Aim To investigate the change of miR-124 expression in methamphetamine-induced addiction in PC12 cells and the possible regulatory mechanism that it involves.Methods PC12 cells were randomly divided into 6 groups as follows: control group, methamphetamine group, agomir Negative Control group, miR-124 agomir group, agomir Negative Control+methamphetamine group and miR-124 agomir+methamphetamine group.After the treatment, the total RNA and protein were extracted in PC12 cells.The expression of miR-124 was measured by Real-time PCR and the expression of GluR2 was determined by Western blot in PC12 cells.Results Compared with those in the control group, the expression of miR-124 was remarkably decreased and the expression of GluR2 was significantly increased in the methamphetamine group in PC12 cells.Compared with those in the agomir Negative Control+methamphetamine group, the expression of miR-124 was remarkably increased and the expression of GluR2 was significantly decreased in the miR-124 agomir+methamphetamine group in PC12 cells.Conclusion MiR-124 might involve in methamphetamine-induced addiction in PC12 cells by inhibiting GluR2.

OBJECTIVETo construct an eukaryotic expression plasmid for AY358935 gene and explore its function.

METHODScDNA of the AY358935 gene was amplified by reverse transcription-PCR and cloned into pGEM-Teasy. The pGEM-T-AY was validated by sequencing and served as a template for the construction of eukaryotic expression plasmid. The pcDNA3.1-AY recombinant was validated by double enzyme digestion and used for transient transfection of M14 cells. Expression of the AY358935 protein and proliferation of the M14 cells were determined respectively by Western blotting and 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) colorimetry.

RESULTSThe amplicons of RT-PCR were confirmed to have similar size with the cDNA fragment of the AY358935 gene as well as cloned region of pcDNA3.1-AY. The cloned region of pGEM-T-AY was sequenced to be identical with cDNA sequence of the AY358935 gene. M14 cells were transfected by the AY358935 gene, pcDNA3.1 and liposomes, respectively. After 48 h, expression of the AY358935 protein in M14 cells transfected with the AY358935 gene was significantly higher than other two groups. They also had a significantly higher absorbance value (A=0.74) than other two groups (A=0.39 and 0.46, respectively; P<0.05).

CONCLUSIONAn eukaryotic expression plasmid of the AY358935 gene was successfully constructed. Product of the AY358935 gene may promote the proliferation of M14 cells.

Objective To mine adverse drug event(ADE)signals of doxycycline using the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide scientific evidence for clinical medication safety.Methods The data from the FAERS database between the first quarter of 2004 and the first quarter of 2024 were extracted.After data cleaning and standardization,ADE reports with doxycycline as the main suspected drug were screened.The system organ class(SOC)of ADE was performed using MedDRA,and the reporting odds ratio method and Medicines and Healthcare products Regulatory Agency method were used to mine ADE signals.The information component method was also used to evaluate signal strength.Results A total of 43 126 ADE reports with doxycycline as the primary suspected drug were collected,involving 14 642 patients,with a higher proportion of female patients(57.32％).There were 555 related ADE signals involving 26 SOC,with the top 5 SOC being gastrointestinal disorders,skin and subcutaneous tissue disorders,injuries,poisonings,and procedural complications,psychiatric disorders,and infections and infestations.The top 5 ADE signals with the highest signal intensity were Hatch reaction,sclerosing cholangitis,esophageal ulcer,gastrointestinal mucosal necrosis,and gastrointestinal injury.Among the ADE signals with the strongest signal strength not listed in the package insert,the top five were sclerosing cholangitis,nephrogenic diabetes insipidus,minimal change glomerular nephritis,diabetes insipidus and Sixth cranial nerve paralysis.Conclusion In clinical practice,particular attention should be paid to the frequent ADEs caused by doxycycline,as well as those not yet documented in the package insert,which involve multiple SOC such as renal and urinary disorders,hepatobiliary diseases,blood and lymphatic system disorders,and endocrine disorders.Therefore,clinical pharmacists should play a key role in assisting clinicians to develop and implement prevention plans for ADEs,thereby improving the safety of doxycycline in clinical use.

Objective:To compare the knowledge of endoscopic screening of gastrointestinal cancers between digestive healthcare workers and new chatbots (chatGPT and new Bing).Methods:A test with twenty-three questions of endoscopic screening of gastrointestinal cancers was conducted, focusing on the appropriate age of screening, high-risk factors, the follow-up time, and the advantages and risks of digestive endoscopy. Digestive healthcare workers were invited to complete the test through electronic questionnaires. New Bing and chatGPT were used to answer each question for 10 rounds. The primary endpoint was the correct rate of all answers. The answer accuracy between digestive healthcare workers and new chatbots were compared using variance analysis, and the factors that affected the accuracy of the answers in digestive healthcare workers were explored using univariate and multivariable liner regression analysis.Results:The results of the test completed by 76 digestive healthcare workers (21 residents, 28 digestive nurses, and 27 digestive doctors) were analyzed. The accuracies were 36.4%±10.9%, 34.5%±10.2%, 52.2%± 12.6%, 46.3%±9.8% and 67.1%±9.3% in residents, digestive nurses, digestive doctors, chatGPT, and new Bing, respectively, with significant difference ( F=22.6, P<0.001). The accuracy was highest in new Bing ( P<0.001). The accuracy was comparable between chatGPT and digestive doctors (LSD- t=-1.398, P=0.166), and both higher than that of digestive nurses (LSD- t=2.956, P=0.004; LSD- t=5.955, P<0.001) and residents (LSD- t=2.402, P=0.018; LSD- t=4.951, P<0.001). Furthermore, the accuracy was comparable between digestive nurses and residents (LSD- t=-0.574, P=0.567). Compared with new Bing, digestive doctors had lower accuracy in answering questions related to adverse events of screening, follow-up recommendation of intestinal metaplasia, high risk factors and screening methods for colon cancer ( P<0.05), but higher accuracy in answering questions related to endoscopic adverse events and screening methods for esophageal cancer ( P<0.05). Multivariable liner regression analysis showed that being digestive doctors ( β=11.7, t=3.054, P=0.003) and questionnaire response time (≥7.6 min) ( β=7.8, t=2.894, P=0.005) were independent factors for the answer accuracy of digestive healthcare workers. Conclusion:Compared with digestive healthcare workers, New chatbots—new Bing has higher accuracy in answering gastrointestinal cancer screening-related questions, but performs poorly in answering questions such as adverse events of endoscopy and screening methods for esophageal cancer.