Objective:To investigate the diagnostic value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 (FAHD1) and growth differentiation factor-15 (GDF-15) in sepsis.Methods:Based on the database of the whole process of sepsis early warning, diagnosis and treatment management, which was established on the study of sepsis early warning and standardized diagnosis and treatment system, adult patients with suspected infection admitted to the department of critical care medicine of Zhejiang Hospital, Second Affiliated Hospital of Zhejiang University, the First Affiliated Hospital of Sun Yat-Sen University, West China Hospital of Sichuan University, Ningbo First Hospital from May 2014 to October 2015 were enrolled. The basic vital signs, and the main blood routine results, liver and kidney function, blood gas, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) score at the time of diagnosis of patients with or without sepsis were analyzed. The preserved serum samples were taken, the levels of procalcitonin (PCT), C-reactive protein (CRP) were detected by electrochemiluminescence method, immunoturbidimetry respectively, and FAHD1 and GDF-15 were detected by enzyme linked immunosorbent assay (ELISA). Univariate and multivariate Logistic regression were used to analyze the risk factors for sepsis diagnose. The indexes' diagnostic efficacy in sepsis were analyzed by receiver operating characteristics curve (ROC curve).Results:A total of 132 patients were enrolled, including 76 cases of sepsis and 56 cases of non-sepsis. Compared with the non-sepsis group, the heart rate in the sepsis group was increased (bpm: 116.4±17.8 vs. 97.4±19.1), while the mean arterial pressure (MAP), platelet count (PLT), arterial partial pressure of oxygen (PaO 2) were significantly decreased [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.8±9.7 vs. 74.7±10.3, PLT (×10 9/L): 120 (69, 204) vs. 163 (117, 239), PaO 2 (mmHg): 83.0 (66.6, 108.0) vs. 108.0 (84.4, 130.0), all P < 0.05], direct bilirubin (DBil), serum creatinine (SCr), lactic acid (Lac), APACHEⅡ score and SOFA score were significantly increased [DBil (μmol/L): 13.00 (5.55, 55.31) vs. 6.20 (2.20, 21.90), SCr (μmol/L): 118.00 (70.00, 191.73) vs. 77.20 (59.65, 110.86), Lac (mmol/L): 2.90 (1.50, 4.10) vs. 1.90 (1.20, 2.80), APACHEⅡ score: 20.0 (16.0, 25.0) vs. 16.0 (10.0, 21.0), SOFA score: 12.0 (8.0, 16.0) vs. 8.0 (5.0, 13.0), all P < 0.05]. In addition, the serum levels of FAHD1, GDF-15, PCT and CRP in sepsis group were significantly higher than those in non-sepsis group [FAHD1 (μg/L): 3.96 (2.25, 5.92) vs. 2.47 (1.03, 3.54), GDF-15 (μg/L): 8.46 (4.37, 19.68) vs. 4.32 (1.74, 10.39), PCT (μg/L): 3.79 (1.37, 11.32) vs. 0.42 (0.12, 2.14), CRP (mg/L): 154.43 (61.33, 283.20) vs. 65.95 (28.15, 144.69), all P < 0.01]. Multivariate Logistic regression showed that serum FAHD1 [odds ratio ( OR) = 1.135, 95% confidence interval (95% CI) was 1.045-1.234], GDF-15 ( OR = 1.090, 95% CI was 1.029-1.155) and CRP ( OR = 1.007, 95% CI was 1.002-1.011) were risk factors for sepsis (all P < 0.05). ROC curve analysis of sepsis showed that the areas under ROC curve (AUC) of serum mitochondrial associated proteins FAHD1 and GDF-15 were 0.727 (95% CI was 0.641-0.802) and 0.677 (95% CI was 0.588-0.757), respectively; and the AUC of classical infection indexes PCT and CRP were 0.767 (95% CI was 0.683-0.837) and 0.680 (95% CI was 0.59-0.760), respectively. There was no significant difference between the AUC of mitochondrial associated proteins and classical infection indexes. The combination of FAHD1, GDF-15, PCT and CRP had the largest AUC, which was 0.809 (95% CI was 0.730-0.874), and the sensitivity was 75.00%, and the specificity was 80.00%. Conclusion:Mitochondrial associated protein FAHD1 and GDF-15 are associated with sepsis, and the diagnostic efficiency is improved when combined with PCT and CRP, which might provide experimental basis for screening diagnostic markers of sepsis.

Objective To analyze the Alb-cre/DTR mouse phenotype, and establish a model of induced liver damage to serve basic researches of liver diseases.Methods The introduced Alb-cre and DTR mice were crossed to obtain Alb-cre/DTR mice and the genomic DNAs were extracted from the tail tissue of the mice for genotying by PCR.Diphtheria toxin was intraperitoneally(i.p.)injected into the Alb-cre/DTR mice, then the body weights were monitored and the sera were collected for the detection of serum ALT and AST levels.Results By crossing Alb-cre and DTR mice we obtained the Alb-cre and DTR double transgenic mouse.The intraperitoneal injection of diphtheria toxin in a dose of 0.625 ng/g body weight significantly induced liver injury in these mice, as showed by the elevated levels of ALT and AST, the gross appearance of liver damage and the pathological changes such as necrosis in the liver tissue.Conclusions We have ob-tained a novel mouse strain of Alb-cre/DTR by crossing Alb-cre and DTR mice.Liver damages in those Alb-cre/DTR mice can be induced by injection of diphtheria toxin.This established mouse model of inducible liver damage is a useful platform for the studies of liver damage and recovery, as well as liver transplantation.

Objective To investigate the role of interleukin-1 receptor type 1 (IL-1R1) signaling in H1N1 influenza virus infection. Methods IL-1R1 knockout ( IL-1R1-/-) mice and wild type ( WT) mice were infected intranasally with 2×104 TCID50(50% tissue culture infective dose) of influenza virus H1N1 PR8. Changes in clinical signs, survivals and bodyweights of those mice were monitored daily for 14 consecutive days. Three mice from each group were sacrificed at 3, 7 and 14 days post infection (d. p. i), from which whole lungs were harvested. A part of the lobes was fixed in 4% paraformaldehyde for histopatho-logical assessment and the rest were split and stored at-80 centigrade for further analysis. Real-time quanti-tative PCR and cytometric bead array ( CBA) were performed to detect viral loads in lungs and inflammatory cytokines in supernatants of lung homogenates. Results The mice in both groups showed severe symptoms after the infection of PR8. The maximum bodyweight loss of IL-1R1-/- mice [(24. 22±0. 80) % at 8 d. p. i] was lower than that of WT mice [(28. 03±1. 51)% at 9 d. p. i] (P<0. 05). The IL-1R1-/- mice with PR8 infection showed a higher survival rate (90%) as compared with that of the control group (40%) (P<0. 05). No statistical differences in virus loads were observed between the two groups at 3, 7 and 14 d. p. i. The lung weight to body weight ratio of IL-1R1-/-mice [(1. 42±0. 03) %] was lower than that of WT mice [(1. 79±0. 08) %] at 3 d. p. i (P<0. 05). Pathological changes in IL-1R1-/- mice were less severe than those in WT mice. CBA detection assay revealed that the proinflammatory cytokines in lungs of IL-1R1-/-mice were less than those in WT mice. Conclusion IL-1R1 signaling plays a pathogenic role in mice infec-ted with 2×104 TCID50 of influenza virus PR8 by promoting inflammatory responses.

Objective: To investigate the current prevalence of latent tuberculosis infection (LTBI) among residents living in Nanchuan District, Chongqing Municipality, so as to provide the evidence for formulating LTBI control measures. Methods: The residents living in one street and one township from Nanchuan District were randomly selected using the multistage cluster sampling method during the period between January and April, 2020, and their demographic information, smoking history, history of alcohol consumption, history of contacts with tuberculosis patients and Bacillus Calmette-Guérin ( BCG ) vaccination scars were collected. The infection of Mycobacterium tuberculosis was detected using interferon gamma release assay ( IGRA ), and a positive IGRA test and exclusion of active tuberculosis was defined as LTBI. The prevalence of LTBI was descriptively analyzed among the study subjects. Results: Totally 1 000 residents were recruited, including 381 males and 619 females, with a male to female ratio of 0.62∶1. The mean age was ( 45.87±18.40 ) years. Among all participants, there were 222 smokers ( 22.20% ), 247 subjects consuming alcohol (24.70%), 62 subjects with a history of contacts with tuberculosis patients ( 6.20% ) and 904 subjects with BCG scars ( 90.40% ). A total of 198 residents were diagnosed with LTBI (19.80% prevalence), and a higher prevalence rate of LTBI was seen in men than in women ( 23.36% vs. 17.61%; χ2=4.911, P=0.027 ). The prevalence of LTBI was significantly higher in married/divorced/widowed residents than in unmarried residents ( 24.22% vs. 2.01%; χ2=49.514, P<0.001 ), and significantly greater prevalence was found in smokers than in non-smokers ( 27.93% vs. 17.48%; χ2=11.871, P=0.001 ). The prevalence of LTBI appeared a tendency towards a rise with age ( χ2trend=59.100, P<0.001 ) and body mass index ( χ2trend=9.479, P=0.002 ). Conclusions The prevalence of LTBI is high among residents living in Nanchuan District, notably among elder, male smokers with high body mass index. Risk monitoring and timely interventions are required.

Objective To analyze the role of cysteinyl aspartate specific proteinase-1 (caspase-1) in a mouse model of D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced acute liver failure (ALF) and to study the possible mechanism. Methods C57BL/ 6 mice were randomly divided into four groups including control group, Z-WEHD-FMK (caspase-1 inhibitor) treatment group, ALF model group and Z-WEHD-FMK-treated ALF group. The mouse model of ALF was established by intraperitoneally injec-ting the mice with D-GalN (450 mg/ kg) and LPS (10 μg/ kg). The damages in liver tissues were evaluated based on the histopathological examination and the levels of alanine transaminase (ALT) and aspartate trans-aminase (AST) in serum samples. Western blot assay was performed to analyze the expression of caspase-1 and the phosphorylation of glycogen synthase kinase 3β (GSK-3β). The qRT-PCR was used to measure the expression of inflammatory cytokines at transcriptional level. Results The expression of caspase-1 at both mRNA and protein levels were gradually increased during the development of ALF. Compared with the mice with ALF, those in the Z-WEHD-FMK-treated ALF group showed less severe liver damages on histopatholog-ical examination and decreased levels of ALT and AST in serum samples [ALT: (479. 2±39. 5) U/ L vs (998. 5±60. 4 ) U/ L, P<0. 05; AST: ( 478. 5±28. 6) U/ L vs ( 1 180. 7±91. 4) U/ L, P<0. 05]. The expression of TNF-α, IL-1β, IL-18 and IL-33 at transcriptional level were significantly suppressed in mice with ALF upon the Z-WEHD-FMK intervention. Results of the Western blot assay indicated that Z-WEHD-FMK suppressed the activities of GSK-3β by enhancing its phosphorylation. Conclusion This study demon-strated that caspase-1 could promote the activation of GSK-3β resulting in the development of inflammation responses and liver damages during the development of ALF in mice.

Objective:The relationship between the effect of early metabolism in 18F-FDG PET/CT and conventional CT based on the RE-CIST standard to evaluate the best objective response after chemotherapy in patients with non-small cell lung cancer (NSCLC). Meth-ods:We studied 40 patients with unresectable locally advanced or advanced NSCLC that were confirmed pathologically. The patients were 35 years old to 78 years old and included 31 males and 9 females. Three patients have unresectable stageⅢA, 8 patients have stageⅢB, 29 patients have stageⅣ, 12 patients have squamous cell carcinoma, and 28 patients have adenocarcinoma. The PET/CT for the effect of chemotherapy was evaluated in NSCLC according to the SUV standard (SUVmax reduction>30%of primary lung can-cer after one cycle of chemotherapy), and the CT for the effect of chemotherapy was evaluated on the basis of NSCLC according to the RECIST standard. The objectives of the study are as follows:compare the differences and consistency between 18F-FDG PET/CT metabol-ic response after the first cycle of chemotherapy and the RECIST best objective response after the first or second cycle of chemothera-py with the paired chi-square test and kappa test;calculate the 18F-FDG PET/CT to predict the best objective response of two cycles of chemotherapy according to RECIST on the basis of NSCLC in terms of sensitivity, specificity, accuracy, positive predictive value, and neg-ative predictive value;compare the differences in SUVmax reduction between the metabolic remission group and metabolic no relief group with the two-sample t-test. All statistical methods were 0.05 for the inspection level, and P<0.05 was considered statistically sig-nificant difference (SPSS19.0). Results:Differences were found between the first cycle of chemotherapy for the RECIST best objective response and 18F-FDG PET/CT metabolic response (χ2=5.063, P=0.021), and the results had bad consistency (Kappa=0.240, P=0.085). No differences were observed between the second cycle of chemotherapy for the RECIST best objective response and 18F-FDG PET/CT metabolic response (χ2=2.083, P=0.146);the results had good consistency (Kappa=0.413, P=0.006). The sensitivity, specificity, accura-cy, positive predictive value, and negative predictive value were 82%, 61%, 70%, 61%, and 82%, respectively. The differences in SUV-max reduction between the metabolic remission group and metabolic no relief group with the two-sample t-test were statistically sig-nificant (P<0.001). Conclusion: 18F-FDG PET/CT may predict the best objective response to chemotherapy for NSCLC patients. Com-pared with conventional CT, 18F-FDG PET/CT can be an early and accurate way to evaluate the chemotherapy effect in NSCLC.

Objective To investigate the effects of peroxisome proliferator-activated receptor α( PPARα) on macrophage-mediated inflammatory responses with the interference of lipopolysaccharide and the possible mechanism.Methods The bone marrow stem cells were isolated from the femora of mice.The granulocyte-macrophage colony stimulating factor ( GM-CSF) was used to stimulate the in vitro differentiation from bone marrow stem cells into primary macrophages.An in vitro model with cultured cells expressing in-flammatory cytokines was established by treating the primary macrophages with lipopolysaccharide ( LPS) .A specific chemical agonist, Wy-14643, was used to activate PPARα. Autophagy inhibitors including 3-methyladenine (3-MA) and small interfering RNA against Atg7 ( Atg7 siRNA) were used to inhibit the autophagy.Western blot assay was performed to detect the expression of autophagy-related proteins ( Atg5, Atg7, Beclin-1 and LC3).The transcriptional levels of TNF-α, IL-1β, IL-6, Atg5, Atg7 and Beclin-1 were analyzed by qRT-PCR.Results Compared with the macrophages treated with LPS alone, those pretreated with various concentrations of Wy-14643 (10 μmol/L, 25 μmol/L and 50 μmol/L) showed inhibited ex-pression of proinflammatory cytokines ( TNF-α,IL-1βand IL-6) and enhanced expression of autophagy-relat-ed proteins (Atg5, Atg7 and Beclin-1) at mRNA level in a dose-dependent manner.The expression of auto-phagy-related proteins (Atg5, Atg7, Beclin-1 and LC3) by macrophages was promoted with the pretreatment of Wy-14643 as indicated by Western blot assay.The transcriptional levels of TNF-α, IL-1βand IL-6 were increased in Wy-14643 pretreated-macrophages after stimulation with 3-MA or Atg7 siRNA .Conclusion PPARαsuppressed the macrophage-mediated inflammatory responses by promoting autophagy, suggesting that the PPARα-autophagy pathway might be one of the signaling pathways regulating LPS induced-inflamma-tory responses.

Objective We aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of ulcerative colitis (UC) in this Meta-analysis.Methods Literature related to FMT for the treatment of UC from PubMed,Embase,Cochrane databases,CNKI,VIP and Wanfang Data were searched and screened with update study in May 2018.Two independent investigators extracted information according to inclusion and exclusion criteria.The Meta-analysis was conducted by Stata 12.0 software.Results A total of 4 randomized controlled trials (RCTs) and 19 non-randomized controlled trials (non-RCTs) including 536 participants met the inclusion criteria.Meta-analysis of RCTs showed that FMT significantly increased the clinical remission rate (OR=2.47,95％CI 1.40-4.33,P=0.02) and clinical response rate (OR=1.86,95％CI 1.15-3.02,P=-0.01) in UC patients without increasing the incidence of severe adverse effects (OR=1.40,95％CI 0.51-3.79,P=-0.51).The results from 19 non-RCTs showed that clinical remission rate in UC patients with FMT treatment was 20％(95％CI 13％-28％) and the clinical response rate was 50％(95％CI 36％-65％).All adverse events were graded as mild and self-resolving.No FMT-related severe adverse effects were reported.Conclusions Our analysis suggests that FMT is a safe and effective method for the treatment of UC.Considering several limitations of this Meta-analysis and previous clinical trials,further large-scale multicenter RCTs are still required to further verify the conclusion.

OBJECTIVE:To know about the hot point and development tendency of traditional Chinese medicine (TCM) in the nearest 20 years and provide reference for the further study. METHODS:Totally 5 000 papers of cited top 1% with the“TCM”themes in CNKI from 1994 to 2013 were collected. With the indicators of cited times and download times,Excel software analysis function,the CiteSpace citation analysis function and bibliometrics were adopted to statistically analyze the research field,main items,chemical constituents,pharmacological activities,published journals,personnel and units,etc. RESULTS:The papers about TCM research quantity in CNKI were increased exponentially in last 20 years,and might enter the platform period hence-forth;totally 15 main research fields,50 TCM and 60 chemical components/portions with strong activity and development prospect were highly noticed and cited;the study of pharmacological activities was the core and the most active area of TCM research,and mainly related to the major diseases and diseases with TCM advantages;totally 60 papers for highly cited were greater than 500 times,devoting 58.8%highly cited papers;40 authors and units screened from annually top 50 cited papers had wider academic in-fluence. CONCLUSIONS:Analyzing the hot point and development tendency of TCM research in the nearest 20 years based on the CNKI highly cited papers can accurately grasp the industry focus,thereby provide a certain reference and data support for tradition-al Chinese medicine research.

Objective Using an adenoviral vector , the wild-type PTEN gene was transduced into activated hepatic stellate cell (HSC) in vitro and the phosphorylation status of Akt were investigated. Methods The wild type PTEN gene was transduced into activated HSC in vitro mediated by adenoviral vector. The expressions of PTEN and total Akt in HSC were measured by Western blot and Real-time fluorescent quantitation PCR. And the expressions of phosphorylated Akt (Thr308) in HSC was determined by Western blot. Results The data showed that exogenous wild type PTEN gene was successfully transduced and expressed in activated HSC in vitro. The over-expression of wild type PTEN resulted in the significant down-regulated expression of phosphorylated Akt (Thr308) in activated HSC (P < 0.01). But no significant defferences were found in the expression of total Akt in activated HSC at both transcriptional and translational levels(P>0.50). Conclusions The overexpression of wild-type PTEN can negatively regulate PI3K/Akt signaling transduction by inhibiting the phosphorylation of Akt in activated HSC in vitro.