Objective In order to investigate the mechanism of the remodeling of pulmonary vascular in hypoxic pulmonary hypertension,normobaric hypoxic rat model (FIO 2=10%)was used to observe the changes of fibronectin(FN)and leminin(LN)within the pulmonary artery by morphological methods. Methods The normobaric hypoxic chamber was used to establish the hypoxic rat model. The lungs were taken off and stained with immunohistochemical method.Some specimens were examined by electromicroscopy. Results Immunohistochemical analysis revealed progressive increase in the deposition of FN and LN,which was most prominent in hypoxia 7d group.The content of FN was higher than LN.Electromicroscope revealed that the SMC of tunia media had transitted from a contractile to a synthetic phenotype. Conclusion Long term hypoxic exposure resulted in increasing of FN and LN in the wall of pulmonary artery.These increase not only raise the tension and make thickening of the vessels themselves,but also provide an environment for the transition of SMC from a contractile to a synthetic phenotype.FN and LN played an important role in the remodeling of pulmonary vascular directly and indirectly. [

AIM: To prepare urokinase-loaded immunoliposomes, with anti-D-dimer mouse monoclonal antibody that can selectively target to thrombotic site and test the thrombolytic effect in the rabbit model of acute pulmonary embolism (PE) in early phase. METHODS: 40 New Zealand white rabbits were randomly divided into five groups: TBS group (TBS buffer, negative control group), urokinase (UK) group (150 000 IU/kg UK, positive control group), Lip group (Lip-UK, containing 50 000 IU/kg UK), Ab group (Ab-Lip-UK, containing 50 000 IU/kg UK) and 2 Ab group (2 Ab-Lip-UK, containing 50 000 IU/kg UK but double DDmAb of Ab group). PE model was established. Five minutes later, five solutions (TBS, UK, Lip-UK, Ab-Lip-UK, 2 Ab-Lip-UK) were transfused through femoral vein respectively. Right ventricular systolic pressure (RVSP) and right ventricular diastolic pressure (RVDP) were estimated within one hour. The pathological changes of lung, heart, liver and kidney were all observed. RESULTS: RVSP in TBS group had no significant changes within one hour after administration. However, RVSP had respective notable decline at 30 min, 40 min, 30 min, 20 min in UK, Lip, Ab and 2 Ab group, respectively. The means of residual emboli were as follows: 4.0±0 in TBS group, 2.4±0.9 in UK group, 3.1±0.6 in Lip group, 2.4±0.9 in Ab group and 1.9±0.6 in 2 Ab group. The lungs in each group showed scattering local congestion, effusion and swelling on the surface. Obvious hemorrhage of heart, kidney and liver was found with HE staining in UK group, no pathologic change was observed in other groups. CONCLUSION: 2 Ab-Lip-UK with early thrombolytic effect and security may be an ideal thrombolytic agent for treating pulmonary embolism.

Objective To investigate the role of spo0A gene in growth and sporulation of Clostridium difficile clinical isolates. Methods ClosTron gene knock-out system was used to knock out the spo0A gene of C. difficile strain C25. Bacterial growth curve was plotted by measuring D600 with spectrophotometer in different phases of bacterial growth. Malachite green staining technique was used to count the number of vegetative cells and spores under optical microscope. The sporulation rate was calculated. Results The spo0A mutant and its C25 parental strain showed similar patterns of growth. However, after knock-out of spo0A gene, an asporogenous phenotype was built, while the parental strain could produce spores as usual.Conclusions The spo0A gene plays a key role in sporulation but not growth of C. difficile strain.

Objective To understand the genotypic characteristics and the neutralizing antibody levels of Japanese encephalitis virus(JEV)and Japanese encephalitis(JE)in both vector mosquitoes and in healthy people of Zhejiang province. Methods Virus was isolated from mosquitos sampled from the Monitoring Stations located in Xianju county during 2012 to 2013. Phylogenetic and homological studies were carried out on the E gene. A total of 1 263 blood specimens from 642 healthy people were collected before and after the seasons of JE epidemics. JEV neutralizing antibody was detected by the micro-neutralization test. Results Twenty-five JEV strains were isolated from a total of 11 650 mosquitoes. The identity of nucleotide appeared as 87.8%-99.7% both from 2012 to 2013 and from 1982 to 2010 while as 87.7%-88.0%with vaccine strain SA14-14-2,in Zhejiang. The phylogeny tree of E gene indicated that the newly isolated virus belonged to genotypeⅠ but no mutation of amino acid sequence coding conformational epitope was identified in the envelop protein. Both positive rates and the geometric mean titer(GMT)of neutralizing antibody in healthy people were 31.5%-42.0%and 1∶2.56-1∶3.53 in Xianju county,during 2012 and 2013,respectively. Both of the two positive rates(χ2≤1.76,P>0.05)and the two GMTs(u≤0.64,P>0.5)for antibodies pre or post the epidemic season did not show significant differences. Conclusion JEV isolated in Xianju during 2012 and 2013 belonged to genotypeⅠ. The positive rates of JEV neutralizing antibody from healthy people in Xianju were less than 42.0%,which showed no significant differendes pre or post JE epidemic season.

Objective To investigate the effect of circ_0114427 on apoptosis and inflammation of alveolar epithelial cells induced by lipopolysaccharide(LPS)and its mechanism.Methods Hu-man alveolar epithelial cells were cultured in vitro and transfected with si-circ_0114427,microRNA(miR)-330-5p mimics or co-transfected with si-circ_0114427 and anti-miR-330-5p,and the cell-swere then treated with 10 mg/L LPS for 24 hours.The expression levels of circ_0114427 and miR-330-5p in the cells were detected using real-time fluorescent quantitative polymerase chain reaction(qRT-PCR).The protein levels of Cleaved-caspase3 and Cleaved-caspase9 were evaluated using western blot.Enzyme-linked immunosorbent assay(ELISA)was used to assess the expression of in-terleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α).Cell apoptosis was analyzed using flow cytometry.The interaction between circ_0114427 and miR-330-5p was validated using a dual lucifer-ase reporter assay.Results After LPS treatment of alveolar epithelial cells,the expression of circ_0114427 was upregulated,while miR-330-5p expression was downregulated in in the cells(P＜0.05).Knockdown of circ_0114427 or upregulation of miR-330-5p could inhibit LPS-induced apop-tosis,Cleaved-caspase3,Cleaved-caspase9,IL-6,and TNF-α levels in alveolar epithelial cells(P＜0.05).Circ_0114427 directly interacted with and negatively regulated miR-330-5p.Downregulation of miR-330-5p reversed the inhibitory effect of circ_0114427 knockdown on LPS-induced cell apoptosis and inflammation.Conclusion Knockdown of circ_0114427 can inhibit LPS-induced apoptosis and inflammation in alveolar epithelial cells,possibly through upregulation of miR-330-5p.

Objective To investigate the effect of circ_0114427 on apoptosis and inflammation of alveolar epithelial cells induced by lipopolysaccharide(LPS)and its mechanism.Methods Hu-man alveolar epithelial cells were cultured in vitro and transfected with si-circ_0114427,microRNA(miR)-330-5p mimics or co-transfected with si-circ_0114427 and anti-miR-330-5p,and the cell-swere then treated with 10 mg/L LPS for 24 hours.The expression levels of circ_0114427 and miR-330-5p in the cells were detected using real-time fluorescent quantitative polymerase chain reaction(qRT-PCR).The protein levels of Cleaved-caspase3 and Cleaved-caspase9 were evaluated using western blot.Enzyme-linked immunosorbent assay(ELISA)was used to assess the expression of in-terleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α).Cell apoptosis was analyzed using flow cytometry.The interaction between circ_0114427 and miR-330-5p was validated using a dual lucifer-ase reporter assay.Results After LPS treatment of alveolar epithelial cells,the expression of circ_0114427 was upregulated,while miR-330-5p expression was downregulated in in the cells(P＜0.05).Knockdown of circ_0114427 or upregulation of miR-330-5p could inhibit LPS-induced apop-tosis,Cleaved-caspase3,Cleaved-caspase9,IL-6,and TNF-α levels in alveolar epithelial cells(P＜0.05).Circ_0114427 directly interacted with and negatively regulated miR-330-5p.Downregulation of miR-330-5p reversed the inhibitory effect of circ_0114427 knockdown on LPS-induced cell apoptosis and inflammation.Conclusion Knockdown of circ_0114427 can inhibit LPS-induced apoptosis and inflammation in alveolar epithelial cells,possibly through upregulation of miR-330-5p.

OBJECTIVETo understand the genotypic characteristics and the neutralizing antibody levels of Japanese encephalitis virus (JEV) and Japanese encephalitis (JE) in both vector mosquitoes and in healthy people of Zhejiang province.

METHODSVirus was isolated from mosquitos sampled from the Monitoring Stations located in Xianju county during 2012 to 2013. Phylogenetic and homological studies were carried out on the E gene. A total of 1 263 blood specimens from 642 healthy people were collected before and after the seasons of JE epidemics. JEV neutralizing antibody was detected by the micro-neutralization test.

RESULTSTwenty-five JEV strains were isolated from a total of 11 650 mosquitoes. The identity of nucleotide appeared as 87.8%-99.7% both from 2012 to 2013 and from 1982 to 2010 while as 87.7%-88.0% with vaccine strain SA14-14-2, in Zhejiang. The phylogeny tree of E gene indicated that the newly isolated virus belonged to genotype I but no mutation of amino acid sequence coding conformational epitope was identified in the envelop protein. Both positive rates and the geometric mean titer (GMT) of neutralizing antibody in healthy people were 31.5%-42.0% and 1 : 2.56-1 : 3.53 in Xianju county, during 2012 and 2013, respectively. Both of the two positive rates (χ(2)≤1.76, P > 0.05) and the two GMTs (u≤0.64, P > 0.5) for antibodies pre or post the epidemic season did not show significant differences.

CONCLUSIONJEV isolated in Xianju during 2012 and 2013 belonged to genotype I. The positive rates of JEV neutralizing antibody from healthy people in Xianju were less than 42.0%, which showed no significant differendes pre or post JE epidemic season.

Amino Acid Sequence ; Animals ; Antibodies, Neutralizing ; blood ; Antibodies, Viral ; blood ; China ; Culicidae ; virology ; Disease Vectors ; Encephalitis Virus, Japanese ; genetics ; immunology ; isolation & purification ; Encephalitis, Japanese ; virology ; Epitopes ; Genotype ; Humans ; Neutralization Tests ; Phylogeny

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Reoperation due to degenerated bioprostheses is an important factor of high-risk thoracic surgeries. In 2020 ACC/AHA guideline, Valve in Valve (ViV) was recommended for high-risk patient instead of surgical mitral valve replacement. This report described a 77-year-old male patient with a failed mitral bioprosthetic valve, evaluated at high risk of surgery, received a transvenous, transseptal transcatheter mitral valve replacement (TMVR). Tracheal intubation was removed at CCU 3 h after surgery without discomfort such as polypnea. The patient was transferred out of the CCU and discharged on the 3rd day. Compared with transapical access, transvenous transseptal access was less invasive, with shorter duration in CCU and hospitalization.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment