Objective To study the expression of programmed death 1(PD-1) on the peripheral T lymphocytes and the serum cytokine levels in different phases of hepatitis B virus (HBV) infection (immune tolerance,immune clearance and non-replicating phases).Methods A total of 105 HBV infected patients in different phases of infection were enrolled in Wuxi No.5 People's Hospital from Apr to Sep 2011,and divided into three groups:the immune tolerance group (35 cases),the immune clearance group (35 cases) and the non-replicating group (35 cases).Meanwhile,20 healthy people were enrolled as controls.The peripheral blood was collected and PD-1 expressions on the surface of T lymphocytes were assessed by flow cytometry.The cytokine levels in different groups were analyzed by enzyme-linked immunosorbent assay (ELISA).The data were analyzed by t test and Pearson correlation analysis.Results The PD-1 expression on surface of CD8+ T lymphocytes of HBV infected patients was (12.35± 3.48)％,which was significantly higher than healthy control group [(4.65±1.21) ％] (t=9.76,P＜0.01).The PD-1 expression on CD4+ T lymphocytes was (4.95±2.87) ％,which was not significantly different from the healthy controls [(4.08±2.14) ％] (t =1.29,P＞0.05).The PD-1 expressions on CD8+ T lymphocytes of patients in the immune tolerance group,the immune clearance group and the non-replicating group were (15.87±3.18)％,(7.69±3.64)％and (10.12±2.84) ％,respectively; that in the immune tolerance group was higher than the immune clearance group (t=10.01,P＜0.01) and that in healthy control group was lower than those in the other 3 groups (t=15.12,3.61 and 8.17,respectively; all P＜0.01).The PD-1 expression on the surface of CD8+ T lymphocytes in chronic HBV infected patients was positively correlated with the serum interleukin-10 (IL-10) level (γ=0.377,P＜0.05),while that was negatively correlated with interferon-γ (IFN-γ) level (r=-0.620,P＜0.05).Conclusions PD-1 is up-regulated on the surface of CD8+ T lymphocytes from chronic HBV infected patients.And PD-1 is negatively correlated with serum IFN-γ levels and positively correlated with serum IL-10 levels.The expression of PD-1 on the surface of CD8+ T lymphocytes influences the balance of helper T cell (Th)1/Th2,which might play a role in the persistence of HBV infection.

Objective To investigate the early diagnostic and prognostic value of plasma D-dimer level in acute aortic dissection.Method Data of totally 500 acute chest pain patients were studied,in which 250 cases were in group of acute aortic dissection (group AAD) confirmed by aortic computerized tomographic angiography (CTA) or cardiac ultrasonography,and the rest 250 cases were in non AAD group (group control).The D-dimer test was performed in all patients within 72 hours after onset of chest pain,and comparison of plasma D-dimer concentration was carried out between two groups.The D-dimer diagnostic value in AAD was analyzed by plotting the receiver operating characteristic (ROC) curve.According to AAD patients with aortic CTA findings,the whole aortic artery was divided into four segments by the major vascular branches,and the false lumen area was measured by degree score,the relationship between the score and D-dimer level were analyzed.To study the prognostic value of D-dimer in AAD,the comparison of D-dimer level was carried out between survival group and death group,and the AAD patients were further stratified by the surgery and Stanford type.Results The plasma D-dimer concentrations in AAD group were significantly higher than those in controls (P ＜0.01).The sensitivity,specificity,positive predictive value and negative predictive value of D-dimer (＞ 1.14 mg/L) in the diagnosis of AAD were 81.2％,79.39％,74.63％ and 72.4％ respectively,and the area under the ROC curve was 0.083.The elevated level of D-dimer was positively correlated with the extent of AAD false lumen (Spearman-Rho =0.418,P ＜ 0.01).D-dimer levels in the death group were higher than those in the survival group.Conclusions D-dimer may be a valuable biomarker in early diagnosis of AAD.The elevated level of D-dimer was useful to evaluate the extent of the dissection and prognosis of AAD.

Objective To investigate the molecular background of the New Delhi-metallo-1 (NDM-1)-producing Morganella morganii.Methods Two carbapenem-resistant M.morganii named 1 and 2 were isolated in the Second Hospital of Jiaxing,Zhejiang on October 4th and 29th,respectively.Antimicrobial susceptibility was determined by agar dilution method.Pulsed-field gel electrophoresis (PFGE) was performed to analyse the homololgy of isolates.Amplification with specific primers,DNA sequencing,conjugation experiments and genetic environment analysis were conducted to investigate the molecular mechanisms of resistance.Results The two M.morganii isolates were resistant to carbapenem and fluoroquinolones,while susceptible to aztreonam.PFGE analysis indicated that the two isolates were distinguishable.Amplification and DNA sequencing confirmed the coexistence of blaNDM-1,blasHv-12,qnrS1 and aac(6')-Ib-cr in both isolates.Transconjugants were detected with blaNDM.1 and qnrS1 simultaneously.Genetic environment analysis demonstrated that the blaNDM-1-bleMBL-trpF-dsbC-cutA1 structure was in consistence with those from known blaNDM-1-carrying Klebsiella pneumoniae.Conclusion The blaNDM-1 in M.morganii isolates possiblely obtained from K.pneumoniae through translatable plasmids.

Objective To investigate the early diagnostic value of plasma D-dimer level in acute aortic dissection (AAD) . Method A total of 80 patients with chest pain were enrolled from January 2006 to March 2009, and 40 patients of them were confirmed to be AAD with computerized tomographic angiography (CTA), and these patients were matched with 40 controls presenting suspected dissection, which were ruled out later. The D-dimer test was performed in all patients within 12 hours after onset of chest pain,and plasma D-dimer concentrations were compared between two groups. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of D-dimer used for diagnosing AAD were analyzed. The receiver operating characteristic (ROC) curve was also established. The statistical analysis of data was carried out by using Mann-Whitney test with SPSS 11.5 software. Results The plasma D-dimer oncentrations in AAD were significantly higher than those in controls [(5.48±7.95) vs. (0.64±0.75), P <0.0l]. Receiver operating characteristic curve analysis showed that D-dimer ( > 0.5 μg/mL) was predictive in the diagnosis of AAD, and the area under ROC curve was 0.848 ± 0.042, (95% CI: 0.766-0.930) with 87.5% sensitivity, 62.5% specificity,70% PPV and 83.3% NPV. Conclu-sions D-dimer may be a valuable biomarker in early diagnosis of AAD.

Objective: To investigate the value of bedside echocardiography in diagnosis and risk assessment of in-hospital death of patients with Stanford type A aortic dissection. Methods: The clinical data of 229 patients with Stanford type A aortic dissection diagnosed by CT angiography in Zhongshan Hospital affiliated to Fudan University between January 2009 and January 2016 were retrospectively analyzed. The patients were divided into survival group(191 cases)and non-survival group(38 cases)according to presence or absence of in-hospital death. The bedside echocardiography features were analyzed, and influence factors of in-hospital death were determined by multivariate logistic regression analysis. Results: (1) Compared with the survival group, the non-survival group had lower surgery rate (60.52%(23/38) vs. 85.34%(163/191), P<0.01). Age, gender and Debakey classification were similar between survival group and death group (all P>0.05). (2) The bedside echocardiography results showed that prevalence of aortic valve involvement(65.79%(25/38) vs.34.03%(65/191), P<0.01) and severe aortic regurgitation (44.74%(17/38) vs. 14.14%(27/191), P<0.01) were significantly higher in non-survival group than in survival group. The non-survival group had larger aortic root diameter than the survival group ((55.5±6.4)mm vs. (42.3±7.8)mm, P<0.01). There were no significant differences in pericardial effusion, expansion of aortic sinus, and left ventricular ejection fraction between survival group and non-survival group (all P>0.05). (3) The multivariate logistic regression analysis showed that aortic valve involvement(OR=3.275, 95%CI 1.290-8.313, P<0.05), aortic root diameter(OR=1.202, 95%CI 1.134-1.275, P<0.01), and surgery (OR=0.224, 95%CI 0.079-0.629, P<0.01) were independent risk factors for in-hospital death in patients with Stanford type A aortic dissection. Conclusions Bedside echocardiography has significant diagnostic value for Stanford type A aortic dissection. Aortic valve involvement, enlargement of aortic root diameter and without surgery are independent risk factors for patients with Stanford type A aortic dissection.

Objective:To analyze the prognostic risk factors of patients with sepsis and the clinical characteristics of patients with septic myocardial injury.Methods:A retrospective study was conducted. The clinical data of 300 patients with sepsis admitted to emergency department of Zhongshan Hospital of Fudan University from September 2017 to June 2020 were enrolled, including basic information, blood test indicators and auxiliary inspection indicators. The patients were grouped according to myocardial injury and the clinical characteristics of patients with septic myocardial injury were analyzed. According to 28-day prognosis, they were divided into survival group and non-survival group. The differences in various indicators between the two groups were compared, and binary Logistic regression was used to explore independent risk factors for death in patients with sepsis.Results:In 300 patients, 47 patients were excluded for previous heart disease or lack of the main inspections, and 253 patients were enrolled finally. ① Myocardial injury occurred in 136 out of 253 patients (53.8%), and 117 without myocardial injury. Compared with the non-myocardial injury group, the myocardial injury group had higher blood white blood cell count [WBC (×10 9/L): 9.7 (6.7, 13.4) vs. 8.3 (5.4, 12.2)] and procalcitonin [PCT (μg/L): 0.61 (0.18, 4.63) vs. 0.23 (0.09, 0.99)] at admission, and more Staphylococcal infections (17.6% vs. 2.6%), more arrhythmia (sinus tachycardia: 30.9% vs. 23.1%), more ST-T changes (26.5% vs. 23.1%), lower left ventricular ejection fraction [LVEF: 0.60 (0.54, 0.65) vs. 0.62 (0.60, 0.66)], higher pulmonary artery systolic pressure [PASP (mmHg, 1 mmHg = 0.133 kPa): 38.0 (32.2, 46.0) vs. 33.0 (30.0, 40.2)], and worse prognosis (28-day mortality: 44.1% vs. 6.0%, all P < 0.05). Logistic regression analysis showed that PCT increased [odds ratio ( OR) = 1.039, 95% confidence interval (95% CI) was 1.018-1.060, P < 0.01], LVEF decreased ( OR = 0.828, 95% CI was 0.729-0.941, P < 0.01) and sinus tachycardia ( OR = 3.512, 95% CI was 1.417-8.702, P < 0.01) were clinical characteristics of septic patients with myocardial injury. ② A total of 186 of the 253 patients survived, and 67 died with 28-day mortality of 26.5%. Compared with the survival group, non-survival group had higher myocardial markers and inflammation markers at admission [cardiac troponin T (cTnT, μg/L): 0.06 (0.02, 0.17) vs. 0.02 (0.01, 0.05), N-terminal pro-brain natriuretic peptide (NT-proBNP, ng/L): 3 037.0 (1 308.7, 12 033.7) vs. 893.9 (272.8, 2 825.5), creatine kinase (CK, U/L): 144.5 (57.5, 660.8) vs. 89.5 (47.8, 201.0), WBC (×10 9/L): 10.5 (6.7, 14.6) vs. 8.6 (6.0, 12.0), C-reactive protein (CRP, mg/L): 89.2 (54.8, 128.5) vs. 63.8 (19.3, 105.6), PCT (μg/L): 2.13 (0.31, 11.79) vs. 0.28 (0.10, 1.25), all P < 0.05], and more sinus tachycardia and atrial arrhythmia (41.8% vs. 22.0%, 29.9% vs. 17.7%, both P < 0.05). Logistic regression analysis showed that cTnT increased ( OR = 2.115, 95% CI was 1.189-5.459, P < 0.05), sinus tachycardia ( OR = 2.557, 95% CI was 1.103-5.929, P < 0.05) and atrial arrhythmia ( OR = 2.474, 95% CI was 1.025-5.969, P < 0.05) were independent risk factors for 28-day death in patients with sepsis. Conclusions:Myocardial injury is an independent risk factor for death in patients with sepsis. PCT elevation, LVEF decreased and sinus tachycardia are main characteristics of patients with septic myocardial injury, which should attract clinical attention.

Objective:To explore the risk stratification value of HEART score combined with cardiac troponin (cTn) in emergency patients with chest pain.Methods:A total of 11 583 patients with chest pain who visited the Emergency Department of Zhongshan Hospital Affiliated to Fudan University from January to December 2019 were retrospectively collected. Patients who unfinished 0 h high-sensitivity cardiac troponin T (hs-cTnT) or electrocardiogram diagnosed ST-segment elevation myocardial infarction (STEMI) or lost to follow-up were excluded, and 7 057 patients were finally included. The final diagnosis of chest pain and the occurrence of major adverse cardiovascular events within 6 mon (6 m MACEs) were followed up by telephone and medical history. The HEART score of each patient was calculated by two attending physicians, and the patients were divided into the low-risk group (0-3 points), intermediate-risk group (4-6 points) and high-risk group (7-10 points) according to the final score. The risk stratification performance and safety of HEART score were observed and analyzed. A total of 1 884 patients who completed serial hs-cTnT tests were divided into groups according to HEART score (≤3 as low-risk group) and HEART score combined with serial hs-cTnT pathway (HEART score ≤3 and two hs-cTnT measurements <0.03 ng/mL as the low-risk group). The sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of each diagnostic method were calculated to compare the diagnostic performance of the two predictive values.Results:The patients were divided into 3 groups by HEART score : 2 765 (39.2%) patients in the low-risk group, 3 438 (48.7%) in the intermediate-risk group, and 854 (12.1%) in the high-risk group. The incidence of 6 m MACEs in each group was 1.2%, 18% and 55.3%, respectively. When the low-risk threshold was 2, 23.1% of patients entered the low-risk group and the incidence of 6 m MACEs was 0.9%. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive performance of the HEART score for 6 m MACEs, and the final AUC was 0.831 ( P=0.006, 95% CI: 0.819-0.843). Regarding the occurrence of NSTEMI at the time of this visit, 4 (0.8%) patients were misdiagnosed by using the HEART score alone. Combined with serial troponin detection, the diagnostic SE and NPV were both 100%; at the same time, the diagnostic SE and NPV of 6 m MACEs in patients increased from 98.1% (95% CI: 96.9%-99.1%), 97.9% (95% CI: 96.2%-99%) to 99.1% (95% CI: 97.9%-99.7%) and 98.9% (95% CI: 97.4%-99.6%), the diagnosis SE and NPV of 6 m myocardial infarction and cardiac death in patients increased from 98% (95% CI: 96%-99.2%), 98.6% (95% CI: 97%-99.4%) to 99.2% (95% CI: 97.6%-99.8%) and 99.3% (95% CI: 98.1%-99.9%). Conclusions:The HEART score can be used for risk assessment in emergency patients with chest pain, and a threshold of 2 is recommended for the low-risk group. The diagnostic performance of HEART score combined with serial cTn is better than that of HEART score alone.

Objective:To investigate the clinical characteristics of patients with acute aortic dissection (AAD) through a retrospective and observational study, and to construct an early warning model of AAD that could be used in the emergency room.Methods:The data of 11 583 patients in the Emergency Chest Pain Center from January to December 2019 were retrospectively collected from the Chest Pain Database of Zhongshan Hospital Affiliated to Fudan University. Inclusion criteria: patients with chest pain who attended the Emergency Chest Pain Center between January and December 2019. Exclusion criteria were 1) younger than 18 years, 2) no chest/back pain, 3) patients with incomplete clinical information, and 4) patients with a previous definite diagnosis of aortic dissection who had or had not undergone surgery. The clinical data of 9668 patients with acute chest/back pain were finally collected, excluding 53 patients with previous definite diagnosis of AAD and/or without surgical aortic dissection. A total of 9 615 patients were enrolled as the modeling cohort for early diagnosis of AAD. The patients were divided into the AAD group and non-AAD group according to whether AAD was diagnosed. Risk factors were screened by univariate and multivariate logistic regression, the best fitting model was selected for inclusion in the study, and the early warning model was constructed and visualized based on the nomogram function in R software. The model performance was evaluated by accuracy, specificity, sensitivity, positive likelihood ratio and negative likelihood ratio. The model was validated by a validation cohort of 4808 patients who met the inclusion/exclusion criteria from January 2020 to June 2020 in the Emergency Chest Pain Center of the hospital. The effect of early diagnosis and early warning model was evaluated by calibration curve.Results:After multivariate analysis, the risk factors for AAD were male sex ( OR=0.241, P<0.001), cutting/tear-like pain ( OR=38.309, P<0.001), hypertension ( OR=1.943, P=0.007), high-risk medical history ( OR=12.773, P<0.001), high-risk signs ( OR=7.383, P=0.007), and the first D-dimer value ( OR=1.165, P<0.001), Protective factors include diabetes( OR=0.329, P=0.027) and coronary heart disease ( OR=0.121, P<0.001). The area under the ROC curve (AUC) of the early diagnosis and warning model constructed by combining the risk factors was 0.939(95 CI:0.909-0.969). Preliminary validation results showed that the AUC of the early diagnosis and warning model was 0.910(95 CI:0.870-0.949). Conclusions:Sex, cutting/tear-like pain, hypertension, high-risk medical history, high-risk signs, and first D-dimer value are independent risk factors for early diagnosis of AAD. The model constructed by these risk factors has a good effect on the early diagnosis and warning of AAD, which is helpful for the early clinical identification of AAD patients.

Objective: To explore the imaging manifestations of multi-slice spiral CT angiography (CTA) and relationship with in-hospital death in patients with aortic dissection (AD). Methods: The clinical data of 429 patients with AD who underwent CTA in Zhongshan Hospital of Fudan University between January 2009 and January 2016 were retrospectively analyzed. AD patients were divided into 2 groups, including operation group who underwent surgery or interventional therapy (370 cases) and non-operation group who underwent medical conservative treatment(59 cases). The multi-slice spiral CTA imaging features of AD were analyzed, and multivariate logistic regression analysis was used to investigate the relationship between imaging manifestations and in-hospital death in AD patients. Results: There were 12 cases (3.24%) of in-hospital death in operation group, and 28 cases (47.46%) of in-hospital death in non-operation group(P<0.001). AD involved different vascular branches. Multi-slice spiral CTA can clearly show the dissection of true and false lumen, and intimal tear was detected in 363 (84.62%) cases, outer wall calcification was revealed in 63 (14.69%) cases, and thrombus formation was present in 227 (52.91%) cases. The multivariate logistic regression analysis showed that the number of branch vessels involved (OR=1.374, 95%CI 1.081-1.745, P=0.009) and tearing false lumen range(OR=2.059, 95%CI 1.252-3.385, P=0.004) were independent risk factors of in-hospital death in AD patients, and the number of branch vessels involved (OR=1.600, 95%CI 1.062-2.411, P=0.025) was independent risk factor of in-hospital death in the operation group, while the tearing false lumen range (OR=2.315, 95%CI 1.019-5.262, P=0.045) was independent risk factor of in-hospital death of non-operation group. Conclusions Multi-slice spiral CTA can clearly show the entire AD, true and false lumen, intimal tear, wall calcification and thrombosis of AD patients. The number of branch vessels involved and tearing false lumen range are the independent risk factors of in-hospital death in AD patients.

Objective:To analyze the clinical features of patients with pyogenic liver abscess (PLA) and the application of mNGS in PLA, thus to provide reference for clinical diagnosis and treatment.Methods:The demographic and clinical data of 549 patients with liver abscess admitted to Zhongshan Hospital Affiliated to Fudan University from December 2015 to June 2020 were analyzed retrospectively. According to the detection of Klebsiella pneumoniae in 246 patients with positive etiological test results, the patients were divided into two groups: KPLA group and nKPLA group, and clinical characteristics of the two groups were compared. At the same time, the application value of mNGS in PLA was analyzed.Results:Among the 549 patients, the main clinical symptom of PLA was fever ( n= 503, 91.6%) and other clinical symptoms included chills and abdominal pain. Most patients had a single abscess ( n= 464, 84.5%) located in the right lobe ( n = 368, 67.0%), with a size between 5 and 10 cm ( n= 341, 62.1%). A total of 246 patients had positive etiological test results, including 202 KPLA patients which was the main pathogen of liver abscess. The prevalence of diabetes and fatty liver was higher in KPLA patients ( P < 0.05), but there were more culture of liver positive factors in nKPLA patients ( P < 0.001). Among the 109 patients with traditional microbiological results, 92 patients were suspected to KPLA (Klebsiella pneumoniae), of which 14 patients (15.2%) were multidrug resistant (MDR) infection; 17 patients were suspected to nKPLA, of which 10 patients (58.8%) were MDR infection; the incidence of MDR infection in patients with nKPLA was significantly higher than that in patients with KPLA ( P < 0.05). The positive rate of mNGS in plasma was 85.2%, the positive rate of traditional microbial culture in plasma was 14.8%, the positive rate of mNGS in pus was 96.2% and traditional microbial culture in pus was 65.4%. The positive rate of traditional culture was significantly lower than that of mNGS ( P < 0.05). Conclusions:PLA is usually manifested as fever, single and at the right lobe of the liver. Klebsiella pneumoniae is the most common pathogenic bacteria of PLA, which is more common in patients with diabetes and fatty liver, while non-Klebsiella pneumoniae is relatively more common in patients with culture of liver positive factors. The positive detection rate of mNGS is high, which has a unique advantage in pathogen detection.