Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9％NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P＜0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P＜0.05),and there were significant differences between CAR-L group and CAR-H group(all P＜0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P＜0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.

Humans ; Mpox (monkeypox) ; China

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed. METHODS: Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System. RESULTS: After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P<0.05), and the pericardium meridian microcirculation perfusion (PMP) showed no significant differences at 3 stages (P>0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P<0.05), and PMP decreased obviously after acupuncture (P<0.05). The PMP in the LU 7 and LI 10 groups were slightly elevated (both P>0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05). CONCLUSIONS Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Electroacupuncture ; Meridians ; Microcirculation ; Myocardial Ischemia ; Perfusion ; Pericardium ; Rats ; Rats, Sprague-Dawley

Objective: To evaluate the effectiveness and safety of Pul-Stent as the treatment of postoperative branch pulmonary artery stenosis in children with congenital heart disease. Methods: This was a retrospective study. Thirty-three patients who underwent Pul-Stent implantation in Shanghai Children's Medical Center due to postoperative residual pulmonary artery stenosis from August 2014 to June 2015 were included. The immediate curative effect, follow-up and complications of Pul-Stent implantation were assessed. Comparisons between groups were performed with unpaired Student t test. Results: Pul-Stent implantation of 33 patients (19 males and 14 females) were performed successfully. Thirty-one patients underwent percutaneous stenting, and 2 patients underwent hybrid stenting. A total of 35 Pul-Stents were implanted (19 of model small, 15 of model medium and one of model large), 23 stents were planted in the proximal left pulmonary artery and 12 stents were in the proximal right pulmonary artery. The initial diameter of dilation balloon ranged from 6 to 16 mm, and the long sheath of percutaneous implantation ranged from 8 to 10 F in 29 patients (29/31, 94%). After stenting, the diameter of the narrowest segment of pulmonary artery increased from (4.0±1.7) mm to (9.1±2.1) mm in all patients (t=-21.60, P<0.001). The pressure gradient at the stenosis in 26 patients after biventricular correction decreased from (30.5±12.3) mmHg (1 mmHg=0.133 kPa) to (9.9±9.6) mmHg (t=12.92, P<0.001), and the right ventricular to aortic pressure ratio decreased from 0.57±0.14 to 0.44±0.12 (t=7.44, P<0.001). The pressure of the superior vena cava after stenting in 5 patients after cavopulmonary anastomosis decreased from (17.0±1.9) mmHg to (14.0±0.7) mmHg (t=2.86, P=0.046). Two patients died during reoperation for repairing other cardiac malformations. The remaining 31 patients were clinically stable during the follow-up period of (5.3±1.6) years, and one stent fracture was found on chest X-ray. Cardiac catheterization reexaminations in 16 patients showed that restenosis was found in one stent, while stent position and patency were satisfactory in the remaining stents. Nine children underwent post-dilation without stent fracture, displacement or aneurysm formation. Cardiac tomography showed no stent stenosis, fracture observed, or significant change in diameter of the stent in 8 patients. The inner diameter and pulmonary blood perfusion could not be accurately evaluated due to artifacts by cardiac magnetic resonance imaging in 4 patients. Conclusions: Pul-Stent has good compliance and adequate radial strength, and can dilate further over time to accommodate for somatic growth. It performs safely and effectively in treating post-operative branch pulmonary artery stenosis in children.
Child ; China ; Female ; Follow-Up Studies ; Heart Defects, Congenital/surgery* ; Humans ; Male ; Pulmonary Artery/surgery* ; Retrospective Studies ; Stenosis, Pulmonary Artery/surgery* ; Stents ; Treatment Outcome ; Vena Cava, Superior

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective To understand the cognition，attitude and awareness on the prevention and control of COVID-19 among recent international travellers back to China（hereinafter referred to as the inbound group）and local residents（domestic group），and to provide scientific evidence for further prevention and control of the epidemic. Methods Using a questionnaire website，a questionnaire entitled “Investigation and analysis of residents’ knowledge，attitude，and practice on COVID-19”was prepared，with the targeted population of the survey being international travelers back to China and local residents who had been quarantined at home for 14 days in Jinqiao Town. Cluster sampling was used to conduct the survey through WeChat. The two groups were then compared using chi-square test by using SPSS 23.0. Results Between the two groups，the awareness on the respiratory droplet transmission and inactivation effectiveness by alcohol，peracetic acid and ultraviolet ray on the SARS-CoV-2 were statistically different（P < 0.05）. In the attitude towards prevention and control measures，there was significant difference between the two groups in selecting prevention and control plans for the whole population during the outbreak（P < 0.05）. In the comparison of behavior，there was a statistical difference between the two groups（P < 0.05）whether to maintain a distance of more than 1 meter in social communication. Regarding the choice of quarantine methods（stay-at-home，intensive quarantine and no quarantine），the difference between two groups was statistically significant（P < 0.05）. Conclusion In terms of the knowledge of COVID-19，attitude towards prevention and control measures，and their own behavior，there are some differences between the inbound group and domestic group.

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

China/epidemiology* ; Coronary Angiography ; Coronary Artery Disease/diagnosis* ; Humans ; Registries ; Risk Assessment ; Risk Factors

OBJECTIVE: To evaluate the quality of the existing studies and summarize evidence of important outcomes of meta-analyses/systematic reviews (MAs/SRs) of CFS. METHODS: Potentially eligible studies were searched in the following electronic databases from inception to 1 September, 2019: Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), Web of Science, Embase, PubMed and Cochrane Library. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. The methodological quality of the literature was evaluated by A Measure Tool to Assess Systematic Reviews-2 (AMSTAR-2) and the quality of the report was assessed by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The intra-class correlation coefficient was used to assess the consistency of the reviewers, with an overall intraclass correlation coefficient score of 0.967. RESULTS: Ten MAs/SRs were included. The overall conclusions were that acupuncture had good safety and efficacy in the treatment of CFS, but some of these results were contradictory. The GRADE indicated that out of the 17 outcomes, high-quality evidence was provided in 0 (0%), moderate in 3 (17.65%), low in 10 (58.82%), and very low in 4 (23.53%). The results of AMSTAR-2 showed that the methodological quality of all included studies was critically low. The PRISMA statement revealed that 8 articles (80%) were in line with 20 of the 27-item checklist, and 2 articles (20%) matched with 10-19 of the 27 items. CONCLUSION We found that acupuncture on treating CFS has the advantage for efficacy and safety, but the quality of SRs/MAs of acupuncture for CFS need to be improved.
Acupuncture Therapy ; China ; Fatigue Syndrome, Chronic/therapy* ; Humans ; Research Report