OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

Objective:To retrospectively analyze the results of auditory examination,vestibular function examination and laboratory examination of 63 patients diagnosed as vestibular neuritis.Methods:A total of 63 patients diagnosed with vestibular neuritis hospitalized in the Department of Otolaryngology, Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University, from October 2012 to December 2022 were recruited. All patients met the diagnostic criteria for the 2022 Bárány association vestibular neuritis. Clinical data and the results of pure tone audiometry, electrocochleogram, video electronystagmogram, caloric test, cervical vestibuloevoked myogenic potential（cVEMP）, ocular vestibuloevoked myogenic potential（oVEMP）, video head impulse test（vHIT） was collected.A total of 63 age-and sex-matched healthy subjects in the physical examination center were randomly selected as the control group. The differences of blood indexs and lipid metabolism indexes between the two groups were compared. Results:In patients with vestibular neuritis, 50 out of 63 patients presented normal threshold in pure tone audiometry, 8 out of 63 patients had bilateral high-frequency sensorineural hearing loss and 5 out of 63 patients had unilateral mild high-frequency sensorineural hearing loss, 56 out of 63 cases completed the electrocochleogram, of which 3 cases had a binaural-SP/AP amplitude ratio≥0.4, 5 cases had monaural amplitude ratio ≥0.4. Fifty-five out of 63 patients completed the caloric test with CP values greater than 30% in all. The ratio of patients completed cVEMP, oVEMP and vHIT were 46 cases, 22 cases and 30 cases, respectively. 17 out of 63 cases completed all the four vestibular function tests. According to these tests, 49 patients could determine the extent of injury，including 27 cases with unilateral superior vestibular nerve injury, 21 cases with unilateral superior and inferior vestibular nerve injury and 1 case with unilateral inferior vestibular nerve injury. There were significant differences in neutrophil value（P<0.001）, lymphocyte value（P<0.005）, neutrophil/lymphocyte ratio（P<0.001） and apolipoprotein A1（P<0.001） between patient group and control group. Inflammatory markers were risk factors for patients with vestibular neuritis. The OR values of neutrophil value and blood neutrophil/lymphocyte ratio were 1.81（1.38-2.37, P<0.001） and 2.11（1.41-3.16, P<0.001）, respectively. Apolipoprotein A1 was a protective factor for patients with vestibular neuritis, and the OR value was 0.004（0.001-0.042, P<0.001）. Conclusion:Electrocochleogram could be used in vestibular neuritis patients with normal pure tone threshold to test whether there is hidden hearing loss in these patients. Neutrophil value, lymphocyte value, neutrophil/lymphocyte ratio and apolipoprotein A1 were correlated with vestibular neuritis. The Neutrophil value and neutrophil/lymphocyte ratio were risk factors for morbidity.
Humans ; Vestibular Neuronitis/physiopathology* ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone ; Hearing Loss, Sensorineural/physiopathology* ; Middle Aged ; Adult ; Vestibular Function Tests ; Vestibular Evoked Myogenic Potentials ; Aged

Objective: To explore the network structure of dietary intake and physical fitness subtypes among junior and senior high school students, so as to provide precise and efficient intervention guidance for improving abnormal physical health issues in adolescents. Methods: Based on the 2020-2021 Database of Youth Health (DYH), a total of 9 730 junior and senior high school students in Shandong Province were included for analysis. Dietary intake was assessed using a modified Chinese Dietary Quality Questionnaire, and physical fitness was evaluated according to the "2014 National Student Physical Fitness Standard". The Kmeans clustering algorithm was employed to identify potential subtypes of physical fitness in junior and high school students. Network analysis was used to construct a network linking dietary intake and physical fitness symptoms and to identify clusters of dietary behaviors and physical fitness symptoms among adolescents of different genders. Results: The physical fitness among junior and senior high school students of different genders were categorized into two subtypes: the baseline steady type (3 427 male students, 4 039 female students) and the morphological deviation type (1 294 male students, 970 female students). Statistically significant differences were observed in network strength and network connectivity strength among different genders and physical fitness subtypes (all P<0.05). Connections between food intake and physical health symptom clusters across different genders and physical health types among junior and senior high school students were primarily achieved through instant noodle intake and physical fitness (males of morphological deviation type, weight=0.06), fruit intake and physical fitness (males of baseline steady type, weight=-0.07), potato intake and vital capacity (females of morphological deviation type, weight=0.09), and processed meat intake and vital capacity (females of baseline steady type, weight=0.05). Conclusions Dietary intake serves as a significant modifiable risk factor for the physical fitness of junior and high school students. Interventions should focus on promoting healthy eating habits.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methy-lomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyl-transferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution pat-terns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolu-tion on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.

[Abstract] Objective: To observe the short-term efficacy and safety of Apatinib combined with radiotherapy and concurrent docetaxel and cisplatin chemotherapy in driver-gene-negative non-small cell lung cancer (NSCLC) patients with brain metastases. Methods: A total of 72 NSCLC patients with brain metastases, who were treated in our hospital from June 2018 to June 2019, were enrolled in this study. The driver gene was proved to be negative by next generation sequencing (NGS). The patients were divided into control group (36 cases) and treatment group (36 cases) by Digital random grouping method.The control group received 2 cycles of chemotherapy with docetaxel and cisplatin and concurrent radiotherapy for brain metastases, and the treatment group was given Apatinib anti-angiogenic treatment based on the regimen in control group. Primary study endpoints: confirmed objective response rate (cORR) and disease control rate (DCR); Secondary study endpoints: progression-free survival (PFS), quality of life (QOL) score, serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), and incidence of adverse drug events (AE). Results: Compared with the control group, cORR and DCR in treatment group were significantly improved [41.67% (15/36) vs 33.33% (12/36), 80.56% (29/36) vs 69.44% (25/36), all P<0.05], the median PFS was significantly prolonged (5.9 vs 4.6 months, P<0.05), and serum CEA and VEGF levels were significantly reduced [(16.5±2.3) vs (22.9±3.7) ng/ml, (291.6±42.6) vs (479.3±50.2) ng/L, all P<0.05], while the QOL score was slightly increased, but the difference was not statistically significant [(69.5±8.5) points vs (64.1±7.3) points, P>0.05]. There was no statistically significant difference in the incidence of acute brain edema, gastrointestinal reaction, bone marrow suppression, and liver dysfunction between the two groups of patients (all P>0.05); however, the incidences of oral mucositis, hand-foot syndrome, hypertension and proteinuria in the treatment group were significantly higher than those in the control group (all P<0.05). Conclusion: The efficacy of Apatinib combined with radiochemotherapy in driver-negative NSCLC patients with brain metastases is significantly better than that of radiochemotherapy alone, and the adverse reactions can be controlled. It is worthy of clinical recommendation.

Objective To compare the effect of intensity modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) combined with intracavitary brachytherapy on patients with cervical stump cancer. Methods A total of 47 patients with cervical stump cancer who were admitted to the First Hospital of China Medical University from October 2007 to September 2017 were retrospectively reviewed. Of the 47 patients, 19 patients received CRT combined with intracavitary brachytherapy (CRT group), and 28 patients received IMRT combined with intracavitary brachytherapy (IMRT group). In order to reduce the effects of selection bias and confounding factors, propensity score matching was performed to compare the groups. Results After the propensity score matching, there were 19 patients in each group. The 1-, 3-and 5-year overall survival (OS) rate for matched patients were 100.0％, 85.1％ and 63.8％ in IMRT group, and 84.2％, 57.9％ and 42.1％ in CRT group, respectively, and the difference in survival between the two groups was statistically significant (PLog-rank= 0.029, PCox= 0.043, HR= 3.723, 95％CI 1.044-13.280). The median progression-free survival (PFS) time of the IMRT group was better than that of the CRT group [median PFS time had not been reached (7-72 months) vs. 17 months (2-125 months), PLog-rank= 0.032, PCox= 0.042, HR=2.773, 95％CI 1.037-7.417]. The incidence of late rectal and bladder radiation injury was 15.8％ (3/19) and 0 (0/19) in IMRT group, and 57.9％ (11/19) and 26.3 ％(5/19) in CRT group, respectively, and the difference was statistically significant (P= 0.017, P= 0.046). Conclusion Compared with CRT combined with intracavitary brachytherapy, IMRT combined with intracavitary brachytherapy has a better effect on patients with cervical stump cancer, and the incidence of complications is low, this method is worthy of clinical application.

Cervical stump cancer is rare in clinic, which leads to insufficient understanding of it by clinicians. Radiotherapy alone is often used in the early stage, but the treatment mode has gradually changed recently. However, there is still no uniform treatment standard for residual cancer, and the prognostic differences of residual cancer patients under the new treatment mode have not been reported in real time. In order to improve the management of cervical stump, this article reviewed its clinical characteristics, treatment and prognosis.

Objective To investigate the pathogenesis of white matter damage (WMD) and the effects of xenon intervention on the expression of EphB4 and EphrinB2 mRNA in the brain tissue of neonatal rats.Method Three-day-old SD rat pups (n =96) were randomly assigned into sham group (n =24),model group (n =24),xenon intervention group 1 (n =24) and xenon intervention group 2 (n =24).The WMD model was established by injected of lipopolysaccharide (LPS) 0.05 mg/kg combined with ligation of the right carotid artery for 1 h in the last three groups.Rats in xenon intervention group 1 inhaled 50％ xenon immediately for 3 h after modeling,while rats in xenon intervention group 2 inhaled 50％ xenon for 3 h at 2 h after modeling.After the completion of xenon intervention,6 rat pups in each groups were sacrificed at 0 h,24 h,48 h and 72 h.The pathologic examination of periventricular tissue was conducted with hematoxylin-eosin staining (HE) and the expression of EphB4 and EphrinB2 mRNA was assayed by real-time quantitative polymerase chain reaction (RT-PCR).Statistical analysis was then performed.Result (1)The structure of white matter in model group became loose,band net-like,with significant nucleus pyknosis.The pathological damages in xenon intervention group 1 and 2 were lighter at 24 h,48 h and 72 h than model group,with less karyopycnosis.(2) Compared with the sham group,the expressions of EphB4 and EphrinB2 mRNA at 0 h,24 h,48 h and 72 h were significantly higher in the model group and xenon intervention group 1 and 2 (P ＜ 0.05),except for the EphB4 mRNA in xenon intervention group 1 at 72 h (P ＞ 0.05).The expressions of EphB4 and EphrinB2 mRNA at each time point in xenon intervention group 1 and 2 were decreased significantly than the model group (P ＜ 0.05),except for the EphB4 mRNA in xenon intervention group 2 at 72 h (P ＞ 0.05).However,there was no statistically significant difference on EphB4 and EphrinB2 mRNA between two xenon intervention groups at each time point (P ＞ 0.05).Conclusion The expression of EphB4 and EphrinB2 mRNA are appreciably increased in brain tissue of neonatal rats with WMD,which indicates the reactive angiogenesis.The intervention with xenon may play a neuroprotective role through reducing the expressions of EphB4/EphrinB2 mRNA and angiogenesis,and early intervention may be better.

Objective To analyze etiology,clinical manifestation and diagnosis process of vertigo and dizziness in children.Method The clinical data of 82 children with vertigo and dizziness treated in our hospital from January 2006 to December 2016 were retrospectively analyzed.Results There were 46 girls and 36 boys with a female:male ration of 1.28:1.The median age of patients was 9.0 years (14 months-18.0 years) and 21 cases were less than 6 years old.The chief complaints were repeatedly falling,crying,walking unsteadily and scratching the ear for unknown reasons.For children aged ＞ 5 years may express " roof or tent rotation";for those aged ＞ 6-＜ 15 years (n =34),the main complaint was more ambiguous "dizziness";for those aged ≥ 15-≤ 18 years (n =27) with the main complaint of " dizziness" may clearly express the " sense of rotation" or " the feeling of feeling drowsy,the top-heavy sense," and the accompanying deafness,earfullness,tinnitus and so on.Among 82 cases,there were 15 cases of benign paroxysmal vertigo (BPV,18.3％),12 cases of secretory otitis media (SOM,14.6％),11 cases of vestibular migraine (VM,13.4％),9 cases of benign paroxysmal positional vertigo (BPPV,11.0％),8 cases of inner ear malformation (9.8％),8 cases of Meniere's disease (9.8％),7 cases of vestibular neuritis (8.5％),6 cases of sudden deafness with vertigo (7.3％),4 cases of central vertigo (4.9％),1 case of rare genetic disease (1.2％) and 1 case of vertigo due to mental psychological (1.2％).The incidence of BPV,VM and Meniere's disease in girls was higher than that in boys.There was a tendency to self heal in BPV with the age increasing,in 15 BPV cases,8 after 12 years of age,3 after 14 years old had no vertigo attacks,and 4 cases were still in follow-up.The attack frequency of VM was decreased,and the extent was reduced with the age.Children older than 6 years were able to cooperate to vestibular function tests,and the majority completed the tests.Conclusion The analysis shows that the etiology of vertigo and dizziness in children is different from that of adults.Central vertigo and rare genetic disorders with dizziness as the first symptom are of great harmfulness,so intensive observation and multidisciplinary consultations are recommended.