Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.
Humans ; Substance-Related Disorders/drug therapy* ; Psychotropic Drugs/therapeutic use* ; Animals

Objective: To investigate the expression of transient receptor polycystic protein 2(TRPP2) in oral squamous epithelial cell and its effect on the invasion and migration of oral squamous cell carcinoma(OSCC), and to explore the potential signaling pathway of TRPP2 affecting OSCC metastasis. Methods: The OSCC model with TRPP2 knockdown was constructed by CRISPR-Cas9 lentivirus plasmid transfection technique. The effect of TRPP2 protein knockdown was verified by Western blot. The effect of TRPP2 on OSCC proliferation was detected by CCK-8 assay and clone formation assay. RT-qPCR was used to detect the target genes associated with TRPP2 metastasis to OSCC. Western blot and RT-qPCR were used to detect the expression of EpCAM and its transcription factors associated with unfolded protein response(UPR). The effects of TRPP2 on the invasion and migration of OSCC were examined by invasion test and scratch test. Results: Compared with HOK in oral epithelial cells, the expression of TRPP2 in OSCC was significantly higher. When TRPP2 was knocked down, OSCC proliferation and clonalformation were significantly enhanced. Compared with the control group, a total of 494 differential genes were significantly expressed in TRPP2 knockdown transcription profile, among which 234 genes were up-regulated and 260 genes were down-regulated. The expression of EpCAM gene, which is related to cell adhesion, was up-regulated. In addition, UPR related genes PERK, ATF6, GRP78 were up-regulated, while ATF6 and EpCAM were down-regulated in OSCC compared to HOK cells. The expression of ATF6 and EpCAM in oral squamous cell carcinoma cells was up-regulated by TRPP2 knockdown, and the cell migration and invasion ability decreased. The ATF6 inhibitor ceapin-A7(5 μmol/L) restored the OSCC migration and invasion ability of TRPP2 knockdown. Conclusion TRPP2 is highly expressed in OSCC. When TRPP2 is knocked down, OSCC proliferation ability is enhanced, migration and invasion ability are inhibited. TRPP2 mediates the expression of EpCAM through activation of UPR, thus affecting the invasion and migration of oral squamous cell carcinoma.

Objective To explore the impact of sex on the efficacy of first-line programmed death-1(PD-1)blockade plus chemotherapy in patients with advanced lung adenocarcinoma and its potential biological mechanisms.Methods The clinical and pathological characteristics and follow-up data of 163 patients with advanced lung adenocarcinoma without driver gene alterations at Shanghai Pulmonary Hospital affiliated to Tongji University from October 2018 to October 2023 were retrospectively collected.Among them,103 patients received first-line PD-1 blockade plus chemotherapy(51 males and 52 females)and 60 patients received first-line standard platinum-based doublet chemotherapy(39 males and 21 females).Patients were divided into male group and female group.Clinical characteristics,efficacy,progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier method was used to plot the survival curves of male and female patients,and log-rank test was used for significance evaluation.Cox proportional hazards model was used to analyze the factors influencing PFS and OS.Multiplex immunofluorescence(mIF)assays were used to analyze the differences of protein expression levels of programmed death-ligand 1(PD-L1),CD8,CD68,CD4,and FOXP3 between male and female groups in baseline tumor sample.Results In patients receiving first-line PD-1 blockade plus chemotherapy,the median PFS in female group and male group was 13.0 months and 6.8 months,respectively(HR=0.39,95% CI 0.25-0.62;P＜0.01).The median OS in female group and male group was 46.2 months and 17.3 months,respectively(HR=0.30,95% CI 0.18-0.50;P＜0.01).In patients receiving first-line chemotherapy,the median PFS in female group and male group was 5.7 months and 5.5 months,respectively(P＞0.05);the median OS in female group and male group was 21.7 months and 17.7 months,respectively(P＞0.05).The results of the Cox proportional hazards model showed that sex was an independent factor influencing PFS and OS in patients receiving first-line PD-1 blockade plus chemotherapy(P＜0.05).The results of mIF showed that pretreatment tumor samples of female patients had a significantly higher expression level of CD8 than male patients(P＜0.05),while the expression level of PD-L1,CD68,CD4 and FOXP3 was similar between female and male groups.Conclusions Compared to male patients,female patients with advanced lung adenocarcinoma benefit more from the first-line PD-1 blockade plus chemotherapy.The increased expression level of CD8 in pretreatment tumor samples of female patients would be the potential mechanism.

Objective To study the effects of improved Wright-Giemsa staining. Methods 40 semen samples by both traditional and improved Wright-Giemsa staining.The morphological characteristics stained by two methods was ob-served. Results The defective rates of the middle and tail parts of sperm were 7.02%± 2.4%and 11.02%± 2.03%respec-tively in improved staining group;while those were 5.48%±2.8%and 8.05%±2.56%in traditional staining group. There was statistical significance between two staining methods (P < 0.05). There was no significant difference of normal sperm and sperm head between these two staining methods;however, improved staining method showed a much clearer nucleus and ac-rosome staining than that of traditional methods. Improved Wright-Giemsa staining is better for sperm, vaginal discharge and Trichomonas vaginalis. More importantly, axostyle and flagella were clearly stained with the improved method. Conclusion Improved Wright-Giemsa staining is simple and can be used in clinical diagnosis.