Small interfering RNAs (siRNAs) are an emerging class of RNA interference (RNAi) therapeutics with unique pharmacokinetic properties. Five siRNA drugs based on two delivery systems have been approved, and an increasing number of siRNA drugs have already moved to the clinical study phase. Physiologically-based pharmacokinetic (PBPK) modeling is a useful tool and has been demonstrated to have wide ranging utility in drug development and regulatory review. However, PBPK modeling is still in its infancy in guiding the development of siRNA-based drugs in the context of its widespread use in small and large molecule areas. This article reviews the pharmacokinetic profiles of siRNA drugs, outlines the current state of PBPK model building in siRNA drug development, and describes the key parameters required for model building. This article provides insights into the future applications of PBPK models and for optimizing the key parameters when building the model for siRNA drug development.

As a tubulin stabilizer, taxanes are widely used in the treatment of breast cancer, ovarian cancer, non-small-cell lung cancer (NSCLC),and part of head and neck malignant tumors, and were confirmed to be significantly effective.However, taxanes-induced peripheral neuropathy(TIPN) still affects the quality of life and psychological status of patients to varying degrees, severe cases can lead to dose reduction, and even chemotherapy interruption.In this paper, we summarize the pathogenesis, risk factors, clinical assessment, the progress of prevention and treatment of TIPN, to provide the basis for the prediction and early prevention of TIPN in the clinical administration, thus we can improve patients’ quality of life while extending their survival.

Objective:To observe the clinical effect of marzulene-S granules combined with phloroglucinol injections in the treat-ment of pregnant women with acute gastritis. Methods:Totally 102 cases of pregnant women with acute gastritis were randomly as-signed into two groups with 51 cases in each. The control group was treated with marzulene-S granules 30min before meals with warm water,0. 67g,tid,and the observation group was additionally given phloroglucinol injection 80 mg in 0. 9% sodium chloride injections 20ml,ivd,qd. The treatment course was 2 weeks. The clinical curative effect of the two groups was observed before and after the treat-ment,and the symptom score changes and symptom remission time were compared as well. Results:The effective rate of the observa-tion group was significantly higher than that of the control group(94. 12% vs 78. 43%,P<0. 05). After the treatment,the integral of epigastric pain,belching and dry mouth in the observation group was decreased significantly than that before the treatment(P<0. 05), and significantly lower than that in the control group(P<0. 05). The time of abdominal pain was(1. 8+0. 4)d and(3. 9+1. 1)d in the observation group and the control group,respectively,and the difference was statistically significant(P<0. 05). üo serious ad-verse reactions were found in the two groups. Conclusion:Marzulene-S granules combined with phloroglucinol injections in the treat-ment of pregnant women with acute gastritis is effective.

ObjectiveTo investigate the effect of transforming growth factor-β1 (TGF-β1) antibody on peripheral neural fibrosis after chronic entrapment.MethodsA total of 75 rats were randomly divided into three groups, ie, Group A (sham operation, only the sciatic nerve exposed), Group B (compression only, treated with sciatic nerve entrapment) and Group C (compression plus antibody injection).Electron microscopy, immunohistoehemistry, RT-PCR and Western blot were performed to observe the morphological changes of the compressed nerve tissue and to determine the level of TGF-β1 , collagen Ⅰ and collagen Ⅲ at 2, 4, 6, 8, 10 weeks after sciatic nerve compression, respectively.Results The levels of TGF-β1 , types Ⅰ and Ⅲ collagen protein were increased significantly in the Group B compared with that in the Group A, when the expression of TGF-β1 was increased in the early phase of the compression, reached the peak at the 4th week, and then decreased slowly.The expressions of collagenⅠand collagen Ⅲ were increased after compression, reached a peak at the 6th week and then maintained a relatively high level.The number of the fibrous tissues was decreased significantly and the content of types Ⅰ and Ⅲ collagen protein declined in the Group C, with statistical difference compared with the Group B (P ＜ 0.05).ConclusionsPeripheral nerve fibrosis can be caused by chronic nerve compression.TGF-β1 plays an important role in effectively inhibiting the collagen synthesis and ameliorating the nervous fibrosis of the protein following peripheral nervous entrapment.

Objective To investigate the effects of connective tissue growth factor (CTGF) on the chronic peripheral nerve compression injury and explore the function of CTGF in peripheral nerve compression injury and repair. Methods From July 2010 to September 2010, fifty aduh male SD rats were randomly divided into group A and B: group A (sham-operated group): only exposed the sciatic nerve; group B (compression group): undergone sciatic nerve entrapment operation on the right hind leg according to the method which Mackinnon adopted when he established the model of chronic sciatic nerve compression.Electron microscopy,immunohistochemistry,RT-PCR and Western-blot were performed to observe the morphological changes of the compressed nerve tissue and to determine the level of CTGF,collagen- Ⅰ,Ⅲ (COL- Ⅰ,Ⅲ),2,4,6,8,10 weeks after the surgery,respectively. Results After sciatic nerve compression,the collagen in nerve increased ; The expression of CTGF and COL- Ⅰ, Ⅲ in sciatic nerve of compressed group increased, which was statistically different compared with the sham-operation group (P ＜ 0.05); In the meanwhile,the contents of CTGF and COL- Ⅰ,Ⅲ were positively correlated in a certain period. Conclusion Peripheral nerve fibrosis can be caused by chronic nerve compression.The expression of COL- Ⅰ,Ⅲ in sciatic nerve increased and CTGF get involved in the pathophysiological process, which suggests that CTGF plays an important role in the process of neural injury and fibrosis.

Objective To investigate the distribution of carbapenemase-resistant genes carried by multi-drug resistant Acineto-bacter baumannii .Methods 80 strains of multi-drug resistant Acinetobacter baumannii were collected .Polymerase chain reaction (PCR)wasusedtodetectcarbapenemase-resistantgenes,suchasOXA-23,OXA-24,OXA-51,OXA-58,SIM,IMP,VIM ,GIMand SPM ,in multi-drug resistant Acinetobacter baumannii .Results Drug resistant gene OXA-23 [49 (61 .3% )] ,OXA-51 [73 (91 .3% )] ,OXA-58[7(8 .8% )] ,OXA-24[1(1 .3% )] ,IMP[17(21 .3% )] and VIM[2(2 .5% )] were found in 80 strains of multi-drug resistant Acinetobacter baumannii ,while GIM ,SIM and SPM gene were not found .Conclusion IMP ,OXA ,VIM is the main genotypes carried by multi-drug resistant Acinetobacter baumannii .

In order to have a better understanding of the role of medical library in medical information service during the implementation of Healthy China strategy,the need of health information service of the public and medical scientific researchers in implementation of Healthy China strategy were analyzed by outlining the development history and major targets of Healthy China strategy,and how to meet the requirements of the development of Healthy China for medical library was studies,namely by improving its resources development,service patterns and staff construction according to the present situation of big data development,the challenges medical library is faced in users needs,resources,platform,space,professionals and funds,and the opportunities brought about by the expanding requirements,improving information academic level,advancing new technologies,favorable policies and environments with relevant suggestions put forward.

ObjectiveTo investigate the clinical efficacy of vastus medialisoblique enhancement plus electroacupuncture intervention in treating patellar chondromalacia.MethodFifty-two patients meeting the inclusion criteria were randomly allocated to a treatment group of 32 cases and a control group of 20 cases. The treatmentgroup received vastus medialis oblique enhancement plus electroacupuncture intervention and the control group, electroacupuncture intervention alone. Both groups were treated once daily, 10 times as a course, for four consecutive courses. The Visual Analogue Scale (VAS) score was counted in the two groups before and after treatment. The clinical therapeutic effects were evaluated in the two groups.ResultThe VAS score improved significantly in both groups of patients after treatment compared with before(P<0.05). It improved significantly more in the treatment group than in the control group (P<0.05). The cure rate and the total efficacy rate were 37.5% and 96.9%, respectively, in the treatment group, which were higher than a cure rate of 20.0% and a total efficacy rate of 75.0% in the control group, respectively. ConclusionVastus medialis oblique enhancement plus electroacupuncture intervention can improve the clinical symptom of pain more markedly and heighten the clinical therapeutic effect in patients with patellar chondromalacia. Its effect is better than that of electroacupuncture intervention alone.

Aged ; Biomarkers ; blood ; Cobalt ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; Myocardial Ischemia ; diagnosis ; Serum Albumin ; metabolism ; Spectrophotometry

Radiopharmaceutical is an essential component of nuclear medicine and molecular imaging, as well as a key component of precision medicine. The United States Food and Drug Administration (FDA) has recently approved the marketing of several peptide-based radiopharmaceuticals, sparking a global trend of research in this area and propelling nuclear medicine into the precision theranostic era. This has created a new wave of technological competition in the field of nuclear medicine. It is the responsibility of Chinese scientists in the radiopharmaceutical field to capitalize on this opportunity, leverage the momentum, and strengthen their independent innovation capability in order to stay ahead in the future global nuclear science and technology competition. This review provides an overview of the remarkable progress made in the research, development, and translation of global peptide-based radiopharmaceuticals. It examines the advantages of peptide-based radiopharmaceuticals and outlines the current hot targets and progress in drug development in this field. Additionally, it proposes six opportunities for China to overtake others in the field of peptide-based radiopharmaceuticals and achieve technological self-reliance, based on interdisciplinary collaboration and independent innovation. Lastly, the future prospect of peptide-based radiopharmaceuticals is discussed.