Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Effectiveness of galvanic vestibular evoked myogenic potential for evaluation of Meniere's disease

Abstract Objectives: Although the cause of Meniere's disease (MD) is not fully understood, endolymphatic hydrops is widely believed to be responsible for MD. Previous studies have used Air-Conducted Sound (ACS)-induced Vestibular Evoked Myogenic Potentials (VEMPs) to evaluate otolithic function in patients with MD. However, the use of Galvanic Vestibular Stimulation-VEMPs (GVS-VEMPs) with other vestibular tests in MD has been rare. This study aimed to explore the application of galvanic VEMPs in assessing MD. Methods: Normal individuals and patients with unilateral definite MD were included in this retrospective study. All participants underwent pure tone audiometry. Ocular and cervical VEMPs induced by GVS, and ACS were recorded. The characteristic parameters of VEMPs (n1 latency, p1 latency, amplitude, and AR) were analyzed. Results: The provocation rates of GVS-VEMPs did not differ between MD patients and control individuals. Compared with ACS, GVS could evoke potentials with longer latencies. MD patients presented GVS-VEMPs with lower amplitudes and ACS-cVEMP with shorter latencies and had a higher response rate in GVS-oVEMP. However, no differences or correlations were found in the characteristic parameters of GVS-VEMPs among the different stages of MD. Conclusions: GVS is as effective as ACS for inducing VEMP, and GVS-VEMP recording can detect retrolabyrinthine degeneration in MD. Further research is needed to assess the utility of GVS-VEMP in the evaluation of MD severity. Level of evidence: Level 4.

Effect of age on virtual reality-assisted subjective visual vertical and subjective visual horizontal at different head-tilt angles

Abstract Objective: Subjective Visual Vertical (SVV) and Subjective Visual Horizontal (SVH) values may reflect bilateral utricle asymmetry. Bilateral utricle static tension balance can be used to evaluate bilateral otolith lesions and otolith-related central neuropathy. Few studies have examined Virtual Reality (VR)-assisted SVV and SVH values at various head-tilt angles across age groups. The present study aimed to determine the effects of age on VR-assisted SVV and SVH values at different head-tilt angles. Methods: We divided 180 healthy subjects into 6 age groups (n = 30 in each group). VR-assisted SVV and SVH measurements were performed at 9 head-tilt angles (head held vertically, 0°; head tilted 30°, 45°, 60°, and 90° to the left/right) in the roll plane. Results: SVV and SVH values significantly differed with head-tilt angle (p < 0.05). No significant difference was detected in the SVH and SVV values between different age groups (p = 0.632 and p = 0.810, respectively), and no interaction between the age group and the head-tilt angle was found for the SVH and SVV values (p = 0.670 and p = 0.084, respectively). Conclusion: These results suggest that age may have little effect on VR-assisted SVV and SVH at different head-tilt angles. Therefore, VR-assisted SVV and SVH can be evaluated as an effective, fast, and simple way to evaluate utricle function. Level of Evidence: Level 4.

Comparison of distal pancreatectomy with celiac axis resection and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer / 中华外科杂志

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ2 test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ2=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ2=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.

Dengzhan shengmai capsule combined with donepezil hydrochloride in the treatment of Alzheimer's disease: preliminary findings, randomized and controlled clinical trial

SUMMARY OBJECTIVE: To observe the effects of Dengzhan Shengmai capsule combined with donepezil hydrochloride on cognitive function, daily living ability, and safety in patients with Alzheimer's disease. METHODS: A total of 294 patients with Alzheimer's disease were randomly divided into a treatment group and a control group, 147 cases each group. The control group was given oral donepezil hydrochloride 5 mg once a day, and the treatment group was given oral Dengzhan Shengmai capsule 0.36 g three times a day, based on the control group. RESULTS: At 3 and 6 months of treatment, the ADAS-cog score of the treatment group was 48.69±6.23 and 44.24±5.53; for the control group, 45.48±5.94 and 41.57±5.10. The difference between the two groups is statistically significant (p<0.05). At 3 and 6 months of treatment, the NO level in the treatment group was (46.28±6.68) umol/l, (43.55±7.92) umol/l, and the control group was (42.95±7.92) umol/l, (38.89±5.93) umol/l. The differences between both groups were statistically significant (p<0.05). At 3 and 6 months of treatment, ET levels in the treatment group were (156.08±17.39) ng/l, (144.91±17.60) ng/l, and the control group was (150.48±22.94) ng/l, (135.04±10.08) ng/l. Correlation analysis showed that ADAS-cog score was negatively correlated with NO and ET (p<0.001). CONCLUSIONS: Dengzhan Shengmai capsule combined with donepezil hydrochloride can improve cognitive function and the living capacity of patients with Alzheimer's disease, reduce the production of neurotoxic substances NO and ET, and provide higher safety.

Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.

Clinical Efficacy of Modified Chaihu Shugansan Combined with Xuanfu Daizhetang on Depression of Patients of Patients with Gastroesophageal Reflux Disease / 中国实验方剂学杂志

Objective:To observe the clinical efficacy modified Chaihu Shugansan combined with Xuanfu Daizhetang on anxiety and depression of patients with gastroesophageal reflux disease （GERD） and Qi stagnation and phlegm obstruction syndromes in clinic and the effect on neuropeptide factor and pro-inflammatory factor. Method:Patients 200 cases were divided into control group and observation group. Patients in control group got omeprazole enteric-coated tablets， 20 mg/time， 1 time/day， flupentixol and melitracen tablets， 1 tablet/time， 2 times/day， and Dalitong granules， 1 bag/time， 3 times/day. In addition to omeprazole enteric-coated tablets in control group， patients in observation group were also added with syndrome differentiation-based treatment of modified Chaihu Shugansan combined with Xuanfu Daizhetang， 1 dose/day. The treatment lasted for 8 weeks. Before and after treatment， scores of acid regurgitation， heartburn， poststernal pain， syndrome of Qi stagnation and phlegm obstruction， gastroesophageal reflux disease questionnaire （GerdQ）， Hamilton anxiety Scale-14 （HAMA-14） and Hamilton depression scale-17 （HAMD-17） were scored； And upper gastrointestinal endoscopy， levels of peripheral vasoactive intestinal peptide （VIP）， 5-hydroxytryptamine （5-HT）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， interleukin-1 （IL-1）， IL-6 were detected. All the patients （GerdQ<8） got follow-up for 16 weeks， and the recurrence and safety were recorded. Result:After treatment， scores of GerdQ， endoscope， main symptoms and syndrome of Qi stagnation and phlegm obstruction on observation group were lower than those in control group （<italic>P</italic><0.01）， and scores of HAMA-14 and HAMD-17 decreased in both groups （<italic>P</italic><0.01）， but with no statistically significant difference in both groups. The comprehensive efficacy of main symptoms in observation group was better than that in control group （<italic>Z</italic>=2.076， <italic>P</italic><0.05）. The curative effect of traditional Chinese medicine （TCM） syndrome in observation group was superior to that in control group （<italic>Z</italic>=2.151， <italic>P</italic><0.01）. The effect of endoscope was better than that in control group （<italic>Z</italic>=2.103， <italic>P</italic><0.05）. And levels of VIP， 5-HT， TNF-<italic>α</italic>， IL-1 and IL-6 in observation group were lower than those in control group. During the 16-week follow-up， the recurrence rate in observation group was 19.23% （15/78）， which was lower than 35.38% （23/65） in control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/EF9122E2-D647-4d34-AB25-83CBA259DE55-M002.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/EF9122E2-D647-4d34-AB25-83CBA259DE55-M002c.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic></alternatives></inline-formula>=4.741， <italic>P</italic><0.05）. The average recurrence time of the observation group was lower than that of the control group（<italic>P</italic><0.01）. Conclusion:Modified Chaihu Shugansan combined with Xuanfu Daizhetang can significantly improve the main symptoms and TCM syndromes， relieve depression， anxiety and other adverse emotions， promote the healing of gastroesophageal mucosa， reduce the recurrence rate and delay the recurrence time among patients with GERD and Qi stagnation and phlegm obstruction syndromes. The mechanism of action may be related to the expression of neuropeptide factor and the inhibition of pro-inflammatory factor.

Epidemiology of genital Chlamydia trachomatis infection among youth aged 15-24 years in Beijing during 2010-2019 / 中国学校卫生

Objective@#To investigate epidemiological features of genital Chlamydia trachomatis(Ct) infection among youth aged 15-24 years in Beijing, so as to provide scientific basis for developing control strategies.@*Methods@#Data regarding genital Ct infection among youth aged 15-24 years were collected from the disease surveillance information reporting system in Beijing between 2010 and 2019 and were analyzed with the descriptive epidemiological method.@*Results@#During 2010-2019, a total of 1 871 cases of Ct infection was reported, 1 287(68.79%) of the cases were female. The reported incidence rate of genital Ct infection increased from 3.16 per 100 000 in 2010 to 25.15 per 100 000 in 2019, with an average annual increasing rate of 25.92%( χ 2=836.86, P < 0.01 ). Increasing trends in the reported incidence were observed among males and females, females being higher than males in the year 2010 and 2012. The reported incidence rates increased annually in all age groups between 2010 and 2019, and the average annual rate of increase was highest in the group aged 15-19 years.@*Conclusion@#The reported rate of genital Ct infection showed an increasing trend among youth aged 15-24 years in Beijing, and increased rapidly among youth aged 15-24 years. More attention should be paid on sexual and reproductive health education among adolescents. Epidemic of genital Ct infection should be concerned, and its surveillance need to be improved.

The relationship between genotype of familial hypercholesterolemia and the efficacy of PCSK9 inhibitors / 中华心血管病杂志

Objective: This study intends to explore the difference in the efficacy of PCSK9 inhibitors in patients with different FH phenotypes by analyzing the level of blood lipids before and after treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia (FH) with different allele grades. Methods: Patients with FH phenotype, who admitted to Beijing Anzhen Hospital from January 2019 to October 2020, were enrolled. Age, sex and other clinical information were collected from enrolled, and the pathogenic genes were detected by the second generation sequencing technique. The patients were divided into five groups according to the number of alleles involved and the degree of gene damage: single allele-null mutation group, single allele-defect mutation group, multi-allele-null mutation group, multi-allele-defect mutation group and no major pathogenic gene mutation group. The results of blood lipids were collected before medication, 4-6 weeks of intensive statin treatment and one month after combined treatment with PCSK9 inhibitor (PCSK9i). The LDL-C level were compared among groups. ASCVD risk stratification was performed in all patients, and the proportion of LDL-C level reaching the corresponding risk stratification target value of each genotype group after treatment was analyzed. Results: A total of 66 patients with FH phenotype were included, including 47 males (71.2%) and 19 females (28.8%),the mean age was(43.1±13.4 years). There were 7 cases in single allele-null mutation group (10.6%), 25 cases in single allele-defect mutation group (37.9%), 8 cases in multi-allele-null mutation group (12.1%), 18 cases in multi-allele-defect mutation group (27.3%) and 8 cases in no major pathogenic mutation group (12.1%). The degree of LDL-C reduction post combined PCSK9 inhibitor therapy was as follows: single allele mutation group>no major pathogenic mutation group>multi-allele mutation group, general distribution was in the range of 0-90.0%. Two groups of single allele mutation and no major pathogenic mutation group>50.0%>multi-allele mutation group. Under the combined treatment of PCSK9 inhibitors, the further decrease of LDL-C was in the order of single allele mutation group>non-major pathogenic mutant group>multi-allele mutation group. The efficacy of combined therapy on reducing LDL-C at 1 month after treatment decreased with the increase of baseline LDL-C level (r = 0.46, P<0.001) in patients with FH phenotype. In addition, the further decrease of LDL-C level post high-intensity statin therapy combined with PCSK9 inhibitors decreased with the increase of baseline LDL-C levels (r = 0.40, P<0.001). The degree of LDL-C decrease was high and stable by statin combined with PCSK9 inhibitor therapy in single allele mutation group. In the single allele-defect mutant group, the decrease of LDL-C increased with the increase of baseline LDL-C level post intensive statin treatment and combined PCSK9 inhibitor treatment ((r=0.54, P=0.009); r=0.45,P=0.030), and the further decrease of LDL-C level decreased with the increase of baseline LDL-C level in single allele-defect mutant group post combined therapy with PCSK9 inhibitor (r=0.43, P=0.040). The decrease of LDL-C in patients with the multi-allele mutation group varied with different pathogenic gene loci and combinations post combined therapy with PCSK9 inhibitor. There was no significant difference in the level of blood lipids between the group without major pathogenic gene mutation and the group with single allele mutation before and after treatment. The percentage of patients achieving LDL-C goals with different genotypes of phenotypic FH were as follows: single allele mutation group (86.7%), non-major pathogenic mutant group (75.0%) and multi-allele mutation grou (<5.0%). Conclusions: All patients with different FH phenotypes could benefit from the intensive lipid-lowering therapy with statins and PCSK9 inhibitors, however, there are significant differences in the efficacy of lowering LDL-C in Chinese patients with FH phenotype with different molecular etiologies. Therefore, the pathogenic gene analysis may suggest the lipid-lowering effect of PCSK9 inhibitors in patients with FH.

Analysis of the clinical characteristics of perianal fistulising crohn's disease in a single center / Análise das características clínicas da doença de crohn fistulizante perianal em um único centro

ABSTRACT Background: Clinical characteristics are keys to improve identification and treatment of Crohn´s disease (CD) so that large sample analysis is of great value. Aim: To explore the clinical characteristics of perianal fistulising CD. Methods: Analysis of 139 cases focused on their clinical data. Results: The proportion of males and females is 3.3:1; the mean age is 28.2 years; 47.5% of patients had anal fistula before CD diagnosis. Patients with prior perianal surgery and medication accounted for 64.7% and 74.1% respectively. The L3 type of lesion was present in 49.6% and the B1 and B2 types for 51.8% and 48.2% respectively; complex anal fistula was diagnosed in 90.6%. Symptoms of diarrhea were found in 46% and perianal lesions alone in 29.5% of patients. Abnormal BMI values was present in 44.6%; active CD activity index in 64.7%; and 94.2% had active perianal disease activity index. A proportion of patients manifest abnormal C-reactive protein, erythrocyte sedimentation rate, platelet, hemoglobin and albumin. Conclusion: We suggest that patients with anal fistula associated to these clinical features should alert the medical team to the possibility of CD, which should be further investigated through endoscopy and imaging examination of alimentary tract to avoid the damage of anal function by routine anal fistula surgery.

RESUMO Racional: As características clínicas são fundamentais para melhorar a identificação e o tratamento da doença de Crohn (DC), de modo que a análise da amostra seja de grande valor. Objetivo: Explorar as características clínicas da DC fistulizante perianal. Métodos: Análise de 139 casos focados em seus dados clínicos. Resultados: A proporção de homens e mulheres foi de 3,3: 1; a média de idade de 28,2 anos; 47,5% dos pacientes tiveram fístula anal antes do diagnóstico de DC. Pacientes com cirurgia perianal prévia e medicação representaram 64,7% e 74,1%, respectivamente. O tipo de lesão L3 estava presente em 49,6% e os tipos B1 e B2, em 51,8% e 48,2%, respectivamente; fístula anal complexa foi diagnosticada em 90,6%. Sintomas de diarréia foram encontrados em 46% e lesões perianais isoladas em 29,5% dos pacientes. Valores anormais de IMC estavam presentes em 44,6%; índice de atividade DC ativa em 64,7%; e 94,2% tinham índice de atividade de doença perianal ativo. Proporção significativa de pacientes tinha proteína-C reativa, taxa de sedimenta do eritrócito, plaquetas hemoglobina e albumina anormais. Conclusão: Sugere-se que pacientes com fístula anal associada às essas características clínicas alertem a equipe médica para a possibilidade de DC, que deve ser investigada por endoscopia e exame de imagem do trato digestivo para evitar dano na função anal pela operação que rotineiramente é realizada no tratamento da fístula anal.

miR-424 modulates radio-sensitivity of breast cancer cells via targeting HMGA1 / 中国肿瘤生物治疗杂志

@# Objective: To explore the effect of miR-424/HMGA1 (high mobility proteinA1) axis on the radio-sensitivity of breast cancer cells and the possible mechanism. Methods:Atotal of 50 cases of breast cancer tissues from patients, who underwent surgical resection at the Department of Oncological Radiotherapy, Wuxi Fourth People’s Hospital from April 2014 to April 2017, were collected for this study. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed to evaluate the mRNA and protein expressions of miR-424 and HMGA1 in breast cancer tissues of radiation sensitive and insensitive patients. After being treated with different doses of 60Co γ-ray radiation (0, 2, 4, 6 and 8 Gy), the expression changes of miR-424 and HMGA1 in breast cancer MDA-MB-468 cells were observed. Subsequently, miR-424 mimic/inhibitor and pcDNA-HMGA1 were transfected into MDA-MB-468 cells, and the effect of miR-424 on cell proliferation, invasion and apoptosis of radiation-treated MDA-MB-468 cells were evaluated by colony formation assay, MTT assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Furthermore, dual luciferase reporter gene assay was used to verify whether HMGA1 was a target gene of miR-424. Results: The patients in radio-sensitive group exhibited higher miR-424 expression but lower HMGA1 expression than the patients in insensitive group (all P<0.01). Compared with the cells treated with 0, 2 and 4 Gy radiation, the cells treated with 6 and 8Gy radiation exhibited significantly higher apoptosis rate and miR-424 expression but lower HMGA1 expression and cell invasion (all P<0.01). Moreover, luciferase reporter gene assay confirmed that miR-424 down-regulated HMGA1 expression. Mechanistically, miR-424 significantly inhibited cell proliferation, invasion and induced apoptosis of MDA-MB-468 cells (all P<0.01) via targeted down-regulating HMGA1, and further upregulated the radio-sensitivity of breast cancer cells. Conclusion: miR-424/HMGA1 axis regulates the radio-sensitivity of breast cancer, and over-expression of miR-424 may increase the sensitivity of MDA-MB-468 cells to γ-ray radiation therapy.

Analysis of correlative factors of fever after percutaneous nephrolithotomy / 中国内镜杂志

Objective To evaluate and study percutaneous nephrolithotomy (PCNL) related factors in the treatment of renal calculi caused postoperative fever and its prevention measures. Methods Making a retrospective analysis of the clinical records of 150 patients who underwent PCNL, including age, gender, diabetes history and previous ipsilateral renal surgery, stone type, stone size, whether the complication of upper ureteral stones, preoperative urinary tract infection, hydronephrosis and pyonephrosis, preoperative renal fistula, postoperative centering vein pressure, intraoperative perfusion and the operation time from January 2015 to June 2017. After the operation, the patients were divided into two groups: fever group and non-fever group, and analyzed the related factors of the fever. Results Among the 150 cases, fever occurred in 27 cases after PCNL, taking up 18%. Gender, history of diabetes, staghorn calculi or staghorn stone, stone size, with ureteral calculi, preoperative urine leukocyte count, renal abscess, preoperative renal fistula, postoperative central venous pressure, intraoperative perfusion and operation time between the two groups, the differences that were statistically significant (P < 0.05). Logistic that multivariate analysis showed that female patients with upper ureteral calculi, perfusion, intraoperative volume,preoperative pyonephrosis, long operation time are independent risk factors of fever after operation (OR

Regulatory T Cell Activity in Immunosuppresive Mice Model of Pseudomonas Aeruginosa Pneumonia / 华中科技大学学报（医学）（英德文版）

Pseudomonas aeruginosa (PA) pneumonia is a refractory,even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process.We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells,i.e.,Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10).Seventy-two BALB/c mice were divided into four groups randomly:control (A),PA pneumonia (B),immunosuppression (C) and immunosuppression with PA pneumonia (D).Mice were sacrificed at 4,8 and 24 h after establishing experimental models.The pathological changes of lung tissue were graded,and the FOXP3 mRNA and serum IL-10 levels were detected.Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C,but significantly pathological changes were found in groups B and D,especially in group D at 8 h (P＜0.05).The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points,which were significantly lower than those in groups B and D (P＜0.05).FOXP3 mRNA levels were lowest at 4 h,and there was significant difference between groups B and D (P＜0.05).The serum levels of IL-10 in groups A and C were almost normal at the three time points,but decreased significantly in groups B and D (P＜0.05).The serum levels ofIL-10 decreased to the lowest at 8 h,especially in group D (P＜0.05).The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly,which may be associated with Treg cells function disturbance.And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

Optimized Exon-Exon Junction Library and its Application on Rodents' Brain Transcriptome Analysis

ABSTRACT Background: Alternative splicing (AS), which plays an important role in gene expression and functional regulation, has been analyzed on genome-scale by various bioinformatic approaches based on RNA-seq data. Compared with the huge number of studies on mouse, the AS researches approaching the rat, whose genome is intermedia between mouse and human, were still limited. To enrich the knowledge on AS events in rodents' brain, we perfomed a comprehensive analysis on four transcriptome libraries (mouse cerebrum, mouse cerebellum, rat cerebrum, and rat cerebellum), recruiting high-throughput sequencing technology. An optimized exon-exon junction library approach was introduced to adapt the longer RNA-seq reads and to improve mapping efficiency. Results: In total, 7,106 mouse genes and 2,734 rat genes were differentially expressed between cerebrum and cerebellum, while 7,125 mouse genes and 1,795 rat genes exhibited varieties on transcript variant level. Only half of the differentially expressed exon-exon junctions could be reflected at gene expression level. Functional cluster analysis showed that 32 pathways in mouse and 9 pathways in rat were significantly enriched, and 6 of them were in both. Interestingly, some differentially expressed transcript variants did not show difference on gene expression level, such as PLCβ1 and Kcnma1. Conclusion: Our work provided a case study of a novel exon-exon junction strategy to analyze the expression of genes and isoforms, helping us understand which transcript contributes to the overall expression and further functional change.

Different active ingredients of medicinal plant based on function differentiation of homologous gene / 中国中药杂志

In the research field of quality control in Chinese medicinal materials, variation in active ingredients of medicinal plant is always the key and hot issues. With the development of high-throughput sequencing technologies and reducing cost, a large numbers of genes from medicinal plant were cloning and provide a solid foundation for further research of gene structure and its biological function, and also provides conditions for explore active ingredient variation and its quality control from the perspective of molecular pharmacognosy. This paper introduces the concept of homologous gene, gene duplication and classification. We prospect the function of duplicated genes in the role of molecular mechanism research about variation in active ingredients, aiming at providing a new way for medicinal materials quality control.

Advances in high-throughput transcriptome research of traditional Chinese medicines / 中国中药杂志

Traditional Chinese medicine is a treasure of Chinese culture, absorbing the wisdom of the Chinese people. Continuous application of new technologies makes traditional Chinese medicine research advance with the times. After several years of development, high-throughput transcriptome study has become a mature research tool in biology. This paper reviewed the advances in medicine transcriptome study, and compared two sequencing platforms, Roche's GS FLX platform and Illumina's HiSeq 2000 platform. Moreover, this paper introduced medicine transcriptome analysis process, with Panax quinquefolius and Lonicera japonica for examples, showing the characteristics of traditional Chinese medicine transcriptome studies. High-throughput transcriptome studies facilitate traditional Chinese medicine research with overall understand of functional genes, give clear elucidation of metabolic pathways, lay molecular foundation for the traditional Chinese medicine research and offer modern interpretation for traditional Chinese medicine theory. However, the current study faces several difficulties, including weak molecular basis, high sequencing cost and staff shortages in data anaysis. In the future, with the development in sequencing technology, the combination of transcriptome and other genomics, such as proteome and metabolome, will lay a solid foundation for the new high-throughput screening and developing model for the traditional Chinese medicine industry.

EST-SSR identification of Lonicera japonica Thunb / 药学学报

Simple and effective methods are needed for the identification of Chinese medicinal material species and their variety. Lonicera japonica Thunb. is one of Chinese herbal medicines widely demanded. A total of 3 705 EST-SSRs of L. japonica and 2 818 EST-SSRs of L. japonica var. chinensis Thunb. were identified from EST database in our lab. In average, there was one EST-SSR per 4.05 kb in L. japonica ESTs and per 7.49 kb in L. japonica var. chinensis ESTs, separately. The identified SSRs in L. japonica were consisted of 51.98% dinucleotide and 34.61% trinucleotide repeats, while SSRs in L. japonica var. chinensis had 57.45% dinucleotide and 30.09% trinucleotide. The results reviewed that the classes AG/TC and GAG/TCT were predominant in the dinucleotide motifs and the trinucleotide motifs, respectively. Total 87 EST-SSRs were identified of significant difference between L. japonica and L. japonica var. chinensis. PCR products were obtained from 52 L. japonica samples in 13 out of 15 SSR markers tested. The polymorphism in L. japonica, L. japonica var. chinensis and other honeysuckles could be distinguished by three markers (jp.ssr4, jp.ssr64 and jp.ssr65) tested.

Toxic epidermal necrolysis after percutaneous coronary intervention: which drug is the culprit? / 中华医学杂志(英文版)

Toxic epidermal necrolysis (TEN) is a serious, usually drug-induced, dermatosis characterized by extensive erythema, necrosis, bullous detachment of the epidermis, constitutional symptoms, and visceral involvement. We report a 62-year-old man who was diagnosed TEN after percutaneous coronary intervention (PCI). After consulting with a cardiologist, all pre-hospital medication was discontinued except clopidogrel. With supportive care, the patient recovered.

A novel mutation in proprotein convertase subtilisin/kexin type 9 gene leads to familial hypercholesterolemia in a Chinese family / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Familial hypercholesterolemia (FH) is an autosomal disorder associated with elevated plasma low density lipoprotein (LDL) levels leading to premature coronary heart disease (CHD). As a result of long-term hyperlipemia, FH patients will present endarterium thickening and artherosclerosis. In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor (LDL-R) metabolism and function alternation.</p><p><b>METHODS</b>Mutation detection was conducted for LDL-R, apolipoprotein B(100) (apoB(100)) and PCSK9 gene with nucleotide sequencing in a Chinese FH family. The full-length cDNA of wild type PCSK9 gene (WT-PCSK9) was obtained from Bel-7402. Site mutagenesis was used to establish the recombinant eukaryotic expression vector carrying pathogenic type of PCSK9 gene and the inserted fragment was sequenced. With the blank vector as control, liposome transfection method was used to transfect the Bel-7402 cells with recombinant plasmid. The expression of LDL-R mRNA was examined by RT-PCR. PCSK9 and the expression of LDL-R protein were determined by Western blotting.</p><p><b>RESULTS</b>The G-->T mutation at the 918 nucleotide of PCSK9 gene resulted in the substitution of the arginine by a serine at the codon 306 of exon 6. After sequencing, it was confirmed that the inserted fragment of established expression vector had correct size and sequence and the mutant was highly expressed in Bel-7402 cells. There was no significant variation in the levels of LDL-R mRNA. LDL-R mature protein was decreased by 57% after the cells were transfected by WT-PCSK9 plasmid. Mature LDL-R was significantly decreased by 12% after the cells were transfected by R306S mutant as evidenced by gray scale scanning, suggesting that the new mutant R306S can significantly decrease the expression of mature LDL-R protein.</p><p><b>CONCLUSIONS</b>A novel missense mutation of PCSK9 gene, R306S, was found and the eukaryotic expression vectors of mutant and wild-type of PCSK9 gene were established. There was no significant variation in the levels of LDL-R mRNA. The R306S mutation could significantly lead to the decrease of LDL-R mature protein expression, which might be the pathogenic gene of the FH family.</p>