OBJECTIVE To study the correlation between the early postoperative symptom groups and quality of life in patients with thyroid cancer. METHODS From July 2023 to October 2023,patients after thyroid cancer at 1 to 3 days in Beijing and Shanxi Hospitals were selected,and the general data questionnaire,thyroid cancer quality of life scale(EORTC QLQ-THY 34) and quality of life core questionnaire(EORTC QLQ-C30) were used. Exploration factors were used to extract the early symptom group of thyroid cancer patients,investigate the scores of the quality of life,and conduct Pearson correlation analysis. RESULTS Factor analysis extracted four symptom groups:throat-voice symptom group,limb numbness-emotional symptom group,swallowing related symptom group,physical stress symptom group,The cumulative variance contribution rate was 64.93％. The overall health status score of patients with thyroid cancer in the early postoperative stage was 5.12±1.65,it was below the normal level. In the functional domain,the cognitive function score was 3.74±0.45,emotional function score 3.21±0.43,social function 2.96±0.76,and role function 2.66±0.73. The highest scores in the symptom domain were fatigue 1.77±0.39 and pain 1.75±0.50. The symptom group scores were negatively correlated with the scores of all dimensions of quality of life(P<0.05). Each symptom group and each dimension of the quality of life showed significant correlation. The throat-voice symptom group had the strongest correlation with sleep disturbance and role function(r=0.646,r=-0.561). Limb numbness-emotional symptom group was most associated with social functioning,insomnia,and general health(r=-0.538,r=0.529,r=-0.529). Groups of abnormal swallowing symptoms were most associated with physical function,sleep disturbance,and fatigue(r=-0.491,r=0.491,r=0.476),Groups of physical stress symptoms were most associated with physical function and fatigue(r=-0.523,r=-0.520). Sleep disorder had strong associations with each symptom group(r>0.400). CONCLUSION There are four symptom groups in thyroid cancer patients in the early postoperative period,which affect the quality of life of the patients after surgery. Medical staff should timely evaluate and identify the relevant symptoms of the patients after surgery,and conduct effective management,so as to improve the quality of life of the patients after surgery and promote recovery.

OBJECTIVE To observe the auxiliary analgesic effect of electroacupuncture at Hegu and Neiguan combined with in-domethacin suppository in patients undergoing transvaginal ultrasound-guided oocyte retrieval(TUGOR and its effect on the outcome of in vitro fertilization(IVF.METHODS 64 IVF-ET patients undergoing TUGOR were randomly divided into a treatment group and a control group,32 cases in each group.One case dropped out of the treatment group during the treatment.The control group was given indomethacin suppository rectal administration,and the treatment group was given electroacupuncture at Hegu and Neiguan in addition to the treatment of the control group.The patients'tenderness threshold,VAS score,pain grade score,respiratory rate,and pulse rate were evaluated before and after TUGOR operation.The number of oocytes obtained,the rate of two pronuclei(2PN,embryo utiliza-tion rate,and high-quality embryo rate were evaluated after TUGOR operation.The adverse reactions of the two groups were monitored during and after operation.RESULTS After TUGOR operation,the VAS score and pain grade of the treatment group were signifi-cantly lower than those of the control group(P<0.01;the tenderness threshold of the two groups was significantly reduced after opera-tion(P<0.05,P<0.01,and the treatment group was better than the control group(P<0.05;the incidence of nausea during opera-tion,abdominal distension and nausea 48 h after operation in the treatment group were better than those in the control group(P<0.05;the high-quality embryo rate in the treatment group was better than that in the control group(P<0.05.CONCLUSION Electroacupuncture at Hegu and Neiguan combined with indomethacin suppository can effectively assist in analgesia,and can reduce the incidence of adverse reactions during and after TUGOR to varying degrees,and may have certain advantages in improving the rate of high-quality embryos.

Objective To analyze the clinical efficacy and safety of glecaprevir/pibrentasvir in the treatment of pa-tients with hepatitis C virus(HCV)and human immunodeficiency virus(HIV)co-infection,and provide scientific basis for clinical treatment.Methods 89 initially treated non-cirrhotic patients with HCV/HIV co-infection in a hospital of Butuo County of Liangshan Prefecture from January 2021 to January 2022 were selected.All patients re-ceived glecaprevir/pibrentasvir treatment for 8 weeks and were followed up for 12 weeks.Virological response rate at the end-of-treatment and sustained virological response rate after 12 weeks(SVR12)of treatment as well as oc-currence of adverse reaction were recorded.Results Among 89 initially treated non-cirrhotic patients with HCV/HIV co-infection,most were middle-aged and young married men(n=79,88.8％).HIV was mainly transmitted through sexual contact(n=62,69.7％)and intravenous drug use(n=27,30.3％).The most common HCV geno-types were genotype 1b(n=33,37.1％)and genotype 3b(n=25,28.1％).All patients completed 8 weeks of treatment successfully and HCV RNA load at the end of treatment was below the detection limit(＜25 IU/mL).Eight patients failed to complete the follow-up,and the remaining 81(100％)patients achieved a sustained virologic re-sponse.There were no serious adverse reactions during the observation period,but 11 patients had mild adverse re-actions.Conclusion The 8-week treatment regimen of glecaprevir/pibrentasvir for non-cirrhotic patients with geno-type 1,3,and 6 HCV/HIV co-infection can achieve 100％SVR12,with high safety and tolerability,which can be used as a good choice for clinical treatment of these patients.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

PLEK2 (Pleckstrin-2) is a subtype of platelets and leukocytes Pleckstrin, located at 14q23.3-q24.1. Its encoded protein contains 353 amino acids. It plays a role in a variety of cells other than immune cells. The research is relatively limited, mainly involved in the reorganization of cytoskeleton proteins and the regulation of cell extension and migration. PLEK2 plays an important role in the occurrence, development and metastasis of a variety of tumors, and can participate in the regulation of a variety of signal pathways, thereby regulating tumor cell proliferation, invasion and metastasis. PLEK2 is up-regulated in a variety of tumors and has carcinogenic properties. This article reviews the regulatory role of PLEK2 in tumorigenesis, development and metastasis and its impact on tumor prognosis.

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.
Aged ; Aged, 80 and over ; Cardiovascular Diseases ; China/epidemiology* ; Colorectal Neoplasms ; Female ; Humans ; Male ; Retrospective Studies ; Risk Factors

AIM: To investigate the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and its correlation with blood Hcy in hypertensive patients and to provide reference for the prevention and treatment of H-type hypertension in southern Anhui Province. METHODS: A total of 657 hypertensive patients were treated in our hospital from October 2019 to August 2020 were selected as the research objects. The MTHFR C677T and A1298C loci were genotyped by fluorescence staining in situ hybridization, and the blood Hcy concentration was determined by the enzyme cycle method. The distribution characteristics of MTHFR gene in the Han nationality hypertensive population in southern Anhui Province were analyzed, and compared with the reported MTHFR gene distribution data of hypertensive populations in other regions and ethnic groups. RESULTS: Among the 657 patients, the distributions of CC, CT and TT types at the C677T site of MTHFR gene were 212(32.27%), 321 (48.86%), 124(18.87%), and the distribution of AA, AC, and TT types at the A1298C site were 467 (71.08%), 171(26.03%), 19(2.89%). There was no gender difference in the distribution of the two loci of this gene in the hypertensive population in southern Anhui Province (P > 0.05). The distribution frequency of CC genotype at C677T locus is lower than that in Foshan and Guangxi, but higher than that in Henan, Xinjiang and Inner Mongolia; the frequency of CT genotype is higher than that in Foshan and Guangxi; the frequency of TT genotype is higher than that in Foshan and Guangxi. Guangxi region was lower than Henan region, Xinjiang region and Inner Mongolia region, and the difference was statistically significant (P < 0.05). The mean blood Hcy of 657 patients was (15.8 ± 7.80) μmol/L, of which 510(77.62%) were in line with the diagnosis of H-type hypertension. The level of Hcy in males was significantly higher than that in females, and the difference was statistically significant (P < 0.000 1). Compared with the different genotypes of the C677T locus, the TT type was higher than the CT type and CC type, and the difference was statistically significant (P < 0.05). There was no significant difference in Hcy levels between different genotypes at the A1298C locus (P > 0.05). CONCLUSION: The distribution of MTHFR gene polymorphism in the Han nationality hypertensive population in southern Anhui is significantly different from other regions, and it is also significantly related to the level of Hcy, which has obvious regional characteristics. The genetic detection technology combined with the determination of Hcy concentration can provide a scientific basis for the prevention and treatment of H-type hypertension in southern Anhui Province.

Objective:To investigate the clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastrointestinal stromal tumor (GIST).Methods:The retrospective cohort study was conducted. The clinicopathological data of 741 duodenal GIST patients who under-went radical surgery in 17 medical centers, including 121 cases in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 121 cases in Chinese PLA General Hospital, 116 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 77 cases in Fudan University Shanghai Cancer Center, 77 cases in West China Hospital, Sichuan University, 31 cases in Guangdong Provincial People′s Hospital, 24 cases in Fujian Cancer Hospital, 22 cases in Fujian Medical University Union Hospital, 25 cases in Shengjing Hospital of China Medical University, 19 cases in Xiangya Hospital, Central South University, 23 cases in Zhejiang Cancer Hospital, 17 cases in Liaoning Cancer Hospital＆Institute, 17 cases in the First Affiliated Hospital of Xiamen University, 15 cases in Sun Yat-sen University Cancer Center, 14 cases in the First Affiliated Hospital of Nanjing Medical University, 14 cases in Zhongshan Hospital Affiliated to Xiamen University and 8 cases in General Hospital of Chinese People′s Liberation Army Air Force, from January 2010 to April 2020 were collected. There were 346 males and 395 females, aged 55(range, 17?86)years. Observation indicators: (1) neoadjuvant treatment; (2) surgical and postoperative situations; (3) follow-up; (4) stratified analysis. Follow-up was conducted using outpatient examination or telephone interview. Patients were followed up once every 3?6 months during neoadjuvant therapy and once every 6?12 months after radical surgery to detect tumor recurrence and survival of patient up to April 2022. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, and the matching tolerance was 0.02. Results:(1) Neoadjuvant therapy. Of the 741 patients, 34 cases received neoadjuvant therapy for 8(range, 3?44)months. Cases assessed as partial response, stable disease and progressive disease before the radical surgery of the 34 cases were 21, 9, 4, respectively. The tumor diameter of the 34 patients before the neoadjuvant therapy and before the radical surgery were 8.0(range, 3.0?26.0)cm and 5.3(range, 3.0?18.0)cm, with the regression rate as 31.9%(range, ?166.7% to 58.3%). (2) Surgical and postoperative situations. Of the 741 patients, 34 cases underwent radical surgery after receiving neoadjuvant therapy, and 707 cases underwent radical surgery directly. All the 741 patients underwent radical surgery successfully, in which 633, 102 and 6 cases received open surgery, laparoscopic surgery and endoscopic treatment, respectively. Of the 633 cases receiving open surgery and the 102 cases receiving laparoscopic surgery, cases with surgical resection range as pancreatoduodenectomy (PD) was 238, and cases with surgical resection range as duodenal limited resection, including duodenal wedge resection, distal gastrectomy, segmental duodenal resection, local resection of duodenal tumor or segmental duodenum combined with subtotal gastrectomy, was 497, 226, 55, 204, 12. Of the 741 patients, 131 cases had post-operative complications including 113 cases with grade Ⅰ?Ⅱ complications and 18 cases with ≥ grade Ⅲ complications of the Clavien-Dindo classification. The duration of postoperative hospital stay of the 741 patients was 13(range, 4?120)days. Of the 707 patients receiving direct radical surgery, 371 cases were evaluated as extremely low risk, low risk, medium risk of the modified National Institutes of Health (NIH) risk classification after surgery, and 336 cases were evaluated as high risk in which 205 cases receive postoperative adjuvant imatinib therapy with the treatment time as 24(range, 6?110)months. (3) Follow-up. All the 741 patients were followed up for 58(range, 7?150)months. During the follow-up, 110 patients had tumor recurrence and metastasis. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 741 patients were 100.0%, 98.6%, 94.5% and 98.4%, 90.9%, 84.9%, respectively. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 707 patients receiving direct radical surgery were 100.0%, 98.5%, 94.3% and 98.4%, 91.1%, 85.4%, respectively. (4) Stratified analysis. ① Analysis of prognostic factors in patients undergoing radical surgery directly. Results of univariate analysis showed that primary tumor location, tumor diameter, mitotic count, modified NIH risk classification and tumor gene information were related factors affecting the overall survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.43, 0.18, 0.22, 0.06, 0.29, 95% confidence intervals as 0.20?0.93, 0.09?0.35, 0.10?0.50, 0.03?0.12, 0.09?0.95, P<0.05). The primary tumor location, tumor diameter, mitotic count, modified NIH risk classification were related factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.65, 0.25, 0.25, 0.10, 95% confidence intervals as 0.41?1.03, 0.17?0.37, 0.15?0.42, 0.07?0.15, P<0.05). Results of multivariate analysis showed that primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation were independent risk factors affecting the overall survival of 365 patients with primary duodenal GIST after removing 342 patients without tumor gene information who underwent direct radical surgery ( hazard ratio=2.85, 2.73, 3.13, 95% confidence intervals as 1.12?7.20, 1.07?6.94, 1.23?7.93, P<0.05). Tumor diameter >5 cm and mitotic count >5/50 high power field were independent risk factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=3.19, 2.98, 95% confidence intervals as 2.05?4.97, 1.99?4.45, P<0.05). ② Effect of postoperative adjuvant therapy on prognosis of high-risk patients of modified NIH risk classification. Of the 336 patients evaluated as high risk of the modified NIH risk classification, the 5-year overall survival rate and 5-year disease-free survival rate were 94.6% and 77.3% in the 205 cases with postoperative adjuvant therapy, versus 83.2% and 64.4% in the 131 cases without postoperative adjuvant therapy, showing significant differences between them ( χ2=8.39, 4.44, P<0.05). Of the 205 patients evaluated as high risk of the modified NIH risk classification who received postoperative adjuvant therapy, there were 106 cases receiving postoperative adjuvant therapy <36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 87.1% and 58.7%, and there were 99 cases receiving post-operative adjuvant therapy ≥36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 100.0% and 91.5%. There were significant differences in the 5-year overall survival rate and 5-year disease-free survival rate between the 106 patients and the 99 patients ( χ2=13.92, 29.61, P<0.05). ③ Comparison of clinical efficacy of patients with different surgical methods. Before propensity score matching, cases with primary tumor located at bulb, descending, horizontal, ascending segment of duodenum, cases with tumor diameter ≤5 cm and >5 cm were 95, 307, 147, 34, 331, 252, in the 583 patients receiving open surgery with complete clinical data, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery with complete clinical data, showing no significant difference in the primary tumor location ( χ2=0.94, P>0.05), and a significant difference in the tumor diameter ( χ2=17.33, P<0.05) between them. After propensity score matching, the above indicator were 16, 39, 20, 8, 67, 16 in the 83 patients receiving open surgery, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery, showing no significant difference between them ( χ2=1.54, 0.00, P>0.05). Cases with postoperative complications, cases with grade Ⅰ?Ⅱ complica-tions and ≥grade Ⅲ complications of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 17, 12, 5, 11(range, 5?120)days, 92.0%, 100.0% in the 83 patients receiving open surgery, versus 9, 7, 2, 11(range, 5?41)days, 91.6%, 97.3% in the 83 patients receiving laparoscopic surgery, showing no signi-ficant difference in postoperative complications, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=2.91, Z=3 365.50, χ2=3.02, 1.49, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification between them ( P>0.05). ④ Comparison of clinical efficacy of patients with primary tumor located at the descending segment of duodenum who underwent surgery with different surgical resection scopes. Before propensity score matching, cases with tumor diameter ≤5 cm and >5 cm, cases with tumor located at opposite side of mesangium and mesangium were 71, 85, 28, 128 in the 156 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 92, 41, 120, 13 in the 133 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing significant differences between them ( χ2=16.34, 150.10, P<0.05). After propensity score matching, the above indicator were 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference between them ( χ2=0.00, 0.00, P>0.05). Cases with postopera-tive complications, cases with grade Ⅰ?Ⅱ complications and ≥grade Ⅲ compli-cations of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 13, 11, 2, 15(range, 9?62)days, 94.2%, 64.3% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 9, 8, 0, 15(range, 7?40)days, 100.0%, 78.8% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference in post-operative complica-tions, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=0.99, 0.34, 1.86, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification ( P>0.05) and there was a significant difference in duration of postopera-tive hospital stay ( Z=614.50, P<0.05) between them. Conclusions:The clinical efficacy of radical surgery for duodenal GIST are ideal. Primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation are independent risk factors affec-ting the overall survival of patients undergoing direct radical surgery and tumor diameter >5 cm and mitotic count >5/50 high power field are independent risk factors affecting the disease-free survival of patients. There is no significant difference in the short-term efficacy and long-term prognosis between patients undergoing open surgery and laparoscopic surgery. For patients with primary tumor located at the descending segment of duodenum, the duration of postoperative hospital stay is longer in patients undergoing PD compared with patients undergoing duodenal limited resection. For patients evaluated as high risk of the modified NIH risk classification, posto-perative adjuvant therapy and treatment time ≥36 months are conducive to improving the prognosis of patients.

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