Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective:To learn about the epidemiological and clinical characteristics of children with brucellosis, in order to provide reference for clinical diagnosis and treatment of brucellosis in children.Methods:Clinical data of children with brucellosis (aged ≤14 years) who visited the Department of Infectious Diseases at Beidahuang Industry Group General Hospital from December 2020 to December 2022 were retrospectively collected, and their epidemiological characteristics, clinical characteristics, laboratory tests, treatment and outcome were summarized and analyzed.Results:A total of 34 children with brucellosis were included, including 25 males (73.53%) and 9 females (26.47%), with a gender ratio of 2.78 ∶ 1.00. The median age was 8 years and 1 month, mainly in the age group of 6 to 14 years (19 cases, 55.88%). Epidemiological investigation showed that most of the affected children were rural residents (25 cases, 73.53%), with more contact with cattle/sheep (26 cases, 76.47%). The onset time was mainly concentrated in summer (15 cases, 44.12%) and spring (13 cases, 38.24%). The clinical symptoms were mainly fever (97.06%, 33/34) and arthralgia (64.71%, 22/34). In the laboratory tests, 25 cases (73.53%) had positive blood cultures, and the white blood cell count (WBC) of 30 cases (88.24%) was (4 - 10) × 10 9/L. Among the abnormalities of liver function, aspartate aminotransferase (AST) increased in 19 cases (55.88%), alanine aminotransferase (ALT) increased in 14 cases (41.18%) and γ-glutamyl transpeptidase (GGT) increased in 6 cases (17.65%). Among the myocardial enzymatic abnormalities, α-hydroxybutyrate dehydrogenase (HBDH) increased in 29 cases (85.29%), lactate dehydrogenase (LDH) increased in 27 cases (79.41%), and creatine kinase isoenzyme (CK-MB) increased in 8 cases (23.53%). After treatment, 25 children with positive blood culture turned negative. Conclusions:Children with brucellosis are mainly male, older and rural residents. The clinical manifestations are mainly fever and arthralgia. Doctors in relevant departments should conduct detailed epidemiological investigations and laboratory tests for such children in clinical work, in order to achieve early detection, diagnosis and treatment of pediatric brucellosis.

Background::Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis.Methods::In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted. Results::Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism. Conclusions::Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.

Objective:To investigate the timing and features of fine-needle aspiration biopsy (FNAB) guided by ultrasound for Bethesda Ⅲ thyroid nodules and to further optimize the puncture scheme.Methods:A retrospective analysis was conducted on data from patients who underwent rFNAB for Bethesda Ⅲ thyroid nodules at the China-japan Union Hospital of Jilin University Thyroid Surgery Department from Dec. 2020 to Dec. 2022. The study included 71 cases (73 nodules), consisting of 57 females and 14 males, with an average age of (45.7±10.4) years. Patients were grouped based on rFNAB results: Bethesda Ⅱ as the benign group ( n=21), Bethesda Ⅴ/Ⅵ as the malignant group ( n=39), and the remaining cases categorized as the indeterminate group ( n=13). Data on rFNAB results, puncture interval time, postoperative pathology, ultrasound features, and FNAB characteristics were recorded. Descriptive statistics were used for categorical data, presented as percentages and numbers, while continuous data were presented as mean ± standard deviation ( ± s). The χ2 test or Fisher's exact test was applied for analysis. Results:In this study, rFNAB was performed on 73 Bethesda Ⅲ thyroid nodules. The results showed that 60 nodules (82.2%) received a definite diagnosis, while 13 nodules (17.8%) were indeterminate. There was a statistically significant difference in the calcification classification between the malignant group and the benign group as well as the indeterminate group ( P<0.05). Among the malignant group, 29 patients underwent surgical treatment, with only 2 cases (8.0%) showing intermediate recurrence risk when surgery was performed more than three months after the initial FNAB. Upon reevaluation of the 31 initial FNAB samples from the malignant group, 9 samples (29.0%) exhibited mild cytological atypia, and 22 samples (71.0%) had poor quality specimens, mainly comprising fibrous and calcified components. Conclusions:For nodules initially classified as Bethesda Ⅲ, if suspicious ultrasound features persist or emerge, especially if microcalcifications are present, rFNAB should be performed after a follow-up period exceeding three months. However, during the puncture, multiple points should be targeted at the non-calcified areas of the nodule to enhance the accuracy and reliability of rFNAB.

Objective To explore and analyze the therapeutic effect of cryotherapy in the removal of granulation tissue under electronic bronchoscope,and find an efficient and safe auxiliary treatment technique for patients undergoing granulation tissue removal surgery.Method A clinical practice study was conducted on 41 patients who underwent granulation tissue removal surgery from June 2021 to June 2022.Patients were divided into groups using single and double numbers,with 21 patients assigned to single numbers included in the control group and 20 patients assigned to double numbers included in the observation group.Both groups underwent electronic bronchoscope granulation tissue removal surgery.During the surgery,the control group received argon-plasma coagulation(APC),while the observation group received cryotherapy.The levels of immune function indicators(including CD4+,CD8+and CD4+/CD8+),postoperative recovery related indicators,and effective rate of the two groups of patients were compared before and after treatment.Result Before treatment,there was no statistically significant difference in CD4+and CD4+/CD8+between the two groups of patients(P>0.05).After treatment,CD4+and CD4+/CD8+in the observation group were significantly higher than those in the control group,and the differences were statistically significant(P<0.05);Before treatment,there was no statistically significant difference in CD8+between the two groups of patients(P>0.05).After treatment,the observation group was significantly lower than the control group,and the difference was statistically significant(P<0.05);The effective rate of the observation group was 95.00%,higher than 80.95%of the control group.The postoperative pain visual analogue scale(VAS)of the observation group was(2.14±0.18)points,significantly lower than the control group's(6.09±0.95)points,and the differences were statistically significant(P<0.05);The first postoperative feeding time of the observation group was(6.08±0.76)hours,and the hospital stay was(5.12±0.68)days,which were shorter than the control group's(15.39±2.97)hours and(7.08±0.93)days;The treatment cost of the observation group was(10 500.60±80.70)yuan,which was lower than the control group's(19 800.00±126.00)yuan,and the differences were statistically significant(P<0.05);The incidence of postoperative complications in the observation group was 5.00%,lower than the control group's 23.81%,and the difference was statistically significant(P<0.05).Conclusion The application of cryotherapy in the removal of granulation tissue under electronic bronchoscope has a significant therapeutic effect.It can not only improve the surgical treatment effect of patients,improve their immune index levels,but also alleviate their postoperative pain,reduce the incidence of postoperative complications,and shorten their postoperative pre-and post cycle.Moreover,the treatment cost is low,and it is worthy of clinical application and promotion.

Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD.

Backgroud Beta-cypermethrin and emamectin benzoate are widely used for the prevention and control of pests in the greenhouse planting industry, and their combined exposure may increase the accumulation of beta-cypermethrin and emamectin benzoate in organisms and affect human health. Objective Based on the changes in reproductive hormone levels in the hypothalamic-pituitary-ovarian (HPO) axis, to investigate the effect of combined exposure to beta-cypermethrin and emamectin benzoate on the estrous cycle of female mice. Methods Twenty-four healthy adult SD rats were randomly divided into a blank control group, a beta-cypermethrin group (Beta-CYP, 53 mg·m⁻³), an emamectin benzoate group (EMB, 8 mg·m⁻³), and a beta-cypermethrin and emamectin benzoate combined exposure group (Beta-CYP+EMB, Beta-CYP 53 mg·m⁻³ + EMB 8 mg·m⁻³). Six rats in each group were exposed to the designed treatment protocol by aerosol inhalation 6 d a week for 13 weeks. The general condition of the rats was observed in real time during the treatment. From the 12th week of exposure, a 10-day reproductive tract smear was performed on the rats to observe the estrous cycle. The rats were neutralized on the second day after the end of the treatment protocol, and the ovarian tissues were stained with HE to observe histopathological changes. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured by ELISA. Experimental results were expressed as mean ± standard deviation (\begin{document}$ \overline{x}\pm s $\end{document}). One-way ANOVA was used for comparison among groups, and LSD test for pairwise comparison between groups. The significance level was α=0.05. Results After four weeks of the treatment protocol, the rats in the Beta-CYP group and the Beta-CYP+EMB group continued to be hyperactive and irritable, while the EMB group showed symptoms of mental disorder, decreased activity, and slow response. On the 90th day of the treatment protocol, the body weight of rats in the control group increased to (314.51±2.44) g, and that in the Beta-CYP+EMB group only increased to (253.47±1.50) g. There was no abnormal cellular morphology in the control group; however, small deeply stained nuclei appeared in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group, and abnormal morphological development of keratinized epithelial cells in the Beta-CYP+EMB group was found. The estrous cycle of rats in the control group was (97.83±4.17) h, and compared with the control group, the estrous cycles of rats in the Beta-CYP group, the EMB group, and the Beta-CYP+EMB group were prolonged to (134.33±7.53) h, (126.50±5.28) h, and (156.00±6.66) h, respectively. The results of ANOVA showed that the numbers of leukocytes (527.17±15.83), keratinized epithelial cells (35.67±4.32), and non-keratinized epithelial cells (70.50±4.51) in the vaginal smears during diestrus in the Beta-CYP+EMB group were significantly lower than those in the control group (752.50±28.89, 50.50±2.74, 101.33±7.92) (P<0.001). The hormone levels of GnRH and FSH in the control group were (5.13±0.59) and (0.76±0.09) IU·L⁻¹ respectively, while the levels in the Beta-CYP+EMB group were increased to (16.86±0.59) and (3.80±0.19) IU·L⁻¹ respectively (P<0.05). The levels of LH and E2 in the control group were (12.93±0.81) IU·L⁻¹ and (22.23±1.44) pmol·L⁻¹ respectively, and the levels in the Beta-CYP+EMB group were decreased to (5.63±0.41) IU·L⁻¹ and (10.45±0.78) pmol·L⁻¹ respectively (P<0.05). Conclusion The combined exposure to beta-cypermethrin and emamectin benzoate may ultimately affect the estrous cycle of female rats by interfering with the secretion of reproductive hormones involved in the HPO axis.

Scleroderma is a rare disease which requires multidisciplinary treatment. Drug-based therapy can partially alleviate or end the progression of the disease, but cannot reverse the lesions that have occurred. Scleroderma patients who seek care in plastic surgery has gradually increased in recent years. With the understanding of the regenerative role of fat and adipose stem cells, physicians have found that surgical treatment of scleroderma can improve morphology while reversing the state of the diseased tissue, acting as a local treatment or slowing progression. This paper briefly described the etiology and classification of scleroderma, analyzed the current status of scleroderma treatment and focused on the surgical treatment strategy of scleroderma, providing guidelines for the surgical management of scleroderma.

Scleroderma is a rare disease which requires multidisciplinary treatment. Drug-based therapy can partially alleviate or end the progression of the disease, but cannot reverse the lesions that have occurred. Scleroderma patients who seek care in plastic surgery has gradually increased in recent years. With the understanding of the regenerative role of fat and adipose stem cells, physicians have found that surgical treatment of scleroderma can improve morphology while reversing the state of the diseased tissue, acting as a local treatment or slowing progression. This paper briefly described the etiology and classification of scleroderma, analyzed the current status of scleroderma treatment and focused on the surgical treatment strategy of scleroderma, providing guidelines for the surgical management of scleroderma.

Objective:The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA).Methods:This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy.Results:A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUC ROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions:CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.