Effects of Standing Time during Pretreatment on the Nitrite Concentration Detected by Spectrophotometric Method

Food safety problems caused by excessive nitrite addition have been frequently reported and the detection of nitrite in food is particularly important. The standing time during the pretreatment of primary sample has a great influence on the concentration of nitrite tested by spectrophotometric method. In this context, three kinds of food samples are prepared, including canned mustard, canned fish and home-made pickled water. A series of standing times are placed during the sample pretreatments and the corresponding nitrite contents in these samples are detected by spectrophotometric method based on N-ethylenediamine dihydrochloride. This study aims to find out a reasonable standing time during the pretreatment of food sample, providing influence factor for precise detection of nitrite.

Comparison of acute pneumonia caused by SARS-CoV-2 and other respiratory viruses in children:a retrospective multi-center cohort study during COVID-19 outbreak

Background:Until January 18,2021,coronavirus disease-2019(COVID-19)has infected more than 93 million individuals and has caused a certain degree of panic.Viral pneumonia caused by common viruses such as respiratory syncytial virus,rhinovirus,human metapneumovirus,human bocavirus,and parainfluenza viruses have been more common in children.However,the incidence of COVID-19 in children was significantly lower than that in adults.The purpose of this study was to describe the clinical manifestations,treatment and outcomes of COVID-19 in children compared with those of other sources of viral pneumonia diagnosed during the COVID-19 outbreak.Methods:Children with COVID-19 and viral pneumonia admitted to 20 hospitals were enrolled in this retrospective multi-center cohort study.A total of 64 children with COVID-19 were defined as the COVID-19 cohort,of which 40 children who developed pneumonia were defined as the COVID-19 pneumonia cohort.Another 284 children with pneumonia caused by other viruses were defined as the viral pneumonia cohort.The epidemiologic,clinical,and laboratory findings were compared by Kolmogorov-Smirnov test,t-test,Mann-Whitney U test and Contingency table method.Drug usage,immunotherapy,blood transfusion,and need for oxygen support were collected as the treatment indexes.Mortality,intensive care needs and symptomatic duration were collected as the outcome indicators.Results:Compared with the viral pneumonia cohort,children in the COVID-19 cohort were mostly exposed to family members confirmed to have COVID-19(53/64 vs.23/284),were of older median age(6.3 years vs.3.2 years),and had a higher proportion of ground-glass opacity(GGO)on computed tomography(18/40 vs.0/38,P<0.001).Children in the COVID-19 pneumonia cohort had a lower proportion of severe cases(1/40 vs.38/284,P=0.048),and lower cases with high fever(3/40 vs.167/284,P<0.001),requiring intensive care(1/40 vs.32/284,P<0.047)and with shorter symptomatic duration(median 5d vs.8d,P<0.001).The proportion of cases with evaluated inflammatory indicators,biochemical indicators related to organ or tissue damage,D-dimer and secondary bacterial infection were lower in the COVID-19 pneumonia cohort than those in the viral pneumonia cohort(P<0.05).No statistical differences were found in the duration of positive PCR results from pharyngeal swabs in 25 children with COVID-19 who received antiviral drugs(lopinavir-ritonavir,ribavirin,and arbidol)as compared with duration in 39 children without antiviral therapy(median 10d vs.9d,P=0.885).Conclusions:The symptoms and severity of COVID-19 pneumonia in children were no more severe than those in children with other viral pneumonia.Lopinavir-ritonavir,ribavirin and arbidol do not shorten the duration of positive PCR results from pharyngeal swabs in children with COVID-19.During the COVID-19 outbreak,attention also must be given to children with infection by other pathogens infection.

Effects of policies and containment measures on control of COVID- 19 epidemic in Chongqing

BACKGROUND Coronavirus disease 2019(COVID-19)is an emerging,rapidly evolving disease that spreads through the respiratory system and is highly contagious.In March 2020,the World Health Organization declared the COVID-19 outbreak a pandemic.In China,the pandemic was controlled after 2 mo through effective policies and containment measures.Describing the detailed policies and containment measures used to control the epidemic in Chongqing will provide a reference for the prevention and control of COVID-19 in other areas of the world.AIM To explore the effects of different policies and containment measures on the control of the COVID-19 epidemic in Chongqing.METHODS Epidemiological data on COVID-19 in Chongqing were prospectively collected from January 21 to March 15,2020.The policies and prevention measures implemented by the government during the epidemic period were also collected.Trend analysis was performed to explore the impact of the main policy measures on the effectiveness of the control of COVID-19 in Chongqing.As of March 15,the cumulative incidence of COVID-19 in Chongqing was 1.84/100000(576 cases)and the infection fatality rate was 1.04%(6/576).The spread of COVID-19 was controlled by effective policies that involved establishing a group for directing the COVID-19 epidemic control effort;strengthening guidance and supervision;ensuring the supply of daily necessities and medical supplies and equipment to residents;setting up designated hospitals;implementing legal measures;and enhancing health education.Medical techniques were implemented to improve the recovery rate and control the epidemic.Policies such as“the lockdown of Wuhan”,“initiating a first-level response to major public health emergencies”,and“implementing the closed management of residential communities”significantly curbed the spread of COVID-19.Optimizing the diagnosis process,shortening the diagnosis time,and constructing teams of clinical experts facilitated the provision of“one team of medical experts for each patient”treatment for severe patients,which significantly improved the recovery rate and reduced the infection fatality rate.CONCLUSION The prevention policies and containment measures implemented by the government and medical institutions are highly effective in controlling the spread of the epidemic and increasing the recovery rate of COVID-19 patients.

A Case of Pediatric Heart Failure Caused by Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Case Report and Literature Review

A female patient aged 3 months and 10 days was admitted to the cardiology department because of symptoms of heart failure.According to the echocardiography results,the patient received a diagnosis of primary endocardial fi broelastosis and was treated withγ-globulin,prednisone,digoxin,and diuretics.Coronary computed tomographic angiography and coronary angiography were performed as there was no improvement after 2 months of treatment.Finally,the patient received a diagnosis of anomalous origin of the left coronary artery from the pulmonary artery(ALCAPA).ALCAPA is a rare congenital heart defect that can cause severe heart failure during infancy,and is easily misdiagnosed clinically.In this report,we show the process of misdiagnosis of the case and consult the relevant literature,hoping to improve the understanding and early diagnosis of ALCAPA.

Association of Meteorological Factors with Labial Adhesions in Children: A 7-year Retrospective Analysis with 9,467 Cases

Labial adhesions (LA)(also called labial agglutination) are defined as partial or complete agglutination of labia minora. The condition commonly occurs in girls during childhood with an estimated prevalence of 0.6%–5%and a peak incidence in the age-group of 13–24 months[1]. Over half of all patients present with symptoms related to urinary outlet obstruction[2].

Magnetic Resonance Spectroscopy and Prognostic Analysis of Molecular Subtypes of Medulloblastoma

Aim: The aim of this study was to investigate whether magnetic resonance spectrum (MRS) and MR imaging features can be used for non-invasive medulloblastoma subgrouping, and analyse patient characteristics and prognosis of molecular subtypes of medulloblastoma. Material and Methods: 32 patients with medulloblastoma underwent MRI prior to surgical resection, 16 of them underwent MRS. MR imaging features and metabolites measured by MRS were analysed to distinguish molecular subtypes of medulloblastoma. Patient demographics, histopathological types, and prognosis of different molecular subtypes were analysed and compared respectively. Results: MRS and MR imaging features differed from different individuals, but without statistical significance that involves acquiring non-quantitative MR imaging features and NAA/Cr, Cho/Cr, Lip/Cr, Glu and Gln/Cr ratio, to be used to determine molecular subtypes. There was no significant difference of the three molecular subtypes in age, gender and pathological type. The 5-year event-free survival (EFS) of SHH, WNT and non SHH/WNT subtype respectively were 75%, 57.1%, 38.1%, with no significant difference (p = 0.382). 5-year EFS of non SHH/WNT subtype was significantly higher in ≤3 years old group than >3 years old group (p = 0.047). Conclusion: MRS and MR imaging features can’t be used to determine molecular subtypes based on our small sample study. There was no significant difference of the prognosis in the three molecular subtypes. The prognosis of ≤3 years old group of non SHH/WNT subtype is better than >3 years old group.

Clinical Analysis of Transcatheter Embolotherapy for Congenital Pulmonary Arteriovenous Fistulas in Children

Objective:To summarize the clinical features and therapeutic effects of transcatheter embolotherapy for congenital pulmonary arteriovenous fi stulas(PAVFs)in children,and to explore the method and therapeutic principle of transcatheter embolotherapy for congenital PAVFs in children.Method:We retrospectively reviewed nine patients with PAVF who underwent transcatheter embolotherapy in the Children’s Hospital of Chongqing Medical University from July 2004 to July 2019,including the demographic characteristics,clinical manifestations,effi ciency of closure,and follow-up.Results:Transcatheter embolotherapy was successful in all cases,and the symptom remission rate was 100%during the follow-up.No residual shunts or other complications occurred during the follow-up period.Compared with before embolotherapy,there were signifi cant changes in the percentage of saturated oxyhemoglobin and total hemoglobin level at the last follow-up(t=10.06,P=0.000;t=3.055,P=0.0076).No signifi cant difference was observed in pulmonary artery pressure before and after embolotherapy(t=0.13,P=0.90).Conclusions:Transcatheter embolotherapy offers the advantages of safety,with a decreased risk of trauma and a specifi c effect of treatment,and therefore is recommended as the fi rst-line treatment for congenital PAVFs in children.However,continued research is necessary to understand the full potential of transcatheter embolotherapy.

Efficacy of corticosteroids injection and autologous bone marrow injection in the treatment of simple bone cyst in children: a meta-analysis

Objective: Evaluating the effectiveness of steroids and autologous bone marrow injection in the treatment of children with simple bone cysts. Methods: The literatures of Pubmed, CBM, CNKI, Wanfang Data, and VIP Database were compared in the database of corticosteroids injection and autologous bone marrow injection for the treatment of children with simple bone cysts. The literature was retrieved until June 2018. Read the abstract or full text of the literature carefully, track the references, evaluate the quality of the included literature and extract the data, and use Rev Man 5.3 for Meta-analysis. Results: There were five studies were included, a total of 246 children with simple bone cysts were enrolled in the study. Of these, 132 received percutaneous steroid injection and 114 received percutaneous autologous bone marrow injection. Comparison of percutaneous steroids injection with autologous bone marrow injection, there was no significant difference in overall cure rate (OR = 1.29, 95%, CI = 0.57~2.88, P = 0.54), incidence of pathological fractures after surgery (OR = 1.04, 95%, CI = 0.47~2.30, P = 0.92), and recurrence rate (OR = 3.24, 95%, CI = 0.96~10.96, P =0.06). Conclusion: There was no significant difference in the efficacy of percutaneous steroid injection and autologous bone marrow injection in the treatment of children simple bone cyst.

Comparative Analysis of the Therapeutic Effect of Disinfectant and Non-disinfectant on the Separation of the Labia Minora in Infants

Objective:To compare the effects of the use and non-use of a disinfectant on the outcomes of separation of the labia minora in infants.Methods:The patients were randomly divided into an experimental group with 24 cases and a control group with 25 cases.In the control group,1%iodophor was used to clean and disinfect the large and small labia and the surrounding skin,while normal saline was used in the experimental group.Other procedures such as the surgery and nursing method were the same in both groups.Results:There were no symptoms of urinary tract infection such as redness of the vulva,swelling,pain,and abnormal urination in the test group and control group after three days of follow-up,and no recurrence was seen at one month of follow-up.There was no statistically significant difference between the two groups(P>0.05).Conclusion:Use or non-use of a disinfectant to clean the urethral opening before separation of the labia minora has no significant effect on the outcomes,and does not cause postoperative urinary tract infection symptoms.Moreover,non-use of a disinfectant can prevent local irritation and reduce the economic burden on the patients.

Magnetic resonance imaging focused on the ferritin heavy chain 1 reporter gene detects neuronal differentiation in stem cells

The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders.Thus,there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells.Our previous study confirmed that magnetic resonance imaging,with a focus on the ferritin heavy chain 1 reporter gene,could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene.However,we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal.To solve this problem,we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells.In this study,we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene;we used this lentivirus to transduce bone marrow mesenchymal stem cells.Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells;this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal.In summary,we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter.This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells,which may be useful in stem cell-based therapies.

Activation of LONP1 by 84-B10 alleviates aristolochic acid nephropathy via re-establishing mitochondrial and peroxisomal homeostasis

Pharmaceutical formulations derived from Aristolochiaceae herbs, which contain aristolochic acids(AAs), are widely used for medicinal purposes. However, exposure to these plants and isolated AAs is linked to renal toxicity, known as AA nephropathy(AAN). Currently, the mechanisms underlying AAN are not fully understood, leading to unsatisfactory treatment strategies. In this study, we explored the protective role of 84-B10(5-[[2-(4-methoxyphenoxy)-5-(trifluoromethyl) phenyl] amino]-5-oxo-3-phenylpentanoic acid) against AAN. RNA-seq analysis revealed that the mitochondrion and peroxisome were the most affected cellular components following 84-B10 treatment in AAN mice. Consistently, 84-B10 treatment preserved mitochondrial ultrastructure, restored mitochondrial respiration, enhanced the expression of key transporters(carnitine palmitoyltransferase 2) and enzymes(acylCoenzyme A dehydrogenase, medium chain) involved in mitochondrial fatty acid β-oxidation, and reduced mitochondrial ROS generation in both aristolochic acid I(AAI)-challenged mice kidneys and cultured proximal tubular epithelial cells. Additionally, 84-B10 treatment increased the expression of key transporters(ATP binding cassette subfamily D) and rate-limiting enzymes(acyl-CoA oxidase 1) involved in peroxisomal fatty acid β-oxidation and restored peroxisomal redox balance. Knocking down LONP1 expression diminished the protective effects of 84-B10 against AAN, suggesting LONP1-dependent protection. In conclusion, our study provides evidence that AAN is associated with significant disturbances in both mitochondrial and peroxisomal functions. The LONP1 activator 84-B10 demonstrates therapeutic potential against AAN, likely by maintaining homeostasis in both mitochondria and peroxisomes.

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

Sodium valproate suppresses abnormal neurogenesis induced by convulsive status epilepticus

Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18–20 hours. Sodium valproate(100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day(4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.

DNA immunoadsorption for childhood-onset systemic lupus erythematosus

We present a retrospective review of DNA immunoadsorption (DNA-IA) therapy on clinical symptoms as well as indicators in pediatric cases with systemic lupus erythematosus (SLE), and follow up the short-term curative effects. 16 SLE cases were treated by DNA-IA for 3 times every other day. We observed the changes on clinical manifestations and immunological indicators, in order to compare the alteration of these indicators including clinical manifestations, Systemic Lupus Erythematosus Disease Active Index (SLEDAI) scores, 24 hurinary protein excretion, autoantibodies, serum IgG and complement C3. 13 cases were followed up regularly, within 3 months after DNA-IA therapy, 12 cases of clinical manifestations improved (92.3%). SLEDAI scores in 10 cases decreased from (16.20 ± 12.54) to less than 5 (76.9%), 8 cases of ANA, anti-DNA antibodies were negative (61.5%), 13 cases with IgG level in serum recovered to normal (10.39 ± 4.38) g/L, C3 level rose to normal (1.06 ± 0.23) g/L. 3 to 6 months after IA, clinical manifestations and laboratory examinations in all cases got maximum improved. 9 months after IA, SLEDAI score in 2 cases (15.4%) rose to more than 5, anti-DNA antibody in 2 cases (15.4%) became positive, and 1case (7.7%) with serum C3 decreased again. 2 cases died from multiple organs dysfunction within 3 to 6 months after IA. No serious complications were found during DNA-IA. We recommend that DNA immunoadsorption is a safe and effective therapy for active childhood-onset SLE, which could improve clinical symptoms, eliminate ANA and anti-DNA antibodies. Combining with corticosteroids and immunosuppressive drugs, DNA-IA could significantly reduce the activity of disease and protect vital organs function in the short term.

Off-label drug use in children over the past decade: a scoping review

To the Editor:Off-label drug use(OLDU)refers to the use of a drug outside of the age,indication,weight,dose,formulation,or route of administration indicated on the label.It is a major concern and a common practice for clinicians around the globe,especially for pediatricians,owing to the lack of pediatric-specific drug information.[1]Research showed that US office-based physicians had ordered 41.2 million off-label orders per year for children and the trend had been increasing from 2006 to 2015.

<i>Lactobacillus</i>GG Supplementation on Anti-<i>Helicobacter pylori</i>Therapy-Related Side Effects and Eradication Rates: A Meta-Analysis

Background: Concerns still exist with respect to unsatisfactory eradication rates and/or therapy-associated side effects for the use of standard triple therapy in the treatment of Helicobacter pylori infection, which prompts considerable interest in new therapy. We systematically reviewed the literature to investigate whether Lactobacillus GG as supplementation to standard triple therapy could improve H. pylori eradication rates and/or reduce therapy-associated side effects. Methods: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from their inception to August 4, 2015 for randomized controlled trials (RCTs). The language was restricted to English only. Results: Four RCTs involving a total of 305 participants (including 83 children) were included. Lactobacillus GG given along with triple therapy significantly reduced the risk of overall H. pylori therapy-related adverse effects (three RCTs, n = 221, RR 0.59, 95% CI 0.45 - 0.78), particularly of diarrhea (four RCTs, n = 285, RR 0.23, 95% CI 0.11 - 0.47), bloating (four RCTs, n = 289, RR 0.61, 95% CI 0.41 - 0.90), and taste disturbance (four RCTs, n = 288, RR 0.38, 95% CI 0.23 - 0.62). There were no significant differences between groups in the risk of other adverse effects. No beneficial effects of Lactobacillus GG were observed for H. pylori eradication rates (four RCTs, n = 284, RR 0.99, 95% CI 0.88 - 1.13). Conclusion: Current evidence indicates that Lactobacillus GG administered along with standard triple therapy is a feasible way to reduce therapy-related side effects, particularly diarrhea, bloating, and taste disturbance. However, Lactobacillus GG shows no effects on eradication rates.

Development of the Scientific,Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines

Background:This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines,named Scientific,Transparent and Applicable Rankings tool(STAR),and test its reliability,validity,and usability.Methods:This study set up a multidisciplinary working group including guideline methodologists,statisticians,journal editors,clinicians,and other experts.Scoping review,Delphi methods,and hierarchical analysis were used to develop the STAR tool.We evaluated the instrument’s intrinsic and interrater reliability,content and criterion validity,and usability.Results:STAR contained 39 items grouped into 11 domains.The mean intrinsic reliability of the domains,indicated by Cronbach’sαcoefficient,was 0.588(95%confidence interval[CI]:0.414,0.762).Interrater reliability as assessed with Cohen’s kappa coefficient was 0.774(95%CI:0.740,0.807)for methodological evaluators and 0.618(95%CI:0.587,0.648)for clinical evaluators.The overall content validity index was 0.905.Pearson’s r correlation for criterion validity was 0.885(95%CI:0.804,0.932).The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.Conclusion:The instrument performed well in terms of reliability,validity,and efficiency,and can be used for comprehensively evaluating and ranking guidelines.

使用大量同位素分布分析未成熟儿胆固醇合成和脂质更新

在发育期间,未成熟儿较足月儿更早地从胎盘供应碳水化合物转换到从肠道吸收脂类。基于这样的新陈代谢后果尚不清楚,但对长期的健康可能有影响。事实上,对于未成熟儿脂质新陈代谢的了解十分有限。对7例未成熟儿(出生体重1349±417g,胎龄30±2周)

PTEN-induced putative kinase 1 regulates mitochondrial quality control and is essential for the maturation of human induced pluripotent stem cell-derived cardiomyocytes

Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)have attracted attention in the field of regenerative medicine due to their potential ability to repair damaged hearts.However,the immature phenotype of these cells limits their clinical application.Cardiomyocyte maturation is accompanied by changes in mitochondrial quality.PTEN-induced putative kinase 1(PINK1)has been linked to mitochondrial quality control.However,whether the changes in mitochondrial quality in hiPSC-CMs are associated with PINK1,and the impact of PINK1 on hiPSC-CMs development are not clear.In this study,we found that knockdown of PINK1 in hiPSC-CMs resulted in mitochondrial fragmentation and impaired mitochondrial functions such as mitophagy and mitochondrial biogenesis.PINK1 deletion also inhibited the maturation of hiPSC-CMs,reverting them to a naive structural and functional state.We found that restoring the mitochondrial structure did not completely rescue the mitochondrial dysfunction caused by PINK1 deletion,while activation of PINK1 kinase activity using kinetin promoted mitochondrial fusion,increased the mitochondrial membrane potential and ATP production,and maintained the development and maturation of hiPSC-CMs.In conclusion,PINK1 regulates the mitochondrial structure and function of hiPSC-CMs,and is essential for the maturation of hiPSC-CMs.

Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study

The aim of this phase I study is to evaluate,for the first time,the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies.During the dose escalation phase,patients received a single intravenous infusion of sintilimab at varying doses of 1,3,and 10 mg/kg.The primary endpoints included the identification of dose-limiting toxicities(DLTs)as well as the evaluation of safety and tolerance.Secondary endpoints focused on assessing objective response rate(ORR),progression-free survival(PFS),and overall survival(OS).A total of 29 patients were enrolled,including 10 individuals diagnosed with Hodgkin lymphoma(HL)and 19 patients with various other tumor categories.Notably,diverse pathological types such as thymoma,choroid plexus carcinoma,and NK/T-cell lymphoma were also included in the study cohort.By the safety data cutoff,most adverse events were grade 1 or 2,with grade 3 or higher treatment-related adverse events(TRAE)occurring in 10%of patients.Among the 27 evaluated subjects,four achieved confirmed complete response(CR)while seven patients exhibited confirmed partial response(PR).Additionally,seven patients maintained disease(SD)during the study period.Notably,sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL.Whole-exome sequencing(WES)was conducted in 15 patients to assess the mutational landscape and copy number variation(CNV)status.The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment.The trial is registered on ClinicalTrials.gov with the identifier NCT04400851.