OBJECTIVE To analysis the clinical and pathological characteristics of lymph nodes metastasis in pediatric patients with differentied thyroid carcinoma(pDTC),and to develop a nomogram for predicting lymph nodes metastasis in patients with pDTC.METHODS Four cohorts were integrated in this study,including internal training cohort(1419 cases)and validation cohort(609 cases)from the Surveillance,Epidemiology,and End Results(SEER)database of the National Cancer Institute,TCGA-pDTC cohort(20 cases from the Cancer Genome Atlas Program)and YHD-pDTC cohort(39 cases from true world).The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to screen factors related to lymph nodes metastasis in the presence and exclusion of T stage in pDTCs based on internal training cohort and construct nomograms.Calibration curve,receiver operating characteristic(ROC)curve,area under the ROC curve(AUC)and decision curve analysis(DCA)were used to evaluate model performance in the other three cohorts.RESULTS Multivariate logistic regression results showed that pathology[OR(95%CI):0.020(0.010-0.060),P<0.001],M stage[OR(95%CI):29.550(3.190-273.490),P=0.003],and T stage[OR(95%CI):2.210(1.820-2.680),P<0.001]were independent factors affecting lymph nodes metastasis in pDTCs.Through the internal training set,internal validation set,YHD-pDTC cohort and TCGA-pDTC cohort,the AUC values were 0.734(0.709,0.758),0.752(0.716,0.788),0.969(0.920,1),and 0.600(0.342,0.858)in that order,and the calibration curves are close to the perfect reference line.T stage is a better predictor of lymph nodes metastasis than extraperitoneal intrusion and tumor size.CONCLUSION Pathology,M stage,and T stage are risk factors for predicting lymph nodes metastasis in pDTCs.The nomogram established on this basis can make individualized predictions of the probability of lymph nodes metastasis in pDTCs.

Drug addiction is a serious public health problem worldwide,for which there are currently no established therapeutic medications.Since the legalization of cannabis and the approval of cannabidiol(CBD)by the US Food and Drug Administration,its therapeutic potential for the treatment of substance abuse has been widely explored.Numerous studies have shown that CBD can reduce drug reward in animal models of addiction such as self-administration,conditioned positional preference,and intracranial self-stimulation.CBD can also reduce withdrawal symptoms from substances such as amphetamines,opioids,cocaine,marijuana,alcohol,and nicotine.The mechanisms by which CBD modulates drug addiction,however,are complex and understudied.Here we review studies of CBD related to addictive drugs to clarify the regulatory mechanisms of CBD in drug addiction and provide references for related studies on substance abuse.

Drug addiction is a serious public health problem worldwide,for which there are currently no established therapeutic medications.Since the legalization of cannabis and the approval of cannabidiol(CBD)by the US Food and Drug Administration,its therapeutic potential for the treatment of substance abuse has been widely explored.Numerous studies have shown that CBD can reduce drug reward in animal models of addiction such as self-administration,conditioned positional preference,and intracranial self-stimulation.CBD can also reduce withdrawal symptoms from substances such as amphetamines,opioids,cocaine,marijuana,alcohol,and nicotine.The mechanisms by which CBD modulates drug addiction,however,are complex and understudied.Here we review studies of CBD related to addictive drugs to clarify the regulatory mechanisms of CBD in drug addiction and provide references for related studies on substance abuse.

Methamphetamine (METH) is a highly addictive synthetic psychoactive drug that is often abused as a psychostimulant.Chronic exposure to METH induces neurotoxic effects through oxidative stress,impairment of mitochondrial function,activation of astrocytes and microglia,and amino acid excitability.METH abuse increases the chance of developing neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,Huntington's disease.However,the mechanism behind METH-induced neurotoxicity remains incompletely understood.So far,there is no specific treatment for METH-induced neurotoxicity.This paper reviews some of the potential mechanisms of METH-induced neurotoxicity in recent years,such as neuroinflammation,glutamatergic excitotoxicity,oxidative stress,and mitochondrial toxicity,and discusses the current therapeutic strategies related to mitigating the neurotoxic effects of METH in the brain through different pathways.

Methamphetamine (METH) is a highly addictive synthetic psychoactive drug that is often abused as a psychostimulant.Chronic exposure to METH induces neurotoxic effects through oxidative stress,impairment of mitochondrial function,activation of astrocytes and microglia,and amino acid excitability.METH abuse increases the chance of developing neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,Huntington's disease.However,the mechanism behind METH-induced neurotoxicity remains incompletely understood.So far,there is no specific treatment for METH-induced neurotoxicity.This paper reviews some of the potential mechanisms of METH-induced neurotoxicity in recent years,such as neuroinflammation,glutamatergic excitotoxicity,oxidative stress,and mitochondrial toxicity,and discusses the current therapeutic strategies related to mitigating the neurotoxic effects of METH in the brain through different pathways.

AIM:To investigate the effect of melatonin(MEL)on the depression behavior in mice induced by chronic restraint stress(CRS).METHODS:Forty-eight SPF-grade male C57BL/6J mice were randomly divided into con-trol group(n=12)and CRS group(n=36).The mice in CRS group were further divided into 3 groups(n=12):CRS+vehi-cle group,CRS+fluoxetine(FLX)group,and CRS+MEL group.Mouse depression model was established by the CRS method for 14 d,and then the depression-like behaviors were observed for modeling validation.After 14 d of drug interven-tion combined with CRS,the behaviors were detected again.Nissl staining,RT-qPCR,Western blot and immunofluores-cence staining were performed in mouse brain tissues.RESULTS:Compared with control group,the weight changes of the mice in CRS group were significantly lowered,the immobility time of forced swimming and tail suspension tests was sig-nificantly increased,the consumption rate of sugar water decreased significantly,and the central time and movement dis-tance in open-field test decreased significantly(P＜0.01).Compared with CRS+vehicle group,the depression-like behaviors induced by CRS were successfully reversed by the drugs in both CRS+FLX and CRS+MEL groups.Furthermore,com-pared with CRS+vehicle group,the mRNA levels of brain-derived neurotrophic factor(BDNF),extracellular signal-regulated kinase(ERK)and cAMP response element-binding protein(CREB),and the protein levels of BDNF,phosphorylated ERK1/2 and CREB were increased significantly in both CRS+FLX and CRS+MEL groups(P＜0.01).The results of Nissl staining showed that the neurons in CRS+vehicle group were irregularly arranged,and the number of Nissl bodies was de-creased(P＜0.01).The neuron status and number of Nissl bodies in both CRS+FLX and CRS+MEL groups were signifi-cantly improved(P＜0.01).Immunofluorescence staining showed that the number of c-Fos-positive cells in the frontal cor-tex and hippocampal CA1 region of the mice in CRS+vehicle group was significantly larger than that in control group(P＜0.01).Conversely,the number of c-Fos-positive cells in CRS+FLX and CRS+MEL groups was significantly smaller than that in CRS+vehicle group(P＜0.01).CONCLUSION:Melatonin can significantly alleviate depression-like behavior in-duced by CRS in mice,which may be related to the activation of BDNF-ERK-CREB signaling pathway.

Background and purpose:Epidermal growth factor receptor (EGFR) gene mutation is the most important predictive factor for determining the effectiveness of EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC). This study aimed to determine the clinical application value of mutation-speciifc immu-nohistochemistry forEGFR mutation detection in NSCLC.Methods:Mutation-specific immunohistochemistry and ampliifcation refractory mutation system (ARMS) were used simultaneously to detectEGFR gene mutation status in 290 lung cancer specimens. The sensitivity, speciifcity, positive predictive value (PPV) and negative predictive value (NPV) of mutation-speciifc immunohistochemistry for detectingEGFR gene mutations were evaluated. The consistency was analyzed between mutation-speciifc immunohistochemistry results and ARMS results.Results:With ARMS testing as the gold standard, when a cutoff value of score 1+ was used as positive by immunohistochemistry, the sensitivity of mutation-speciifc immunohistochemistry forEGFR gene mutation was 72.92%, speciifcity 95.20%, positive predictive value 93.75% and negative predictive value 78.08%. The accuracy of immunohistochemistry was obviously different when variousEGFR gene mutations were detected. The sensitivity of immunohistochemistry for exon 19 deletion was only 55.55%, but speciifcity was above 99%. When immunohistochemistry score was 1+, the sensitivity for L858R mu-tation was 90.27%, whereas speciifcity was 95.86%. When immunohistochemistry score was 2+ or 3+, the speciifcity for L858R mutation was 98.63%-100%. The results of mutation-speciifc immunohistochemistry were ifnely correlated with mutation status determined by ARMS assay (P<0.001, Kappa value: 0.612-0.864). Mutation-speciifc immunohis-tochemistry can directly determineEGFR gene mutation abundance at the cellular level.Conclusion:Mutation-speciifc immunohistochemistry could be an effective supplemental method toEGFR molecular tests.

Objective To investigate influencing factors of disability after craniocerbral injury caused by road traffic accident.Methods We collected 486 cases with craniocerebral injury caused by traffic accident,and conducted analysis.Factors related to disability were found by univariate analysis,and multivariate logistic regression analysis was conducted to filter the most important factors.Results Degrees of brain injury,drunk driving,age and types of accident were the major influencing factors.Drunk driving and age were positively related with disability grade while the degree of brain injury and type of accident were negatively related.Concuusiorn It is helpful to reduce disability and the burden on society by taking intervening measures on the related factors of disability after brain injury in road traffic accident.

Adenocarcinoma ; pathology ; Animals ; Carcinoma, Squamous Cell ; chemically induced ; pathology ; Cell Line, Tumor ; Dimethylnitrosamine ; analogs & derivatives ; Disease Models, Animal ; Esophageal Neoplasms ; chemically induced ; pathology ; Humans ; Neoplasm Transplantation

Objective To investigate the prevalence of BRCA1/2 mutations in breast cancer patients of Han ethnic group in southcrn China,and to provide the genetic basis for early diagnosis and treatment of breast cancer.Methods 70 samples of breast cancer patients of Han ethnic group in southern China and 70 normal control samples were tested.The whole coding exons of BRCA1 and BRCA2 genes were analyzed using hybridization based enrichment and next-generation sequencing (NGS).According to the results of NGS,we detected pathogenic mutations of BRCA genes.Results In 70 breast cancer patients,a total of 5 deleterious mutations were identified,4 of these were novel mutations,and no pathogenic variation was found in normal control group.Furthermore,we detected 3 low frequency mutations which are likely to relate to cancer susceptibility.Conclusions 4 novel deleterious mutations were reported,as well as some variants of unknown clinical significance for the prevalence of BRCA1/2 mutations of 70 breast cancer patients of Han ethnic group in southern China.