Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans

In order to solve the problem of continuous monitoring and automatic regulation of patient airbag pressure in intensive care unit, the study designed an intelligent management system of artificial airway airbag pressure. It can realize real-time monitoring and automatic control of airbag pressure. Its pressure data was sent to the PC in real time by the serial port. It can realize the display, store, review and analysis of pressure data. Its clinical application effect was discussed. Experiments showed that the system can monitor airbag pressure in real time and control the pressure to stabilize at 25~30 cmH
Air Bags ; Critical Care ; Humans ; Intensive Care Units ; Monitoring, Physiologic

Objective: To evaluate the indication, safety and effectiveness of transoral robotic surgery (TORS) for oropharyngeal cancer based on our preliminary experience. Methods: Twelve patients, including six with tonsil cancer, five with tongue base cancer and one with posterior pharyngeal wall cancer, who underwent TORS with Da Vinci Si surgical system from March 2017 to October 2018 at Tongji Hospital of Huazhong University of Science Technology were respectively analyzed. And the surgical time, intraoperative blood loss, postoperative local bleeding, dyspnea, nerve function injury, oral intake time, whether or not to receive chemoradiotherapy were analyzed. Results: All tumors in the 12 patients were en bloc removed by TORS. Surgical time ranged from 25 to 80 min with an average of 34.2 min. The blood loss ranged from 10 ml to 50 ml with an average of 20.8 ml. The recovery time for oral intake ranged from 1 day to 30 days with an average of 8.4 days. No patient underwent tracheostomy after TORS. Also, no patient manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All 12 patients reached pathologically negative surgical margins. The patients were followed up for 4 to 22 months, with a median of 12 months. All patients who combined with more advanced than T3 stage, or more advanced than N2 stage were recommended to oncologist, then, followed with radiotherapy or chemoradiotherapy if no relevant contradictions occurred. No local recurrence or distant metastasis case was found. Conclusion With proper indications, the application of TORS in oropharyngeal cancer is a relatively safe, effective and minimal invasive therapy, which merits more clinical applications.

Since the outbreak of COVID-19, the hospital is faced with such challenges as sustained input in patient screening, referral and rescue, supportive medical supplies including the management of personal protective supplies and the maintenance of medical equipment. In the face of increasing workload, the medical materials support team of the hospital took the following measures in the principles of " discovering new sources of supplies and minimizing consumption" . These measures taken include proactive supply procurement strategy, prioritizing allocations based on risk exposure, uniform distribution of supplies based on inventory and usage, and traceable management for donated supplies; optimal and central deployment of equipments, emergency installation, pre-maintenance and emergency repairs for equipments; efficient and safe sterilization of reusable materials and equipments using sterilizers; enhanced personnel training and management to keep updating the medical supplies capacity of the team. All these efforts have contributed significantly to the orderly work of epidemic control.

Objective: To understand the status quo and differences of the rights and interests of primary medical staff in a community, and to provide targeted suggestions for improving the rights of such staff. Methods: From October to November 2018, a questionnaire survey was conducted on all the medical staff of 8 community health service centers in a district of Shanghai, and 562 valid samples were obtained. Results: The primary medical staff had the highest demands for " pay rise" (4.783±0.598), " paid vacation" (4.569±0.873)and " additional reserve fund" (4.553±0.963); the lowest demands were placed on " education-based promotion" (3.797±1.382), " refresher training" (3.801±1.314), and " opinion feedback mechanism" (4.018±1.223). At the same time, the rights and interests of these staff in different occupational categories were significantly different(P<0.05)in " daily reimbursement" , " housing subsidy" , " refresher training" and " opinion feedback mechanism" . Conclusions The salary demands of the primary medical staff are the most obvious, and there are differences in the demands of medical staff in different occupational categories. It is suggested to establish a more reasonable salary system and pay attention to the differentiated appeals of different medical personnel.

BACKGROUND: Cisplatin acquired resistance is a vital problem in the chemotherapy of non-small cell lung cancer, which needs to be further addressed. In recent years, obtaining drug resistant cells from cell cultivation and serving for metabolomics research to find differential metabolites and get potential biomarkers, is a good reference for clinical research and cancer treatment. This study aimed to obtain metabolite information related to cisplatin resistance through metabolomics analysis. METHODS: Metabolites were extracted from A549 cells and cisplatin resistant A549/DDP cells, and ultraperformance liquid chromatography coupled with time of flight mass spectrometry was used to perform metabolomic analysis of endogenous molecules of the two cells and obtain metabolic differences. RESULTS: Through data analysis, 40 metabolites were identified as differential metabolites, mainly involving phospholipids, fatty acids, amino acids and metabolites related to energy metabolism. CONCLUSIONS The drug resistance of A549/DDP cells may be caused by the changes of cell membrane structure and related metabolic pathways.
A549 Cells ; Carcinoma, Non-Small-Cell Lung ; pathology ; Chromatography, High Pressure Liquid ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; pathology ; Mass Spectrometry ; Metabolomics ; methods

Summarize the application of SOAP in the medical field and find out its problems in the course of traditional Chinese medicine, to explore the significance and value of SOAP in teaching practice in TCM. Organize relevant literature and discuss the application of SOAP in the course of Chinese medicine. SOAP is widely used in various aspects of medicine, and there are still some problems in the course of TCM. The use of SOAP model for teaching and assessment has important practical significance and value in the course of Chinese medicine internal medicine practice, and SOAP emphasize the practice of the post competence oriented teaching, which is worth promoting.

Objective: To understand the serotypes, genotypes and transmission source of dengue viruses(DENV) isolated in Yunnan from 2013 to 2015. Methods: Viral RNA was extracted from serum samples of dengue fever(DF) cases at the acute stage in Yunnan, then the gene fragments of envelope protein(E) region were amplified by RT-PCR. The homology and phylogenetic analysis was made on the nucleotide and deduced amino acid sequences by bioinformatics softwares including Clustal X, DNAStar and MEGA5. Results: Viral nucleic acid detection and sequencing indicated that 40 E genes of DENV were obtained. The serotypes and genotypes of DENV were revealed by homology and phylogenetic analysis based on E genes of DENV. Fifteen virus strains belonged to DENV serotype 1(DENV-1), of these, 14(11 from Ruili, 1 from Lincang and 2 from Kunming) were genotype I(G-I), 1 from Kunming was G-V. Twenty-two virus strains belonged to DENV serotype 2(DENV-2), of these, 10 from Ruili were G-I and 12 from Xishuangbanna were G-IV. Two virus strains belonged to DENV serotype 3(DENV-3) and G-II. One virus strain belonged to DENV serotype 4(DENV-4) and G-I. All detected DENV genotypes were mainly predominant in Southeast Asia. All the 40 Yunnan DENV strains shared high homology with the DENV strains in Southeast Asia countries. Conclusions Four serotypes and multiple genotypes of DENV had been co-circulating in Yunnan from 2013 to 2015. The DENV transmitted from Southeast Asia countries was the main cause of DF in Yunnan. It is necessary to strengthen the surveillance and management on the imported cases of DF in Yunnan.

Objective: The burden of chronic disease has been continuously increasing in China since the early 1980s. Besides the worsening of risk factors, the change in diagnostic criteria is very likely an important explanation for the increase in the prevalence of hypertension, hyperlipidemia and diabetes mellitus, three commonest, major chronic conditions that can lead to major vascular events and deaths. This study aims to estimate the contribution of changes in diagnostic criteria to the increase in the prevalence of the three conditions in China. Methods: The data from two representative nation-wide surveys in China in 2002 and 2009, with 145 254 and 8 813 adults included respectively, were used to estimate the prevalence rate of the three conditions and the proportion attributable to the change in diagnostic criteria around year 2000. The new and old cutoff values for hypertension, hyperlipidemia, and hyperglycemia were 140/90 and 160/95 mmHg (1 mmHg=0.133 kPa), 5.7 and 6.2 mmol/L, and 7.0 and 7.8 mmol/L, respectively. The prevalence was standardized according to the distribution of age, sex and rural-urban residence of the 2000 national census of the country so as to compare between the old and new diagnostic criteria and project the situation for the entire country. Results: The standardized prevalence of hypertension, hyperlipidemia, and diabetes mellitus for the entire Chinese adult population in 2002 was 8.21%, 1.71% and 1.43% according to the immediate previous diagnostic criteria, and 19.18%, 3.53% and 2.66% according to the new criteria. In 2009, the prevalence was 11.89%, 9.34% and 4.29% according to the old criteria, and 24.78%, 18.36% and 6.55% according to the new criteria. The total cumulative prevalence of the three conditions was increased by 124% in 2002 and 95% in 2009 as a result of change in diagnostic criteria. Put it differently, the change in diagnostic criteria increased the number of the three conditions from 2002 to 2009 by approximately 359 million and could increase the annual drug costs by some 271 billion RMB if all the conditions are treated. The drug costs alone of treating all the three conditions could consume 56% of the total health budget of the Government in 2010. Conclusion About half of the number of the three conditions is a result of the change in diagnostic criteria. These criteria were adopted from western populations, which are designed to meet the population need and suit healthcare resources available in these countries. It is important for China to consider the resources available and needs and values of the population in addition to the benefits, harms and costs of treatment in determining the cutoff values for defining these conditions for drug interventions.