Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

As a traditional Chinese medicine (TCM), borneol has shown superior ability for anti-inflammatory and analgesic activities when coupled with other active ingredients from ancient times. Furthermore, borneol is believed to improve blood concentration and bioavailability of drugs. Thus, it has been paired with various TCM formulas since ancient time. The physiological barriers in human can cause significant limitations in drug efficiency as the drug is primarily restricted from entering into blood and brain. Borneol has been proven to enhance the permeability of biological barriers such as the blood-brain, transdermal, corneal, and intestinal barriers. Moreover, growing interest has been shown in the drug delivery system design for trans-barrier transport involving borneol. Nano-drug delivery system with increased surface area and improved active sites, has been applied to increase the bioactivity of water insoluble drugs. Nano-drug delivery system has been used to enhance drug efficacy by reducing the time of action as compared to conventional administration approach of TCM formulas. Given its ability to enhance cross-barrier permeation and drug efficacy, borneol has been integrated into TCM formulas of drug delivery system for precise and prolonged targeting at tumor sites. However, the design and preparation of a drug delivery system consisting of borneol still face great challenges. Current research fails to unravel the difference in mechanism of action between nano-drug delivery systems comprised of borneol and conventional drug systems coupled with borneol. Enhanced penetration of borneol in drug delivery system is rarely verified compared to conventional administration with identical drug formulation consisting of borneol regarding dosage and medical indications. This study outlines the current state of research on the properties, formulation and pharmacological effects of borneol, allowing cross-comparison of borneol coupled with single compound and classical TCM formulas for various medical indications. This study aims to provide insights into the design of borneol-based enhanced cross-barrier delivery drug formulation, and the potential development of nano-drug system for TCM formulas with borneol for enhanced bioavailability.

Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.
Hyperuricemia/microbiology* ; Humans ; Gastrointestinal Microbiome/physiology* ; Probiotics/therapeutic use* ; Uric Acid/blood* ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional

Objective:To clarify the safety, repair rate, durability, and risk factors for recurrent mitral regurgitation(MR) in patients with Barlow disease(BD) who total thoracoscopic minimally invasive mitral valvuloplasty(TMVP).Methods:Clinical data, mid-term and long-term outcomes of BD patients who underwent TMVP at Guangdong Provincial People's Hospital from January 2009 to June 2022 were retrospectively analyzed. Patients were divided into a group with no MR recurrence(group A) and a group with MR recurrence(group B) according to whether recurrent MR appeared in the postoperative period, and the data of the two groups of patients were compared with each other for the risk factor analysis.Results:The repair rate of TMVP was 98.4%, and no patient died perioperatively. The median follow-up time was 3.1(1.7, 5.2) years, the follow-up rate was 95.8%, and there was no patient died. As of March 2023, 112 patients developed no recurrent MR(group A), 11 patients developed recurrent MR(group B), and 2 patients in group B underwent repeated mitral valve surgery. The left atrial diameter(LAD) and left ventricular end-systolic diameter(LVESD) were higher in group B than in group A patients[LAD: (50.9±7.7)mm vs.(43.7±8.7)mm, P=0.009; LVESD: (37.1±5.5)mm vs.(33.2±4.7)mm, P=0.011], and the percentage of tendon cord rupture was higher in group B than in group A( P=0.022), while the rest of the baseline data were not statistically significant. There was no statistically significant difference between two groups in terms of the use of different surgical techniques, aortic cross-clamp time, cardiopulmonary bypass time, and operative time. Postoperative LAD, postoperative LVESD, and postoperative left ventricular end-diastolic diameter of group B patients were higher than those of group A( P<0.05). There was no statistically significant difference in perioperative and long-term complication rates between the two groups. Multifactorial Cox regression analysis revealed that advanced age( HR=1.049, 95% CI: 0.997-1.103, P=0.066) and large preoperative LVESD( HR=1.168, 95% CI: 1.053-1.295, P=0.003) were the risk factors for postoperative recurrence MR. Conclusion:Total thoracoscopic minimally invasive BD repair is safe, which has a high success rate and good long-term results. Advanced age and large preoperative LVESD are risk factors for recurrent MR in the long term.

Objective To explore the real experiences of nutrition impact symptoms in esophageal cancer patients during diagnosis and treatment,and to provide references for developing nutritional management strategies.Methods Using purposive sampling,15 esophageal cancer patients admitted to the thoracic surgery department of a tertiary grade A hospital in Guangzhou from October to December 2024 were selected for semi-structured interviews.Thematic analysis was used for data analysis.Results 4 themes and 12 sub-themes were identified:①Multiple symptom perceptions:esophageal obstruction-dysphagia,appetite-affecting symptoms,multiple symptom over-lap,and individual differences in symptom perception.② Insufficient symptom cognition:overestimation of symptom controllability and biased symptom attribution.③ Negative emotional reactions:anxiety and fear about eating,frustration with declining eating function,and helplessness and guilt about losing control over eating.④ Di-verse symptom coping strategies:avoidance coping,adaptive coping,and active nutritional management.Conclusion The nutrition impact symptom experiences of esophageal cancer patients are complex and diverse.Healthcare professionals should promptly identify and assess nutrition impact symptoms,provide nutrition health education,strengthen psychological guidance,and develop culturally distinctive individualized nutritional management strategies.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. METHODS: A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children's Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole-exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords "RELA" "NF-κB" "autoinflammatory disease" "tofacitinib" "sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: The child primarily manifested with recurrent fever, vomiting, and oral ulcers. WES identified a heterozygous nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Despite treatment with adalimumab and tocilizumab, the child's symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient's growth and development remained normal. A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. CONCLUSION The nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child's recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.
Humans ; Male ; Transcription Factor RelA/genetics* ; Female ; Hereditary Autoinflammatory Diseases/genetics* ; Child ; Pedigree ; Exome Sequencing

Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.

Objective To examine the safety, efficacy and durability of totally endoscopic minimally invasive (TEMI) mitral valve repair in Barlow’s disease (BD). Methods A retrospective study was performed on patients who underwent mitral valve repair for BD from January 2010 to June 2021 in the Guangdong Provincial People’s Hospital. The patients were divided into a MS group and a TEMI group according to the surgery approaches. A comparison of the clinical data between the two groups was conducted. Results A total of 196 patients were enrolled, including 133 males and 63 females aged (43.8±14.9) years. There were 103 patients in the MS group and 93 patients in the TEMI group. No hospital death was observed. There was a higher percentage of artificial chordae implantation in the TEMI group compared to the MS group (P=0.020), but there was no statistical difference between the two groups in the other repair techniques (P>0.05). Although the total operation time between the two groups was not statistically different (P=0.265), the TEMI group had longer cardiopulmonary bypass time (P<0.001) and aortic clamp time (P<0.001), and shorter mechanical ventilation time (P<0.001) and postoperative hospitalization time (P<0.001). No statistical difference between the two groups in the adverse perioperative complications (P>0.05). The follow-up rate was 94.2% (180/191) with a mean time of 0.2-12.4 (4.0±2.4) years. Two patients in the MS group died with non-cardiac reasons during the follow-up period. The 3-year, 5-year and 10-year overall survival rates of all patients were 100.0%, 99.2%, 99.2%, respectively. Compared with the MS group, there was no statistical difference in the survival rate, recurrence rate of mitral regurgitation, reoperation rate of mitral valve or adverse cardiovascular and cerebrovascular events in the TEMI group (P＞0.05). Conclusion TEMI approach is a safe, feasible and effective approach for BD with a satisfying long-term efficacy.

ObjectiveTo characterize the changes of metabolites of Blumea balsamifera in the process of sweating by non-targeted metabolomics， and to investigate the influence of sweating processing on the constituents of B. balsamifera. MethodsUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） metabolomics was used to identify the metabolites in no sweating group（F1）， sweating 2 d group（F2） and sweating 4 d group（F3）， the differences of metabolites between the groups were compared by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and differential metabolites were screened according to the variable importance in the projection（VIP） value>1 and P<0.05， and the pathway enrichment of the differential metabolites was analyzed by Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsThe results of PCA and OPLS-DA showed a clear distinction between the three groups of samples， indicating significant differences in the compositions of the three groups of samples. A total of 433 differential metabolites were screened between the F1 and F2， with 154 up-regulated and 279 down-regulated， the significant up-regulated metabolites were tangeritin， 5-O-demethylnobiletin and so on， while the metabolites with significant down-regulation included alternariol， fortunellin， etc. A total of 379 differential metabolites were screened between the F2 and F3， with 150 up-regulated and 229 down-regulated， the significant up-regulated metabolites were isoimperatorin， helianyl octanoate and so on， and the significant down-regulated metabolites were hovenoside I， goyasaponin Ⅲ， etc. KEGG pathway enrichment analysis showed that tyrosine metabolism， isoquinoline alkaloid biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， tryptophan metabolism， valine， leucine and isoleucine biosynthesis， pantothenate and coenzyme A biosynthesis may be the key pathways affecting metabolite differences of B. balsamifera after sweating treatment. ConclusionSweating can reduce the content of endophytic mycotoxins in B. balsamifera and has a great impact on the synthesis and metabolic pathways of total flavonoids and auxin. This study can provide a reference for the process research on the sweating conditions of B. balsamifera.