Objective:To investigate the impact of Waardenburg syndrome（WS） -associated Sox10 p.S100Rfs*9 mutation on inner ear function and its mechanism in noise-induced hearing impairment. Methods:A mice model carrying the Sox10 p.S100Rfs*9 mutation was established using CRISPR-Cas9 gene editing technology. Auditory phenotypes were assessed under baseline conditions and after noise exposure（96 dB SPL, 2 hours）. Auditory brainstem response（ABR） tests were performed to evaluate hearing function, combined with immunofluorescence staining of cochlear basilar membrane whole-mounts to observe hair cells and ribbon synapses. Transcriptome sequencing was conducted to analyze molecular mechanisms. Results:Sox10 p.S100Rfs*9 heterozygous mice exhibited normal hearing thresholds with characteristic ventral pigmentation abnormalities under baseline conditions. Following noise exposure, mutant mice showed significantly higher ABR thresholds at 24 000 Hz compared to wild-type controls（[60.00±6.12]vs[48.13±4.28]dB SPL, P<0.000 1）, and a significant reduction in ribbon synapses（CtBP2-positive puncta） in the basal turn（[55.0±2.3]vs[64.8±3.3]per inner hair cell, P=0.006 6）, while hair cell morphology and number remained intact. Transcriptome analysis revealed altered expression of genes involved in immune regulation, membrane structures, ion channels, and neuroactive ligand-receptor interactions. Conclusion:The Sox10 p.S100Rfs*9 mutation does not alter baseline hearing function but significantly increases inner ear susceptibility to noise damage, primarily manifested as enhanced ribbon synapse vulnerability, especially in high-frequency regions. This gene-environment interaction reveals that Sox10 haploinsufficiency may compromise noise tolerance by affecting synaptic stability and inner ear protective mechanisms. These findings provide new perspectives on the phenotypic heterogeneity in WS patients and theoretical basis for individualized noise protection strategies for patients carrying SOX10 mutations.
Animals ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/physiopathology* ; Mice ; Hearing Loss, Noise-Induced/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Mutation ; Noise ; Disease Models, Animal ; Ear, Inner/physiopathology*

Objective:To estimate the incidence of pediatric bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) by meta-analysis, and to provide scientific basis for postoperative respiratory follow-up management.Methods:We searched PubMed, Embase, Web of science, Chinese Medical Journal full-text database, Wanfang data, and China National Knowledge Network database to obtain related studies on postoperative BOS in children with HSCT from March 31, 2023. Literature screening, quality evaluation and information extraction were carried out, and Stata 16.0 software was used for analysis.Results:A total of 19 literatures were included, with a total sample size of 3 955 and 180 cases of BOS. The meta-analysis showed that the incidence of BOS after HSCT was 4%(95% CI: 3%-5%), and the heterogeneity was I2=76.1%( P<0.01). Heterogeneity among studies was explained by different regions of the study population, different BOS diagnostic criteria, study sample size, and subgroup analysis of single or multi-center studies. Sensitivity analysis showed that the results were stable, but publication bias was detected. Conclusions:The incidence of BOS in children after HSCT is 4%, but there is a large heterogeneity, and more large-scale multi-center studies are needed to determine the incidence. Pediatricians should conduct scientific management and follow-up of children after HSCT, so as to make early diagnosis and treatment and timely detection of BOS, and improve the quality of life of children.

Objective:To estimate the incidence of pediatric bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) by meta-analysis, and to provide scientific basis for postoperative respiratory follow-up management.Methods:We searched PubMed, Embase, Web of science, Chinese Medical Journal full-text database, Wanfang data, and China National Knowledge Network database to obtain related studies on postoperative BOS in children with HSCT from March 31, 2023. Literature screening, quality evaluation and information extraction were carried out, and Stata 16.0 software was used for analysis.Results:A total of 19 literatures were included, with a total sample size of 3 955 and 180 cases of BOS. The meta-analysis showed that the incidence of BOS after HSCT was 4%(95% CI: 3%-5%), and the heterogeneity was I2=76.1%( P<0.01). Heterogeneity among studies was explained by different regions of the study population, different BOS diagnostic criteria, study sample size, and subgroup analysis of single or multi-center studies. Sensitivity analysis showed that the results were stable, but publication bias was detected. Conclusions:The incidence of BOS in children after HSCT is 4%, but there is a large heterogeneity, and more large-scale multi-center studies are needed to determine the incidence. Pediatricians should conduct scientific management and follow-up of children after HSCT, so as to make early diagnosis and treatment and timely detection of BOS, and improve the quality of life of children.

Objective:To investigate the expulsion rate of GyneFix postpartum intrauterine device (PPIUD) placed immediately after cesarean section within one year and its influencing factors.Methods:A prospective cohort study was conducted. Women who volunteered to use a GyneFix PPIUD placed immediately after cesarean section (within 10 min after placenta delivery) for postpartum contraception were recruited from September 2017 to November 2020. The relevant information was collected through questionnaires before, during and 24 h after cesarean section. Outpatient follow-up was conducted at 42 d, 3 months, 6 months and 12 months after delivery to obtain information on expulsion of GyneFix PPIUD and unwanted pregnancy. Life table and Cox regression model were used to analyze the cumulative expulsion rate and related influencing factors.Results:A total of 470 subjects were recruited and 461 (98%) subjects were eligible for this study. The cumulative expulsion rate of GyneFix PPIUD within one year after cesarean section was 8.4% (95% CI: 7.0%-9.8%). Multivariate Cox regression analysis showed that women aged >35 years had significantly lower risk of PPIUD expulsion than those aged <25 years ( HR=0.16, 95% CI: 0.04-0.64). The risk of GyneFix PPIUD was not statistically significantly associated with cesarean section history and breastfeeding mode (all P>0.05). Nevertheless, this risk was statistically significant between hospitals. The Pearl index of contraceptive failure of the device was 2.37 (95% CI: 1.09-4.50) per 100 person-years. The rate of contraceptive failure was not associated with maternal age, breastfeeding mode, and history of cesarean delivery (all P>0.05). Conclusion:The one-year cumulative expulsion rate of GyneFix PPIUD placed immediately after cesarean section is 8.4%. Young mothers were at a higher risk of expulsion than their older counterparts. The device users should be counseled regarding the signs of expulsion. In case of expulsion, women should be offered reinsertion or other contraceptive methods. The training of service skills of GyneFix PPIUD should be strengthened in order to mitigate the risk of the device expulsion.

Objective:To investigate the expulsion rate of GyneFix postpartum intrauterine device (PPIUD) placed immediately after cesarean section within one year and its influencing factors.Methods:A prospective cohort study was conducted. Women who volunteered to use a GyneFix PPIUD placed immediately after cesarean section (within 10 min after placenta delivery) for postpartum contraception were recruited from September 2017 to November 2020. The relevant information was collected through questionnaires before, during and 24 h after cesarean section. Outpatient follow-up was conducted at 42 d, 3 months, 6 months and 12 months after delivery to obtain information on expulsion of GyneFix PPIUD and unwanted pregnancy. Life table and Cox regression model were used to analyze the cumulative expulsion rate and related influencing factors.Results:A total of 470 subjects were recruited and 461 (98%) subjects were eligible for this study. The cumulative expulsion rate of GyneFix PPIUD within one year after cesarean section was 8.4% (95% CI: 7.0%-9.8%). Multivariate Cox regression analysis showed that women aged >35 years had significantly lower risk of PPIUD expulsion than those aged <25 years ( HR=0.16, 95% CI: 0.04-0.64). The risk of GyneFix PPIUD was not statistically significantly associated with cesarean section history and breastfeeding mode (all P>0.05). Nevertheless, this risk was statistically significant between hospitals. The Pearl index of contraceptive failure of the device was 2.37 (95% CI: 1.09-4.50) per 100 person-years. The rate of contraceptive failure was not associated with maternal age, breastfeeding mode, and history of cesarean delivery (all P>0.05). Conclusion:The one-year cumulative expulsion rate of GyneFix PPIUD placed immediately after cesarean section is 8.4%. Young mothers were at a higher risk of expulsion than their older counterparts. The device users should be counseled regarding the signs of expulsion. In case of expulsion, women should be offered reinsertion or other contraceptive methods. The training of service skills of GyneFix PPIUD should be strengthened in order to mitigate the risk of the device expulsion.

Objective:To analyze the correlation between nasal resistance and lung function in children with allergic rhinitis（AR）, and explore whether AR children with increased nasal resistance are accompanied by potential lower respiratory tract involvement. Methods:A total of 88 children diagnosed with AR from December 2021 to December 2022 were selected as the study group, while 20 normal children were selected as the control group during the same period. Both the study group and the control group children underwent lung function tests, bronchodilator tests, and nasal resistance measurements. Spearman correlation analysis and multiple linear regression analysis were performed on the results of nasal resistance and lung function tests to explore the relationship and influencing factors between the two groups.According to the results of nasal resistance measurement, children with increased nasal resistance and abnormal lung function were divided into a mild increase in nasal resistance with abnormal lung function group and a moderate to severe increase in nasal resistance with abnormal lung function group. The degree of increased nasal resistance was analyzed to determine whether it would affect lung function. Results:The FEF25, FEF50, and FEF75 levels in the study group were significantly lower than those in the control group（P<0.05）. The FEV1of children with moderate to severe increase in AR nasal resistance was significantly lower than that of children with mild increase in AR nasal resistance（P<0.05）. There was a correlation between nasal resistance and FEV1/FVC, R20 in AR children, and FEV1/FVC, R20 were the influencing factors of nasal resistance in AR children（P<0.05）. There was no correlation between total serum IgE, lung function, and bronchodilation test in AR patients（P>0.05）. Conclusion:The nasal ventilation function of AR patients has changed, and there is a downward trend in small airway function. Children with moderate to severe increase in AR nasal resistance have a more significant decrease in lung ventilation function than those with mild increase. The nasal resistance of AR children is influenced by FEV1/FVC and R20, and FEV1/FVC and R20 decrease as the nasal resistance value increases. The improvement rate of lung function and FEV1 are not influencing factors for the elevation of total serum IgE.
Humans ; Child ; Rhinitis, Allergic/diagnosis* ; Nasal Polyps ; Respiratory Function Tests ; Nose ; Immunoglobulin E

Objective:To evaluate the methodological quality and reporting quality of clinical practice guidelines or consensuses in the field of Chinese pancreatic diseases from 2016 to 2021, and provide reference for formulating clinical practice guidelines and consensuses in this field.Methods:VIP, Wanfang , CNKI and CBM databases were searched for articles published from January 2016 to March 2021. The main index terms were " pancreas" , " guideline" , " consensus" , and the supplementary index terms were " pancreatitis" , " pancreatic cancer" , " pancreatic head cancer" . Two researchers independently selected the literature. The appraisal of guidelines for research and evaluation (AGREE-China) was utilized to assess the methodological quality of the guidelines or consensuses, and the reporting items for practice guidelines in healthcare (RIGHT) tool was used to assess the reporting quality.Results:A total of 14 literature were included, including 7 literature on pancreatic cancer, 3 literature on acute pancreatitis, 1 literature on chronic pancreatitis and 3 literature on others. The results of the assessment by the AGREE-China tool showed that there were no document with a total score greater than or equal to 60.0 points, two with 40.0 to 59.9 points, eleven with 20.0 to 39.9 points, and one with less than 20.0 points. Among the results of RIGHT list, basic information was reported the highest(72.62%) and funding and declaration was the lowest(0).Conclusions:The methodological and reporting quality of the guidelines or consensuses on pancreatic disease in China from 2016 to 2021 are generally not high. In the process of developing domestic guidelines or consensuses on pancreatic diseases, the guideline developer should refer to AGREE-China and RIGHT to improve the quality of clinical practice guidelines or consensuses.

OBJECTIVE：To inv estigate the effects of 4-hydroxy-2（3H）-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease （NAFLD）model rats. METHODS ：SD rats were divided into normal control group（10 rats）and modeling group （50 rats）. Normal control group was given basic diet ，and modeling group were given high-fat diet to induce NAFLD model. After modeling ，the rats were divided into normal control group ，model group ，silibinin group （26.25 mg/kg），and 4-hydroxy-2（3H）-benzoxazolone high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 8 rats in each group. Normal control group and modeling group were given 0.6％ CMC-Na intragastrically ，and other groups were given relevant medicine 10 mL/kg intragastrically ，once a day ，for consecutive 4 weeks. After last medication ，the serum levels of albumin（ALB），total protein （TP），globulin（GLB），ALB/GLB and free fatty acid （FFA）were detected ；TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4（TLR4），myeloid differentiation factor 88（MyD88）， nuclear factor-κB p65（NF-κB p65），NF-κB inhibitor protein（IκBα）] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2（Bcl-2），Bax，caspase-3]. RESULTS ：Compared with model group ，serum levels of TP （except for low-dose group ），GLB and FFA ，the protein expression of TLR 4（except for low-dose group ），MyD88 （except for medium-dose group ）and caspase- 3，the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly（P＜0.05 or P＜0.01）. The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased（P＜0.05 or P＜0.01），and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS ：4-hydroxy-2 （3H）-benzoxazolone can ameliorate NAFLD in rats ，and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues.

OBJECTIVE：To s tudy improvement effect and mech anism of ilicifoliosids alkaloid A （HBOA）on non-alcoholic fatty liver disease in rats. METHODS ：SD rats were randomly divided into blank control group ，model group ，Silybin capsule group（positive control ，26.25 mg/kg），HBOA high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 10 rats in each group. Except that blank control group fed normal feed ，the other groups were continuously fed with high-fat diet for 8 weeks to induce non-alcoholic fatty liver disease model. Form the 9th week ，blank control group and model group were given constant volume of 0.6％ CMC-Na solution ，and administration groups were given corresponding drugs by intragastric admini- stration，once a day ，for consecutive 4 weeks. The general information of rats were observed and the body weight increase ，organ （liver，kidney and spleen ）indexes were calculated ；the contents of AST ，ALT，TC，TG and NEFA in liver tissue were detected ， and SOD，GSH-Px activities and MDA content in the serum were also determined. The protein expression of PPARα in liver tissue was detected by immunohistochemistry. RESULTS ：Compared with blank control group ，the body mass increase and liver index of rats in model group were increased significantly （P＜0.01）；fat deposition could be observed in the liver ；the activities of SOD and GSH-Px in serum were reduced significantly ，and the contents of MDA ，the contents of AST ，ALT，TC，TG and NEFA in liver tissue were significantly increased ，and the protein expression of PPARα was decreased significantly（P＜0.01）. Compared with model group ，the body mass increase and liver index of the rats were decreased significantly in administration groups （P＜0.05 or P＜0.01），liver fat deposition was improved ，the activity of SOD and GSH-Px in serum （except for HBOA low-dose group ）were increased significantly while MDA content ，the contents of AST ，ALT，TC（except for HBOA low-dose group ），TG（except for HBOA low-dose group ） and NEFA in liver tissue were decreased significantl y，while protein expression of PPAR α 15177460685@163.com was increased significantly （P＜0.05 or P＜0.01）. Some of the above indexes of HBOA high-dose group were 电话：0771-5302433。E-mail：junlin898@126.com significantly better than HBOA medium- and low-dose group（P＜0.05）. CONCLUSIONS ：HBOA has a certain improvement effect on non-alcoholic fatty liver disease in rats caused by high-fat diet ，and its mechanism may be related to improving lipid metabolism disorders ，anti-oxidative stress and up-regulating the expression of PPARα.

The “universal two-child” policy has brought an increase in the number of pregnant women with advanced age. Many medical problems and ethical conflicts have emerged, and maternal-child health and prenatal and postnatal care are facing great challenges. How to help elderly women realize their reproductive aspiration according to the ethical principle of “safety of mothers and health of children” is a problem that needs our great attention. The transfer of multiple embryos at a time is an independent factor leading to multiple pregnancies. However, there are no strict regulations on single embryo transfer in China. In view of a series of maternal and infant hazards caused by multiple pregnancies, this paper elaborates on the ethics of assisted pregnancy in elderly women with the number of embryos transferred.