (4.2%) patients in the BAT group, while in 2 (14.3%), 6(42.9%) and 6 (42.9%) patients in the conventional group, respectively (P=0.000).Incidence of forearm hematoma was 8.3% and 20% in the BAT group and the conventional group, and the difference was not statistically significant.Conclusions:The BAT technique is a safe and effective way to guide the catheter through the spasm of radial and/or brachial artery via percutaneous coronary intervention.BAT is superior to the conventional technique.

OBJECTIVETo evaluate the sensitivity and specificity of CD8CD28/CD8CD28T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD).

METHODSForty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8CD28and CD8CD28T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8CD28/CD8CD28T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8T lymphocytes and the factors were analyzed.

RESULTSThe utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8CD28T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8CD28T cells, CD8CD28T cells, and especially CD8CD28/CD8CD28ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ=9.730, P=0.002; Χ=15.981, P=0.000). CD8CD28/CD8CD28ratio was significantly related to both BA (P=0.009) and surgery (P=0.038).

CONCLUSIONBoth decreased CD8CD28T cells and elevated CD8CD28T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.