Research progress of tumor microenvironment-responsive RNA drug delivery systems / 药学学报

Cancer is considered as one of the major diseases endangering human health in the world, it is urgent to find a safer and more efficient treatment for cancer therapy. Gene therapy with ribonucleic acid (RNA) drugs could regulate the expression of tumor related genes, and exhibit good anti-tumor therapeutic potential in preclinical and clinical trials. Based on the differences between tumor tissues and normal tissues in microenvironment signal characteristics such as pH, specific enzyme concentration or redox gradient, various microenvironment responsive nanocarriers had been studied and developed to deliver RNA drugs to tumor tissues and cells, improving the anti-tumor efficacy of RNA drugs and reducing toxic and side effects. This paper reviews the pathophysiological characteristics of tumor microenvironment and various strategies of tumor microenvironment responsive nanocarriers, in order to provide reference for the design of safe and efficient RNA drug delivery system for cancer therapy.

Analysis of technical difficulties and new strategies of oral liquid pharmaceutical preparation for children / 药学学报

With the implementation of the two-child policy and the growing demand for child health, pediatric medication has been arousing widespread social concern. To develop the drugs suitable for children, including new compounds, new specifications and new dosage forms, is urgently required for pharmaceutical researchers. In this review, several technical bottlenecks for pediatric oral liquid preparations, as well as the novel strategies involved in drug nanocrystals, self-microemulsion, ion exchange resin and Pickering emulsion were discussed, which may be benefit to play a theoretical guiding role in the research and development of children's oral liquid formulation.

Analysis of projects without nanotechnology funded by National Natural Science Foundation of China in the field of pharmaceutics from 2001 to 2020 / 药学学报

Nanotechnology has been widely used in the field of pharmaceutics. In recent years, research projects related to nanotechnology account for a high proportion (nearly 90%) in the application and funded projects of pharmaceutics (application code is H3408) of National Natural Science Foundation of China (NSFC). In addition, there are many other research directions in the field of pharmaceutics. This paper makes statistics and analysis on the research projects of pharmaceutics without nanotechnology funded by NSFC from 2001 to 2020, so as to provide reference for the pharmaceutical researchers to reasonably choose research direction.

Applications of microfluidic technology to delivery of nanoparticulate drug / 药学学报

Microfluidics is a technology that involves the use of micro-nanoscale pipelines to manipulate fluid mixing. Precise control of the mixing process of laminar flows or liquid droplets by using microfluidics will contribute to the preparation of nanoparticles, which are difficult to be achieved by the conventional methods. Based on the progress in delivery systems of nanoparticulate drug, we provide a summary to introduce the applications of microfluidics in construction of nanoparticulate drug delivery system such as liposomes, polymer nanoparticles and hybrid nanoparticles, and analyze the assembling mechanisms of different nanostructures by using microfluidic precise control. This review will provide a reference in utilization of microfluidic technology more scientifically and reasonably.

Shenqi Fuzheng Injection for advanced gastric cancer: a systematic review of randomized controlled trials / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of Shenqi Fuzheng Injection (, SFI) combined with chemotherapy for advanced gastric cancer.</p><p><b>METHODS</b>Randomized controlled trials (RCTs) from 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 software was applied for data analyses.</p><p><b>RESULTS</b>Thirteen RCTs involving 860 patients met the selection criteria (all articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3-4, oral mucositis at grade 1-2, leucopenia at grade 3-4, and myelo-suppression at grade 1-2.</p><p><b>CONCLUSIONS</b>This systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment.</p>

Assessment of different genetic distances in constructing cotton core subset by genotypic values / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

One hundred and sixty-eight genotypes of cotton from the same growing region were used as a germplasm group to study the validity of different genetic distances in constructing cotton core subset. Mixed linear model approach was employed to unbiasedly predict genotypic values of 20 traits for eliminating the environmental effect. Six commonly used genetic distances (Euclidean, standardized Euclidean, Mahalanobis, city block, cosine and correlation distances) combining four commonly used hierarchical cluster methods (single distance, complete distance, unweighted pair-group average and Ward's methods) were used in the least distance stepwise sampling (LDSS) method for constructing different core subsets. The analyses of variance (ANOVA) of different evaluating parameters showed that the validities of cosine and correlation distances were inferior to those of Euclidean, standardized Euclidean, Mahalanobis and city block distances. Standardized Euclidean distance was slightly more effective than Euclidean, Mahalanobis and city block distances. The principal analysis validated standardized Euclidean distance in the course of constructing practical core subsets. The covariance matrix of accessions might be ill-conditioned when Mahalanobis distance was used to calculate genetic distance at low sampling percentages, which led to bias in small-sized core subset construction. The standardized Euclidean distance is recommended in core subset construction with LDSS method.

Relationships between ascitic bacterial DNA and plasma endotoxin, gut flora and intestinal permeability in cirrhotic patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the relationship of ascitic bacterial DNA and plasma endotoxin, intestinal permeability, gut flora in cirrhotic patients.</p><p><b>METHODS</b>Fifty-five decompensated cirrhotic patients with ascites were included in the study. A paracentesis was performed for every patient at admission and ascites fluid was collected for bacterial DNA isolation and amplification, plus other routine studies and cultured for aerobic and anaerobic bacteria. Plasma endotoxin, intestinal permeability, and gut flora were studied on the day following admission. Blood from the patients was obtained for routine hematologic, biochemical, and coagulation studies. Thirty healthy subjects were studied as normal controls.</p><p><b>RESULTS</b>No bacteria were found in the ascites cultures in the 55 patients, but bacterial DNA was found in 19 (34.55%). Compared with the bacterial DNA negative group, the bacterial DNA positive group showed a significantly lower level of PTA (t= -3.184, P=0.002), a higher Child-Pugh score (t=3.224, P=0.002) and a higher quantity of WBC in their ascitic fluid (t=4.088, P=0.001). Compared with normal controls, cirrhotic patients showed significantly higher levels of plasma endotoxin (t=13.705, P=0.000), lactulose/mannitol (L/M, t=28.568, P=0.000) in urine, and the quantity of enteric bacilli (t=2.912, P=0.005); the quantity of their intestinal bifidobacteria was significantly lower (t= -3.669, P=0.000). The variables correlative with the presence of bacterial DNA were the quantities of enteric bacilli (P=0.007) and PTA (P=0.011).</p><p><b>CONCLUSION</b>Intestinal bacterial overgrowth plays a key role in the pathogenesis of ascitic bacterial translocation (ABT) in cirrhotic patients. ABT is correlated with the degrees of the liver disease.</p>

The characteristic of severe acute pancreatitis and the selection of the therapeutic strategy / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the clinical character and therapeutic strategy and prognosis in severe acute pancreatitis.</p><p><b>METHODS</b>From January 2001 to December 2005, 783 patients with SAP were treated. Therapeutic strategy was selected based on the preliminary scheme for diagnosis and treatment of severe acute pancreatitis by pancreatic surgery society of CMA. All the patients were divided into biliary group and non-biliary group, while 375 patients in biliary group, with 182 patients treated operatively and 193 patients treated nonoperatively; and 408 patients in non-biliary group, with 147 patients treated operatively and 261 patients treated nonoperatively.</p><p><b>RESULTS</b>There were 698 survivals, the overall survival rate was 89.1%. 357 survivals in the biliary SAP group, the survival rate was 95.0%, in which 171 survivals from operation treated cases, with the survival rate of 94.0%, and 186 survivals from non-operation treated cases, with the survival rate of 96.4%; 341 survivals in the non-biliary SAP group, the survival rate was 84.0%, in which 110 survivals from operation treated cases, with the survival rate of 74.8%, and 231 survivals from non-operation treated cases, with the survival rate of 88.5%. 48.3% patients of the survival group had organ dysfunction, and 18.3% patients had multiple organ dysfunctions, while 100% patients of the death group had organ dysfunction, and 97.6% patients had multiple organ dysfunction. Respiratory dysfunction was found to be the most common cause totally followed by nerve system dysfunction and shock, with the rates of 26.3%, 11.7% and 10.3%, respectively. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are most commonly in death group, with the rate of 94.1%, 60.0% and 60.0%, respectively. The rate of fungi infection in the survival group and death group were 8.9% and 37.6%. The rates of alimentary tract fistula in the survival and death group were 0.9% and 14.1%, respectively.</p><p><b>CONCLUSIONS</b>The therapy aiming at the cause for biliary SAP and the operation aiming at infected pancreatic necrosis is helpful to improve curative rate; MODS is the main cause of death in severe acute pancreatitis. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are high risk factors.</p>

Effects of absorption enhancers on intestinal absorption of lumbrokinase / 药学学报

<p><b>AIM</b>To explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption.</p><p><b>METHODS</b>The absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo.</p><p><b>RESULTS</b>YJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD.</p><p><b>CONCLUSION</b>The results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.</p>

The in vitro cytotoxicity and in vivo toxicity of doxorubicin antiresistant stealth liposomes / 药学学报

<p><b>AIM</b>Multidrug resistance ( MDR) as a major obstacle to successful clinical cancer chemotherapy, searching a novel effective antiresistant drug would be necessary.</p><p><b>METHODS</b>A novel doxorubicin anti-resistant stealth liposomes (DARSLs) was prepared by co-encapsulating doxorubicin (DOX) and verapamil (VER) into stealth liposomes with ammonium sulfate gradient remote loading approach. In vitro cytotoxity of various DOX formulations and in vivo toxicity of DARSLs were evaluated using DOX-resistant rat prostate cancer cell line (MLLB2), human uterus sarcoma cell line (MES-SA/DX5) and normal SD rats, separately.</p><p><b>RESULTS</b>The DARSLs liposome suspensions mainly consisted of homogeneous large unilamellar vesicles (LUV) with average particle size of (118.1 +/- 22.3) nm. Encapsulation efficiencies of DOX and VER in DARSLs were more than 90% and about 70%, respectively, when the ratio of DOX/VER/Lipid was 1: 0.11 :10 (w/w/w). In vitro cytotoxicity tests of the DARSLs using rat prostate cancer cell line (MLLB2) and human uterus sarcoma cell line (MES-SA/DX5) showed that 5 micromol x L(-1) VER significantly reversed DOX-resistance of these 2 cell lines and DARSLs was the most effective on inhibition of DOX-resistant cell growth. Besides, compared to FDFV, much slower DOX distribution (confocal microscopy) to nuclei and cytoplasm in MLLB2 cells for DARSLs suggested that it might possess distinct mechanism of cytotoxicity. Systemic and cardiac toxicity evaluations in normal SD rats suggested that liposomal encapsulation could significantly improve the severe cardiotoxicity arising from simultanous administration of DOX and VER.</p><p><b>CONCLUSION</b>DARSLs is a novel anticancer liposome formulation with lower cardiotoxicity, effective drug-resistance reversal and intravenous injection.</p>