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.

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

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.

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

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.

Objective: To investigate the correlation between campus bullying and suicidal tendency symptoms comorbidity with addictive behavior among middle and high school students in Hainan Province, so as to provide a theoretical basis for health education and behavioral intervention in schools. Methods: In July 2023, an anonymous questionnaire survey was conducted among 6 654 middle and high school students in Hainan Province, selected by probability proportional sampling and stratified cluster random sampling method. Campus bullying, suicidal tendency and addictive behavior were determined according to the relevant items in the questionnaire on health related behaviors of Chinese students health status and influencing factors questionnaire, and self designed questionnaire. The co occurrence of campus bullying and suicidal tendency among students was analyzed. The binary Logistic regression method was used to analyze the correlation between the co occurrence of campus bullying and suicidal tendency and the addictive behavior of middle school students. Results: The report rate of campus bullying among middle and high school students in Hainan Province was 28.48%, the suicidal tendency was 15.25%, and the co occurrence of campus bullying and suicidal tendency was 8.00%. The results of Logistic regression analysis showed that middle school students and left behind students were prone to campus bullying and suicide tendency ( OR =1.55, 1.52, P <0.05), while Internet addiction, gambling and current smoking showed significant positive correlation with comorbidity of campus bullying and suicide tendency ( OR =3.14, 2.18, 2.07, P < 0.05 ). Conclusions Middle and high school students with addictive behavior have a higher possibility of comorbidity of campus bullying and suicidal tendency. The comprehensive intervention of addictive behavior can reduce the incidence of co occurrence of campus bullying and suicidal tendency, so as to improve health and wellbeing of middle school students.

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.

Purpose To analyze the correlations between PD-L1 expression and clinicopathological factors and their prognostic values in esophageal squamous cell carcinoma (ESCC) patients.Methods PD-L1 expression in the primary tumors from 253 patients with ESCC was evaluated using tissue microarray and immunohistochemistry (IHC).PD-L1 positivity was defined as positive staining of 1％ and 5％ tumor cells.Survival curves were constructed by using the Kaplan-Meier method.Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.Results Overall,tumoral PD-L1 expression was potentially associated with favorable DFS and OS.When the patients were stratified into stage Ⅰ + Ⅱ (60.9％,154/253) and stage Ⅲ + Ⅳa (39.1％,99/253),the prognostic role was not consistent.In patients with stage Ⅰ + Ⅱ disease,tumoral PD-L1 expression was associated with better DFS and OS upon multivariate analysis (1％ as the cutoff:P =0.046 and 0.021,5％ as the cutoff:P=0.011 and0.004).However,PD-L1 expression was not correlated with prognosis in patients with stage Ⅲ + Ⅳa disease (1％ as the cutoff:P =0.586 and 0.682,5％ as the cutoff:P =0.807 and 0.620).Conclusion The prognostic role of tumoral PDL expression is variable in different stages of ESCC,and tumoral PDL expression is an independent favorable predictor in ESCC patients with Stage Ⅰ-Ⅱ disease,but not in stage Ⅲ-Ⅳa or lymph node metastasis.

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.