The starting material L-tryptophan reacted with 4-chlorobenzaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the 1-(4-chlorophenyl)-beta-carboline. The intermediate was further reacted with alkyl halogenide by N(9)-alkylation and N2-quaternarization to obtain 12 novel 1-(4-chlorophenyl)-beta-carboline derivatives. The chemical structures of all target compounds were characterized by elemental analyses, MS and 1H NMR spectra. The antitumor activities of the target compounds were evaluated by MTT method. The results demonstrated that N2-quaternarized compounds enhanced the antitumor activity significantly. In particular, compound 15 was found to be the most potent compound with IC50 values lower than 5 micromol x L(-1) against 6 human tumor cells. These results confirmed that the N2-alkyl or aralkyl substituent on the beta-carboline ring played an important role in the modulation of the antitumor activities.

Objective To investigate the anti-tumor effect of interferon-?(IFN-?) gene therapy on colon cancer. Methods BALB/c mice were inoculated subcutaneously with CT26 (murine colon carcinoma cell line) cells to prepare an in vivo tumor model. Eight days after tumor inoculation,the tumor-bearing mice were divided into 3 groups and injected intra-tumorally with one of the following preparations: pcDNA3-IFN-?/Lipofectamine,pcDNA3 /Lipofectamine,and PBS respectively. The expression of IFN-?,the immunity function of mice,the histological changes of the tumor,the tumor volume in tumor-bearing mice were tested after gene therapy. ResultsThe level of IFN-? in the serum and the CTL activity increased significantly( P

Objective:To summarize the clinical experience of transurethral columnar balloon dilation of prostate (TUCBDP) in the treatment of patients with benign prostatic hyperplasia(BPH).Methods:A retrospective analysis of 379 BPH clinical data from the Hubei Provincial Hospital of Traditional Chinese Medicine using TUCBDP was performed between June 2015 and June 2018.Their age was (71.3±14.5)years old. The history of disease ranged from 1 month to 36 years. The prostate volume was(47.4±2.1) ml. Preoperative maximum urinary flow rate was (Q max)(9±4) ml/s, postvoid residual urine(PVR) was (123.1±72.4) ml. Their international prostate symptom score (IPSS) was (21±6) points. The quality of life score (QOL)was (5±1) points. The international index erectile function questionnaire (IIEF-5)in 32 patients, who had sex before surgery, was 15±4. We set the time of catheter structure improvement in June 2016 as the boundary, including the early stage (June 2015 to May 2016, 121 cases) and the recent stage (June 2016 to June 2018, 258 patients). In the early stage, the principle of operation is the inner balloon of the catheter to dilate the membrane urethra, and the outer balloon to dilate the urethra of the prostate and the bladder neck. The main surgical steps include the insertion of a dilatation catheter, localization by touching the skin of the scrotum bottom, the inner and outer balloon are filled with water, the first time of drainage and decompression in the inner and outer balloon, the catheter continuous irrigation, drainage and decompression of the inner and outer balloon again, removing the dilatation catheter, and the ordinary urinary catheter was replaced and continuous irrigation. In the recent stage, the principle of surgery is that the inner balloon only served for positioning and fixation. The outer balloon is used to dilate the membrane urethra, prostate urethra, and bladder neck. The inner and outer balloon are drained and decompressed at one time after surgery. The main surgical steps are that the resectoscope was used to examine the bladder and urethra and to guide the dilatation catheter into the bladder. The apex of the prostate touching was used to conform the location. The inner balloon water filling was used for fix the positioning. The inner and outer balloon are filled with water, decompressed and pulled out for urination test, the gland expansion is observed under the resectoscope, and ordinary urinary catheter is replaced for continuous flushing. We observed the changes in Q max, PVR, IPSS, and QOL at 1, 3, 6, 12, and 24 months after the operation. the complications differences in two-stage patien, including the International Incontinence Advisory Committee Urinary Incontinence Questionnaire (ICI-Q-SF) score; those who had sex before surgery were recorded changes in the IIEF-5 score, was compared. Results:There were no deaths during and after operation in this study. The operation time was (18.5±6.7) min. The number of follow-up cases at 1, 3, 6, 12, and 24 months after operation were 326, 253, 201, 194, and 181, respectively. The Q max at 1, 3, 6, 12, and 24 months after operation were (17±9)ml/s, (15±2)ml/s, (12±4)ml/s, (13±6)ml/s and (13±4)ml/s, respectively. The PVR were (17.4± 11.6) ml, (20.6±9.8)ml, (25.4±13.1)ml, (31.5±11.5)ml, and (29.1±12.4)ml, respectively. The IPSS were(7±5) points, (4±4) points, (4±4) points, (6±5) points, (4±4) points, respectively. The QOL were (2±1) points, (2±1) points, (2±1) points, (2±1) points, and (2±1), respectively. All those results that were significantly different from those before surgery ( P<0.05). There were 32 patients who had sex before the operation. The postoperative IIEF-5 score was (17± 6), which was not significantly different from that before the operation ( P>0.05). Two patients had transient retrograde ejaculation, which relieved spontaneously within the 6 month. 4 cases with pseudourinary incontinence in the recent stage (1.5%) were not statistically different from 6 cases (4.9%) in the early stage ( P>0.05). one case(0.4%) of major bleeding in the recent stage was statistically different from 6 cases (4.9%) in the early stage ( P<0.05). 2 cases (0.7%) of patients with acute urinary retention in the recent stage were significantly different from 15 cases (12.4%) in the early stage ( P<0.05). Conclusions:TUCBDP has a positive overall effect and high safety. The major complications of surgery in the recent stage, except for pseudo-urinary incontinence, are significantly lower than that in the early stage, which may be related to the improvement of the catheter structure and the accumulation of clinical experience.

OBJECTIVE： To establish a method for the determination of harmine derivative DH-330 in rat plasma and to use it for pharmacokinetic behavior evaluation of DH-330 in rats after intragastric administration. METHODS： Using tinidazole as internal standard， after pre-treatment of acetonitrile precipitated protein， UPLC-MS method was adopted to determine the plasma concentration of DH-330. UPLC analysis was performed on Waters ACQUITY BEH C18 column （50 mm×2.1 mm，1.7 μm） with mobile phase consisted of acetonitrile-methanol-0.5％ formic acid aqueous solution（15 ∶ 55 ∶ 30， V/V/V） at flow rate of 0.4 mL/min， while the column temperature was 30 ℃， and sample size was 5 μL. MS analysis was conducted by electrospray ionization source， positive ion scanning， ion source temperature at 124 ℃， DH-330 detection of mass to charge ratio （m/z） of 335.8→334.8， and internal standard m/z of 247.0→81.0. Six Wistar rats were given DH-330 suspension（50 mg/kg） intragastrically. Blood samples were collected from fundus venous plexus capillary before administration （0 h） and 0.25，0.5，1，2，4，6，8，12，24 h after administration. Plasma concentration of DH-330 was determined and plasma concentration-time curves were drawn. Pharmacokinetic parameters were calculated by using Kinetica 5.0 software. RESULTS： The linear ranges of DH-330 were 25.05-2 004 ng/mL（r＝0.999 8），and the limits of quantitation was 25.05 ng/mL. RSDs of intra-day and inter-day were all less than 10％. The accuracy RE was －9.76％ to 4.55％. The extraction recovery was higher than 85％（RSD＜5％）. Stability RE was －2.53％ to 2.29％. They were not affected by matrix effect or residual effect of injection. The pharmacokinetic parameters of DH-330 in rats after intragastric administration included that cmax was （1 162.43±241.72）ng/mL，AUC0-∞ was （3 242.93±652.31）ng·h/mL，t1/2 was （1.93±0.61）h， MRT was （3.23±0.30）h，CL was （16.80±5.30）L/h·kg， Vss was （54.78±19.64）L/kg. CONCLUSIONS： The established method is simple， specific， sensitive， precise and recovery， which can be used for the plasma concentration determination of DH-330 in rats. DH-330 has short half-life， rapid absorption and large apparent distribution volume after intragastric administration in rats， which indicates that it has high lipophilicity and may be mainly distributed in tissues.