Objective To evaluate clinical efficacy of multiple regimen combination in treatment of osteoporosis of perimenopausal or postmenopausal women. Methods From Jul. 2008 to Dec. 2009, 109 women with low bone mineral density (BMD) or osteoporosis treated in Department of Obstetrics and Gynecology, Affiliated Second Hospital, Wenzhou Medical College were enrolled randomly into 3 group,including 36 women in Group A managed by osteoform 1000 mg/d + alfacalcidol 0. 25 μg/bid orally, 40 women in group B managed by osteoform 1000 mg/d + alfacalcidol 0. 25 μg/bid + tibolone 1.25 mg/d orally and 33 women in group C managed by ostcoform 1000 mg/d + alfacalcidol 0. 25 μg/bid +bisphosphonates 70 mg/w orally. After 48 weeks BMD on lumbar 1 -4 (L1-4) and left femur were detected by X-ray. Bone alkaline phosphatase(BALP) ,cross linked clelopeptide of type Ⅰ collagen(CTX) and 25-hydroxychole calciferol [25 (OH) D3] was measured by enzyme linked immunosorbent assay (ELISA).Result Seven women (6. 4%, 7/109) were withdrawed form this study, including 2 cases losing follow up in group A, 3 cases stopping treatment in group B, 2 cases giving up treatment due to severe adverse effect (burning in upper abdomen) in group C. (1) Pain relieve: after 48 weeks treatment, women in 3 groups improved symptom of pain significantly, the rates of pain relieve were 85% (29/34)in group A, 92% (34/37) in group B and 94% (29/31) in group C. (2) BMD: BMD was improved significantly in women in 3 groups after treatment. BMD of L1-4 were (0.88±0.15) g/cm2 in group A,(0.89±0.18) g/cm2 in group B and (0.87±0.10) g/cm2 in group C before treatment, and converted to (0.90±0.01) g/cm2 in group A, (0.93±0.09) g/cm2 in group B and (0.91±0.11) g/cm2 in group C after treatment. BMD of left femur were (0.87±0.07) g/cm2 in group A, (0.87±0.07) g/cm2 in group B and (0.85±0. 12) g/cm2 in group C before treatment and converted to (0.90± 0.03) g/cm2 in group A, (0.91±0.08) g/cm2 in group B and (0.89 ±0.12) g/cm2 in group C after treatment. It was shown significantly different BMD between group B or C and group A (P < 0. 01), however, there was no significant different BMD between group B and C (P >0. 05). (3) Index of bone metabolism: BALP were (26±6) μg/L in group A, (26±9) μg/L in group B and (28±7) μg/L in group C before treatment and converted to (22±5) μg/L in group A, (20±9)μg/L in group B and (22±8)μg/L in group C after treatment, which showed statistical difference (P < 0.05). CTX were (0.85±0.20) ng/L in group A, (0.84±0.47) ng/L in group B, and (0. 88 ±0. 11) ng/L in group C before treatment and converted to (0. 81 ±0. 19) ng/L in group A, (0. 77±0.33) ng/L in group B, and (0.82 ±0. 14) ng/L in group C after treatment, which showed statistical difference (P < 0. 05). Conclusions Those 3 regimens combination could be used in treatment of osteoporosis by decreasing bone conversion, increasing bone density, decreasing bone absorption. Regimen A was only suitable for basic therapy,the other two regimens could provide better treatment.

Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

Objective To assess the utility of changes of muscle strength and compound muscle action potential (CMAP) of abductor digiti minimi (ADM) muscle after the exercise test in diagnosis of hypokalaemic periodic paralysis during inter-attack period. Methods Exercise test was applied on 59 patients with hypokalaemic periodic paralysis and 38 control subjects during inter-attack period. The changes of CMAP amplitude, muscle strength and the range of abduction of ADM muscle at 120 minutes after exercise were calculated and compared between the two groups. Results At 120 minutes after exercise, the M50 (M25, M75 ) of decrease in amplitude of CMAP recorded in ADM muscles were 54. 1% ( 43.1%,66. 3% ) in patients with periodic paralysis and 11.1% (2. 0%, 21.3% ) in control subjects(Z =6. 731,P=0.000), M5o(M25,M75) of decrease in range of abduction of ADM muscles were 39.4% (26.3% ,48. 9% ) in patients with periodic paralysis and 7. 8% ( 1.3%, 13.7% ) in control subjects ( Z = 5. 519,P=0. 000). The muscle strength of ADM muscle was less than Ⅳ grade in 96. 3% (52/54) patients with periodic paralysis and 8.6% ( 3/35 ) in control subjects ( x2 = 68.2, P = 0. 000 ). The sensitivity and specificity for decrease in CMAP amplitude ( best cutoff = 30% ) in diagnosis of hypokalaemic periodic paralysis were 87.5% and 93.7%, respectively. The sensitivity and specificity for decrease in range of abduction of ADM muscle ( best cutoff = 20% ) were 87.5% and 90. 5%, respectively. Conclusion Exercise test is recommended to apply on patients with suspected hypokalaemic periodic paralysis during inter-attack period. The decrease in range of abduction of ADM muscle more than 20% at 120 minutes after exercise supports the diagnosis of hypokalaemic periodic paralysis.

BACKGROUND:The enamel matrix derivative has been used in the clinical treatment of severe periodontitis; however, the mechanism(s) by which enamel matrix derivative promotes periodontal regeneration is stil obscure. OBJECTIVE:To explore the effects of enamel matrix derivatives on the differentiation and proliferation of periodontal ligament stem cels. METHODS:Periodontal ligament stem cels were isolated and identified from human teeth. Cloning forming efficiency, surface antigen expression and pluripotency were detected and identified. Enamel matrix derivatives with different concentrations (20, 50, 100 mg/L) were used to culture periodontal ligament stem cels for 2 and 4 weeks. Colagen synthesis and mineralized nodule formation were detected using Trichrom staining and Von Kosa’s staining, respectively; real-time RT-PCR was employed to detect expressions of colagen type I, osteocalcin, and RUX2; MTT and cel growth rate assay were used to detect the proliferation of periodontal ligament stem cels. RESULTS AND CONCLUSION:Periodontal ligament stem cels were spindle-shaped and showed a higher colony forming efficiency than periodontal ligament cels. The expressions of surface antigens of periodontal ligament stem cels-CD105, CD29, CD45, CD44 were respectively 99.8%, 99.7%, 1.26%, 98.8%, indicating periodontal ligament stem cels have the multilineage differentiation potential. Enamel matrix derivatives improve the colagen synthesis and mineralization nodule formation of periodontal ligament stem cels in a time-dose dependent manner. They also can improve the expression of osteogensis-related genes colagen type I, osteocalcin, RUX2 and proliferation of periodontal ligament stem cels.

To investigate such physical indexes as hygroscopicity, angle of repose, bulk density, fillibility of compression of mixed powder of directly compressed auxiliary materials and fermented cordyceps powder by using micromeritic study methods. The results showed that spray-dried lactose Flowlac100 and microcrystalline cellulose Avicel PH102 had better effect in liquidity and compressibility on fermented cordyceps powder than pregelatinized starch. The study on the impact of directly compressed auxiliary materials on the powder property of fermented cordyceps powder had guiding significant to the research of fermented cordyceps powder tablets, and could provide basis for the development of fermented cordyceps powder tablets.
Cellulose ; chemistry ; Cordyceps ; chemistry ; Drug Compounding ; methods ; Fermentation ; Lactose ; chemistry ; Powders ; chemistry ; Tablets ; chemistry ; Technology, Pharmaceutical ; methods

Objective To establish the cell model of ethanol-induced liver injury and explore the protective effects of tea poly-phenols (TP)on ethanol-induced liver injury .Methods Cell morphology were observed by microscope ,and then alanine aminotrans-ferase (ALT) ,nmda transaminase (AST) ,gamma GGTP ,GGT and ROS changes were detected .Results Alcohol maked L02 hepa-tocyte fatty degeneration .Compared with ethanol group ,steatosis in TP + ethanol group was lighter ,its ALT ,AST ,GGT content and intracellular ROS reduced .Conclusion TP can decrease cell fatty change degree in vitro experiments ,improue the enzymology indexes ,reduce the generation of reactive oxygen species to avoid liver damage .

Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).

Aim To observe the influences of dexmen-detomidine on the spontaneous contraction of duodenal smooth muscle of rabbits in vitro and explore the mech-anisms.Methods The rabbits ( male or female ) were stunned and the duodenums were isolated .The sam-ples of duodenal segments were connected with tension transducer , which were then put into oxygen saturation Krebs-Henseleit ( K-H) solution .The influences of dex-mendetomidine on amplitude ( AM ) and frequency ( FR ) of duodenal smooth muscle were recorded by BL-420 F biological signal processing system .The cu-mulative dosing method was used to observe the differ-ent concentrations of dexmedetomidine on duodenal smooth muscle spontaneous contraction .Glibenclamide ( Gli) was added to K-H solution before dexmendeto-midine.In the calcium-free K-H solution, calcium chloride and rynodine were added before dexmendeto-midine.The mechanisms of dexmendetomidine were studied .Results ① Dexmendetomidine reduced the amplitude of spontaneous contraction of duodenal smooth muscle in rabbits in a dose-dependent manner ( P<0.05 or P<0.01 ) , while the frequency was not obviously influenced ( P >0.05 ) .② Gli ( P <0.05 ) partly abolished the inhibitory effects of dexmendetomi-dine on duodenal smooth muscle .③ Dexmendetomi-dine inhibited the contraction of duodenum smooth muscle induced by calcium chloride ( P <0.05 ) and rynodine ( P<0.05 ) application into calcium-free K-H solution.Conclusion Dexmendetomidine inhibits the spontaneous contraction of duodenal smooth muscle of rabbits in vitro.The mechanisms may be related to ac-tivating ATP sensitive potassium channels , inhibition of the extracellular calcium influx via cell membrane and intracellular calcium release via sarcoplasmic reticulum in duodenal smooth muscle .

Objective To evaluate the relative efficacy of different dosages of Calf Pulmonary Surfactant (Calsurf) administration in premature infants with established respiratory distress syndrome (NRDS).Methods Four neonatal intensive care units in Jiangsu province were enrolled.Premature infants,birth weight ＜ 2 500 g,with NRDS,received 70 mg/kg (61 cases)or 100 mg/kg (69 cases)Calsurf.Clinical and respiratory parameters were recorded.The primary outcome measures were blood gas analysis of 1 h,12 h and 36 h after administration,the need for oxygenation and ventilatory requirements and the adverse events of NRDS.Results Arterial oxygen tension[pa (O2)] results in a significant improvement(80.27-±36.81) mmHg,(73.03 ±24.94) mmHg and (72.35 ± 24.72) mmHg at 1 h,12 h and 24 h in higher dose group(P ＜ 0.05),(67.95 ± 23.79) mmHg,(72.35 ± 24.72) mmHg in 24 h,as compared with the lower dose group at the same time [(67.07 ± 19.94) mmHg,(62.93 ± 21.71) mmHg,(67.95 ±-23.79) mmHg] (P ＞ 0.05).Inspired oxygen (FiO2) and pa (O2) decreased after administration in two groups and the duration of FiO2 decline lasted to 48 h (all P ＜ 0.05).The oxygen index (OI) was improved after Calsurf administration,especially in the infants who received 100 mg/kg of Calsurf with 6.1 ± 2.8,5.6 ± 3.3,5.5 ± 3.5,5.8 ± 4.5,5.3 ± 3.1 in 1 h,12 h,24 h,36 h,48 h,respectively(P ＜ 0.01).The arterial-to-alveolar oxygen tension ratio (a/APO2) of 100 mg/kg group was reduced significantly in 1 h,12 h,24 h,36 h,48 h with 0.39 ±0.22,0.42 ±0.20,0.45 ± 0.22,0.44 ± 0.22,0.46 ± 0.21 as compared with 0.27 ± 0.18 which was at the time point before administration (P ＜ 0.01).Although not statistically significant,the mean time of duration of mechanical ventilation and oxygen inhalation of higher dose group were decreased as compared to the lower dose group [(94.54 ± 113.44) h vs (109.27 ± 124.87) h (P＞0.05) and (259.10 ±280.45) vs (372.31 ±398.08) h(P ＞0.05)].There were no significant differences in the rates of other adverse events such as pneumonia,pneumothorax,intracranial hemorrhage,patent ductus arteriosus (PDA),pneumorrhagia,necrotizing enterocolitis,septicemia between two groups (P ＞ 0.05).Conclusions Calsurf given to preterm infants with NRDS at a dose of 100 mg/kg resulted in a higher Pa (O2),a/APO2,better OI and lower FiO2 as compared with those receiving 70 mg/kg.The need for mechanical ventilation and oxygen supplement were reduced with higher-dose administration.Large dose of Calsurf did not increase the risk of complications as mentioned above.

Objective:To explore the cytogenetic characteristics of hypospadias in children by karyotype analysis.Methods:From June 2008 to May 2018, 45 children with hypospadias in Tianjin Children's Hospital had cytogenetic abnormalities. Their median age was 10 months(range 3 hours to 5 years old). Of the 45 cases, 20 were proximal hypospadias, 1 was middle hypospadias. All 24 cases had varying degrees of genitourinary malformations. Among them, 15 cases had unilateral or bilateral cryptorchidism, 5 cases had scrotal division, 3 cases had penile scrotal transposition, 3 cases had small penis, 3 cases had indirect inguinal hernia, 1 case had repeated urethra, 1 case had hydrocele and 1 case had concealed penis. To the other systemic malformations, there was 1 with cleft lip and palate and 1 with congenital heart disease. G-banding karyotype analysis of peripheral blood lymphocytes was performed in all 45 cases.Results:Among the 45 cases of hypospadias with abnormal karyotypes, with an abnormal rate of 14.0%, 28 cases (62.22%) had sex chromosome abnormalities, including (47, XXY), (46, XX/47, XXY), (45, X0/47, XYY), etc. Sexual inversion occurred in 8 cases (17.78%), all of which were 46, XX. There were 4 autosomal abnormalities (8.89%), including (46, XY, 9p+ ), (46, XY, 10p+ ) and (46, XY, 1q+ ). Chromosome polymorphism was found in 4 cases (8.89%), including [46, XY, inv(9)] and [46, XY, 16qh+ ], and the equilibrium translocation of 1 case (2.22%) was [45, XY, -21, -22, + t(21; 22)]. Among the 45 cases, 8 sex reversal children with (46, XX) chromosome karyotype were all proximal hypospadias.Conclusions:Children with hypospadias may be associated with chromosomal karyotype abnormalities, including sex chromosomal abnormalities, autosomal abnormalities, chromosome polymorphism and balanced translocation. Among them, sex chromosome abnormality was the most common and balanced translocation was the least.