An interpretable machine learning-based prediction model for risk of death for patients with ischemic stroke in intensive care unit / 南方医科大学学报

OBJECTIVE@#To construct an inherent interpretability machine learning model as an explainable boosting machine model (EBM) for predicting one-year risk of death in patients with severe ischemic stroke.@*METHODS@#We randomly divided the data of 2369 eligible patients with severe ischemic stroke in the MIMIC-Ⅳ(2.0) database, who were admitted in ICU in 2008 to 2019, into a training dataset (80%) and a test dataset (20%), and assessed the prognosis of the patients using the EBM model. The prediction performance of the model was evaluated by calculating the area under the receiver operating characteristic (AUC) curve. The calibration curve and Brier score were used to evaluate the degree of calibration of the model, and a decision curve was generated to assess the net clinical benefit.@*RESULTS@#The EBM model constructed in this study had good discrimination power, calibration and net benefit, with an AUC of 0.857 (95% CI: 0.831-0.887) for predicting prognosis of severe ischemic stroke. Calibration curve analysis showed that the standard curve of the EBM model was the closest to the ideal curve. Decision curve analysis showed that the model had the greatest net benefit rate at the prediction probability threshold of 0.10 to 0.80. The top 5 independent predictive variables based on the EBM model were age, SOFA score, mean heart rate, mechanical ventilation, and mean respiratory rate, whose significance scores ranged from 0.179 to 0.370.@*CONCLUSION@#This EBM model has a good performance for predicting the risk of death within one year in patients with severe ischemic stroke and allows clinicians to better understand the contributing factors of the patients' outcomes through the model interpretability.

CRISPR-assisted transcription activation by phase-separation proteins

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.

Three-dimensional reconstruction reveals the correlation between the extent of alveolar clefts and secondary nasal deformity in adults / 华西口腔医学杂志

OBJECTIVES@#This study aimed to explore the relationship between alveolar cleft and secondary nasal deformity post unilateral cleft lip repair in adults.@*METHODS@#A total of 27 patients aged 16-30 years old with unilateral secondary nasal deformity and alveolar cleft were included, 13 of whom underwent bone grafting. Spiral CT data of all preoperative and postoperative patients who had alveolar bone grafting were collected. Then, Mimics software was used for three-dimensional reconstruction to evaluate the correlation between the width, height, and volume of the alveolar cleft and those of the nasal deformity. The difference in nasal deformity before and after alveolar bone grafting was also explored.@*RESULTS@#The width of the alveolar cleft was positively correlated with the difference in bilateral nostril floor width (P<0.05). As the effective depth of the alveolar cleft increased, the sub-alare inclination angle largened (P<0.05). However, no significant difference was found in the nasal deformity between before and after alveolar bone grafting.@*CONCLUSIONS@#Alveolar cleft is closely related to secondary nasal deformities post unilateral cleft lip repair, especially nasal floor deformities. Alveolar bone grafting benefits adult patients for the improvement of secondary nasal deformities post unilateral cleft lip repair.

Development and preliminary application of the information monitoring system for radiological protection / 中华放射医学与防护杂志

Objective:To develop an information system for testing radiological protection that can interface with National Radiation Health Information Platform/Medical Radiation Monitoring Subsystem and to improve the testing efficiency.Methods:Complying with the relevant national regulations and standards, the analysis was carried out of demand investigation and system modeling. An information system for testing radiological protection was established using B/S architecture, comprising three modules such as testing, audit and system management. The users at four levels were set of administrator, inspector, auditor and report issuer.Results:Based on test result, the developed information system has been shown to realize the informatization of the whole process from filling, auditing, issuing, issuing of the testing report to data uploading, with improved testing efficiency.Conclusions:The developed information system for testing radiological protection can improve the testing efficiency, and can be successfully interfaced with the National Radiation Health Information Platform/Medical Radiation Protection Monitoring Subsystem.

Correlation between platelet distribution width and anticoagulant stability of warfarin in patients with persistent atrial fibrillation / 中国医师杂志

Objective:To explore the correlation between platelet distribution width (PDW) and the stability of warfarin anticoagulant therapy in patients with persistent atrial fibrillation.Methods:138 patients with persistent atrial fibrillation treated with warfarin in Jiujiang First People′s Hospital from January 2018 to December 2019 were selected. They were divided into groups according to whether PDW increased (PDW decreased group, normal group, PDW increased group) and subgroups stratification was performed. After stratification, the relationship between PDW and the stability of warfarin anticoagulation treatment [expressed as the percentage of time of International normalized ratio(INR) within the treatment target range (TTR)] was analyzed. At the same time, the predictive value of PDW for the stability of warfarin anticoagulation treatment was analyzed.Results:There were significant difference in PDW and TTR among the PDW decreased group, normal group, PDW increased group ( F=30.322, 10.745, all P<0.01). The PDW distribution of patients with different anticoagulation quality was significantly different (χ 2=9.532, P<0.05). Receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of PDW in predicting warfarin anticoagulant stability was 0.621(95% CI: 0.524-0.737). There was significant difference in PDW and TTR among the PDW<14%, 14%-<16%, 16-<18% and ≥18% groups( F=18.075, 11.638, all P<0.01). There was no significant difference in PDW and TTR among the three subgroups of PDW<14%, 14%-<16% and 16-<18% ( P=0.843, P=0.401). There were significant difference in PDW and TTR between the two subgroup of PDW 16-<18%、≥18% ( t=4.154, 6.712, all P<0.01). Conclusions:PDW is correlated with the standard rate of warfarin anticoagulant stability, and can be used to predict the standard rate of warfarin anticoagulant stability.

Application research of objective teaching guided by immersion education theory in psychiatry practice teaching / 中华医学教育探索杂志

Objective:To explore the role of objective teaching guided by immersion education theory in the practice teaching of undergraduates majoring in psychiatry.Methods:Two classes of undergraduates majoring in psychiatry in Batch 2018 were randomly selected as the study group and the control group. A total of 35 students in the control group had traditional teaching, and 37 students in the study group had objective teaching guided by immersion education theory, both with half a semester of teaching. After the teaching, the theoretical knowledge examination scores and skills assessment scores, comprehensive ability (self-learning ability, communication ability, clinical thinking, innovation ability, and humanistic care ability), and teaching satisfaction of the two groups were compared. SPSS 26.0 was used for t-test, Chi-square test, and rank sum test. Results:After the teaching, the theoretical knowledge examination scores (basic medicine, clinical medicine, clinical psychology, and psychiatry), skill assessment scores (physical examination, and mental examination), self-learning ability, communication ability, clinical thinking, innovation ability, and humanistic care ability of the study group were all higher than those of the control group ( P<0.05). The teaching satisfaction degree of the study group was higher than that of the control group, and the difference was statistically significant ( P<0.05). Conclusion:Objective teaching guided by immersion education theory can improve the scores of professional theoretical knowledge scores and skills assessment scores of undergraduates majoring in psychiatry, and improve teaching satisfaction.

Expression and significance of fork head box protein N2 and F2 in gliomas / 解剖学报

Objective To observe the expression levels of fork head box protein N2 (FOXN2) and fork head box protein F2 (FOXF2) in normal brain tissue, low-grade glioma and high-grade glioma, and to explore the relationship between the two and the grade of glioma, and then deduce their roles in the occurrence and development of glioma, to look for possibilities target of drug therapy. Methods From January 2016 to December 2020, 36 glioma specimens were collected from the Department of Pathology, Yijishan Hospital, Wannan Medical College. The expressions of F0XN2 and F0XF2 were detected by immunohistochemistry and immunofluorescence with the double-blind method, and analyzed by SPSS18. 0 software, with a statistical significance of P<0. 05. Then Western blotting and Real-time PCR experiments were carried out on fresh normal brain tissues, low-grade glioma tissues, high-grade glioma tissues during neurosurgery in Yijishan Hospital of Wannan Medical College from January 2020 to January 2021 (normal brain tissues were all trauma patients). Results The results of immunohistochemistry and immunofluorescence showed that the higher grade of glioma, the lower expressions of FOXN2 and FOXF2 would be (P<0. 05). Western blotting showed that the expressions of FOXN2 and FOXF2 in normal brain tissue and low-grade glioma were higher than those in high-grade glioma (P<0. 05). The result of Real-time PCR showed that the expressions of FOXN2 and FOXF2 in normal brain tissue were higher than those in high-grade glioma (P<0. 01). Conclusion FOXN2 and FOXF2 are expressed in normal brain tissues, and their expression is low in glioma in a grade-dependent manner, suggesting that FOXN2 and FOXF2 are related to the grade and poor prognosis of glioma. Enhancing the expression of F0XN2 and F0XF2 ma)' provide a new idea for target therapy of glioma.

Correlation between intestinal glucagon-like peptides-1 and major depressive disorder / 中华行为医学与脑科学杂志

Objective:To explore the pathogenesis of major depressive disorder(MDD) by comparing the serum glucose and lipid metabolism indicators, levels of glucagon-like peptide-1(GLP-1) in plasma and feces, and the content of specific intestinal flora ( Lactobacillus, Bifidobacterium) between patients with MDD who were diagnosed for the first time and healthy controls. Methods:Totally 80 MDD patients hospitalized from January 1, 2020 to March 30, 2021 and 80 healthy volunteers with normal physical examination in the same period were selected. Blood and fecal samples of patients with MDD and healthy controls were collected respectively. The indicators of serum glucose and lipid metabolism were detected by automatic biochemical analyzer, the concentrations of GLP-1 in plasma and feces were detected by ELISA, and the relative contents of Lactobacillus and Bifidobacterium in feces were detected by real-time PCR. The differences between two groups of glucose and lipid metabolism indicators, GLP-1 levels and the relative contents of Lactobacillus and Bifidobacterium in feces were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and analysis of variance were used for inter group comparison, and Pearson correlation analysis was used for correlation analysis. Results:Compared with the control group, the levels of serum TC, HDL, and LDL in the MDD group decreased ((3.99±0.85)mmol/L , (4.78±0.86)mmol/L; (1.18±0.29)mmol/L, (1.30±0.28)mmol/L; (2.64±0.70)mmol/L, (3.19±0.69)mmol/L; t=5.559, 2.371, 4.695, all P<0.05). The plasma and fecal GLP-1 levels of the MDD group were lower than those of the control group (plasma: (0.81±0.22)pmol/mL, (1.05±0.26)pmol/mL , t=4.509, P<0.01; feces: (2.23±0.46)pmol/mL , (2.47±0.37)pmol/mL, t=2.533, P<0.05). Compared with the control group, the relative contents of Lactobacillus(2.56±1.59, 3.51±2.21) and Bifidobacterium(2.24±1.89 , 3.17±2.08) in the MDD group decreased ( t=2.218, 2.082, both P<0.05). The level of plasma GLP-1 in the MDD group was negatively correlated with FPG, TG, and disease severity ( r=-0.281, -0.221, -0.437, P<0.05). The level of plasma GLP-1 in the control group was negatively correlated with FPG ( r=-0.580, P<0.01). The fecal GLP-1 level of the MDD group was negatively correlated with the severity of the disease ( r=-0.298, P<0.01), and the fecal GLP-1 level of the control group was positively correlated with fecal Lactobacillus and Bifidobacterium ( r=0.685, 0.428, P<0.01). Conclusion:MDD patients have abnormal glucose and lipid metabolism, decreased GLP-1 level and decreased relative content of intestinal Lactobacillus and Bifidobacterium. Changes in intestinal flora affect GLP-1 levels. GLP-1 can affect glucose and lipid metabolism and depressive symptoms in patients with MDD by binding to specific receptors in intestinal tract and central nervous system.

Unilateral vertebroplasty and kyphoplasty by digital subtraction angiography for the treatment of osteoporotic vertebral compression fractures / 中国骨伤

OBJECTIVE@#To explore the methods and efficacy of unilateral extra-pedicle precision puncture percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty(PKP) by digital subtraction angiography (DSA) for the treatment of osteoporotic vertebral compression fractures (OVCFs).@*METHODS@#The clinical data of 68 patients with osteoporotic vertebral compression fractures treated from August 2015 to December 2018 were retrospectively analyzed. There were 20 males and 48 females, aged 56 to 90(73.5±8.0) years, 40 cases of double segments, 28 cases of three segments, a total of 168 vertebrae. All the patients were performed PVP orPKP through unilateral extra pedicle precision puncture under the guidance of DSA. The vertebrae were distributed in T@*RESULTS@#All the punctures were successful in 68 patients. All the puncture needles reached the midline of vertebral body, and the bone cement was well dispersed in the vertebral body with symmetrical distribution. The operation time was 35 to 60 (41.6±3.2) minutes, and there was no puncture complications. The injection volume of bone cement was 3 to 5 (3.6±0.5) ml in each vertebra. There were 8 cases of bone cement leakage, with a leakage rate of 11.76%. All 68 patients were followed up from 12 to 27 (14.3±3.5) months in the study. VAS score and ODI at 3 days after surgery and at final follow-up time were significantly improved (@*CONCLUSION@#PVP or PKP under the guidance of DSA via a unilateral extrapedicular approach with precision puncture can effectively relieve pain, restore vertebral body height and spinal function, which is a safe, fast and effective method in the treatment of osteoporotic vertebral compression fractures.

Mechanism of Magnoliae Officinalis Cortex in treatment of peptic ulcer based on network pharmacology and molecular docking / 中国中药杂志

Magnoliae Officinalis Cortex(Houpo) can treat peptic ulcer disease(PUD), the mechanism of which remains unclear. In this study, network pharmacology and molecular docking were employed to predict the mechanism of Houpo in the treatment of PUD. Through literature review and TCMSP screening, 15 main active ingredients were obtained. The SwissTargetPrediction database was used to predict the potential targets of the ingredients, and Therapeutic Target Database(TTD), DrugBank, and Human Phenotype Ontology(HPO) to screen the disease-related targets. A total of 49 potential targets were obtained by the intersection of active ingre-dients-related targets and disease-related targets. Cytoscape 3.6.1 was employed to construct the protein-protein interaction network for the targets with high confidence(score>0.700) screened out by STRING. The DAVID database was used for GO and KEGG pathway enrichment of potential targets. GO enrichment analysis showed that the treatment mechanism was mostly related to nuclear receptor activity, ligand-activated transcription factor activity, and G protein-coupled acetylcholine receptor activity. KEGG enrichment analysis found that Houpo could regulate material metabolism, endocrine system, p53 signaling pathway, and PPAR signaling pathway. Molecu-lar docking verified that all 15 ingredients had good binding activities with key targets(CHRM1, CHRM2, FABP1, mTOR, and STAT3). The results mean that Houpo can treat PUD by participating in cell metabolism, inhibiting inflammatory cytokines, and regulating cell proliferation and apoptosis.

Q-marker prediction of Magnoliae Officinalis Cortex before and after "sweating" / 中国中药杂志

Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.

Observation on Tuina plus needling the distal acupoints along the pathway of meridians for shoulder periarthritis / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus needling the distal acupoints along the pathway of meridians for shoulder periarthritis (SP). Methods: A total of 70 patients with SP were divided into an observation group and a control group using the random number table method, with 35 cases in each group. The patients in the observation group were treated by Tuina combined with needling distal acupoints along the pathway of meridians, while those in the control group only received the same Tuina treatment as in the observation group. The visual analog scale (VAS) and shoulder joint function were scored before and after treatment, and the efficacy after treatment was evaluated. Results: After three courses of treatment, the total effective rate of the observation group was 94.3％, while the total effective rate of the control group was 80.0％, showing a statistical difference (P<0.05). After treatment, the VAS scores of the two groups were significantly lower than the baseline scores (P<0.01), and the VAS score of the observation group was lower than that of the control group (P<0.01). After treatment, the total scores of internal rotation, external rotation, back touching, ear touching and motion function in the two groups were significantly higher than those before treatment (P<0.01), and the above five scores in the observation group were significantly higher than those in the control group (P<0.01). Conclusion: Tuina combined with needling the distal acupoints along the pathway of meridians is more effective than Tuina alone in treating SP. The combined therapy can relieve the pain and improve joint function more effectively.

Role of T 2* mapping and ZOOMit IVIM in differentiating benign and malignant thyroid nodules / 中华放射学杂志

Objective:To evaluate the efficacy of T 2* mapping and zoomed imaging with parallel transmission technique (ZOOMit) intravoxel incoherent motion (IVIM) DWI in differentiating benign and malignant thyroid nodules. Methods:The data of 67 patients with thyroid nodules confirmed by surgery and pathology in Ma′anshan People′s Hospital from July 2019 to March 2020 were retrospectively collected. There were a total of 80 nodules, of which 39 were benign nodules and 41 were malignant nodules. All patients underwent MRI including T 2WI, T 2* mapping, and ZOOMit IVIM sequence scans before surgery to measure the T 2*, D, D *, and f values of the nodules. The comparison of the parameters between benign and malignant nodules was evaluated by independent sample t test or Wilcoxon rank sum test. A combined parameter model was established through two-class logistic regression and the predicted probability value was calculated. The ROC curve was used to evaluate the diagnostic efficacy of each parameter and the combined parameter model in differentiating between benign and malignant thyroid nodules. Results:The T 2*, D, f values of benign thyroid nodule group were higher than that in malignant group, and the difference was statistically significant ( P<0.05). The difference of D * value between two groups was not statistically significant ( Z=1.258, P= 0.215). The area under ROC curve (AUC) of T 2*, D, and f values for identifying benign and malignant nodules was 0.703, 0.892, and 0.743, the diagnostic sensitivity was 80.2%, 84.1%, and 80.0%, and the specificity was 65.6%, 81.3%, and 75.0%, respectively. The AUC of T 2*combined with D, T 2*with D * and T 2* with f was 0.925, 0.709, and 0.743, the diagnostic sensitivity was 96.2%, 80.4%, and 80.0%, and the specificity was 81.2%, 65.6%, and 75.0%, respectively. Conclusion:D, f and T 2* derived from ZOOMit IVIM have good value in differentiating between benign and malignant thyroid nodules, and the combination of T 2* and D parameters has the higher diagnostic efficacy.

The association of gene polymorphism related with alcohol metabolism with the risk of alcohol dependence and subjective response to alcohol / 中华行为医学与脑科学杂志

Objective:To explore the relationship between rs671 (ALDH2), rs1229984 (ADH1B), RS141973904 (ADH1C), RS1799971 (OPRM1), rs1997794 (PDYN) polymorphism and individual's alcohol subjective response and drinking behavior.Methods:From January to December 2018, patients with alcohol dependence who were hospitalized in the First Affiliated Hospital of Xinjiang Medical University and Xinjiang mental health center and met the DSM-IV were selected (alcohol dependence group, n=100). Alcohol dependence patients and normal healthy subjects (control group, n=100) completed general demographic questionnaire, including drinking behavior such as the frequency of drinking each week and the maximum alcohol consumption at one drink, and informed consent, then were extracted of venous blood for DNA test.After that, alcoholics completed the alcohol challenge test.Biphasic alcohol effect scale(BAES) and drug effect questionnaire (DEQ) were completed before drinking and after drinking 30, 60, 120, 180 minutes respectively.Hardy-Weinberg equilibrium for genetic linkage analysis was calculated by utility program.Pearson Chi-square test was used to analyze the odds ratio(OR) value, and the chi-square test of repeated measured variables were used to analyze the variation trend of individual subjective response to alcohol after drinking. Results:rs671 allele A was associated with alcohol dependence risk (χ 2=23.97, P<0.01, OR=7.11, 95% CI=2.93~17.30), and for rs1229984 polymorphism the dominant genetic model " T/T-C/T" was taken as the best fitting model ( P<0.01, OR=0.16, 95% CI=0.08-0.32), which was a protective factor for alcohol dependence.Alcoholics with TT genotype in rs1229984 had lower maximum alcohol consumption ( F=4.86, P=0.01) and weekly alcohol consumption ( F=4.51, P=0.01) than those with CC and CT genotype.The maximum alcohol consumption ( F=20.28, P<0.01) and weekly alcohol consumption ( F=12.46, P<0.01) of individuals with GG and GA genotype in rs1799971 were higher than those with AA genotype.The AA genotype of rs1799971 showed lower stimulative effect ( F=7.99, P=0.01), higher sedative effect ( F=57.04, P<0.01), and lower " like" ( F=13.38, P<0.01) and " more" effect ( F=26.37, P<0.01) than that with GG and GA genotype. Conclusion:rs671 and rs1229984 are more closely related to individual drinking behavior and volume of alcohol consumption.rs1799971 is not only related to individual drinking behavior, but also has a more closed relationship with subjective response to alcohol.

Application and thoughts of team-based learning combined with flipped classroom in physiological teaching / 中华医学教育探索杂志

Objective:To explore the application and effect of team-based learning (TBL) combined with flipped classroom in the teaching of physiology.Methods:A total of 70 medical students were selected and randomly divided into two groups, experimental group ( n=34) and control group ( n=36). Both groups studied digestion physiology by different method. In the experimental group, the students were taught by TBL combined with flipped classroom. The control group was given traditional teaching. The students studied and discussed problems in a team, and shared the answers in the flipped classroom. The effects of teaching were evaluated by the final test scores and the self-made questionnaire. SPSS 17.0 was used for t test on data comparison between the two groups. Results:The test scores of digestion physiology in the experimental group were (5.47±1.02) points, which were significantly higher than those of the control group (4.42±1.63) points, with significant differences ( P=0.020). A total of 34 questionnaires were issued and 34 valid questionnaires were collected, with an effective rate of 100%. The questionnaire results showed that TBL combined with flipped classroom was accepted and approved by about 82% of students in the experimental group who agreed that the teaching model helps enhance students' initiative and interest in learning, develop their sense of cooperation and comprehensive application ability. Conclusion:TBL combined with flipped classroom is feasible and effective in the physiological teaching, and it can be popularized in medical courses.

Genotype-phenotype and genetic analysis in five patients with Kallmann syndrome / 中华内分泌代谢杂志

To study the genotype-phenotype and genetic characteristics of Kallmann syndrome. Five patients with Kallmann syndrome were enrolled. Clinical data collection, chromosome karyotyping, whole exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA) were used. All the five patients were males, aging from 2 months to 45 years old. Three of the five patients complained cryptorchidism, one complained gonadal dysgenesis, and one complained fasting hyperglycemia. The clinical feature was hypogonadotropic hypogonadism with anosmia, and all karyotype was 46 XY. Magnetic resonance imaging (MRI) showed undeveloped olfactory bulbs and tracts. Kallmann syndrome related gene novel variants were found in all the 5 patients. The hypoplasia of right kidney was found in a patient with c. 1795_1799del (p.Asn599Profs*66) of anosmin 1 (ANOS1) variant. Clinical heterogeneity and incomplete penetrance were seen in a patient with c. 2824A>G (p.Thr942Ala) of chromodomain helicase DNA binding protein 7 (CHD7). Besides, WES indicated a 109 bp-deletion on Xp22.31 (chrX: 8507699-8507804), which was the deletion of exon 10 on ANOS1 gene verified by MLPA. The deletion variant was inherited form his mother, and conformed to X-linked recessive inheritance. Kallmann syndrome is genetic and clinical heterogeneous. WES is helpful for early diagnosis. MLPA and genome copy number variation analysis (CNV) are also recommend if necessary.

Effect of high-fat diet and exercise on asprosin and CTRP6 expression in subcutaneous and retroperitoneal adipose tissues in rats during mid-gestation / 南方医科大学学报

OBJECTIVE@#To study the effects of high-fat (HF) diet and exercise on the expressions of asprosin and CTRP6 in adipose tissues in different regions of rats during mid-gestation.@*METHODS@#Pregnant SD rats were fed on a standard chow diet or a high-fat (60% fat content) diet for 14 days starting on gestation day (GD) 1. Starting from GD3, the rats fed either on normal or high-fat diet in the exercise groups (CH-RW and HF-RW groups) were allowed access to the running wheels for voluntary running, and those in sedentary groups (CH-SD and HF-SD groups) remained sedentary. At the end of the 14 days, adipose tissues were sampled from different regions of the rats for detecting the mRNA and protein expressions of asprosin and CTRP6 using RT-qPCR and Western blotting.@*RESULTS@#The mRNA expression of asprosin in retroperitoneal adipose tissues was significantly higher in HF-RW group than in the other 3 groups (@*CONCLUSIONS@#High-fat diet and exercise during mid-gedtation can affect the expression levels of asprosin and CTRP6 in adipose tissues of rats in a site-specific manner.

To investigate of relationship between long non-coding RNA CDKN2B-AS1 and idiopathic pulmonary fibrosis coexisting with lung cancer / 中华老年医学杂志

Objective:To investigate the role and its mechanism of long non-coding RNA cell cyclin-dependent kinase inhibitor gene CDKN2B-AS1 and its adjacent gene CDKN2A in idiopathic pulmonary fibrosis coexisting with lung cancer.Methods:The cancerous lung tissue specimens and adjacent normal lung tissue specimens were collected from 8 patients with lung adenocarcinoma.The expression level of CDKN2B-AS1 and CDKN2A mRNA were determined by reverse transcription quantitative real-time PCR(RT-qPCR)assays.Pulmonary fibrosis cell model was established by treating human fetal lung fibroblast MRC-5 cell line that was selected as the study object.And the cells were randomly divided into 4 groups: the normal group, the intervention group[induced by transforming growth factou-β(TGF-β1)], the negative siRNA intervention group(induced by TGF-β1 and transfected by nonsense sequence siRNA)and the positive siRNA intervention group TGF-β1 and transfected by siRNA of CDKN2B-AS1). The morphological changes of each group were observed by using the inverted phase contrast microscope after 24 hours intervention.The expression levels of CDKN2B-AS1 and CDKN2A mRNA were determined by RT-qPCR, and the protein amounts of CDKN2A and P53 were measured by Western blotting.Results:The expression levels of CDKN2B-AS1 and CDKN2A mRNA were lower in lung cancer tissue than in adjacent normal lung tissues(2.60±1.33 vs.21.90±19.83, 0.34±0.10 vs.19.83±7.67, t=2.747 and 7.187, P<0.05), which were consistent with the results in IPF.In cell experiments, we observed that TGF-β1 intervention gradually transformed MRC-5 cells from multi-spindled or stellate structures to flattened fibroblasts with varying degrees of differentiation.Compared with the normal group, TGF-β1 intervention group showed that the expression levels of CDKN2B-AS1 and CDKN2A mRNA were significantly decreased(6.80±0.30 vs.56.12±2.46, 9.39±0.37 vs.64.54±3.89, t=47.746 and 33.797, both P<0.001). Compared with the intervention group, the expression levels of CDKN2B-AS1 and CDKN2A mRNA were further decreased in the positive siRNA intervention group(2.38±0.29 vs.6.80±0.30, 2.81±0.36 vs.9.39±0.37, t=4.279 and 4.032, P=0.003 and 0.004), and there was a positive correlation between the mRNA expressions of CDKN2B-AS1 and CDKN2A( r=0.988, P=0.000). Compared with the normal group, the intervention group showed that the protein expressions of CDKN2A and P53 were decreased(3.12±0.06 vs.4.12±0.59, 1.12±0.07 vs.2.11±0.06, t=2.921 and 19.599, P=0.043 and 0.000), and there was a positive correlation between the expression of CDKN2A and P53( r=0.772, P=0.000). Conclusions:Long non-coding RNA CDKN2B-AS1 has a low expression level in both idiopathic pulmonary fibrosis and lung cancer tissues, and it may participate in the P53 pathway by regulating the expression of the neighboring gene CDKN2A, which may be one reason for the high incidence of lung cancer in IPF patients.

Association analysis of PPP1R3A gene polymorphism with schizophrenia in Uygur Chinese population / 中国神经精神疾病杂志

Objective To explore the correlation between exon region polymorphism of PPP1R3A gene and schizophrenia in Uygur Chinese population. Methods PPP1R3A gene exon region DNA amplification was performed using multiple PCR targeted capture next-generation sequencing method in 528 patients with schizophrenia and 576 healthy controls of Uyghur descent, Illumina HiSeq X Ten was used for sequencing, the symptoms of schizophrenia were assessed by positive and negative symptoms scale (PANSS). Results The allelic and genotypic distributions in rs1800000 of PPP1R3A gene between patients with schizophrenia and healthy controls had significant difference (P＜0.05), rs1799999 in genotype frequency between the female case and control groups showed significant difference (P＜0.05). Furthermore, the allelic distributions of rs8192686 between male cases and controls had significant difference (P＜0.05). Conclusion PPP1R3A gene rs1800000 may be associated with the development of schizophrenia in Uygur Chinese population; rs1799999 may be a risk factor for susceptibility of female Uygur Chinese schizophrenia; The C allele at rs8192686 may be associated with male Uygur Chinese schizophrenia.

Timeliness of β3 adrenergic receptor agonist-induced browning of white adipose tissues in mice / 中南大学学报(医学版)

To characterize the timeliness of β3 adrenergic receptor agonist CL316,243-induced browning of white adipose tissues in mice.
 Methods: Male C57BL/6J mice at 10 weeks of age were housed in conventional cages and given sterile saline for the control group or CL316,243 (1 μg/g) for the experimental group via intraperitoneal injection for 1, 3, and 5 days. Food intake and body weight were measured daily. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous white adipose (sWAT) and epididymal white adipose tissue (eWAT) were harvested for histological and gene expression analysis.
 Results: Compared with the control group, intraperitoneal injection of CL316,243 reduced the weight of eWAT on the first day. Meanwhile, CL316,243 continuously promoted the mRNA and protein expression of uncoupling protein-1 (UCP-1) in sWAT and eWAT. Furthermore, CL316,243 injection significantly decreased the food intake and weight gain of the mice, and reduced the diameter of adipocyte and accumulation of small lipid droplets in adipose tissues.
 Conclusion: CL316,243 can induce the brown-like remodeling in adipose tissues of mice in vivo, which show different time-dependent manners in different adipose tissues.