Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Diabetes mellitus(DM)stands as a chronic metabolic ailment predominantly characterized by elevated blood glucose lev-els,stemming from either a resistance to insulin or aberrations in insulin secretion.The ensuing persistent hyperglycemia,a direct con-sequence of pancreatic β-cell devastation,acts as a catalyst for a myriad of complications,inclusive of extensive neuropathies.The dis-ease has substantial prevalence and mortality rates,underscoring the gravity of its impact on public health.Dental pulp stem cells(DPSCs)are readily obtainable,and they exhibit a profound capacity for self-renewal,multi-lineage differentiation,and vigorous pro-liferation.Remarkably,DPSCs can differentiate into pancreatic β-cells,subsequently participate in insulin secretion and play a pivotal role in immune modulation.This has achieved notable advancements in the therapeutic domain,particularly in the treatment of chronic diseases.Furthermore,DPSCs harbor the potential to mitigate symptoms in patients afflicted with type 1 diabetes.They navigate this therapeutic pathway through mechanisms that involve suppressing autoimmunity,modulating inflammatory responses,and counteracting oxidative stress.This article meticulously reviews the biological characteristics inherent to DPSCs and explores their multifaceted thera-peutic potential in addressing DM and its associated complications.Through this endeavor,the article aims to contribute to the refine-ment and enhancement of DM management strategies.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To report the clinical and genetic characteristics of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) induced by a new homozygous mutation in the SACS gene, and to improve the clinicians′ recognition of the disease. Methods:Detailed nervous system physical examination was performed on the patient and his parents from a consanguineous family admitted to the Genetics and Metabolism Clinic of the Department of Neurology, the First Affiliated Hospital of Kunming Medical University in March 2022. The peripheral blood DNA of the patient and his parents was extracted, and whole exon sequencing (WES) was performed on the patient and his parents using second-generation sequencing technology. The mutation sites were verified by Sanger sequencing, and the mutation sites were analyzed by software.Results:The 18-year-old Han ethnic male patient developed a progressive stiffness of his bilateral lower limbs and gait unsteadiness since the age of 3. He had pyramidal tract sign in his bilateral lower limbs, cerebellar ataxia, pes cavus and hammer toes. Brain magnetic resonance imaging (MRI) showed symmetrical low signal of bilateral pons, cerebellar atrophy and thinning of corpus callosum in T 2WI and T 2 fluid attenuated inversion recovery (FLAIR) sequences. Neuroelectrophysiological examination showed sensory motor peripheral neuropathy. Ophthalmic examination revealed concomitant exotropia and ametropia in both eyes. WES revealed a homozygous variant of c.6958T>C (p.Tyr2320His) in exon 10 of the SACS gene of the patient, and his parents were heterozygous variant carriers confirmed by Sanger sequencing. The variant was classified as possibly pathogenic (PM1+PM2+PP3+PP4) according to the American Society for Medical Genetics and Genomics. The patient was clearly diagnosed as ARSACS caused by homozygous mutation of c.6958T>C in the SACS gene. Conclusions:A novel pathogenic variant (c.6958T>C) in the SACS gene identified in this study leads to the manifestation of ARSACS. The primary clinical manifestations include cerebellar ataxia, pyramidal tract signs, and sensorimotor peripheral neuropathy. Head MRI examination of T 2WI and T 2FLAIR sequences with symmetrical low signal on both sides of the pons helps to narrow down the scope of differential diagnosis.

OBJECTIVE: The World Health Organization’s (WHO’s) Field Epidemiology Fellowship Programme in the Western Pacific Region aims to strengthen countries’ capacities for surveillance and risk assessment and build a workforce to tackle public health emergencies. A survey was conducted to assess the on-the-job training experience of the Regional Fellows, evaluate the strengths of the Programme and gain feedback on areas for improvement. Methods: Between 25 September and 25 October 2018, an online survey was sent to Regional Fellows who had participated in the Programme between July 2006 and September 2018. The survey was shared with WHO country offices in the Western Pacific Region and directly with graduates of the Programme. Responses were recorded electronically and analysed. Results: A total of 53 former Regional Fellows responded (54% response rate; 53/98). At the time of Programme participation, the Fellows’ median age was 35, 62% (33/53) were female and 72% (38/53) were affiliated with a national or subnational health department. Fellows gained experience in event-based surveillance and risk assessment and worked among a diverse group of professionals in various Member States. Altogether, 77% (41/53) of respondents believed that the Programme had helped them move into a better career position with greater responsibility. Ninety-four percent (50/53) would recommend the Programme to their colleagues. Discussion Alumni from the Western Pacific Region’s Field Epidemiology Fellowship Programme perform key health security roles, particularly within governmental systems, and directly contribute to managing health emergencies in their countries, in the Region and globally. The Programme is building a workforce with surge capacity to ensure that public health events in the Region can be addressed. Furthermore, connections developed through the Programme are helping to develop an alumni network, and enhance communications among Member States and between Member States and WHO.
*Epidemiology/education

Abstract In the Western Pacific Region, event-based surveillance has been conducted for over a decade for rapid detection and assessment of acute public health events. This report describes the establishment and evolution of the Western Pacific regional event-based surveillance system and presents an analysis of public health events in the Region. Between July 2008 and June 2017 there was a total of 2396 events reported in the Western Pacific Region (average of 266 events per year). Events related to infectious diseases in humans account for the largest proportion of events recorded (49%). Maintaining this well-established system is critical in supporting rapid detection, assessment and response to acute public health events, to maintain regional health security.

Highlights • The International Health Regulations, or IHR (2005), establishes timely communication between the World Health Organization (WHO) and Member States to manage acute public health events and protect health security. Experiences of the WHO IHR contact point for the Western Pacific Region demonstrated the communication mechanism has achieved its functions in the Region. • Investment in IHR communication as part of the Asia Pacific Strategy for Emerging Diseases and Public Health Emergencies (APSED III) during peaceful times between public health emergencies builds capacity, confidence and trust in information sharing during emergencies. • IHR communication is integral to the national, regional and global epidemic intelligence and risk assessments system. • Regular simulation exercises (for example, IHR Exercise Crystal) play an important role in testing and strengthening IHR communication. • IHR communication continues to be vital for Member States and WHO Country Offices to advise on health security.

Objective To investigate the training expectations and training strategies of orthopedic clinical specialist nurses (OCSN).Methods Totally 5 020 orthopedic nurses from 342 hospitals from 30 provinces and cities were selected bv convenience sampling.Participants were investigated hy WeChat platform with self-designed questionnaire.Results A total of 4 982 effective questionnaires were collected.Among investigated nurses,13.7％ of them received orthopedic specialist nurses training;91.4％ believed that training should be carried out.Qualifications should be:college degree and above,senior nurse and above,at least 3 ～5 years of nursing experience,1～3 years of nursing experience in orthopedic department.For curriculum,public courses expected to be arranged were communieation skills,nursing teaching,nursing management,and nursing research;expected professional courses were functional exercises,pain management,extremity injury nursing,common treatment techniques in orthopedic department,traction nursing,and position nursing.It was suggested that training was divided into subspecialties and off-duty;classroom teaching,teaching rounds,case discussion and experience exchange were expected training methods;"theory-practice-theory-practice" was most preferable traiuing mode.The preferred teachers were orthopedic doctors,orthopedic head nurses,orthopedic specialist nurses,and senior orthopedic nurses.The length of training was expected to be three months,time for clinical practice should be greater than or equal to theoretical teaching,and the practice bases should be tertiary hospitals.Evaluation should be performed before completion,recertification could be later than completion,and the interval time of recertification should be within 5 years.Conclusion Training needs of orthopedic nurses for OCSN are strong.Training expectations(contents,length,modes and teachers) of orthopedic nurses should be considered when designing systematic training program on OCSN.

Objective To evaluate the effect of deferoxamine on ventilator-associated lung injury in rats.Methods Twenty-four healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 250-300 g,were divided into 3 groups (n =8 each) using a random number table method:control group (group C),ventilator-associated lung injury group (group VALI),and ventilator-associated lung injury plus deferoxamine group (VALI+DFO group).Normal saline 2 ml was intraperitoneally injected in C and VALI groups,and deferoxamine 200 mg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected in group VALI+DFO.The animals were connected to a small animal ventilator 15 min later and mechanically ventilated in volume-controlled mode,with tidal volume 40 ml/kg,respiratory rate 40-60 breaths/min,inspiratory/expiratory ratio 1 ∶ 1,and inspired oxygen fraction ratio 1.0.The rats were sacrificed after the end of mechanical ventilation,and the left lung tissues were removed for examination of the pathological changes (with a light microscope) which were scored and for determination of wet/dry weight ratio (W/D ratio).The right lung was lavaged,and lavage fluid was collected to prepare macrophage suspension,and the alveolar macrophage and mitochondrial reactive oxygen species (ROS) levels were determined using flow cytometry.Results Compared with group C,the pathological score,W/D ratio of lung tissues,and alveolar macrophage and mitochondrial ROS levels were significantly increased in group VALI,and the pathological score was significantly increased in group VALI (P＜0.05).Compared with group VALI,the pathological score,W/D ratio of lung tissues,and alveolar macrophage and mitochondrial ROS levels were significantly decreased in group VALI and DFO (P＜0.05).Conclusion Deferoxamine can reduce ventilator-associated lung injury,and the mechanism may be related to inhibiting oxidative stress in rats.

Objective To evaluate the feasibility of chest limit low dose CT in children using Philips iCT scanner as an example.Methods A total of 28 consecutive children aged between 1 month and 7 years(median age 8 months)who were claimed CT exam by clinicians and received limit low dose CT scans were enrolled.The limit low dose CT were undertaken on a 256-slice CT scanner(Brilliance iCT,Philips)with parameters as 80 kV,10 mAs,0.625 mm×128,and pitch＝1.Firstly,lung algorithm group and standard algorithm group 4 mm slice-thickness image series were reconstructed with lung and standard algorithm respectively using iterative reconstruction(IR)algorithm(iDose44).Then a series of 0.67 mm slice-thickness images were reconstructed with IR(iDose44)and smooth A algorithm,and was transformed into transverse 4 mm images(image transformation group)and coronal multiple planar reformatted(MPR)and volume-rendered(VR)images along the central airway.The transverse images in above three groups were displayed in the same lung window for SD measurement and subjective image quality evaluation on a 5-point scale.The dose length product(DLP)was recorded and the effective dose(E)was calculated.Results The SD values of lung algorithm group,standard algorithm group and image transformation group were 26.7 ±7.6,15.1 ±5.5 and 16.7 ±4.9,respectively,which showed statistically significant difference(F＝29.6,P＜0.05).The noise of lung algorithm group was higher than those of standard algorithm group and image transformation group(mean difference values were 11.6 and 9.6,respectively,P＜0.05),but there were no significant difference between standard algorithm group and image transformation group(P ＞0.05).All images had enough diagnostic image quality.The coronal MPR and VR images were helpful for interpretation of axial images.The mean DLP and E were(8.65 ± 2.97)mGy· cm and(0.21 ±0.10)mSv,respectively.The lowest DLP and E were 4.40 mGy· cm and 0.08 mSv,respectively.Conclusions Using Philips iCT scanner as an example,chest limit low dose CT scanning was feasible for children.Combining with IR and image transformation,the image quality was fully guaranteed and 3D images increased diagnostic confidence.