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.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Child ; Cord Blood Stem Cell Transplantation ; Hematopoietic Stem Cell Transplantation ; Humans ; Primary Myelofibrosis/therapy* ; Thiotepa ; Transplantation Conditioning

ObjectiveTo investigate the therapeutic effect of Xuebijing injection （XBJ） on sodium taurocholate （Na-Tc）-induced severe acute pancreatitis （SAP） in rats. MethodForty rats were randomly assigned into 5 groups： sham operation group， SAP model group， and low-， medium-， and high-dose （4， 8， 12 mL·kg·d^-1， respectively） XBJ groups. SAP model was established by retrograde injection of Na-Tc （1 mL·kg^-1） into the biliary and pancreatic ducts. XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling. The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured. The pathological changes of pancreatic tissue were observed via hematoxylin-eosin （HE） staining. The protein levels of formyl peptide receptor 1 （FPR1） and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in pancreatic tissue were detected by immunohistochemistry. Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6 （MT-ND1， MT-ND2， MT-ND3， MT-ND4， MT-ND5， and MT-ND6） in rat plasma. ResultCompared with sham operation group， the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.05）， serious lesions in pancreatic tissue， increased total pathological score （P<0.05）， and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.05）. The model group had lower MT-ND2 level （P<0.05） and higher MT-ND1， MT-ND3， and MT-ND6 levels in plasma （P<0.05） than the sham operation group， while MT-ND4 and MT-ND5 had no significant differences between the two groups. Compared with SAP model group， the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.01）， ameliorated pancreatic lesions， and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.01）. The treatments， especially high-dose XBJ （P<0.01）， down-regulated the expression of MT-ND1 （P<0.01）， MT-ND3 （P<0.01）， MT-ND6 （P<0.01）， and MT-ND4 and did not change that of MT-ND5. ConclusionXBJ may antagonize partial mitochondrial N-formyl peptides and excessive inflammatory response mediated by FPR1/NLRP3 to treat SAP in rats.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Adaptation, Psychological ; Adult ; Age Factors ; Aged ; Beijing/epidemiology* ; Breast Neoplasms/psychology* ; Case-Control Studies ; Educational Status ; Female ; Humans ; Middle Aged ; Risk Factors

OBJECTIVE: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes. METHODS: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation. RESULTS: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03). CONCLUSION Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.
Bone Marrow ; Calreticulin ; genetics ; China ; Humans ; Janus Kinase 2 ; genetics ; Male ; Mutation ; Receptors, Thrombopoietin ; genetics ; Thrombocythemia, Essential

Objective To analyze the status of quality indicators(QI) on specimen acceptability and establish preliminary qual ity specification.Methods Web based External Quality Assessment system was used to collect data of laboratories partici pated in "Medical quality control indicators in clinical laboratory" from 2015 to 2017,including once in 2015 and 2017 and twice in 2016.Rate and sigma scales were used to evaluate incorrect sample type,incorrect sample container,incorrect fill level and anticoagulant sample clotted.The 25th percentile (P25) and 75th percentile (P75) of the distribution of each QI were employed to establish the high,medium and low specification.Results 5 346,7 593,5 950 and 6 874 laboratories sub mitted the survey results respectively.The P50 of biochemistry (except incorrect fill level),immunology and microbiology reach to 6σ.The P50 of clinical laboratory is 4 to 6σ except for incorrect sample container.There is no significant change of the continuous survey results.Based on results in 2017 to establish the quality specification,the P25 and P75 of the four QIs is 0 and 0.084 4 ％,0 and 0.047 6 ％,0 and 0.114 2 ％,0 and 0.078 4 ％,respectively.Conclusion According to the results of the survey,most laboratories had a faire performance in biochemistry,immunology and microbiology,and clinical laboratory needs to be strengthened.Laboratories should strengthen the laboratory information system construction to ensure the actual and reliable data collection,and make a long time monitoring to achieve a better quality.

Humans ; Infant ; Male ; Phenotype ; Wiskott-Aldrich Syndrome ; diagnosis ; genetics ; immunology

The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.
Animals ; China ; Diabetes Mellitus ; drug therapy ; Disease Models, Animal ; Drug Discovery ; Humans ; Hypoglycemic Agents ; Medicine, Chinese Traditional