Objective To investigate the clinical features and pathogenic genes of a familial hypokalemic periodic paralysis ( HOKPP).Methods PCR amplification and DNA sequencing were used to screen candidate genes of the HOKPP family members (CACNA1S, SCN4A, KCNE3), and the clinical features were carefully analyzed at the same time.Results The sequencing analyses of the SCN4A gene in the proband identified three nucleotide sequence mutations, which influenced the amino acid sequence of the skeletal sodium channel.One of the mutations was identified as a C/T heterozygous pattern at the 2111th nucleotide position in exon 13, resulting in a change from Thr to Met at the 704th amino acid position of the sodium channel protein.All affected patients carried the Thr704Met mutation, whereas unaffected family members did not.Clinical symptoms in this family followed an autosomal dominant inheritance pattern.Muscles weakness, pain and hypokalemia in the period between attacks were seen in all patients.Paralytic symptoms occurred early, lasted longer and recurred frequently, while cold was the main predisposing factor.With the progress of the disease, patients represented persistent weakness and atrophy in proximal muscles.Conclusions Mutation (Thr704Met) in the SCN4A gene should be responsible for this family.This mutation causes severe HOKPP and progressive muscle atrophy.

Objective: The characteristics and differences of the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia were investigated to provide references and suggestions for the compilation of the Chinese Pharmacopoeia.
Methods: From the perspective of frame structure and main contents, the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia was compared.
Results: Each volume of the Chinese Pharmacopoeia had its general notice, including 34 to 48 items and 10 to 12 chapters based on different varieties collected in each volume. The Japanese Pharmacopoeia had 49 items not arranged by chapters. There are many differences on the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia, such as the definitions and expressions of names, determination of appearance, revision rules, risk assessment and quality control conception. The framework of the general notice in the Chinese Pharmacopoeia was clear, the content was specific and the operation was friendly. The term description of the general notice in the Japanese Pharmacopoeia was concise, and some terms need to be implemented under the guidance of professional knowledge.
Conclusion: In light of comparative study, every volume’s general notice of the Chinese Pharmacopoeia has its own characteristics. By integrating advanced analytical technique, combining the requirements with laws and regulations, and optimizing content and terms, all volume’s general notice could be explored to be coordinated and unified.

Objective:To evaluate the association between the efficacy and safety of metformin and the influence of variants in SLC47A1 rs2289669 G>A polymorphism in the treatment of systemic lupus erythematosus (SLE).Methods:A multicenter, randomized, double-blind, placebo-controlled trial was conducted. Patients were consented at enrollment for blood donation for genotyping, and their peripheral blood were used to detect the distribution frequency of SLC47A1 mutations. The major or mild/moderate flares defined by modified safety lupus erythematosus national assessment (SELENA)-systemic lupus erythematosus disease activity index (SLEDAI) Flare Index (SFI) and adverse events were recorded at 12 months of follow-up. The correlation between efficacy/safety and genotype was analyzed. Student's t test and χ2 test was used to assess the continuous variables and categorical variables. Results:Between May 24, 2016, and Dec 13, 2017, a total of 31 patients in the metformin group and 35 in the placebo group were detected. There were no statistical significant differences in the clinical manifestations, SELENA-SLEDAI scores, and therapy of the participants at baseline. There was no significant difference in the frequency of AA genotype, GA genotype, and GG genotype of SLC47A1 rs2289669 distribution between the metformin group and the placebo group. In the metformin group, patients who flared had a lower frequency of A alleles than those non-flared [25%(4/16) vs 61%(28/46), χ2=6.116, P=0.019 8]; the flare rate was significantly lower in patients with AA genotype than in GG genotype [0%(0/8) vs 57%(4/7), χ2=6.234, P=0.012 5]. The infection rate was lower in the metformin group than that in the placebo group [38%(12/31) vs 69%(24/35), χ2=5.913, P=0.015 0], but there was no significant difference among different genotypes in the metformin group. Compared to GG geno-type, AA genotype showed a trend of decrease in infection rate[38%(3/8) vs 72%(5/7), χ2=1.727, P=0.188 8]. Conclusion:Metformin has a favorable safety profile and may reduce the frequency of flares in SLE patients with low-grade lupus disease activity. The metformin therapeutic efficacy in SLE is relevant to the SLC47A1 gene polymorphism. Patients of the AA genotype may benefit most from metformin than those of the GG and GA genotypes.

The purpose of this study is to investigate the basic situation of self-regulated learning among clinical medical undergraduates in the stage of professional courses and construct a structural model suitable for them to carry out self-regulated learning . Zimmerman's self-regulated learning concept framework was determined as the theoretical basis of this study. A questionnaire survey was performed to identify five main dimensions affecting self-regulated learning including expression of learning intention, self-efficacy, adjustment of learning behavior, management of curriculum strategies, and adaption of learning environment, and then, Amos 24.0 software was used to construct the structural model and draw the conclusion that self-regulated learning in this group centers on the regulation of learning behavior, with learning intention and self-efficacy as sub-centers.

The establishment of outcome-based or competency-based education is an important feature of today's curriculum plans. This paper reviews the development and application of outcome-based education (OBE) in medical education. Based on the concept of OBE, the curriculum framework system of Higher Medical Education is reformed and optimized, and the frameworks of course learning outcome, curriculum teaching theme and curriculum competency are redesigned and determined. Outcome-based curriculum reform reflects the requirements of global healthcare education for medical talents in the new era. Driven by the learning outcomes of postgraduates, the curriculum reform focuses on cultivating the postgraduates' recognition, understanding, analysis and research of the phenomena and problem-solving abilities in medical education by providing courses with different teaching topics, clear learning objectives and requirements. The systematic improvement of teaching quality is helpful to further promote the scientific research of medical education and the cultivation of professional talents in medical education management.

OBJECTIVE: To explore the pathogenesis of two siblings (including a fetus) from a pedigree affected with Joubert syndrome. METHODS: Peripheral blood samples of the proband and his parents as well as amniotic fluid and abortion tissues of the fetus were collected. Part of the samples were used for the extraction of DNA, and whole exome sequencing (WES) was carried out to screen potential variants in the proband and his parents. Suspected variants were subjected to bioinformatics analysis with consideration of the clinical phenotype, and were verified by Sanger sequencing of the proband, fetus and their parents.The remainders were used for the extraction of RNA, and the mechanism of splicing variant was validated by reverse transcription-PCR (RT-PCR). RESULTS: WES showed that both patients have carried c.175C>T (p.R59X) and c.553+1G>A compound heterozygous variants of the TMEM237 gene. Among these, c.175C>T was a nonsense mutation inherited from the asymptomatic mother, while c.553+1G>A was an alternative splicing mutation inherited from the asymptomatic father. RT-PCR showed that this variant has resulted in aberrant splicing by exon skipping. CONCLUSION The compound heterozygous variants of the TMEM237 gene probably underlay the etiology of Joubert syndrome in this pedigree. Above finding has enriched the phenotype and variant spectrum of the TMEM237 gene, and facilitated genetic counseling and prenatal diagnosis for the family.
Abnormalities, Multiple/genetics* ; Cerebellum/abnormalities* ; Eye Abnormalities ; Female ; Genotype ; Humans ; Kidney Diseases, Cystic ; Mutation ; Pedigree ; Phenotype ; Pregnancy ; Retina/abnormalities*

Objective:To investigatethe heterogeneity of career growth recognition amongphysicians at the stage of standardized training and the growth characteristics of clinical physicians in the early stage, and to provide a reference for improving the quality of standardized training.Methods:The trainees who received standardized residency trainingwere randomly selected from three grade A tertiary hospitals in Chongqing, China. Mplus7.4 was used for latent profile analysis to explain the relationship between explicit continuous indicators, and the subtypes of career growth recognition were analyzed.Results:Career growth recognition at the stage of standardized training was classifiedinto three subtypes of all-round growth recognition, high resource and expectation recognition, and unclassified growth recognition, among which the subtype of unclassified growth recognition accounted for the highest percentage of 40.27% (207 trainees).Conclusions:Physicians at the stage of standardized training show obvious uncertainty aboutcareer growth recognition, and it is necessary to strengthen the education on career growth recognition during standardized training and design a development pathway based on the characteristics of career growth recognition.

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[Abstrcat] Objectives To analyze 3 cases of 17q12 microdeletion syndrome diagnosed prenatally, and to demonstrate clinical phenotype of the syndrome in prenatal setting.Methods From January 2013 to July 2017,1 370 women received invasive prenatal diagnosis and chromosome microarray analysis(CMA)in Peking Union Medical College Hospital. Among them, 3 fetuses were diagnosed as 17q12 microdeletion syndrome.All 3 cases were low-risk pregnancies.Abnormal structures in fetal kidney were found in all 3 cases, including 1 case of multiple renal cysts,2 cases of bilateral hyperechogenic kidneys.These women accepted invasive prenatal diagnosis followed by karyotyping, parental fluorescence in situ hybridization or CMA validation.Results The second and third trimester ultrasound showed that all 3 fetuses had bilateral renal structural abnormalities, including hyperechogenic kidney, multiple cysts and renal pelvis dilatation. The karyotyping of the 3 fetuses were normal.CMA examination showed that each case had 1.4-1.6 Mb deletion in 17q12 region.Two cases were de novo deletion and 1 case was inherited from the mother who had mild symptoms. The 3 women decided to terminate pregnancies after genetic counseling. Conclusion 17q12 microdeletion syndrome is a recurrent chromosome microdeletion syndrome, and the unique phenotype in prenatal setting is the abnormal structure of bilateral kidneys.A few cases of 17q12 microdeletion syndrome even inherited normally phenotypical parents, and prenatal genetic counseling of 17q12 microdeletion syndrome is relatively difficult.

Objective:To determine the characteristics of hospitalized newly diagnosed systemic lupus erythematosus (SLE) patients with high disease activity, and identify the risk factors.Methods:Data from 194 newly diagnosed SLE patients at Shanghai Renji Hospital between May 2013 and December 2018 were collected retrospectively. All patients were followed up for 1 year or until death. Patients' demographic, clinical, and laboratory characteristics on admission and medication history were retrospectively collected as baseline data. Patients were divided into two groups, lupus patients with infection (51 cases) and lupus patients without infection (143 cases). The method of univariate analysis of data depended on the data distribution type. Variables that suggested association in the univariate analysis ( P<0.05) were entered into Cox regression model. Results:Among 194 patients with newly diagnosed SLE, 21 cases (11%) died and 51 cases (26%) were infected during 1-year follow-up. Regarding the infection site, 34 cases (67%) had lung infection, 9 cases (18%) had central nervous system infection and 9 cases (18%) had blood stream infection. Common bacteria were identified in 19 cases (45%), followed by fungal infection in 18 cases (43%) and mycobacterium infection in 7 cases (17%). Among the 51 patients with infection, 38 patients (75%) had infection within the first 3 months after diagnosis, and mortality in this group was significantly higher than that in the uninfected group (39%, 15/38 vs 2%, 3/143 , P<0.01). Comparing baseline parameters between patients with 3-month infection and without, significant differences ( P<0.05) were detected in age (≥40 years), systemic lupus erythematosus disease activity index (SLEDAI) score (>10 points), Systemic Lupus International Collaborating Clinic (SLICC)/American College of Rheumatology(ACR) systemic lupus erythematosus damage index (SDI) (≥1 point), pericardial effusion, nephritis, gastrointestinal vasculitis, diabetes, lymphocyte count <0.8×10 9/L platelet count <100×10 9/L, serum creatinine >104 mmol/L and serum globulin level <20 g/L. Finally, clinically meaningful candidate predictors were included in the Cox regression model and it showed that lymphocyte count <0.8×10 9/L, nephritis and gastrointestinal vasculitis were independently predictive for 3-month infection in new-onset lupus patients. Conclusion:Understanding disease spectrums and risk factors of infection in newly diagnosed SLE patients will help clinicians to manage those patients with infection effectively to achieve favorable prognosis.