Liver transplantation for the treatment of acute liver failure in 3 cases with NBAS gene deficiency and literature review / 中华儿科杂志

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.

Application of Case-PBL method combined with SPSS software in teaching of medical statistics course / 中华医学教育探索杂志

Objective To evaluate the effect of case-PBL method and case-PBL method combined with SPSS software on the teaching of medical statistics for medical undergraduates. Methods Students from two classes major in experimental medicine from Nantong University Xingling College were selected as Experimental Class 1 ( using case-PBL teaching ) and Experimental Class 2 ( using case-PBL teaching combined with SPSS software). Each class attended lessons for five times. The teachers would send cases for each lesson one week in advance, and students would form into groups to access information, learn and discuss independently. Representatives from groups spoke in class, members would complement and discuss, while teachers offered guidance, review, analysis and summary. We shortened the discussion time in the class, and added instructions on the operation steps of SPSS software for case analysis and how to interpret the analysis result correctly in Experiment Class 2 . The Control Class received traditional teaching . Questionnaires, process assessment and final assessment were used to evaluate teaching effectiveness. SPSS 21.0 software was used to implement variance analysis and chi-square test for comparison between groups. Results The scores of the two experimental classes were higher than those of the control class in the five process assessments ( P<0 . 05 ) . Experimental Class 2 was the best in three section process assessments including those of t-test, the rank sum test and the straight-line correlation (P<0.05). However, there was no difference in the theoretical test scores among the three classes (P=0.670). 94％-100％of the students in the two experimental classes believed that the teaching effects of the case-PBL method and case-PBL method combined with SPSS software were better than the traditional teaching method (P<0.05) in such areas as stimulating interest in learning, improving learning efficiency, etc. Students in Experimental Class 2 were more prone to think these methods improved teaching effect. Conclusion The case-PBL teaching combined with the application of SPSS software will further help students to systematically grasp the statistical knowledge and cultivate statistical practice ability . However , neither methods will improve students' theoretical test scores.

Endometrial MicroRNA Signature during the Window of Implantation Changed in Patients with Repeated Implantation Failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis.</p><p><b>METHODS</b>A total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs.</p><p><b>RESULTS</b>Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis.</p><p><b>CONCLUSIONS</b>There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.</p>

The prevalence of burnout and active interventions of graduate students of clinical medicine during residency training / 中华医学教育探索杂志

The research data at home and abroad show that the overall burnout rate of clinical professional graduate students was high. They are vulnerable to burnout because of long duty hours, learn-ing pressure, intense and overloading work and especially the significantly reduced personal accomplish-ment in the situation of the contradiction between doctors and patients in our country. Burnout not only re-sults in psychological distress and physical symptoms, but also has negative effect on the quality of graduate medical education during residency training. Therefore, educators need to develop an active awareness of burnout and ought to perform interventions such as formulating the appropriate learning goals, improving the work efficiency, reducing work hours, positive psychological counseling and stress management training to prevent such occurrences.

The investigation of urine iodine and blood TSH levels in 695 neonates and urine iodine level in their mothers in ;Yunnan province / 临床儿科杂志

Objective To explore the levels of urine iodine in mothers and urine iodine and blood thyroid-stimulating hormone (TSH) in their neonates, and the correlations. Methods A total of 695 pairs of mothers and their neonates were included. Urine sample of both mothers and newborns were collected and the levels of urine iodine were detected. Heel blood sample of newborns were collected and the levels of TSH were detected. Results The median urine iodine level in 695 mothers was 212 . 9μg/L, among whom 163 case ( 34 . 39%) were iodine deifcient (?5 mIU/L in neonates whose mother were iodine deifcient or excessive were higher than those in neonates whose mother were iodine adequate or more than adequate, and the difference was statistically signiifcant (P

A randomized, single-blind, parallel-controlled and multicentre study：compare the efficacy and safety of domestic and imported human recombinant FSH in WHO group Ⅱ anovulatory infertility / 中华妇产科杂志

Objective To evaluate the efficacy and safety of domestic human recombinant FSH (rhFSH) in women with anovulation of WHO groupⅡ. Methods A randomized, blind, parallel-controlled, non-inferiority and multicenter study was performed. A total of 534 admitted to 13 hospitals from May 2008 to August 2009. There were 531 women with ovulatory disorder was included in the statistical analysis, were randomly divided into test group (domestic rhFSH, n=352) and control group (imported rhFSH, n=179). Percentage of cycle with mature follicle, ovulation rate, clinical pregnancy rate, multiple pregnancy rate, ovarian hyperstimulation syndrome (OHSS) and adverse events were observed. Results No statistical significant differences (P>0.05) were observed between the two groups in terms of the efficiency on mature follicle [91.8%(323/352) versus 88.8%(159/179)], ovulation rate [91.3%(295/323) verus 90.6%(144/159)], clinical pregnancy rate [19.2%(62/323) verus 18.2%(29/159)], the number of the follicles0.05), and no other adverse events were observed in test group during treatment. Conclusion Ovarian stimulation with domestic rhFSH is effective, safe and economical in women with anovulation of WHO groupⅡ.

Efficacy and safety of mifepristone combined with misoprostol for termination of pregnancy ;between 8 and 16 weeks of gestation / 中华妇产科杂志

Objective To assess the efficacy and safety of mifepristone combined with oral or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of gestation. Methods This was a randomized, multi-center, open clinical trial. A total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either oral misoprostol 400 μg every 3 hours or vaginal misoprostol 400μg every 6 hours for a maximum of 4 doses 36-48 hours later. There were 417 women in oral group with 198 at 8-9 weeks and 219 at 10-16 weeks, while 208 women in vaginal group with 99 at 8-9 weeks and 109 at 10-16 weeks. The outcome measures were the success abortion rate, induction to abortion interval, the amount of bleeding, reoccurrence of menstruation and adverse events. Results Abortion rate was significantly higher in vaginal group [98.1% (202/206)] than that in oral group [94.0%(390/415), P=0.023]; concerning termination of pregnancy at 8-9 weeks and 10-16 weeks respectively, there were no significant differences between oral and vaginal groups (P=0.156, P=0.073). The induction to abortion interval was no significant difference in oral and vaginal group in different gestational weeks ( P=0.238, P=0.273). The average induction to abortion interval was (4.1 ± 6.6) hours and (6.0 ± 4.5) hours respectively in terminating 8-9 weeks and 10-16 weeks of gestation. Concerning the amount of bleeding within 2 hours of placenta expulsion, there was significant difference between oral group [(63±46) ml] and vaginal group [(55 ± 45) ml] in terminating 8-9 weeks of gestation (P=0.047), while there was no significant difference between groups in terminating 10-16 weeks of gestation [oral group (76 ± 52) ml versus vaginal group (76 ± 61) ml, P=0.507]. The reoccurrence of menstruation was about 37 days in both oral and vaginal groups. Two cases of incomplete abortion were serious adverse events (SAE) relating to treatment. The common adverse events (AE) of nausea and vomiting were significantly higher in oral group [57.2% (239/417), 36.3% (151/417)] than those in vaginal group [45.4% (94/208), 26.1% (54/208); P=0.005, 0.011]. Conclusion Oral or vaginal misoprostol combined with mifepristone, is effective and safe for termination of pregnancy between 8 and 16 weeks of gestation.

Cytotoxic effects of mono-(2-ethylhexyl) phthalate on human embryonic stem cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mono-(2-ethylhexyl) phthalate (MEHP), the metabolite of di-(2-ethylhexyl) phthalate (DEHP), was suspected to be toxic to human embryos. This study contributes to investigating its toxic effects by an embryonic stem cell test (EST) based on two human embryonic stem cell (hESCs) lines.</p><p><b>METHODS</b>CH1 established in our own lab and H1, a federally registered cell line were two human embryonic stem cell lines used in this test. Four endpoint measurements were performed consisting of cell viability, proliferation ability, apoptosis as well as changes of gene expression patterns after spontaneous differentiation were determined. For measuring effects on the first three endpoints, the cells were treated with various concentrations of MEHP dissolved in dimethyl sulfoxide (DMSO) and only with DMSO which served as control and harvested after 5 days. For measuring effects during spontaneous differentiation, the RNA of embryoid bodies (EBs) formed after 8 days' MEHP exposure was collected and changes in differentiation specific gene expression patterns were analyzed by quantitative real time RT-PCR.</p><p><b>RESULTS</b>As a result the viability and proliferation ability of both cell lines decreased significantly at 1000 µmol/L MEHP, while there was no effect on apoptosis or cell morphology. In addition MEHP also changed the gene expression pattern in the EBs of both cell lines.</p><p><b>CONCLUSION</b>MEHP in a high dose was cytotoxic and affected the development of hESCs, which indicates its embryo toxicity in human embryos.</p>

Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Late onset hypogonadism negatively impacts on men's psychological well-being. This study was conducted to examine the interrelationship among symptoms of testosterone deficiency, psychological well-being, and quality of life.</p><p><b>METHODS</b>Eligible subjects were randomized into active treatment and control groups, and were asked to complete the following questionnaires at baseline and month 6: aging male's symptoms (AMS) rating scale, hospital anxiety and depression scale (HADS), perceived stress scale (PSS) and the short form health survey-12 (SF-12). In this study, men were treated and monitored for 6 months with oral testosterone undecanoate (TU) capsules or vitamin E/C capsules in a single-blinded fashion. All in the active treatment group were administered a total of 120 - 160 mg TU orally on a daily basis. Total and free T levels between baseline and month 6 were compared.</p><p><b>RESULTS</b>One hundred and sixty eligible subjects were recruited and followed up. In the active treatment group, total serum testosterone concentrations before and after intervention were (7.98 ± 0.73) nmol/L and (13.7 ± 1.18) nmol/L. The mean HADS anxiety subscale scores for the subjects at baseline and at month 6 were 3.47 ± 0.4 and 1.72 ± 0.2, respectively (t = 1.526, P < 0.05). Additionally, the mean HADS depression subscale scores were 4.91 ± 0.6 and 2.39 ± 0.3, respectively (t = 3.466, P < 0.05). The mean scores on PSS for the subjects at baseline and at month 6 were 12.88 ± 2.1 and 9.83 ± 1.7, respectively (t = 4.009, P < 0.05). Significantly improved SF-12 could be observed (t = 1.433 and 1.118, respectively; both P < 0.05). No significant changes were observed in the control group at month 6.</p><p><b>CONCLUSION</b>Androgen replacement not only improves androgen deficiency associated symptoms, but also enhances comprehensive improvement in psychological issues.</p>

A live birth of activated one-day-old unfertilized oocyte for a patient who experienced repeatedly near-total fertilization failure after intracytoplasmic sperm injection / 中华医学杂志(英文版)

Total or near-total fertilization failure after intracytoplasmic sperm injection (ICSI) is a rare event, but it occurs repeatedly because of sperm defects in activating oocyte. The case presents a successful pregnancy and live birth after calcium ionophore A23187 (A23187) activation on one-day-old unfertilized oocytes in a patient whose husband suffered oligoasthenoteratozoospermia, and who had experienced repeated near-total fertilization failure after ICSI. In the second ICSI cycle, only one oocyte was fertilized while nine were unfertilized. Oocyte activation with A23187 were performed on the one-day-old unfertilized oocytes after ICSI and resulted in fertilization and embryo transfer. A clinical pregnancy was achieved and a healthy baby was born. To our knowledge, this is the first reported case of a healthy birth after oocyte activation on the one-day-old unfertilized oocyte. This indicates that "rescue oocyte activation" on one-day-old unfertilized oocytes after ICSI may be helpful for preventing total or near-total fertilization failure after ICSI.

Derivation and characterization of Chinese human embryonic stem cell line with high potential to differentiate into pancreatic and hepatic cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embryonic stem cell lines with clarified directly differentiation ability.</p><p><b>METHODS</b>Donated embryos that exceeded clinical use in our in vitro fertilization-embryo transfer (IVF-ET) center were collected to establish human embryonic stem cells lines with informed consent. The classic growth factors of basic fibroblast growth factor (bFGF) and recombinant human leukaemia inhibitory factor (hLIF) for culturing embryonic stem cells were used to capture the stem cells from the plated embryos. Mechanical and enzymetic methods were used to propagate the newly established human embryonic stem cells line. The new cell line was checked for pluripotent characteristics with detecting the expression of stemness genes and observing spontaneous differentiation both in vitro and in vivo. Finally similar step-wise protocols from definitive endoderm to target specific cells were used to check the cell line's ability to directly differentiate into pancreatic and hepatic cells.</p><p><b>RESULTS</b>We generated a new Chinese human embryonic stem cells line, CH1. This cell line showed the same characteristics as other reported Chinese human embryonic stem cells lines: normal morphology, karyotype and pluripotency in vitro and in vivo. The CH1 cells could be directly differentiated towards pancreatic and hepatic cells with equal efficiency compared to the H1 cell line.</p><p><b>CONCLUSIONS</b>This newly established Chinese cell line, CH1, which is pluripotent and has high potential to differentiate into pancreatic and hepatic cells, will provide a useful tool for embryo development research, along with clinical treatments for diabetes and some hepatic diseases.</p>

Effect of gonadotropin-releasing hormone agonist on fertility potential in patients with stage Ⅰ endometriosis after laparoscopy / 中华妇产科杂志

Objective To investigate the impact on fertility potential of patients with stage Ⅰ endometriosis treated by gonadotropin-releasing hormone agonist (GnRH-a) treatment followed by laparoscopy surgery.Methods From Jan.2006 to Jun.2008, medical documents of 102 patients with minimal or mild endometriosis (stage Ⅰ) treated by laparoscopy and hysteroscopy surgery and excluded the other causes of infertility were reviewed retrospectively in Peking University People's Hospital.The pelvic endometriosis teisions were destructed by electric burning.Those patients were divided into GnRH-a treatment group(n = 60) and non-GnRH-a treatment group(n = 42) after surgery.The patients in GnRH-a treatment group were administered by GnRH-a injection once or twice after surgery, in the mean time, no adjuvant therapy were given for the patients in the other group.All the patients were followed-up for 24 months after surgery to evaluate the effect of postoperative GnRH-a treatment on pregnancy outcome and fertility potential(number of pregnancy per 100 women in one month, expressed as percentage).Results The total pregnancy rate of 78% (47/60) in GnRH-a treatment group is significantly higher than 55% (23/42) in non-GnRH-a treatment group(P =0.012).There is no significant difference in spontaneous abortion rate between the GnRH-a treatment group and non GnRH-a treatment group(19% vs.13%, P = 0.465).The fecundity rate of were 6.17% in GnRH-a treatment group and 3.26% in non-GnRH-a treatment group, which the relative risk is 1.9 (95% CI: 1.1-3.0).Conclusion Low-dose GnRH-a treatment after laparuscopy can improve the pregnancy rate and fertility potential of patients with stage Ⅰ endometriosis.

Expression of chlamydia pneumoniae DNA in peripheral blood in patients with atherosclerosis obliterans / 中国综合临床

Objective To investigate the association between chlamydia pneumoniae(Cpn)and atherosclerosis obliterans(ASO). Methods Sixty ASO patients and 40 healthy persons were selected,and their Cpn DNA expressions in venous blood determined by polymerase chain reaction(PCR). Results The ASO patients had significantly higher positive expression rate of Cpn DNA than that of healthy persons(78. 33% vs. 47.50% ,P ＜0.05). In all 60 cases the Cpn DNA expressions were positively correlated with the severity of ASO. Conclusions Cpn DNA expression closely relates with ASO severity,and it plays an important role in the ASO pathogenesis.

Analysis of clinical knowledge and clinical skills scores in obstetrics and gynecology training / 中华医学教育探索杂志

Objective To evaluate obstetrics and gynecology training quality by analysis of clinical knowledge and clinical skills scores for long-term graduates.Methods A retrospective analysis of clinical knowledge and clinical skills scores was performed in obstetrics and gynecology training for 134 long-term graduates.Results The clinical knowledge and clinical skills scores of obstetrics and gynecology training were 82.27?7.68,87.69?7.24.There was no,P﹥0.05.Only the scores of clinical skills judged by one teacher in interview was correlated with clinical knowledge scores,while there were no correlation between clinical knowledge judged by other five teachers and scores of clinical skills.Conclusion There was no correlation between clinical knowledge and the scores of clinical skills scores.Culturing students’practical ability and communication ability is worth strengthening,while the consistency of teachers’evaluation standard should be improved.

Cell-cycle negative regulatory gene ANA is over-expressed in the brain tissues of patients with Down syndrome / 北京大学学报(医学版)

Objective: To investigate the expression level of genes located in chromosome 21 in the brain tissues of Down syndrome(DS). Methods: An optimized semi-quantitative RT-PCR method was used to evaluate the expression levels of seven genes encoded in chromosome 21 in fetal cortex brain and cerebellum of DS and the control at the end of 20 weeks of gestation. B2M was used as internal reference to normalize cell loss. Results: The expression levels of 6 genes in cortex and cerebellum, including DYRK1A, SYNJ1, PCP4, C21orf5, C21orf2 and C21orf106, were comparable between DS and the control. ANA, a cell-cycle negative regulatory gene, was over-expressed dramatically in the cortex but not in the cerebellum of DS. Conclusion: Over-expression of ANA may contribute to the reduction of neuronal density in DS brain.

Study on the association of estrogen receptor genotypes with bone mineral density in Chinese postmenopausal Han women in Beijing / 北京大学学报(医学版)

Objective:To investigate the distribution of polymorphism of estrogen receptor (ER) gene in postmenopausal Han women in Beijing as well as its relationship with bone mineral density (BMD).Methods:Xba Ⅰ,and Pvu Ⅱ polymorphisms of ER gene were studied by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) and BMD were determined by DEXA (dual-energy X-ray absorptiometry).The relationship between BMD and polymorphism of ER gene was studied by variance analysis.Results:Pvu Ⅱ polymorphism of ER gene was not associated with BMD of spongy and compact bone of radius;while Xba Ⅰ polymorphism of ER gene was associated with BMD of spongy and compact bone of radius.The lowest BMD was found with XX genotype while the highest BMD was found with xx genotype.Conclusion:There is high correlation between of Xba Ⅰ polymorphism and BMD of spongy and compact bone of radius.Our study suggested some bases to explore the pathogenesis of osteoporosis and to prevent the development of osteoporosis.

EXPRESSION OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 IN HUMAN OVARY AND ITS RELATIONSHIP WITH POLYCYSTIC OVARY SYNDROME / 解剖学报

Objective Insulin resistance is a possible cause of polycystic ovary syndrome(PCOS).It is presumed that ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1) is associated with insulin resistance.The purpose of this study is to explore the expression of ENPP1 in granulosa cells of the ovary and its relationship with PCOS. Methods Twelve aliquots of follicular granulosa cells were isolated from 12 samples of the patients with PCOS and 22 aliquots from 22 samples of the patients without PCOS,respectively.ENPP1 expression was analyzed by reverse transcription polymerase chain reaction(RT-PCR) and in situ hybridization.The relative expression of ENPP1 mRNA was detected by real-time quantitative polymerase chain reaction(real-time PCR). Results ENPP1 was expressed in granulosa cells of the ovary.ENPP1 expression's 2~(-?Ct) in granulosa cells of PCOS was significantly higher than non-PCOS(1.67?0.89 vs.0.94?0.76,P=0.017).Conclusion ENPP1 expression plays a role in ovary function and may be closely associated with the development of PCOS.