Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct（EVA） using the linear mixed effect model（LMM）, providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type（Type C） demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans ; Vestibular Aqueduct/abnormalities* ; Genotype ; Sulfate Transporters ; Mutation ; Auditory Threshold ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Child, Preschool ; Hearing Loss/genetics* ; Hearing Tests ; Linear Models ; Infant

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Objective:To investigate the effect of oral administration of vitamin D3 on intestinal barrier function in patients after gastric cancer surgery,and to provide a reference for perioperative nutritional therapy in patients with gastric cancer.Methods:The conve-nience sampling method was used to select 80 patients with gastric cancer who were admitted to Department of Gastrointestinal Surgery in a grade A tertiary hospital in Xiamen,China,from June 2021 to May 2023,and the patients were divided into intervention group and control group using a random number table.The patients in the intervention group were given oral administration of vitamin D3 800 IU/d for 14 consecutive days before surgery.ELISA was used to measure the serum levels of 25-hydroxyvitamin D3[25(OH)D3],intestinal barrier indicators(D-lactate,Zonulin),and inflammatory indicators(C-reactive protein,interleukin-6)within 24 hours after admis-sion and on days 1,4,and 7 after surgery,and the changes in these indicators were compared between the two groups.Results:A total of 71 patients were enrolled finally,with 34 in the intervention group and 37 in the control group.On days 1,4,and 7 after surgery,the intervention group had a significantly lower level of D-lactate than the control group(F=3.978,P=0.026;F=9.649,P=0.005;F=4.389,P=0.021).On day 4 after surgery,the intervention group had a significantly lower level of Zonulin than the control group(F=3.198,P=0.035).Conclusion:Oral administration of vitamin D3 before surgery may accelerate the recovery of intestinal barrier function in pa-tients with gastric cancer.

OBJECTIVE To investigate the relationship between 23-site chip genetic screening failures and the results of newborns hearing screening,and to provide clinical reference for the diagnosis and treatment of genetic screening failures.METHODS There were 1 916 newborns born in the Beijing area from November 2022 to May 2024,who did not pass the 23-site chip genetic screening tests and underwent newborn hearing screening with definite initial screening results.Chi-square test was used to analyze the relationship between different mutation types and genotypes and the initial hearing screening results.RESULTS The overall neonatal hearing screening failure rate was 5.27%(101/1 916),with a higher failure rate of 61.54%(56/91)for homozygous and compound heterozygous mutations than the failure rate of 2.54%(45/1 772)for heterozygous mutations,0%(0/34)for digenic gene heterozygous mutations,and 0(0/19)for mtDNA 12S rRNA mutations,with a statistically significant difference(P<0.001).Among the homozygous and compound heterozygous mutations,the failure rates of homozygous and compound heterozygous for GJB2 gene and SLC26A4 gene were 59.76%(49/82)and 77.78%(7/9),respectively,with no statistically significant difference between the two groups(P=0.488).The homozygous and compound heterozygous for GJB2 gene were divided into three groups based on genotype:c.109G>A homozygous mutations,c.109G>A compound heterozygous mutations,and other homozygous and compound heterozygous mutations.The hearing screening failure rates of the three groups,from highest to lowest,were as follow:other homozygous and compound heterozygous mutations(88.89%,8/9),c.109G>A homozygous mutations(65.12%,28/43),and c.109G>A compound heterozygous mutations(43.33%,13/30),with a statistically significant difference(P=0.029).The failure rates of heterozygous for GJB2 gene,SLC26A4 gene and GJB3 gene were 2.86%(40/1 398),1.25%(4/321)and 1.89%(1/53),respectively,with no statistically significant difference among the three groups(P=0.241).The failure rate of hearing screening for individuals with GJB2 heterozygotes of different genotypes and individuals with SLC26A4 heterozygotes of different genotypes did not show statistically significant differences.CONCLUSION The failure rate of newborn hearing screening for homozygous and compound heterozygous mutation of 23-site chip genetic screening is higher than that of other mutation types,verifying the effectiveness of the newborn hearing screening program.Some newborns of homozygous and compound heterozygous mutation can pass the hearing screening,especially those with the c.109G>A homozygous and compound heterozygous mutation,who need clinical follow-up.

Objective:To investigate the nutritional risk, incidence of malnutrition, and intake of three major energy-supplying nutrients, analyze changes in their body composition and the possible influencing factors in patients with stomach neoplasms during perioperative period in order to provide a theoretical basis for the nutritional management of patients with stomach neoplasms during perioperative period.Methods:This was a cross-sectional study. A total of 105 patients who underwent gastric cancer radical surgery in the Gastrointestinal Department of Zhongshan Hospital Affiliated to Xiamen University from June 2021 to May 2023 were taken as the research subjects using fixed-point continuous sampling method. They were recruited for screening and assessment using Nutritional Risk Screening 2002 (NRS 2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Nutrients intake during the perioperative period were investigated using the 24-h recall method and dietary diary method, etc. Body compositions were measured using the bioelectrical resistance method.Results:Among the 105 patients, there were 78 males and 27 females, with an average age of (61.5 ± 10.3) years. About 83.8% (88/105) gastric cancer patients were at nutritional risk and 82.9% (87/105) were malnourished. The preoperative and postoperative energy intake were (1 646.1 ± 321.5) and (1 317.2 ± 365.8) kcal (1 kcal=4.184 kJ), respectively, which were significantly lower than the target amount of (1 896.7 ± 262.9) kcal, the difference was statistically significant ( t=6.23, 8.29, both P<0.05).The preoperative body mass, muscle mass, skeletal muscle, fat mass, and skeletal muscle index were (51.5 ± 9.6), (40.8 ± 6.0), (23.6 ± 4.0), (8.3 ± 4.9) kg, and 6.7 ± 0.8 respectively, while the postoperative values were (50.0 ± 9.1), (39.8 ± 6.0), (22.8 ± 3.6), (7.8 ± 5.2) kg, and 6.5 ± 0.8 respectively, with statistically significant differences between the two groups ( t values were 2.89-10.61, all P<0.05). Logistic multivariate regression analysis showed that the operation time ( OR=3.984, 95% CI 1.433-11.080, P<0.05) and energy satisfaction ( OR=0.053, 95% CI 0.005-0.610, P<0.05) were independent influencing factors for the degree of skeletal muscle loss. Conclusions:During perioperative period, the gastric cancer patients had poor nutritional status with insufficient nutrient intake and accelerated loss of body muscle and fat. Therefore, it was necessary to conduct a comprehensive nutritional evaluation for patients with stomach neoplasms during perioperative period in time and take steps to promote recovery by providing individualized nutritional therapy.

Objective To investigate the effects of the physical parameters of radiotherapy and intestinal flora on the risk of secondary radiation enteritis(RE)in patients with abdominal malignant tumors.Methods Ninety-eight patients with malignant abdominal tumors who were treated with radiotherapy from April 2020 to August 2023 at Anyang District Hospital in Puyang City were selected and assigned to the RE group(n=26)or the non-RE group(n=72).The clinical data,physical parameters of radiotherapy,and changes in the intes-tinal flora were compared between the two groups.Pearson's correlation analysis was used to determine the correlation between the phy-sical parameters of radiotherapy and changes in the intestinal flora,and logistic analysis was used to analyze the relationship between the physical parameters of radiotherapy,changes in the intestinal flora,and risk of RE.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to analyze the physical parameters of radiotherapy and changes in intestinal flora in predicting risk of RE.Results The doses of V20,V40,and D2cc in the small intestine,D2cc in the rectum,and D2cc in the colon were higher in the RE group than in the non-RE group(P＜0.05).The α diversity Chao1 index,Shannon index,and Simpson index of the intestinal flora in the RE group were lower than in the non-RE group,at the third week of radiotherapy,and the decrease in the α diversity Chao1 index,Shannon index,and Simpson index of the intestinal flora in the RE group was greater than in the non-RE group,before and after radiotherapy(P＜0.05).The doses of V20,V40,and D2cc in the small intestine,D2cc in the rectum,and D2cc in the colon were posi-tively correlated with decreases in the α diversity Chao 1 index,Shannon index,and Simpson index of the intestinal flora,before and after radiotherapy(P＜0.05).The logistic analysis showed that the decrease in V20,V40,and D2cc in the small intestine,D2cc in the rectum,D2cc in the colon,α diversity Chao1 index,Shannon index,and Simpson index of the intestinal flora were independent risk factors for occurrence of RE(P＜0.05).The AUC of the physical parameters of radiotherapy and changes in intestinal flora combined to predict the risk of RE as 0.920,which was greater than that of each indicator alone.Conclusion The physical parameters of radiotherapy are closely related to the changes of intestinal flora in patients with malignant abdominal tumors,which,in combination,can increase the risk of RE,and have a high predictive value for the risk of RE.

Objective:To investigate the correlation between thyroid hormone resistance and hyperuricemia in euthyroid population.Methods:It was a cross-sectional study. A total of 548 euthyroid subjects who were hospitalized or underwent physical examination in the Heart Center and Health Management Center of the First Affiliated Hospital of Tsinghua University from January 2021 to December 2022 were selected. Thyroid function, uric acid, blood lipid and other indicators were collected in the subjects, and thyroid function parameters were calculated: thyroid-stimulating hormone index (TSHI), thyrotropin T4 resistance index (TT4RI), parametric thyroid feedback quantile-based index (PTFQI), free triiodothyronine/free thyroxine (FT3/FT4), the sum activity of peripheral deiodinases (SPINA-GD) and the secretory capacity of the thyroid gland (SPINA-GT). According to uric acid level, the subjects were divided into high uric acid group and normal group, the clinical characteristics and thyroid function parameters of the two groups were compared, the correlation between thyroid hormone resistance and hyperuricemia was further explored.Results:Compared with the normal group, male proportion (94.4% and 52.5%), smoking rate (5.2% and 21.3%), body mass index [(27.10±3.96) and (24.26±3.42) kg/m 2], waist-to-hip ratio [0.90(0.86, 0.94) and 0.86(0.80, 0.91)], serum creatinine [(85.50±12.27) and (73.77±28.79) μmol/L], total cholesterol [(5.08±0.99) and (4.72±0.86) mmol/L], triglyceride [2.10(4.40, 5.59) and 1.14(0.79, 1.67)mmol/L], low-density lipoprotein [(3.19±0.97) and (2.85±0.84) mmol/L] and homocystine [(15.07±9.13) and (12.50±10.85) μmol/L] were all higher in the high uric acid group, and the level of high-density lipoprotein [1.15(1.43, 2.88) and 1.39(1.16, 1.64) mmol/L] was lower (all P<0.05). In the aspect of thyroid hormone and thyroid function parameters, the FT4[16.90(5.40,17.95) and 16.00(14.30,17.80) pmol/L], FT3[5.56(5.25, 5.94) and 5.22(4.81, 5.63) pmol/L], FT3/FT4 [0.34(0.31, 0.37) and 0.32(0.29, 0.36)], TSHI (2.70±0.50 and 2.58±0.60), PTFQI (0.406±0.332 and 0.335±0.353) and SPINA-GD [3.72(3.41, 4.05) and 3.52(3.18, 4.00) ]were all higher in high uric acid group than those in normal group(all P<0.05). Spearman correlation analysis showed that blood uric acid level was positively correlated with FT4 ( r=0.185), FT3 ( r=0.422), FT3/FT4 ( r=0.16), TSHI ( r=0.134), TT4RI ( r=0.09), PTFQI ( r=0.121) and SPINA-GD ( r=0.157) (all P<0.05). Conclusion:In people with euthyroid function, central resistance to thyroid hormone is correlated with hyperuricemia.

Objective To study the prognostic factors of progressive hearing loss among children with large vestibular aqueduct syndrome(LVAS).Methods The clinical data of 49 children(95 ears)with LVAS who re-ceived at least two hearing tests from January 2017 to January 2023 in our hospital were retrospectively analyzed,and they were divided into two groups according to the progression of hearing loss:the stable group(55 ears)and the progressive group(40 ears).The effects for progressive hearing loss of initial age,gender,laterality,imaging features,audiometric data,and incomplete partition type Ⅱ(IP-Ⅱ)and SLC26A4(type A,B,C,D)genotypes were analyzed by univariate and multivariate Cox regression analysis.The potential prognostic factors were further verified by Kaplan-Meier survival analysis.Results Each dB decrease in the initial average hearing threshold in-creased the expected hazard by 7.03％(P=0.02).Incomplete partition type Ⅱ(IP-Ⅱ)was associated with 5.11 hazard ratio(95％CI,1.81 to 14.45,P=0.002).Genotype C was associated with 6.13 hazard ratio for progressive hearing loss(95％CI,2.07 to 18.13,P=0.001).Conclusion The initial average hearing threshold,IP-Ⅱ,and SLC26A4 genotype C were significant effect factors of progressive hearing loss in patients with LVAS.This could predict the progression of hearing loss in children with LVAS and help identify patients at high risk for progressive hearing loss.

Objective To screen differentially expressed miRNAs(DEMs)by comparing the expression of miRNAs in serum exosomes between Alzheimer's disease(AD)patients and healthy controls.Methods A total of 71 AD patients admitted to Department of Geriatric Neurology of Xiangya Hospital from March 2017 to August 2018 and another 71 healthy individuals who taking physical examination in the hospital during same period were recruited and assigned into AD and HC groups,respectively.Four AD patients and four healthy subjects were selected for high-throughput second-generation sequencing of exosome miRNAs.The results were analyzed to obtain the DEMs between them,and the top 4 DEMs were finally selected.Then real-time quantitative real-time PCR was applied for all the subjects to detect the expression of the 4 DEMs.Results High-throughput second-generation sequencing detected 775 miRNAs,and 44 DEMs were found with statistical difference between the 2 groups(P＜0.05).Compared with the HC group,34 miRNAs were up-regulated and 10 were down-regulated in the AD group.The top 4 DEMs were miRNA-148a-3p,miRNA-16-5p,miRNA-19b-3p and miRNA-483-5p.MiRNA-148a-3p was significantly up-regulated in the AD group than the HC group(P＜0.01),but there were no significant differences in the expression level in the other 3 DEMs between the 2 groups.ROC curve analysis showed that the area under the curve of miRNA-148a-3p was 0.7113(95％CI:0.622～0.801),with a sensitivity of 71.6％and a specificity of 69.7％.Conclusion Serum exosome miRNA-148a-3p can be used as a biomarker for the diagnosis of AD.