Objective: To synthesize novel tetrahydroisoquinolines with both anti-fungal and contraceptive activities, so as to provide precursor structures for contraceptives with anit-fungal activities. Methods: 3,4-dimethoxyphenylethylamine was taken as the template and the title compounds were synthesized through Pictet-Spengler reaction, neutralization reaction, substitution, hydrolysis, and acylation. The anti-fungal activity and sperm-killing activity of the target compounds were tested in vitro. Results: Fourteen title compounds were obtained and they were: 2-octyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrochloride(1), 2-nonyl-6, 7-dimethyl-1,2, 3,4-tetrahydro-isoquinoline hydrochloride(2), 2-decyl-6, 7-dimethy-1, 2, 3, 4-tetrahydro-isoquinoline hydrochloride(3), 2-dodecyl-6, 7-dimethyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride(4), 2-dodecyl 6, 7-diacetoxy-1, 2,3,4-tetrahydro-isoquinoline hydrochloride(5), 2-pentyl-6,7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide(6), 2-hexyl-6, 7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide(7), 2-heptyl-6, 7-diacetoxy-1,2,3,4-tetrahydro isoquinoline hydrobromide (8), 2-octyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(9), 2-nonyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(10), 2-decyl-6, 7-dimethy-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(11), 2-dodecyl-6, 7-dihydroxyl 1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(12), 2-tetradecyl-6, 7-dihydroxyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(13), and 2-cetyl-6, 7-dihydroxyl-1,2,3,4-tetrahydro-isoquinoline hydrobromide(14). Compounds 5-14 were firstly reported. It was found that all the 14 compounds had anti-fungal activity and 6 compounds also showed sperm-killing activities, with compounds 11, 12 having the strongest activities. Conclusion: A group of novel compounds with both anti-fungal and contraceptive activities have been synthesized, which provide a precursor structure for developing new contraceptives with anti-fungal activities.

OBJECTIVETo investigate the changes in the quantity of colonizing Streptococcus mutans(S. mutans) and Actinomyces on the root surface plaque before and after post-core crown restoration of the mandibular first molars in the elderly patients.

METHODSA total of 30 elderly patients, each with one post-core crown restoration of the mandibular first molar, were randomly chosen to participate in the studies. Patients with mandibular first molars with post-core crown restoration and those with healthy contralateral mandibular first molars were divided into the test and control groups, respectively. Root surface plaques of the two groups were collected before tooth preparation, 72 h after preparation, one week after preparation, and one month after restoration. S. mutans, Actinomyces naeslundii (A. naeslundii) and Actinomyces viscosus (A. viscosus), were identified using colony morphology, biochemical techniques, and polymerase chain reaction (PCR). Plaque count was measured using microbial colony count.

RESULTSThe number of S. mutans and A. viscosus and A. naeslundii in the test group, which was statistically significant (P<0.05), increased 72 h after preparation. The quantities of S. mutans, A. viscosus, and A. naeslundii one week after preparation were significantly different (P<0.05). The plaque count of S. mutans, A. viscosus, and A. naeslundii in the test group decreased one month after restoration (P<0.05).

CONCLUSIONThe quantities of S. mutans, A. viscosus and A. naeslundii increase one week after preparation but decrease one month after restoration. The finding suggests that dentists should educate patients about plaque control during the early period after tooth preparation.

Actinomyces ; Actinomyces viscosus ; Aged ; Bacteria ; Crowns ; Dental Plaque ; Humans ; Post and Core Technique ; Streptococcus mutans ; Tooth Root

OBJECTIVETo investigate the histological changes of cervical cancer after neoadjuvant chemotherapy (NACT) and to establish histological criteria for interpretation of chemotherapeutical effects.

METHODSFifty-six patients with FIGO stage Ib2-IIa cervical cancers treated by NACT and subsequent radical surgery were retrospectively analyzed, in which the pre- and post-chemotherapeutic histopathological changes were assessed.

RESULTSThe post-chemotherapeutic histopathological changes of 56 cases included grade 3 effects in 11 cases (19.6%), grade 2 in 24 cases (42.9%), grade 1 in 13 cases (23.2%) and no response in only 8 cases (14.3%). The histologic response rate was 62.5% (35/56) and the overall clinical response rate was 67.9% (38/56). The overall coincidence by both criteria was 78.6% (44/56). Four cases (7.1%, 4/56) had only histological response and 8 cases (14.3%, 8/56) had response by imaging. In comparison with the pre-chemotherapy specimens, the chemotherapy-associated histological changes included shrinkage and scattering of tumor nests,decrease of tumor cellularity,tumor cell degeneration and necrosis.

CONCLUSIONSThe histological changes in locally advanced cervical cancers induced by NACT are significant, which may challenge the diagnosis in the final specimens. There are some discreqancies between the histological criteria and imaging/gynecological ones for the therapeutic evaluation of cervical cancers,and it is thus recommended to use the pathological criteria for clinic practice.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; analogs & derivatives ; Carcinoma, Adenosquamous ; drug therapy ; pathology ; surgery ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Female ; Humans ; Hysterectomy ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Preoperative Period ; Prognosis ; Retrospective Studies ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; surgery ; Vincristine ; administration & dosage ; Young Adult

AIMTo study the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane hydrochloride(DDPH) on brain ischemia injury in rats.

METHODSBy using the middle cerebral artery occlusion (MCAO) induced by nylon surgical thread inserted through the internal carotid artery into the anterior cerebral artery in rats, the effects of DDPH on neuron defects(ND) and infarct size(IS) were investigated. Using incomplete cerebral ischemia in rats, the effects of DDPH on superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in brain tissue and pathological changes in rats were studied.

RESULTSDDPH at the dose of 10 mg.kg-1 i.p. 30 min before ischemia decreased the ND 3 h after ischemia. The IS declined 24 h after ischemia as well. Meanwhile, DDPH was found to increase SOD activity and reduce the MDA content, as well as mitigate pathological damage, of neuron after brain ischemia in rats.

CONCLUSIONDDPH showed protective effects on brain ischemia, probably related to its properties of calcium antagonistic effect and increasing the activity of superoxide dismutases.

Animals ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; Female ; Infarction, Middle Cerebral Artery ; pathology ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; pharmacology ; Phenethylamines ; pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; pathology ; Superoxide Dismutase ; metabolism

ObjectiveTo evaluate the safety and efficacy of 30 mg pioglitazone hydrochloride combined with sulphonyurea in the treatment of type 2 diabetic patients.MethodsA randomized, double blind, placebo-controlled, parallel group, multicenter study was performed.A total of 236 patients, who had fasting plasma glucose(FPG) 7.5-13.0 mmol/L and glycosylated hemoglobin A1c(HbA1 c) 7.0％ -12.0％,treated with stable dosage of a sulphonyurea for at least 30 days previously, were randomized to receive placebo or pioglitazone 30 mg once daily for 16 weeks.The sulphonyurea and dosage remained unchanged.ResultsThe patients who had been treated with pioglitazone 30 mg showed significant decrease than that in the placebo group on the average from baseline in FPG [(1.48 ±2.08) mmol/L vs (-0.17 ± 1.92)mmol/L, P＜0.05], and in HbAlc [(0.92 ±0.10)％ vs (0.28 ±0.11)％, P＜0.05].Since fasting plasma insulin (Flns) levels decreased (0.24 ±0.04) mU/L and (0.09 ±0.04) mU/L in the two groups.The homeostatic model assessment insulin resistant (HOMA-IR) decreased 1.42 ± 2.90 and 0.46 ± 3.53 in two groups.The triglyceride level was decreased 0.36 mmol/L and 0.14 mmol/L, and the HDL-C level increased 0.17 mmol/L and 0.05 mmol/L in two groups.There were significant differences in two groups (all P ＜ 0.05).ConclusionsThe 16-week clinical study demonstrated that pioglitazone hydrochloride with a dosage of 30mg daily, could significantly improve the blood glucose control and enhance the insulin sensitivity, lower triglyceride and raise HDL-C level as an additional therapy to a stable-dose sulphonyurea in Chinese type 2 diabetic patients previously poorly controlled by single sulphonyurea therapy, and furthermore had good safety and compliance.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVETo study the prevalence of hepatitis B virus (HBV) genotype in 5 cities of Fujian province and the clinical implications of distinct genotypes in HBV-related liver diseases.

METHODSHBV genotype was determined by the restriction fragment length polymorphism analysis in patients with chronic HBV infection in 5 cities of Fujian province. The relationship between HBV genotype and its clinical implications was studied by multinomal logistic regression and correspondence analysis.

RESULTSOf the 431 HBV DNA positive patients detected by PCR, 275 (63.8%) belonged to HBV genotype B, 100 (23.2%) to genotype C, 51 (11.8%) to genotype D and D-mixed genotype. Genotype A, E and F were not found. Multinomal logistic regression showed that genotype B was more prevalent in Quanzhou and Sanming cities than in Fuzhou (P = 0.002, P = 0.006), and genotype B appeared significantly more common in asymptomatic carriers (ASC), chronic hepatitis B (CHB) and severe hepatitis (SH). Genotype C was most prevalent in patients with liver cirrhosis (LC) (47.0%) than in those with ASC (14.5%) and SH (14.7%) (P = 0.009, P < 0.001). The positive rate of hepatitis B e antigen was higher in patients with genotype C than in those with genotype B and genotype D (56.0% vs. 52.4%, P = 0.008, and 56.0% vs. 30.8%, P = 0.051, respectively). By correspondence analysis, genotype D and D-mixed genotype seemed to be correlated with hepatocellular carcinoma (HCC).

CONCLUSIONS(1) The major popular genotypes of HBV were B, C and D in Fujian. (2) Data of our study suggested that the geographic distribution of genotype B and C might be different in some cities of Fujian. (3) Genotype B might have a tendency to lead to SH in younger patients with chronic hepatitis B and the development of LC might be associated with genotype C among the elder patients. (4) Genotype D appeared to associate with development of HCC, which called for further study to confirm.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Female ; Gene Frequency ; Genotype ; Hepatitis B ; virology ; Hepatitis B virus ; genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length

OBJECTIVETo investigate the effects of Cox7a2 on the LH-induced testosterone production and the involved autophagy regulating signals in TM3 mouse Leydig cells.

METHODSThe Cox7a2-pEYFP-N1 fluorescent protein vector was constructed and transfected into TM3 mouse Leydig cells. The level of testosterone was determined by ELISA, and the effects of Cox7a2 on the expression of the steroidogenic acute regulatory protein (StAR) and the phosphorylation of the autophagy regulatory factor P70S6K were detected by Western blot.

RESULTSLH stimulation increased the StAR protein expression and testosterone production, while Cox7a2 decreased P70S6K phosphorylation, reduced StAR expression and consequently inhibited LH-induced testosterone biosynthesis in the TM3 Leydig cells.

CONCLUSIONCox7a2 inhibits testosterone production by decreasing the StAR protein expression, which might be at least in part related with the activation of autophagy in TM3 mouse Leydig cells.

Animals ; Autophagy ; Cells, Cultured ; Electron Transport Complex IV ; genetics ; Leydig Cells ; metabolism ; Luteinizing Hormone ; pharmacology ; Male ; Mice ; Phosphoproteins ; metabolism ; Phosphorylation ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Testosterone ; biosynthesis

AIMA series of triazole antifungals were synthesized to search for novel triazole antifungals with more potent activity, less toxicity and broader spectrum.

METHODSNineteen 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols were designed and synthesized, on basis of the three dimensional structure of P450 cytochrome 14 alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.

RESULTSAll the title compounds were first reported. Results of preliminary biological tests showed that most of the title compounds exhibited high activity against the eight common pathogenic fungi and the activities against deep fungi were higher than that against shallow fungi.

CONCLUSIONMost of the title compounds showed higher antifungal activities than Fluconazole and Terbinafine. Compound VIII-1, 10, 12, 17 showed best antifungal activity with broad antifungal spectrum and were chosen for further development.

Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Aspergillus fumigatus ; drug effects ; Candida albicans ; drug effects ; Cryptococcus neoformans ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

BACKGROUNDThe prevalence of chronic pancreatitis has increased during recent years in Asia-Pacific areas as well as in China. The etiologies vary in different regions and periods. This study aimed to investigate the changing etiologies of chronic pancreatitis within 20 years at Peking Union Medical College Hospital in China.

METHODSRetrospective analysis of the etiologies of 636 cases of chronic pancreatitis at Peking Union Medical College Hospital from 1990 to 2010 was performed. Patients were divided into two groups according to two time periods (1990 - 2000 and 2001 - 2010). Statistical analysis was performed using the chi-square test.

RESULTSThe morbidity rate of chronic pancreatitis in China has recently increased. The main etiology changed from biliary diseases in the 1990s (decreased from 36.8% to 28.1%) to alcohol abuse after the year 2000 (increased from 26.5% to 36.8%). The main etiology of biliary diseases is stones in the cholecyst or bile duct, and the percentage of cholecystitis cases has increased. Autoimmune disease, including autoimmune pancreatitis, has increased quickly and currently accounts for 7.3% of cases because a greater number of autoimmune pancreatitis cases are being diagnosed. Approximately 9.5% of chronic pancreatitis cases are caused by multiple factors such as alcohol abuse and bile duct stones. Other factors include cholecystectomy and acute pancreatitis.

CONCLUSIONSThe main etiology of chronic pancreatitis has changed from biliary disease to alcohol abuse in recent years. Autoimmune factors have also obviously increased.

Adult ; Alcoholism ; complications ; Bile Duct Diseases ; complications ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Chronic ; epidemiology ; etiology ; immunology ; Retrospective Studies ; Risk Factors