Application progress of ROS-responsive liposomes in anti-tumor research / 药学实践杂志

Reactive oxygen species（ROS） responsive liposomes are prepared based on the high level of ROS expression in the tumor microenvironment, enabling precise drug delivery to the tumor site. With the addition of photosensitizer, the controllability of drugs in liposomes can be further enhanced.

Cupping therapy for patients with chronic urticaria: A systematic review and meta-analysis / 中西医结合学报

BACKGROUND@#Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed.@*OBJECTIVE@#This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU.@*SEARCH STRATEGY@#The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms.@*INCLUSION CRITERIA@#RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English.@*DATA EXTRACTION AND ANALYSIS@#Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions.@*RESULTS@#Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported.@*CONCLUSION@#Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO, CRD42019137451.

The cardiovascular protection of irisin and its research progress in sports field / 生理学报

Irisin is a circulating myokine induced by exercise, which is a cleaved version of fibronectin type III domain containing protein 5 (FNDC5). It can promote the browning of white fat tissue, increase energy consumption, and decrease weight. Irisin plays an important role in the regulation of various diseases, such as diabetes and coronary heart disease. Different types of exercise have different effects on irisin level in blood circulation, and moderate exercise can reduce cardiovascular symptoms. In this paper, the cardiovascular protective effect of irisin and its research progress in the field of exercise are reviewed, hoping to provide a new target for the prevention and treatment of cardiovascular diseases.

Expression of Wnt2b in cholangiocarcinoma and its relationship with epithelial-mesenchymal transition / 中华肝胆外科杂志

Objective@#To study the expression of Wnt2b protein and the epithelial-mesenchymal transition related markers in tissues of carcinoma of bile duct and normal bile duct to determine the clinical significance. The relationships between the expression levels and clinicopathological characteristics were analyzed, and the correlation between Wnt2b and epithelial interstitial transformation (EMT), tumor invasion and metastasis were studied.@*Methods@#A total of 60 patients with cholangiocarcinoma and 30 patients with normal bile duct tissues admitted to the Affiliated Hospital of Qingdao University from December 2008 to December 2013 were studied. The expressions of Wnt2b, E-cadherin and Vimentin protein were detected by SP immunohistochemical staining. The patients were classified according to the expressions of these proteins. Analyses were conducted on the relationships of these proteins with clinical characteristics of the patients with cholangiocarcinoma.@*Results@#The positive expression rate of Wnt2b protein in carcinoma of bile duct tissues was 90.0%, which was significantly higher than that in normal bile duct tissues (χ2=38.1, P<0.05). The positive expression rate of Wnt2b in T3 + T4 was significantly higher than that in T1 + T2 (P<0.05). There were no correlations of the expression with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). Patients with lymph node metastasis had a significantly higher positive expression of Vimentin than patients with no lymph node metastasis, and the loss of E-cadherin expression was increased (all P<0.05). There were no relationship of the expressions of these proteins with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). The increased expression of Wnt2b in bile duct cancer cells was related to increase in EMT marker of the positive expression of vimentin and the loss of E-cadherin expression (both P<0.05).@*Conclusions@#Wnt2b protein overexpression in cholangiocarcinoma correlated with epithelial-mesenchymal transition related markers. The Wnt2b protein was correlated with cholangiocarcinoma occurrence, development, invasion and metastasis. Wnt2b has the potential to develop into a new therapeutic target for carcinoma of bile duct.

Expression of Wnt2b in cholangiocarcinoma and its relationship with epithelial-mesenchymal transition / 中华肝胆外科杂志

Objective To study the expression of Wnt2b protein and the epithelial-mesenchymal transition related markers in tissues of carcinoma of bile duct and normal bile duct to determine the clinical significance. The relationships between the expression levels and clinicopathological characteristics were analyzed, and the correlation between Wnt2b and epithelial interstitial transformation (EMT), tumor inva-sion and metastasis were studied. Methods A total of 60 patients with cholangiocarcinoma and 30 patients with normal bile duct tissues admitted to the Affiliated Hospital of Qingdao University from December 2008 to December 2013 were studied. The expressions of Wnt2b, E-cadherin and Vimentin protein were detected by SP immunohistochemical staining. The patients were classified according to the expressions of these proteins. Analyses were conducted on the relationships of these proteins with clinical characteristics of the patients with cholangiocarcinoma. Results The positive expression rate of Wnt2b protein in carcinoma of bile duct tissues was 90. 0％, which was significantly higher than that in normal bile duct tissues (χ2 =38. 1, P<0. 05). The positive expression rate of Wnt2b in T3 + T4 was significantly higher than that in T1 + T2(P<0. 05). There were no correlations of the expression with patients' age, gender, tumor location and degree of tumor differentiation (P>0. 05). Patients with lymph node metastasis had a significantly higher positive expression of Vimentin than patients with no lymph node metastasis, and the loss of E-cadherin expression was increased (all P<0. 05). There were no relationship of the expressions of these proteins with patients'age, gender, tumor location and degree of tumor differentiation (P>0. 05). The increased expression of Wnt2b in bile duct cancer cells was related to increase in EMT marker of the positive expression of vimentin and the loss of E-cadherin expression (both P <0. 05). Conclusions Wnt2b protein overexpression in cholangiocarcinoma correlated with epithelial-mesenchymal transition related markers. The Wnt2b protein was correlated with cholangiocarcinoma occurrence, development, invasion and metastasis. Wnt2b has the poten-tial to develop into a new therapeutic target for carcinoma of bile duct.

Prevention value of four treatments of pancreatic stump for pancreatic fistula after distal pancreatectomy: a Meta-analysis / 中华消化外科杂志

Objective To systematically evaluate the clinical effects of four treatments of pancreatic stump including stapler closure,hand-sutured closure,stapler with hand-sutured closure,and manual anastomosis on the prevention of postoperative pancreatic fistula after distal pancreatectomy.Methods Databases including PubMed,Embase,the Cochrane Library,CBM,CNKI,and VANFUN were searched for from January 1979 to January 2019 with the key words including "distal pancreatectomy,left pancreatectomy,distal pancreatic resection,left pancreatic resection,pancreatic fistula,fistula,leak,stapler,suture,anastomosis,胰腺远端切除 术,胰体尾切除术,闭合器,手工缝合,吻合,胰瘘”.Patients undergoing dissection of distal pancreas with Endo-GIA stapler were allocated into stapler group,patients undergoing hand-sutured closure of pancreatic stump after dissection of distal prancreas with electrotome or ultrasonic scalpel were allocated into hand-sutured closure group,patients undergoing dissection of distal pancreas with Endo-GIA stapler and hand-sutured closure of pancreatic stump were allocated into stapler with hand-sutured closure group,patients undergoing pancreaticojejunostomy or pancreatogastrostomy after dissection of distal pancreas were allocated into manual anastomosis group,respectively.Two reviewers independently screened literatures,extracted data and assessed the risk of bias.Count data were described as odds ratio (OR) and 95％ confidence interval (95％ CI).The heterogeneity of the studies included was analyzed using the I2 test.Funnel plot was used to test potential publication bias if the studies included ≥ 5,and no test was needed if the studies included ＜5.Results (1) Document retrieval:a total of 10 available prospective studies were included.There were 1 363 patients,including 565 in the stapler group,484 in the hand-sutured closure group,182 in the stapler with hand-sutured closure group,and 132 in the manual anastomosis group.(2) Results of Meta-analysis.① There was no statistically significant difference in postoperative fistula after distal pancreatectomy between the stapler group and the handsutured closure group (OR =0.75,95％CI:0.45-1.25,P＞0.05).Further study showed that there was no statistically significant difference in the incidence of grade B and C postoperative fistula between the two groups (OR=0.45,95％CI:0.14-1.52,P＞0.05).The left-right asymmetry was presented in the funnel plot based on the 8 studies,suggesting that publication bias may exsited.② There was no statistically significant difference in postoperative fistula after distal pancreatectomy between the stapler group and the stapler with hand-sutured closure group (OR =0.96,95％ CI:0.48-1.91,P ＞ 0.05).③ There was no statistically significant difference in postoperative fistula after distal pancreatectomy between the stapler with hand-sutured closure group and manual anastomosis group (OR =0.80,95％ CI:0.49-1.32,P＞ 0.05).④ There was no statistically significant difference in postoperative fistula after distal pancreatectomy between the manual anastomosis group and the stapler group (OR=0.73,95％CI:0.39-1.34,P＞0.05).Further study showed that there was no statistically significant difference in the incidence of grade B and C postoperative fistula between the two groups (OR =0.60,95％CI:0.21-1.68,P＞0.05).The bilateral symmetry was presented in the funnel plot based on the 5 studies,suggesting that publication bias had little influence on results of Meta-analysis.⑤ There was no statistically significant difference in postoperative fistula after distal pancreatectomy between the manual anastomosis group and the handsutured closure group (OR=0.24,95％CI:0.08-0.74,P＜0.05).The bilateral symmetry was presented in the funnel plot,suggesting that publication bias had little influence on results of Meta-analysis.Conclusions Compared with hand-sutured closure,pancreaticojejunostomy or pancreatogastrostomy after distal pancreatectomy can help to reduce the incidence of postoperative pancreatic fistula.However,there was equivalent prevention value of stapler,hand-sutured closure,and stapler with hand-sutured closure for postoperative fistula after distal pancreatectomy.The manual anastomosis group has equivalent prevention value with stapler group.

Effects of Paclitaxel-conjugated N-Succinyl-Hydroxyethyl Chitosan Film for Proliferative Cholangitis in Rabbit Biliary Stricture Model / 中华医学杂志(英文版)

<p><b>Background</b>Paclitaxel (PTX) could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film (N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]) and evaluated its safety and efficiency using in vivo and in vitro experiments.</p><p><b>Methods:</b>The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FT-IR) measurements. Drug releases in vitro and in vivo were determined using high-performance liquid chromatography. Cell viability in vitro was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Rabbit biliary stricture model was constructed. All rabbits randomly divided into five groups (n = 8 in each group): the sham-operated rabbits were used as control (Group A), Groups B received laparotomies and suture, Group C received laparotomies and covered SHEC suture without the PTX coating, Group D received laparotomies and covered PTX-SHEC suture, and Group E received laparotomies and 1000 μmol/L PTX administration. Liver function tests and residual dosage of PTX from each group were measured by enzyme-linked immunosorbent assay. Histological data and α-smooth muscle actin (SMA) immunohistochemical staining of common bile duct were examined.</p><p><b>Results:</b>NMR and FT-IR indicated that PTX was successfully introduced, based on the appearance of signals at 7.41-7.99 ppm, 1.50 ppm, and 1.03 ppm, due to the presence of aromatic protons, methylene protons, and methyl protons of PTX, respectively. No bile leak was observed. The PTX-conjugated film could slowly release PTX for 4 weeks (8.89 ± 0.03 μg at day 30). The in vitro cell viability test revealed significantly different levels of toxicity between films with and without PTX (111.7 ± 4.0% vs. 68.1 ± 6.0%, P < 0.001), whereas no statistically significant difference was observed among the three sets of PTX-contained films (67.7 ± 5.4%, 67.2 ± 3.4%, and 59.1 ± 6.0%, P > 0.05). Histological examinations revealed that after 28 days of implantment, Groups D and E (but not Group C) had less granulation tissue and glandular hyperplasia in the site of biliary duct injury than Group B. The pattern was more obvious in Group D than Group E. Less α-SMA-positive cells were found in tissue from Groups D and E. Comparing with Group E, the liver function was improved significantly in Group D, including total bilirubin (2.69 ± 1.03 μmol/L vs. 0.81 ± 0.54 μmol/L, P = 0.014), alanine aminotransferase (87.13 ± 17.51 U/L vs. 42.12 ± 15.76 U/L, P = 0.012), and alkaline phosphatase (60.61 ± 12.31 U/L vs. 40.59 ± 8.78 U/L, P < 0.001).</p><p><b>Conclusions</b>PTX-SHEC film effectively inhibites the myofibroblast proliferation and extracellular matrix over-deposition during the healing process of biliary reconstruction. This original film might offer a new way for reducing the occurrence of the benign biliary stricture.</p>

Evaluation of the effect of different routes of administrating flumazenil against hypnosis / 药学实践杂志

Objective To study the effect of flumazenil on hypnotic mice induced by diazepam and zolpidem ,and to eval-uate the possibility of flumazenil oral administration .Methods First ,Kunming mice were injected intraperitoneally with nor-mal saline and sodium pentobarbital (S + W) ,diazepam and pentobarbital sodium (D + W) ,zolpidem and pentobarbital sodi-um (Z + W) .The hypnotic effect of diazepam and zolpidem on prolonging the sleep time of pentobarbital sodium would be ver-ified by (D + W) group and (Z + W) group .Then the mice were injected intraperitoneally with flumazenil .The sleep time was used as the evaluation index to evaluate the effect of flumazenil against hypnosis . Finally , the oral administration of flumazenil was observed against hypnosis ,which was evaluated by using sleep time as an index .Results Compared with the control group (S+W) ,the diazepam group (D+W) and the zolpidem group (Z+W) significantly prolonged the sleep time in-duced by pentobarbital sodium (P<0 .001 ,P<0 .05);After Intraperitoneal injection of flumazenil ,compared with the diazepam group (D+W) and the zolpidem group (Z+W) ,the sleep time of the diazepam group [F(ip)+D+W] and the zolpidem group [F(ip)+Z+W] were significantly shorter (P<0 .001 ,P<0 .05);After oral administration of flumazenil ,the sleep time of the diazepam group [F(ig)+ D+ W] and the zolpidem group [F(ig)+ Z+ W] were also significantly shorter (P< 0 .001 ,P<0.05) .Conclusion Flumazenil ,whether intraperitoneal injection or intragastric administration ,could antagonize the hypnotic effect of diazepam and zolpidem .It was proved that oral administration of flumazenil had the same effect compared with intrap-eritoneal injection of flumazenil ,which provided the possibility of preparation of oral administration of flumazenil .

A propensity score matching analysis of hepatectomy and radiofrequency ablation for patients with solitary hepatocellular carcinoma less than or equal to 5 cm and portal hypertension / 中华消化外科杂志

Objective To compare the clinical efficacy of hepatectomy and radiofrequency ablation (RFA) for patients with solitary hepatocellular carcinoma (HCC) less than or equal to 5 cm (≤5 cm) and portal hypertension (PHT).Methods The propensity score matching and retrospective case-control study was conducted.The clinicopathological data of 154 patients with solitary HCC ≤ 5 cm and PHT who were admitted to the Qingdao University between January 2011 and July 2016 were collected.Of 154 patients,61 and 93 underwent R0 hepatectomy and RFA,respectively.Observation indicators:(1) the propensity score matching conditions and comparison of general data between groups after the propensity score matching:patients' data were matched by the propensity score matching,patients undergoing hepatectomy and RFA were respectively allocated into the hepatectomy group and RFA group;(2) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative tumor-free and overall survival up to July 31,2018.Patients received enhanced scans of computed tomography (CT) or magnetic resonance imaging (MRI) in 1 month postoperatively,and then reexaminations of liver function,level of alpha-fetoprotein (AFP),B ultrasound and pulmonary CT within 3 months postoperatively,once every 3 months from 3 months postoperatively to 2 years and once every 6 months after 2 years postoperatively.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using chi-square test.The Logistic regression model was used for the propensity score matching.The survival curve and rate were respectively drawn and calculated by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) The propensity score matching conditions and comparison of general data between groups after the propensity score matching:118 of 154 patients had successful matching,including 59 in each group.There were statistically significant differences in the tumor diameter and level of preoperative albumin (Alb) before the propensity score matching between groups (x2 =11.050,6.687,P＜0.05),and no statistically significant difference after the propensity score matching between groups (x2=2.366,2.484,P＞0.05).(2) Follow-up and survival:all the 154 patients were followed up for 4.5-91.4 months before the propensity score matching,with a median time of 44.4 months.The postoperative 1-,2-,3-and 5-year tumor-free survival rates were respectively 88.1％,79.5％,64.1％,40.3％ in patients of hepatectomy group and 84.9％,68.6％,52.8％,43.4％ in patients of RFA group,with no statistically significant difference in the tumor-free survival between groups (x2 =0.997,P＞0.05).The postoperative 1-,2-,3-and 5-year overall survival rates were respectively 95.1％,88.5％,85.0％,70.1％ in patients of hepateetomy group and 100.0％,95.7％,85.6％,73.7％ in patients of RFA group,with no statistically significant difference in the overall survival between groups (x2 =0.053,P＞0.05).One hundred and eighteen patients were followed up for 4.5-91.4 months after the propensity score matching,with a median time of 49.4 months.The postoperative 1-,2-,3-and 5-year tumor-free survival rates were respectively 89.4％,82.3％,66.4％,41.7％ in patients of hepatectomy group and 83.1％,64.2％,47.4％,38.5％ in patients of RFA group,with no statistically significant difference in the tumor-free survival between groups (x2=2.612,P＞0.05).The postoperative 1-,2-,3-and 5-year overall survival rates were respectively 94.9％,89.8％,86.1％,70.8％ in patients of hepatectomy group and 100.0％,91.5％,79.4％,67.6％ in patients of RFA group,with no statistically significant difference in the overall survival between groups (x2 =0.383,P＞0.05).Conclusion The both hepatectomy and RFA are reliable radical treatments for solitary HCC ≤ 5 cm and PHT.

Preparation and evaluation of photo-sensitive reactive oxygen species responsive liposomes / 药学学报

Photo-sensitive reactive oxygen species (ROS) responsive liposomes loaded with 1,4,8,11,15, 18,22,25-octabutoxypalladium phthalocyanine[PdPC(OBu)8] and doxorubicin hydrochloride (DOX) (LPD) were prepared by (NH4)2SO4-gradient method. LPD was characterized with transmission electron microscopy (TEM), dynamic light scattering particle size, zeta potentials, photo-sensitive ROS-responsive DOX release behaviors and the serum stability in vitro. LPD cytotoxicity, DOX uptake and singlet oxygen production in MCF-7 cells were evaluated. The results showed that the particle size of LPD was (169.3 ±1.2) nm, PDI of LPD was 0.198 ±0.003 and zeta potentials of LPD was (-39.8 ±0.8) mV. The accumulated release of DOX reached 95.5% in 5 min under 730 nm laser irradiation (300 mW·cm-2). The DOX uptake of liposome was increased and 1O2 was generated. The half inhibition concentration (IC50) of DOX in LPD with irradiation group was decreased by 85.7% and no irradiation group was decreased by 67.9% compared with free DOX group in MCF-7 cells. Therefore, photo-sensitive ROS-responsive liposomes would be a promising drug delivery system for tumor therapy.

Recent progress of reactive oxygen species-responsive drug delivery systems / 药学学报

Excessive reactive oxygen species (ROS) is associated with an array of pathological conditions, including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. However, ROS-responsive materials have drawn attention in the development of drug delivery systems. There are many types of ROS-responsive materials explored in drug delivery applications, including sulfur-based responsive polymers, selenium-based responsive polymers, tellurium-based responsive polymers, oxalate ester-containing polymers, phenylboronic ester-containing polymers and unsaturated lipids. When integrated with ROS-responsive drug delivery systems, a photosensitizer is used as a light-sensitive element to generate ROS, mainly singlet oxygen (1O2), which in turn activates the ROS-triggered drug delivery.

Expression and clinical significance of HSPA9 in hepatocellular carcinoma / 重庆医学

Objective To investigate the expression of HSPA9 in hepatocellular carcinoma(HCC) and its relationship with clinicopathological features and prognosis.Methods Forty-nine cases HCC treated by operative resection and follow up data in our hospital from January 2006 to January 2010 were retrospectively analyzed.Immunohistochemistry was performed to determine the expression of HSPA9 in HCC and paratumor tissues.The relationship between HSPA9 expression and clinicopathological features and prognosis was statistically analyzed.Results The HSPA9 protein expression in tumor tissue was higher that that in the paratumor tissue(t=6.601,P＜0.01),moreover the over expression of HSPA9 was significantly correlated with lymph node metastasis (P =0.005),TNM-stage(P =0.015),tumor differentiation (P =0.033),microvascular invasion (P =0.009) and recurrence (P =0.047).In the survival analysis results,the patients with over expression of HSPA9 had a much lower total survival rate(P=0.002)and much higher postoperative cumulative recurrence rate(P =0.003).There were significant differences in TNM-stage,microvascular invasion,lymph node metastasis,tumor differentiation and HSPA9 staining for overall survival and cumulative recurrence rate based on a univariate analysis(P＜0.05).Conclusion HSPA9 has over expression in HCC.The over expression of HS-PA9 is closely related to invasion and metastasis pathological features and can serve as an independent prognostic risk factor for predicting the prognosis of HCC.

To explore the preparation method of different animal erythrocytehemolysin in experimental teaching of medical immunology / 国际检验医学杂志

Objective To detect different animal erythrocyte hemolysins titer,and compare the application of these hemolysins in immunological experimental teaching,for selecting the better method of preparing high titer hemolysin for experimental teaching of medical immunology.Methods A total of 40 experiment rabbits were divided into 4 groups in this study,and immunized by sheep red blood cell(SRBC) and porcine red blood cell(PRBC) through different immunization procedures to prepare the hemolysin,detect and compare these 4 groups hemolysins titer by the complement hemolysis test.Results Rabbit Anti-SRBC in the group A was 1∶4 800,rabbit Anti-PRBC in the group B was 1∶1 200,rabbit Anti-SRBC in the group C was 1∶1 000,rabbit Anti-PRBC in the group D was 1∶200.Conclusion The hemolysin titer of the rabbit Anti-PRBC was lower than that of the rabbit Anti-SRBC by the same immunization procedures,and the immunization procedure by intradermal multi-point and auricular vein injection is the better method of preparing high titer hemolysin,so PRBC could replace SRBC as antigen,and immunize the rabbits for preparing hemolysin,which could be used in experimental teaching of medical immunology.

Recent progress in pharmacology ,efficacy and dosage forms of flumazenil / 药学实践杂志

Flumazenil ,a benzodiazepine antagonist ,specifically binds the benzodiazepine receptors in central nervous system and reduces the release of gamma-aminobutyric acid .It is used for the reversal of sedative effects of benzodiazepine and benzodiazepine-induced anesthesia .In this article ,the clinical applications of flumazenil and the developments of different dos-age forms were reviewed .

Preparation and characterization of co-delivery of doxorubicin and elacridar in nanoparticles / 药学实践杂志

Objective To establish methods for the determination of doxorubicin and elacridar, and prepare PLGA nanoparticles for the co-delivery of doxorubicin and elacridar.Methods Ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC) were used to establish the determination method of doxorubicin and elacridar, respectively;co-delivery nanoparticles system was prepared by nanoprecipitation method, and optimizing the prescription was by adjusting the dosage ratio of the two drugs to investigate the particle size,morphology, encapsulation efficiency (EE), drug loading (DL) and in vitro release.Results The linearity of doxorubicin was better in the rang of 1 to 40 μg/ml, A=0.021C+0.002,r=0.999 5;the linearity of elacridar was better in the rang of 0.5 to 100 μg/ml,A=120 742.462 6C+1 974.570 4,r=1.000 0;the particle size was about 50 nm;transmission electron microscope (TEM) showed that nanoparticles were round in shape and had a good dispersion;EE of doxorubicin and elacridar were 56.58%、51.66%,respectively, DL of doxorubicin and elacridar were 1.48%、1.85%,respectively,the molar ratio of two drugs was about 1∶1;the nanoparticles released slowly in vitro.Conclusion The established methods of doxorubicin and elacridar were convenient and efficient, accurate and repeatable.The Co-delivery nanoparticles system was well dispersionand smaller size, which could be used for further studies.

Effect of Fragile Site WWOX Gene on Regulating Proliferation of Human Gallbladder Cancer Cells in Vitro / 昆明医科大学学报

Objective To explore the effect and mechanism of fragile site WWOX gene on regulating proliferation of gallbladder cancer cells in vitro. Methods The pcDNA3.0 - WWOX recombinant plasmid which was previous successfully built was transfected to GBC-SD cells and empty carrier by liposome medium. Liposome and GBC-SD were served as the negative control and the blank control,respectively. After 48 hours transfection, inverted microscope was used to observe the changes of gallbladder cancer cells' morphology,MTT and BrdU were used to detect the proliferation level of gallbladder cancer cells,and flow cytometry instrument was used to detect the change of the cell proliferation cycle. Results The results of inverted microscope shown: the number of GBC-SD cells in pcDNA3.0-WWOX group decreased significantly,the suspension cells and cell debris increased,while cells in the vector control,NC and Mock groups were in normal proliferation state. MTT test showed the proliferation levels of GBC-SD cells in pcDNA3.0-WWOX group was lower than those in the control group in 24 h,48 h,72 h,96 h and 120 h,and the differences were statistically significant(P 0.05). Conclusion The overexpression of WWOX gene in vitro could effectively inhibit the proliferation activity of gallbladder cancer cells. WWOX might participate in the development of the malignant biological behavior of gallbladder cancer cells. It is expected to become a new potential target for the gene therapy to gallbladder cancer.

Analysis of problems on tumor-targeting drug delivery system / 药学实践杂志

Objective To analyze the current problems on tumor‐targeting nanoparticle drug delivery system .Methods Recent researches of tumor‐targeting nanoparticle drug delivery system were collected ,read and summarized .Results Three research fields on tumor‐targeting nanoparticle drug delivery system were reviewed in this article .Conclusion Not only a deeper understanding of the human physiology and tumor biology ,but changes in strategies and experimental methods are needed to make new achievements on nanoparticle drug delivery system .

The effect of targeting miRNA interfering with Bmi-1 expression on human gallbladder cancer cell proliferation / 实用医学杂志

Objective Via targeted inhibition of oncogene Bmi-1 expression by RNAi interfering technology in vitro, to observe its effect on the proliferation and cell cycle of gallbladder cancer cells. Methods Four miRNABmi-1 recombinant plasmids were constructed according to different Bmi-1 sites. RT-PCR and Western blot were used to mRNA and protein expression of Bmi-1 in gallbladder cancer cells were measured by RT-PCR and Western blot. mRNA and protein expression of Bmi-1 in gallbladder cancer cells. The most effective interfering plasmids in the miRNABmi-1 groups were transfected into GBC-SD cells. Cell proliferation and cell cycle were analyzed 48 h after transfection by BrdU and flow cytometry. Results Bmi-1mRNA expression in miRNAbmi1-1,-3 and-4 was significantly lower than the control group (P<0.05);and Bmi-1 protein expression in miRNAbmi1-2,-3 and-4 was significantly lower than the control group (P<0.05). The recombinant plasmid in miRNAbmi1-4, with the strongest inhibitive effect of Bmi-1mRNA and protein expression, was transfected into GBC-SD cells,then the cell proliferation rate (46.63 ± 5.31) was significantly lower in mRNABmi1-4 group than the control groups (P<0.05);G0/G1 phase cells increased (72.20 ± 1.71) and G2/M and S phase cells decreased (18.30 ± 7.21, 9.50 ± 6.01) in miRNABmi1-4 group. Both were significantly different from the control groups (P<0.05). Conclusions Targeting and silencing Bmi-1 expression can effectively inhibit the proliferation of GBC-SD cells and restrain the cell cycle atin G0/G1 phase. Bmi-1 gene may be a novel target for geneic therapy of gallbladder carcinoma.

An experimental study of the combination of paclitaxel therapy and ezrin-siRNA treatment in meta-static liver cancer / 中华肝胆外科杂志

Objective To investigate paclitaxel and ezrin-siRNA therapy for metastatic liver cancer.Methods Human metastatic liver cancer cells MHCC97-H were divided into four groups in vitro and in vivo,including control cells,exposure to paclitaxel alone,ezrin-siRNA alone,and the combination of paclitaxel and ezrin-siRNA.Nude mice lung lesions were formed by tail vein injection of tumor cells.The tumor cells'apoptosis rate,wound healing ability,the ability to cross an artificial membrane,and the numbers of metastatic lung lesions were measured.Results The apoptosis rate in normally cultured MHCC97-H tumor cells was 2.52％,compared to the other three groups at 11.66％,2.35％,7.38％ respectively.The wound healing ability was best in the negative control and weakest in cells treated with combination paclitaxel and ezrin-siRNA.The numbers of cells which could cross the artificial membrane in the negative,paclitaxel,ezrin-siRNA,and combination paclitaxel and ezrin-siRNA group were 52.5 ± 3.9,32.2 ± 3.2,26.6 ± 2.4,and 19.4 ± 1.1 respectively.The numbers of metastatic lung lesions in the nude mice (n =40) were 12.5 ±2.4,8.2 ± 1.5,7.0 ± 1.3,and 3.8 ± 0.3 respectively.Conclusions The ezrin-siRNA combined with paclitaxel therapy demonstrated a greater efficacy over single agent therapy for depressing liver cancer growth,motility,aggression,and metastasis in vitro and in vivo.

Experimental research of combined hepatocyte growth factor with epidermal growth factor cultured human gallbladder epithelial cell / 重庆医学

Objective To establish the method of combined hepatocyte growth factor (HGF) with epidermal growth factor (EGF) cultured human gallbladder epithelial cells(HGBECs) in vitro .Methods The epithelial layer was peeled away from human gallbladder ,epithelial layer were digested with collagenase Ⅳ and scraped repeatedly .HGBECs were isolated and seeded in cell cul-ture plates containing medium supplemented with or without 10 ng/mL EGF or with 10 ng/mL HGF and 10 ng/mL EGF respec-tively .Then the morphologic changes of the cells were observed and taken photos with inverted phase contrast microscope ,and counted number of cells ,MTT assay detected vigor of cells in different groups .Results The number of the HGBECs of the HGF+EGF group was obviously more than the EGF group ,the duration of the HGBECs of the HGF+ EGF group was obviously longer than the EGF group(19 .3 ± 2 .5)d vs .(14 .2 ± 2 .4)d ,P< 0 .05 .And the HGBECs of the group with HGF+ EGF had better cell vigor .Conclusion HGF combines with EGF added to medium can obviously promote the proliferation of HGBECs and prolong the duration and stabilize morphology of HGBECs in vitro .