AIM To study the protective effects and mechanism of pueraria isoflavones on myocardial injury in ovariectomized rats.METHODS Thirty-six rats were randomly divided into the sham operation group,the model group,the estradiol valerate group(0.1 mg/kg)and the low,medium and high dose pueraria isoflavones groups(55,110,220 mg/kg).In contrast to the rats of the sham operation group having their small pieces of adipose tissue removal around the ovaries,rats of the other groups had their bilateral ovaries excised,followed by the 16-week corresponding oral drug administration 2 weeks later at a once daily frequency for,6 days a week.At the end of the 16th week,the rats had their hemodynamics[systolic pressure(SBP),diastolic pressure(DBP),mean pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVMP),and the maximum rate of increase and decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)]detected by PowerLab;their cardiac pathological changes observed by HE staining;their levels of creatine kinase(CK),lactate dehydrogenase(LDH),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and glucose(Glu)in plasma detected by biochemical analyzer;their myocardial level of adenosine triphosphate(ATP)detected by colorimetry;their mRNA expressions of glucose transporter 4(GLUT4),lactate dehydrogenase A(LDHA),carnitine palmitoyl transferase-1(CPT-1α),acyl coenzyme A carboxylase(ACC),liver kinase B1(LKB1),adenylate-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor γ coactivator factor 1α(PGC-1α)detected by RT-qPCR;and their myocardial expressions of energy metabolism related proteins LKB1,p-AMPK/AMPK and PGC-1α detected by Western blot.RESULTS Compared with the model group,the pueraria isoflavones groups displayed decreased levels of SBP,DBP,MBP,LVSP,LVMP(P＜0.05,P＜0.01);increased-dp/dtmax(P＜0.05,P＜0.01);improved myocardial fibrinolysis,gap widening and inflammatory infiltration caused by ovariectomy;decreased activities of LDH and CK(P＜0.05);increased myocardial ATP level(P＜0.05,P＜0.01);decreased levels of TC,TG,LDL-C and Glu(P＜0.05,P＜0.01);increased HDL-C level(P＜0.05,P＜0.01);increased myocardial mRNA expressions of GLUT4,LDHA,CPT-1α,ACC,LKB1,AMPK and PGC-1α(P＜0.05,P＜0.01);and increased protein expressions of myocardial LKB1,p-AMPK/AMPK and PGC-1α(P＜0.05,P＜0.01).CONCLUSION Pueraria isoflavones are protective to myocardial injury in ovariectomized rats,and the mechanism may lie in the improvement of energy metabolism-related myocardial proteins via LKB1/AMPK/PGC-1α signaling pathway.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

Objective This study aimed to investigate the effect of stage Ⅰ comprehensive cardiac rehabili-tation in patients with acute ST elevation myocardial infarction(STEMI)after emergency percutaneous coronary intervention(PCI).Methods A total of 72 patients with acute ST-segment elevation myocardial infarction combined with PCI admitted to the Department of Cardiovascular Medicine of Beijing Electric Power Hospital of State Grid Corporation from June 2021 to June 2022,which were selected as the research objectsand divided into control group and observation group randomly(36 cases in each group).The control group was treated with routine nursing and health education,and the observation group with stage Ⅰ comprehensive cardiac rehabilitation,including initial assessment(cardiovascular comprehensive assessment),exercise training(exercise training and breathing train-ing),daily activity suggestions and health education,discharge assessment(six-minute walking test and Barthel index assessment).The score of Barthel index(BI)at discharge,the 6-minute walking test distance(6MWD)at discharge,the incidence of major adverse cardiovascular event(MACE)during hospitalization and within one month of discharge,and the length of stay were compared between the two groups.Results After intervention,the six-minute walking test distance(6MWD)and Barthel index(BI)score in the observation group were better than those in the control group,the difference was statistically significant(P<0.05).The incidence of major adverse cardiovascular events(MACE)during hospitalization and one month after discharge was lower in the observation group than in the control group,and the difference was statistically significant(P<0.05).The length of hospital-ization in observation group was lower than that in control groupbut there was no statistical difference(P>0.05).Conclusion The application of phase Ⅰ comprehensive cardiac rehabilitation training in patients with acute ST-segment elevation myocardial infarction combined with emergency PCI could improve the patients'exercise ability,improve their ability of daily activity,reduce the incidence of major adverse cardiovascular events(MACE)in the early stage of the disease,facilitate the patients to return to their families and society as soon as possible,and improve their quality of life.It has high clinical application value.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To investigate the effect and mechanism of lycium barbarum polysaccharide(LBP)on hepatocyte injury induced by homocysteine(Hcy).Methods Normal C3H/An mouse hepatocytes(NCTC 1469)were cultured in vitro and treated with different concentrations of Hcy(0,50,100,200,500 μmol/L).The optimal concentrations of Hcy-treated NCTC 1469 cells were detected by MTT assay.When the cells reached the logarithmic growth stage,the conditions were set up as follows:(1)control group(cultured with DMEM medium supplemented with 10%horse serum)and Hcy group(treated with 100 μmol/L Hcy solution for 48 h),and the cells were collected.Cell viability staining was used to detect apoptosis,aspartate aminotransferase(AST)/alanine aminotransferase(ALT)activity detection kit was used to detect AST and ALT activities,RT-qPCR was used to detect the expression levels of YAP1,DNMT1,DNMT3a and DNMT3b mRAN,and Western blotting was used to detect the expression of YAP1 protein,nested methylation specific PCR(nMS-PCR)was used to detect DNA methylation rates in the YAP1 promoter region.(2)Control group,LBP group,Hcy group and Hcy+LBP group.LBP group was treated with 4 mg/ml LBP solution for 2 h,Hcy group and Hcy+LBP group were treated with 100 μmol/L Hcy solution for 48 h,and Hcy+LBP group was treated with 4 mg/ml LBP solution at 46 h,and the cells were collected.The expression levels of YAP1,DNMT1,DNMT3a and DNMT3b mRAN were detected by RT-qPCR;the expression of YAP1,Bax and Bcl-2 proteins was detected by Western blotting;AST/ALT activity detection kit was used to detect AST and ALT activities.Prediction of DNA methylation CpG islands in YAP1 promoter region by bioinformatics.Results NCTC 1469 cells were treated with 100 μmol/L Hcy according to the results of MTT assay.Compared with control group,the apoptosis rate of Hcy group increased(P<0.01),the activities of ALT and AST increased(P<0.001),the mRAN and protein expression levels of YAP1 decreased(P<0.001),and the methylation rate of YAP1 promoter region increased(P<0.01),the mRNA expression levels of DNMT1,DNMT3a and DNMT3b increased(P<0.01 or P<0.001).Compared with Hcy group,the mRNA expression levels of DNMT1,DNMT3a and DNMT3b in the Hcy+LBP group decreased(P<0.001),the mRAN and protein expression levels of YAP1 significantly increased(P<0.01 or P<0.001).In addition,in the Hcy+LBP group,cells showed significantly elevated of Bcl-2 protein(P<0.001),but decreased Bax protein(P<0.001),and decreased activities of ALT and AST(P<0.001).Conclusions The decrease of YAP1 expression may be the key process of Hcy induced injury of NCTC 1469 cells,and the methylation of the YAP1 promoter region may be the molecular mechanism of Hcy induced YAP1 expression change.LBP may improve NCTC 1469 cell damage induced by Hcy by positively regulating YAP1 expression.

AIM: To identify the pathogenic gene in a family with primary open angle glaucoma(POAG)from Nantong, Jiang Province, and to analyze its clinical phenotype and pathogenic mechanism.METHOD: A POAG pedigree was reviewed and recruited from January 2020 to December 2020, which spans 5 generations, with 33 people in total. A total of 13 family members were enrolled in our study, of whom 4 members were diagnosed with POAG, 1 with ocular hypertension(OHT), and the other 8 members were unaffected. Detailed medical history was collected and a comprehensive ophthalmic examination was performed. High throughput sequencing was used to screen for possible pathogenic gene, and Sanger sequencing was used to verify candidate pathogenic gene.RESULT: All patients in this family were found to have elevated intraocular pressure(IOP)and diagnosed with glaucoma at a young age, requiring surgical treatments to control the IOP. The highest IOP of proband was up to 55mmHg. A heterozygous mutation(c.1197C>A, p.Phe399Leu)of LTBP2 gene was found in the proband genome by whole exon sequencing(WES). Sanger sequencing verified that the mutation was not isolated from the family disease.CONCLUSION: LTBP2 (c.1197C>A)mutation was not the pathogenic gene of POAG in this family. However, the pathogenic potential of LTBP2 gene in POAG cases is worth studying.

Objective: To examine the association of greenness exposure with waist circumference (WC) and central obesity in older adults in China. Methods: Based on the cross-sectional data from the Chinese Longitudinal Healthy Longevity Survey in 2017-2018, 14 056 participants aged 65 years and over were included. Demographic characteristics, lifestyle, WC, and other information were collected through a questionnaire and physical examination. Based on the satellite monitoring data of moderate-resolution imaging spectroradiometer (MODIS) provided by NASA, the annual mean of normalized difference vegetation index (NDVI) within a radius of 1 000 meters was obtained as the measurement value of greenness exposure. Multivariate linear regression model, multivariate logistic regression model, and restricted cubic splines (RCS) model were used to analyze the association and dose-response relationship between greenness exposure and WC and central obesity in older adults in China. Results: A total of 14 056 participants were enrolled with a median age of 84.0 years [IQR: 75.0-94.0 years]. About 45.0% (6 330) of them were male and 48.6% (5 853) were illiterate. There were 10 964 (78.0%) participants from rural. The mean of WC was (84.4±10.8) cm. Central obesity accounted for 60.2% (8 465), and the NDVI range was (-0.06, 0.78). After adjusting for confounding factors, the multivariate linear regression model showed that the change value of WC in the urban group [β (95%CI):-0.49 (-0.93, -0.06)] was smaller than that in the rural [-0.78 (-0.98, -0.58)] for every 0.1 unit increase in NDVI (P_interaction=0.022). Compared with the Q₁ group in NDVI, WC of Q₂ and Q₃ groups in rural decreased, and the β (95%CI) values were-1.74 (-2.5, -0.98) and-2.78 (-3.55, -2.00), respectively. The multivariate logistic regression model showed that after adjusting for confounding factors, the risk of central obesity decreased for urban and rural older adults with an increase of 0.1 unit in NDVI, and the OR (95%CI) values were 0.87 (0.80, 0.95) and 0.86 (0.82, 0.89), respectively (P_interaction=0.284). Compared with the Q₁ group in NDVI, the risk of central obesity in the Q₂ and Q₃ groups in rural was lower, and the OR (95%CI) values were 0.68 (0.58, 0.80) and 0.57 (0.49, 0.68), respectively. The results of the multivariate regression model with RCS showed that there was a non-linear association of NDVI with WC (P_nonlinear=0.006) and central obesity (P_nonlinear=0.025). Conclusion: Greenness exposure is negatively associated with WC and central obesity in older adults in China.

Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×10⁹/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×10⁹/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
Male ; Female ; Humans ; Child ; Retrospective Studies ; RUNX1 Translocation Partner 1 Protein/genetics* ; Core Binding Factor Alpha 2 Subunit/therapeutic use* ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Cytarabine/therapeutic use* ; Oncogene Proteins, Fusion/genetics* ; Chromosome Aberrations

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.
Humans ; Neoplasms/pathology* ; Biomarkers ; Prognosis ; Oceans and Seas ; China/epidemiology*