Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Powders ; Retrospective Studies

Klinefelter syndrome (KS) is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting (HRM) assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS, the ratios of ZFX/ZFY are altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts (5 ng-50 ng) and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity (100%) and specificity (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD per sample), easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.
DNA/genetics* ; Dried Blood Spot Testing ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Klinefelter Syndrome/diagnosis* ; Kruppel-Like Transcription Factors/genetics* ; Male ; Mass Screening/methods* ; Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity

Objective: To assess the feasibility of HEAD-US scale in the clinical application of hemophilic arthropathy (HA) and propose an optimized ultrasound scoring system. Methods: From July 2015 to August 2017, 1 035 joints ultrasonographic examinations were performed in 91 patients. Melchiorre, HEAD-US (Hemophilic Early Arthropathy Detection with UltraSound) and HEAD-US-C (HEAD-US in China) scale scores were used respectively to analyze the results. The correlations between three ultrasound scales and Hemophilia Joint Health Scores (HJHS) were evaluated. The sensitivity differences of the above Ultrasonic scoring systems in evaluation of HA were compared. Results: All the 91 patients were male, with median age of 16 (4-55) years old, including 86 cases of hemophilia A and 5 cases hemophilia B. The median (P₂₅, P₇₅) of Melchiorre, HEAD-US and HEAD-US-C scores of 1 035 joints were 2(0,6), 1(0,5) and 2(0,6), respectively, and the correlation coefficients compared with HJHS was 0.747, 0.762 and 0.765 respectively, with statistical significance (P<0.001). The positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 63.0% (95%CI 59.7%-65.9%), 59.5% (95%CI 56.5%-62.4%) and 56.6% (95%CI 53.6%-59.6%) respectively, and the difference was statistically significant (P<0.001). Even for 336 cases of asymptomatic joints, the positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 25.0% (95%CI 20.6%-29.6%), 17.0% (95%CI 12.6%-21.1%) and 11.9% (95%CI 8.4%-15.7%) respectively, and the difference was statistically significant (P<0.001). There were significant changes (P<0.05) in the ultrasonographic score of HA before and after onset of hemorrhage in 107 joints of 40 patients. The difference in variation amplitude of HEAD-US-C scores and HEAD-US scores before and after joint bleeding was statistically significant (P<0.001). Conclusion: Compared with Melchiorre, there were similar good correlations between HEAD-US, HEAD-US-C and HJHS. HEAD-US ultrasound scoring system is quick, convenient and simple to use. The optimized HEAD-US-C scale score is more sensitive than HEAD-US, especially for patients with HA who have subclinical state, which make up for insufficiency of sensitivity in HEAD-US scoring system.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Hemarthrosis ; Hemophilia A ; Hemophilia B ; Humans ; Male ; Middle Aged ; Ultrasonography ; Young Adult

AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.

Araloside A is one of the main active ingredients of Aralia taibaiensis. In this study, HPLC-MS/MS analysis method of araloside A in the main organs of SD rats was established. At the same time, the content of araloside A in the main organs (heart, liver, spleen, lung, kidney, brain) after oral administration with araloside A (50 mg•kg⁻¹) were determined to explore the tissue distribution characteristics of araloside A in vivo. The results showed that the methodological study of araloside A in the main organs of SD rats met the requirements, araloside A distributed in heart, liver, spleen, lung, kidney and brain tissues reached peak at 1 h or 2 h after oral administration with 50 mg•kg-1.The distributions of araloside A at different time points after administration were distinct as follows： the content of araloside A at 20 min：liver>heart>spleen>lung>kidney>brain; the content of araloside A at 1 h： liver>spleen>kidney>lung>heart>brain; the content of araloside A at 2 h： liver>kidney>heart>spleen>lung>brain; the content of araloside A at 4 h： kidney>liver>spleen>heart>lung>brain; the content of araloside A at 8 h： spleen>heart>liver>kidney>lung>brain. Therefore, araloside A was mainly distributed in liver tissue, which had a certain correlation with the common use of Aralia taibaiensis in the treatment of hepatic disease. In addition, araloside A shows a low content but an obvious distribution in brain tissues, which indicates that the drug can pass through blood-brain barrier, and provides the basis for the study of araloside A in brain tissue.

AIM: To compare intraocular pressure (IOP) fluctuations measured at home and in the clinic over a 24-hour period.METHODS: A prospective investigational study.A total of 120 Chinese participants were selected from five communities in the Chengdu area.Patients underwent a clinical interview and IOP was measured both at home and in the clinic.IOP were measured at 8 a.m., 10 a.m., 12 a.m., 2 p.m., 4 p.m., 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m.using the same pneumatonometer.Measurements were taken in the sitting position.RESULTS: The average 24-hour IOP measured in the clinic was slightly lower than that at home.The mean difference in 24-hour IOP measurements between home and clinic was 0.27 mmHg.The IOP fluctuation in the clinic was higher than at home (the mean difference was 0.01 mmHg).There was no statistically significant difference in the average 24-hour IOP measured at home vs in the clinic.The average IOP measured at 2 p.m.at home (16.04±5.95 mmHg) was significantly higher compared with the measurement in the clinic (15.43±5.16 mmHg) (P<0.05).The overall agreement between 24-hour IOP measurements made in the clinic and at home in diagnosis of primary open angle glaucoma was 85.0% (K coefficient: 0.68).CONCLUSION: The 24-hour IOP measured in the clinic was similar to that measured at home, and the method of measuring IOP in the clinic is acceptable in diagnosing primary open angle glaucoma.

Objective: To investigate the impact of discontinued dual antiplatelet therapy(DAPT) of aspirin combining clopidogrel within 5 days on peri-operative bleeding in patients with coronary artery bypass grafting (CABG). Methods: A total of 2012 patients with off-pump CABG were retrospectively enrolled in our study including 1506 male and the mean age was at 61.92 years. All patients received regular DAPT previously and discontinued the medication≤5 days due to emergency or prior limited CABG. Based on the days from discontinued DAPT to operation, the patients were divided into 6 groups: 0-day group, n=220, 1-day group, n=240, 2-day group, n=360, 3-day group, n=332, 4-day group, n=428 and 5-day group, n=432. Relationships between risk factors of bleeding and discontinued DAPT time were studied. Results: Bleeding was defined by BARC (bleeding academic research consortium) standard. The incidences of bleeding events in 0-day group, 1-day group, 2-day group, 3-day group, 4-day group and 5-day group showed a decreasing trend as 29.1%, 24.6%,19.4%, 13.0%, 14.5% and 13.0% respectively, P<0.01. Post-operative chest drainage volume≥2L within 24h (P=0.13) and intracranial bleeding (P=0.60) had no obvious tendency changes; occurrence rates of 48h peri-operative transfusion≥5 U whole blood or red blood cells (P<0.01) and re-operation(P<0.01) had a decreasing trend by prolonged time of discontinued medication. The minor endpoint events were similar. Compared to (3-5) days discontinued medication, the patients with (0-2) days discontinued DAPT were with the higher incidences of overall bleeding, re-operation and 5U transfusion, the differences had statistical meaning. Conclusion: The incidence of bleeding presented a decreasing trend by prolonged time of discontinued DAPT before CABG;transfusion and re-operation had the statistical meaning for bleeding. Discontinued medication less than 3 days may increase bleeding events and therefore, in high risk patients, prior CABG discontinued medication should be more than 3 days.

Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
AMP-Activated Protein Kinases ; metabolism ; Acetyl-CoA Carboxylase ; metabolism ; Adipose Tissue ; metabolism ; Animals ; Diet, High-Fat ; Flavonoids ; pharmacology ; Glycogen Synthase Kinase 3 beta ; physiology ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal ; metabolism ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; physiology

Objective To study the temporal distribution regular pattern of under 5 mortality rate(U5MR)from 1 998 to 201 4 in Zhejiang Province,and to predict the under 5 mortality rate in 201 5.Methods A time series ARIMA (p,d,q) forecasting model for U5MR was conducted using IBM SPSS Statistics 20.0 statistical analysis software.Results The UMAR showed downward trend.The ARIMA(2,1 ,2)model of U5MR from 1 998 to 201 4 in Zhejiang Province is yt =-0.696 +0.636yt -1 +0.024yt -2 +0.340yt -3 +αt -0.003αt -1 +0.997αt -2 ,and the model fitting was good.Each of the actual mortality was consistent with the trend of model prediction,and was within the 95% confidence interval.The predicted value of U5MR was 4.08‰ (95% CI:1 .52‰ -6.64‰)in 201 5.Conclusion Time series analysis is an effective way to analyze the temporal distribution regular pattern of U5MR,which could be used for short -term prediction.