Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Burden of malignant mesothelioma in China during 1990-2019 and the projections through 2029

Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.

Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis

BACKGROUND The prevention and treatment of Hirschsprung-associated enterocolitis(HAEC)is a serious challenge in pediatric surgery.Exploring the mechanism of HAEC is conducive to the prevention of this disease.AIM To explore the possible mechanism of glycyrrhizic acid(GA)and its therapeutic effect on HAEC.METHODS We developed a model of enteritis induced by trinitrobenzenesulfonic acid(TNBS)in zebrafish,and treated it with different concentrations of GA.We analyzed the effect of GA on the phenotype and inflammation of zebrafish.RESULTS After treatment with TNBS,the area of the intestinal lumen in zebrafish was significantly increased,but the number of goblet cells in the intestinal lumen was significantly reduced,but these did not increase the mortality of zebrafish,indicating that the zebrafish enteritis model was successfully developed.Different concentrations of GA protected zebrafish with enteritis.In particular,high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area,increased the number of goblet cells in the intestinal lumen,and reduced the levels of interleukin(IL)-1βand IL-8.CONCLUSION GA significantly reduced the intestinal luminal area,increased the number of intestinal goblet cells,and decreased IL-1βand IL-8 in zebrafish,and is important for prevention and control of HAEC.

Ultrasound diagnosis of congenital Morgagni hernias: Ten years of experience at two Chinese centers

BACKGROUND Morgagni hernias are rare anomalies that are easily misdiagnosed or missed.AIM To summarize the ultrasound(US)imaging characteristics of Morgagni hernias through a comparison of imaging and surgical results.METHODS The records of children with Morgagni hernias who were hospitalized at two hospitals between January 2013 and November 2023 were retrospectively re-viewed in terms of clinical findings,US features,and operative details.RESULTS Between 2013 and 2023,we observed nine(five male and four female)children with Morgagni hernias.Upper abdominal scanning revealed a widening of the prehepatic space,with an abnormal channel extending from the xiphoid process to the right or left side of the thoracic cavity.The channel had intestinal duct and intestinal gas echoes.Hernia contents were found in the transverse colon(n=6),the colon and small intestine(n=2),and the colon and stomach(n=1).Among the patients,seven had a right-sided lesion,two had a left-sided lesion,and all of them had hernial sacs.CONCLUSION US imaging can accurately determine the location,extent,and content of Morgagni hernias.For suspected Mor-gagni hernias,we recommend performing sonographic screening first.

Functional biomaterials for modulating the dysfunctional pathological microenvironment of spinal cord injury

Spinal cord injury(SCI)often results in irreversible loss of sensory and motor functions,and most SCIs are incurable with current medical practice.One of the hardest challenges in treating SCI is the development of a dysfunctional pathological microenvironment,which mainly comprises excessive inflammation,deposition of inhibitory molecules,neurotrophic factor deprivation,glial scar formation,and imbalance of vascular function.To overcome this challenge,implantation of functional biomaterials at the injury site has been regarded as a potential treatment for modulating the dysfunctional microenvironment to support axon regeneration,remyelination at injury site,and functional recovery after SCI.This review summarizes characteristics of dysfunctional pathological microenvironment and recent advances in biomaterials as well as the technologies used to modulate inflammatory microenvironment,regulate inhibitory microenvironment,and reshape revascularization microenvironment.Moreover,technological limitations,challenges,and future prospects of functional biomaterials to promote efficient repair of SCI are also discussed.This review will aid further understanding and development of functional biomaterials to regulate pathological SCI microenvironment.

Perinatal outcomes of re-recurrent gestational diabetes mellitus and their prognostic factors:A retrospective cohort study in China

To the Editor:Gestational diabetes mellitus(GDM)is a pathologic condition in which glucose intolerance and insulin resistance develop to different degrees during pregnancy.Women with GDM have higher odds of adverse maternal and fetal outcomes.Patients with a history of GDM were at a significantly increased risk for recurrence of GDM in subsequent pregnancies.Our previous and some other studies found an increased incidence of adverse perinatal outcomes in pregnant with recurrent GDM.^([1])So far,women with a prior history of GDM are not recommended to refrain from subsequent pregnancy in light of the limited available data.What about those women with a history of recurrent GDM?Should women with recurrent GDM be recommended to avoid further pregnancy?Currently,studies on perinatal outcomes of women with re-recurrent GDM and their prognostic factors are very rare.Therefore,this retrospective cohort study was performed to explore perinatal outcomes of pregnant woman with re-recurrent GDM and their prognostic factors.

Clinical significance of extended high-risk human papillomavirus genotyping and viral load in cervical cancer and precancerous lesions

Persistent infections with specific high-risk human papillomavirus(HR-HPV)strains are the leading cause of cervical cancer and precancerous lesions.HPV-16 and HPV-18 are associated with more than 70%of cervical cancer.However,with recent widespread vaccination efforts against cervical cancer,the infection rates of HPV-16 and HPV-18 have decreased across all age groups,while the infection rates of other HR-HPV strains have increased.The non-16/18 HR-HPV strains play an important role in cervical lesions.These strains can be identified with extended genotyping,and the 2019 American Society for Colposcopy and Cervical Pathology(ASCCP)guidelines recommended an HPV-based testing to assess the risk of cervical disease in patients.We reviewed and analyzed the clinical benefits of applying extended HR-HPV genotyping,which was published by the International Agency for Research on Cancer(HPV-16,18,31,33,35,39,45,51,52,56,58,59,66,and 68),to cervical cancer screening.This review concluded that cervical cancer screening needs to include extended HR-HPV genotyping.The examination of extended HR-HPV genotyping in cervical intraepithelial lesions and cervical cancers can help guide clinical practices.

The effect of scrotal versus inguinal orchiopexy on the testicular function of children with clinically palpable,inguinal undescended testis:a randomized controlled trial

To compare the impact of the scrotal vs inguinal orchidopexy approach on the testicular function of infants with cryptorchidism,a randomized controlled trial was conducted involving boys who were 6–12 months old at surgery and were diagnosed with clinically palpable,inguinal undescended testis.Between June 2021 and December 2021,these boys at Fujian Maternity and Child Health Hospital(Fuzhou,China)and Fujian Children’s Hospital(Fuzhou,China)were enrolled.Block randomization with a 1:1 allocation ratio was employed.The primary outcome was testicular function assessed by testicular volume,serum testosterone,anti-Müllerian hormone(AMH),and inhibin B(InhB)levels.Secondary outcomes included operative time,amount of intraoperative bleeding,and postoperative complications.Among 577 screened patients,100(17.3%)were considered eligible and enrolled in the study.Of the 100 children who completed the 1-year follow-up,50 underwent scrotal orchidopexy and 50 underwent inguinal orchidopexy.The testicular volume,serum testosterone,AMH,and InhB levels in both groups increased markedly after surgery(all P<0.05),but there were no apparent differences between groups at 6 months and 12 months after operation(all P>0.05).No differences between the scrotal and inguinal groups were noted regarding the operative time(P=0.987)and amount of intraoperative bleeding(P=0.746).The overall complication rate(2.0%)of the scrotal group was slightly lower than that of the inguinal group(8.0%),although this difference was not statistically significant(P>0.05).Both scrotal and inguinal orchiopexy exerted protective effects on testicular function in children with cryptorchidism,with similar operative status and postoperative complications.Scrotal orchiopexy is an effective alternative to inguinal orchiopexy in children with cryptorchidism.

Status of the neonatal follow‑up system in China:survey and analysis

Background There is little information about neonatal follow-up programs(NFUPs)in China.This study aimed to conduct a survey of hospitals participating in the Chinese Neonatal Network(CHNN)to determine the status of NFUPs,including resources available,criteria for enrollment,neurodevelopmental assessments,and duration of follow-up.Methods We conducted a descriptive study using an online survey of all 72 hospitals participating in CHNN in 2020.The survey included 15 questions that were developed based on the current literature and investigators’knowledge about followup practices in China.Results Sixty-four(89%)of the 72 hospitals responded to the survey,with an even distribution of children’s(31%),maternity(33%)and general(36%)hospitals.All but one(98%)hospital had NFUPs,with 44(70%)being established after 2010.Eligibility criteria for follow-up were variable,but common criteria included very preterm infants<32 weeks or<2000 g birth weight(100%),small for gestational age(97%),hypoxic ischemic encephalopathy(98%)and postsurgery(90%).The average follow-up rate was 70%(range:7.5%–100%).Only 12%of hospitals followed up with patients for more than 24 months.There was significant variation in neurodevelopmental assessments,follow-up schedule,composition of staff,and clinic facilities and resources.None of the staff had received formal training,and only four hospitals had sent staff to foreign hospitals as observers.Conclusions There is significant variation in eligibility criteria,duration of follow-up,types of assessments,staffing,training and facilities available.Coordination and standardization are urgently needed.

A modified fixation technique for the treatment of buried penis in children

For many years,surgical treatment of buried penis in children has been researched by several scholars,and numerous methods exist.This study aimed to explore the clinical effect of a modified fixation technique in treating buried penis in children.Clinical data of 94 patients with buried penis who were treated using the modified penile fixation technique from March 2017 to February 2019 in Fujian Maternity and Child Health Hospital(Fuzhou,China)were retrospectively collected,compared,and analyzed.Clinical data of 107 patients with buried penis who were treated using traditional penile fixation technique from February 2014 to February 2017 were chosen for comparison.The results showed that at 6 months and 12 months after surgery,the penile lengths in the modified penile fixation group were longer than those in the traditional penile fixation group(both P<0.05).The incidence of postoperative skin contracture and penile retraction in the modified penile fixation group was less than that in the traditional penile fixation group(P=0.034 and P=0.012,respectively).When the two groups were compared in terms of parents'satisfaction scores,the scores for penile size,penile morphology,and voiding status in the modified penile fixation group were higher than those in the traditional penile fixation group at 2-week,6-month,and 12-month follow-ups after surgery(all P<0.05).We concluded that the modified penile fixation technique could effectively reduce the incidence of skin contracture and penile retraction and improve the penile length and satisfaction of patients'parents.

Maternal weight,blood lipids,and the offspring weight trajectories during infancy and early childhood in twin pregnancies

Background The intrauterine environment has a profound and long-lasting influence on the health of the offspring.However,its impact on the postnatal catch-up growth of twin children remains unclarified.Therefore,this study aimed to explore the maternal factors in pregnancy associated with twin offspring growth.Methods This study included 3142 live twin children born to 1571 mothers from the Beijing Birth Cohort Study conducted from 2016 to 2021 in Beijing,China.Original and corrected weight-for-age standard deviation scores of the twin offspring from birth to 36 months of age were calculated according to the World Health Organization Child Growth Standards.The corresponding weight trajectories were identified by the latent trajectory model.Maternal factors in pregnancy associated with the weight trajectories of the twin offspring were examined after adjustment for potential confounders.Results Five weight trajectories of the twin children were identified,with 4.9%(154/3142)exhibiting insufficient catch-up growth,30.6%(961/3142),and 46.8%(1469/3142)showing adequate catch-up growth from different birth weights,and 15.0%(472/3142)and 2.7%(86/3142)showing various degrees of excessive catch-up growth.Maternal short stature[adjusted odds ratio(OR)=0.691,95%confidence interval(CI)=0.563–0.848,P=0.0004]and lower total gestational weight gain(GWG)(adjusted OR=0.774,95%CI=0.616–0.972,P=0.03)were associated with insufficient catch-up growth of the offspring.Maternal stature(adjusted OR=1.331,95%CI=1.168–1.518,P<0.001),higher pre-pregnancy body mass index(BMI)(adjusted OR=1.230,95%CI=1.090–1.387,P<0.001),total GWG(adjusted OR=1.207,95%CI=1.068–1.364,P=0.002),GWG rate(adjusted OR=1.165,95%CI=1.027–1.321,P=0.02),total cholesterol(TC)(adjusted OR=1.150,95%CI=1.018–1.300,P=0.03)and low-density lipoprotein-cholesterol(LDL-C)(adjusted OR=1.177,95%CI=1.041–1.330)in early pregnancy were associated with excessive growth of the offspring.The pattern of weight trajectories was similar between monochorionic and dichorionic twins.Maternal height,pre-pregnancy BMI,GWG,TC and LDL-C in early pregnancy were positively associated with excess growth in dichorionic twins,yet a similar association was observed only between maternal height and postnatal growth in monochorionic twins.Conclusion This study identified the effect of maternal stature,weight status,and blood lipid profiles during pregnancy on postnatal weight trajectories of the twin offspring,thereby providing a basis for twin pregnancy management to improve the long-term health of the offspring.