Study on the value of prothrombin time for predicting the severity and prognosis of septic patients / 中华危重病急救医学

Objective:To explore the predictive efficacy of prothrombin time (PT) with regarding for the severity and prognosis of septic patients, along with comparing with other routine coagulation parameters.Methods:A retrospective analysis was conducted. The clinical data of 302 septic patients who were admitted to the intensive care unit (ICU) of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 1 to December 31 in 2019 were enrolled. Demographic and basic clinical data were collected. Laboratory data, including PT, activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer, fibrin (fibrinogen) degradation product (FDP), antithrombin (AT), platelet count (PLT) at ICU admission were recorded, and sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score within 24 hours of admission to ICU were also collected. What's more, some major clinical events, such as septic shock, disseminated intravascular coagulation (DIC), etc. during ICU stay were also monitored. A follow-up 28 days observation of prognosis was performed. The patients were divided into the septic shock group and the non-septic shock group according to the occurrence of septic shock, and they were divided into the survival group and the non-survival group according to the 28-day prognosis. The differences in terms of above parameters between each two groups were compared. Spearman correlation method was used to analyze the correlation between routine coagulation parameters and SOFA score or APACHEⅡ score. Receiver operator characteristic curve (ROC curve) was plotted to determine the predictive efficacy of each routine coagulation parameter with regarding to predict septic shock and 28-day mortality. Based on the cut-off value of PT, the septic patients were divided into two risk stratifications, and then the major clinical and end point outcome were compared. Kaplan-Meier survival curve analysis was applied to investigate the difference of the 28-day cumulated survival rate based on the different risk stratifications of PT level. Finally, multivariate Logistic regression analysis was used to explore whether prolonged PT level was an independent risk factor for septic shock and 28-day mortality.Results:The 302 patients were all enrolled, including 120 patients with septic shock and 182 patients without. Seventy-five patients died within 28 days, while 227 survived. Comparing with the non-septic shock group or the survival group, the septic shock group or the non-survival group patients both had longer PT, APTT and TT, higher D-dimer, FDP and lower PLT, FIB and AT. Correlation analysis revealed that PT and PLT were better correlated with SOFA score ( r values were 0.503 and -0.524, both P < 0.01), and PT was better correlated with APACHEⅡ score ( r = 0.407, P < 0.01). ROC curve analysis showed that PT had the most powerful predictive efficacy for septic shock and 28-day mortality. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were 0.831 (0.783-0.879) and 0.739 (0.674-0.805), respectively. The cut-off value were 16.8 s and 16.3 s, respectively, with the sensitivity of 64.2%, 72.0% and the specificity of 89.0%, 70.9%, respectively. Risk stratification based on PT level revealed that the patients with PT > 16.5 s ( n = 103) had higher rate of 28-day mortality, incidence of septic shock and DIC, and score of SOFA and APACHEⅡ comparing to those with PT ≤ 16.5 s ( n = 199). Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate was significantly lower in the patients with PT > 16.5 s than those with PT ≤ 16.5 s (52.43% vs. 86.93%; Log-Rank test: χ 2 = 49.428, P < 0.001). Multivariate Logistic regression analysis revealed that PT > 16.5 s was an independent risk factor both for septic shock and 28-day mortality [model 1 (enrolled SOFA score): odds ratio ( OR) and 95% CI were 6.003 (3.040-11.855), 4.842 (2.114-11.089); model 2 (enrolled APACHEⅡ score): OR and 95% CI were 7.675 (4.007-14.702), 5.160 (2.258-11.793)]. Conclusions:Compared with other routine coagulation parameters, PT has the potential best predictive value for evaluating the severity of sepsis and the prognosis. When a patient is diagnosed with sepsis and has a result of PT longer than 16.5 s at ICU admission, the patient may have a higher risk of progression to septic shock and short-term death.

Single-dose AAV-based vaccine induces a high level of neutralizing antibodies and provides long-term protection against SARS-CoV-2 in rhesus macaques

Coronavirus disease 2019 (COVID-19), which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, continues to threaten global public health. Developing a vaccine that only requires single immunization but provides long-term protection for the prevention and control of COVID-19 is important. Here, we developed an adeno-associated virus (AAV)-based vaccine expressing a stable receptor-binding domain (SRBD) protein. The vaccine requires only a single shot but provides effective neutralizing antibodies (NAbs) over 598 days in rhesus macaques (Macaca mulatta). Importantly, our results showed that the NAbs were kept in high level and long lasting against authentic wild-type SARS-CoV-2, Beta, Delta and Omicron variants using plaque reduction neutralization test. Of note, although we detected pre-existing AAV2/9 antibodies before immunization, the vaccine still induced high and effective NAbs against COVID-19 in rhesus macaques. AAV-SRBD immune serum also efficiently inhibited the binding of ACE2 with RBD in the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1/P.2 (Gamma), B.1.617.2 (Delta), B.1.617.1/3(Kappa), and C.37 (Lambda) variants. Thus, these data suggest that the vaccine has great potential to prevent the spread of SARS-CoV-2.

The infection evidence of SARS-COV-2 in ocular surface： a single-center cross-sectional study

PurposeThe aim of this study was to identify whether SARS-COV-2 infected in ocular surface. MethodsCross-sectional study of patients presenting for who received a COVID-19 diagnosis, from December 30, 2019 to February 7, 2020, at Tongji hospital, Tongji medical college, Huazhong University of Science and Technology. Demographics, temperature was recorded, blood routine test (Rt), chest Computed Tomography (CT) were took intermittently, and SARS-COV-2 real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were arranged for the nasopharyngeal and conjunctival swab samples. ResultsA total of 102 patients (48 Male [50%] and 54 Female [50%]) with clinical symptoms, Rt, and chest Computed Tomography (CT) abnormalities were identified with a clinical diagnosis of COVID-19. Patients had a mean [SD] gestational age of 57.63 [14.90] years. Of a total of 102 patients identified, 72 patients (36 men [50%] and 36 women [50%]; mean [SD] age, 58.68 [14.81] years) confirmed by laboratory diagnosis with SARS-COV-2 RT-PCR assay. Only two patients (2.78%) with conjunctivitis was identified from 72 patients with a laboratory confirmed COVID-19. However, SARS-COV-2 RNA fragments was found in ocular discharges by SARS-COV-2 RT-PCR only in one patient with conjunctivitis. ConclusionsAlthough we suspect the incidence of SARS-COV-2 infection through the ocular surface is extremely low, the nosocomial infection of SARS-CoV-2 through the eyes after occupational exposure is a potential route. The inefficient diagnostic method and the sampling time lag may contribute to the lower positive rate of conjunctival swab samples of SARS-COV-2. Therefore, to lower the SARS-COV-2 nosocomial infection, the protective goggles should be wore in all the health care workers.

Comparison of contrast-enhanced ultrasound targeted biopsy versus standard systematic biopsy for clinically significant prostate cancer detection: results of a prospective cohort study with 1024 patients.

PURPOSE: To assess contrast-enhanced ultrasound (CEUS) targeted biopsy (TB) for clinically significant prostate cancer (PCa) detection compared with systematic biopsy (SB). METHODS: A total of 1024 consecutive patients scheduled for prostate biopsy were enrolled in this prospective study. CEUS was performed by an experienced radiologist blinded to all clinical data. Suspicious lesions on postcontrast images were sampled in addition to standard 12-core SB. The clinically significant PCa detection rate by CEUS-TB was evaluated in comparison with SB in the total cohort and in different subgroups. RESULTS: In 378 of 1024 patients (36.9%), the diagnosis of PCa was histologically confirmed. PCa was detected by CEUS-TB in 306 patients (29.9%, 306/1024) and SB in 317 patients (31.0%, 317/1024, P = 0.340). Among 378 PCa patients, 326 (86.2%, 326/378) were diagnosed with significant PCa using Epstein criteria. The significant PCa detection rate of CEUS-TB was 28.7% (294/1024), which was higher than that of SB (25.3%, 259/1024, P = 0.000). CEUS-TB resulted in 67 additional cases of clinically significant PCa, including 51 patients missed by SB and 16 patients under-graded by SB. Conversely, SB detected 32 additional significant PCa missed by TB. In the subgroup analysis, CEUS-TB yielded a higher significant cancer detection rate than SB in patients with a PSA level ≤ 10.0 ng/ml or prostate volume from 30 to 60 ml. CONCLUSION: The clinically significant PCa detection rate could be improved by the extra sampling of abnormalities on postcontrast images, especially in patients with a PSA level ≤ 10.0 ng/ml or prostate volume from 30 to 60 ml.

The clinical value of bedside lung ultrasound in the diagnosis of chronic obstructive pulmonary disease and cardiac pulmonary edema / 中华危重病急救医学

Objective To study the diagnostic accuracy of bedside lung ultrasound examination in chronic obstructive pulmonary disease (COPD) and cardiac pulmonary edema.Methods A prospective pilot and single-blind trial was conducted.A total of 89 patients with respiratory failure admitted to the Department of Critical Care Medicine of Anhui Provincial Hospital from September 2012 to September 2013 were enrolled.There were 32 patients with COPD,31 patients with cardiac pulmonary edema,8 patients with interstitial lung disease,12 with lung infection,and 6 patients with other diseases.Another group of 30 patients without respiratory disease were enrolled as the control group.Bedside lung ultrasound examinations were performed in all patients within 24 hours,and chest radiograph was performed at the same time.The signs to be revealed were the A lines or horizontal lines arising from the pleural line,and the comet-tail artifact (B lines) arising from the lung wall interface.Results Of 89 patients,33 patients were shown a mean of 2.94 ± 1.87 A lines per case with the bedside lung ultrasound,and 38 patients with a mean of 3.27 ± 1.72 B lines per patient.1.94 ± 0.96 A lines a case and 1.74 ± 0.82 B lines a case in control group.There were significant difference between the test group and control group (Aline:t=3.835,P=0.000; B line:t=6.540,P=0.000).Among 32 cases with COPD,28 patients had a positive result of A line with a coincidence rate of 81.2％.In the 31 patients with cardiac pulmonary edema,25 patients presented B line,with a coincidence rate of 80.6％.The A lines or horizontal lines arising from the pleural line showed a sensitivity of 81.30％ and a specificity of 87.70％ with a positive predictive value (PPV) 78.80％ and a negative predictive value (NPV) 89.30％ of in the diagnosis of COPD,and the B lines showed a sensitivity of 80.60％ and a specificity of 77.60％ with a PPV of 65.80％ and a NPV of 88.20％ in the diagnosis of cardiac pulmonary edema.However,X-ray examination showed a sensitivity of 65.50％,a specificity of 86.00％,a PPV of 72.40％ and a NPV of 81.70％ in the diagnosis of COPD,and it showed a sensitivity of 74.20％,a specificity of 69.00％,a PPV of 56.10％ and a NPV of 83.30％ in the diagnosis of cardiac pulmonary edema.Bedside ultrasound was highly consistent with X-ray in diagnosis of COPD [area under receiver operating characteristic curve (AUC):0.833 vs.0.816,P＞0.05],but Kappa value of ultrasound technology A line in the diagnosis of COPD was greater than the value of X-ray imaging techniques (0.685 vs.0.527).There was little diagnostic value of ultrasound A line in cardiac pulmonary edema (AUC was 0.305),while the B line was superior to X-ray (AUC:0.888 vs.0.747,P＜0.001),and had a higher Kappa value than the value of X-ray imaging techniques (0.553 vs.0.481) in cardiac pulmonary edema.Conclusions We conclude that bedside ultrasound is cost-effective,easy for repeated examination,and suitable for differential diagnosis of lung diseases.It might be useful in screening for COPD and cardiac pulmonary edema.

Preparation and antithrombogenicity of oxidated low molecular weight heparin-antithrombin complex coated-polyvinyl chloride tubing / 生物医学工程学杂志

Based on non-enzymatic protein glycated reaction, the sodium periodate-oxidated low molecular weight heparin-antithrombin covalent complex (SPLMWATH) was produced. By using polyethyleneimine-glutaraldehyde bonding technique, polyvinyl chloride (PVC) tubings were coated with SPLMWATH, heparin and low molecular weight heparin (LMWH). Spectrophotometry and dynamic clotting time experiment were used to determine the synthetic ratio of SPLMWATH, graft density, coating leaching ratio and to evaluate the antithrombogenicity of different coating on the PVC tubings. The results showed that the synthetic ratio of SPLMWATH was approximately 55%, and compared with heparin coating and LMWH coating, the graft density of SPLMWATH coating on the PVC tubing was smaller, but its coating stability and antithrombogenicity were significantly better than that of heparin coating and LMWH coating on the PVC tubings.

Cyclooxygenase-2 suppresses polymorphonuclear neutrophil apoptosis after acute lung injury.

BACKGROUND: Polymorphonuclear neutrophil (PMN) apoptosis is suppressed after acute lung injury (ALI), and strategies aimed at inducing PMN apoptosis are thought to be promising therapies for ALI. However, the mechanisms underlying PMN apoptotic suppression are unknown. Cyclo-oxygenase-2 (COX-2) has been shown to regulate tumor cell apoptosis and is up-regulated by inflammatory mediators in PMN. Therefore, we set out to determine whether up-regulation of COX-2 expression contributes to PMN apoptosis after ALI. METHODS: Experimental ALI was established in New Zealand rabbits by blunt chest trauma, and a correlation analysis of COX-2 immunohistochemical staining in lung tissue and PMN apoptosis in bronchoalveolar lavage fluid (BALF) was performed. Apoptosis was measured by flow cytometric analysis of annexin V and propidium iodide dual staining. As an in vitro correlate, normal PMNs were treated with BALF from injured lung (BALFALI) in the presence or absence of the COX-2 inhibitor, NS398. COX-2 mRNA levels and PMN apoptosis were then measured. RESULTS: PMN apoptosis was significantly decreased in BALF after injury. In contrast, COX-2 expression was significantly increased after injury. COX-2 protein expression and PMN apoptosis exhibited a strong inverse correlation (gamma = -0.75, p < 0.01). In vitro experiments revealed apoptosis of normal PMNs was significantly decreased by the addition of BALFALI. The addition of BALFALI was also associated with increased COX-2 mRNA levels. Treatment of cultures with NS398, 10 minutes before BALFALI addition, partially reversed all of these effects. CONCLUSIONS: Up-regulation of intrapulmonary COX-2 expression contributes to the suppression of PMN apoptosis after ALI.

Comparative study on cell extraction with different reagents in porcine aortic valves / 中华胸心血管外科杂志

Objective To remove cellular compenents from porcine aortic valve with different reagents, providing acellular tissue matrix(ACTM) scaffolds for tissue engineering of heart valve. Methods Different detergents (TritonX-100、Sodium dodecyl sulfate and sodium deoxycholate) and enzyme (trypsin) were used to remove cells and its, compenents from porcine aortic valves, respectively. According to the different detergents, specimens of porcine aortic valve were divided into three groups(Sodium dodecyl sulfate, sodium deoxycholate, and Triton X-100). Specimens were observed grossly uncroscopically. Haematoxylin-eosin and DNA assay was performed to confirm the removal of cells. Transmission electron microscope was used to observe the integrity of collagen and elastin. The changes of mechanical properties were also studied. Results The cells were removed effectively from cusps and roots of porcine aortic valves by Triton X-100 and sodium dodecyl sulfate in 96 h. Sodium deoxycholate could not effectively remove the cells from the root of aortic valve. Treatment with SDS disrupted collagen fiber structure of porcine aortic valve, resulting in poor mechanical properties. Treatment with TritonX-100 result in an acellular porcine aortic valve matrix with retention of near normal structure and mechanical properties. Conclusion Porcine aortic valve can be successfully decellularised with retention of near normal structure and mechanical properties by Triton X-100.

Expression and significance of nuclear transcription factor in myocardium of rheumatic heart disease / 中华风湿病学杂志

Objective To investigate the effects of nuclear transcription factor- kappa B (NF-!B) and activated protein- 1 (AP- l) on rheumatic myocardial fibrosis. Methods Thirty rheumatic myocardial specimens and 10 normal samples were examined by Masson′s staining, immunohistochemical staining and image analy- sis. Results Both NF- !B and AP- 1 were expressed in the nuclei of myocardium with rheumatic heart disease (RHD). The degree of positive staining in myocardiurn with RHD was significantly correlated with the cardial collagen volume (NF-!B: r=0.8945, AP- 1: r=0.9011, P

Changes of plasma epinephrine and norepinephrine in rabbits with firearm thoracic wounds / 中华创伤杂志

Objective　To investigate the changes of plasma epinephrine (E) and norepinephrine (NE) in rabbits with firearm thoracic wounds. 　Methods　 A total of 24 rabbits were divided into 3 groups randomly, the simple thoracic penetrating injury group (Group A, n = 8), the pseudo-injury group (Group B, n = 8)and the normal control group ( Group C, n = 8). The pressures of carotid artery and jugular vein were recorded by eight-road physiological recorder at 5 minutes before injury. And the concentrations of plasma E and NE were detected through high-performance liquid chromatography (HPLC) and electrochemical detection (ED) at 5 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours and 24 hours after injury in all the rabbits. 　Results　The concentrations of plasma E and NE in Group A were significantly higher than those of Group C (P<0.01) and changed regularly. There was no significant difference between Group B and Group C. The pressures of carotid artery and jugular vein of Group A increased by 1.8 and 6.8 times, respectively, during 2 millisecond after injury, then decreased to normal immediately. They decreased to the minimum (0.63 and 0.25 time, respectively) in 30 minutes and 5 minutes respectively and averagely, and raised to normal slowly after 6 hours and 12 hours respectively and averagely. There was no significant difference between Group B and Group C.　Conclusions 　 The concentrations of plasma E and NE increase significantly in the rabbits with thoracic firearm wounds. Their changes have close relationship with the severity of wound and can be used as a judging criterion during the early period of wound.

Interstitium revascularization and related cytokine regulation in myocardium of rheumatic heart disease / 中华风湿病学杂志

Objective To investigate the interstitial revascularization and related cytokine regulation in myocardium of rheumatic heart disease.Methods The specimens were stained by HE to examine the ratios between arteriolar inner and outer diameters and by immunohistochemical staining and in situ hybridization to measure the expression of bFGF,vascular endothelial growth factor (VEGF),? SMA and mRNA of bFGF.Then the relationship between ratios of arteriolar inner and outer diameters and expression of bFGF,VEGF and ? SMA.Results The imaging analysis indicated that there was significant myocardium fibrosis,and the arteriolar wall became thick (0 68?0 15 vs 0 40?0 04).The expression of bFGF,VEGF and ? SMA in the myocardium of rheumatic heart disease was significantly higher than that of healthy adult control group.There was a positive relationship between ratios of arteriolar inner and outer diameters and expression of bFGF,VEGF and ? SMA (bFGF r =0 719, P

Experimental study on hemorheological and pathological changes following severe myocardial contusion / 中华创伤杂志(英文版)

OBJECTIVE: To investigate the mechanism of severe myocardial contusion in rabbits. METHODS: A total of 32 New Zealand rabbits were randomly divided into 2 groups, the severe myocardial contusion group (the experimental group, n=16) and the sham-impact control group (the control group, n=16). Hemorheological parameters, interleukin-8 (IL-8) in serum, the water contents of myocardium and polymorphonuclear neutrophil (PMN) infiltration in contused myocardium were observed at 24 hours after the experiment. RESULTS: As compared with the control group, the hemorheological parameters in the experimental group including the whole blood viscosity (etab), erythrocyte aggregation index (EAI), hematocrit (HCT), serum fibrinogen (Fib), Casson viscosity (Gammay) and erythrocyte sedimentation rate (ESR), significantly increased. The IL-8, PMN infiltration and the water contents of the contused myocardium also significantly increased. CONCLUSIONS: It suggests that the hemorheological disorder, increase of IL-8 in serum, and PMN infiltration in contused myocardium may contribute to the development of cardiac edema and secondary myocardial damage following severe myocardial contusion in rabbits.

Expression of human mannose-binding lectin in mice liver / 中国免疫学杂志

Objective:To amplify and clone the human mannose-binding lectin(MBL) gene and to express its recombinant protein in mouse liver tissue.Methods:After the human MBL cDNA was amplified by PCR and identified by sequencing and restriction mapping,it was inserted into eukaryotic expression vector pcDNA3.The recombinant plasmid pcDNA3-MBL was injected into mice in large quantity and large volume in a short time through tail vein.These mice were sacrificed 8 h after the injection.MBL were examined in serum and hepatic tissue with Western blot and immunohistochemistry.Results:After the human MBL gene was amplified and sequenced correctly,it was successfully inserted in the eukaryotic expression vector pcDNA3.Eight hours after the pcDNA3-MBL plasmid were injected into mice through tail veins,human MBL could be found both in serum and hepatic tissue with Western blot and immunohistochemistry examination.Conclusion:Systemic injection of pcDNA-MBL can result in human MBL protein expression in mice liver and secretion into blood.This result may provide a new idea to treat the congenital MBL insufficient patients,who have the predisposition of infectious diseases.

Research on Medical Ethics of Tissue-Engineered Cardiae Valve / 中国医学伦理学

This article discusses the material and methods of establishing tissue-engineered cardiac valve,the ethical problems of tissue engineered cardiac valve and the relationship between advanced technology and ethics.

DOUBLE-CHAMBERED RIGHT VENTRICLE: ITS PATHOANATOMIC CHARACTERISTICS AND TREATMENT PROBLEMS / 解放军医学杂志

In the past ten years, 52 patients with double-chambered right ventricle (DCRV) were operated on in Xijing Hospital. They constituted 2.2% (52/1881) of all patients with congenital heart diseases. Of them, there were 32 males and 20 females, whose ages ranged from 4.5 to 30 years old. In one patient there was pure DCRV, and the remaining 51 patients DCRV was associated with other congenital cardiac anomalies, in which VSD was the most common (50), followed in order by pulmonary stenosis (6), aortic valve prolapse (4), atrial septal defect (2), and subaortic stenosis (1). The repair of DCRV and other intracardiac defects was done through the right ventricolotomy in 47 cases and through the right ventricolotomy plus atriotomy in 2 cases. In another 2 cases the operation was done via the right atriotomy and 1 case pulmonary arteriotomy, and only VSDs were closed, but DCRVs were missed. The major postoperative complications included cardiac arrhythmia (11) and low output syndrome (8). Three patients died, with the operative mortality of 5.8%. In this series, according to characteristics of the anomalous muscle bundle and its resulting obstruction, we divided 52 case DCRVs into two types: fibromuscular diaphragmatic type (24 cases, 44.7%) and muscular bundle-gap type (28 cases, 55.7%). In both types, there were not only hypertrophied anmalous muscle bundles on the septal side, but also hypertro-phied ventricoinfundibulum fold on the parietal side. In a few cases, the ventricoinfundibulum fold was more hypertrophic than the anomalous muscle bundle on the septal side.

BIOMECHANICS AND BIOCOMPATIBILITY STUDY OF ACELLULAR PORCINE AORTIC HEART VALVE LEAFLETS / 解放军医学杂志

Tissue engineering heart valves need a scaffold with good quality for cell growth and adherence. The psesent work was to investigate the biomechanics and biocompatibility of acellular porcine heart valves. The method used in this study could completely remove the cellular components in the porcine heart valve leaflets. Compared with fresh leaflets,the water content of acellular leaflets increased, and the soluble protein content decreased significantly. But the shrinkage temperature, thickness, stretch rate and strength at rupture of the acellular leaflets were not altered significantly compared with the fresh leaflets. After implanting the acellular leaflets subcutaneously in rabbits,it was proved that host cells could grow into the leaflets along the collagen fibers. These results suggested that acellular porcine heart valve leaflets could be used as a scaffold to construct tissue engineering heart valves with satisfacfory mechanical property and tissue compatibility.