Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.
Humans ; Computed Tomography Angiography/methods* ; Coronary Angiography/methods* ; Coronary Artery Disease/diagnostic imaging* ; Coronary Stenosis/diagnostic imaging* ; Death, Sudden, Cardiac/pathology*

ObjectiveTo investigate the practicability and efficacy of Inlay preputial graft urethroplasty combined with Buck fascia integral covering technique （Inlay-BFIC） in the treatment of hypospadias. MethodsA total of 85 surgeries of hypospadias with urethral plate width of 3-5mm at the level of the glans navicular fossa from January 2018 to August 2020 were retrospectively analyzed. The patients were divided into two groups according to the time of technique applied. Group A： from November 2018 to December 2020， 38 consecutive patients， including 5 re-operation cases， were operated with Inlay-BFIC urethroplasty. Surgical approach： a thin and full-thickness free preputial graft was embedded in the middle incision of the urethral plate when patients underwent TIP procedure； after the urethroplasty， the pre-reserved Buck fascia combined with glans wings was sutured at the midline as an intermediate layer to cover the neo-urethra. Group B： from January 2018 to December 2018， 47 consecutive primary hypospadias patients underwent conventional TIP procedure. The data of perioperative period and postoperative follow-up were recorded and analyzed statistically. ResultsTotally 85 patients were repaired by one-stage procedure. Group A with Inlay-BFIC vs. group B with conventional TIP： the mean age （39.46±34.66） vs.30.23±26.02） m， t=1.362， P=0.178， the mean length of penis （3.53±1.00） vs. （3.46±0.76） cm， t=0.373， P=0.710， the mean width of glans （1.32±0.36） cm vs. （1.37±0.22） cm， t=-0.779， P=0.438， the mean length of urethroplasty （2.10±0.68） vs.（1.92±0.61） cm， t=1.282， P=0.203. There was no significant difference between the two groups. The preoperative degree of ventral curvature and the mean operative time between group A and group B were （28.29±21.38） vs. （19.68±7.62）°， t=2.364， P=0.023 and （135.29±39.79） vs. （96.60±27.21） min， t=5.107， P=0.000. There was significant difference between the two groups. The postoperative follow-up time was 4 to 36 months. There were 2 cases of urinary fistula in Group A and 6 cases in Group B （χ²=1.387，P=0.239）， 1 cases of urethral stricture in Group A and 3 in Group B （χ²=0.659，P=0.417）. There was no significant difference between the two groups. There was no recurrent ventral curvature and urethral diverticulum in both groups. There were 4 cases of glans or urethral dehiscence in Group A and 17 cases in Group B （χ²=7.428，P=0.006）. There was significant difference between the two groups. Fifteen patients in each group received urinary flow rate test. There was no significant difference between two groups in maximum flow rate （Qmax）， average flow rate （Qavc）， flow time （FT） and voided volume （V）. ConclusionsFor the treatment of hypospadias by Buck fascia integral covering technique combined with Inlay preputial graft urethroplasty， the incidence of urinary fistula， urethral stricture， urethral diverticulum， residual penis curvature and postoperative urinary flow rate are similar to those of conventional TIP procedure， but it can significantly reduce the occurrence of glans or urethral dehiscence.

Objective To explore the expression level of CD36 in peripheral blood mononuclear cells(PBMCs) from patients with crytococcal meningitis and its clinical significance.Methods The experimental group was the peripheral blood samples from 36 patients diagnosed as crytococcal meningitis in Changhai Hospital and Changzheng Hospital in Shanghai from September 2013 to February 2017,while the control group was the peripheral blood samples from 36 health individuals examined at the same time.PBMCs were separated by density gradient centrifugation method,the relative mRNA expression of CD36,TLR4 in PBMCs was tested by qRT-PCR,the expression level of cytokines such as TNF-α in plasma was tested by ELISA,the comparison of the examined values of experimental and control groups performed by two independent samples' t test,Pearson correlation analysis was performed on the relative mRNA expression of CD36 in PBMCs and cytokines such as TNF-α in experimental group.Results The relative mRNA expression of CD36 in PBMCs of experimental group was 2.01 ± 0.63,the control was 1.49 ± 0.47,and there was statistical difference (t =3.969,P =0.000 2).Pearson analysis results showed that in experimental group CD36 was positively related with the protein expression level of IFN-γ in plasma (r=0.384,P＜0.05) and negatively related with TGF-β(r=-0.487,P＜0.005).Conclusion CD36 might involve in the immunopathology process of crytococcal meningitic by influencing the expression of cytokines such as IFN-γ,TGF-β,and was the potential target for monitoring and treating this disease.

Objective To study the expression of CD69 in exosomes existed in serum from patients with autoimmune pancrea titis (AIP) and primarily discuss its affection on the pathology of disease progression.Methods Serum samples from 35 cases diagnosed as AIP and 35 healthy individuals examined at the same time were collected during October 2012 to December 2016 in Changhai Hospital,they were defined as experimental and control groups,separately.The cytokine levels in serum were measured by ELISA.The expression of surfaced molecules in exosomes existed in serum was tested by magnetic bead conjunct antibody method in flow cytometry.The comparison between the two groups' measurement data was measured by two independent samples' t test,correlation between two variables was showed by Pearson coefficient.Results The flow cy tometry analysis showed that the expression level of CD69 in serum exosomes in experiment and control groups were (85.76 ±19.45 vs 17.01±5.89)％,with statistical difference(t=20.01,P＜0.0001).CD69+ exosomes in experiment group were positively related with serum IL-4,IFN-γ and TGF-β (r 0.456,0.678,0.548,all P＜0.05),while CD69 exosomes were negatively related with serum IL-4,IFN-γ,IL-10 and TGF-β (r=0.589,-0.399,-0.784,-0.657,all P＜0.05).Conclusion The expression of CD69 in exosomes might participate in AIP progression through influencing the function of CD4 +T cell,and it was the potential examined biomarker and therapeutic target.

Objective To examine the expression of CD93 in serous exosomes from patients with cryptococcal meningitis,fur-ther explore its clinical significance.Methods The 38 experimental serum samples were from patients who received the diag-nosis with cryptococcal meningitis in Changhai Hospital and Changzheng Hospital in Shanghai from November 2012 to De-cember 2016.The diagnosis standardization was that the cerebrospinal fluid dyeing was positive or the culturing was posi-tive.The 38 controls were collected from the health individuals examined at the same time.The exosomes in serum was sepa-rated by the ultracentrifuge method.Magnetic bead-capture combined with the flow cytometry method was used to identify antigens on the surface of exosomes.The protein level of cytokines in serum was quantified by ELISA method.The compari-son of tested values from experimental and controlled groups was measured by two independent samples't test,and the cor-relation between two variates was showed by Pearson coefficient.Results The results of flow cytometry showed that the ex-pression of CD93 on exosomes in the serum samples from experimental group was higher than that in the controlled group, which was(79.11±19.31 vs 23.98±6.56)%,with difference in statistics(t=16.66,P<0.000 1).The expression levels of IFN-γin serum samplefrom experimental and control groups were(39.78±10.77 vs 58.98±16.99)pg/ml,with differ-ence in statistics(t=5.884,P<0.000 1).The expression levels of IL-17 in serum sample from experimental and control groups were(16.32±4.03 vs 3.11±0.87)pg/ml,with difference in statistics(t=19.75,P<0.000 1).The expression lev-els of IL-1β in serum sample from experimental and control groups were(57.12 ± 12.98 vs 13.45 ± 4.78)pg/ml,with difference in statistics(t=19.46,P<0.000 1).The percentage of CD93+exosomes was positively correlative with IFN-γ, IL-17,IL-1β(r=0.488,0.456,0.532,P<0.01)in serum samples from the experimental group and there was statistical difference.Conclusion In the disease process of cryptococcal meningitis,the expression of CD93 on exosomes might involve in the diseases'processes by affecting the CD4+T cells.

Objective To evaluate the association of cervical cancer and the G/C single nucleotide polymorphism at codon 72 in p53 gene exon -4 in Chinese population.Methods Literatures were searched in CNKI,VIP,CBM, PubMed,EMBase,the Cochrane Library (Issue 1,2015),WanFang Data Database (1980—2015)with computer. Results Thirteen studies involving 1 780 cervical cancer patients and 1 5 17 healthy volunteers were included.According to the situation of the HPV infection in research object,thirteen studies were divided into two subgroups.The results of meta-analyses in the subgroup of non-HPV infection showed that the Chinese women having the genotype G/G presented no increased relative risk compared to that with the genotype C/C(OR=0.980,95%CI:0.558 -1.723).The allele G showed no increased relative risk compared to the allele C (OR=1.070,95%CI:0.789-1.449)The results of meta-analyses in the subgroup of HPV infection showed that the Chinese women having the genotype G/G presented no increased relative risk compared to that with the genotype C/C(OR=0.891,95%CI:0.213 -3.722).The allele G showed no increased relative risk compared to the allele C (OR =0.981,95%CI:0.493 -1.951 ).Conclusion This meta -analysis demonstrates that G/C single nucleotide polymorphism at codon 72 in p53 gene exon-4 were not associated with cervical cancer in Chinese women.

Objective To search for the bone mesenchymal stem cell (MSC) subgroup which might be more effective on repairing myocardial damage.Methods In this experiment,four MSC subgroups were defined based on the surface differentiation antigen detection of mouse bone mesenchymal stem cells (mBMSCs):SCA-1 +/CD45 +/CD31 +,SCA-1 +/CD45 +/CD31-,SCA-1 +/CD45-/CD31-and SCA-1 +/CD45-/CD31 +.These subgroup cells and unselected mBMSCs were injected into infarcted mouse via tail vein.Echocardiographic heart function measurement and in vivo DiR-labeled stem cells imaging were performed at 48 h after injection.In situ C-kit (a flag antigen of cardiac stem cells) and cardiac-specific differentiation antigen immunohistochemistry detection was made in the infarcted myocardium.Results The capacity of the SCA-1 +/CD45 +/CD31 + cells on improving heart function was significantly higher than other cell groups(all P ＜ 0.05).In vivo imaging showed that the mean fluorescence intensity of the SCA-1 +/CD45 +/CD31 + cells was also higher than other cell groups (all P ＜ 0.05).Number of cardiac stem cells in the infracted myocardium was significantly increased after the injection of all subgroup cells and unsorted mBMSCs cells for 48 h compared untreated infracted myocardium.The capacity of mobilizing cardiac stem cells is as follows:SCA-1 +/CD45 +/CD31 + ＞ SCA-1 +/CD45-/CD31 + ＞ SCA-1 +/CD45-/CD31-＞ SCA-1+/CD45+/CD31-.Conclusion The SCA-1+/CD45+/CD31+ subgroups of mBMSCs exhibites the highest capacity to improve cardiac function after myocardial infarction and to mobilize autologous cardiac stem cells compared with other mBMSCs subgroups and unsorted mBMSCs cells.

We report the effects of biventricular pacing in a patient with hypertrophic obstructive cardiomyopathy (HOCM) refractory to medical therapy. A 58-year-old man with HOCM had suffered from dyspnea, chest pain and palpitation for 5 years. Cardiac catheterization showed a left ventricular outflow tract (LVOT) gradient of 80 mmHg. He refused septal myomectomy and the septal ablation was not available. Based on intraoperative pressure measurements, he was implanted with biventricular pacing and LVOT gradient decreased to 10 mmHg. During the follow-up period of 6 months, the patient's symptoms were markedly improved. Biventricular pacing may be an alternative therapy for patients with HOCM.
Cardiac Resynchronization Therapy ; methods ; Cardiomyopathy, Hypertrophic ; diagnostic imaging ; pathology ; therapy ; Coronary Angiography ; Electrocardiography ; Humans ; Male ; Middle Aged