Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Serum ferritin and the risk of early-onset colorectal cancer

BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced stages.Low serum ferritin is often incidentally discovered in young adults,however,the indication for endoscopy in EO-CRC is unclear.AIM To compare serum ferritin between patients with EO-CRC and healthy controls(HCs),and examine the association of serum ferritin in EO-CRC with patient-and disease-specific characteristics.METHODS A retrospective study of patients<50 years with newly-diagnosed EO-CRC was conducted from 1/2013-12/2023.Patients were included if serum ferritin was measured within 2 years prior to 1 year following CRC histologic diagnosis.To supplement the analysis,a cohort of HCs meeting similar inclusion and exclusion criteria were identified for comparison.A sensitivity analysis including only patients with serum ferritin obtained at or before diagnosis was separately performed to minimize risk of confounding.RESULTS Among 85 patients identified with EO-CRC(48 females),the median serum ferritin level was 26 ng/mL(range<1-2759 ng/mL).Compared to HCs(n=80211),there were a higher proportion of individuals with EO-CRC with serum ferritin<20 ng/mL(female 65%,male 40%)versus HCs(female 32.1%,male 7.2%)age 29-39 years(P=0.002 and P<0.00001,respectively).Stage IV disease was associated with significantly higher serum ferritin compared to less advanced stages(P<0.001).Serum ferritin obtained before or at the time of diagnosis was lower than levels obtained after diagnosis.Similar findings were confirmed in the sensitivity analysis.CONCLUSION Severe iron deficiency may indicate an increased risk of EO-CRC,particularly at earlier stages.Further studies defining the optimal serum ferritin threshold and routine incorporation of serum ferritin in screening algorithms is essential to develop more effective screening strategies for EO-CRC.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6(IL-6)contributes to the pathophysiology of psychiatric disorders.However,there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia(EOS).AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia,including 33 with age at onset<21 years(EOS group)and 41 with onset≥21 years in[adult-onset schizophrenia(AOS)group],and from 41 healthy controls.Symptom severities were evaluated using the Positive and Negative Syndrome Scale(PANSS).RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls(F=22.32,P<0.01),but did not differ significantly between EOS and AOS groups(P>0.05)after controlling for age,body mass index,and other covariates.Negative symptom scores were higher in the EOS group than the AOS group(F=6.199,P=0.015).Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score(r=-0.389,P=0.032)and avolition/asociality subscore(r=-0.387,P=0.026).CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness.IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Research Progress in Early-onset Colorectal Cancer

Colorectal cancer used to be a common disease among middle-aged and elderly people.In recent years,the incidence of colorectal cancer(Early-onset colorectal cancer,EOCRC)under 50 years old has increased year by year.Different from the traditional late-onset colon cancer(LOCRC),the diagnosis stage of EOCRC is mostly in the late stage,with poor cell differentiation and poor diagnosis,and there is a layer of consensus and guidance on the diagnosis,treatment or screening of EOCRC at presentation.Therefore,fully understanding the disease characteristics and risk exposure factors of EOCRC is helpful to guide early screening and treatment,which ultimately reduces the mortality of EOCRC.In this review article,we summarized the epidemiology,physiology,risk exposure factors and pathological diagnosis of EOCRC,and discussed the diagnosis and treatment prospect of EOCRC.

Molecular genetics of early-onset colorectal cancer

Early-onset colorectal cancer(EOCRC)has been rising in global prevalence and incidence over the past several decades.Environmental influences,including generational lifestyle changes and rising obesity,contribute to these increased rates.While the rise in EOCRC is best documented in western countries,it is seen throughout the world,although EOCRC may have distinct genetic mutations in patients of different ethnic backgrounds.Pathological and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer(LOCRC).Recent studies have identified DNA,RNA,and protein-level alterations unique to EOCRC,revealing much-needed biomarkers and potential novel therapeutic targets.Many molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts,however,studies of other ethnic backgrounds are limited.In addition,certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC,including high-throughput analyses of histone modifications,mRNA splicing,and proteomics on large cohorts.We propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of EOCRC.In this review,we summarize current EOCRC literature,focusing on sporadic molecular alterations in tumors,and their clinical implications.We conclude by discussing current challenges and future directions of EOCRC research efforts.

Advantage of log odds of positive lymph nodes in prognostic evaluation of patients with early-onset colon cancer

BACKGROUND Colon cancer(CC)is one of the most common cancers of the digestive tract,the third most common cancer worldwide,and the second most common cause of cancer-related deaths.Previous studies have demonstrated a higher risk of lymph node metastasis(LNM)in young patients with CC.It might be reasonable to treat patients with early-onset locally advanced CC with extended lymph node dissection.However,few studies have focused on early-onset CC(ECC)patients with LNM.At present,the methods of predicting and evaluating the prognosis of ECC patients with LNM are controversial.From the data of patients with CC obtained from the Surveillance,Epidemiology,and End Results(SEER)database,data of young patients with ECC(≤50 years old)was screened.Patients with unknown data were excluded from the study,while the remaining patients were included.The patients were randomly divided into a training group(train)and a testing group(test)in the ratio of 7:3,while building the model.The model was constructed by the training group and verified by the testing group.Using multiple Cox regression models to compare the prediction efficiency of LNM indicators,nomograms were built based on the best model selected for overall survival(OS)and cause-specific survival(CSS).In the two groups,the performance of the nomogram was evaluated by constructing a calibration plot,time-dependent area under the curve(AUC),and decision curve analysis.Finally,the patients were grouped based on the risk score predicted by the prognosis model,and the survival curve was constructed after comparing the survival status of the high and low-risk groups.RESULTS Records of 26922 ECC patients were screened from the SEER database.N classification,positive lymph nodes(PLN),lymph node ratio(LNR)and log odds of PLN(LODDS)were considered to be independent predictors of OS and CSS.In addition,independent risk factors for OS included gender,race,marital status,primary site,histology,grade,T,and M classification,while the independent prognostic factors for CSS included race,marital status,primary site,grade,T,and M classification.The prediction model including LODDS is composed of minimal Akaike information criterion,maximal concordance indexes,and AUCs.Factors including gender,race,marital status,primary site,histology,grade,T,M classification,and LODDS were integrated into the OS nomogram,while race,marital status,primary site,grade,T,M classification,and LODDS were included into the CSS nomogram.The nomogram representing both cohorts had been successfully verified in terms of prediction accuracy and clinical practicability.CONCLUSION LODDS is superior to N-stage,PLN,and LNR of ECC.The nomogram containing LODDS might be helpful in tumor evaluation and clinical decision-making,since it provides an appropriate prediction of ECC.

Transcription profiles of skin and head kidney from goldfish suffering hemorrhagic septicemia with an emphasis on the TLR signaling pathway

DEAR EDITOR, Hemorrhagic septicemia is an acute, highly fatal disease that affects goldfish (Carassius auratus). To gain a better understanding of related immune genes, the transcriptomes of the skin and head kidney of goldfish suffering hemorrhagic septicemia were sequeneed, assembled, and characterized.

Pseudomonas aeruginosa Community Acquired Pneumonia with Septicemia in a Previously Healthy Woman

A previously healthy 53-year-old woman was urgently hospitalized due to septic shock. She was diagnosed with bacterial pneumonia based on chest radiograph and computed tomography findings of right upper lobe consolidation. Sputum Gramstain at the time of admission showed gram-negative rods with phagocytosis. Intravenous meropenem was immediately initiated as empiric antibacterial therapy. Bacterial culture specimens from sputum and blood were positive for Pseudomonas aeruginosa. Following appropriate antibiotic therapies, the patient recovered from a shock state and gradually became well. There has been no evidence of recurrence at 6 months after discharge. P. aeruginosa community acquired pneumonia with septicemia is rapidly progressive and often fatal. The choice of initial empiric antibiotic treatment that is active against P. aeruginosa is critical in improving outcome.

Establishment of Pyrosequencing Technology for Detecting Viral Hemorrhagic Septicemia Virus (VHSV)

[Objective] The paper was to establish pyrosequencing methods for detecting viral hemorrhagic septicemia virus （VHSV）. [ Method ] One pair of PCR primers and one pyrosequencing primer of VHSV were designed. The pyrosequencing reaction system and conditions were optimized and the pyrosequencing method for detecting VHSV was established. [ Result] This method was only able to specifically detect the objective viruses in the eight fish viruses, and the method had the advantage of high sensitivity. The minimum detectable limit of nucleic acid was 82 copies/μL. The method was verified by detecting VHSV in 1 924 batches of samples collected from domestic and imported fishes. The detection results were consistent with that of traditional RT-PCR, and the specificity and sensitivity of the method could meet the detection requirement for aquatic animal diseases. [ Conclusion] The study provides a new detection method for monitoring and prevention and control of aquatic animal virus diseases.

<i>Vibrio vulnificus</i>septicemia and necrotizing fasciitis in the patients with liver cirrhosis and diabetes mellitus

Vibrio vulnificus (V. vulnificus) infection is a rare disease in Japan but the leading cause of death related to raw seafood consumption. We hereby reported a successfully treated case of V. vulnificus septicemia, severe necrotizing fasciitis, disseminated intravascular coagulation and multiple organ failure after raw perch consumption with underlying alcoholic liver cirrhosis and diabetes mellitus. It is the first report of a case of V. vulnificusinfection caused by eating raw perch, whereas V. vulnificus infection should be suspected in all of middle-aged to elderly men with underlying immunosuppressive diseases, who have recent consumption of raw seafood or contact with seawater, especially in the summer. The levels of HbA1c and glycoalbumin were not high in the present case, however, obvious hyperglycemia was found even after the infection had completely healed. On reviewing 166 case of V. vulnificus infection in Japan including ours, the complication of diabetes mellitus, one of immunocompromised condition, was found only in 11%, although it had been reported that individuals strongly suspected of having diabetes were 17.2% among the Japanese male population aged from 40 to 74 years. Because diabetes mellitus might be underdiagnosed in the previous reports, intensive examinations are considered to be necessary in order to correctly diagnose diabetes mellitus in patients with severe V. vulnificus infection.

Development of an Indirect Sandwich ELISA for Detection of Duck Swollen Head Septicemia Virus

[Objective] To develop an indirect sandwich ELISA for rapid detection of duck swollen head septicemia virus （DSHSV）. [Method] DSHSV hyperimmune sara were prepared in ducks and rabbits by inoculation with DSHSV XD strain and then purified using saturated ammonium sulfate and Sephadex G-150 column chromatography to obtain anti-DSHSV IgG. An indirect sandwich ELISA was developed using the purified duck anti-DSHSV IgG and rabbit anti-DSHSV IgG after reaction conditions were optimized. Its specificity, sensitivity and repeatability were evaluated, and its accuracy was confirmed by observation with immunoelectron microscopy. Then, distribution of DSHSV in tissues of challenged ducks was also detected. [Result] Through optimizing conditions, the ELISA was developed. Only DSHSV could be detected by the developed method, but other pathogens could not be detected. Compared with agar gel diffusion test, the developed method was more sensitive. The coefficient of variation was less than 10%, and the developed method had good repeatability. In addition, the ELISA-positive samples contained DSHSV, as confirmed by im- munoelectron microscopy. All heart, liver, lung and kidney collected from the DSHSV-challenged ducks were positive when they were detected by the developed ELISA. [ Conclusion] The developed ELISA method is rapid, simple, specific and sensitive, and it is suitable for large-scale quaran- tine of DSHS. Heart, liver, lunq and kidney should be selected preferentially as specimens for diaclnosis of DSHS.

Autosomal recessive 333 base pair interleukin 10 receptor alpha subunit deletion in very early-onset inflammatory bowel disease

BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations.METHODS From May 2016 to September 2020,four young patients with clinically diagnosed VEO-IBD were recruited.Before hospitalization,using targeted gene panel sequencing and trio-whole-exome sequencing(WES),three patients were found to harbor a IL10RA mutation(c.301C>T,p.R101W in one patient;c.537G>A,p.T179T in two patients),but WES results of the fourth patient were not conclusive.We performed whole-genome sequencing(WGS)on patients A and B and reanalyzed the data from patients C and D.Peripheral blood mononuclear cells(PBMCs)from patient D were isolated and stimulated with lipopolysaccharide(LPS),interleukin 10(IL-10),and LPS+IL-10.Serum IL-10 levels in four patients and tumor necrosis factor-α(TNF-α)in the cell supernatant were determined by enzyme-linked immunosorbent assay.Phosphorylation of signal transducer and activator of transcription 3(STAT3)at Tyr705 and Ser727 in PBMCs was determined by western blot analysis.RESULTS The four children in our study consisted of two males and two females.The age at disease onset ranged from 18 d to 9 mo.After hospitalization,a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data.Patient D was homozygous for the 333 bp deletion.All four patients had elevated serum IL-10 levels.In vitro,IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-αproduction induced by LPS.Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS+IL-10 in both healthy subjects and in patient D.CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD,whereas the WES results were inconclusive.

Value of PCT content for adjuvant diagnosis of neonatal septicemia and assessment of its severity

Objective:To evaluate the value of procalcitonin (PCT) content for adjuvant diagnosis of neonatal septicemia and assessment of its severity.Methods: A total of 100 newborns who were diagnosed with septicemia in the First People's Hospital of Xianyang City between January 2017 and January 2018 were selected as the septicemia group of the research, and the newborns who were born in the First People's Hospital of Xianyang City during the same period, with the general data matched with those of septicemia group and without neonatal diseases after born were selected as the control group. Serum was collected to determine the contents of PCT, inflammatory cytokines and immune cytokines, and peripheral blood was collected to determine the expression intensity of inflammatory signaling molecules and immune transcription factors.Results: Serum PCT, TNF-α, HMGB1, ICAM-1, IL-10 and IL-17 contents as well as peripheral blood TLR4, NF-κB, MPO, RORγt and FOXP3 expression intensity of septicemia group were significantly higher than those of control group whereas peripheral blood HLA-DR expression intensity was lower than that of control group;peripheral blood TLR4, NF-κB, MPO, RORγt and FOXP3 expression intensity as well as serum TNF-α, HMGB1, ICAM-1, IL-10 and IL-17 contents of septicemia group of newborns with high PCT were significantly higher than those of newborns with low PCT whereas peripheral blood HLA-DR expression intensity was lower than that of newborns with low PCT.Conclusion: The increase of PCT in serum of newborns with septicemia is related to the change of inflammatory response and immune response, and its content detection is valuable for assessing the severity of the disease.

Value of serum PCT content for evaluating inflammatory factor release and organ function injury in neonatal septicemia

Objective: To explore the value of serum PCT content for evaluating inflammatory factor release and organ function injury in neonatal septicemia. Methods: 48 children who were diagnosed with neonatal septicemia in our hospital between March 2015 and May 2018 were selected as the septicemia group, and 50 healthy neonates delivered in our hospital during the same period were selected as the normal control group. The differences in PCT and inflammatory factor contents in serum as well as liver and kidney function index levels in peripheral blood were compared between the two groups. Pearson test was used to evaluate the correlation of serum PCT content with inflammatory factor release as well as liver and kidney function injury in children with neonatal septicemia. Results: The serum PCT content of septicemia group was significantly higher than that of normal control group;serum hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1) contents were higher than those of normal control group;peripheral blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GGT) and alkaline phosphatase (ALP) levels were higher than those of normal control group;peripheral blood blood urea nitrogen (BUN), serum creatinine (Scr) and serum β2-microglobulin (β2-M) levels were higher than those of normal control group (P<0.05). Correlation analysis showed that serum PCT content in children with neonatal septicemia was directly correlated with the degree of inflammatory response as well as the degree of liver and kidney function injury (P<0.05). Conclusion: The serum PCT content abnormally increases in children with neonatal septicemia, and the specific content is consistent with the disease severity and has certain clinical value for the judgment of children's condition.

Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer

Colorectal cancer(CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, Mut YH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach.

Molecular alterations in gastric cancer with special reference to the early-onset subtype

Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.

Clinical Features and Microvascular Complications Risk Factors of Early-onset Type 2 Diabetes Mellitus

The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus(T2DM).We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital.Subjects were divided into early-onset T2DM group(diagnostic age<40 years)and late-onset T2DM group(diagnostic age>40 years).All subjects underwent a standardized assessment of microvascular complications.Data were compared with independent-samples t test or Chi-square test.Multiple logistic regression was used to determine the risk factors of microvascular complications.Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure(SBP),a longer duration of diabetes and higher levels of body mass index(BM1),uric acid(UA),fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG)and glycosylated hemoglobin(HbAlc)than those with lateonset T2DM(P<0.05).The prevalence of diabetic retinopathy(DR)was significantly higher and that of diabetic peripheral neuropathy(DPN)was significantly lower in early-onset group than in late-onset group(P<0.05).For DN,UA was an independent risk factor in early-onset T2DM.SBP and TG were independent risk factors in late-onset T2DM.For DR,duration of diabetes and SBP were independent risk factors in early-onset T2DM.Duration of diabetes,SBP and HbAlc were independent risk factors in late-onset T2DM.This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders,including glucose metabolism,lipid metabolism and amino acid metabolism.Early-onset T2DM was more likely to be associated with DR.The potential pathogenesis of early and late-onset T2DM might be different.The management of metabolic risk factors especially HbA1c,SBP,TG and UA is advised to be performed in the early stage of diabetes.

Circulating MicroRNAs as Novel Diagnostic Biomarkers for Very Early-onset(≤40 years) Coronary Artery Disease

Objective Very early-onset coronary artery disease （CAD） is a great challenge in cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs （miRNAs） could be used as potential biomarkers for patients with very early-onset CAD. Methods We performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls. Results A total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls （P〈0.05）. The areas under the receiver operating characteristic curve for these miRNAs were 0.824 （95% CI, 0.731-0.917; P〈0.001）, 0.758 （95% CI, 0.651-0.864; P〈0.001）, 0.753 （95% CI, 0.643-0.863; P〈0.001）, and 0.782 （95% CI, 0.680-0.884; P〈0.001）, respectively, in the validation set. Conclusion To our knowledge, this is an advanced study to report about four serum miRNAs （miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p） that could be used as novel biomarkers for the diagnosis of very early-onset CAD.

Serial elongation-derotation-flexion casting for children with early-onset scoliosis

Various early-onset spinal deformities, particularly infantile and juvenile scoliosis(JS), still pose challenges to pediatric orthopedic surgeons. The ideal treatment of these deformities has yet to emerge, as both clinicians and surgeons still face multiple challenges including preservation of thoracic motion, spine and cage, and protection of cardiac and lung growth and function. Elongation-derotation-flexion(EDF) casting is a technique that uses a custom-made thoracolumbar cast based on a three-dimensional correction concept. EDF can control progression of the deformity and- in some cases-coax the initially-curved spine to grow straighter by acting simultaneously in the frontal, sagittal and coronal planes. Here we provide a comprehensive review of how infantile and JS can affect normal spine and thorax and how serial EDF casting can be used to manage these spinal deformities. A fresh review of the literature helps fully understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in patients with early-onset spinal deformities, particularly infantile and juvenile scolisois.

Role of DYT1 gene in early-onset primary torsion dystonia

Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia （DYT1） Due to DYT1 gene mutation, defective wild torsinA and the accumulation of mutant torsinA （GAG-deleted DYT1 gene encoded the mutant torsinA, torsinA＆E） play an important role in DYT1 pathogenesis. Intracellular inclusion bodies are formed, and dopamine transport and release are disturbed by interfering functions of endoplasmic reticulum, nuclear membrane, and cytoskeleton of neural cells, resulting in DYT1 onset. Small interfering RNA could serve as a potential therapy for DYT1. However, the exact function of wild torsinA and the pathological effects of torsinAAE require further studies.