天津市合法药物滥用人群特征分析

采用“麻醉药品、精神药物成癮者监测登记表”,对到天津市各医疗单位求诊的药物成瘾者进行监测登记,由有经验的医生根据药物成瘾诊断标准做出技术判断。收回有效调查表163份,结果如下:(1)在调查者中有94人已成瘾,62人有成瘾倾向;(2)致瘾药物的种类主要是弱镇痛药、苯二氮(艹卓)类、麻醉性镇痛药和巴比妥类;(3)在调查者中有157人是通过医生处方得到的药物,占总数的96.32％;(4)在这些用药者中平均用药时间为10年,最长的达35年之久。因此存在着严重的医源性药物滥用即处方药物滥用问题。

Increased fatty acid synthase as a potential therapeutic target in multiple myeloma

Objective： To determine fatty acid synthase （FAS） expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods： FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction （RT-PCR） and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma （MM patients） and peripheral blood mononuclear cells （PBMCs） obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations （5 to 320 μg/ml） for 24 h, and metabolic activity was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assays. Apoptosis was evaluated by dual Annexin V/Pl （propidium iodide） labeling and flow cytometry （FCM） in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results： By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^＋/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^＋/Pl^＋ cells. Conclusion： Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.

Updates on treatment of irritable bowel syndrome

Irritable bowel syndrome （IBS） is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated tD affect 10%-15% of the Western population, and has a large impact on quality of life and （in）direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications （alosetron and tegaserod） because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for anticonvulsant activity

Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

Study on the Synthesis of 3,4,5-Trimethoxytoluene

The 3,4,5 trimethoxytoluene(TMT) was systhesized using p cresol by three steps including bromination, methoxylation, and methylation with an overall yield of 84%. The structure of TMT was identified by NMR, GC/MS and IR.“One pot”method was used in methoxylation and methylation for economical and convenient consideration. The mechanism for the methoxylation of 2,6 dibromo 4 methylphenol was discussed.

Carbon quantum dot preparation and application to detecting active ingredients in traditional Chinese medicine

Carbon quantum dots(CQDs)are fluorescent carbon nanomaterials that have been applied to biology,medicine,and optoelectronics,owing to their significant advantages such as simple synthesis methods,low cost,and widely available sources of raw synthesis materials.This review summarizes CQD preparation methods,which include hydrothermal and microwave-assisted synthesis methods,as well as separation methods such as centrifugation,dialysis,and filtration.Additionally,we review the application of CQDs in the detection of active ingredients,primarily phenolic compounds,in traditional Chinese medicine.We also discuss the quenching mechanism of CQD fluorescence using the active ingredients of traditional Chinese medicine.Limitations such as insufficient test selectivity,weak fluorescence intensity,and an unclear quantitative relationship between preparation methods and properties should be resolved for the efficient use of CQDs to detect active ingredients in Chinese medicine.

Limitations of the use of MTT assay for screening in drug discovery

The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay is a routine cell viability assay for cell proliferation and cytotoxicity, which is widely used in many fields, especially in screening for drug discovery. However, this assay exhibits limitations in the presence of particular compounds and under certain assay conditions, which may yield false screening results. For example, polyphenols that are extracted from natural sources can react with MTT in the absence of living cells and thus interfere with the screening results. We measured the absorbance of 15 polyphenols extracted from green tea and showed that the phenolic hydroxyl groups in the polyphenols are responsible for the reduction of MTT to formazan. When three or more phenolic hydroxyl groups were present on a conjugated polyphenol, a significantly increased MTT reduction was observed. Moreover, the type of medium also had an effect on the absorbance value, in the following order： ct-MEM ＋ 10% FBS〉 a-MEM〉DMEM/F12〉PBS. The absorbance of the MTT assay recorded at 570 nm is more sensitive than that measured at 595 nm. These results will improve the cell-based assay of polyphenols and clarify the limitations of the MTT assay as a method of screening in drug discovery.

Observations on the Efficacy of Electroacupuncture plus TDP Irradiation for Treating Noninfectious Urethral Syndrome

Objective： To investigate the efficacy of electroacupuncture plus TDP irradiation for treating noninfectious urethral syndrome. Method： Sixty patients with noninfectious urethral syndrome were randomly divided into an electroacupuncture plus TDP irradiation treatment group of 40 cases and a medication group of 20 cases as a control. Results： The effective rate was 85% in the treatment group and 35% in the control group. There was a significant difference in curative effect between the treatment and control groups（P〈0.01）. Conclusion： Treatment by electroacupuncture plus TDP irradiation has an exact effect on noninfectious urethral syndrome. Its curative effect was significantly better than that in the medication control group.

Integrated combination delivery of IDO inhibitor and paclitaxel for cancer treatment

In order to realize the combination of chemotherapy and immunotherapy,a reduction-responsive paclitaxel(PTX)prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PEG-SS-PTX/CY-1-4 NPs.PEG-SS-PTX/CY-1-4 NPs were evaluated by cytotoxicity,immunogenic cell death(ICD)induction ability and anti-tumor efficacy.Dynamic light scattering(DLS)results showed that the size of PEG-SS-PTX/CY-1-4 NPs was about 149 nm.In vitro experiments indicated that its cytotoxicity was in a concentration-dependent manner,and it induced the ICD of B16-F10 cells.In vivo studies in melanoma mouse model indicated that PEG-SS-PTX/CY-1-4 NPs significantly inhibited the tumor growth and reduced the expression of IDO in tumor tissues.Moreover,it increased the rate of CD8+T cells in the spleen.In summary,PEG-SS-PTX/CY-1-4 NPs achieved good anti-tumor effects and reduced the dose of chemotherapy drugs,which was a safe and effective combined delivery system.

Effects of Moxibustion Therapy on Preventing and Treating Side Effects from Chemotherapy of Malignant Tumor Patients

Objective： To observe the clinical effects of moxibustion therapy on preventing and treating toxic and side effects of chemotherapy in malignant tumor patients. Methods： A total of 63 cases were randomly divided into three groups. Twenty-three cases in the moxibustion group were treated by moxibustion, and 22 cases in the hydro-acupuncture group were treated by acupoint injection, and 18 cases in the control group were treated by oral administration of Batilol tablets. The changes of the white blood cell count and the content of immunoglobulin before and after the treatments were observed. Results： After treatments, the total leukocyte count and the content of immunoglobulin were all elevated in the moxibustion group and the hydro-acupuncture group, with statistical difference when compared with the control group （P〈0.05, P〈0.01）. In the elevation of the white blood cell count, the hydro-acupuncture group was better than the moxibustion group （P〈0.05）. Conclusion： Moxibustion and hydro-acupuncture can be used to treat and prevent toxic and side effects of chemotherapy. From this aspect, the different needling techniques possess different effects.