Molecular Typing of Brucella Suis Collected from 1960s to 2010s in China by MLVA and PFGE

Brucellosis is a bacterial anthropozoonosis usually caused by Brucella abortus, Brucella melitensis, Brucella suis and Brucella canis. Brucella suis, the causative agent of swine brucellosis, is classified into five biovars and preferentially infects different animal hostsIll. In China, brucellosis is a national notifiable communicable disease both in animals and in human. In 2009, 35 816 brucellosis cases were reported. The annual incidence was 2.7 per 100 000 population.

Overview of Molecular Typing Tools for The Characterization of Salmonella enterica in Malaysia

Salmonella is a member of the family Enterobacteriaceae. This genus comprises two species, namely Salmonella enterica and Salmonella bongori. Salmonella enterica is further divided into six subspecies, namely enterica, salamae, arizonae,

Distribution of Candida Species and Molecular Typing of C. albicans Isolates in a Mexico City Tertiary Care Hospital from 2011 to 2013

The incidence of yeast infections has increased significantly over the past few years, constituting a leading cause of morbidity and mortality among hospitalised patients. The rapid identification of candidiasis is important for the clinical management of patients and to facilitate tracing the sources of infections in hospitalized patients. Here, we report a retrospective, single-centre study of Candida spp. distribution and antifungal susceptibility from January 2011 to May 2013 at a hospital in México City, regarding the importance of elucidating the identity of the infection-causing Candida species in order to improve prophylactic measures and treatment. Clinical data were collected from patient medical records and the laboratory database. Isolates were initially identified using standard mycology techniques, and then confirmed by PCR-based system using amplification of intergenic spacers (rDNA ITS) and restriction length polymorphism of PCR products after sequence-specific enzymatic cleavage (PCR-RFLP). We observed no shift from C. albicans to non-albicans Candida species: Candida albicans (73.7%) was the most prevalent species isolated, while C. dubliniensis was not identified in this study. Antifungal susceptibility was determined using FUNGITEST®;17.4% of C. albicans isolates were resistant to fluconazole and 21.7% to itraconazole. Multiplex PCR microsatellite analysis of the clinical C. albicans isolates using primers for the CAI, CAIII and CAVI loci identified 29 different alleles for CAI, 8 alleles for CAIII and 31 for CAVI. The combined discriminatory power of these three microsatellites was 0.98, which was considered reliable for molecular typing. Genetic analysis of these isolates revealed a clonal population with a total of 62 genotypes from the examined isolates

Molecular typing guiding treatment and prognosis of endometrial cancer

Genetic abnormalities,such as PTEN,PIK3CA,CTNNB1,ARID1A,and ERBB2,which frequently occur in endometrial cancer(EC),are potential therapeutic targets.In 2013,integrated genomic analysis conducted by The Cancer Genome Atlas identified four molecular subtypes,including POLE ultra-mutated,microsatellite instability hypermutated,copy-number low,and copy-number high,which strongly correlate with prognosis.Surrogate markers-based molecular classification methods have been developed to make these molecular classifications accessible and affordable,achieving classification into POLEmut,mismatch repair deficient(MMRd),p53abn,and no specific molecular profile(NSMP)with normal p53 expression.Although POLEmut EC has aggressive pathologic features,there are few cases of advanced and/or recurrence.Therefore,the possibility of de-escalating adjuvant therapy can be considered.Additionally,immune checkpoint inhibitors(ICI)may be a candidate for treating advanced and recurrent POLEmut EC because of their high immunogenicity.MMRd EC shows an intermediate prognosis between those of POLEmut and p53abn EC.MMRd EC is generally characterized by high immunogenicity similar to POLEmut EC,suggesting that ICI can also be a potential therapeutic agent.Among the four molecular subtypes,p53abn EC has the worst prognosis.However,some p53abn tumors have the molecular hallmark of homologous recombination deficiency and could be treated with poly(ADP-ribose)polymerase inhibitors.In addition,some p53abn tumors overexpress the human epidermal growth factor receptor 2,which can also be a potential therapeutic target.NSMP EC are a heterogeneous population because they lack characteristic molecular biological features.Approximately half of the NSMP EC show high expression of estrogen receptor/progesterone receptor,suggesting the possibility of hormonal therapy.In addition,the PI3K/AKT/mTOR pathway frequently altered in EC may be a therapeutic target.This review summarizes the molecular biological characteristics and potential therapeutic agents in molecularly featured EC.Several clinical trials are in progress to stratify EC into molecular classifications and demonstrate the efficacy and safety of molecularly matched treatment and management strategies.

Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Molecular Beam Epitaxy of Zero Lattice-Mismatch InAs/GaSb Type-Ⅱ Superlattice

Type-Ⅱ InAs/GaSb superlattiees made of 13 InAs monolayers （MLs） and 7 GaSb MLs are grown on GaSb substrates by solid source molecular beam epitaxy. To obtain lattice-matched structures, thin InSb layers are inserted between InAs and GaSb layers. We complete a series of experiments to investigate the influence of the InSb deposition time, Ⅴ/Ⅲ beam-equivalent pressure ratio and interruption time between each layer, and then characterize the superlattice （SL） structures with high-resolution x-ray diffraction and atomic force microscopy. The optimized growth parameters are applied to grow the 100-period SL structure, resulting in the full-width half-maximum of 29.55 arcsee for the first SL satellite peak and zero lattice-mismatch between the zero-order SL peak and the GaSb substrate peak.

ON SIMULTANEOUS SUBSTITUTION OF TI AND V INTO MCM-41 TYPE MOLECULAR SIEVE

The new crystalline V-Ti-silicalite with mesoporous MCM-41 type molecular sieve structure is synthesized hydrothermally; The framework IR spectra associated with ESR, Si-29 MAS NMR, DRS and XPS data shows that V and Ti are simultaneously incorporated into V-TiMCM-41 framework.

STRUCTURE OF MOLECULAR COMPOUND CRYSTAL A_2B(A =1, 6, 7, 8,-TETRA-PHENYL (3, 4-BENZO)BICYCLO[4, 2, 0]OCTA-7-ENE, B=CIS, CIS-1,2,3,4,-TETRAPHENYLBUTADIENE)

C100H78, (A: C36H28, B: C28H22) Mr = 1279. 74, monoclinic, P21/a, a=17. 282(3), b=10. 669(4), c= 19, 927(3) A , β =102. 99(1)°,V = 3580. 1(2) A3, Z=2, μ(MoKα) = 0. 623cm-1, F(000) = 1356, Dc=1. 187g/cm3, room temperature. The final R=0. 084, Rw = 0. 086 for 1255 independent observed reflections (I≥3σ(I)). Owing to the existence of 1,6,7, 8-Tetraphenyl (3,4-benzo)-bicyclo[4, 2, 0]octa-7-ene(A) , cis, cts-1, 2, 3, 4-Tetraphenylbutadiene (B) in A2B can take the different conformation from the one in the pure B crystal. The reason of the formation of this molecular compound crystal is put forward.

Designing a risk prognosis model based on natural killer cell-linked genes to accurately evaluate the prognosis of gastric cancer

Background:This study was aimed at identifying natural killer(NK)cell-related genes to design a risk prognosis model for the accurate evaluation of gastric cancer(GC)prognosis.Methods:We obtained NK cell-related genes from various databases,followed by Cox regression analysis and molecular typing to identify prognostic genes.Various immune algorithms and enrichment analyses were used to investigate the mutations,immune status,and pathway variations among different genotypes.The key prognostic genes were assessed using the least absolute shrinkage and selection operator(Lasso)regression analysis and univariate Cox regression analysis.Thereafter,the risk score(RS)prognosis model was constructed based on the selected important prognostic genes.A Receiver Operating Characteristics(ROC)curve was plotted for analyzing the robustness of the model.Subsequently,the decision and calibration curves were used for assessing the reliability and prediction accuracy of the proposed model.The‘pRRophetic’R software package was utilized for predicting the half-maximal inhibitory concentration(IC50)of immunotherapy and chemotherapy drugs.Results:We screened 21 prognostic genes and three molecular subtypes and found that the C1 subtype had the worst prognosis.Further,the pathways promoting tumor proliferation,such as epithelial-mesenchymal transition were significantly up-regulated.The results also showed that the macrophages in the M2 stage were significantly infiltrated in the C1 subtype,and there was significant overexpression in the C1 subtype,accompanied by a severe inflammatory reaction.The C1 was highly sensitive to drugs like 5-fluorouracil and paclitaxel.The ROC,calibration curve,and decision curve showed that the risk model was robust and strongly reliable.Conclusion:Overall,our proposed NK cell-related RS model can be used as a more accurate prediction index for GC patients,providing a valuable contribution to personalized medicine.

Fluconazole Susceptibility and Genotypic Heterogeneity of Oral Candida albicans Colonies from the Patients with Cancer Receiving Chemotherapy in China

Aim To identify heterogeneity of Candida albicans （C. albicans） isolated from the population with cancer in China by using identification medium, subculture molecular typing, and antifungal susceptibility test. Methodology Oral cheek mucosal specimens from 52 cancer patients receiving chemotherapy were cultured on CHROMagar CandidaTM plates for Candida identification. All the C. albicans colonies on the plates were subcultured and reconfirmed by API20C, then submitted to the antifimgal drug susceptibility test with fluconazole and molecular typing using randomly amplified polymorphic DNA-PCR （RAPD） with primers RSD6 and RSD12.Results 54% （28/52） patients were oral yeast carriage in which C. albicans predominated. More than 7 C. albicans colonies were isolated from each of 12 patients （Group A）, while less than 5 colonies were isolated from each of 16 patients （Group B）. RSD6 and RSD12 were successful in eliciting 17 （A1-A17） and 2 （B1-B2） genotypes, respectively from among the 205 isolates. The two primers were combined to generate 21 genotypes. The C. albicans isolates obtained from the same patient and episode showed a diversity for fluconazole revealed by MIC50 and MIC90. Conclusion The heterogeneity of the C. albicans colonies isolated from the same patients can be detected. C. albicans with varied fluconazole susceptibility and genotypic characteristics may coexist in the same oral Candida population.

Research progress of individualized precision treatment for pancreatic cancer

Currently,there is the extremely poor prognosis for pancreatic cancer.Despite the continuous development of various technologies,the long-term survival rate is not improved well.With the rapid development of genomics and biotechnology,the concept of tumor precision treatment has attracted much attention.Gene sequencing technology and biomarker detection have been used to deeply explore the mechanism of the occurrence and development of pancreatic cancer and applied it to clinical diagnosis and treatment,making it possible for patients to carry out individualized precision treatment for pancreatic cancer.Multiple-factor analysis combined with meaningful biological indicators is more helpful to determine individualized diagnosis and treatment measures.This paper summarizes the research results in the above aspects.

Genetic source tracking of an anthrax outbreak in Shaanxi province,China

Background:Anthrax is an acute zoonotic infectious disease caused by the bacterium known as Bacillus anthracis.From 26 July to 8 August 2015,an outbreak with 20 suspected cutaneous anthrax cases was reported in Ganquan County,Shaanxi province in China.The genetic source tracking analysis of the anthrax outbreak was performed by molecular epidemiological methods in this study.Methods:Three molecular typing methods,namely canonical single nucleotide polymorphisms(canSNP),multiple-locus variable-number tandem repeat analysis(MLVA),and single nucleotide repeat(SNR)analysis,were used to investigate the possible source of transmission and identify the genetic relationship among the strains isolated from human cases and diseased animals during the outbreak.Results:Five strains isolated from diseased mules were clustered together with patients’isolates using canSNP typing and MLVA.The causative B.anthracis lineages in this outbreak belonged to the A.Br.001/002 canSNP subgroup and the MLVA15-31 genotype(the 31 genotype in MLVA15 scheme).Because nine isolates from another four provinces in China were clustered together with outbreak-related strains by the canSNP(A.Br.001/002 subgroup)and MLVA15 method(MLVA15-31 genotype),still another SNR analysis(CL10,CL12,CL33,and CL35)was used to source track the outbreak,and the results suggesting that these patients in the anthrax outbreak were probably infected by the same pathogen clone.Conclusions:It was deduced that the anthrax outbreak occurred in Shaanxi province,China in 2015 was a local occurrence.

Genomic characterization of multidrug-resistant extraintestinal pathogenic Escherichia coli isolated from grain culture soils

Multidrug-resistant(MDR)Escherichia coli,mainly extraintestinal pathogenic E.coli(ExPEC),has been widely reported in infections worldwide.In agricultural soils,manure is a hotspot for the dissemination of antimicrobial resistance genes(ARGs)and pathogenic bacteria;however,MDR bacteria have also been reported in soils with no history of manure use.In addition,cross-resistance and co-resistance have been described as responsible for the metal-driven selection of bacteria resistant to antimicrobials.Therefore,the aim of this study was to analyze three MDR E.coli isolates obtained from Brazilian grain culture soil samples with no history of manure use by whole-genome sequencing.The MDR E.coli isolates were recovered from soils from corn and coffee fields,and presented resistance toβ-lactams,quinolones,aminoglycosides,tetracyclines,sulphonamides,and dihydrofolate reductase inhibitor.Resistome analysis showed ARGs to several antimicrobials(i.e.,β-lactams,tetracyclines,aminoglycosides,sulphonamides,trimethoprim,phenicols,fosfomycin,and macrolides)as well as several metal resistance genes and antibacterial biocide resistance genes.In addition,known mutations in quinolone-resistance-determining regions of GyrA(Ser83Leu and Asp87Asn),ParE(Ser458Thr),and ParC(Ser80Ile)were also detected.Virulome analysis showed the presence of virulence genes(lpfA,mcmA,gad,mchF,iroN,cma,and iss)associated with ExPEC.Multidrug-resistant ExPEC isolates were assigned to phylogenetic group B1.The presence of MDR B1-ExPEC in soil samples shows the ability of these isolates to survive in soils.This study reports for the first time some sequence types(i.e.,ST345,ST448,and ST1146)of MDR E.coli in Brazilian soils.Therefore,these findings contribute to the monitoring of antimicrobial resistance and surveillance studies based on whole-genome sequencing worldwide.

Reconsider the safety of laparoscopic surgery in endometrial cancer

General introduction The 20th century witmessed the development of laparoscopic surgical technologies and its successful applications in gynecological and general surgeries.In 1901,Russian doctor Dimitri Ott,for the first time,inspected the human a bdominal cavity with a speculum through a small incision,which marked the origin of the concept of minimally invasive techniques."During the following decades,clinical diagnosis of intra-abdominal lesions was performed by some doctors in Europe and the US.with instuments similar to modern laparoscopy.But it was until 1980s that modem sense laparoscopic surgeries,induding laparoscopic appendicectomy and laparoscopic cholecystectomy,were conducted.In 1989,Dr.Reich Harry performned the first laparoscopic hysterectomy,'which is regarded as a comerstone in the history of gynecologic surgery.Afterwards,laparoscopic surgery rapidly stepped into the mainstream of gynecology practice during the 1990s,delivered for both benign and malignant diseases.Starting from the 2000s,the master-slave mode ro-botic system,exemplified by the da Vinci@robot,has been accepted wordwide,and currently,robot assisted laparoscopic approaches have taken up a major proportion of general,urologic and gynecologic sur-geries,especially in developed countries.5 From a historical perspective,the broad application of laparoscopic surgeries nowadays stands on solid foundations established in decades of technical revolutions and refinements.

Allergic fungal sinusitis caused by Schizophyllum commune

A case of allergic fungal sinusitis (AFS) due to Schizophyllum commune was reported.The pathogen was identified using molecular bioanalysis.The patient underwent the functional endoscopic sinus surgery followed by the radical maxillary sinusotomy with canine fossa trephine.This case suggested that complete surgery allowed optimal disease clearance for AFS caused by Schizophyllum commune.

Opportunities and challenges of immune checkpoint inhibitors for extensive-stage small-cell lung cancer

Small-cell lung cancer(SCLC)accounts for 15%–20%of primary lung cancers,and it is characterized by low differentiation,rapid proliferation,and early metastasis.At least two-thirds of SCLC patients present with the extensive stage(ES)at the time of initial clinical diagnosis.Over the last 2 decades,platinum-based combination chemotherapy has remained the standard first-line treatment for SCLC.With the introduction of the immunotherapy era,immunotherapy plus chemotherapy has replaced conventional chemotherapy as the first-line treatment option for ES-SCLC and is recommended by National Comprehensive Cancer Network clinical guidelines.Therefore,in this review,we present the latest research advances in SCLC treatment,predictive biomarkers,and other topics of high interest to provide options for patients with SCLC.

Identification of A-to-I RNA editing profiles and their clinical relevance in lung adenocarcinoma

Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma(LUAD)patients from our Nanjing Lung Cancer Cohort(NJLCC)and 486 LUAD patients from the TCGA database.The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients.The high RNA editing level in tumors was attributed to both RNA(ADAR1 expression)and DNA alterations(mutation load).Consensus clustering on RNA editing sites revealed a new molecular subtype(EC3)that was associated with the poorest prognosis of LUAD patients.Importantly,the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation.We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients.The model was further validated in the TCGA dataset and had an area under the curve(AUC)of the receiver operating characteristic curve of 0.93(95%CI:0.91-0.95).In addition,we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs.These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer.