Objective:To investigate the safety and efficacy of balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension (PH) of chronic thromboembolic pulmonary hypertension(CTEPH) after pulmonary endarterectomy (PEA).Methods:Patients diagnosed as PH after PEA in China-Japan Friendship Hospital from Oct 2016 to Jun 2022 were included. The indication for BPA was decided on the basis of a consensus of the multi-disciplinary team for all patients with CTEPH. Before treatment, the patient′s exercise tolerance and pulmonary artery flow parameters were evaluated. A comparative analysis of various parameters before BPA treatment and at the last BPA was conducted. 6-min walk distance (6MWD) was analyzed using the paired Wilcoxon test; N-terminal pro-brain natriuretic peptide (NT-proBNP), mixed venous oxygen saturation, mean pulmonary arterial pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were compared using the paired-samples t-test. WHO functional class was compared using McNemar′s test. Results:Twenty patients with a total of 130 vessels underwent 46 sessions of BPA treatment. The postoperative 6-minute walk distance (6MWD) [447 (415, 485) m] showed a significant improvement compared to the preoperative baseline [389 (335, 470) m] ( Z=6.52, P<0.05), Postoperative mixed venous oxygen saturation (72.0%±1.9%) showed a significant improvement compared to the preoperative levels (64.0%±2.7%) ( t=2.14, P<0.05).Postoperatively, plasma NT-proBNP [(351.9±129.9) pg/ml], mPAP [(24.2±1.9) mmHg], and PVR [(3.0±1.4) WU] significantly decreased compared to preoperative levels [(982.5±426.2) pg/ml, (33±2.1) mmHg, (8.0±1.6) WU)] ( t=3.38, 1.22, 2.10, P<0.05 for all). Postoperatively, there was a significant improvement in WHO functional class (Ⅰ，Ⅱ，Ⅲ，Ⅳ: 14, 4, 2, 0 cases) compared to preoperative status (Ⅰ，Ⅱ，Ⅲ，Ⅳ: 0, 13, 5, 2 cases) ( χ2=20.17, P<0.05). Four cases of pulmonary artery dissection and one episode of hemoptysis occurred postoperatively, with no other complications reported. Conclusions:BPA can significantly improve exercise tolerance and hemodynamic parameters for residual PH after PEA. BPA is a relatively safe and effective treatment for residual PH after PEA.

Objective To investigate the role and potential mechanisms of tumor necrosis factor alpha-inducible protein 8-like molecule 1(TNFAIP8L1)in acute liver injury in mice.Methods The second generation of C57BL/6J male wild-type(WT)mice and the C57BL/6J female TNFAIP8L1+/-mice and WT mice were selected to further self-breed the third generation of male TNFAIP8L1-/-mice and the third generation of WT male mice.Five normal third-generation male WT mice and five normal third-generation male TNFAIP8L1-/-mice were selected.The serum alanine aminotransferase(ALT)levels of the two types of normal mice were measured and compared.The infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of normal mice were observed after hematoxylin & eosin(HE)staining.Flow cytometry was used to detect the percentages of neutrophils(Neu),eosinophils(EOS),dendritic cells(DC),bone marrow-derived macrophages(BMDMs),and bone marrow-derived mononuclear cell(BMNCs)in the liver myeloid cell subsets of the two types of normal mice.Another 5 third-generation male WT mice and 4 third-generation male TNFAIP8L1-/-mice were selected to induce acute liver injury mouse models using lipopolysaccharide(LPS)/D-galactosamine(D-Gal).After 24 hours,the serum ALT levels of the two types of acute liver injury mice were detected and compared,the infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of acute liver injury mice were observed,and the percentages of Neu,EOS,DC,BMDMs and BMNCs in the liver myeloid cell subsets of the two types of acute liver injury mice were measured by using the above methods.Results There was no significant difference in the percentages of Neu,EOS,DC,BMDMs and BMNCs,and serum ALT levels in the livermyeloid cell subsets of normal WT mice and TNFAIP8L1-/-mice(P＞0.05).HE staining results of liver tissues in normal WT mice and TNFAIP8L1/mice showed that hepatic lobules were structurally complete and clear,hepatocytes were morphologically normal and arranged neatly,and there was no obvious inflammatory cell infiltration or cell necrosis.Twenty-four hours after acute liver injury,the percentages of Neu and BMNCs in the liver myeloid cell subsets and the serum ALT levels in the liver tissues of TNFAIP8L1-/-mice were significantly higher than those of WT mice(P＜0.05);there was no significant difference in the percentages of EOS,DC and BMDMs in the liver myeloid cell subsets of mice between the two groups(P＞0.05).In the liver tissues of WT mice with acute liver injury,hepatic lobules were structurally blurred,hepatocytes were swollen with scattered vacuolated steatosis,and a small amount of inflammatory cells were infiltrated.In the liver tissues of TNFAIP8L1/mice with acute liver injury,hepatic lobules were structurally non-existent,and hepatocytes were severely damaged and extensively necrotic,with a large amount of inflammatory cell infiltration.Conclusion The deficiency of the TNFAIP8L1 gene in mice does not affect the development of liver myeloid cells and the homeostasis of the liver.TNFAIP8L1 plays an inhibitory role in the occurrence and development of acute liver injury.TNFAIP8L1 gene deficiency aggravates LPS/D-Gal-induced acute liver injury,possibly by increasing Neu and BMNCs infiltration and recruiting other types of immune cells to infiltrate liver tissues,thereby exacerbating liver cell necrosis.

To investigate the effects of on behavior and blood brain barrier (BBB) in Alzheimer's disease mice. Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, low-dose group and high-dose group. Saline, and 12 g·kg·d were given to each group by continuous gavage once a day for respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Compared with model mice, activities of daily live were significantly improved in low-dose and high-dose groups (both <0.01), the fear memory ability was significantly increased in high-dose group (<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly in high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region in low-dose group also decreased (all <0.05). The proportions of CD34 positive area of cortex in low and high dose groups increased, the percentage of fibrinogen positive area decreased (all <0.05). The proportion of CD34 positive area in hippocampal CA1 region in high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both <0.05). especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.
Alzheimer Disease ; Amyloid beta-Protein Precursor ; Animals ; Blood-Brain Barrier/metabolism* ; Disease Models, Animal ; Hippocampus/metabolism* ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic

Objective:To explore the incidence rates, clinical features, risk factors and its impacts on survival of central nervous system complications (CNSC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:From June 2011 to October 2018, 237 consecutive patients undergoing allo-HSCT were retrospectively analyzed.Results:The incidence of CNSC was 10.5%(25/237) and the median time 82(-4 - 810) days post-transplantation. The most common instances of CNSC were drug-associated encephalopathy (n=6), CNS infection (n=5), unexplained convulsions (n=4), metabolic encephalopathy (n=3), immune-related encephalopathy (n=3), primary central relapse (n=3) and cerebrovasculopathy (n=1). The most common clinical symptom was epileptic seizure (n=11). CsA-related encephalopathy was manifested mainly as posterior reversible encephalopathy syndrome on brain MRI. Metabolic encephalopathy is mostly demyelination. Most hippocampal lesions were caused by immune-related encephalopathy or CNS infection. Analysis of risk factors indicated that umbilical cord blood transplantation, HLA incompatible transplantation and delayed platelet implantation were high risk factors for post-transplantation occurrence of CNSC. Survival analysis suggested that non-relapse mortality rate (42.9%, 9/21) in group with CNSC of malignant hemoblastosis was higher than that in group without CNSC (15.3%, 27/176) and inter-group difference was statistically significant ( χ2=9.511, P=0.005). The 1/3-year OS rates in group with CNSC were lower than those in group without CNSC (56.6% vs 77.8%; 37.1% vs 65.7%). And the difference was statistically significant ( P=0.022). Conclusions:With a complex etiology, CNSC is one of serious complications after allo-HSCT and it significantly reduces the overall survival rate of patients. Umbilical cord blood transplantation, HLA incompatible transplantation and delayed platelet implantation are high-risk groups for CNSC.

The transcription factor nuclear factor kappa B (NF-B) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-B remains to be established in the hepatic steatosis. In this study, the subunit of NF-B was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. The activity was supported by the phenotypes of knockout (-KO) mice and knockout (-KO) mice. Hepatic steatosis was reduced in the -KO mice, but not in the -KO mice. The reduction was a result of inhibition of HDAC1 activity in the -KO cells. Knockdown of gene led to suppression of hepatocyte steatosis in HepG2 cells. A decrease in sterol-regulatory element binding protein 1c (SREBP1c) protein was observed in the liver of -KO mice and in cell with knockdown. The decrease was associated with an increase in succinylation of SREBP1c protein. The study suggests that stabilizes HDAC1 to support the SREBP1c activity in hepatic steatosis in the pathophysiological condition. Interruption of this novel pathway in the -KO, but not the -KO mice, may account for the difference in hepatic phenotypes in the two lines of transgenic mice.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Objective To observe the changes of serum sphingosine-1-phosphate (S1P) level in acute attack of adult bronchial asthma (simplified as asthma) and explore its clinical significance in the pathogenesis of the disease.Methods Forty-five patients of outpatient and hospitalized admitted to the Department of Respiratory Medicine in First Affiliated Hospital of Jiamusi University from November 2015 to July 2016 were arranged to an asthma group;in thc samc period,25 healthy peoples in our hospital having passed physical examination were chosen and assigned in a healthy control group.Serum S1P levels were determined by enzyme-linked immunosorbent assay (ELISA) in the subjects,the differences of pulmonary function indexes,the percentage of 1 second forced expiratory volume (FEV1)in predicted FEV1 value,FEV1/forced vital capacity (FVC) ratio were compared between the two groups,and the correlations between FEV1％,FEV1/FVC and S1P level were analyzed by Pearson analysis.Results The level of S1P in serum of asthma group was significantly higher than that of the healthy control group (μmol/L:1.90 ± 0.32 vs.0.89 ± 0.17,P ＜ 0.01),the levels of FEV1％,FEV1/FVC were significantly lower in the asthma group than those in healthy control group [FEV1％:(68.26 ±22.83)％ vs.(97.46 ± 10.44)％,FEV1/FVC:0.69 ±0.13 vs.0.82 ±0.05,both P ＜ 0.01].In the asthma group,the levels of FEV1％,FEV1/FVC were negatively correlated to the serum S1P level (r =-0.801 and -0.648,both P ＜ 0.01).While the levels of FEV1％,FEV1/FVC were not correlated to the serum S1P level in the healthy control group (r =-0.048 and 0.183,P ＞ 0.05).Conclusion The serum S1P is increased significantly in patients with asthma,and it being an important inflammatory mediator may play a crucial role in the pathogenesis of asthma.

Objective To observe the changes of serum sphingosine-1-phosphate (S1P) level in asthmatic patients with different severity of bronchial asthma, and to explore the evaluation value of S1P on the severity of asthma.Methods A prospective observational study was conducted. Fifty-two patients with asthma admitted to Department of Respiratory Medicine of the First Affiliated Hospital of Jiamusi University from November 2015 to January 2017 were enrolled. According to the severity of the disease, the patients were divided into mild, moderate and severe groups. In the same period, 25 healthy subjects were served as healthy control group. All the subjects got the peripheral venous blood collection in the morning fasting, the level of serum S1P was determined by enzyme linked immunosorbent assay (ELISA), the peripheral blood eosinophil (EOS) was counted, and the pulmonary function test was performed. The correlation among the parameters was analyzed by Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted, and the value of serum S1P on evaluating the severity of asthma was analyzed.Results Fifty-two asthma patients were enrolled, including 17 patients of the mild, 19 of the moderate, and 16 of the severe. Compared with the healthy control group, serum S1P level and peripheral blood EOS in different degree asthma groups were significantly increased, and forced expiratory volume in 1 second (FEV1) was decreased significantly; and with asthma exacerbations, serum S1P levels and peripheral blood EOS were gradually increased [mild, moderate and severe S1P (nmol/L) were 1537.0±120.3, 1980.7±149.5, 2202.2±117.2 (F= 274.624, P= 0.001); EOS (×109/L) were 0.13±0.06, 0.20±0.07, 0.37±0.14 , respectively (F= 44.093,P = 0.001)], and FEV1 was decreased gradually [mild, moderate and severe were 0.89±0.05, 0.63±0.06, 0.42±0.10, respectively (F= 159.756,P = 0.001)]. Correlation analysis showed that there were significant positive correlations between serum S1P level and peripheral blood EOS in patients with mild, moderate and severe asthma (r value was 0.696, 0.746,0.508, allP < 0.05), and negatively correlations with FEV1 were found (r value was -0.761, -0.655, -0.815, all P < 0.01). There was no significant correlation between serum S1P level and EOS, FEV1 in healthy control group (r value was 0.324 and -0.048, bothP> 0.05). ROC curve analysis showed that the area under curve (AUC) of serum S1P for assessing mild, moderate and severe asthma was 0.948, 1.000, 1.000, respectively; when the cut-off of S1P was 1181.8, 1534.2, 1708.6 nmol/L, the sensitivity was 88.2%, 100%, 100%, and the specificity was 88.0%, 100% and 100%, respectively.Conclusions During asthma attack, the serum S1P level was gradually increased with the exacerbation of the disease. Serum S1P level has significant evaluative effect on the severity of asthma.

Objective To analyze the correlation factors that promote or impede the residents to preferentially use essential medicines.Methods Adopting stratified random sampling method,1 700 households selected from 5 cities of Shandong province were investigated with a questionnaire.The framework of Andersen behavior model of health service utilization was used as the framework,with such methods as descriptive analysis and univariate logistic regression models for the analysis and evaluation of relevant information.Results The residents′ tendency factor,ability factor and environmental factor influence their preference to use essential medicines,while the requirement factor plays a minimal role.There was a significant difference for the preference of combined medication,first visit preference and self-medication experience,the efficacy and policy response of essential medicine from logistic regression analysis.Conclusion At present,the government should focus on the construction of the formation mechanism of the residents′drug use behavior and the policy response mechanism of essential medicine system.

OBJECTIVETo evaluate the clinical characteristics and prognostic factors of patients with primary gastro-intestinal marginal zone lymphoma (MALT).

METHODSRetrospective analysis was performed in 90 patients diagnosed with primary gastro-intestinal MALT lymphoma clinical characteristics and survival analyses.

RESULTSAmong 90 patients, 78 cases were originated from the stomach and 12 cases with extra-gastric origin. Eighty patients were classified as low-risk (IPI score 0-2), and 10 patients high-risk (IPI score 3-5). Compared to gastric MALT patients, extra-gastric cases presented with higher IPI score (7.7% vs 33.3%, P=0.025) and higher Hp infection rate (50.0% vs 87.2%, P<0.01). Treatment options for low risk patients (IPI score 0-2) included Hp eradication, surgery, radiotherapy and chemotherapy. Chemotherapy could improve progression-free survival (PFS) in low-risk patients. For high-risk patients, those receiving chemotherapy had 100% 3-year overall survival (OS). Univariate analysis revealed that ECOG (P=0.006), Mussh-off staging (P=0.008), IPI score (P=0.000), elevated LDH (P=0.019) and chemotherapy (P=0.026) were correlated with PFS. Multivariate analysis showed that higher IPI score (IPI 3-5) (OR=8.325, 95% CI 3.171-21.853, P=0.000) and chemotherapy (OR=0.319, 95% CI 0.121-0.838, P=0.020) were independent prognostic factors for PFS. ECOG (≥ 2) was independent prognostic factor for OS (OR=5.092, 95%CI 1.005-25.788, P=0.049).

CONCLUSIONPrimary gastro-intestinal MALT lymphoma was an indolent subtype of non-Hodgkin's lymphoma. Patients usually had low risk IPI and achieved long-term survival. Frontline therapy for low-risk patients was radiotherapy or Hp eradication, and chemotherapy for high-risk ones.