Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension

BACKGROUND Portal hypertension(PHT),primarily induced by cirrhosis,manifests severe symptoms impacting patient survival.Although transjugular intrahepatic portosystemic shunt(TIPS)is a critical intervention for managing PHT,it carries risks like hepatic encephalopathy,thus affecting patient survival prognosis.To our knowledge,existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes.Consequently,the development of an innovative modeling approach is essential to address this limitation.AIM To develop and validate a Bayesian network(BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS.METHODS The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed.Variables were selected using Cox and least absolute shrinkage and selection operator regression methods,and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT.RESULTS Variable selection revealed the following as key factors impacting survival:age,ascites,hypertension,indications for TIPS,postoperative portal vein pressure(post-PVP),aspartate aminotransferase,alkaline phosphatase,total bilirubin,prealbumin,the Child-Pugh grade,and the model for end-stage liver disease(MELD)score.Based on the above-mentioned variables,a BN-based 2-year survival prognostic prediction model was constructed,which identified the following factors to be directly linked to the survival time:age,ascites,indications for TIPS,concurrent hypertension,post-PVP,the Child-Pugh grade,and the MELD score.The Bayesian information criterion was 3589.04,and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16.The model’s accuracy,precision,recall,and F1 score were 0.90,0.92,0.97,and 0.95 respectively,with the area under the receiver operating characteristic curve being 0.72.CONCLUSION This study successfully developed a BN-based survival prediction model with good predictive capabilities.It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM： To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B （CHB）. METHODS： A total of 137 consecutive patients with CriB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase （ALT） level. The sensitivity, specificity, positive predictive value （PPV）, negative predictive value （NPV）, the likelihood ratio （LR） of aminotransferase/platelet ratio index （APRI） ≥ 1.5 or 〈 1.5 in combination with different hyaluronic acid （HA） cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis （fibrosis stages 2 and 4） and no to mild fibrosis/cirrhosis （fibrosis stages 0 and 1）. RESULTS： The APRI correlated with fibrosis stage in CriB patients. The APRI ≥1.5 in combination with a cut-off HA cut-off point 〉 300 ng/mL could detect moderate to severe fibrosis （stages 2-4） in Crib patients. The PPV was 93.7%, the specificity was 98.9%. The APRI 〈 1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION： The APRI ≥ 1.5 in combination with a HA cut-off point 〉 300 ng/mL can detect moderate to severe fibrosis （stages 2-4） in Crib patients.

Indirect Enzyme-Linked Immunosorbent Assay Based on the Nucleocapsid Protein of SARS-like Coronaviruses

The nucleocapsid protein(N) is a major structural protein of coronaviruses. The N protein of bat SARS-like coronavirus(SL-CoV) has a high similarity with that of SARS-CoV. In this study,the SL-CoV N protein was expressed in Escherichia coli,purified and used as antigen. An Indirect Enzyme-Linked Immunosorbent Assay(indirect ELISA) was developed for detection of SARS-or SL-CoV infections in bat populations. The detection of 573 bat sera with this indirect ELISA demonstrated that SL-CoVs consistently circulate in Rhinilophus species,further supporting the proposal that bats are natural reservoirs of SL-CoVs. This method uses 1-2 μl of serum sample and can be used for preliminary screening of infections by SARS-or SL-CoV with a small amount of serum sample.

Ecological study of cave nectar bats reveals low risk of direct transmission of bat viruses to humans

Bats are reservoirs of various viruses.The widely distributed cave nectar bat(Eonycteris spelaea)is known to carry both filoviruses and coronaviruses.However,the potential transmission of theses bat viruses to humans is not fully understood.In this study,we tracked 16 E.spelaea bats in Mengla County,Yunnan Province,China,using miniaturized GPS devices to investigate their movements and potential contact with humans.Furthermore,to determine the prevalence of coronavirus and filovirus infections,we screened for the nucleic acids of the Měnglàvirus(MLAV)and two coronaviruses(GCCDC1-CoV and HKU9-CoV)in anal swab samples taken from bats and for antibodies against these viruses in human serum samples.None of the serum samples were found to contain antibodies against the bat viruses.The GPS tracking results showed that the bats did not fly during the daytime and rarely flew to residential areas.The foraging range of individual bats also varied,with a mean cumulative nightly flight distance of 25.50 km and flight speed of up to 57.4 km/h.Taken together,these results suggest that the risk of direct transmission of GCCDC1-CoV,HKU9-CoV,and MLAV from E.spelaea bats to humans is very low under natural conditions.

Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans,China

Dear Editor,Severe acute respiratory syndrome coronavirus(SARSCo V)is the causative agent of the 2002–2003 SARS pandemic,which resulted in more than 8000 human infections worldwide and an approximately 10%fatality rate(Ksiazek et al.2003;Peiris et al.2004).The virus infects both upper airway and alveolar epithelial cells,resulting in mild to severe lung injury in

Chevrier＇s Field Mouse(Apodemus chevrieri) and Père David＇s Vole(Eothenomys melanogaster) in China Carry Orthohepeviruses that form Two Putative Novel Genotypes Within the Species Orthohepevirus C

Hepatitis E virus(HEV)is the prototype of the family Hepeviridae and the causative agent of common acute viral hepatitis.Genetically diverse HEV-related viruses have been detected in a variety of mammals and some of them may have zoonotic potential.In this study,we tested 278 specimens collected from seven wild small mammal species in Yunnan province,China,for the presence and prevalence of orthohepevirus by broad-spectrum reverse transcription(RT)-PCR.HEV-related sequences were detected in two rodent species,including Chevrier’s field mouse(Apodemus chevrieri,family Muridae)and Père David’s vole(Eothenomys melanogaster,family Cricetidae),with the infection rates of 29.20%(59/202)and 7.27%(4/55),respectively.Further four representative full-length genomes were generated:two each from Chevrier’s field mouse(named Rd HEVAc14 and Rd HEVAc86)and Père David’s vole(Rd HEVEm40 and Rd HEVEm67).Phylogenetic analyses and pairwise distance comparisons of whole genome sequences and amino acid sequences of the gene coding regions showed that orthohepeviruses identified in Chinese Chevrier’s field mouse and Père David’s vole belonged to the species Orthohepevirus C but were highly divergent from the two assigned genotypes:HEV-C1 derived from rat and shrew,and HEV-C2 derived from ferret and possibly mink.Quantitative real-time RT-PCR demonstrated that these newly discovered orthohepeviruses had hepatic tropism.In summary,our work discovered two putative novel genotypes orthohepeviruses preliminarily named HEVC3 and HEV-C4 within the species Orthohepevirus C,which expands our understanding of orthohepevirus infection in the order Rodentia and gives new insights into the origin,evolution,and host range of orthohepevirus.

Longitudinal Surveillance of Betacoronaviruses in Fruit Bats in Yunnan Province,China During 2009–2016

Previous studies indicated that fruit bats carry two betacoronaviruses,BatCoV HKU9 and BatCoV GCCDC1.To investigate the epidemiology and genetic diversity of these coronaviruses,we conducted a longitudinal surveillance in fruit bats in Yunnan province,China during 2009–2016.A total of 59(10.63%)bat samples were positive for the two betacorona-viruses,46(8.29%)for HKU9 and 13(2.34%)for GCCDC1,or closely related viruses.We identified a novel HKU9 strain,tentatively designated as BatCoV HKU9-2202,by sequencing the full-length genome.The BatCoV HKU9-2202 shared 83%nucleotide identity with other BatCoV HKU9 stains based on whole genome sequences.The most divergent region is in the spike protein,which only shares 68%amino acid identity with BatCoV HKU9.Quantitative PCR revealed that the intestine was the primary infection organ of BatCoV HKU9 and GCCDC1,but some HKU9 was also detected in the heart,kidney,and lung tissues of bats.This study highlights the importance of virus surveillance in natural reservoirs and emphasizes the need for preparedness against the potential spill-over of these viruses to local residents living near bat caves.

Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft

Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.

Longitudinal surveillance of SARS-like coronaviruses in bats by quantitative real-time PCR

Dear Editor,The 2002–2003 severe acute respiratory syndrome coronavirus（SARS-CoV）（Drosten et al.,2003）caused human pandemics that began in China and spread globally.Subsequently,

A large-scale fatal outbreak of Pasteurella multocida among wild rodents in southwestern China

Background:Pasteurella multocida is an important and old zoonotic pathogen worldwide which has an impressive host spectrum including numerous domestic and wild animals as well as birds,causing specific diseases or outbreak with great economic impact.It has never been reported that P.multocida can cause an epidemic in wild rodents.In June 5–17,2016,more than 1000 rodent deaths of an unknown cause quickly spread in the PuEr City,Yunnan province,southwestern China.Methods:The rodents in affected areas and outside of the epidemic areas were collected and screened for possible known pathogens including Yersinia pestis,rabies virus and hantavirus as well as other bacteria.The possible bacterial pathogens were isolated both by culture medium and by mouse inoculation in parallel.The isolates were identified by the Vitek GNI card and PCR assays for 16S rRNA genes.The pathogen strains were selected for whole genome sequencing analysis.Results:A total of 123 rodents were collected from 25 sample sites at affected area,among of which,all 119 dead rodents were negative for the pathogen under consideration except P.multocida,and all four live rodents were negative for P.multocida.In addition,480 rodents collected from other 23 counties outside of the epidemic area in Yunnan were negative for with P.multocida.A total of 14 strains of P.multocida(six directly isolated from the field rodents and eight from the experimental mice that were injected with the organ substrates from the dead rodents)belonged to serogroup A and serogroup F represented by 9 N and 20 N were identified in these epidemic areas.Whole genome sequencing revealed that the serogroup F strain shared 99%similarity to P.multocida Pm70 from chicken,but contained a 50 k bp insertion sequence.The serogroup A strain shared 95%similarity to P.multocida FDAARGOS_385 from a human patient,but contained four large structural differences.Histological abnormalities were identified in the livers,lungs,hearts and brains of the inoculated mice.Conclusions:The simultaneous occurrence of both serotypes of P.multocida may have caused this sudden onset of mortality across the local rodent population in Yunnan Province,China.Further attention should be paid to this old bacterium in the world.