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 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 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.

Abstract Since the first confirmed human infection with avian influenza A(H5N1) virus was reported in Hong Kong SAR (China) in 1997, sporadic zoonotic avian influenza viruses causing human illness have been identified globally with the World Health Organization (WHO) Western Pacific Region as a hotspot. A resurgence of A(H5N1) occurred in humans and animals in November 2003. Between November 2003 and September 2017, WHO received reports of 1838 human infections with avian influenza viruses A(H5N1), A(H5N6), A(H6N1), A(H7N9), A(H9N2) and A(H10N8) in the Western Pacific Region. Most of the infections were with A(H7N9) (n = 1562, 85%) and A(H5N1) (n = 238, 13%) viruses, and most (n = 1583, 86%) were reported from December through April. In poultry and wild birds, A(H5N1) and A(H5N6) subtypes were the most widely distributed, with outbreaks reported from 10 and eight countries and areas, respectively. Regional analyses of human infections with avian influenza subtypes revealed distinct epidemiologic patterns that varied across countries, age and time. Such epidemiologic patterns may not be apparent from aggregated global summaries or country reports; regional assessment can offer additional insight that can inform risk assessment and response efforts. As infected animals and contaminated environments are the primary source of human infections, regional analyses that bring together human and animal surveillance data are an important basis for exposure and transmission risk assessment and public health action. Combining sustained event-based surveillance with enhanced collaboration between public health, veterinary (domestic and wildlife) and environmental sectors will provide a basis to inform joint risk assessment and coordinated response activities.

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.

In 1918, near the close of the First World War, pandemic influenza swept across the world. Spread by the movement of troops and fueled by dense military-camp living quarters, the virus caused unusually high mortality rates in people 20–40 years old. An estimated 500 million people were infected, and up to 50 million died. Since then, pandemics caused by newly emerging influenza viruses have occurred every 10–40 years, with each of the pandemics in 1957, 1968 and 1977 taking the lives of roughly one million people.1 More recently, the 2009 H1N1 influenza pandemic resulted in an estimated half a million deaths and raised concerns about how prepared the global community was to cope with future public health events.2 Past pandemics can teach us important lessons about preventing and responding to emerging global health threats. This special issue highlights significant achievements across the Western Pacific Region in global pandemic preparedness and response.