Objective To study the role of JAK-STAT singal transduction pathway in the interstitial fibrosis of unilateral ureter obstruction (UUO)mice. Methods Mice UUO model was established and the phosphorylation of JAK-STAT was examined at day 1,4,7 and 14 after ligation of the ureter.Mice in the treatment group were treated with daily injection of selective JAK2 inhibitor AG490 starting 2 h before ureter ligation until sacrifice while vehicle alone was given to mice in the model control group.Mice were sacrificed at day 14 after the establishment of model.Renal tubular lesion and interstitial fibrosis were assessed on paraffin section.Immunohistochemistry was used to detect renal macrophage infihration and α-SMA expression.The expression of collagen Ⅲ and MCP-1 mRNA was measured by RT-PCR.Phosphorylation of JAK2and STAT1 was examined by Western blotting. Results JAK2-STAT1 signaling transduction pathway was activated in UUO model.The activation of JAK2-STAT1 was closely correlated with the progression of renal injury,tubular histological lesions and interstitial fibrosis.AG490 treatment significantly inhibited the phosphorylation of JAK2 and STAT1 (P＜0.01).AG490 treatment also significantly reduced tubular lesions[(21.7 ±1.7)% vs (49.4±1.0)%]and interstitial fibrosis(1.0±0.1 vs 2.3±0.2),α-SMA expression(0.9±0.1 vs 2.1±0.2)and maerophage accumulation[(13.3±1.6)cells/HPF vs (34.4±1.0)cells/HPF](all P＜0.01).In addition,AG490 significantly inhibited the expression of collagen Ⅲ and MCP-1 mRNA. Conclusion JAK-STAT signaling plays an important role in renal tubulointerstitial inflammation and fibrosis.

Objective To develop a duplex fluorescence RT-PCR assay for detection of scavenger receptor class B, typeⅠ(SRBⅠ) knockout mice. Methods Primers and probes were designed according to knockout region of SRBⅠgene and related substituted sequence. DNA samples were extracted from tails of mice and performed amplification using real-time PCR. SRBⅠgenotypes of mice were analyzed according to amplification curves of FAM and CY5 channels. Finally, the sensitivity of the method was detected and the accuracy was verified by the direct sequencing. Results The homozygous SRBⅠwild genotype showed an amplification curve only in FAM channel. When the homozygous SRBⅠknockout genotype was present, the typical S amplification curve appeared only in the CY5 channel. Heterozygous genotype showed two typical S amplification curves in both FAM and CY5 channels, respectively. The results showed that the sensitivity reached 4×101 copies/μL, and there was complete concordance between this method and direct DNA sequencing. Conclusion The new method is simple, rapid and accurate, which is suitable for genotyping SRBⅠknockout mice.

Objective:To explore therapeutic effect of bisoprolol with CYP2D6 and CYP3A4 gene targeting therapy for hypertension .Methods :A total of 100 cases with essential hypertension (EH) were selected ,among them 20 ca-ses were randomly chosen to receive routine medication (bisoprolol 5 mg/d ,routine treatment group ) ,the other 80 patients were equally divided into group A (CYP2D6*10) and group B (CYP3A4*1G) .According to detection results of CYP2D6*10 and CYP3A4*1G gene polymorphism ,they were dived into group ACC (n=13) ,group ACT (n=14) ,group ATT (n=10) ,group BCC (n=21) ,group BCT (n=17) and group BTT (n=0) .Bisoprolol dosage was adjusted according to genotypes :group ACC and group BCC received 10 mg/d ,group ACT and group BCT received 5 mg/d ,group ATT and group BTT received 2.5 mg/d .Blood drug concentration ,blood pressure and heart rate were compared among above groups after two weeks .Relationship between plasma concentration of bisoprolol and gene polymorphism of drug metabolism enzyme was evaluated .Results:Comparison between related groups with same bi-soprolol dosage :there were no significant difference in blood drug concentration ,heart rate and blood pressure be-tween ACT and routine treatment group , P>0.05 all;compared with routine treatment group ,there was significant rise in blood drug concentration [ (33.5 ± 19.1) ng/ml vs .(50.13 ± 23.21) ng/ml] ,significant reduction in heart rate [ (71.4 ± 5.16) times/min vs .(66.5 ± 6.04) times/min] and blood pressure [ (127.22 ± 10.44/82.4 ± 7.27) mmHg vs .(119.48 ± 11.97/71.2 ± 10.30) mmHg] in BCT group , P<0.05 all .Conclusion:Because gene possesses polymorphism ,therapeutic effect of bisoprolol treating hypertension is differing ;the gene targeting therapy may significantly improve therapeutic effect for hypertension .

Objective To summarize the diagnosis and treatment in neonatal cow’s milk protein allergy (CMPA) with sepsis like initial symptom. Methods CMPA patients with the sepsis like initial symptom (n=10) were selected in our hospital from July 2009 to December 2013. History data, clinical manifestation, laboratory results and the treatment outcome of them were retrospectively analyzed. Results Among these 10 cases, 6 have family history of allergy. Main clinical mani-festations include skin, gastrointestinal symptoms and 1 case of anaphylactic shock. IgE mediated 6 cases with acidophilic cells count of (1.40±0.17)×109/L (5%); The rest 4 cases were not mediated by IgE, with acidophilic cells count of (0.71± 0.08)×109/L (0.02-0.03). Blood cultures were all negative;Blood leukocyte count is (24.5±3.3)×109/L;Rod nucleus granulo-cyte/neutrophils count is (0.161±0.035) ×109/L;The platelet count is (655±39)×109/L;Blood interleukin (IL)-6 is 0.31-0.93μg/L;C reactive protein (CRP) is 85-144 mg/L. All 10 cases were with extensively hydrolyzed formular or amino acid formu-lar feeding. Then their clinical symptoms improved or disappeared significantly and the inflammatory indexes returned to nor-mal. Conclusion It is necessary to make the differential diagnosis between sepsis and neonatal CMPA,which is accompa-nied by increased platelet and acidophil. The most effective treatment of neonatal CMPA is hypoallergenic formular replace-ment therapy.

Objective To investigate the clinical characteristics of pulmonary artery sarcoma (PAS) and pulmonary thromboembolism(PTE), to improve doctors' awareness and the early diagnosis of PAS.Methods The clinical data of 10 PAS cases confirmed with biopsy were retrospectively analyzed,and 10 cases with PTE were selected as control group.Results (1) Main clinical manifestations of the two groups were chest tightness, shortness of breath, intermittent syncope, palpitations, chest pain and cough, and there were no statistical significance differences between the two groups (P＞0.05).(2)There were 2 cases (20.0％) PaO2 ＜80 mmHg in patients with PAS.However, there were 8 cases (80.0％)PaO2 ＜ 80 mmHg in control group.The two groups had statistically significant difference (x2 =7.200, P =0.023).(3) Wells score : the cases with PAS was in low risk (80.0％ and 10.0％),however, the cases of control group was in medium and high risk(90.0％ and 20.0％).The two groups had statistically significant difference (P =0.005, 0.001).(4) The two groups had no statistically significant difference in ECG, UCG, X-ray, lung ventilation/perfusion (P＞ 0.05).(5) There had statistically significant difference in terms of LDH and CRP between PAS and PET group (100％ vs.0, x-2 =10.796,P=0.003;100％ vs.0, x2 =15.000, P =0.000).There was faster ESR in PAS group than control group,and the two groups had statistically significant difference (75％ vs.0, x2=1.400, P =0.011).There was no case of D-Dimer＞500 μg,/L in PAS group, while 10 cases in control group, and the two groups had significant statistical difference (x2 =17.000, P =0.000).(6) There was 1 case (12.5％) with DVT in PAS group, 6 cases (60.0％) in PTE group, and the two groups had significant statistical difference (x2=10.568, P =0.001).(7) The CTPA in PAS group showed filling defect in the main pulmonary artery trunk (85.7％ vs.0) ,left pulmonary artery (85.7％ vs.10.0％) ,right pulmonary artery(100％ vs.10.0％) and both left and right pulmonary artery (85.7％ vs.10.0％), the two groups had significant statistical difference (x2 =13.247, P =0.001;x2 =9.746, P=0.004;x2 =13.388, P =0.000;x2 =9.746, P =0.004).Conclusion PAS and PTE can' t be distinguished from the clinical symptoms, ECG, UCG, X-ray,lung ventilation/perfusion imaging.PAS is easily misdiagnosed as PTE.More attention should be given.PAS can be identified early through the blood gas analysis, hypoxemia,Wells score, LDH, CRP, ESR, D-Dimer, DVT and CTPA.

Objective To establish a dual real-time fluorescence quantitative polymerase chain reaction (dual real-time PCR) assay to detect human vitamin D receptor (VDR) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Methods GAPDH gene was used as the internal control. The specific primers and TaqMan probes were designed by Primer Premier 5.0 software, which were applied to detect the VDR/GAPDH mRNA levels. The obtained PCR products were puri-fied to construct the VDR/GAPDH recombinant plasmid, which was taken as the standard to analyze the sensitivity and re-peatability of the method. Results The amplification products were confirmed as the specific fragment of VDR/GAPDH by DNA sequencing instrument. The results showed that the sensitivity, linear range, the determinate coefficient, the amplifica-tion efficiency, the intra-assay and inter-assay coefficient of variation were 40 copies/μL, 4.00 × 101-4.00 × 105 copies/μL, 0.998, 96.10%, 0.09%-1.21%, 0.17%-0.51%for VDR, and 40 copies/μL, 4.00 × 101-4.00 × 105 copies/μL, 0.999, 85.15%, 0.35%-0.88%, 0.51%-2.46% for GAPDH, respectively. Conclusion These results demonstrate that the dual real-time PCR assay with high sensitivity and specificity can detect the relative expressions of human VDR by single reaction tube, which can effectively shorten the time and reduce the experimental error.

Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine the anti-remodeling effect of intravenous MSCs (VMSCs) and intratracheal MSCs (TMSCs) in rats with PH, and the underlying mechanisms. MSCs were isolated from rat bone marrow and cultured. PH was induced in rats by intraperitoneal injection of MCT. One week after MCT administration, the rats were divided into 3 groups in terms of different treatments: VMSCs group (intravenous injection of MSCs), TMSCs group (intratracheal injection of MSCs), PH group (no treatment given). Those receiving saline instead of MCT served as negative control (control group). Pulmonary arterial structure was pathologically observed, pulmonary arterial dynamics measured, and remodeling-associated cytokines Smad2 and Smad3 detected in the lungs, three weeks after MCT injection. The results showed that PH group versus control group had higher pulmonary arterial pressure (PAP) and wall thickness index (WTI) 21 days after MCT treatment. The expression of phosphorylated (p)-Smad2 and the ratio of p-Smad2/Smad2 were much higher in PH group than in control group. Fluorescence-labeled MSCs were extensively distributed in rats' lungs in VMSCs and TMSCs groups 3 and 14 days after transplantation, but not found in the media of the pulmonary artery. WTI and PAP were significantly lower in both VMSCs and TMSCs groups than in PH group three weeks after MCT injection. The p-Smad2 expression and the ratio of p-Smad2/Smad2 were obviously reduced in VMSCs and TMSCs groups as compared with those in PH group. In conclusion, both intravenous and intratracheal transplantation of MSCs can attenuate PAP and pulmonary artery remodeling in MCT-induced PH rats, which may be associated with the early suppression of Smad2 phosphorylation via paracrine pathways.

Objective: To study the relationship between CYP2D6*10 gene polymorphism and metoprolol therapeutic effect for hypertension. Methods: A total of 60 patients with essential hypertension (EH) received metoprolol 47.5mg/d for 3d. After 3d the plasma metoprolol concentration after oral 2h was measured. Polymorphism of CYP2D6*10 gene was detected by PCR-RFLP. According to results of gene detection, the patients were divided into CC genotype group (wild type homozygote, fast metabolism type, n=14), CT genotype group (heterozygous mutation, intermediate metabolism type, n=25) and TT genotype group (homozygous mutation, slow metabolism, n=19). Metoprolol dosage was adjusted according to CYP2D6*10 genotype. After one week, plasma concentration of metoprolol after oral 2h was measured again, and mean heart rate and blood pressure were measured before and after gene-directed therapy. Results: Before gene-directed therapy, compared with CC and CT group there was significant increase in plasma concentration of metoprolol [(26.57±19.40) ng/ml vs. (23.88±12.86) ng/ml vs. (64.74±32.94) ng/ml, P<0.01] in TT group; compared with TT group, there were significant rise in mean systolic blood pressure [mSBP, (132.84±13.40) mmHg vs. (144.14±14.28) mmHg], mean diastolic blood pressure [mDBP, (76.95±9.07) mmHg vs. (81.36±7.33) mmHg] and mean heart rate [mHR, (69.13±11.83) times/min vs. (76.66±7.33) times/min] in CC group, P<0.05 all. After gene-directed therapy, there were no significant difference in plasma concentration of metoprolol, mSBP, mDBP and mHR among all groups, P>0.05 all; Compared with before gene-directed therapy, there was significant increase in plasma concentration of metoprolol, and significant decrease in mSBP, mDBP and mHR in CC group (P<0.05). There were no significant difference in blood pressure and heart rate between before and after treatment in CT group and TT group (P>0.05). Conclusion: CYP2D6*10 gene polymorphism affects metoprolol metabolism and its therapeutic effect on hypertension, gene-directed therapy can significantly improve drug therapeutic effect and reach ideal therapeutic goal in short time.

Objective:To explore the effects of WeChat-based health education on management of hypertensive outpatients under medical consortium.Methods:Totally 180 hypertensive patients who attended the Multidisciplinary Clinics of Beijing Anzhen Hospital, Capital Medical University, and Datun Community Health Service Center from communities under our medical consortium from November 2018 to April 2019 were selected and divided into the observation group ( n=91) and the control group ( n=89) according to the visit time. Patients in the control group received routine health education, while patients in the observation group received WeChat-based health education under medical consortium for 6 months. The self-management ability (using Hypertension Patients Behavior Rating Scale, HPSMBRS) , treatment compliance (using Therapeutic Adherence Scale for Hypertensive Patients, TASHP) , the 24 h average systolic and diastolic blood pressure, the average systolic and diastolic blood pressure at daytime, and the average systolic blood pressure and diastolic blood pressure at night were compared between the two groups. Results:After the intervention, the diet management, medication management, disease monitoring, exercise management, work and rest and emotional management scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the medication-taking behavior, bad medication-taking behavior, daily activity management behavior and tobacco and alcohol addiction scores were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the 24 h average systolic and diastolic blood pressure, average systolic and diastolic blood pressure at daytime and average systolic and diastolic blood pressure at night decreased in the observation group, and the differences were statistically significant compared with the control group ( P<0.05) . Conclusions:The WeChat platform under medical consortium provides standardized, consistent, continuous and effective health education, which can improve the self-management ability and treatment compliance of hypertensive outpatients, and can effectively control blood pressure levels. It shows sound effects in clinical use.

Objective:To analyze the characteristics of the ocular vestibular evoked myogenic potential on three different eye positions and to explore the appropriate eye position for oVEMP.Methods:15 patients (30 ears) with vertigo who underwent oVEMP test from December 2017 to May 2018 were selected as the patient group, including seven males and eight females, with an average age of (51±13) years. Another 22 (44 ears) healthy young people were recruited into the control group, including 10 males and 12 females, with an average age of (23±5) years. oVEMPs were measured on the following three eye positions respectively: 30 degrees straight up(upper median position),45 degrees upper right(upper right position), and 45 degrees upper left(upper left position). oVEMP elicitation rate, oVEMP latencies, amplitudes and interaural amplitude asymmetry ratio were analyzed by SPSS 23.0 statistical software.Results:There was no statistical significance ( P>0.05) in the oVEMP elicitation rate, oVEMP latency, amplitude and asymmetry ratio on the three eye positions among the control group, the patient group and the overall subjects. Conclusions:The three eye positions can be used to detect oVEMP in clinic. There is no difference in the extraction rate and waveform characteristics. When one of the eye positions is difficult to gaze or not easy to obtain the coincidence curve, the other two can be used to obtain the ideal oVEMP curves as well.