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Background The process of initiating and completing clinical drug trials in hospital settings is highly complex, with numerous institutional, technical, and record-keeping barriers. In this study, we independently developed an integrated clinical trial management system (CTMS) designed to comprehensively optimize the process management of clinical trials. The CTMS includes system development methods, efficient integration with external business systems, terminology, and standardization protocols, as well as data security and privacy protection. Methods The development process proceeded through four stages, including demand analysis and problem collection, system design, system development and testing, system trial operation, and training the whole hospital to operate the system. The integrated CTMS comprises three modules: project approval and review management, clinical trial operations management, and background management modules. These are divided into seven subsystems and 59 internal processes, realizing all the functions necessary to comprehensively perform the process management of clinical trials. Efficient data integration is realized through extract-transform-load, message queue, and remote procedure call services with external systems such as the hospital information system (HIS), laboratory information system (LIS), electronic medical record (EMR), and clinical data repository (CDR). Data security is ensured by adopting corresponding policies for data storage and data access. Privacy protection complies with laws and regulations and de-identifies sensitive patient information. Results The integrated CTMS was successfully developed in September 2015 and updated to version 4.2.5 in March 2021. During this period, 1388 study projects were accepted, 43,051 electronic data stored, and 12,144 subjects recruited in the First Affiliated Hospital, Zhejiang University School of Medicine. Conclusion The developed integrated CTMS realizes the data management of the entire clinical trials process, providing basic conditions for the efficient, high-quality, and standardized operation of clinical trials.

pH-sensitive smart polymeric nanocarriers have been under development in the field of biomedicine due to permeabilization the physiological barriers readily to address the limitation of conventional chemotherapeutics delivery systems of low intracellular transport and targeting efficiency. Where traditional polymers kept stable under physiological neutral or acidic conditions, pH-sensitive polymeric nanocarriers underwent rapid degradation with a labile group in tumor acidic environment (around 5.0–6.0), allowing these biomaterials to achieve controlled drug release, drug pharmacokinetics improvement and antitumor biotherapeutic molecules efficiency enhancement compared with traditional polymers. This review mainly concentrated on properties of pH-sensitive polymers for biomedical purposes to construct the smart drug delivery system based on acid liable linkers which were categorized into pH-sensitive polymeric prodrugs composed of antitumor drugs (doxorubicin and paclitaxel) bounded to the polymer via acid liable linkers and pH-sensitive copolymeric nanocarriers prepared by block copolymers containing polymer blocks linked with acid-cleavable groups. Besides, advanced platforms in biomedicine for special biotherapeutic molecules delivery were reviewed in the article. Furthermore, several acid-sensitive linkages were reviewed to study the mechanism of the controlled pH-responsive drug delivery, such as hydrazone, acetal, cis-aconityl linker and β-thioether ester, as well as improvement of drug pharmacokinetics.

AKT serves as an epigenetic modulator that links epigenetic regulation to cell survival and proliferation while the epigenetic mediator OCT4 critically controls stem cell pluripotency and self-renewal. Emerging evidence indicated their complicated interplays in cancer cells and cancer stem cells (CSCs), and inhibiting either one may activate the other. Thus, in this study, we propose a strategy to targeting both factors simultaneously. Firstly, a combination of an OCT4-specific shRNA and the specific AKT inhibitor Akti-1/2 potently suppressed the propagation of human embryonal carcinoma cells, adherent cancer cells and stem-like cancer cells, establishing the proof-of-concept that dual inhibiting OCT4 and AKT can effectively target various cancer cells. Next, we combined Akti-1/2 with metformin, a widely-prescribed drug for treating type 2 diabetes, which was reported to down-regulate OCT4 expression. The metformin + Akti-1/2 combo significantly altered multiple signaling and epigenetic pathways, induced growth arrest and cell death of adherent and stem-like glioblastoma U87 cells, and attenuated their tumorigenicity in vivo. Taken together, we demonstrate here that simultaneously targeting an epigenetic mediator and an epigenetic modulator, by dual inhibiting OCT4 and AKT, can have significantly improved efficacies over single treatment in suppressing the propagation of CSCs as well as the entire bulk of differentiated cancer cells.

With the widespread applicability of the Wireless Sensor Networks (WSN), localization of nodes is becoming more and more essential because of the invalidity of the massages without localization information. An algorithm called Weighted Centroid Localization (WCL) provides a simple method to localize the unknown nodes. The algorithm obtains the localization of unknown nodes by averaging the coordinates of their anchor nodes whose positions are inherently known. To improve the localization accuracy, WCL introduces the weights to attract the estimated position to approach the anchor node which has more influence, but its accuracy still has some margin for improvement. So some algorithms are presented to improve the accuracy of WCL and the modified-WCL (MWCL) algorithm is an efficient algorithm. Based on MWCL, WCL with difference of estimated distances (WCL-DED) is presented in this paper which further improves the accuracy.

No prior study has examined the effect of intravenous injection of bone marrow mononuclear cells (MNCs) on myocardial infarction size (IS). We tested the hypothesis that transplantation of MNCs decreases IS through the release of vascular endothelial growth factor (VEGF). Immediately after ligation of the left coronary artery of immunodeficient mice, PBS or MNCs were intravenously administered. Myocardial IS was significantly less in MNCs-treated mice than in PBS-treated mice. Trace experiments showed accumulation of exogenously administered MNCs into the vicinity of infarcted myocardium. Injection of MNCs did not affect capillary density after infarction, but did reduced myocardial cell apoptosis. Blockade of VEGF by a neutralizing antibody or by gene transfer of a soluble form of Flt-1 VEGF receptor diminished the IS-limiting effects of MNCs. In conclusion, injection of MNCs can reduce myocardial IS through the release of VEGF. The MNC therapy for acute myocardial infarction might improve prognosis of patients with myocardial infarction.