Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Objective:This study aimed to investigate the association between genetic factors and the risk of developing treatment-resistant depression (TRD), as well as the efficacy of modified electroconvulsive therapy (MECT), with a specific focus on identifying gene polymorphisms that can differentiate TRD from non-TRD.Methods:This case-control study included inpatients with depression in Adult Psychiatry Department, Affective Disorders Department and Geriatrics Department of Guangzhou Medical University Affiliated Brain Hospital from January 2023 to June 2024, as well as healthy individuals undergoing physical examinations in the outpatient department. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was utilized to genotype 16 loci across 10 candidate genes in 107 non-TRD patients, 101 TRD patients and 281 healthy controls. Hardy-Weinberg equilibrium testing, genotype frequency distribution analysis, and genetic association studies were conducted using PLINK software. Univariate binary logistic regression under a dominant model was performed using R software to analyze gene loci associated with non-TRD and TRD.Results:All 16 gene loci in the control group, the TRD group, and the non-TRD group were found to be in Hardy-Weinberg equilibrium ( P>0.05). No significant differences were observed in the genotype distribution of these gene loci across the groups ( P>0.05). Univariate binary logistic regression analysis revealed that individuals with depression carrying the HTR2A-rs7997012 G allele had a significantly lower risk of developing TRD ( OR=0.26, P=0.047). Among the patients receiving MECT, the proportion of G allele carriers who showed improvement at 2, 4, and 6 weeks of treatment was significantly higher compared to those who did not show improvement (96.61% vs. 80.95%, 96.55% vs. 50.00%, 96.59% vs. 46.15%, respectively), with χ2 values of 6.743, 29.295, and 32.300, respectively, and all P values <0.05. Conclusion:The HTR2A-rs7997012 polymorphism may represent a genetic distinction between TRD and non-TRD. Depressed patients with the rs7997012 G allele have a reduced likelihood of developing TRD, moreover, MECT demonstrates superior efficacy in this patient population.

Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.

Objective:This study aimed to investigate the association between genetic factors and the risk of developing treatment-resistant depression (TRD), as well as the efficacy of modified electroconvulsive therapy (MECT), with a specific focus on identifying gene polymorphisms that can differentiate TRD from non-TRD.Methods:This case-control study included inpatients with depression in Adult Psychiatry Department, Affective Disorders Department and Geriatrics Department of Guangzhou Medical University Affiliated Brain Hospital from January 2023 to June 2024, as well as healthy individuals undergoing physical examinations in the outpatient department. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was utilized to genotype 16 loci across 10 candidate genes in 107 non-TRD patients, 101 TRD patients and 281 healthy controls. Hardy-Weinberg equilibrium testing, genotype frequency distribution analysis, and genetic association studies were conducted using PLINK software. Univariate binary logistic regression under a dominant model was performed using R software to analyze gene loci associated with non-TRD and TRD.Results:All 16 gene loci in the control group, the TRD group, and the non-TRD group were found to be in Hardy-Weinberg equilibrium ( P>0.05). No significant differences were observed in the genotype distribution of these gene loci across the groups ( P>0.05). Univariate binary logistic regression analysis revealed that individuals with depression carrying the HTR2A-rs7997012 G allele had a significantly lower risk of developing TRD ( OR=0.26, P=0.047). Among the patients receiving MECT, the proportion of G allele carriers who showed improvement at 2, 4, and 6 weeks of treatment was significantly higher compared to those who did not show improvement (96.61% vs. 80.95%, 96.55% vs. 50.00%, 96.59% vs. 46.15%, respectively), with χ2 values of 6.743, 29.295, and 32.300, respectively, and all P values <0.05. Conclusion:The HTR2A-rs7997012 polymorphism may represent a genetic distinction between TRD and non-TRD. Depressed patients with the rs7997012 G allele have a reduced likelihood of developing TRD, moreover, MECT demonstrates superior efficacy in this patient population.

Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients( n=92), post-operative breast cancer patients( n=64) and healthy subjects( n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA ( r=0.274, P=0.008) and CA15-3 ( r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95 %CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients( n=92), post-operative breast cancer patients( n=64) and healthy subjects( n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA ( r=0.274, P=0.008) and CA15-3 ( r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95 %CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

Since the outbreak of COVID-19 pandemic, the detection capability has been improving and the detection techniques have been evolving with innovations. qRT- PCR and mNGS, which represent the current mainstay diagnostic technologies, play key roles in disease diagnosis and monitoring of virus variation. The detection technologies based on serum and plasma IgM and IgG antibodies are important for auxiliary diagnosis. RT-LAMP is highly specific for a diagnostic purpose. Digital PCR could quantitatively detect nucleic acid and SHERLOCK has a higher sensitivity. These techniques all have great potential for future development and application for pathogen detection. In this review the authors summarize the basic rationales, technical characteristics and the current application of the SARS-CoV-2 detection techniques.
Antibodies, Viral ; Betacoronavirus ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Pandemics ; Pneumonia, Viral ; diagnosis

OBJECTIVE: To investigate the expression of ZNF652 in breast cancer tissues and cells and explore its role in breast cancer cell proliferation, invasion and migration. METHODS: We exploited the data from the TCGA database to analyze the differential expression of ZNF652 in breast cancer tissues and adjacent tissues and the correlations of ZNF652 expression with the clinicopathological characteristics of breast cancer patients including molecular subtypes, pathological types, TNM stages and clinical stages. RT-qPCR and Western blotting were used to detect the expression of ZNF652 in 5 breast cancer cell lines including MCF-7, MDA-MB-231, SK-BR-3, UACC-812 and BT-474. Using a lentivirus system and siRNA technique, we assessed the effects of ZNF652 over-expression and knockdown on proliferation, colony forming ability, migration and invasion of breast cancer cells with CCK-8 assay, clonogenic assay, Transwell assay and wound healing assay. The subcellular localization of ZNF652 in 293T cells was determined using immunofluorescence assay. RESULTS: ZNF652 was significantly up-regulated in breast cancer tissues ( CONCLUSIONS ZNF652 is highly expressed in breast cancer tissues and cells to promote the development and progression of breast cancer and may serve as a potential molecular target for diagnosis and treatment of the malignancy.
Breast Neoplasms/genetics* ; Carcinogenesis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans

A large amount of non-coding RNA are found existing in eukaryotic transcriptome, which play an important role in regulating the expression of genes as well as participating in physiological and pathological process of various cells.In recent years,the research of ncRNA in diagnosis of breast cancer is extremely hot. In this review, the research of three types of peripheral blood ncRNAs as breast cancer diagnostic biomarkers were reviewed, including microRNA(miRNA), long non-coding RNA(lncRNA), and circular RNA(circRNA).Also,the prospect of ncRNA in clinical research and translational medicine of breast cancer was mentioned, in order to provide a new idea for breast cancer with the discovery of diagnostic markers in early detection and the monitoring of diagnosis and treatment process.