OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Subclinical ptosis is a common congenital abnormality of bilateral upper eyelid development; the clinical manifestations are upper eyelid skin covering the upper corneal margin of more than 2 mm, upper eyelid bloat, narrow lid fissure, often accompanied by epicanthus and eyebrow elevation when the eyes are opened. Patients often present with a single eyelid, which can be easily missed and misdiagnosed. The cause of subclinical ptosis is an increase in the afterload of the levator muscle during contraction due to a variety of reasons, such as gravitational, volumetric, and tensile loads; the clinical manifestations and the normalisation of the levator muscle strength are the main basis for diagnosis and identification of true ptosis. Depending on the type of afterload, different surgical treatments are available, such as blepharoplasty, orbicularis oculi myotomy, upper eyelid tissue reduction, fibrous mesh band release, anterior displacement of the levator complex, and shortening of the levator complex.

Objective To observe brain function changes in insomnia disorder(ID)patients and therapeutic effect of repeated transcranial magnetic stimulation(rTMS)based on resting-state functional MRI(rs-fMRI).Methods Totally 37 patients with ID(ID group)and 20 healthy subjects(control group)were prospectively enrolled.The scores of sleep condition and psychological state scales were compared between groups,also within ID group before and after rTMS treatment.Brain regions with amplitude of low frequency fluctuations(ALFF)and regional homogeneity(ReHo)being significantly different between groups were evaluated based on brain rs-fMRI,and voxel-based resting-state functional connectivity(FC)analysis was performed in the above regions and the predefined regions of interest.Results Before treatment,Pittsburgh sleep quality index(PSQI),insomnia severity index(ISI),Epworth sleepiness score(ESS),Beck depression inventory(BDI)score and Beck anxiety inventory(BAI)score in ID group were all higher than those in control group(all P＜0.05).ALFF values and ReHo of the right median cingulate and paracingulate gyrus(Cingulum_Mid_R)were lower in ID group than those in control group(all FWE correctedP＜0.05).FC between Cingulum_Mid_R and the left anterior cingulate gyrus and cingulate gyrus(Cingulum_Ant_L)decreased,so did that between the left hippocampus(Hippocampus_L)and the right frontal gyrus(Frontal_Mid_R)(all FWE corrected P＜0.05).After rTMS,PSQI,ISI and ESS scores of ID patients decreased compared to those before treatment(all P＜0.05),but no significant change of the above neuroimaging indicators was detected(all FWE corrected P＞0.05).Conclusion ID caused synchronous decrease of Cingulum_Mid_R ALFF value and ReHo,as well as weakened FC between frontal cingulate gyrus and frontal with lobe limbic system.rTMS could improve sleep and mental state of ID patients,but its impact on neuroimaging needed further investigation.

Subclinical ptosis is a common congenital abnormality of bilateral upper eyelid development; the clinical manifestations are upper eyelid skin covering the upper corneal margin of more than 2 mm, upper eyelid bloat, narrow lid fissure, often accompanied by epicanthus and eyebrow elevation when the eyes are opened. Patients often present with a single eyelid, which can be easily missed and misdiagnosed. The cause of subclinical ptosis is an increase in the afterload of the levator muscle during contraction due to a variety of reasons, such as gravitational, volumetric, and tensile loads; the clinical manifestations and the normalisation of the levator muscle strength are the main basis for diagnosis and identification of true ptosis. Depending on the type of afterload, different surgical treatments are available, such as blepharoplasty, orbicularis oculi myotomy, upper eyelid tissue reduction, fibrous mesh band release, anterior displacement of the levator complex, and shortening of the levator complex.

Objective To observe brain function changes in insomnia disorder(ID)patients and therapeutic effect of repeated transcranial magnetic stimulation(rTMS)based on resting-state functional MRI(rs-fMRI).Methods Totally 37 patients with ID(ID group)and 20 healthy subjects(control group)were prospectively enrolled.The scores of sleep condition and psychological state scales were compared between groups,also within ID group before and after rTMS treatment.Brain regions with amplitude of low frequency fluctuations(ALFF)and regional homogeneity(ReHo)being significantly different between groups were evaluated based on brain rs-fMRI,and voxel-based resting-state functional connectivity(FC)analysis was performed in the above regions and the predefined regions of interest.Results Before treatment,Pittsburgh sleep quality index(PSQI),insomnia severity index(ISI),Epworth sleepiness score(ESS),Beck depression inventory(BDI)score and Beck anxiety inventory(BAI)score in ID group were all higher than those in control group(all P＜0.05).ALFF values and ReHo of the right median cingulate and paracingulate gyrus(Cingulum_Mid_R)were lower in ID group than those in control group(all FWE correctedP＜0.05).FC between Cingulum_Mid_R and the left anterior cingulate gyrus and cingulate gyrus(Cingulum_Ant_L)decreased,so did that between the left hippocampus(Hippocampus_L)and the right frontal gyrus(Frontal_Mid_R)(all FWE corrected P＜0.05).After rTMS,PSQI,ISI and ESS scores of ID patients decreased compared to those before treatment(all P＜0.05),but no significant change of the above neuroimaging indicators was detected(all FWE corrected P＞0.05).Conclusion ID caused synchronous decrease of Cingulum_Mid_R ALFF value and ReHo,as well as weakened FC between frontal cingulate gyrus and frontal with lobe limbic system.rTMS could improve sleep and mental state of ID patients,but its impact on neuroimaging needed further investigation.

This article reports on the nursing experience in the rehabilitation of laryngeal function with primary tracheoesophageal puncture for voice prosthesis rehabilitation after laryngectomy.The core elements of postoperative nursing included:the use of a Heat and Moisture Exchanger(HME)for airway humidification to maintain pulmonary health;the implementation of progressive speech training to aid in the reconstruction of speech function;continuous monitoring and dilatation training to ensure the appropriate size of the stoma,thereby ensuring smooth breathing and speech;nasal airflow-inducing training for the promotion of olfactory rehabilitation;standardized maintenance of the voice prosthesis to extend its lifespan and reduce the occurrence of complications.After meticulous postoperative care,the patient showed good recovery of speech,olfaction,and respiratory function at the one-month follow-up,with the stoma diameter maintained at an ideal size and no complications occurred.

Digital health technologies (DHT) not only enhance patient engagement in healthcare but also enable personalized treatment and care services, empowering patients to manage their own health well. This paper reviews the composition and characteristics of digital vulnerable groups, as well as the current application status, influencing factors, intervention measures, and insights of DHT in their care. This paper aims to provide theoretical and practical references for enhancing the quality of DHT care for digital vulnerable groups, thereby promoting targeted and effective development of DHT within the nursing field.

Objective To observe the effect of a heavy load exercise on the ultrastructure,function and fission of skeletal muscle mitochondria in rats,and to analyze the changes of the phosphorylation expression of mitochondrial fission protein and upstream kinase at different times postexercise,and to explore the effect of acute heavy load exercise on mitochondrial fission in skeletal muscle of rats and its possible mechanism.Methods Forty-eight adult male Sprague-Dawley rats were randomly divided in-to a quiet control group(C,n=8)and an exercise group(E,n=40).Rats in the E group exercised on a treadmill down a 16° decline at 16 m/min for 90 min and were further divided into 0 h,12 h,24 h,48 h,and 72 h postexercise subgroups.Soleus muscle was isolated and mitochondria were ex-tracted at the corresponding time points after exercise.The ultrastructure of mitochondria in the soleus muscle was observed using transmission electron microscopy,and mitochondrial quantity and morphomet-ric analysis were conducted.Moreover,the colocalization and quantity of dynamin-related protein 1(Drp1)and cytochrome C oxidease subunit Ⅳ(COXⅣ)in the soleus muscle were detected using im-munofluorescence double-labeling techniques.Meanwhile,protein levels of soleus musclep-Drp1Ser616,p-Drp1Ser637,p-extracellular regulatory protein kinaseThr202/Tyr204(p-ERKThr202/Tyr204),p-protein kinaseAThr197(p-PKAThr197),and mitochondrial NADH of ubiquinone oxidoreductase subunit B8(NDUFB8)and ubiqui-nol-cytochrome C reductase core protein 2(UQCRC2)were determined by using Western blotting.An-other twenty-four rats were randomly divided into a DMSO group(CD),a U0126 group(CU),an Ex-ercise+DMSO group(ED),and an Exercise+U0126 group(EU).Six mice in each group were giv-en a single intra-bitoneal injection of DMSO or ERK inhibitor U0126 20 min before acute downhill running.Then,their phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 in soleus muscle were de-tected by Western blotting.Results(1)From 0 h to 48 h after exercise,the soleus muscle mitochon-dria showed swelling,rounding,and uneven distribution of mitochondria,among which the degree of mitochondrial damage was the most serious at 12 h and 24 h after exercise.Moreover,the protein ex-pression of NDUFB8 and UQCRC2 in the mitochondria fractions from soleus muscle was significantly lower at 12 h post-exercise(P<0.05).(2)The co-localization of Drp1 and COXⅣ in the skeletal muscle increased significantly at 12 h to 24 h after a heavy load exercise compared with group C and group E0(P<0.01).Moreover,the mitochondrial area,circumference,aspect ratio and Ferret diameter in the skeletal muscle were significantly lower at 12 h to 24 h postexercise(P<0.05).Meanwhile,the number of mitochondria was significantly higher at 24 h after exercise(P<0.01).(3)The phosphoryla-tion of ERKThr202/Tyr204,PKAThr197 and Drp1Ser616 was significantly higher at 24 h after exercise(P<0.01),while that of Drp1Ser637 was significantly lower at 48 h and 72 h post-exercise(P<0.01).However,the phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 were significantly down-regulated by U0126 treatment before exercise.Conclusion A session of heavy load exercise caused mitochondrial structure and function damage and induced mitochondrial fission in the skeletal muscle,and then to maintain the homeostasis of skeletal muscle cells by cleaving damaged mitochondria.The mechanism of promot-ing skeletal muscle repair may be related to the positive and negative regulation of Drp1 activity by the phosphorylation of Drp1Ser616 and Drp1Ser637,respectively.Among them,the activation of ERKThr202/Tyr204 mediates the phosphorylation activation of Drp1Ser616,but PKAThr197 is not an upstream kinase that medi-ates the inactivation of Drp1Ser637 phosphorylation.

Objective To analyze the relationship between frailty and acute kidney injury(AKI)after hip fracture surgery in the elderly.Methods A total of 405 elderly patients who underwent hip fracture surgery in Jieyang People's Hospital from August 2021 to January 2023 were retrospectively analysed.According to the modified frailty index(mFI),they were divided into frail group(mFI≥0.27,n=112)and non-frail group(mFI<0.27,n=293).Postoperative AKI was defined according to the Kidney Disease:Improving Global Outcomes(KDIGO)criteria.After 1:1 propensity score matching(PSM),100 cases in each group were successfully matched.Univariable and multivariable logistic regression models,propensity score adjustment,PSM,inverse probability of treatment weighting(IPTW),standardized mortality ratio weighting(SMRW),pairwise algorithm(PA)weighting,and overlap weighting(OW)methods were used to analyze the relationship between frailty and postoperative AKI.Stratified analyses were performed according to age(≥80 or<80 years),gender,whether angiotensin-converting enzyme inhibitors(ACEI)/angiotensin Ⅱreceptor antagonists(ARB)were used,and whether intraoperative hypotension occurred.Results After PSM,there were no significant differences between the two groups in age,sex,surgical type,ACEI/ARB,blood urea nitrogen,serum creatinine,intraoperative blood loss,and intraoperative hypotension[standardized mean difference(SMD)<0.1].In both the original cohort and the matched cohort,the incidence of AKI was higher in frail group than in non-frail group(25.9%vs.8.9%,P<0.001;28.0%vs.11.0%,P=0.002).Analysis of the risk of postoperative AKI in elderly hip fracture patients in frail group found that compared with the non-frail group,in the univariate logistic regression model the odds ratio(OR)and a 95%confidence interval(CI)for the frail group was 3.59(2.00-6.43),P<0.001,and in the multivariable logistic regression model,the OR(95%CI)for frail group was 3.04(1.55-5.95),P=0.001.After adjustment for propensity score,the OR(95%CI)for frail group was 2.85(1.52-5.34),P=0.001,and the OR(95%CI)for frail group after PSM was 3.15(1.47-6.75),P=0.003.After IPTW,SMRW,PA weighting,and OW,the OR(95%CI)for frail group were 2.48(1.37-4.50),2.43(1.41-4.19),2.63(1.25-5.54),and 2.69(1.07-6.78),respectively,with P<0.05.The interaction tests were not statistically significant for age,sex,use of ACEI/ARB,and intraoperative hypotension(P>0.05).Conclusion In elderly patients with hip fractures,preoperative frailty may be a risk factor for postoperative AKI.

Diabetic kidney disease(DKD)is a microvascular complication of diabetes mellitus with a complex pathogenesis.Recent studies have revealed that autophagy and ferroptosis,as two forms of programmed cell death,exhibit dynamic interactions in DKD:autophagy maintains homeostasis by eliminating damaged organelles,while ferroptosis is driven by iron-dependent lipid peroxidation.Imbalance between the two exacerbates renal injury.This review systematically summarizes the signaling pathways and key regulatory factors related to autophagy and ferroptosis,as well as their interaction mechanisms[such as nuclear receptor coactivator 4(NCOA4)-mediated ferritinophagy,clock autophagy,and lipid autophagy].It further elaborates the molecular network by which these processes synergistically regulate DKD progression.Additionally,the potential of modern pharmaceuticals and active components of traditional Chinese medicine to improve kidney injury by targeting autophagy and ferroptosis is discussed,proposing that targeting their cross-talk pathways may provide novel therapeutic strategies for DKD,aiming to lay a theoretical foundation for the development of targeted intervention strategies and precision therapeutic regimens.