This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Aim To explore the mechanism of process¬ing and increasing efficiency of Arisaematis rhizomz preparatum. Methods UPLC-Q-TOF-MS/MS tech¬nology was used to detect the chemical components be¬fore and after processing of Arisaematis rhizomz prepara¬tum, and its mechanism of action was analysed in the treatment of 44 asthma and phlegm " by using network pharmacology. A rat model of allergic asthma was es- tablished to compare the efficacy of Arisaematis rliizoma before and after processing. Results A total of 27 chemical components were identified, among which cur- cumin ,6-gingerol and other components increased after processing. Combined with the database prediction, the action mechanism of the 36 chemical components in the treatment of 44 asthma and phlegm" diseases was dis¬cussed and predicted through network pharmacology. The results of animal experiments showed that the effect of processed Arisaematis rhizoma on allergic asth¬ma was better than that of Arisaematis rhizoma, but there was no significant difference. Conclusions The addition of curcumin, 6-gingerol, camphor, demethyl- curcumin and other components after the processed Ari¬saematis rhizomz preparatum may be the reason for the synergistic effect of Arisaematis rhizomz preparatum in the treatment of allergic asthma.

Objective: To evaluate the safety and efficacy of catheter ablation in patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma. Methods: Nine patients with new onset atrial arrhythmia and a prior history of left atrial myxoma, who received surgical myxoma excision and catheter ablation between September 2014 and November 2019, were included in the present study. Baseline characteristics, procedural parameters during catheter ablation, severe perioperative adverse events, recurrence rate of arrhythmia and clinical prognosis were analyzed. Kaplan Meier survival analysis was used to define the maintenance rate of sinus rhythm after catheter ablation in this patient cohort. Results: Nine patients were included. The average age was (55.8 ± 9.1) years old (3 male), there were 3 patients (3/9) with paroxysmal atrial fibrillation (PAF) and 6 patients (6/9) with atrial flutter or atrial tachycardia (AFL or AT). Ablation was successful in all patients, there were no perioperative complications such as stroke, pericardial effusion, cardiac tamponade, vascular complications or massive hemorrhage. During a mean follow-up time of 40.0 (27.5, 55.5) months, sinus rhythm was maintained in six patients (6/9) after the initial catheter ablation. The overall sinus rhythm maintenance rate was 2/3. In addition, 1 out of the 3 AF patients (1/3) developed recurrence of AF at 3 month after ablation, and 2 out of the 6 AFL or AT patients (2/6) developed late recurrence of AF or AFL (19 months and 29 months after ablation), two out of three patients with recurrent AFs or AFL received repeated catheter ablation and one patient remained sinus rhythm post repeat ablation. Meanwhile, there was no recurrence of atrial myxoma, no death, stroke, acute myocardial infarction and other events during the entire follow-up period. Conclusions: Catheter ablation is a safe and feasible therapeutic option for patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma.

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

ObjectiveUsing Chromium-51 release assay, lactate dehydrogenase release assayand other methods to detect the cytotoxicity of CD19 CAR-T cells is cumbersome, with low repeatability and poor stability. This study aims to establish a label-free and real-time method for detectingspecific cytotoxicity of CD19 CAR-T cells.MethodsIn order to establish target cell models for cytotoxic assay of CD19 CAR-T cells by using Real Time Cellular Analysis (RTCA) system,the adherent human breast cancer cells were infected with lentiviral vectors encoding CD19. CD19 expression on the transduced cells was detected by flow cytometry. The cellsexpressing CD19 stably werethen sorted by fluorescence activated cell sorting (FACS).With such cells as target cells, CD19 CAR-T cells and BCMA CAR-T cells as effector cells, RTCAsystem was used to evaluate the cytotoxicity of CAR-T cells against target cells.ResultsMDA-MB-231 and SKBR3cells with stable expression CD19were obtained in this study.The results of flow cytometry showed that positive expression rate of CD19 in MDA-MB-231/CD19 cells and SKBR3/CD19 monoclonal cells were 99.03% and 98.91%,respectively.RTCA results showed that with MDA-MB-231 and MDA-MB-231/CD19 cells as target cells,CD19 CAR-T cells showed significant cytotoxicity to MDA-MB-231/CD19 cellsat the effector-target ratio of 5∶1, 1∶1 and 1∶5,but not to MDA-MB-231 cells. With SKBR3 and SKBR3/CD19 cells as target cells, CD19 CAR-T cells showed significant cytotoxicity to SKBR3/CD19 cellsat the effector-target ratio of 5∶1and 1∶1. When the effector-target ratio was 1∶5, there was no obvious cytotoxicity.The data of MDA-MB-231/CD19 or SKBR3/CD19 as target cells and CD19 CAR-T as effector cells were analyzed separately, showing that when the number of target cells was the same, the cytotoxicity detected by RTCA increased as the number of CD19 CAR-T cells increased.The cytotoxic assays of CD19 CAR-T cells showed specificity and dose-response relationship of CD19 CAR-T cytotoxicity against the target cells.ConclusionThis study established a method for evaluating cytotoxicity of CD19 CAR-T cells that is real-time, label-free, simple and convenient.

BACKGROUND: Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells. METHODS: We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry. RESULTS: The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. CONCLUSION Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.

Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA₂DS₂-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA₂DS₂-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA₂DS₂-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA₂DS₂-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA₂DS₂-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA₂DS₂-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA₂DS₂-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA₂DS₂-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA₂DS₂-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA₂DS₂-VASc score 2, especially female patients aged 65-74 years old with CHA₂DS₂-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.
Adult ; Aged ; Anticoagulants ; Atrial Fibrillation ; China ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; Stroke ; Thromboembolism

Objective To ascertain the characteristics of the parturient women in the district, the requirement and satisfaction for postpartum visits, and to explore the present situation of postpartum visits in the district, providing theoretical basis for the formulation and improvement of targeted work mechanism for postpartum visits. Methods A total of 540 parturients were selected to complete the questionnaire survey according to the proportion of parturients in each community, then statistical analysis of questionnaire information was made. Results Among the 540 parturients, 400 were primiparas and 140 multiparas.More than 94% of the respondents believed that postpartum visits were necessary.The demand for postpartum visits was different between primiparas and multiparas.The primiparas needed more guidance on the nursing of the newborn, and the multiparas wanted to have more concern for postpartum recovery and health care.Respondents had high satisfaction with postpartum visits. Conclusion The form and content of postpartum visits directly affect the satisfaction of puerperants, who need higher quality and personalized services.The professional quality of visitors should be improved by professional training.And the personalized postpartum visiting service should be properly carried out by making full use of modern means of information dissemination.And postpartum psychological health care also needs attention in this regard.

Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments.
Adolescent ; Child ; Double-Blind Method ; Female ; Follow-Up Studies ; Fontan Procedure ; Heart Defects, Congenital ; drug therapy ; pathology ; surgery ; Humans ; Liver ; drug effects ; pathology ; Male ; Palliative Care ; Prognosis ; Sulfonamides ; administration & dosage ; Treatment Outcome