The chemical reprogramming of unipotent adult germ cells towards authentic pluripotency and de novo establishment of imprinting

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.

Modified Sanpiantang Treats Nitroglycerin-induced Migraine in Rats via p38 MAPK/iNOS Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo decipher the mechanism of modified Sanpiantang in the treatment of nitroglycerin-induced migraine in rats. MethodSeventy-two Wistar rats were randomized into the control， model （nitroglycerin， 10 mg·kg-1）， positive control （rizatriptan， 0.89 mg·kg-1）， and high- （12.96 g·kg-1）， medium- （6.48 g·kg-1）， and low-dose （3.24 g·kg-1） modified Sanpiantang groups. The rat model of migraine was established by intraperitoneal injection of 10 mg·kg-1 nitroglycerin. The behavioral test was carried out to measure the mechanical pain thresholds （MPT） of the periorbital region and hindpaw after successful modeling. The serum levels of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， and interleukin-1β （IL-1β） in rats were determined by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was employed to determine the expression of inducible nitric oxide synthase （iNOS） in the trigeminal nucleus caudalis （TNC）. Western blot was employed to determine the protein levels of iNOS and phospho-p38 mitogen-activated protein kinase （p-p38 MAPK） in the TNC. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to measure the mRNA levels of iNOS， p38 MAPK， and IL-1β in the TNC. ResultCompared with the control group， the model group showed decreased MPT （P<0.01）， elevated serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.01）， and up-regulated expression levels of p38 MAPK， iNOS， and IL-1β in the TNC （P<0.05， P<0.01）. Compared with the model group， modified Sanpiantang increased the MPT （P<0.05）， and the medium-dose group showed the most significant effect （P<0.01）. In addition， modified Sanpiantang down-regulated the mRNA levels of iNOS， p38 MAPK， and IL-1β and the protein levels of p-p38 MAPK and iNOS in the TNC of migraine rats （P<0.05， P<0.01） and lowered the serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.05， P<0.01）. ConclusionModified Sanpiantang may treat migraine by down-regulating the expression of pro-inflammatory factors such as NO， TNF-α， IFN-γ， and IL-1β in the p38 MAPK/iNOS signaling pathway to reduce the neurogenic inflammation.

Effect analysis of BOPPPS model in online teaching activities of radiobiology / 中华放射医学与防护杂志

Objective:To explore the effect of a new teaching mode, which includes bridge-in, outcome, pre-test, participation, post-test and summary (BOPPPS), on the online teaching of radiobiology related knowledge for cancer radiotherapy practitioners.Methods:Taking the cell survival curve, cell cycle and radiosensitivity as examples, the radiotherapy practitioners in multiple university-affiliated hospitals were organized to carry out a multicenter prospective randomized control study. All practitioners were randomly divided into BOPPPS group and control group. The courses for BOPPPS group were designed as an online classroom, consisting of pre-class preparation, online teaching and post-class stages. The online teaching stage included video viewing, basic knowledge learning, literature discussion, group discussion and others. The control group employed the traditional teaching mode. The χ2 test was used to compare the consistency of general conditions between the two groups, and nonparametric test was used to compare the differences in scores between two or more groups. Results:The score of the pre-class test was 58.56 ± 0.99. Post-class average score for BOPPPS group was 85.48±0.85 and for control group 77.79±1.10, with the former being higher 7.69 ( Z=5.31, P<0.001) than the latter. The average answer time was (296.62±15.40) s for BOPPPS group and (386.41±21.27) s for control group, with the former being shorter 89.79 s ( Z=3.34, P=0.001) than latter. Subgroup analysis shown that the scores of BOPPPS group were significantly rising, regardless of whether or not the students had studied radiobiology courses. Among the students who have not studied these courses, the scores were rising greatly. Moreover, From the analysis of different positions, it was found that both the scores of BOPPPS group and control group have risen, especially for doctors, deputy chief doctors, physicists and technicians. There were also statistically differences between different degrees, with significantly rise in scores for undergraduate and doctoral students ( Z=3.64, 4.18, P<0.001). Conclusions:The flexible application of BOPPPS teaching mode to the online education of such boring disciplines, like radiobiology, is of great significance to raise the theoretical basis of radiotherapy practitioners.

Study of gene correlation between endothelial growth factor family in mouse eye / 中华眼底病杂志

Objective:To compare the function and action pathways of VEGFA, VEGFB and VEGFC in VEGF family of mouse eye.Methods:Using the BXD mouse gene data in Genenetwork database as template to compare and study the similarities and differences of VEGFA, VEGFB and VEGFC molecular pathways or potential functions in the whole genome expression spectrum of BXD recombinant mouse inbred line population, with multiple analytical methods and statistical strategies were used, such as gene expression level, target genes comparison, top genes comparison associated to target genes, expression Quantitative Trait Loci (eQTL).Results:Matrix comparison showed strong positive correlation between two probes of VEGFC ( r=0.732, P<0.01), weak correlation between VEGFA 1420909 and VEGFC 1440739, VEGFA 1451959 and VEGFC 1451803, VEGFC 1419417959 and VEGFC 1439766, VEGFC 1451803 and VEGFC 1439766 ( P<0.05); there was no correlation between VEGFA 1420909 and four other genes except VEGFC 1440739, VEGFA 1451959 and VEGFC 1440739, VEGFB 1451803 and VEGFA 1420909/VEGFC 1419417/VEGFC 1440739 ( P >0.05). In the comparative analysis of the relevant Top 50 genes of each VEGF gene, most of the genes in BXD mouse were not significantly correlated with VEGFA, VEGFB and VEGFC except for the weak association of individual related genes. The results of eQTL analysis showed that each probe of VEGF gene was located on different chromosomes. Conclusions:The expression levels and positive and negative correlations of VEGFA, VEGFB and VEGFC were different in the VEGF family of mouse eye, suggesting that these genes may play their role through different pathways.

Clinical characteristics and prognosis related risk factors in nonalcoholic steatosis liver cirrhosis / 中华消化杂志

Objective To investigate the clinical features and prognosis related risk factors in nonalcoholic steatosis liver cirrhosis(NASLC).Methods From January 1st,2006 to December 31st, 2013,in a prospective cohort of 12 489 patients with liver cirrhosis set,174 patients were with NASLC and 306 patients with hepatitis B were the control.The patients were followed up every three months. The clinical data of patients were collected,including gender,age,height,body weight,blood pressure, history of hypertension,history of diabetes,family history of tumor,blood glucose level,high density lipoprotein cholesterol(HDL-C)level,low density lipoprotein cholesterol(LDL-C)level,triglyceride level,white blood cell,platelet,prothrombin time activity,total bilirubin,albumin,cholinesterase,blood urea nitrogen,creatinine,alpha-fetoprotein,abdominal ultrasound,abdominal computer tomography and endoscopy.Body mass index(BMI)and Child-Pugh scores were calculated.The differences between the two groups were analyzed in the incidence of ascites,hepatic encephalopathy,hepatorenal syndrome, esophageal varices bleeding,liver failure,hepatocellular carcinoma and mortality.Chi square test and t test were performed for statistical analysis.logistic regression analysis was used to analyze the risk factors associated with hepatocellular carcinoma in patients with NASLC.Results The proportion of female in NASLC group was higher than that in posthepatic cirrhosis group(56.0%,47/84 vs 28.7%,49/171), and the difference was statistically significant(χ2 =17.653,P<0.01).BMI,systolic pressure,diastolic pressure,level of fasting blood glucose,LDL-C,triglyceride,prothrombin time activity,albumin, cholinesterase,cases number of hypertension,diabetes and metabolic syndrome of NASLC group were all significantly higher than those of posthepatic cirrhosis group(t=6.267,4.091,5.773,2.914,1.877, 2.044,2.326,1.935 and 2.023;χ2=7.241,9.399 and 81.367;all P<0.05),however,serum levels of HDL-C,total bilirubin and creatinine were significantly lower than those of posthepatic cirrhosis group (t=6.127,8.487 and 3.261;all P < 0.05).T he three-year accumulative incidences of hepatic encephalopathy,hepatorenal syndrome and liver failure of NASLC group(8.3%,7/84;1.2%,1/84;0) were all lower than those of posthepatic cirrhosis control group(22.2%,38/171;9.9%,17/171 and 5.8%, 10/171;χ2 = 5.751,3.862 and 3.927,all P< 0.05).The three-year accumulative incidence of hepatocellular carcinoma of NASLC was 8.3%(7/84).The three-year accumulative incidence of mortality was lower than that of posthepatic cirrhosis group(2.4%,2/84 vs 13.5%,23/171;χ2 = 3.884,P=0.049).The results of logistic regression analysis showed that BMI(odds ratio(OR)= 1.469,95%confidence interval(CI)1.093 to 2.176,P=0.016)and diabetes(OR=1.734,95% CI 1.269 to 2.388, P=0.012)were independent risk factors associated with hepatocellular carcinoma in NASLC patients. Conclusions NASLC occurrs mainly in female with good liver function.BMI and diabetes are the risk factors associated with hepatocellular carcinoma in patients with NASLC.

Effect of PLTP on CSE-induced IL-8 production in A549 cells / 中国免疫学杂志

Objective:To investigate the effect of PLTP gene on CSE-induced IL-8 production in human alveolar Type Ⅱcells ( Adenocarcinomic human alveolar epithelial cells , A549 ) .Methods: The different concentrations of CSE co-cultured with human alveolar epithelial cell line ( A549 ) for 24 hours.MTT assay was performed to study the effect of CSE on human alveolar epithelial cell line(A549) growth.Expression levels of PLTP mRNA and IL-8 mRNA were examined by RT-PCR,protein of PLTP were examined by Western blot ,and protein of IL-8 was examined by ELISA .Results: MTT assay showed that the proliferation of A 549 cell line were stimulated by the 0.125%CSE,while the proliferation of A549 cell tends to decrease at high concentrations of CSE (2.0% CSE and 4.0%CSE),and in this middle concentrations of CSE (0.25%CSE ,0.5%CSE and 1.0%CSE),the proliferation of A549 cell was not significantly affected .Our studys suggested that PLTP and IL-8 release were induced by CSE in a concentration-dependent and time-dependent manner ,and expression levels of IL-8 obviously increased after silence PLTP gene .Conclusion:PLTP siRNA can increased CSE-induced IL-8 production in human alveolar epithelial cells (A549).

Study on skeletal muscle mass of 1 836 check-up adults and its association with age in Qiqihar / 中华预防医学杂志

<p><b>OBJECTIVE</b>To analyze the correlation between skeletal muscle mass and age among check-up adults.</p><p><b>METHODS</b>The study objects were those who aged 18-87 years old and came to a city hospital of Qiqihar for health examination from December, 2013 to September, 2014, excepted those with coronary heart disease, infectious disease, endocrine system disease, hypertension, anemia, cancer, liver disease, kidney disease and those carrying with heart pacemaker. A total of 1 836 respondents were finally enrolled into analysis. Appendicular Skeletal Muscle (ASM) was measured by a Body Composition Analyzer, and relative skeletal muscle index (RSMI) was calculated. The relationship among ASM, RSMI and age was assessed by linear regression analysis. The difference of height, weight, BMI, waist-hip-ratio (WHR), total muscle mass and percentage of body fat between genders were tested by t-test. The difference of ASM and total skeletal muscle mass between genders and among age groups was tested by multi-factor variance analysis. The difference of the muscle decline between genders was compared by Chi-square test.</p><p><b>RESULTS</b>The total muscle mass in males was (52.22 ± 6.65) kg, which was significantly higher than that in females ((38.05 ± 4.39) kg) (t=28.20, P<0.001). ASM in 18-29, 30-39, 40-49, 50-59, 60-69, 70-87 years was (24.64 ± 3.23), (24.00 ± 3.12), (24.35 ± 3.03), (23.33 ± 2.97), (22.54 ± 2.91) and (21.40 ± 3.36) kg (F=16.12, P<0.001) in males, respectively, and (16.48 ± 3.14), (16.72 ± 1.93), (16.75 ± 1.93), (16.84 ± 2.28), (16.52 ± 2.35) and(14.70 ± 2.37)kg (F=4.38, P=0.001) in females, respectively. ASM in males ((23.72 ± 3.16) kg) was higher than that in females ((16.65 ± 2.25) kg) (t=55.97, P<0.001). There was a negative correlation between age and ASM in males after 50 years old, the regression equation was y=28.31-0.09x (P<0.001). While a negative correlation between age and ASM in females occurred after 60 years old, the regression equation was y=27.69-0.18x (P<0.001). The prevalence of low ASM was 16.85% (124/736) in females, which was significantly higher than that in males (8.73%, 96/1 100) (χ(2)=27.57, P<0.001).</p><p><b>CONCLUSION</b>A negative correlation was found between age and ASM in males after 50 years old and in females after 60 years old. The prevalence of low RSMI in females was significantly higher than that in males.</p>

Application research of data mining technology in hospital management / 中国医学装备

Objective: Medical data mining can provide automatic data analysis and generate valuable knowledge from medical database in existence. Besides, it offers strong technical support to various decision-making in the hospital management. Methods: This paper introduces the concept of data mining, states its main tasks and then clarifies its present application status. Results:Moreover, a variety of application examples of data mining technology are elaborated in the management of medical quality, consumable items stocking, operation room infection and radiology. Conclusion:Finally, some issues which need to be paid attention to are advanced in the process of data mining application, and meanwhile it is confirmed that the rapidly developing image data mining technology possesses the high professional value and wide application prospect.

Modeling and analyzing of medical material purchasing workflow based on Petri net / 中国医学装备

Objective: In the purchasing process of medical material, it is important that the proper design of each part concerned as well as the optimization and allocation of suitable resources for the model be solved. Methods:Based on the structure and formal definition and process modeling of Petri net, the modeling is established for the mapping from the route mode of workflow to Petri net. Results:Moreover, a rationality validation algorithm for the workflow and a workflow optimization algorithm are proposed. Conclusion: The results indicate that this method is brief and direct in modeling and analyzing of workflow, which will also provide theoretical support for the development of a purchasing software system.

Advances in the targeted therapy for chronic lymphocytic leukemia in the 54th ASH annual meeting / 白血病·淋巴瘤

Recognition has been achieved in the molecular targeting of several key signaling transduction pathways governing cell survival and proliferation in chronic lymphocytic leukemia (CLL).A milestone in CLL treatment is reached.This review provides a brief summary of the 54th ASH annual meeting,focusing on recent advances in the preclinical and clinical investigation of promising target-directed therapeutic agents.

Application of Field Programmable Gate Array(FPGA) to medical instruments / 医疗卫生装备

This paper introduces the theory and structure of FPGA.The excellent performance and powerful developing system of FPGA greatly reduce the designing and developing cost,and promote modern medical instruments in the aspects of micromation,multi-function and seriation.Emphasis is put on the application of FPGA to ECG,ultrasonic instruments and endoscope.

Application Security Control of VersaPulse PowerSuite 100W Holmium Laser System / 医疗卫生装备

The basic construction of VersaPulse PowerSuite 100W holmium laser system is introduced, then focuses on the discussion of its application security control, application furthermore, and analyses its preoperative, intraoperative and postoperative manipulation, and finally elaborates on the corresponding calibration process.