Combining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide. The preliminary structure-activity relationship (SAR) has been explored.
Adenosine Diphosphate ; Drug Design ; Phthalic Acids ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Sulfonamides ; chemical synthesis ; chemistry

Background The rapid diagnosis can win more treating opportunities for patients with fungal keratitis.Even though the fungal culture is the gold standard for the diagnosis of fungal keratitis,it is difficult in early diagnosis due to the long duration of cultivation and false-negative rate.Objective This trial was to explore the clinical value in the rapid diagnosis of fungal keratitis by the combination of corneal scraping with laser scanning confocal microscopy.Methods Corneal scraping and laser scanning confocal microscopy were separately performed in 167 eyes of 167 patients with fungal keratitis.All the eyes were examined by the slit lamp,followed by laser scanning confocal microscope,and then the 10％ KOH corneal smear was examined under the optical microscope.Results The positive rate of diagnosis was 75％ (125/167) by corneal scraping,and that by laser scanning confocal microscopy was 91％ (152/167).The positive rate of examining outcome was significantly higher in laser scanning confocal microscopy than that of corneal scraping (x2 =14.88,P =0.00).The positive results were 114 cases and negative results were 4 cases by two methods,with the concordance rate 70.7％ (118/167).The hyphae or spore were seen in 32 cases by laser scanning confocal microscopy in 42 negative cases by corneal scraping,and in 15 negative cases by confocal laser scanning microscopy,11 positive outcomes were offered by corneal scraping.Conclusions The combined application of corneal scraping with confocal laser scanning microscopy can improve and speed up the diagnosis positive rate of fungal keratitis.

OBJECTIVETo assess the clinical effect and safety of the Chinese medicine Longbishu Capsule combined with mesylate doxazosin in the treatment of benign prostatic hyperplasia (BPH) of the kidney deficiency and blood stagnation type.

METHODSThis was a randomized, double-blind, double-simulation control study. We equally assigned 60 men diagnosed with BPH of the kidney deficiency and blood stagnation type to an experimental and a control group, the former treated with mesylate doxazosin plus Longbishu Capsule and the latter with mesylate doxazosin plus placebo. We compared the International Prostate Symptom Score (IPSS), quality of life (QOL), Chinese symptom score (CSS), maximal urinary flow rate (Qmax), and prostate volume between the two groups of patients before and after 6 months of medication.

RESULTSAfter treatment, there were 5 cured cases, 13 markedly effective cases, 9 effective cases, 1 ineffective case, and 2 eliminated cases in the experimental group, as compared with 2 cured cases, 8 markedly effective cases, 10 effective cases, 7 ineffective cases, and 3 eliminated cases in the control group. The total effectiveness rate was obviously higher in the former (96.4%) than in the latter (74.1%). IPSS, Qmax, and CSS were improved in both of the groups after medication, even more significantly in the experimental than in the control group (IPSS: 15.22 ± 2.98 vs 18.15 ± 5.88, P <0.05; Qmax: [13.56 ± 2.26] ml/s vs [11.78 ± 2.97] ml/s, P <0.05; CSS: 6.18 ± 2.13 vs 9.52 ± 3.15, P <0.05). Because of the difference in the QOL score between the two groups at the baseline (P = 0.038 <0.05), no more comparison was made in this aspect after treatment.

CONCLUSIONThe combination of Longbishu Capsule with mesylate doxazosin is safe and effective for the treatment of BPH.

Adrenergic alpha-Antagonists ; therapeutic use ; Capsules ; Double-Blind Method ; Doxazosin ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Prostatic Hyperplasia ; drug therapy ; physiopathology ; Quality of Life ; Treatment Outcome ; Urination

OBJECTIVETo investigate the correlation of International Prostate Symptom Score (IPSS) with the levels of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the prostate tissue and expressed prostatic secretion (EPS) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis.

METHODSWe divided 80 BPH patients to be treated by transurethral resection of the prostate (TURP) into a simple BPH group (n = 30) and a BPH with prostatitis group (n = 50) based on the pathologic features. We statistically analyzed IPSS and the levels of IL-8 and COX-2 in EPS before surgery and the IL-8 and COX-2 levels in the prostate tissue after surgery.

RESULTSIPSS was positively correlated with the IL-8 and COX-2 levels in the prostate tissue and EPS of the BPH patients, moderately in the simple hyperplasia group (r > 0.5) and highly in the other (r > 0.8). The levels of IL-8 and COX-2 in the prostate tissue and EPS were significantly higher in the BPH with prostatitis group than in the simple BPH group (P < 0.05).

CONCLUSIONThe levels of IL-8 and COX-2 in EPS indirectly reflect those in the prostate tissue. IPSS and the levels of IL-8 and COX-2 in EPS can help determine whether BPH is complicated by histological prostatic inflammation.

Aged ; Aged, 80 and over ; Cyclooxygenase 2 ; metabolism ; Humans ; Interleukin-8 ; metabolism ; Male ; Middle Aged ; Prostate ; metabolism ; Prostatic Hyperplasia ; complications ; diagnosis ; metabolism ; Prostatitis ; complications ; diagnosis ; metabolism

OBJECTIVETo observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.

METHODSModels of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.

RESULTSCompared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).

CONCLUSIONBy upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fas Ligand Protein ; drug effects ; metabolism ; Germ Cells ; Glycosides ; Infertility, Male ; chemically induced ; drug therapy ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; drug effects ; Semen Analysis ; Signal Transduction ; Sperm Count ; Sperm Motility ; drug effects ; Tablets ; Testis ; drug effects ; metabolism ; Tripterygium

ObjectiveTo investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS).

METHODSA total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-β1 in the semen measured by ELISA.

RESULTSThe AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue (［9.20 ± 3.07］ vs ［42.20 ± 9.17］ %, P<0.01), but decreased level of TGF-β1 in the semen (［627.67 ± 26.07］ vs ［566.73 ± 68.44］ ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis (［42.20 ± 9.17］ vs ［21.60 ± 5.94］ %, P<0.01; ［42.20 ± 9.17］ vs ［33.95 ± 6.39］ %, P<0.05). The concentration of TGF-β1 in the semen was markedly lower in the high-dose QJT than in the AS model control group (［621.78 ± 30.80］ vs ［566.73 ± 68.44］ ng/ml, P < 0.05).

CONCLUSIONSQiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.

Animals ; Apoptosis ; Asthenozoospermia ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinases ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; Semen Analysis ; Signal Transduction ; Spermatozoa ; Testis ; metabolism ; ultrastructure ; Transforming Growth Factor beta1 ; metabolism ; Vimentin ; metabolism

To establish a genetic susceptibility assessment model of lung cancer risk potentially associated with polycyclic aromatic hydrocarbon (PAH) inhalation exposure among non-smokers in China, a total of 143 patients with lung adenocarcinoma and 143 cancer-free individuals were recruited. Sixty-eight genetic polymorphisms in 10 pathways related to PAH metabolism and tumorigenesis were selected and examined. It was observed that 3 genetic polymorphisms, along with 10 additional genetic polymorphisms via gene-gene interactions, significantly influenced lung cancer risk potentially associated with PAH inhalation exposure. Most polymorphisms were associated with PAH metabolism. According to the established genetic susceptibility score (GSS), lung cancer risk increased with a rise in the GSS level, thereby indicating a positive dose-response relationship.
Adenocarcinoma ; chemically induced ; epidemiology ; genetics ; Air Pollutants ; toxicity ; China ; Genetic Predisposition to Disease ; Humans ; Inhalation Exposure ; Lung Neoplasms ; chemically induced ; epidemiology ; genetics ; Polycyclic Aromatic Hydrocarbons ; toxicity