Correlation between serum markers and transjugular intrahepatic portosystemic shunt prognosis in patients with cirrhotic ascites.

BACKGROUND: Individuals with refractory ascites in the context of liver cirrhosis typically face an adverse prognosis. The transjugular intrahepatic portosystemic shunt (TIPS) is an efficacious intervention, but there is a lack of reliable tools for postoperative prognosis assessment. Previously utilized clinical biochemical markers, such as the serum albumin concentration (Alb), sodium (Na+) concentration, and serum creatinine (Scr), have limited predictive value. Therefore, the quest for novel, specific biomarkers to evaluate the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites holds significant practical importance. AIM: To investigate the associations between the Child-Pugh score, model for end-stage liver disease (MELD) score, and serum cystatin C (Cys C) level and post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. METHODS: A retrospective analysis was conducted on 75 patients with liver cirrhosis and refractory ascites who underwent TIPS at our institution from August 2019 to August 2021. These patients were followed up regularly for two years, and the death toll was meticulously documented. The patients were allocated into a survival group (n = 45 patients) or a deceased group (n = 30 patients) based on their prognosis status. The clinical data of the two groups were collected, and Child-Pugh scores and MELD scores were calculated for analysis. Spearman correlation analysis was carried out to evaluate the correlation of prognosis with Child-Pugh grade, MELD score, and Cys C level. Additionally, a multiple-factor analysis utilizing the Cox proportional hazard model was used to identify independent risk factors affecting the post-TIPS prognosis of patients with liver cirrhosis and refractory ascites. The receiver operating characteristic curve (ROC) ascertained the predictive value of the Cys C concentration, Child-Pugh grade, and MELD score for the prognosis of liver cirrhosis with refractory ascites in post-TIPS patients. RESULTS: During a 2-year follow-up period, among 75 patients with liver cirrhosis and refractory ascites who underwent TIPS treatment, 30 patients (40.00%) passed away. The deceased cohort exhibited heightened aspartate aminotransferase, alanine aminotransferase, total bilirubin, Scr, prothrombin time, Cys C, international normalized ratio, Child-Pugh, and MELD scores compared to those of the survival cohort, while Alb and Na+ levels were attenuated in the deceased group (P < 0.05). Spearman analysis revealed moderate to high positive correlations between prognosis and Child-Pugh score, MELD score, and Cys C level (r = 0.709, 0.749, 0.671, P < 0.05). Multivariate analysis using the Cox proportional hazard model demonstrated that the independent risk factors for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites were Cys C (HR = 3.802; 95%CI: 1.313-11.015), Child-Pugh (HR = 3.030; 95%CI: 1.858-4.943), and MELD (HR = 1.222; 95%CI: 1.073-1.393) scores. ROC analysis confirmed that, compared to those of the classic prognostic models for Child-Pugh and MELD scores, the predictive accuracy of Cys C for post-TIPS prognosis in patients with liver cirrhosis and refractory ascites was slightly lower. This analysis yielded sensitivity and specificity values of 83.33% and 82.22%, respectively. The area under the curve value at this juncture was 0.883, with an optimal cutoff value set at 1.95 mg/L. CONCLUSION: Monitoring the serum Cys C concentration is valuable for assessing the post-TIPS prognosis in patients with liver cirrhosis and refractory ascites. Predictive models based on serum Cys C levels, as opposed to Scr levels, are more beneficial for evaluating the condition and prognosis of patients with ascites due to cirrhosis.

Avian Influenza A Virus Infection among Workers at Live Poultry Markets, China, 2013-2016.

We conducted a 3-year longitudinal serologic survey on an open cohort of poultry workers, swine workers, and general population controls to assess avian influenza A virus (AIV) seroprevalence and seroincidence and virologic diversity at live poultry markets (LPMs) in Wuxi City, Jiangsu Province, China. Of 964 poultry workers, 9 (0.93%) were seropositive for subtype H7N9 virus, 18 (1.87%) for H9N2, and 18 (1.87%) for H5N1. Of 468 poultry workers followed longitudinally, 2 (0.43%), 13 (2.78%), and 7 (1.5%) seroconverted, respectively; incidence was 1.27, 8.28, and 4.46/1,000 person-years for H7N9, H9N2, and H5N1 viruses, respectively. Longitudinal surveillance of AIVs at 9 LPMs revealed high co-circulation of H9, H7, and H5 subtypes. We detected AIVs in 726 (23.3%) of 3,121 samples and identified a high diversity (10 subtypes) of new genetic constellations and reassortant viruses. These data suggest that stronger surveillance for AIVs within LPMs and high-risk populations is imperative.

Nosocomial transmission of avian influenza A (H7N9) virus in China: epidemiological investigation.

STUDY QUESTION: Can avian influenza A (H7N9) virus be transmitted between unrelated individuals in a hospital setting? METHODS: An epidemiological investigation looked at two patients who shared a hospital ward in February 2015, in Quzhou, Zhejiang Province, China. Samples from the patients, close contacts, and local environments were examined by real time reverse transcriptase (rRT) polymerase chain reaction (PCR) and viral culture. Haemagglutination inhibition and microneutralisation assays were used to detect specific antibodies to the viruses. Primary outcomes were clinical data, infection source tracing, phylogenetic tree analysis, and serological results. STUDY ANSWER AND LIMITATIONS: A 49 year old man (index patient) became ill seven days after visiting a live poultry market. A 57 year old man (second patient), with a history of chronic obstructive pulmonary disease, developed influenza-like symptoms after sharing the same hospital ward as the index patient for five days. The second patient had not visited any poultry markets nor had any contact with poultry or birds within 15 days before the onset of illness. H7N9 virus was identified in the two patients, who both later died. Genome sequences of the virus isolated from both patients were nearly identical, and genetically similar to the virus isolated from the live poultry market. No specific antibodies were detected among 38 close contacts. Transmission between the patients remains unclear, owing to the lack of samples collected from their shared hospital ward. Although several environmental swabs were positive for H7N9 by rRT-PCR, no virus was cultured. Owing to delayed diagnosis and frequent hospital transfers, no serum samples were collected from the patients, and antibodies to H7N9 viruses could not be tested. WHAT THIS STUDY ADDS: Nosocomial H7N9 transmission might be possible between two unrelated individuals. Surveillance on patients with influenza-like illness in hospitals as well as chickens in live poultry markets should be enhanced to monitor transmissibility and pathogenicity of the virus. FUNDING, COMPETING INTERESTS, DATA SHARING: Funding support from the Program of International Science and Technology Cooperation of China (2013DFA30800), Basic Work on Special Program for Science and Technology Research (2013FY114600), National Natural Science Foundation of China (81402730), Special Program for Prevention and Control of Infectious Diseases in China (2013ZX10004218), US National Institutes of Health (1R01-AI108993), Zhejiang Province Major Science and Technology Program (2014C03039), and Quzhou Science and Technology Program (20111084). The authors declare no other interests and have no additional data.

Transmissibility of tuberculosis among school contacts: an outbreak investigation in a boarding middle school, China.

Tuberculosis (TB) outbreak occurred in a boarding middle school of China. We explored its probable sources and quantified the transmissibility and pathogenicity of TB. Clinical evaluation, tuberculin skin testing and chest radiography were conducted to identify TB cases. Mycobacterium tuberculosis isolates underwent genotyping analysis to identify the outbreak source. A chain-binomial transmission model was used to evaluate transmissibility and pathogenicity of TB. A total of 46 active cases were ascertained among 258 students and 15 teachers/staff, an attack rate of 16.8%. Genetic analyses revealed two groups of M. tuberculosis cocirculating during the outbreak and possible importation from local communities. Secondary attack rates among students were 4.1% (2.9%, 5.3%) within grade and 7.9% (4.9%, 11%) within class. An active TB case was estimated to infect 8.4 (7.2, 9.6) susceptible people on average. The smear-positive cases were 28 (8, 101) times as infective as smear-negative cases. Previous BCG vaccination could reduce the probability of developing symptoms after infection by 70% (1.4%, 91%). The integration of clinical evaluation, genetic sequencing, and statistical modeling greatly enhanced our understanding of TB transmission dynamics. Timely diagnosis of smear-positive cases, especially in the early phase of the outbreak, is the key to preventing further spread among close contacts.

Characterization of a novel reassortant influenza A virus (H2N2) from a domestic duck in Eastern China.

While H2N2 viruses have been sporadically isolated from wild and domestic birds, H2N2 viruses have not been detected among human populations since 1968. Should H2N2 viruses adapt to domestic poultry they may pose a risk of infection to people, as most anyone born after 1968 would likely be susceptible to their infection. We report the isolation of a novel influenza A virus (H2N2) cultured in 2013 from a healthy domestic duck at a live poultry market in Wuxi City, China. Sequence data revealed that the novel H2N2 virus was similar to Eurasian avian lineage avian influenza viruses, the virus had been circulating for ≥ two years among poultry, had an increase in α2,6 binding affinity, and was not highly pathogenic. Approximately 9% of 100 healthy chickens sampled from the same area had elevated antibodies against the H2 antigen. Fortunately, there was sparse serological evidence that the virus was infecting poultry workers or had adapted to infect other mammals. These findings suggest that a novel H2N2 virus has been circulating among domestic poultry in Wuxi City, China and has some has increased human receptor affinity. It seems wise to conduct better surveillance for novel influenza viruses at Chinese live bird markets.

Comparison of commercial influenza A virus assays in detecting avian influenza H7N9 among poultry cloacal swabs, China.

BACKGROUND: Avian H7N9 virus emerged in China in February 2013 and has since spread widely among China's poultry, causing numerous human infections. OBJECTIVES: To compare World Health Organization (WHO) and US commercial influenza assays in detecting avian H7N9 virus in poultry cloacal specimens. STUDY DESIGN: Between April 6 and July 15, 2013, 261 cloacal swabs were collected from commercial poultry in Nanjing and Wuxi City, Jiangsu Province, China. Swabs were screened with the WHO's influenza A and H7N9 real-time RT-PCR (qRT-PCR) assays. A blinded panel of 97 specimens (27 H7N9-positive and 70 influenza A-negative) was then used to compare 3 antigen based commercial assays (Remel Xpect Flu A&B, Quidel Quickvue influenza, and Quidel Sofia Influenza A+B), and 2 molecular commercial assays (Quidel Molecular Influenza A+B assay and Life Technologies VetMAX™-Gold SIV Detection Kit). None of these commercial assays were approved for use with poultry specimens. RESULTS: Considering the WHO H7N9 qRT-PCR assay as the gold standard, all assays except the Quidel Quickvue influenza assay had high specificity (ranging from 96 to 99%). Regarding sensitivity, the Life Technologies VetMAX™-Gold SIV Detection Kit (100%; 95% CI 87-100%) and the Quidel Molecular Influenza A+B assay (85%; 95% CI 66-96%) performed the best. The sensitivities of the non-molecular antigen detection assays were either unable to detect small amounts of H7N9 viral RNA or were inhibited by specimen type. CONCLUSIONS: The Life Technologies VetMAX™-Gold SIV Detection Kit and the Quidel Molecular Influenza A+B assay are comparable in performance to the WHO H7N9 qRT-PCR assay in detecting H7N9 from poultry cloacal specimens.

Cdc37p is involved in osmoadaptation and controls high osmolarity-induced cross-talk via the MAP kinase Kss1p.

Cdc37p, the p50 homolog of Saccharomyces cerevisiae, is an Hsp90 cochaperone involved in the targeting of protein kinases to Hsp90. Here we report a role for Cdc37p in osmoadaptive signalling in this yeast. The osmosensitive phenotype that is displayed by the cdc37-34 mutant strain appears not to be the consequence of deficient signalling through the high osmolarity glycerol (HOG) MAP kinase pathway. Rather, Cdc37p appears to play a role in the filamentous growth (FG) pathway, which mediates adaptation to high osmolarity parallel to the HOG pathway. The osmosensitive phenotype of the cdc37-34 mutant strain is aggravated upon the deletion of the HOG gene. We report that the hyper-osmosensitive phenotype of the cdc37-34, hog1 mutant correlates to a reduced of activity of the FG pathway. We utilized this phenotype to isolate suppressor genes such as KSS1 that encodes a MAP kinase that functions in the FG pathway. We report that Kss1p interacts physically with Cdc37p. Like Kss1p, the second suppressor that we isolated, Dse1p, is involved in cell wall biogenesis or maintenance, suggesting that Cdc37p controls osmoadapation by regulating mitogen-activated protein kinase signalling aimed at adaptive changes in cell wall organization.

Cdc37p is required for stress-induced high-osmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p).

The yeast Saccharomyces cerevisiae utilizes rapidly responding mitogen-activated protein kinase (MAPK) signaling cascades to adapt efficiently to a changing environment. Here we report that phosphorylation of Cdc37p, an Hsp90 cochaperone, by casein kinase 2 controls the functionality of two MAPK cascades in yeast. These pathways, the high-osmolarity glycerol (HOG) pathway and the cell integrity (protein kinase C) MAPK pathway, mediate adaptive responses to high osmotic and cell wall stresses, respectively. Mutation of the phosphorylation site Ser14 in Cdc37p renders cells sensitive to osmotic stress and cell wall perturbation by calcofluor white. We found that levels of the MAPKs Hog1p and Slt2p (Mpk1p) in cells are reduced in a cdc37-S14A mutant, and consequently downstream responses mediated by Hog1p and Slt2p are compromised. Furthermore, we present evidence that Hog1p and Slt2p both interact in a complex with Cdc37p in vivo, something that has not been reported previously. The interaction of Hsp90, Slt2p, and Hog1p with Cdc37p depends on the phosphorylation status of Cdc37p. In fact, our biochemical data show that the osmosensitive phenotype of the cdc37-S14A mutant is due to the loss of the interaction between Cdc37p, Hog1p, and Hsp90. Likewise, during cell wall stress, the interaction of Slt2p with Cdc37p and Hsp90 is crucial for Slt2p-dependent downstream responses, such as the activation of the transcription factor Rlm1p. Interestingly, phosphorylated Slt2p, but not phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these observations suggest that Cdc37p acts as a regulator of MAPK signaling.

The molecular chaperone Hsp90 is required for high osmotic stress response in Saccharomyces cerevisiae.

Exposure of Saccharomyces cerevisiae to high osmotic stress evokes a number of adaptive changes that are necessary for its survival. These adaptive responses are mediated via multiple mitogen-activated protein kinase pathways, of which the high-osmolarity glycerol (HOG) pathway has been studied most extensively. Yeast strains that bear the hsp82T22I or hsp82G81S mutant alleles are osmosensitive. Interestingly, the osmosensitive phenotype is not due to inappropriate functioning of the HOG pathway, as Hog1p phosphorylation and downstream responses including glycerol accumulation are not affected. Rather, the hsp82 mutants display features that are characteristic for cell-wall mutants, i.e. resistance to Zymolyase and sensitivity to Calcofluor White. The osmosensitivity of the hsp82T22I or hsp82G81S strains is suppressed by over-expression of the Hsp90 co-chaperone Cdc37p but not by other co-chaperones. Hsp90 is shown to be required for proper adaptation to high osmolarity via a novel signal transduction pathway that operates parallel to the HOG pathway and requires Cdc37p.