Omadacycline in the treatment of scrub typhus:Three case reports

BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.

Pulmonary abscess caused by Streptococcus pseudopneumoniae in a child:A case report and review of literature

BACKGROUND Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children.Several pathogens can cause lung abscesses,with the most common pathogens being anaerobes,Streptococci and Staphylococcus aureus.Streptococcus pseudopneumoniae(S.pseudopneumoniae)is a member of the Streptococcaceae family,and is mainly isolated from respiratory tract specimens.There are currently no cases of lung abscess caused by S.pseudopneumoniae in the literature.CASE SUMMARY A 2-year-old boy was admitted to hospital due to persistent cough and fever.Lung computed tomography examination suggested the formation of a lung abscess.His diagnosis was not confirmed by testing for serum respiratory pathogens(6 items),respiratory pathogen nucleic acid(27 items),and laboratory culture.Finally,metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S.pseudopneumoniae,confirming its role in causing the lung abscess.After receiving antibiotic treatment,reexamination with lung computed tomography showed that the abscess was resorbed and the patient’s outcome was good.CONCLUSION This is the first report of a lung abscess in a child caused by S.pseudopneumoniae infection.Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.

Biomarkers for hepatocellular carcinoma: What's new on the horizon?

Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.

Transcriptome exploration to provide a resource for the study of Auricularia heimuer

Auricularia heimuer,an edible jelly fungus,is in considerable demand in Asia due to its high nutritive,economic and medicinal values.RNA-Seq was used to investigate and analyze the mycelium transcriptome of A.heimuer for gene discovery.A total of 26,857 unigenes with an N50 length of 1333 bp were assembled by de novo sequencing.In addition,unigenes were annotated by publicly available databases,including gene descriptions,gene ontology(GO),clusters of orthologous group(COG),Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathways,and protein family(Pfam)terms.A.heimuer was also studied for its wood degradation ability.Thirty-eight putative FOLymes(fungal oxidative lignin enzymes)and 251 CAZymes(carbohydrate-active enzymes)were located from A.heimuer transcriptome.Our study provides a comprehensive sequence resource for A.heimuer at the transcriptional level,which will lay a strong foundation for functional genomics studies and gene discovery of this promising fungus.

Prognostic role of multiple abnormal genes in non-small-cell lung cancer

BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years,the prognosis remains poor.Therefore,it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIM To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODS We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas(TCGA)database.We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients.Multivariate Cox regression analysis and survival analysis were performed.RESULTS Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival:TP53(P=0.79),PTEN(P=0.94),RB1(P=0.49),CTNNB1(P=0.24),STK11(P=0.32),and PIK3CA(P=0.013).However,the probability of multiple genes(TP53,PTEN,RB1,and STK11)affecting survival was 0.025.Retrospective analysis of clinical data revealed that sex(hazard ratio[HR]=1.29;[95%CI:0.64-2.62]),age(HR=1.05;[95%CI:1.02-1.07]),smoking status(HR=2.26;[95%CI:1.16-4.39]),tumor histology(HR=0.58;[95%CI:0.30-1.11]),cancer stage(HR=16.63;[95%CI:4.8-57.63]),epidermal growth factor receptor(EGFR)mutation(HR=1.82;[95%CI:1.05-3.16]),abundance(HR=4.95;[95%CI:0.78-31.36]),and treatment with tyrosine kinase inhibitors(TKIs)(HR=0.58;[95%CI:0.43-0.78])affected patient survival.Co-occurring mutations of TP53,PTEN,RB1,and STK11 did not significantly affect the overall survival of patients receiving chemotherapy(P=0.96)but significantly affected the overall survival of patients receiving TKIs(P=0.045).CONCLUSION Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients.Combined with TKI treatment,the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

Consensus molecular subtypes of colorectal cancer in clinical practice:A translational approach

The identification of several genetic mutations in colorectal cancer(CRC)has allowed a better comprehension of the prognosis and response to different antineoplastic treatments.Recently,through a systematic process,consensus molecular subtypes(CMS)have been described to characterize genetic and molecular mutations in CRC patients.Through CMS,CRC patients can be categorized into four molecular subtypes of CRC by wide transcriptional genome analysis.CMS1 has microsatellite instability and mutations in CIMP and BRAF pathways.CMS2,distinguished by mutations in specific pathways linked to cellular metabolism,also has a better prognosis.CMS3 has a KRAS mutation as a hallmark.CMS4 presents mutations in fibrogenesis pathways and mesenchymalepithelial transition,associated with a worse prognosis.CMS classification can be a meaningful step in providing possible answers to important issues in CRC,such as the use of adjuvant chemotherapy in stage II,personalized first-line chemotherapy for metastasic CRC,and possible new target treatments that address specific pathways in each molecular subtype.Understanding CMS is a crucial step in personalized medicine,although prospective clinical trials selecting patients by CMS are required to pass proof-of-concept before becoming a routine clinical tool in oncology routine care.

Metagenomic approach revealed effects of forest thinning on bacterial communities in the forest soil of Mt. Janggunbong, South Korea

The soil microbiome that plays important ecological roles in mountains and forests is influenced by anthropogenic and natural causes.Human activity,particularly harvesting or thinning,affects the soil microbiome in forests by altering environmental conditions,such as vegetation,microclimate,and soil physicochemical properties.The purpose of this study was to investigate the effects on forest thinning on the diversity and composition of the soil bacterial community.From next-generation sequencing results of the 16S rRNA gene,we examined differences in soil bacterial diversity and community composition before and after thinning at Mt.Janggunbong,South Korea.We identified 40 phyla,103 classes,192 orders,412families,947 genera,and 3,145 species from the soil samples.Acidobacteria and Proteobacteria were the most dominant bacterial phyla in the forest soil of Mt.Janggunbong.Soil bacterial diversity measures(richness,Shannon diversity index,and evenness)at the phylum level increased after thinning,whereas species-level taxonomic richness decreased after thinning.Thinning provided new opportunities for bacterial species in Chloroflexi,Verrucomicrobia,Nitrospirae,and other nondominant bacterial taxa,especially for those not found in Mt.Janggunbong before thinning,to settle and adapt to the changing environment.Our results suggested that thinning affected the diversity and composition of soil bacterial communities in forests and mountains.

Discrepancy among microsatellite instability detection methodologies in non-colorectal cancer:Report of 3 cases

BACKGROUND Microsatellite instability(MSI)is a predictive biomarker for cancer immunotherapy.The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors.It can be assessed using next-generation sequencing(NGS),fluorescent multiplex PCR,and immunohistochemistry(IHC).CASE SUMMARY Here,we report 3 cases with discordant MSI results detected using different methods.A cholangiocellular carcinoma case revealed proficient mismatch repair(MMR)by IHC but high MSI(MSI-H)by liquid NGS.A cervical cancer case revealed deficient MMR by IHC,microsatellite stable by PCR,and MSI-H by NGS.Lastly,an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS.CONCLUSION IHC for MMR status is the first choice due to several advantages.However,in cases of indeterminate IHC results,molecular testing by MSI-PCR is preferred.Recently,NGS-based MSI assays are being widely used to detect MSI-H tumors.All three methods have high accuracy;however,the inconsistencies between them may lead to misdiagnosis.

Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas

Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.

Inflammatory myofibroblastic tumor of the distal common bile duct:Literature review with focus on pathological examination

Inflammatory myofibroblastic tumor(IMT)of the biliary tract is rare,and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features.Histologically,IMTs are(myo)fibroblastic neoplasms with a prominent inflammatory infiltrate.They are characterized by receptor tyrosine kinase gene rearrangements,most often involving an anaplastic lymphoma kinase(ALK)translocation.The final diagnosis of IMT depends on histopathology and immunohistochemical examination.In this manuscript,we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.

Antibiotic resistance mechanisms of Myroides sp.

Bacteria of the genus Myroides （Myroides spp.） are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA （rRNA） gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that ob- taining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infec- tions. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.