BACKGROUND In multisystem inflammatory syndrome in children(MIS-C)with coronavirus disease 2019,there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal ...BACKGROUND In multisystem inflammatory syndrome in children(MIS-C)with coronavirus disease 2019,there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes.We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters.To study the time-line for resolution of various abnormalities.METHODS In this prospective study done in a tertiary care hospital,270 were recruited from June 2020 to January 2022.Baseline demographic data and clinical presentation were recorded.Laboratory parameters and echocardiography were done at admission.Follow-up was done at 2 weeks,3 months,6 months and 1 year after diagnosis.Descriptive statistics were used for parametric and non-parametric data.Risk factors were identified by multivariate regression analysis.RESULTS The 211(78.2%)had cardiac involvement and 102 needed intensive care unit(ICU)admission.Cardiovascular abnormalities observed were shock 123(45.6%),coronary dilatation 28(10.4%),coronary aneurysm 77(28.5%),left ventricular(LV)dysfunction 78(29.3%),mitral regurgitation(MR)77(28.5%)and pericardial effusion 98(36.3%).Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7%and 0.9%respectively.Multivariate regression analysis revealed breathlessness[odds ratio(OR)=3.91,95%CI:1.25-12.21,P=0.019]and hi-flow nasal cannula(HFNC)support(OR=8.5,95%CI:1.06-68.38,P=0.044)as predictors of cardiovascular involvement.Higher mean age(OR=1.16,95%CI:1.02-1.32,P=0.026),breathlessness(OR=4.99,95%CI:2.05-12.20,P<0.001),gallop(OR=4.45,95%CI:0.41-2.52,P=0.016),MR(OR=3.61,95%CI:1.53-8.53,P=0.004)and invasive ventilation(OR=4.01,95%CI:1.28-12.58,P=0.017)were predictive of LV dysfunction.Altered sensorium(OR=4.96,95%CI:2.23-11.02,P<0.001),headache(OR=6.61,95%CI:1.46-29.92,P=0.014),HFNC(OR=7.03,95%CI:2.04-24.29,P=0.002),non-rebreathing mask usage(OR=21.13,95%CI:9.00-49.61,P<0.001)and invasive ventilation(OR=5.64,95%CI:1.42-22.45,P=0.014)were risk factors for shock.Anemia was a risk factor for coronary involvement(OR=3.09,95%CI:1.79-5.34,P<0.001).CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management.Although shock resolved quickly,resolution of ventricular function and coronary abnormalities were slower,and hence warrants a structured long-term follow-up protocol.展开更多
Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal funct...Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.展开更多
Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An...Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.展开更多
BACKGROUND Not all islet transplants desirably achieve insulin independence.This can be attributed to the microarchitecture and function of the islets influenced by their dimensions.Large islets enhance insulin secret...BACKGROUND Not all islet transplants desirably achieve insulin independence.This can be attributed to the microarchitecture and function of the islets influenced by their dimensions.Large islets enhance insulin secretion through paracrine effects but are more susceptible to hypoxic injury post-transplant,while small islets offer better viability and insulin independence.In vivo studies suggest large islets are essential for maintaining euglycemia,though smaller islets are typically preferred in transplantation for better outcomes.AIM To document the impact of islet dimension on clinical and preclinical transplant outcomes to optimize procedures.METHODS PubMed,Scopus and EMBASE platforms were searched for relevant literature up to 9 April 2024.Articles reported on either glucose-stimulated insulin-secreting(GSIS)capacity,islet viability and engraftment,or insulin independence based on the islet dimension were included.The risk of bias was measured using the Appraisal Tool for Cross-Sectional Studies.Extracted data was analyzed via a narrative synthesis.RESULTS Nineteen studies were included in the review.A total of sixteen studies reported the GSIS,of which nine documented the increased insulin secretion in the small islet,where the majority reported insulin secretion per islet equivalent(IEQ).Seven studies documented increased GSIS in large-sized islets that measure insulin secretion per cell or islet.All the articles that compared small and large islets reported poor viability and engraftment of large islets.CONCLUSION Small islets with a diameter<125μm have desired transplantation outcomes due to their better survival following isolation.Large-sized islets receive blood supply directly from arterioles in vivo to meet their higher metabolic demands.The large islet undergoes central necrosis soon after the isolation(devascularization);failing to maintain the viability and glucose stimuli leads to a decline in GSIS and the overall function of the islet.Improved preservation of large islets after islet isolation,enhances the islet yield(IEQ),thereby reducing the likelihood of failed islet isolation and potentially improves transplant outcome.展开更多
Antimicrobial resistance is a global public health threat,and the World Health Organization(WHO)has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed.The ...Antimicrobial resistance is a global public health threat,and the World Health Organization(WHO)has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed.The discovery and introduction of novel antibiotics are time-consuming and expensive.According to WHO’s report of antibacterial agents in clinical development,only 18 novel antibiotics have been approved since 2014.Therefore,novel antibiotics are critically needed.Artificial intelligence(AI)has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics.Here,we first summarized recently marketed novel antibiotics,and antibiotic candidates in clinical development.In addition,we systematically reviewed the involvement of AI in antibacterial drug development and utilization,including small molecules,antimicrobial peptides,phage therapy,essential oils,as well as resistance mechanism prediction,and antibiotic stewardship.展开更多
BACKGROUND Thiocolchicoside(TCC),a muscle relaxant with anti-inflammatory properties,is often used alongside nonsteroidal anti-inflammatory drugs(NSAIDs)to treat musculoskeletal pain.This synergistic approach leverage...BACKGROUND Thiocolchicoside(TCC),a muscle relaxant with anti-inflammatory properties,is often used alongside nonsteroidal anti-inflammatory drugs(NSAIDs)to treat musculoskeletal pain.This synergistic approach leverages the complementary mechanisms of action,providing more effective relief for conditions such as arthritis,muscle spasms,and soft tissue injuries.AIM To evaluate the comparative efficacy of the combination therapy of TCC and NSAIDs vs NSAID monotherapy in pain management.METHODS A systematic search of PubMed and Google Scholar databases through October 2024 was performed to evaluate the effectiveness of combined TCC and NSAID therapy vs NSAIDs alone.A retrospective analysis of electronic medical records from India spanning 3 years(2020-2023)examined treatment patterns and focused on clinical outcomes including pain relief,functional improvement,and adverse effects.Key metrics for assessment included visual analog scale scores and hand-to-floor distance,with secondary outcomes assessing patient satisfaction and adverse event(AE)incidence.RESULTS A systematic literature search revealed seven studies,involving 1137 subjects,aligning with the eligibility criteria from a total of 833 hits.Combination therapy using parenteral TCC with NSAIDs significantly reduced pain intensity[standardised mean difference(SMD):-1.33,P<0.001]and enhanced functional improvement(SMD:-1.08,P<0.001)compared to NSAIDs alone.Patients on combination therapy are 6.7 times more likely to experience over 30%pain relief and 5.2 times more likely to achieve over 50%pain relief.Post surgery pain reduction and patient satisfaction were notably higher in the combination group[odds ratio(OR)=10.14,P<0.001].There were no significant differences in mild/moderate AE rates between the groups(OR=1.30,P=0.378).CONCLUSION Evidence indicates that multimodal therapy,including parenteral TCC with NSAIDs,provides quicker and effective pain relief,reduces muscle spasms,and improves hand-to-floor distance compared to using NSAIDs or TCC alone.展开更多
Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and t...Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.展开更多
Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabo...Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.展开更多
Objective This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease(NAFLD)in children with obesity.Methods We conducted a two-step case-control study.Ninety-three ...Objective This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease(NAFLD)in children with obesity.Methods We conducted a two-step case-control study.Ninety-three participants were subjected to whole-exome sequencing(exploratory set).Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing(validation set).Results In the exploratory set,14 genes from the NAFLD-associated pathways were identified.In the validation set,after adjusting for sex,age,and body mass index,ECI2 rs2326408(dominant model:OR=1.33,95%CI:1.02–1.72;additive model:OR=1.22,95%CI:1.01–1.47),C6orf201 rs659305(dominant model:OR=1.30,95%CI:1.01–1.69;additive model:OR=1.21,95%CI:1.00–1.45),CALML5rs10904516(pre-ad dominant model:OR=1.36,95%CI:1.01–1.83;adjusted dominant model:OR=1.40,95%CI:1.03–1.91;and pre-ad additive model:OR=1.26,95%CI:1.04–1.66)polymorphisms were significantly associated with NAFLD in children with obesity(P<0.05).Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516,COX11 rs17209882,and SCD5 rs3733228 was optional(P<0.05),demonstrating a negative interaction between the three genes.Conclusion In the Chinese population,the CALML5 rs10904516,C6orf201 rs659305,and ECI2rs2326408 variants could be genetic markers for NAFLD susceptibility.展开更多
Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s hea...Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s health.The oral and gut microbiota,constituting the largest ecosystem within the human body,are important for maintaining human health and notably contribute to the healthy aging of menopausal women.Therefore,a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance.This paper presents the current understanding of the microbiome during menopause,with a particular focus on alterations in the oral and gut microbiota.Our study elucidates the complex interplay between the microbiome and sex hormone levels,explores microbial crosstalk dynamics,and investigates the associations between the microbiome and diseases linked to menopause.Additionally,this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases.Given that menopause can last for approximately 30 years,gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions,which may result in symptomatic relief from menopause and an increase in quality of life in women.展开更多
BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has...BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.展开更多
Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear....Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial heterogeneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8^(+)T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.展开更多
AIM:To evaluate the safety and effectiveness of intravenous ketamine-midazolam sedation during pediatric endoscopy in the Arab world.METHODS:A retrospective cohort study of all pediatric endoscopic procedures performe...AIM:To evaluate the safety and effectiveness of intravenous ketamine-midazolam sedation during pediatric endoscopy in the Arab world.METHODS:A retrospective cohort study of all pediatric endoscopic procedures performed between 2002-2008 at the shared endoscopy suite of King Abdullah University Hospital,Jordan University of Science & Technology,Jordan was conducted.All children were > 1 year old and weighed > 10 kg with American Society of Anesthesiologists class 1 or 2.Analysis was performed in terms of sedation-related complications(desaturation,respiratory distress,apnea,bradycar-dia,cardiac arrest,emergence reactions),adequacy of sedation,need for sedation reversal,or failure to complete the procedure.RESULTS:A total of 301 patients(including 160 males) with a mean age of 9.26 years(range,1-18 years) were included.All were premedicated with atropine;and 79.4%(239/301) had effective and uneventful sedation.And 248(82.4%) of the 301 patients received a mean dose of 0.16 mg/kg(range,0.07-0.39) midazolam and 1.06 mg/kg(range,0.31-2.67) ketamine,respectively within the recommended dosage guidelines.Recommended maximum midazolam dose was exceeded in 17.6% patients [34 female(F):19 male(M),P = 0.003] and ketamine in 2.7%(3 M:5 F).Maximum midazolam dose was more likely to be exceeded than ketamine(P < 0.001).Desaturation occurred in 37(12.3%) patients,and was reversible by supplemental oxygen in all except 4 who continue to have desaturation despite supplemental oxygen.Four(1.3%) patients had respiratory distress and 6(2%) were difficult to sedate and required a 3rd sedative;12(4%) required reversal and 7(2.3%) failed to complete the procedure.None developed apnea,bradycardia,arrest,or emergence reactions.CONCLUSION:Ketamine-midazolam sedation appears safe and effective for diagnostic pediatric gastrointestinal endoscopy in the Arab world for children aged > 1 year and weighing > 10 kg without co-morbidities.展开更多
Objective To characterize carbapenem （CPM）-non-susceptible Klebsiella pneumoniae （K. pneumoniae） and carbape-nemase produced by these strains isolated from Beijing Children＇s Hospital based on a five-year surveil...Objective To characterize carbapenem （CPM）-non-susceptible Klebsiella pneumoniae （K. pneumoniae） and carbape-nemase produced by these strains isolated from Beijing Children＇s Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 （53.1%） strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 （96.8%） and 3 （3.2%） IMP-producing isolates, respectively. 65 （36.3%） strains carried the blaNDM_1 gene. 6 （3.4%） strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 （NDM-1） producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children＇s Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.展开更多
Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained...Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.展开更多
Childhood-onset systemic lupus erythematosus （cSLE） is a severe multisystem autoimmune disease. Renal involvement occurs in the majority of cSLE patients and is often fatal. Renal biopsy is an important investigatio...Childhood-onset systemic lupus erythematosus （cSLE） is a severe multisystem autoimmune disease. Renal involvement occurs in the majority of cSLE patients and is often fatal. Renal biopsy is an important investigation in the management of lupus nephritis. Treatment of renal lupus consists of an induction phase and main-tenance phase. Treatment of childhood lupus nephritis using steroids is associated with poor outcome and excess side-effects. The addition of cyclophosphamide to the treatment schedule has improved disease control. In view of treatment failure using these drugs and a tendency for non-adherence, many newer agents such as immune-modulators and monoclonal antibodies are being tried in patients with cSLE. Trials of these novel agents in the pediatric population are still lacking making a consensus in the management protocol of pediatric lupus nephritis diffcult.展开更多
We describe and summarize the diagnosis,treatment,and reasons for delayed treatment of children with cryptorchidism torsion in Children's Hospital of Chongqing Medical University.The study included 19 cases of cry...We describe and summarize the diagnosis,treatment,and reasons for delayed treatment of children with cryptorchidism torsion in Children's Hospital of Chongqing Medical University.The study included 19 cases of cryptorchidism torsion.The age of the children ranged from 16 days to 12 years(median:6 years).The interval from diagnosis to surgery varied from 4 h to 16 days(median:3 days).Ultrasound was performed in all cases.Fifteen cases had cryptorchidism torsion,2 cases had a soft tissue mass in the inguinal region,and 2 cases had an inguinal/abdominal teratoma.Five cases were treated with an orchidopexy,12 cases were treated with orchiectomy,and 2 cases received resection of a testicular tumor.The 5 children with an orchidopexy were followed up from 1 month to 7 years(median:3 years),with 1 child having a testis retraction and no blood supply.Of the 12 children who had an orchiectomy,three had delayed diagnosis due to family unawareness of the condition,while other delays were due to delayed referral from primary care facilities.The relative rarity and insufficient awareness of cryptorchidism torsion resulted in a low rate of testicular salvage.Therefore,hospitals of all levels should be fully aware of cryptorchidism with torsion and ensure a male child's genital system and inguinal region are examined to improve the success rate of testicular salvage.展开更多
BACKGROUND Reports on perioperative anesthesia management in pediatric patients with difficult airways are scarce.In addition to relatively more difficulties in the technique of endotracheal intubation,the time for ma...BACKGROUND Reports on perioperative anesthesia management in pediatric patients with difficult airways are scarce.In addition to relatively more difficulties in the technique of endotracheal intubation,the time for manipulation is restricted compared to adults.Securing the airways safely and avoiding the occurrence of hypoxemia in these patients are of significance.CASE SUMMARY A 9-year-old boy with spastic cerebral palsy,severe malnutrition,thoracic scoliosis,thoracic and airway malformation,laryngomalacia,pneumonia,and epilepsy faced the risk of anesthesia during palliative surgery.After a thorough preoperative evaluation,a detailed scheme for anesthesia and a series of intu-bation tools were prepared by a team of anesthesiologists.Awake fiberoptic intubation is the widely accepted strategy for patients with anticipated difficult airways.Given the age and medical condition of the patient,we kept him sedated with spontaneous breathing during endotracheal intubation.The endotracheal intubation was completed on the second attempt after the failure of the first effort.Fortunately,the surgery was successful without postoperative complications.CONCLUSION Dealing with difficult airways in the pediatric population,proper sedation allows time to intubate without interrupting spontaneous breathing.The appropriate endotracheal intubation method based on the patient’s unique characteristics is the key factor in successful management of these rare cases.展开更多
Background:Congenital heart disease(CHD)is a chronic medical condition often diagnosed at birth and requires surgical intervention,multiple hospitalizations,and lifelong care.This can put significant stress on the fami...Background:Congenital heart disease(CHD)is a chronic medical condition often diagnosed at birth and requires surgical intervention,multiple hospitalizations,and lifelong care.This can put significant stress on the family,leading to altered maternal mental health,bonding and attachment issues,and the potential for child abuse.The purpose of this study is to explore the characteristics of a sample of young children with CHD who experienced hospitalization with concurrent concern for child abuse in a free-standing pediatric tertiary care hos-pital.Methods:Electronic medical records were reviewed for children aged 0–5 years old who were hospitalized with concern for child abuse between 2016 and 2020.Variables were extracted related to the history of presenta-tion,and sociodemographics including SDOH,admission,and discharge condition/follow-up.Descriptive statis-tics were used to characterize the sample and correlations to identify an association with abuse type.Results:Out of 251 hospitalizations involving concern for child abuse,49(19.5%)had a diagnosis of CHD.The majority of cases were neglect(51%),<1 year of age(80%),male(57%),Hispanic ethnicity(45%),and publicly insured(90%).CHD severity was moderate to severe(71%)with multiple co-occurring medical conditions(genetic syn-drome,failure to thrive(FTT),prematurity,history of a feeding tube,developmental delay,and intrauterine drug exposure).Correlations associated with physical abuse were age,maternal mental health,head injury,and history of Child Protective Services(CPS)involvement.Neglect correlated with age,FTT,head injury,history of a feeding tube,previous CPS involvement,and substance use.Correlates specifically related to prenatal substance use included age,maternal mental health status,history of domestic violence,CPS involvement,feeding tube,FTT,lack of housing,employment status,and public insurance.Conclusions:Our study highlights the risk for abuse in children with CHD,regardless of defect severity.The most common abuse type was neglect(mostly prenatal substance use)which was associated with few child characteristics,but many parent/caregiver and neighborhood factors.This underscores the need for individual and/or family-based screening and approaches to provide psy-chological support and needed resources to assist parents of children with CHD to prevent abuse.Interventions should focus on families of low socioeconomic status with limited support and/or resources.展开更多
The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease...The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.展开更多
文摘BACKGROUND In multisystem inflammatory syndrome in children(MIS-C)with coronavirus disease 2019,there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes.We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters.To study the time-line for resolution of various abnormalities.METHODS In this prospective study done in a tertiary care hospital,270 were recruited from June 2020 to January 2022.Baseline demographic data and clinical presentation were recorded.Laboratory parameters and echocardiography were done at admission.Follow-up was done at 2 weeks,3 months,6 months and 1 year after diagnosis.Descriptive statistics were used for parametric and non-parametric data.Risk factors were identified by multivariate regression analysis.RESULTS The 211(78.2%)had cardiac involvement and 102 needed intensive care unit(ICU)admission.Cardiovascular abnormalities observed were shock 123(45.6%),coronary dilatation 28(10.4%),coronary aneurysm 77(28.5%),left ventricular(LV)dysfunction 78(29.3%),mitral regurgitation(MR)77(28.5%)and pericardial effusion 98(36.3%).Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7%and 0.9%respectively.Multivariate regression analysis revealed breathlessness[odds ratio(OR)=3.91,95%CI:1.25-12.21,P=0.019]and hi-flow nasal cannula(HFNC)support(OR=8.5,95%CI:1.06-68.38,P=0.044)as predictors of cardiovascular involvement.Higher mean age(OR=1.16,95%CI:1.02-1.32,P=0.026),breathlessness(OR=4.99,95%CI:2.05-12.20,P<0.001),gallop(OR=4.45,95%CI:0.41-2.52,P=0.016),MR(OR=3.61,95%CI:1.53-8.53,P=0.004)and invasive ventilation(OR=4.01,95%CI:1.28-12.58,P=0.017)were predictive of LV dysfunction.Altered sensorium(OR=4.96,95%CI:2.23-11.02,P<0.001),headache(OR=6.61,95%CI:1.46-29.92,P=0.014),HFNC(OR=7.03,95%CI:2.04-24.29,P=0.002),non-rebreathing mask usage(OR=21.13,95%CI:9.00-49.61,P<0.001)and invasive ventilation(OR=5.64,95%CI:1.42-22.45,P=0.014)were risk factors for shock.Anemia was a risk factor for coronary involvement(OR=3.09,95%CI:1.79-5.34,P<0.001).CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management.Although shock resolved quickly,resolution of ventricular function and coronary abnormalities were slower,and hence warrants a structured long-term follow-up protocol.
基金supported by the National Natural Science Foundation of China,No.82201582(to QT)Scientific and Technological Research Program of Chongqing Municipal Education Commission,No.KJQN202200457(to QT)+3 种基金General Project of Changqing Natural Science Foundation,No.cstc2021jcyjmsxmX0442(to ZL)CQMU Program for Youth Innovation in Future Medicine,No.W0044(to ZD and GH)Direct Research Project for PhD of Chongqing,No.CSTB2022BSXM-JCX0051(to ZL)the Project of the Top-Notch Talent Cultivation Program For the Graduate Students of Chongqing Medical University,No.BJRC202310(to CG)。
文摘Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.
基金supported by the Beijing Natural Science Foundation (grant number: 7232060)National Key Research and Development Program of China (grant number: 2023YFC2307301)Top Level Public Health Technical Personnel Training Plan (grant number: LJRC-03-09)。
文摘Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
文摘BACKGROUND Not all islet transplants desirably achieve insulin independence.This can be attributed to the microarchitecture and function of the islets influenced by their dimensions.Large islets enhance insulin secretion through paracrine effects but are more susceptible to hypoxic injury post-transplant,while small islets offer better viability and insulin independence.In vivo studies suggest large islets are essential for maintaining euglycemia,though smaller islets are typically preferred in transplantation for better outcomes.AIM To document the impact of islet dimension on clinical and preclinical transplant outcomes to optimize procedures.METHODS PubMed,Scopus and EMBASE platforms were searched for relevant literature up to 9 April 2024.Articles reported on either glucose-stimulated insulin-secreting(GSIS)capacity,islet viability and engraftment,or insulin independence based on the islet dimension were included.The risk of bias was measured using the Appraisal Tool for Cross-Sectional Studies.Extracted data was analyzed via a narrative synthesis.RESULTS Nineteen studies were included in the review.A total of sixteen studies reported the GSIS,of which nine documented the increased insulin secretion in the small islet,where the majority reported insulin secretion per islet equivalent(IEQ).Seven studies documented increased GSIS in large-sized islets that measure insulin secretion per cell or islet.All the articles that compared small and large islets reported poor viability and engraftment of large islets.CONCLUSION Small islets with a diameter<125μm have desired transplantation outcomes due to their better survival following isolation.Large-sized islets receive blood supply directly from arterioles in vivo to meet their higher metabolic demands.The large islet undergoes central necrosis soon after the isolation(devascularization);failing to maintain the viability and glucose stimuli leads to a decline in GSIS and the overall function of the islet.Improved preservation of large islets after islet isolation,enhances the islet yield(IEQ),thereby reducing the likelihood of failed islet isolation and potentially improves transplant outcome.
基金supported by the National Natural Science Foundation of China(32300157)the Shanghai Municipal Science and Technology Commission(19411964900)+1 种基金the Major Research and Development Project of Innovative Drugs,Ministry of Science and Technology of China(2017ZX09304005)the Wellcome Trust.
文摘Antimicrobial resistance is a global public health threat,and the World Health Organization(WHO)has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed.The discovery and introduction of novel antibiotics are time-consuming and expensive.According to WHO’s report of antibacterial agents in clinical development,only 18 novel antibiotics have been approved since 2014.Therefore,novel antibiotics are critically needed.Artificial intelligence(AI)has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics.Here,we first summarized recently marketed novel antibiotics,and antibiotic candidates in clinical development.In addition,we systematically reviewed the involvement of AI in antibacterial drug development and utilization,including small molecules,antimicrobial peptides,phage therapy,essential oils,as well as resistance mechanism prediction,and antibiotic stewardship.
文摘BACKGROUND Thiocolchicoside(TCC),a muscle relaxant with anti-inflammatory properties,is often used alongside nonsteroidal anti-inflammatory drugs(NSAIDs)to treat musculoskeletal pain.This synergistic approach leverages the complementary mechanisms of action,providing more effective relief for conditions such as arthritis,muscle spasms,and soft tissue injuries.AIM To evaluate the comparative efficacy of the combination therapy of TCC and NSAIDs vs NSAID monotherapy in pain management.METHODS A systematic search of PubMed and Google Scholar databases through October 2024 was performed to evaluate the effectiveness of combined TCC and NSAID therapy vs NSAIDs alone.A retrospective analysis of electronic medical records from India spanning 3 years(2020-2023)examined treatment patterns and focused on clinical outcomes including pain relief,functional improvement,and adverse effects.Key metrics for assessment included visual analog scale scores and hand-to-floor distance,with secondary outcomes assessing patient satisfaction and adverse event(AE)incidence.RESULTS A systematic literature search revealed seven studies,involving 1137 subjects,aligning with the eligibility criteria from a total of 833 hits.Combination therapy using parenteral TCC with NSAIDs significantly reduced pain intensity[standardised mean difference(SMD):-1.33,P<0.001]and enhanced functional improvement(SMD:-1.08,P<0.001)compared to NSAIDs alone.Patients on combination therapy are 6.7 times more likely to experience over 30%pain relief and 5.2 times more likely to achieve over 50%pain relief.Post surgery pain reduction and patient satisfaction were notably higher in the combination group[odds ratio(OR)=10.14,P<0.001].There were no significant differences in mild/moderate AE rates between the groups(OR=1.30,P=0.378).CONCLUSION Evidence indicates that multimodal therapy,including parenteral TCC with NSAIDs,provides quicker and effective pain relief,reduces muscle spasms,and improves hand-to-floor distance compared to using NSAIDs or TCC alone.
基金funded by the Beijing Natural Science Foundation(5242007,L222076,L246011)the High-level Public Health Technical Talents Project by the Beijing Municipal Commission of Health(Key discipline personnel-02-05)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-12M-5-026,2022-I2M-CoV19-006)the Reform and Development of the Beijing Municipal Health Commission,and the Respiratory Research Project of the National Clinical Research Center for Respiratory Diseases(HXZX-202106).
文摘Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.
基金supported by grants from the National Natural Science Foundation of China(32371030,82371194,and 82071395)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-LZX0010 and CSTB2024NSCQ-MSX0269)the CQMU Program for Youth Innovation in Future Medicine(W0044).
文摘Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
基金supported by the Hunan Provincial Natural Science Foundation of China(2024JJ6257)Hunan Children’s Hospital Cultivation Project Fund(2024GZPY04)+2 种基金Opening fundings of Hunan Provincial Key Laboratory of Pediatric Orthopedics(2023TP1019)Science and Technology Project of Furong Laboratory(2023SK2111)Hunan Provincial Clinical Medical Research Center for pediatric Limb Deformities(2019SK4006)。
文摘Objective This study aimed to evaluate the association between susceptibility genes and non-alcoholic fatty liver disease(NAFLD)in children with obesity.Methods We conducted a two-step case-control study.Ninety-three participants were subjected to whole-exome sequencing(exploratory set).Differential genes identified in the small sample were validated in 1,022 participants using multiplex polymerase chain reaction and high-throughput sequencing(validation set).Results In the exploratory set,14 genes from the NAFLD-associated pathways were identified.In the validation set,after adjusting for sex,age,and body mass index,ECI2 rs2326408(dominant model:OR=1.33,95%CI:1.02–1.72;additive model:OR=1.22,95%CI:1.01–1.47),C6orf201 rs659305(dominant model:OR=1.30,95%CI:1.01–1.69;additive model:OR=1.21,95%CI:1.00–1.45),CALML5rs10904516(pre-ad dominant model:OR=1.36,95%CI:1.01–1.83;adjusted dominant model:OR=1.40,95%CI:1.03–1.91;and pre-ad additive model:OR=1.26,95%CI:1.04–1.66)polymorphisms were significantly associated with NAFLD in children with obesity(P<0.05).Interaction analysis revealed that the gene-gene interaction model of CALML5 rs10904516,COX11 rs17209882,and SCD5 rs3733228 was optional(P<0.05),demonstrating a negative interaction between the three genes.Conclusion In the Chinese population,the CALML5 rs10904516,C6orf201 rs659305,and ECI2rs2326408 variants could be genetic markers for NAFLD susceptibility.
基金supported by Science&Technology Fundamental Resources Investigation Program(2022FY100800)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-12M-1-023/2023-12M-C&T-B-005)+1 种基金Funding for Reform and Development of Beijing Municipal Health Commissionthe National High Level Hospital Clinical Research Funding(2022-PUMCH-B-094).
文摘Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s health.The oral and gut microbiota,constituting the largest ecosystem within the human body,are important for maintaining human health and notably contribute to the healthy aging of menopausal women.Therefore,a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance.This paper presents the current understanding of the microbiome during menopause,with a particular focus on alterations in the oral and gut microbiota.Our study elucidates the complex interplay between the microbiome and sex hormone levels,explores microbial crosstalk dynamics,and investigates the associations between the microbiome and diseases linked to menopause.Additionally,this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases.Given that menopause can last for approximately 30 years,gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions,which may result in symptomatic relief from menopause and an increase in quality of life in women.
基金Supported by Baoding Science and Technology Plan Project,No.2272P011Hebei Province Scientific Research Project,No.20241734Hebei Natural Science Foundation Project,No.H2024104011.
文摘BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.
基金supported by the National Natural Science Foundation of China(82002432 to J.W.,82302068 to M.Z.,and 32300568 to T.W.)the Natural Science Foundation of Shandong Province(ZR2024MH159 to Y.Z.,ZR2020QH179 to J.W.,ZR2022QH057 to M.Z.,and ZR2021QH005 to T.W.)the China Postdoctoral Science Foundation(2024M752006 to S.M.)。
文摘Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial heterogeneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8^(+)T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.
文摘AIM:To evaluate the safety and effectiveness of intravenous ketamine-midazolam sedation during pediatric endoscopy in the Arab world.METHODS:A retrospective cohort study of all pediatric endoscopic procedures performed between 2002-2008 at the shared endoscopy suite of King Abdullah University Hospital,Jordan University of Science & Technology,Jordan was conducted.All children were > 1 year old and weighed > 10 kg with American Society of Anesthesiologists class 1 or 2.Analysis was performed in terms of sedation-related complications(desaturation,respiratory distress,apnea,bradycar-dia,cardiac arrest,emergence reactions),adequacy of sedation,need for sedation reversal,or failure to complete the procedure.RESULTS:A total of 301 patients(including 160 males) with a mean age of 9.26 years(range,1-18 years) were included.All were premedicated with atropine;and 79.4%(239/301) had effective and uneventful sedation.And 248(82.4%) of the 301 patients received a mean dose of 0.16 mg/kg(range,0.07-0.39) midazolam and 1.06 mg/kg(range,0.31-2.67) ketamine,respectively within the recommended dosage guidelines.Recommended maximum midazolam dose was exceeded in 17.6% patients [34 female(F):19 male(M),P = 0.003] and ketamine in 2.7%(3 M:5 F).Maximum midazolam dose was more likely to be exceeded than ketamine(P < 0.001).Desaturation occurred in 37(12.3%) patients,and was reversible by supplemental oxygen in all except 4 who continue to have desaturation despite supplemental oxygen.Four(1.3%) patients had respiratory distress and 6(2%) were difficult to sedate and required a 3rd sedative;12(4%) required reversal and 7(2.3%) failed to complete the procedure.None developed apnea,bradycardia,arrest,or emergence reactions.CONCLUSION:Ketamine-midazolam sedation appears safe and effective for diagnostic pediatric gastrointestinal endoscopy in the Arab world for children aged > 1 year and weighing > 10 kg without co-morbidities.
基金supported by Scientific Research Project of Beijing Children's Hospital(2012MS08)Beijing Municipal Science and Technology Project(D131100005313014)
文摘Objective To characterize carbapenem （CPM）-non-susceptible Klebsiella pneumoniae （K. pneumoniae） and carbape-nemase produced by these strains isolated from Beijing Children＇s Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 （53.1%） strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 （96.8%） and 3 （3.2%） IMP-producing isolates, respectively. 65 （36.3%） strains carried the blaNDM_1 gene. 6 （3.4%） strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 （NDM-1） producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from Beijing Children＇s Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.
基金funded by the following grants and contracts:Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38020400 to S.W.)the National Natural Science Foundation of China(32325013 to S.W.,32271186 to J.T.,31900408 to M.Z.)+5 种基金the CAS Project for Young Scientists in Basic Research(YSBR-077 to S.W.)Shanghai Science and Technology Commission Excellent Academic Leaders Program(22XD1424700 to S.W.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-066 to L.J.and J.W.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01 to L.J.and S.W.)the National Science and Technology Basic Research Project(2015FY111700 to L.J.)the 111 Project(B13016 to L.J.).
文摘Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.
文摘Childhood-onset systemic lupus erythematosus （cSLE） is a severe multisystem autoimmune disease. Renal involvement occurs in the majority of cSLE patients and is often fatal. Renal biopsy is an important investigation in the management of lupus nephritis. Treatment of renal lupus consists of an induction phase and main-tenance phase. Treatment of childhood lupus nephritis using steroids is associated with poor outcome and excess side-effects. The addition of cyclophosphamide to the treatment schedule has improved disease control. In view of treatment failure using these drugs and a tendency for non-adherence, many newer agents such as immune-modulators and monoclonal antibodies are being tried in patients with cSLE. Trials of these novel agents in the pediatric population are still lacking making a consensus in the management protocol of pediatric lupus nephritis diffcult.
基金supported by the Basic Research and Frontier Exploration Project of Chongqing Science and Technology Bureau of Yuzhong District(No.20200151).
文摘We describe and summarize the diagnosis,treatment,and reasons for delayed treatment of children with cryptorchidism torsion in Children's Hospital of Chongqing Medical University.The study included 19 cases of cryptorchidism torsion.The age of the children ranged from 16 days to 12 years(median:6 years).The interval from diagnosis to surgery varied from 4 h to 16 days(median:3 days).Ultrasound was performed in all cases.Fifteen cases had cryptorchidism torsion,2 cases had a soft tissue mass in the inguinal region,and 2 cases had an inguinal/abdominal teratoma.Five cases were treated with an orchidopexy,12 cases were treated with orchiectomy,and 2 cases received resection of a testicular tumor.The 5 children with an orchidopexy were followed up from 1 month to 7 years(median:3 years),with 1 child having a testis retraction and no blood supply.Of the 12 children who had an orchiectomy,three had delayed diagnosis due to family unawareness of the condition,while other delays were due to delayed referral from primary care facilities.The relative rarity and insufficient awareness of cryptorchidism torsion resulted in a low rate of testicular salvage.Therefore,hospitals of all levels should be fully aware of cryptorchidism with torsion and ensure a male child's genital system and inguinal region are examined to improve the success rate of testicular salvage.
文摘BACKGROUND Reports on perioperative anesthesia management in pediatric patients with difficult airways are scarce.In addition to relatively more difficulties in the technique of endotracheal intubation,the time for manipulation is restricted compared to adults.Securing the airways safely and avoiding the occurrence of hypoxemia in these patients are of significance.CASE SUMMARY A 9-year-old boy with spastic cerebral palsy,severe malnutrition,thoracic scoliosis,thoracic and airway malformation,laryngomalacia,pneumonia,and epilepsy faced the risk of anesthesia during palliative surgery.After a thorough preoperative evaluation,a detailed scheme for anesthesia and a series of intu-bation tools were prepared by a team of anesthesiologists.Awake fiberoptic intubation is the widely accepted strategy for patients with anticipated difficult airways.Given the age and medical condition of the patient,we kept him sedated with spontaneous breathing during endotracheal intubation.The endotracheal intubation was completed on the second attempt after the failure of the first effort.Fortunately,the surgery was successful without postoperative complications.CONCLUSION Dealing with difficult airways in the pediatric population,proper sedation allows time to intubate without interrupting spontaneous breathing.The appropriate endotracheal intubation method based on the patient’s unique characteristics is the key factor in successful management of these rare cases.
文摘Background:Congenital heart disease(CHD)is a chronic medical condition often diagnosed at birth and requires surgical intervention,multiple hospitalizations,and lifelong care.This can put significant stress on the family,leading to altered maternal mental health,bonding and attachment issues,and the potential for child abuse.The purpose of this study is to explore the characteristics of a sample of young children with CHD who experienced hospitalization with concurrent concern for child abuse in a free-standing pediatric tertiary care hos-pital.Methods:Electronic medical records were reviewed for children aged 0–5 years old who were hospitalized with concern for child abuse between 2016 and 2020.Variables were extracted related to the history of presenta-tion,and sociodemographics including SDOH,admission,and discharge condition/follow-up.Descriptive statis-tics were used to characterize the sample and correlations to identify an association with abuse type.Results:Out of 251 hospitalizations involving concern for child abuse,49(19.5%)had a diagnosis of CHD.The majority of cases were neglect(51%),<1 year of age(80%),male(57%),Hispanic ethnicity(45%),and publicly insured(90%).CHD severity was moderate to severe(71%)with multiple co-occurring medical conditions(genetic syn-drome,failure to thrive(FTT),prematurity,history of a feeding tube,developmental delay,and intrauterine drug exposure).Correlations associated with physical abuse were age,maternal mental health,head injury,and history of Child Protective Services(CPS)involvement.Neglect correlated with age,FTT,head injury,history of a feeding tube,previous CPS involvement,and substance use.Correlates specifically related to prenatal substance use included age,maternal mental health status,history of domestic violence,CPS involvement,feeding tube,FTT,lack of housing,employment status,and public insurance.Conclusions:Our study highlights the risk for abuse in children with CHD,regardless of defect severity.The most common abuse type was neglect(mostly prenatal substance use)which was associated with few child characteristics,but many parent/caregiver and neighborhood factors.This underscores the need for individual and/or family-based screening and approaches to provide psy-chological support and needed resources to assist parents of children with CHD to prevent abuse.Interventions should focus on families of low socioeconomic status with limited support and/or resources.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82071395)the Natural Science Foundation of Chongqing(Grant Nos.cstc2021ycjh-bgzxm0186,cstc2020jcyj-zdxmX0004,and cstc2021jcyj-bsh0023)the CQMU Program for Youth Innovation in Future Medicine(Grant No.W0044).
文摘The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.
