OBJECTIVE: The haplotypes of Killer cell immunoglobulin-like receptors (KIR) can be divided into centromeric and telomeric ones. As the terminal gene at the centromeric end, KIR3DP1 plays an important role in stabilizing the haplotype structure. This study aimed to analyze the distribution of KIR3DP1 gene haplotypes among Han Chinese population in Zhejiang in order provide a basis for further analyzing the role of KIR3DP1 in the KIR haplotypes. METHODS: A total of 166 unrelated blood donors from Zhejiang were collected (Blood donation period: March 2020 to August 2020), and genotyping was performed by next-generation sequencing based on exon capture. The copy number and allelic frequency of the KIR3DP1 gene and the distribution of centromeric haplotypes were statistically analyzed. This study was approved by the Medical Ethics Committee of Zhejiang Blood Center (Ethics No.: 2023-001). RESULTS: The KIR3DP1 gene was positive for all individuals but with different copy numbers. Among these, 4 cases (2.4%) had only 1 copy, 156 cases (94.0%) had 2 copies, and 6 cases (3.6%) had 3 copies. A total of 10 KIR3DP1 alleles were found in the population, which could be classified into the KIR3DP1*001-L type, KIR3DP1*003-L type, and KIR3DP1 full deletion type. The KIR3DP1*003 L type allele was linked to the Cen-A01 and Cen-B01 types, and the KIR3DP1*001*L type allele and the KIR3DP1 deletion type were only present in the Cen-B02 type haplotype. CONCLUSION This study has derived a high-resolution distribution map of the KIR3DP1 gene in the Han population from Zhejiang, and found that the KIR3DP1 alleles showed different linkage with the centromeric haplotypes, which has provided a basis for further studying the role of KIR3DP1 in genetic immunity.
Adult ; Female ; Humans ; Male ; Alleles ; China/ethnology* ; Gene Frequency ; Genotype ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; East Asian People/genetics* ; Receptors, KIR/genetics*

Objective:The haplotypes of Killer cell immunoglobulin-like receptors (KIR) can be divided into centromeric and telomeric ones. As the terminal gene at the centromeric end, KIR3DP1 plays an important role in stabilizing the haplotype structure. This study aimed to analyze the distribution of KIR3DP1 gene haplotypes among Han Chinese population in Zhejiang in order provide a basis for further analyzing the role of KIR3DP1 in the KIR haplotypes. Methods:A total of 166 unrelated blood donors from Zhejiang were collected (Blood donation period: March 2020 to August 2020), and genotyping was performed by next-generation sequencing based on exon capture. The copy number and allelic frequency of the KIR3DP1 gene and the distribution of centromeric haplotypes were statistically analyzed. This study was approved by the Medical Ethics Committee of Zhejiang Blood Center (Ethics No.: 2023-001). Results:The KIR3DP1 gene was positive for all individuals but with different copy numbers. Among these, 4 cases (2.4%) had only 1 copy, 156 cases (94.0%) had 2 copies, and 6 cases (3.6%) had 3 copies. A total of 10 KIR3DP1 alleles were found in the population, which could be classified into the KIR3DP1*001-L type, KIR3DP1*003-L type, and KIR3DP1 full deletion type. The KIR3DP1*003-L type allele was linked to the Cen- A01 and Cen- B01 types, and the KIR3DP1*001-L type allele and the KIR3DP1 deletion type were only present in the Cen- B02 type haplotype. Conclusion:This study has derived a high-resolution distribution map of the KIR3DP1 gene in the Han population from Zhejiang, and found that the KIR3DP1 alleles showed different linkage with the centromeric haplotypes, which has provided a basis for further studying the role of KIR3DP1 in genetic immunity.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

Objective:The haplotypes of Killer cell immunoglobulin-like receptors (KIR) can be divided into centromeric and telomeric ones. As the terminal gene at the centromeric end, KIR3DP1 plays an important role in stabilizing the haplotype structure. This study aimed to analyze the distribution of KIR3DP1 gene haplotypes among Han Chinese population in Zhejiang in order provide a basis for further analyzing the role of KIR3DP1 in the KIR haplotypes. Methods:A total of 166 unrelated blood donors from Zhejiang were collected (Blood donation period: March 2020 to August 2020), and genotyping was performed by next-generation sequencing based on exon capture. The copy number and allelic frequency of the KIR3DP1 gene and the distribution of centromeric haplotypes were statistically analyzed. This study was approved by the Medical Ethics Committee of Zhejiang Blood Center (Ethics No.: 2023-001). Results:The KIR3DP1 gene was positive for all individuals but with different copy numbers. Among these, 4 cases (2.4%) had only 1 copy, 156 cases (94.0%) had 2 copies, and 6 cases (3.6%) had 3 copies. A total of 10 KIR3DP1 alleles were found in the population, which could be classified into the KIR3DP1*001-L type, KIR3DP1*003-L type, and KIR3DP1 full deletion type. The KIR3DP1*003-L type allele was linked to the Cen- A01 and Cen- B01 types, and the KIR3DP1*001-L type allele and the KIR3DP1 deletion type were only present in the Cen- B02 type haplotype. Conclusion:This study has derived a high-resolution distribution map of the KIR3DP1 gene in the Han population from Zhejiang, and found that the KIR3DP1 alleles showed different linkage with the centromeric haplotypes, which has provided a basis for further studying the role of KIR3DP1 in genetic immunity.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

Objective To explore the treatment of infection after spinal internal fixation.Methods The clinical data of 6 patients with infection after spinal internal fixation in our hospital were analyzed retrospectively.The bacterial culture and drug susceptibility testing were performed to identify the pathogenic bacteria and sensitive antibiotics.Moxifloxacin and/or vancomycin were used empirically for anti-infective therapies first,and then sensitive antibiotics were used according to the results of bacterial culture and drug susceptibility testing.At the same time,imaging examination was performed to determine the infection site and internal fixation,and surgical treatment was decided based on the patients'condition.After operation,the body temperature,inflammatory indexes and drainage of patients were monitored continuously,and the drainage fluid was taken for bacterial culture regularly to evaluate the therapeutic effect.Results The results of bacterial culture in 5 patients were positive and the pathogenic bacteria was staphylococcus aureus,with the susceptibility to vancomycin by susceptibility testing.Among them,1 patient was treated with vancomycin for about 8 weeks because of his advanced age,more basic diseases and high risk of operation;the other 4 patients were received surgery combined with anti-infective treatment with vancomycin for 2 to 4 weeks.One case with negative bacterial culture received surgery combined with anti-infective treatment with imipenem and moxifloxacin.The wound of all patients healed in grade A,the body temperature and inflammatory indexes returned to normal,the low back pain disappeared,and the nerve root symptoms of lower extremities were significantly improved.Conclusion Once the patients with infection after spinal internal fixation are diagnosed,the pathogenic bacterial should be identified as early as possible and sensitive antibiotics should be used.Meanwhile,the internal fixation is removed or re-implanted depending on whether it is infected.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.