To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.

AIM　To predict skin permeability of drugs with theoretical parameters. METHODS　The semiempirical self-consistent field molecular calculation AM1 method is utilized to obtain the structural parameters of drug molecules. Stepwise multiple regression analysis or BP neural network is then utilized to establish the correlation between skin permeability of drugs and their structural parameters. RESULTS　The calculated human skin permeability coefficients (kp) of 22 model drugs in vitro or the R values (R=absorbed/unabsorbed) of 17 drugs in vivo are in good agreement with their observed values. CONCLUSION　Theoretical parameters can be used to predict skin permeability of drugs.

Objective To investigate the effects of hypoxia on malignant phenotype of a hepatocellular carcinoma(HCC)cell line and its molecular basis.Methods Human HCC cell line with highly metastatic potential(MHCC97H)was grown under hypoxia(induced by 100 μmol/L CoCl_2)and normoxic conditions respectively.To observe the effects of hypoxia on MHCC97H cells was observed,the tumorigenicity was carried out by soft agar cloning method in vitro and inoculation in nude mice in vivo;Invasive and metastatic potential were measured.Experiments with and/or without Matrigel in vitro and a metastatic human HCC orthotopic nude mice model by HAL in vivo.To clarify the molecular background,the proliferation of cells were analyzed by MTT assay and the cell cycle was detected by flow cytometry;The expression of embryonic stem cell(ES)-like genes(Oct4,Nanog and Sox2)were detected by real-time RT-PCR;CD90~+ and CD133~+ subpopulation from MHCC97H cells were isolated by flow cytometry and the expressions of CD90 and CD133 of MHCC97H cells were analyzed by immunofluorescence.Results Hypoxia increased tumor migration(t=2.792,P=0.023),invasiveness(t=7.624,P＜0.0001)and clone forming ability(t=3.292,P=0.011)of MHCC97H cells in vitro,and promoted tumorigenesis(x~2=8.571,P=0.015)and pulmonary metastasis(x~2=5.507,P=0.031)in vivo.The proliferation of MHCC97H cells arrest under hypoxic conditions accompanied with increased proportion of cells in G1 phase,the expressions of Oct4,Nanog,Sox2 significantly increased in response to hypoxia,but the fluorescence intensity and number of CD90~+ and CD133~+ MHCC97H cells decreased or unchanged.Conclusion Hypoxia increases aggressiveness of MHCC97H cells,which was correlated with the acquisition of embryonic stem cell-like characteristics.

Objective To evaluate the influence of the placement of instant hand disinfectant in compliance and qualified rate of hand hygiene of clinicians.Methods Hand hygiene compliance of clinicians in departments of gyne-cology,obstetrics,and general surgery were observed after the placement of instant hand disinfectant at the door-way of wards,hand specimens were taken to check hand hygiene effectiveness.Results Before and after placement of instant hand disinfectant at the doorway of wards of above departments,hand hygiene behaviors of 300 person-times were observed.Hand hygiene compliance rate among clinicians in department of gynecology,obstetrics,and general surgery increased from 32.33% to 74.33%,33.67% to 85.67%,and 26.33% to 64.00%,respectively(all P <0.001).Each department selected 98 hand hygiene specimens,the qualified rate was 98.98%,100.00% and 94.90% respectively.Conclusion The placement of instant hand disinfectant at the doorway of each ward can effec-tively improve clinicians’hand hygiene compliance and hand hygiene effectiveness.

Objective To investigate the effects of inhibiting epithelial mesenchymal transition (EMT) on metastastic potential of hepatocellular carcinoma (HCC) enhanced by hepatic arterial occlusion in mice. Methods Using a metastatic human HCC orthotopic nude mice model (MHCC97),the effects of hepatic artery ligation (HAL) alone,combination of HAL and phosphatidylinositol 3-kinase (PI3K)inhibitor LY294002,or combination of HAL and interferon-α (IFN-α) on the growth of planted human HCC cells and pulmonary metastasis were evaluated,respectively.The cells and tumor tissues specimens were analyzed through expression of Akt,p-Akt,E-cadhein,N-cadherin and Twist. Results HAL inhibits tumor growth (2002.97 ± 331.28 ) mm3 vs.( 3921.23 ± 786.21 ) mm3,t =4.052,P ＜ 0.01 ),while promoting pulmonary metastatsis ( 10/12 vs.4/12,P ＜ 0.05).HAL combined with LY294002 represses significantly enhanced pulmonary metastasis rate by HAL alone (0/6 vs.6/6,P ＜ 0.01 ).Moderate-dose IFN-α (7.5 × 106 U/kg) combined with HAL failed to further reduce tumor volume compared with that of HAL alone,but inhibited markedly pulmonary metastasis (2/6 vs.6/6,P ＜ 0.05 ).The augmented level of N-cadherin and Twist in tumor tissues due to HAL reduced by LY294002 or 7.5 × 106 U/kg IFN-α.The arrest of EMT by LY294002 or IFN-α in HAL-treated xenografts was further demonstrated by the in vitro response of hypoxic cells to both agents. Conclusions Inhibition of EMT in HCC cells could repress enhanced metastastic potential due to hepatic arterial occlusion.

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.

OBJECTIVETo screen the formulations of cryptotanshinone gel for treatment of topical diseases such as acne.

METHODDifferent cryptotanshinone gels incorporating various penetration enhancers at different concentrations were prepared using carbopol 934L as matrix. The steady transdermal fluxes and drug retention amounts in skin of the gels were investigated on single chamber diffusion cells using excised rat abdomen skin as model and 40% polyethylene glycol-400 saline as releasing media. The optimal formulation would be the gel which had the maximum drug retention amount/ transdermal drug flux ratio.

RESULTThe promotion effects of menthol at different concentrations were as follows: 5% > 3% > 1%, and the effects on drug retention amount in skin were followed as: 5% approximately equal 3% > 1%; The promotion effects of a zone at different concentrations were as follows: 5% approximately equal 3% > 1%, and the effects on drug retention amount in skin were as follows: 5% > 3% approximately equal 1%. Combination of enhancers showed no superior effects compared to single uses. 5% azone had the maximum retention amount/ transdermal flux ratio.

CONCLUSIONThe optimal formulation was the cryptotanshinone gel containing 5% azone.

Administration, Topical ; Animals ; Chemistry, Pharmaceutical ; Gels ; Male ; Permeability ; Phenanthrenes ; administration & dosage ; chemistry ; metabolism ; Rats ; Rats, Sprague-Dawley ; Skin ; metabolism

The genus Xestospongia is one of the most widespread genera of sponges, containing abundant secondary metatolites with novel structures and potent bioactivities. The main structure types of secondary metatolites found in this genus are alkaloids, quinines, terpens, steroids, lipids, polyketones, etc. These metatolites exhibit a variety of bioactivities, such as cytotoxic, antibacterial and antiviral activities. This paper reviews the progress in the chemistry and pharmacological activities of the second metabolities from sponges of Xestospongia, especially for recent five years, with the aim for further research.

Objective The occurrence and progression of renal cell carcinoma ( RCC) is complicated process associated with DNA abnormal methylation , histone modification , and Wnt signaling pathway .This study aimed to investigate the expression of histone methylase SET8 in RCC, its relationship with the Wnt signaling pathway , its action mechanism in RCC , and its clinical significance . Methods We selected 50 cases of RCC treated by radical nephrectomy , detected the expression of SET 8 in the RCC and adjacent noncancerous kidney tissues by immunohistochemical EliVision two-step staining with β-catenin.We compared the expression levels of SET8 and β-catenin in the two types of tissue and analyzed their relationship with the patients′clinical information and the pathologic stage and grade of tumor as well as the correlation between the SET 8 andβ-catenin expressions . Results SET8 was mainly express in the cytoplasm of the RCC and noncancerous kidney tissues , partially in the cell membrane and nucleus , while theβ-catenin protein chiefly in the cell membrane of renal tubular epithelial cells in the normal kidney tissue .The expression levels of SET 8 and β-catenin in the RCC tissue were closely related to the TNM stage and tumor grade (P<0.05).The positive expression of SET8 in the RCC tissue (76%[38/50]) showed no significant difference from that in the ad-jacent noncancerous kidney tissue (66% [33/50]) (P>0.05), but that of β-catenin was remarkably higher in the former (68%[34/50]) than in the latter (4%[2/50]) (P<0.01).There was a positive correlation between the positive expression of SET 8 and the abnormal expression of β-catenin (r=0.219, P<0.05). Conclusion SET8-activated H4K20me-1 controls the activation and abnormal activities of the Wnt signaling pathway , affects the gene transcription and cell activity , and participates in the occurrence , progression, and distant metastasis of RCC .

Objective:To analyze the reflux parameters of patients with gastroesophageal reflux disease (GERD) in upright position, supine position and at 2 h after meals, and to explore the cut-off value, sensitivity and specificity of the reflux parameters in different positions and at 2 h after meals in GERD diagnosis.Methods:From January 2016 to July 2020, 200 GERD patients (GERD group) and 61 non-GERD patients (control group) who visited Huazhong University of Science and Technology Union Shenzhen Hospital (Former Nanshan District People′s Hospital), were selected. All the patients of the two groups received gastroesophageal reflux disease questionnaire (GERDQ), upper gastrointestinal endoscopy, esophageal high resolution manometry and 24 h esophageal pH combined impedance monitoring. T test, non-parametric test and chi-square test were used to compare the related parameters in upright position, supine position and at 2 h after meals between two groups and within each group. Receiver oparative characteristic (ROC) curves of reflux parameters in upright position, supine position and 2 h after meals were drawn to determine the cut-off value, sensitivity and specificity in GERD diagnosis. Results:The proportion of patients with acid reflux in supine position of the control group was higher than that of the GERD group (41.0%, 25/61 vs. 8.50%, 17/200), and the difference was statistically significant ( χ2=36.53, P<0.01). In the control group, the acid reflux time in upright position, number of acid reflux, acid exposure time (AET), longest reflux time and number of weak acid reflux were more than those of in supine position in the same group (6.00 min(2.00 min, 13.50 min) vs. 0.00 min(0.00 min, 1.50 min), 16.00(8.00, 27.00) vs. 1.00(0.00, 3.00), 0.90%(0.33%, 1.88%) vs. 0.00%(0.00%, 0.30%), 2.00 min(1.00 min, 4.00 min) vs. 0.00 min(0.00 min, 1.00 min), 7.00(3.00, 11.00) vs. 1.00(0.00, 2.00), respectively) and the differences were statistically significant ( Z=5.43, 6.61, 5.06, 3.58 and 6.24, all P<0.01). In the GERD group, the acid reflux time, number of acid reflux, AET, longest reflux time and number of weak acid reflux in upright position were higher than those in supine position (51.00 min, (31.00 min, 86.75 min) vs. 8.00 min(1.00 min, 42.00 min), 60.00(48.00, 83.75) vs.6.00(2.00, 19.50), 7.30%(3.90%, 12.10%) vs. 1.50%(0.20%, 6.50%), 7.00 min(4.00, 12.00 min) vs. 4.00 min(1.00 min, 17.00 min), 1.00(0.00, 3.00) vs. 0.00(0.00, 2.00), 7.00(3.00, 12.00) vs. 0.00(0.00, 1.00), respectively) and the differences were statistically significant ( Z=7.92, 11.22, 6.90, 2.56, 5.11 and 11.76, all P<0.05). The acid reflux time, number of acid reflux, AET, longest reflux time and number of weak acid reflux at 2 h postprandial were 3.00 min(2.00 min, 9.00 min), 10.00(5.00, 18.00), 0.90%(0.40%, 1.98%), 1.00 min(0.00 min, 3.00 min), 4.00(1.50, 8.50)and 28.50 min(15.00 min, 54.75 min), 35.00(24.00, 52.00), 8.30%(4.32%, 15.83%), 6.00 min(3.00 min, 11.00 min), 4.00(2.00, 7.25), in the control and GERD groups, respectively, which were significantly higher than those in supine position in the same group ( Z=4.30, 6.33, 5.50, 3.40, 5.71 and 3.76, 9.21, 5.76, 1.97, 10.46, all P<0.05). Among 200 GERD patients, 125 patients had symptoms recorded during the 24 h esophageal pH combined impedance monitoring, the incidence of reflux symptoms in upright position was higher than that in supine position (89.6%, 112/125 vs. 65.6%, 82/125), and the difference was statistically significant ( χ2=20.71, P<0.01). The results of ROC curve analysis showed that the accuracy of acid reflux time in upright position in GERD prediction was the highest, with AUC value of 0.94 and cut-off value of 24.5 min, and the sensitivity and specificity in GERD diagnosis were 81.50% and 95.08%, respectively. The prediction accuracy of acid reflux times in upright position and AET in upright position for GERD was secondary, AUC value both were 0.93 and the cut-off value of the acid reflux number in upright position was 39.5, and the sensitivity and specificity in GERD diagnosis were 84.00% and 95.08%, respectively. The cut-off value of AET in upright position was 2.75%, the sensitivity and specificity in GERD diagnosis were 85.00% and 93.33%, respectively. The AUC value, cut-off value, sensitivity and specificity of AET at 2 h postprandial were 0.91, 4.60%, and 73.49% and 95.00%, respectively. Conclusions:Both GERD patients and non-GERD patients have more reflux in upright position, especially within 2 h after meals. The diagnostic values of acid reflux time in upright position, number of acid reflux, AET and AET 2 h after meals for GERD is high, and the AUC values are all >0.90, which can be used as a more comprehensive basis for the analysis and diagnosis of GERD.