Objective To establish a personalized Stanford type B aortic dissection numerical simulation model, and using computational fluid dynamics (CFD) numerical simulation to obtain the hemodynamic behavior and law of the type B aortic dissection at different stages of development. Methods Based on the theory of three-dimensional model reconstruction, we used CT images of a patient with type B aortic dissection in the Xiamen Cardiovascular Hospital of Xiamen University, relevant medical image processing software to reconstruct a personalized aortic three-dimensional model, and CFD to reconstruct the model which was simulated in fluid mechanics. Results The three-dimensional reconstruction model could intuitively observe the changing trend of the false cavity at different stages of the dissection development. Through fluid mechanics simulation, the blood flow rate, pressure, wall shear stress, vascular wall Von Mises stress and other parameters at different stages of the dissection development were obtained. Conclusion The hemodynamic behavior and law of relevant parameters in the development stage of aortic dissection are analyzed. The combination of the values of relevant parameters and clinical medical detection and diagnosis can well predict the development of the disease, and finally provide more theories and methods for the scientific diagnosis of aortic dissection.

The pathological classification and diagnostic criteria for lung neuroendocrine neoplasms (NENs) in the 2021 World Health Organization (WHO) lung tumor classification are similar to the prior classifications. However, the advances on the molecular studies of lung NENs have shown that both small cell lung carcinoma and large cell neuroendocrine carcinoma are highly heterogeneous tumors with neuroendocrine characteristics and can be subclassified based on the features of genomics or transcriptomics, which are valuable in the diagnosis of lung NENs subtypes and patient treatment. In addition, it is necessary to interpret emerging concepts such as "lung neuroendocrine tumor G3" and "histological transformation" from pathological perspectives, as well as to know the novel neuroendocrine biomarkers such as INSM1 and POU2F3. This article summarized the diagnostic changes and the advances of molecular pathology of lung NENs based on the latest WHO classification and molecular research.

BACKGROUND: The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer. METHODS: One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared. RESULTS: The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type. CONCLUSIONS The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.
B7-H1 Antigen/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms/drug therapy* ; Male

As a typical food safety industrial model strain, Bacillus subtilis has been widely used in the field of metabolic engineering due to its non-pathogenicity, strong ability of extracellular protein secretion and no obvious codon preference. In recent years, with the rapid development of molecular biology and genetic engineering technology, a variety of research strategies and tools have been used to construct B. subtilis chassis cells for efficient synthesis of biological products. This review introduces the research progress of B. subtilis from the aspects of promoter engineering, gene editing, genetic circuit, cofactor engineering and pathway enzyme assembly. Then, we also summarized the application of B. subtilis in the production of biological products. Finally, the future research directions of B. subtilis are prospected.
Bacillus subtilis/genetics* ; Bacterial Proteins/genetics* ; Gene Editing ; Metabolic Engineering ; Promoter Regions, Genetic

Objective:To explore the clinical prognosis of early endarteritis (within 2 weeks) and late endarteritis (after 2 weeks) after renal transplantation.Methods:A total of 81 cases with higher creatinineand receiving renal biopsy after renal transplantation were recruited from September 2001 to December 2014. They were divided into early endarteritis group (n=43) and late endarteritis group (n=38). Baseline profiles, serum creatine, glomerular filtration rate (GFR) before and after treatment, steroid resistance, reversal rate, graft loss and survival rate were analyzed for two groups.Results:Early endarteritis group showed worse serum creatine and GFR than late endarteritis group before rejection. Early endarteritis group had a higher rate of treatment with steroid plus antibody (86 %) than that of late endarteritis group (86 %vs.18.6 %, P<0.05). No significant inter-group difference existed in graft loss (23.3 % vs.10.5 %, P=0.131). The survival curve of transplanted kidney showed no significant inter-group difference insurvival time. Conclusions:The status of patients with early simple endothelitis is significantly worse than that of those with late simple endothelitis. However, after active treatments, the prognosis of patients with early simple endothelitis is not inferior to that of those with late simple endothelitis.

Objective:To analyze the early mortality and related risk factors of new hemodialysis patients in Zhejiang province, and provide basis for reducing the death risk of hemodialysis patients.Methods:The early mortality and related factors of new hemodialysis patients from January 1, 2010 to June 30, 2018 were retrospectively analyzed using the database of Zhejiang province hemodialysis registration. The early mortality was defined as death within 90 days of dialysis. Cox regression model was used to analyze the related risk factors of the early mortality in hemodialysis patients.Results:The mortality was the highest in the first month after dialysis (46.40/100 person year), and gradually stabilized after three months. The early mortality was 25.33/100 person year. The mortality within 120 days and 360 days were 21.40/100 person year and 11.37/100 person year, respectively. The elderly (≥65 years old, HR=1.981, 95% CI 1.319-2.977, P<0.001), primary tumor ( HR=3.308, 95% CI 1.137-5.624, P=0.028), combined with tumors (not including the primary tumor, HR=2.327, 95% CI 1.200-4.513, P=0.012), temporary catheter (the initial dialysis pathway, HR=3.632, 95% CI 1.806-7.307, P<0.001), lower albumin (<30 g/L, HR=2.181, 95% CI 1.459-3.260, P<0.001), lower hemoglobin (every 0.01 g/L increase, HR=0.861, 95% CI 0.793-0.935, P=0.001), lower high density lipoprotein (<0.7 mmol/L, HR=1.796, 95% CI 1.068-3.019, P=0.027) and higher C reactive protein (≥40 mg/L, HR=1.889, 95% CI 1.185-3.012, P=0.008) were the risk factors of early death for hemodialysis patients. Conclusions:The early mortality of hemodialysis patients is high after dialysis, and gradually stable after 3 months. The elderly, primary tumor, combined with tumors, the initial dialysis pathway, lower albumin, lower hemoglobin, lower high density lipoprotein and higher C reactive protein are the risk factors of early death for hemodialysis patients.

Objective To study the expression level of cathepsin S in elderly patients with different degree of coronary heart disease(CHD),and to evaluate the correlation between cathepsin S level and the severity of CHD.Methods A total of 126 elderly patients with CHD were enrolled,including 36 cases with acute myocardial infarction(group AMI),48 cases with unstable angina(group UAP),and 42 cases with stable angina(group SAP).During the same period,40 healthy subjects were selected as controls.Venous blood was collected immediately after admission.Arterial blood was taken through radial/femoral artery sheath in AMI patients who underwent primary percutaneous coronary intervention,and coronary arterial blood was taken in AMI patients undergoing intracoronary thrombus aspiration.SYNTAX score was assessed in patients undergoing coronary angiography.Serum levels of high sensitivity C reactive protein(hs-CRP),matrix metalloproteinase-9 (MMP-9) and cathepsin S were determined in all specimens and compared between groups.Results Serum levels of cathepsin S,MMP-9 and hs-CRP were higher in CHD patients than in the control group(P＜0.05).Among CHD patients,group AMI had the highest serum levels of cathepsin S,MMP-9 and hs-CRP,followed by group UAP and group SAP(F =106.830,197.035 and 310.442,all P =0.000).Spearman's rank correlation test suggested that cathepsin S level was positively correlated with serum levels of MMP-9 (r=0.816,P =0.000)and hs-CRP(r =0.827,P =0.000).SYNTAX score was positively correlated with serum levels of cathepsin S(r=0.581,P=0.000),MMP-9(r=0.511,P=0.000),and hs-CRP (r=0.557,P =0.000).Among the 24 patients with AMI who underwent intracoronary thrombus aspiration,the levels of cathepsin S,MMP-9 and hs-CRP were higher in coronary artery blood than in peripheral artery blood (t =217.288,3.177 and 681.479,all P =0.000).Cathepsin S and hs-CRP levels in peripheral arterial blood had positive correlations with those in coronary arterial blood respectively(r =0.962 and 0.494,P =0.000 and 0.014),but such correlation between in peripheral arterial blood versus in coronary artery blood was not found in MMP-9 levels (r =-0.188,P =0.380).Conclusions Serum cathepsin S level is higher in elderly CHD patients than in healthy people,increases along with the increased severity of CHD,and positively correlates with the degree of coronary stenosis.

Objective To evaluate the effects of baseline and changes of peritoneal transport characteristics on the prognosis of maintaining peritoneal dialysis (PD) patients.Methods Five hundred and eight-six PD patients who started PD from September 11,2006 to October 30,2014 in a single center were included and followed up until March 30,2016.According to their baseline D/Pcr value in peritoneal equilibrium test (PET),the patients were divided into high transport (H) group (D/ Pcr 0.82-1.03),high average transport (HA) group (D/Pcr 0.65-0.81),low average transport (LA) group (D/Pcr 0.50-0.64) and low transport (L) group (D/Pcr 0.34-0.49).According to the changes of follow-up D/Pcr comparing with baseline D/Pcr,the patients were also divided into ascending group,descending group and no-change group.The patient and technical survival rates were estimated by Kaplan-Meier analysis.Cox proportional hazards analyses were used to analyze the risk factors for PD patient death and technical failure.Results There were 67 patients in L group,229 patients in LA group,252 patients in HA group,and 38 patients in H group.The patient survival rate in H group was significantly lower than those of L group (P=0.036),LA group (P=0.008) and HA group (P=0.041).There was no significant difference on technical survival rate among these 4 groups.According to the tendency of follow-up D/Pcr changes,there were 127 patients in ascending group,101 patients in descending group and 179 patients in no-change group.There was no significant difference on patient survival among these 3 groups (P=0.064).However in patients with a high transport rate (D/Pcr≥0.65),the patient survival was lower in descending group than those in ascending group (P=0.033) and nochange group (P=0.049).Age over 65 years old (HR=2.499),malnutrition during follow-up (HR=3.144),ultrafiltration less than 400 ml/d during follow-up (HR=1.863) and high sensitive C reactive protein≥ 10 mg/L (HR=4.526) were the independent risk factors for patient death (all P ＜ 0.05).Gender (HR=1.609),age over 65 years old (HR=1.929),ultrafiltration less than 400 ml/d during follow-up (HR=1.708),high sensitive C reactive protein ≥10 mg/L (HR=1.829),malnutrition (HR=1.876) and change of peritoneal transport function (HR=0.579) affect technical failure (all P ＜ 0.05).Conclusions The survival rate of PD patients with basal high peritoneal transit is relatively low,especially for patients with descending transport rate during follow-up.The concern on the peritoneal transport status is constructive for the prognosis of PD patients.

Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24％ vs.23.08％).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07％ vs.21.37％).There was no significant difference in the incidence of DGF between SD group and MD group (12.07％ vs.6.84％,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55％ vs.98.29％,P =0.6714;94.83％ vs 98.29％,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.

Objective To analyze the prognosis and risk factors for antineutrophil cytoplasmic antibody?associated vasculitis (AAV) patients on maintaining dialysis. Methods AAV patients on maintaining peritoneal dialysis (PD) or hemodialysis (HD) in First Affiliated Hospital Zhejiang University from June 2007 to June 2015 were included, and were followed up until death, kidney transplant, changed dialysis modalities or January 31, 2016. Patients were divided into PD group and HD group for comparison. Their survival rates and risk factors were analyzed by Kaplan?Meier analysis and COX regression model respectively. Results A total of 123 cases were chosen, with a median duration of dialysis for 854 (388, 1573) days, and with 88 cases (71.5%) on HD and 35 cases (28.5%) on PD. Fifty?two patients (42.3%) were more than 65 years old. At the median follow?up time of 36 months, 39 patients (31.7%) died. The main causes of death were cardiovascular events (30.8%) and infection (23.1%). COX regression analysis showed that patients older than 65 years old (HR=3.289, P=0.001), with cardiovascular disease (HR=3.241, P=0.003) and interstitial pneumonia (HR=2.173, P=0.048) at the dialysis onset were independent risk factors affecting survival. Conclusions Factors including age (older than 65 years), pre?dialysis cardiovascular disease and interstitial pneumonia were independent risk factors affecting survival of AAV patients on maintaining dialysis, then infections and cardiovascular events were the main causes of death.