OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

The eutR gene deletion mutant of Salmonella enteritidis was successfully constructed by homologous recombination.Through the study of its biochemical characteristics,motility,resist-ance to stress in vitro and survival ability in RAW 264.7 cells,it was found that the biochemical characteristics and motility of the eutR gene deletion mutant of Salmonella enteritidis had no sig-nificant change compared with the wild type of Salmonella enteritidis.The ability of eutR gene de-letion strain of Salmonella enteritidis to resist acid,alkali and oxidation was significantly reduced,while the ability to resist heat was not significantly changed;the survival ability of eutR gene dele-tion strain in RAW 264.7 cells was significantly reduced compared with the wild type.In order to further analyze the effect of eutR gene on the expression of virulence factors of Salmonella enterit-idis,the relative expression levels of invH,ssav,ssrA,xthA,orf245,sodC,lrp,mrr1 and hflk virulence genes of the deletion strain and the wild strain were detected by SYBR Green PCR.It was found that the expression of the virulence factors mentioned above in the eutR gene deletion strain of Salmonella enteritidis was significantly down-regulated compared with that in the wild-type strain.The LD50 of the eutR gene-deleted strain of Salmonella enteritidis was determined by ani-mal experiments,and the results showed that the LD50 of the eutR gene-deleted strain was higher than that of the wild-type strain,indicating that the eutR gene could affect the virulence of Salmonella.This study clarified the effect of eutR gene on the survival ability,some biological characteristics and virulence of Salmonella enteritidis in macrophages,and provided a new gene knockout target for the development of attenuated Salmonella enteritidis genetic engineering vac-cine.

Objective:To explore the clinical characteristics, related factors, and prognostic effect of patients with T cell large granular lymphocytosis following allo-HSCT.Methods:Consecutive patients with T-LGL following allo-HSCT who visited our center from June 2013 to February 2020 were studied retrospectively. We compared patients undergoing allo-HSCT during this period. The clinical characteristics, related factors, cumulative incidence of patients with T-LGL and rates of overall survival (OS) , disease free survival (DFS) , relapse, and non-relapse mortality (NRM) were analyzed.Results:Total 359 patients were enrolled, including 17 with T-LGL and 342 without T-LGL following allo-HSCT. The median follow-up duration was 38 (3-92) month. The cumulative incidence at 1-, 2- and 3-years of T-LGL was 3.64% (95% CI 1.09%-6.19%) , 4.50% (95% CI 1.36%-7.64%) , and 4.84% (95% CI 1.10%-8.76%) , respectively. CMV reactivation ( P=0.013) , EB viremia ( P=0.034) , and aGVHD ( P=0.027) were associated with the development of T-LGL following allo-HSCT. Multivariate analysis showed that benign hematologic diseases[ P=0.027, OR=3.36 (95% CI 1.15-9.89) ] and haploidentical hematopoietic stem cell transplantation[ P=0.030, OR=4.67 (95% CI 1.16-18.75) ], unrelated donor transplantation[ P=0.041, OR=5.49 (95% CI 1.10-28.16) ] were independent predictive factors of T-LGL following allo-HSCT. There was a significant difference in the 3-year OS (100.0% vs. 78.6%, P=0.04) , DFS (100.0% vs. 70.0%, P=0.01) , and NRM (0 vs. 12.6%, P=0.02) between the 2 cohorts. Subgroup analysis showed that malignant diseases recipients who developed T-LGL had better outcomes after allo-HSCT, and there was a significant difference in the NRM ( P=0.042) , DFS ( P=0.013) , and cumulative relapse rate ( P=0.028) between the 2 cohorts. In contrast, the appearance of T-LGL after allo-HSCT in patients with benign diseases had no significant effect on the prognosis. Conclusions:T-LGL was a durable and clinically benign phenomenon occurring in allo-HSCT recipients with malignant diseases. Factors associated with immune reconstitution and T-cell regulatory mechanisms might be major predictors of T-LGL following allo-HSCT.

Objective To explore the effect of iron overload on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patiems with non-hepatitis related severe aplastic anemia (SAA).Methods The clinical data were retrospectively analyzed for 98 patients with non-hepatitis related SAA undergoing allo-HSCT from July 2012 to late July 2018 at a single center.Serum ferritin (SF) was measured within 2 momhs before HSCT.They were divided into iron overload (SF＞800.0 ng/ml,n =49) and control (SF＜800.0 ng/ml,n =49) groups according to SF level.Overall survival (OS),hematopoietic reconstitution and common complications after allo-HSCT were analyzed.Results The median pre-transplantation SF value was 798.7 (52.0-11060.01) ng/ml.Patients with pre-transplantation iron overload had a higher incidence of cytomegaloviremia (P =0.041),delayed recovery of neutrophil/platelet (P =0.001,P =0.005 respectively) and transfusion-dependence in donor-recipient blood group-matched patients (P =0.043) after allo-HSCT.The 3-year OS was (65.1 ± 7.1) ％ in iron overload group and (93.3 ± 3.7) ％ in control group (P =0.001).Multivariate analysis indicated that 3-year OS was independently correlated with pre-transplantation iron overload (P =0.022),blood group of donor & recipient (P =0.015),early bacteremia (P=0.003) and cytomegaloviremia (P =0.003).Conclusions Iron overload is common in patients with non-hepatitis-related SAA before transplantation.Pre-transplantation iron overload has a significant impact on OS,hematopoietic reconstitution and cytomegaloviremia after allo

Objective To explore the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myelomonocytic leukemia (CMML) patients .Methods The clinical data were retrospectively analyzed for 19 CMML patients undergoing allo-HSCT .Engraftment ,graft versus host disease (GVHD ) , infection , relapse , splenomegaly and survival were observed . And the clinical outcomes of allo-HSCT for CMML were analyzed .Results Hematopoiesis reconstitution was not attained in 2 recipients due to early death post-transplantation .Neutrophil engraftment was obtained in 17 recipients with a median time of 14(11-18) days .Neutrophil engraftment and platelet engraftment were achieved in 15 recipients with a median time of platelet engraftment at 15 (12～70) days .Seven patients developed acute GVHD (grade 1 ,n=5;grade 2～4 ,n=3) while another 8 patients had chronic GVHD (extensive ,n=5) . Ten patients (52 .6 ％ )had palpable splenomegaly (SPM ) before allo-HSCT ,8 patients were diagnosed ultrasonically after transplantation ,all 4 patients without a significant reduction of spleen died while all 4 patients with a significant reduction of spleen survived . After a median follow-up period of 31 (6-68 ) months ,3-year overall survival (OS) ,disease-free survival (DFS) ,cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were (58 .2 ± 12 .5)％ ,(36 .3 ± 14)％ ,(39 .9 ± 19)％ and (37 ± 12 .6)％ respectively .Conclusions As an effective therapy for CMML ,allo-HSCT may improve the survival of CMML patients .Palpable SPM pre-transplantation and no significant reduction post-transplantation are probably poor prognostic factor .

Vena cava filter (VCF)has been increasingly applied in clinical to efficiently prevent the pulmonary embolism (PE) with the rapid development of VCF. This article summarized the development of VCF, analyzed the relationship between structure and function, described the clinical behaviour of VCF, and final y forecasted the development trend of VCF products.

ObjectiveTo study the mechanism of myocardial dielectric property changes in radio frequency during hypothermic preservation and explore myocardial viability evaluative method. Methods Hybrid young pigs (20-30 kg) were used in the experiment. Heart arrest was induced with GIK solution. According to preservative temperature, the animals were divided into three groups: group A (4 ℃),group B (15 ℃) and group C (25 C). The heart was preserved in saline for 12,6 and 4 h respectively. Myocardial dielectric properties and ATP content were tested every 5 and 30 min during hypothermic preservation respectively. The relationship between tanoδm and ATP content was analyzed. ResultsTanδm of three groups was decreased significantly at the beginning, most slightly in group A and most obviously in group C. There was no significant difference in Tanδm between group B and group C with group A at 1 h,but there was obvious difference at 2,3 and 4 h (P＜0. 05,P＜0. 05,P＜0. 01 ). There was correlation between tanδm and ATP in the three groups. ConclusionTanδm in three groups is dropped with preservation time and temperature, and tanδm had a correlation with ATP content. Detection of myocardial dielectric property in radio frequency is a kind of quick, accurate and noninvasive method.

To study the chemical constituents of Senecio nemorensis.,12 known compounds were isolated and identified,which were niacinamide(Ⅰ),vanillin(Ⅱ),syringic acid(Ⅲ),syringalddehyde(Ⅳ),3-acetyl-4-hydroxy-benzoic acid(Ⅴ),4,4-dimethyl-1,7-heptanedioic acid(Ⅵ),1H-indole-3-carboxaldehyde(Ⅶ),ethyl caffeate(Ⅷ),1-0-(E)-p-methoxycinnamoyl-β-D-glucopyranoside(Ⅸ),(6S,7E)-6-hydroxy-4,7-megastigmadien-3,9-dione(Ⅹ),Annuionone D(Ⅺ),and(1 'S,6'R)-abscisic acid(Ⅻ),respectively.