Objective To investigate the safety and efficacy of interventional therapy in patients with secondary atrial septal defect(ASD)with complete aortic rim deficiency.Methods 402 patients with ASD who underwent transcatheter closure and followed up in outpatient at both 6-month and 1-year in the Department of Cardiology,Zhongshan Hospital,Fudan University from January 2018 to June 2020 were enrolled.They were divided into complete aortic rim deficiency group and normal aortic rim group.The clinical features,interventional parameters,and complications were compared between the two groups.Echocardiographic were used to evaluate the outcome.Results The occluder size was larger in the aortic rim deficiency group([26.4±6.9]mm,n=128)than that in normal aortic rim group([23.4±7.7]mm,P＜0.001;n=274).Both groups exhibited no major postoperative complications,and significant improvements were observed in right heart remodeling following the operation,including pulmonary artery pressure decreasing,the diameters of the right atrium and right ventricle reducing,and the degree of tricuspid regurgitation reducing(P＜0.001).There was no significant change in left ventricular ejection fraction in all patients.Conclusion Transcatheter closure of ASD with complete aortic rim deficiency is safe and feasible.

Cardiac Catheterization ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Treatment Outcome ; Tricuspid Valve/surgery* ; Tricuspid Valve Insufficiency/surgery*

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Prosthesis Failure ; Transcatheter Aortic Valve Replacement ; Treatment Outcome

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of β-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.
Acrolein ; analogs & derivatives ; Animals ; Candida albicans ; Colitis, Ulcerative ; Colon ; Dextran Sulfate ; Disease Models, Animal ; Lectins, C-Type ; Mice ; NF-kappa B ; Signal Transduction

To investigate the mechanism of n-butanol extract of Pulsatilla decoction (BAEB) against murine ulcerative colitis (UC) model induced by DSS combined with Candida albicans (CA) colonization, mice were randomly divided into normal control group, DSS group, DSS+CA group, BAEB high, medium and low dose group, and positive drug Mesalazine group. The general condition of mice was observed, fungal loads of murine intestinal contents were detected by plate method, colonic pathological change of mice was examined by HE staining. ASCA in serum and IL-6, IL-8, IL-1β, HBD-2, HBD-3 in colonic mucosa were detected by ELISA. The results showed that, compared with DSS group, the general condition and ASCA in serum had no obvious change for DSS+CA group, but the fungal loads in intestinal contents, the colonic pathological damage, and the levels of IL-6, IL-8, IL-1β, HBD-2, HBD-3 in colonic mucosa were greater than that of DSS group. High dose of BAEB group and Mesalazine group could improve the colonic pathology, decrease IL-6, IL-8, IL-1β, HBD-2, HBD-3 expression level. In conclusion, BAEB could effectively improve the UC symptoms in mice induced by DSS combined with CA colonization, and inhibit the inflammatory factors such as IL-6, imply that BAEB is of important value for the treatment of intestinal fungal-related colitis.

Objective:To evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) in 40 patients with aortic valve stenosis in our center.Methods:Totally 40 consecutive patients who underwent TAVR in our center were enrolled.The endpoints included success rate of operation,complications,follow-up results 30 days after operation,etc.Results:There were 27 males and 13 females with mean age of (78.3±5.0) years old.The success rate of operation was 100 ％.After operation,the mean aortic valve pressure gradient decreased significantly ([10.77 ± 3.90] rnmHg vs [61.80± 18.62] mmHg,P＜0.001),while the mean flap area increased significantly ([1.80 ± 0.24] cm2 vs [0.65 ± 0.17] cm2,P＜ 0.001).The NYHA class was significantly improved (1.80±0.62 vs 2.95±0.75,P＜0.001) after TAVR.One day after operation,there were 13 with paravalvular regurgitation (12 of mild cases and 1 of moderate case),1 with acute occlusion of right coronary artery,1 with valve dislodgement then ischemic stroke,and 1 with intractable pericardial effusion and pericardial tamponade.In the 30-day follow-up,the mortality rate was 2.5 ％ (1 patient) and the incidence of permanent cardiac pacemaker for abnormal cardiac conduction was 10％ (4 patients).Conclusions:TAVR is safe and effective for aortic stenosis patients with high-risk or surgical contradication in our country.

BACKGROUND:Stem cells have been widely used in the treatment of spinal cord injury,but the clinical application is limited by immune rejection,difficulty in cell harvesting and purification.However,human nasal mucosa mesenchymal stem cells (hNM-MSCs) have no such problems,and its clinical application in the treatment of spinal cord injury has been not reported yet.OBJECTIVE:To observe the biological characteristics of autologous hNM-MSCs and its clinical efficacy in the treatment of advanced incomplete spinal cord injury.METHODS:NM-MSCs were isolated from the human nasal mucosa,cultured and identified in vitro.The ultrastructure of NM-MSCs was observed by transmission electron microscope and scanning electron microscope.Then the NM-MSCs were induced to differentiate into osteocytes,adipocytes,stem cell spheres,or neurons in vitro.Totally eight patients with incomplete spinal cord injury were enrolled and subjected to hNM-MSCs transplantation via lumbar puncture for 1-3 sessions of about 5× 107 cells each,with an interval of 5-7 days,after the approval of the medical ethics committee.All the patients were followed up for 6 months.Preoperative and postoperative therapeutic effect evaluations were performed on the basis of American Spinal Injury Association (ASIA) scores.RESULTS AND CONCLUSION:Under light microscope,the NM-MSCs were mainly spindle-shaped,positive for STRO-1 and exhibited a radial arrangement.NM-MSCs highly expressed CD73,CD90 and CD105,but did not express CD34 and CD45,with the purity of over 97％.And lots of podgy microvilli were seen on the surface of NM-MSCs under the scanning electron microscope,and two kinds of cell morphologies were seen under the transmission electron microscope.Moreover,hNM-MSCs had the ability to differentiate into osteocytes,adipocytes,stem cell spheres and neurons.During the 6-month follow-up,seven patients achieved neurological function recovery to different extents except for one patient,and no side effects were found.It is concluded that hNM-MSCs can become the ideal seed cells for tissue-engineered cell repair.Autologous NM-MSCs transplantation for the treatment of spinal cord injury can achieve the ideal effect,with the value of clinical application.

BACKGROUND: Human olfactory mucosa mesenchymal stem cells (hOM-MSCs) not only have the basic characteristics of mesenchymal stem cells, but also originate from the ectoderm and are prone to differentiate into neurons, which are a kind of ideal seed cells for nerve repair and regeneration. Cells are conventionally cultured in about 21% in vitro, while only 3%-9% oxygen is found in the human body and tissue space. There is still no report on the effect of hypoxia on the proliferation and activity of hOM-MSCs.OBJECTIVE: To explore whether hypoxic microenvironment can promote hOM-MSCs proliferation and activity and the related mechanism. METHODS: hOM-MSCs were isolated, cultured and identified by flow cytometry and immunofluorescence. The passage 4 hOM-MSCs were divided into three groups: 21% O2 group, 3% O2 group and 3% O2+20 μmol/L YC-1 (HIF-1α inhibitors) group. Proliferation and apoptosis of hOM-MSCs was detected by flow cytometry after 72 hours of culture. The proliferating cell nuclear antigen protein expression was detected by western blot. The mRNA and protein expression of HIF-1α and TWIST were detected by Q-PCR and western blot. RESULTS AND CONCLUSION: The purity of hOM-MSCs was up to 97%, as defined by flow cytometry. The proliferation index of 3% O2 group was higher than the 21% O2 group (P < 0.05), and cell survival and apoptosis ratio (apoptotic cells included mechanical death + early apoptosis + late apoptosis) between the two groups had no significant difference (P > 0.05). Western blot results showed that the proliferating cell nuclear antigen protein expression in the 3% O2 group was significantly higher than that in the other groups (P < 0.05). The HIF-1α and TWIST expressions at mRNA and protein levels in the 3% O2 group were significantly higher than those in the other groups (P < 0.05). To conclude, hypoxic microenvironment can promote the hOM-MSCs proliferation and has no effect on the apoptosis, and the HIF-TWIST signal pathway plays an important role in this progress.

OBJECTIVETo investigate the effect of total flavonoids of astragalus on the expression of endoplasmic reticulum chaperone, calumenin and connecxin 43 (CX43) in suckling mouse myocardium with myocarditis caused by coxsackievirus B3 (CVB3).

METHODSThe primary culture of suckling mouse myocardium cells were randomly divided into control group, CVB3 infected group and total flavonoids of astragalus group. Firstly, to confirm the identity of the suckling mouse myocardium, α-SMA was monitored by immunohistochemistry method. Then the protein expression changes of endoplasmic reticulum chaperone-glucose regulatory protein 78 ( GRP78), calumenin and CX43 were detected by Western blot.

RESULTS(1) Compared with that of the control group, the GRP78 expression level in CVB3 infected group was improved, the expression levels of calumenin and CX43 were all reduced. (2) Compared with that of CVB3 infected group, GRP78 expression level was decreased, and the expression levels of calumenin and CX43 were increased in total flavonoids of astragalus group.

CONCLUSIONCVB3 infection may cause endoplasmic reticulum stress of rat myocardium cells by increasing the expression of GRP78 and decreasing the expression of calumenin and CX43. On the other hand, total flavonoids of astragalus can reduce the expression of GRP78 and increase the expression of calumenin and CX43.The results of this experiment may be closely related to the effects of anti-arrhythmia with viral myocarditis caused by CVB3.

Animals ; Astragalus Plant ; chemistry ; Blotting, Western ; Calcium-Binding Proteins ; metabolism ; Cells, Cultured ; Connexin 43 ; metabolism ; Coxsackievirus Infections ; drug therapy ; Endoplasmic Reticulum ; metabolism ; Endoplasmic Reticulum Stress ; drug effects ; Flavonoids ; pharmacology ; Heat-Shock Proteins ; metabolism ; Mice ; Myocarditis ; drug therapy ; virology ; Myocardium ; cytology ; Myocytes, Cardiac ; drug effects ; virology ; Rats

Tapentadol is a novel drug of opioid pain reliever, which is extensively metabolized primarily through conjugation. Tapentadol glucuronide and tapentadol sulfate are major drug-related metabolites in circulation. The objectives of this study were to develop a simple and rapid method to determine tapentadol and evaluate the effects of conjugated metabolites on tapentadol quantification using liquid chromatography with tandem mass spectrometry in dog plasma. The analyte and tramadol (IS) were extracted from plasma by protein precipitation with methanol, and chromatographied on a XDB C₁₈ (50 mm×4.6 mm, 1.8 μm) column using a mobile phase of methanol and 5 mmol·L^-1 ammonium acetate (0.01% ammonia). Mass spectrometric detection was performed using the m/z 222→121 transition for tapentadol and the m/z 264→58 transition for the internal standard tramadol, the m/z 398→m/z 121 transition for glucuronides conjugate and the m/z 302→m/z 222 transition for sulfate conjugate. Conjugated metabolites could undergo in-source conversion to generate an ion that interfered the quantification of tapentadol. Chromatographic separation was achieved to elimination interferences due to in-source conversion of the conjugated metabolites. The standard curves were demonstrated to be linear in the range of 0.100 to 20.0 ng·mL^-1 for tapentadol. The intra-and inter-day precisions were within 5.1%, and accuracy ranged from -3.2% to 0. This method was successfully applied to the pharmacokinetics of tapentadol hydrochloride sustained release tablets in Beagle dogs.