Objective:To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP).Methods:32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1,2020 to March 31,2022,who had never received any tyrosine kinase inhibitor(TKI)were included in the study.The patients were treated by flumatinib mesylate 600mg once daily.The hematologic,cytogenetic and molecular responses were assessed at 3-,6-and 12-month,and adverse effects of the drug were evaluated.Results:31 patients were treated with flumatinib for≥3 months,of which 24 patients were treated for ≥ 6 months and 14 patients were treated for ≥ 12 months.At 3rd month of treatment,30 out of 31 patients achieved complete hematologic response(CHR);24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR),of which 21 cases achieved complete cytogenetic response(CCyR);Among 25 patients who underwent molecular testing,22 patients had BCR-ABLIS ≤ 10％,including 10 patients with BCR-ABLIS ≤ 0.1％,and 6 patients with BCR-ABLIS≤0.01％.At 6th month of treatment,23 out of 24 patients achieved CHR;17 patients underwent cytogenetic testing and all achieved CCyR;Among 23 patients who underwent molecular testing,20 patients had BCR-ABLIS ≤1％,including 16 patients with BCR-ABL1S≤0.1％and 12 patients with BCR-ABLIS ≤ 0.01％.At 12nd month of treatment,all 14 patients achieved CHR and CCyR;Among them,10 patients had BCR-ABLIS ≤ 0.1％,including 9 patients with BCR-ABLIS ≤ 0.01％.The grade Ⅲ/Ⅳ leukopenia,thrombocytopenia and anemia rates in the patients were 13.3％,20.0％and 3.3％,respectively.One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity.The major non-hematologic adverse events were abnormal liver function(20％),diarrhea(10％),bone/joint pain(10％),muscle spasm(10％),rash(6.7％),acute kidney injury(6.7％)and nausea(3.3％),most of which were grade Ⅰ-Ⅱ.No patient experienced grade Ⅳnon-hematologic adverse events.No drug toxicity-related death occurred.Conclusion:Flumatinib mesglate,as the first-line treatment for newly diagnosed CML-CP,can enable the patients to achieve early and deep molecular and cytogenetic responses,and shows good safety.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Objective:To explore the influence of environment temperature on the incidence of testicular torsion.Methods:We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from De-cember 2013 to December 2020.According to the local environment temperature on the day of onset,we divided the patients into groups A(below 0℃),B(0-10℃),C(10-20℃)and D(above 20℃),and compared the incidence rates of testicular torsion among the four groups,followed by correlation analysis.Results:The incidence rate of testicular torsion was 12.8％(n=22)in group A,35.5％(n=61)in B,34.9％(n=60)in C and 16.9％(n=29)in D,the highest at 0-10℃ in group B,with sta-tistically significant difference among the four groups(x2=29.07,P＜0.001).Spearman correlation analysis indicated that the inci-dence of testicular torsion was negatively correlated with the environment temperature(r=-0.261,P＜0.01),with no statistically significant difference among different seasons(x2=5.349,P＞0.05),but higher in autumn and winter than in the other two sea-sons.Conclusion:The incidence of testicular torsion is negatively correlated with the environment temperature,elevated when the temperature decreases,but has no statistically significant difference among different seasons,though relatively higher in autumn and winter.

Attributed to the miniaturized body size and active mobility, micro- and nanomotors (MNMs) have demonstrated tremendous potential for medical applications. However, from bench to bedside, massive efforts are needed to address critical issues, such as cost-effective fabrication, on-demand integration of multiple functions, biocompatibility, biodegradability, controlled propulsion and in vivo navigation. Herein, we summarize the advances of biomedical MNMs reported in the past two decades, with particular emphasis on the design, fabrication, propulsion, navigation, and the abilities of biological barriers penetration, biosensing, diagnosis, minimally invasive surgery and targeted cargo delivery. Future perspectives and challenges are discussed as well. This review can lay the foundation for the future direction of medical MNMs, pushing one step forward on the road to achieving practical theranostics using MNMs.

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.
Humans ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Liver Cirrhosis/drug therapy* ; Prospective Studies ; Treatment Outcome

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective:To investigate the expressions of matrix metalloproteinase 7(MMP7)and secretory leukocyte protease inhibitor(SLPI)in papillary thyroid carcinoma(PTC)and their signifi-cances.Methods:Based on the gene expression data of thyroid cancer in the tumor Genome Atlas(TCGA)database,a total of 567 samples were collected,including 509 cancer tissues and 58 normal tissues.The gene matrix data were extracted and sorted out.Two groups of differentially expressed genes were screened by using the R language edger package,and the potential key genes were screened by the mcode plug-in in Cytoscape.Select a key gene and mine closely related genes through the UALCAN database.Immunohistochemical SABC method was used to detect the ex-pressions of MMP7 and SLPI proteins in PTC tissues and their paracancerous tissues collected from 69 patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2020 to June 2021,and the association of expression levels of MMP7 and SLPI with the clinico-pathological factors of PTC patients was also analyzed.Results:Based on the data of TCGA database,1471 genes were obtained,of which 1000 were up-regulated and 471 were down-regu-lated.Through the mcode plug-in in Cytoscape,20 key genes were screened(MMP7,CCL18,CYR61,SPECC1,CRABP2,PLXNA3,KRT17,TMEM59L,RETN,SRF,ITGB4,PPL,PLEKHN1,RMI2,LCN6,SPX,NRIP1,ARHGEF28,SLC39A14,SNCA).Through the UALCAN database,the correlation between MMP7 and SLPI was retrieved(Pearson correlation coefficient was 0.5,P＜0.05).The results of immunohistochemistry showed that the positive expression rates of MMP7 and SLPI proteins in PTC tissues were significantly higher than those in paracancerous tissues[82.6％(57/69)vs 29.0％(20/69),71.0％(49/69)vs 15.9％(11/69)],and the differences were statistically significant(x2 val-ues were 40.222 and 42.579,both P＜0.01).The expressions of MMP7 and SLPI in PTC tissues were correlated with TNM stage,differentiation,extramembranous invasion and lymph node metastasis(all P＜0.05).There was a positive correlation between MMP7 and SLPI proteins expressions in PTC(r=0.381,P=0.001).Conclusions:The interaction between MMP7 and SLPI proteins can be in-volved in the development and progression of PTC.

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies