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??OBJECTIVE To evaluate the effects of hormone replacement therapy(HRT) on the quality of life in climacteric women.METHODS The 202 patients were collected and divided into three groups according to whether or not they were treated with HRT: group 1 (not HRT), group 2 (HRT for the first time), group 3 (HRT for more than one year). All patients received follow-up visiting once per three months for one year. They were evaluated by the professionals through Kupperman index(KI), menopause-specific quality of life questionnaire(MENQOL), self-rating anxiety scale(SAS), self-rating depression scale(SDS). All patients were guided to improve the way of life.RESULTS After a year, KI, MENQOL and SAS in the three groups were improved significantly (P=0.003, 0.007, 0.014). KI and MENQOL were improved earlier than SAS. SDS was improved but not significantly(P=0.109). KI, MENQOL, SAS and SDS of patients in group 1 were improved significantly, but improved more weakly than those in group 2 and group 3. There is negative correlation between HRT and the values of every scale, and there is positive correlation between culture degree and SAS, SDS score values. CONCLUSION HRT canim prove the quality of life in climacteric women. The improvement in physical symptoms is earlier than that in mental symptoms. Anxiety and depression are more likely to occur in menopausal patients with high degree of education. Traditional Chinese medicine, exercise therapy and physical rehabilitation can be used as an auxiliary treatment for patients who are unable or unwilling to accept the HRT.     

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??OBJECTIVE To establish an RP-HPLC analytical method for simultaneous determination of crysoeriol and centaureidin in the aeries parts of Echinops integrifolius. METHODS The separation was achieved on a Kromasil C₁₈ column ( 4. 6 mm??250 mm,5 ??m)at 30 ?? using acetonitrile-water-acetic acid solution (35??65??2) as mobile phase at a flow rate of 1.0 mL??min^-1 and 350 nm as the detection wavelength. RESULTS The linear ranges of crysoeriol and centaureidin were 0.4-2.4 mg??L^-1(r=0.999 8), 0.6-2. 6 mg??L^-1 (r=0.999 9), respectively. The average recoveries (n=6) were 91.6% and 92.7%, and RSDs were 1.37% and 1.08% respectively. CONCLUSION The methodology validation shows that this method is accurate,simple and reliable,which is applicable for the simultaneous determination of two flavonols crysoeriol and centaureidin in the aeries parts of Echinops integrifolius.     

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??OBJECTIVE To analyze the regularity, clinical reactions and outcomes of the adverse reaction of sorafenib to provide reference for safe medication in clinical practice. METHODS The case reports of sorafenib ADR which were published at international medical academic periodicals during 2006-2016 were collected and analyzed statistically in respect of gender, age, disease informations, clinical manifestation and RESULTS of treatment. RESULTS A total of 93 adverse reactions were identified and included in the analysis, 22 cases were unexpected ADR. The ADR happened in male was more than in female, and the age of 61-80 was the most common population (45.16%). The ADR was mostly happened in 1 month (71.11%) after therapy. Lesions of skin and its appendants were the most commonly reported ADRs (51.52%), followed by the lesions of digestive system (22.73%) ,which reported the most of the death cases (n=19 , 6 death). The ADR correlation rate was high in these case reports. CONCLUSION Multiple organ systems are involved in the ADRs of sorafenib, amd careful clinical observation and symptomatic treatment in time are necessary.     

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??Quercetin could affect both the in vivo and in vitro transport of a variety of commonly used drugs by modulating the uptake transporter organic anion transporter polypeptides (OATPs), organic anion transporters (OATs), efflux transporter P-glycoprotein (P-gp), multidrug resistance-related protein (MRP) and breast cancer resistance protein (BCRP), respectively. Quercetin can regulate various drug transporters, thereby affecting other drugs in vivo process.     

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??OBJECTIVE To prepare the total alkaloids of Strychni Semen(TASS)-total glucosides of Paeony(TGP) gel and study its in vitro transdermal absorption of two alkaloids(strychnine and brucine) after the combination of TASS and TGP. METHODS The excised abdominal skin of mice was used as the permeation model. Utilizing the modified Franz diffusion cell, the suitable receiving solution was elected to test the content of two alkaloids by HPLC, and thus the percutaneous rates and permeability coefficients were obtained. RESULTS 20% Ethanol-normal saline was taken as receiving solution. With combination use of TASS and TGP, the penetration quantities of strychnine and brucine in different (1:1,1:3,1:6) gels were felled by 22.7%,48.4%,69.1% and 5.93%,23.8%,80.7% after 24 h. And with the increase of compatibility proportion, infiltration rate and skin retention rate also gradually reduced. CONCLUSION The compatibility of TASS and TGP drug delivery can reduce the toxic ingredients through capacity, there is a “attenuated” effect, the best ratio is 1:6.     

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??OBJECTIVE To examine the in vitro release profile and in vivo retention of estradiol vaginal thermosensitive gel (E2-VTG).METHODS E2-VTISG was prepared by cold dissolving method.The dynamic membrane dialysis method and HPLC-fluorometric method were used to determine the in vitro release characteristic of the estradiol vaginal thermosensitive gel.CRi Maestro was applied to evaluate the retention of E2-VTG in ICR mice with IR820 as the fluorescent marker. RESULTS Estradiol could be released slowly from the thermosensitive gel and the release profile was fitted with Higuchi equation. It was speculated that estradiol was mainly released through diffusion.NIR imaging and fluorescence quantitative analysis showed that thermosensitive gel could reside in vagina for at least 8 h. CONCLUSION Estradiol thermosensitive gel can prolong the drug residence time in vagina and sustain the drug release rate.     

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??OBJECTIVE To establish dose-related lung inflammatory injury in rats model with intratracheal atomization of lipopolysaccharide (lipopolysaccharides, LPS). METHODS Four groups of 4 rats were subjected to solvent or a single dose of LPS by intratracheal route using a IA-1B-2 inches-microsprayer. The male rats received 200 ??L solvent (control), LPS solutions (15, 5, 0.5 mg??kg^-1). All rats were sacrificed 24 h after dose administration, biochemical analysis and cell counts on bronchoalveolar lavage fluid (BALF) were performed on each rat. Lung, trachea and kidney were examined histologically. Serum chemistry profiles of creatinine, ALB, Na, K, Cl^- were detected. RESULTS Cell counts in BALF showed LPS groups had different degrees of inflammatory reaction. The alkaline phosphatase and total protein concentration were higher in LPS high dose group compared with other groups. In addition, the concentration of TNF-?? increased consistently with LPS dose and has statistical significance compared with the control group. Histopathology findings demonstrated that LPS produced an accumulation of foamy macrophages in the lungs and high degree of inflammation. CONCLUSION The results recommends intratracheally atomizing doses of LPS in rats model produced ranks of lung inflammatory injury.     

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??OBJECTIVE To study the pharmacokinetics of hot-melt spray-dried andrographolide granules and compare it with andrographolide bulk drug. METHODS A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for determination of the concentration of andrographolide in plasma of rats which were respectively given micronized andrographolide and hot-melt spray-dried andrographolide granules, then the pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of andrographolide after a single dose administration of micronized andrographolide and hot-melt andrographolide were as following: t_1/2 were (347.33??9.32) and (390.82??8.78) min, t_max were (30.00??5.94) and (60.00??3.48) min, ??_max were (1 940.14??21.21) and (1 818.22??23.64) ng??mL^-1, AUC_0-t were (427 515.71??37 350.03) and (426 406.31??20 577.75) ng??min??mL^-1, AUC_0-inf were (545 423.14??47 969.18) and (593 569.87??30 247.35) ng??min??mL^-1, Vz/F were (43.48??4.75) and (44.96??3.81) kg??L^-1, CL/F were (86.78??3.35) and (79.74??2.89) kg??L^-1??min^-1, respectively. CONCLUSION Compared with the bulk drug, the hot-melt spray-dried andrographolide granules have a longer t_1/2, lower ??_max and delayed t_max in rats.     

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??To improve the in vitro dissolution and in vivo absorption as well as the bioavailability after oral administration by increasing the solubility with the formation of solid dispersion remains a great challenge for the oral dosage form design of poorly water-soluble drugs. Compared with the other pharmaceutical techniques in improving the solubility for poorly water-soluble drugs, priorities are usually given to solid dispersion for its manufacturing convenience. Following the characteristics introduction, we were focused this review on the novel carriers and advanced techniques used for preparing solid dispersions. Amphiphilic polymers used as novel solid dispersion carriers are Solutol HS 15, Soluplus and poly [MPC-co-BMA]. Inorganic materials like magnesium aluminum metasilicat, mesoporous silica microparticle and mesoporous magnesium carbonate are introduced together with the advanced solid dispersing techniques such as supercritical fluid technology, high speed electro-spinning and microenvironmental pH modified technology.     

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??OBJECTIVE To investigate the chemical constituents of the seeds of Lepidium apetalum Willd. METHODS The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, MCI Gel CHP-20, ODS, silica gel chromatography combined with Pre-HPLC and the structures were identified on the basis of spectral data and physiochemical properties. RESULTS Sixteen compounds were isolated and identified from the water extract as catechol(1), protocatechuic aldehyde(2), 2-phenyl acetamide(3), methyl- 5-hydroxypyridine-2-carboxlate(4), benzylcarbamic acid(5), N-benzylacetamide(6), raphanuside C(7), 1-phenyl-1,2-ethanediol(8), 2-(4-hydroxyphenyl)-ethanol(9), isorhamnetin-7-O-??-L-rhamnopyranoside(10), kaempferol(11), methyl 2,4,6-trihydroxybenzoate(12), 2-(4-hydroxyphenyl)acetonitrile(13), syringic acid(14), protocatechuic acid(15), and methyl sinapate(16). CONCLUSION Compounds 1-16 are isolated from this plant for the first time.     

溃结灵对UC大鼠结肠黏膜pERK1/2、pMEK1/2蛋白水平的影响

目的观察溃结灵对TNBS法UC大鼠模型结肠黏膜pERK1/2、pMEK1/2蛋白水平的影响,并对其作用机制进行探讨。方法采用溃结灵对TNBS法UC大鼠模型进行治疗,治疗结束后采集结肠黏膜标本并提取全细胞蛋白,运用蛋白免疫印迹(Western blot)方法对PERK1/2和PMEK1/2的蛋白表达水平进行检测,以β-actin作为内参,以目的蛋白与β-actin密度的比值作为目的蛋白的相对含量,进行组间比较分析。结果模型组pERK1/2、pMEK1/2蛋白相对表达量分别是0.3974±0.1017和0.6994±0.1372,均高于正常组(分别为0.2037±0.1234、0.4092±0.1177,P0.05,P0.01);溃结灵组相对表达量分别为0.7060±0.1607和0.8928±0.1801,明显高于模型组(P0.01,P0.05);SASP组相对表达量分别为0.7299±0.2710和0.9053±0.1591,明显高于模型组(P0.01,P0.05)。结论溃结灵对TNBS法UC大鼠模型结肠黏膜pERK1/2、pMEK1/2蛋白表达有上调作用,提示溃结灵治疗作用可能与激活ERK信号转导途径有关。     

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??OBJECTIVE To abserve the antidepressant effect and mechanism of honokiol on acute and chronic stress mouse. METHODS Forced swimming model of acute stress (FST) and chronic stress mice model were used. The acute stress mouse were randomized into a control group, a fluoxetine group (3.3 mg??kg^-1), honokiol groups (2.5,5,10 mg??kg^-1). The chronic stress mouse were randomized into a blank group, a model group, a fluoxetine group(3.3 mg??kg^-1), honokiol groups (2.5,5,10 mg??kg^-1). Then, the immobility time of forced swimming, 5-hydroxytryptamine (5-HT) and 2,3- indole dioxygenase (IDO) contents in mouse brain tissue by Elisa Kit, and the expression of IDO mRNA in brain tissue used by quantitative real-time PCR were studied. RESULTS ??After acute stress, the immobility time of forced swimming in each treatment group was significantly shorter than that in the model group (P<0.05). The 5-HT content of fluoxetine and honokiol medium and high dose group was significantly higher than that of model group (P<0.05, P<0.01). The IDO content of honokiol high dose group was significantly higher than that of model group (P<0.05). ??After chronic stress, the immobility time of the model group were significantly higher than the blank group (P<0.01). The 5-HT content in brain tissue of the model group was significantly lower than that of the blank group (P<0.01), the IDO content in brain tissue and its expression level of mRNA increased comparing with the normal group (P<0.01). For each treatment group, the immobility time of forced swimming, IDO content and the expression level of IDO mRNA was significantly decreased, and the 5-HT content was significantly increased, comparing with the model group with significant difference (P<0.05). CONCLUSION Honokiol can relieve the depression behavior of mouse and have certain antidepressant effect. The main mechanism may be associated with the increase of 5-HT, reduction of the tryptophan pathway enzyme IDO content and its gene expression level.     

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??OBJECTIVE To observe the effect of guhong injection(GHI) on tibial fracture healing in rats and to explore the mechanism of the action of GHI. METHODS One hundred and eighty male SD rats were randomly divided into 6 groups with 30 rats in each group: sham operation group, model group, positive drug group(compound ossotide injection, 5 mL??kg^-1), low, medium and high dose of GHI groups(2.5, 5, 10 mL??kg^-1). In addition to the sham operation group, the other groups established the rat model of tibial fracture. All were given once daily intraperitoneal injections and samples were taken at 1st, 2nd, 4th and 6th week. Blood biochemical analysis and Elisa kit detection were performed on blood samples. X-rays, biomechanical tests, immunohistochemistry and RT-PCR were performed on the tibial samples. RESULTS ??After administration for one, two and four weeks, the levels of serum calcium(Ca) and phosphorus(P) in medium and high dose of GHI groups were higher than those in model group(P<0.05). ??X-ray showed that the outer callus growth and the disappearance of fracture line in all dose groups of GHI were faster than those in model group. ??Compared with model group, the maximum load and rigidity of medium and high dose of GHI groups were increased at each time point(P<0.05), and the trend of stress line graph were improved obviously. ??The content of alkaline phosphatase(ALP) in medium and high dose of GHI groups were higher than that in model group at each time point(P<0.05). Compared with model group, the serum levels of PDGF were increased in all dose groups of GHI(P<0.05 or P<0.01). After administration for one, two and four weeks, the serum BMP-2 in all dose groups of GHI were higher than those in model group(P<0.05 or P<0.01). ??Compared with model group, the expression of Runx2 mRNA were increased in medium and high dose of GHI groups, as well as Smad5 protein expression(P<0.05 or P<0.01). CONCLUSION GHI could significantly improve the biomechanical properties of bone in fracture rats. The promotion of fracture healing might be through the upregulation of PDGF and BMP-2 expression in different stages of bone healing, and the regulation of BMP/Smad5/ Runx2 signaling may be one of the mechanisms of promoting fracture healing.     

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??OBJECTIVE To explore the effects of glucose on the growth of algae, the content of fucoxanthin, and expressions of genes related to biosynthesis of fucoxanthin. METHODS The cell growth of algae induced by glucose was researched by using spectrophotometric method. The content of fucoxanthin was measured by HPLC. The expressions of the genes which were related to biosynthesis of fucoxanthin were detected by using quantitative PCR. RESULTS At the end of the platform period, the density of cells treated by glucose was higher than that of the control group. The growth of P. tricornutum was promoted by glucose. The result of HPLC analysis showed that fucoxanthin content in the algae treated by different concentrations of glucose was decreased than that in the control group. When the concentration of glucose reached 50 mg??L^-1, the content of fucoxanthin was the lowest (0.26 mg??g^-1 DW), which was 67.5% lower than the control, indicating that glucose inhibited the biosynthesis of fucoxanthin in P. tricornutum. RT-qPCR result showed that the expression of genes related to the biosynthesis pathway of fucoxanthin, i.e., zep, pys, zds, lcyb, crtiso, and pds, were all lower than those of the control when the concentration of glucose was in the range from 10 to 50 mg??L^-1. This result was consistent with the change of fucoxanthin content. CONCLUSION This result further illustrates that glucose may inhibit the biosynthesis of fucoxanthin in P. tricornutum by down-regulating the expression of related genes.     

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??OBJECTIVE To study the effect of kangfuxin on damp-heat syndrome combined with TNBS-induced ulcerative colitis in rats and to explore its mechanism. METHODS Rat model of damp-heat was established by high-fat and high-sugar diet, and then combined with TNBS to establish rat model of damp-heat, respectively, to give sulfasalazine, rehabilitation, high, medium and low dose enema, by measuring disease activity index(DAI), colonic mucosal injury index(CMDI) and histopathological score(HS). The levels of IL-8, IL-17 and IL-2, MPO, EGF and TNF-?? in serum were measured by enzyme-linked immunosorbent assay(ELISA). RESULTS Compared with the model control group, the high dose group can significantly reduce the DAI, HS and CMDI scores of the damp-heat type UC rats(P<0.01, P<0.05). Each group type can reduce the heat UC rat serum IL-8, IL-17 and expression of MPO,TNF-?? in colon tissue, increases, the expression of rat IL-2 EGF(P<0.01). CONCLUSION Kangfuxin has a certain therapeutic effect on damp-heat type UC rats, and its mechanism may be related to down-regulating the expression of IL-8, IL-17,MPO and TNF-??, up-regulating the expression of IL-2 and EGF.     

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??OBJECTIVE To study the effects of Kadsura coccinea alcohol extract(KCAE) on rats with immunologic hepatic fibrosis and research the possible mechanisms in it. METHODS Totally 60 SD male rats were randomly divided into 6 groups: a normal control group,a model group, a compound Biejia-ruangan tablets group(0.7 g??kg^-1), KCAE high, middle and low dose groups(1.68, 0.84, 0.42 g??kg^-1) at ten in each groups. Except for the normal control group,other groups were duplicated intraperitoneal injection of porcine serum twice a week at dose of 0.5 mL??time^-1. The rats in treatment groups were intragastric administration respectively, meanwhile, the rats in normal control and model groups were treated with the same volume of distilled water, once a day for 15 weeks. The liver was weighed to calculate the liver index. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), total protein(TP), albumin(ALB) and total bilirubin(TB) were evaluated by the Mind-Ray automatic biochaemical analyzer. The expression level of procollagen ??(PC??), collagen type ??(??-C), laminin(LN), hyaluronic acid(HA), transforming growth factor-??1(TGF-??1), interkeukin-10(IL-10), interferon-??(IFN-??) and tumor necrosis factor-??(TNF-??) in serum were detected by ELISA. The degrees of fibrosis were evaluated by HE and Masson straining, and the expression levels of TGF-??₁ in liver tissue were assessed by Western blot. RESULTS Compared with model group, the liver index of KCAE high-dose group was decreased significantly(P??0.01). The expression levels of ALT, AST, TP, ALB, TB were within normal range, the differences were not statistically significant(P>0.05). KCAE could decrease the level of PC??, IV-C, LN, HA, TGF-??₁, TNF-?? and increase the level of IFN-?? in serum. KCAE could alleviate the hepatic fibrosis in rats(P??0.01) and inhibit the expression of TGF-??₁ in the liver tissues significantly(P??0.01). CONCLUSION KCAE has an anti-immunologic hepatic fibrosis effect in rats and the mechanisms possibly involve effectively regulating inflammatory cytokines, reducing extracellular matrix expression and inhibiting the expression of TGF-??₁.     

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??OBJECTIVE To assess the cost-effectiveness of clinical pharmaceutical care in the H. pylori(HP) eradication in outpatients with peptic ulcer.METHODS Ninty-six Outpatients with HP positive peptic ulcer from July 2015 to June 2016 were prospectively collected, and randomly divide into control group and intervention group. Patients in the control group were given the traditional outpatient service. The intervention group patients were given with pharmaceutical education and follow-up by clinical pharmacist. The score of compliance with medication, HP eradication rate and the improvement of gastrointestinal symptom were selected as outcome indicator. Time cost of intervention and fee of clinical pharmacist training were estimated and recorded as the cost of clinical pharmacy intervention. RESULTS ??Improvement of the score of compliance with medication of intervention group patients was significantly higher than the control group (1.71 vs. 0.44, P<0.01). Forty-four patients of the intervention group, while 36 patients in the control group reported less gastrointestinal symptoms (91.67% vs. 75.00%, P=0.028). The HP eradication rate of the intervention group was significantly higher than the control group (91.67% vs. 72.92%, P=0.016). ??For the hospital, the cost of pharmacy service of control group was 292.31 yuan, and 821.61 yuan of the intervention group. ??The cost-effectiveness ratio of the score of compliance with medication of control group was 664.34, while the intervention group was 480.47, which was superior to the control group. It was cost-effective. However, the cost-effectiveness ratio of HP eradication rate and the improvement of gastrointestinal symptom of the intervention group were both higher than the control group. CONCLUSION Clinical pharmaceutical care increase the cost of the hosipital. However, clinical pharmaceutical care can result in cost-effective improvement of the medication compliance.     

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??OBJECTIVE To compare the efficacy of different interventions on chemotherapy induced thrombocytopenia (CIT) in solid tumors. METHODS Patients, registered at Fudan University Shanghai Cancer Center, who developed CIT (defined as platelet count < 100??10⁹??L^-1) during May 2014 and April 2015 were retrospectively enrolled. The patients were divided into recombinant human interleukin 11 (rhIL-11) group, recombinant human thrombopoietin (rhTPO) group, combination group and non-treatment group. Complete remission rate (CR), recovery time and recurrence rate were calculated to compare the efficacy of interventions. P<0.05 was considered as statistical significant. RESULTS A total of 281 eligible patients were enrolled. No significant difference were found on recovery rate of different interventions in each grade of CIT (P>0.05). Recovery time were similar between interventions, most group had a median recovery time of 6 or 7 d. In grade ?? CIT, the recovery time of combination group is shorter than the other intervention groups (5.5 d in combination group vs 7 d in rhTPO group and rhIL-11 group), but there was no significant difference (P=0.609, 0.605). In grade ?? CIT, the recurrence rate was significantly higher in rhTPO group and rhIL-11 group than untreated group (35%, 38% vs 0%, P=0.008, P=0.006). In grade ?? CIT, the recurrence rate of rhTPO group was significantly higher than that of rhIL-11 group (55% vs 21%, P=0.017). CONCLUSION The result of the current study suggests that thrombopoietic agents are not recommended for patients with ??-?? CIT. For ??-?? CIT, no significant differences are found in the efficacy between different interventions, thus rhIL-11 is recommended in consideration of cost.     

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??OBJECTIVE To clone and isolate the major facilitator superfamily(MFS)genes of Polyporus umbellatus and carry out bioinformatic analysis. METHODS Nine major facilitator superfamily(MFS)genes were cloned from Polyporus umbellatus sclerotia by RT-PCR and the expression analysis of the nine genes in different parts of Polyporus umbellatus sclerotia was carried out using quantitative Real-time PCR.RESULTS The full open reading frame cDNA sequence of these nine genes was between 1 321 and 1 860 bp, the putative encoding proteins were between 441 and 620 amino acids, the molecular weight was between 48.45??10³ and 64.79??10³ and the theoretical pI was between 6.59 and 9.56. The amino acids of these nine genes possessed 11 to 14 membrane-spanning domains. Phylogenetic tree analysis indicated that Comp34750,Comp34832, Comp29252, Comp42895, Comp32579 and Comp27555 had the highest similarity with MFS general substrate transporter,Comp28872 and Comp26306 had the highest similarity with MFS monosaccharide transporter, and Comp33117 had the highest similarity with MFS sugar transporter. Quantitative real-time PCR showed that these nine genes were expressed in both the symbiotic part and non-symbiotic part. Meanwhile,the expressions of seven genes were significantly up-regulated in the symbiotic part except Comp34382 and Comp32579. CONCLUSION The investigated nine genes might play an important role during the defense response and nutrient absorption of P.umbellatus.