Objective To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.Methods A total of 130 mice were randomly divided into a cecal ligation and puncture(CLP)group(n=100)and a Sham group(n=30)Mouse model of sepsis was established with CLP procedure.Flow cytometry was used to analyze the proportions of peripheral blood CD4+T and CD8+T cells and programmed cell death protein 1(PD-1)positive T cell subsets in mice.Bacterial colonization in organs such as the heart,liver and kidneys was quantified by plating homogenates of the organs.Pathological changes in immune organs were observed with HE staining.The expression and localization of CD4?,CD8?,and PD-1?cells in immune organs were detected with immunohistochemical staining,and Image J software was employed for subsequent quantification of the number of the positive cells.Results HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression.Compared with the Sham mice,the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood(P<0.05),notably in the liver,which showed the most severe infection.In the CLP group,the proportion of CD4+T lymphocytes in peripheral blood at days 1,3,and 5 postoperatively was decreased by 56%,70.57%,and 87.42%,respectively,when compared with the Sham group(P<0.001).The proportion of CD8+T lymphocytes was decreased by 48.33%relative to the Sham group only at day 5(P<0.001).In contrast,the proportion of CD4+T cell subsets expressing PD-1 was increased to 673.08,423.08,and 600 times that of the Sham group,respectively,at the same postoperative time points(P<0.001).Immunohistochemical results showed that,in the CLP group,the proportion of CD4+T cells in the thymus,spleen,and mesenteric lymph nodes was increased to 7.65,2.66,and 3.7 times that of the Sham group,respectively,at the early-stage peak(P<0.001),and then these proportions were decreased by 82.8%(P<0.001),41.9%(P<0.01),and 60.15%(P<0.001),respectively,at the late-stage trough when compared with the early-stage peak in the corresponding organs.The proportion of CD8+positive cells was increased in the early stage and then decreased insignificantly,while the proportion of PD-1+positive cells was increased continuously,and reached 6.24,13.9,and 20.96 times that of the Sham group at the peak in the thymus,spleen,and mesenteric lymph nodes respectively(P<0.001),with their expression regions showing a rough overlap with those of CD4+cells.Conclusion During sepsis,the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4?T lymphocytes,leading to declined defenses against infection,which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

Objective:To investigate the risk factors associated with mortality in patients with severe traumatic liver injury (TLI) and to establish and validate an early prediction model for mortality.Methods:A retrospective cohort study was conducted to analyze the clinical data of 273 patients with severe TLI admitted to the ICU from the medical information mart for the intensive care-IV (MIMIC-IV) database. The cohort consisted of 176 males and 97 females, with age ranging from 18 to 83 years [35.6 years(25.7,57.5)years]. The patients were divided into two groups based on in-hospital mortality: the survival group (253 patients, 92.7%) and the death group (20 patients, 7.3%). The two groups were compared with regards to gender, age, cause and type of injury, treatment method, massive blood transfusion, comorbidities as well as vital signs and laboratory tests measured within 24 hours of ICU admission. Univariate analysis was used to screen for risk factors associated with mortality in severe TLI patients. Independent risk factors for mortality were determined using multivariate Logistic regression analysis. Lasso regression was used to screen for predictors of mortality, and a nomogram prognostic model was then established through a multivariate Logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discrimination of the model, while the Hosmer-Lemeshow goodness-of-fit test and calibration curve were used to evaluate the calibration of the model. The model′s clinical applicability was evaluated through decision curve analysis (DCA). Internal validation was performed by the 200 Bootstrap samples, and external validation was performed by using 163 patients with severe TLI from the emergency ICU collaborative research database (eICU-CRD). Finally, the predictive efficacy of the nomogram model was compared to other trauma or severity scores.Results:Univariate analysis showed that the age, cause of injury, massive blood transfusion, chronic liver disease and laboratory tests measured within 24 hours of ICU admission, including temperature, systolic blood pressure, diastolic blood pressure, mean arterial pressure, shock index, platelets, red blood cell distribution width (RDW), mean red blood cell hemoglobin concentration (MCHC), blood glucose, blood urea nitrogen, creatinine, anion gap, bicarbonate, prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were associated with the mortality of severe TLI patients ( P<0.05 or 0.01). Multivariate Logistic regression analysis revealed that age ( OR=1.08, 95% CI 1.03, 1.12, P<0.01), body temperature <36 ℃ ( OR=8.00, 95% CI 2.17, 29.53, P<0.01), shock index ( OR=9.59, 95% CI 1.76, 52.18, P<0.01) and anion gap ( OR=1.32, 95% CI 1.15, 1.53, P<0.01) were significantly associated with mortality in severe TLI patients. Lasso regression analysis selected 7 predictors, including age, body temperature<36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT. Based on these 7 predictors, a nomogram prediction model was developed. The AUC of the nomogram for predicting mortality was 0.96 (95% CI 0.94, 0.99), and the Hosmer-Lemeshow goodness-of-fit test indicated a good fit ( P>0.05). The calibration curve demonstrated excellent consistency between the predicted and actual probabilities, and DCA demonstrated that the model had good clinical net benefit at all risk threshold probability ranges. Internal validation confirmed the stability of the model ( AUC=0.96, 95% CI 0.92, 0.98), and external validation demonstrated good generalization ability ( AUC=0.95, 95% CI 0.91, 0.98). Moreover, the nomogram exhibited superior predictive efficacy compared with injury severity score (ISS), revised trauma score (RTS), trauma injury severity score (TRISS), sequential organ failure score (SOFA), acute physiological score III (APS III), Logistic organ dysfunction score (LODS), Oxford acute severity of illness score (OASIS) and simplified acute physiological score II (SAPS II). Conclusions:Age, body temperature <36 ℃, shock index and anion gap are independent risk factors for mortality in severe TLI patients. A nomogram prognosis model based on 7 predictors, namely age, body temperature <36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT exhibits good predictive efficacy and robustness, and is contributive to accurately assess the risk of mortality in severe TLI patients at an early stage.

The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China.
Amino Acid Sequence ; Base Sequence ; Capsid Proteins ; chemistry ; genetics ; China ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny ; Poliomyelitis ; virology ; Poliovirus ; chemistry ; genetics ; metabolism ; Poliovirus Vaccines ; adverse effects ; chemistry ; genetics ; metabolism ; Sequence Alignment

Objective To analyze the prognostic factors in treating variceal hemorrhage patients of liver cirrhosis and portal hypertension with transjugular intrahepatic portosystemic shunt (TIPS).Methods From January 2003 to December 2008, the data of 162 variceal hemorrhage patients with liver cirrhosis and portal hypertension treated with TIPS was collected, which included basic information, biochemical examination results within 7 days before the operation, regular follow-up observation after the surgery and survival data. The survival prognostic indexes were assessed with Cox regression model. Results The successful rate of TIPS was 99% (161/162). The median follow up duration was 21 months. Child-Pugh score and blood platelet count (PLT) were closely correlated with survival (P = 0. 003 and 0. 024). The total cumulative survival rate in patients with Child-Pugh score below nine (75%, 102/136) was higher than over nine (50%, 13/26) (χ2 = 9. 12,P=0. 003).The total cumulative survival rate of patients with PLT count over 47 ×109/L (74%, 82/112) was higher than below 47 × 109/L(66 %, 33/50, χ2 =4. 528, P = 0. 033). The one year after operation cumulative survival rate of liver function Child-Pugh class A, B, and C was 92%, 85%, 55% respectively. Conclusion Child-Pugh score and platelet count are independent predictable factors for the survival of variceal hemorrhage patients with liver cirrhosis and portal hypertension treated by TIPS. The risk increase after operation when Child-Pugh score over 9 and/or PLT count less 47×109 /L.

Objective To evaluate the safety and efficacy of percutaneous transluminal angioplasty (PTA) in treating Budd-Chiari syndrome (BCS) and to analyze the long-term follow-up results. Methods From October 1998 to May 2008,98 BCS patients (inferior vena cava obstruction,n = 34 ; hepatic vein obstruction, n = 22; combined obstruction, n = 42) who accepted PTA treatment successfully were investigated. The changes of clinical manifestations and liver function post-operation were observed; the long term survival rate was evaluated. Results Only two patients were complicated with transhepatic puncture tract bleeding, the prognosis was good after emergency operation. Sixty patients presented with low extremities edema, which was fully subsided after PTA.Of eighty-eight ascites patients, ascites disappeared in eighty patients after operation, and in the other eight patients combined with oral diuretic treatment post-operation. The median Rotterdam prognostic score of one month post-operation and the last follow-up time point was 0. 11 and 0. 09, significantly lowered than pre-operation (1.12). The difference was statistical significance (P=0. 000). At 1, 3, 5 years postoperative, the cumulative vessel patency rates were 96%, 94% and 94% respectively, and the cumulative survival rates were 94%, 91% and 87%. Conclusions Treating BCS with PTA has a high success rate, a good safety and a long-term survival rate.

Objective To evaluate the effect of hepatic vein occlusion and stent replacement in treatment for Budd-Chiari syndrome(BCS).Methods Forty three patients with BCS were underwent percutanous puncture,radiography,transjugular angioplasty,balloon dilation and stent placement for hepatic vein under Doppller ultrasounographic guidance from July 2001 to September 2006. Results Technical success was 100%with no complications.The medium vein pressure was reduced from 32.5 tO 20 cm H2O(1 cm H2O-0.098 kPa)after stents replacement(P＜0.01).The hepatic vein angioplasty revealed that all stents were patent and branches were disappeared.The symptoms in 38 patients were disappeared immediately,and improved in 5 patients.All patients were followed up of 32 months(ranged 1-62).Except one patient died of severe gastric bleeding,the 42 patients were survived with symptoms free.Conclusion Hepatic vein occlusion and stent replacement are safe and effective in treatment of BCS.