基于“态靶辨证”分析葛根芩连汤加减在早中期糖尿病肾病的治疗作用

“态靶辨证”之“态”为整体证候及特征,“靶”为疾病具体的症状或异常指标。从“态”来看,热邪在早中期DKD的发生发展中发挥了主要作用。从“靶”来看,早中期DKD的临床表现、病理特征及理化指标等亦体现了热邪的致病作用。“态靶结合”以葛根芩连汤清内热,根据病情的轻重、症状变化及理化指标等加黄芪、水蛭、大黄,水蛭用量多为3~6 g,大黄常用剂量为3~15 g,对于素体亏虚、年老体弱等不耐重剂之人,宜从小量开始。对于部分存在出血倾向的患者来说,水蛭亦当慎用甚至禁服,可少量代替选用桃仁、红花等药性平和之品。

Preparation and Analysis of Fe3O4 Magnetic Nanoparticles Used as Targeted-drug Carriers

Fe3O4 magnetic nanoparticles were prepared by the aqueous co-precipitation of FeCl3-6H2O and FeCl2-4H2O with addition of ammonium hydroxide. The conditions for the preparation of Fe3O4 magnetic nanoparticles were optimized, and Fe3O4 magnetic nanoparticles obtained were characterized systematically by means of transmission electron microscope （TEM）, dynamic laser scattering analyzer （DLS） and X-ray diffraction （XRD）. The results revealed that the magnetic nanoparticles were cubic shaped and dispersive, with narrow size distribution and average diameter of 11.4 nm. It was found that the homogeneous variation of pH value in the solution via the control on the dropping rate of aqueous ammonia played a critical role in size distribution. The magnetic response of the product in the magnetic field was also analyzed and evaluated carefully. A 32.6 mT magnetic field which is produced by four ferromagnets was found to be sufficient to excite the dipole moments of 0.05 g Fe3O4 powder 2 cm far away from the ferromagnets. In conclusion, the Fe3O4 magnetic nanoparticles with excellent properties were competent for the magnetic carders of targeted-drug in future application.

Signaling pathway/molecular targets and new targeted agents under development in hepatocellular carcinoma

Advances in molecular cell biology over the last de- cade have clarified the mechanisms involved in can- cer growth, invasion, and metastasis, and enabled the development of molecular-targeted agents. To date, sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase 111 randomized controlled trials, and has been approved worldwide. Phase 111 clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are ongoing. Those agents target the vascular endothelial growth factor, platelet-derived growth factor receptors, as well as target the epidermal growth factor receptor, insulin- like growth factor receptor and mammalian target of rapamycin, in addition to other molecules targeting other components of the signal transduction pathways. In addition, the combination of sorafenib with standard treatment, such as resection, ablation, transarterial em- bolization, and hepatic arterial infusion chemotherapy are ongoing. This review outlines the main pathways involved in the development and progression of hepato- cellular carcinoma and the new agents that target these pathways. Finally, the current statuses of clinical trials of new agents or combination therapy with sorafenib and standard treatment will also be discussed.

Recent advances in lymphatic targeted drug delivery system for tumor metastasis

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

Role of taxanes in pancreatic cancer

Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.

Research development of the relationship between thymidine phosphorylase expression and colorectal carcinoma

Thymidine phosphorylase (TP) is a key enzyme that contributes to the composition and decomposition of pyrimidine nucleotides. TP seems homologous to platelet-derived endothelial cell growth factor, and its effects on inducing vascularization and anti-apoptosis are closely related to growth and metastasis of colorectal carcinoma. In addition, TP is a key enzyme that catalyzes the transformation from 5-fluorouracil (FU) prodrugs of 5′-deoxy-5-fluorouridine (5′- DFUR) to 5-FU. The activity of TP is closely related to the sensitivity of colorectal carcinoma cells to fluorouracil drugs and targeted therapy. Given the important functions of TP in growth, metastasis, tumor treatment, and prognosis, determining its expression mechanism is significant. This article summarizes the research development of TP expression in colorectal carcinoma, tumor neovascularization, cytotoxicity activation of 5′-DFUR, and colorectal carcinoma therapy.

In Vitro Inhibition of β-Hematin by 2, 4-Diamino-6- Mercaptopyrimidine ＆ 2-Mercaptopyrimidine

Malaria is a disease that has drawn worldwide attention due to the alarming rise of mortality rates particularly in third world countries. During the Plasmodium parasite intraerythrocytic life cycle, metabolic processes include the formation of hemozoin or malaria pigment. This pigment functions in the prevention of oxygen radical-mediated damage to the parasite. Drugs targeting hemozoin formation such as chloroquine and amodaquine are effective and are still used, but recently Plasmodium parasites have become resistant to these drugs, especially against chloroquine. In this study we looked at the potential use of two heterocyclic pyrimidine derivatives as anti-malaria drugs; 2,4-Diamino-6-Mercaptopyrimidine （DAMP） and 2-Mercaptopyrimidine （2-MP）. These compounds bear various coordination sites that enable them to react with metal ions to form coordination compounds. We used two methods for testing the inhibition of ferriprotoporphyrin IX （FP） biomineralisation： semi-quantitative microassay used by Deharo, and a quantitative assay used by G. Blaner and M. Akkawi. We report here the finding that （DAMP） has an in vitro inhibitory effect on I%hematin formation at concentrations and magnitude of nearly similar order to that of chloroquine, 2-MP was found to be effective but to a lower degree than DAMP.

Research progression of PD-1/PD-L1 in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite great progress in the development of target agents, most people who do not harbor a mutation do not benefit from these agents. Immunotherapy, which stimulates the body's immune system to improve the anti-tumor immunity effect, is a new therapeutic method for non-small cell lung cancer(NSCLC). Programmed cell death 1(PD-1) and its ligand(PD-L1) belong to the CD28/B7 immunoglobulin super-family and are co-stimulatory molecules that show negative regulation effects. Combined with its ligand, PD-1 can modulate the tumor microenvironment, enabling tumor cells to escape host immune surveillance and elimination and play a key role in the clinical significance of NSCLC. An increasing number of clinical trials have suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies, are beneficial and safe for NSCLC. Here, we review the brief history of PD-L1 as a biomarker, mechanism of action, and critical role of PD-1/PD-L1 in the treatment of NSCLC as well as the current research status and future directions.

Research progress in nanoparticles as anticancer drug carrier

Nanoparticles drug delivery system has sustained and controlled release features as well as targeted drug delivery, which can change the characteristics of drug distribution in vivo. It can increase the stability of the drug and enhance drug bioavailability. The selective targeting of nanoparticles can be achieved through enhanced permeability and retention effect and a conjugated specific ligand or through the effects of physiological conditions, such as pH and temperature. Nanoparticles can be prepared by using a wide range of materials and can be used to encapsulate chemotherapeutic agents to reduce toxicity, which can be used for imaging, therapy, and diagnosis. In this research, recent progress on nanoparticles as a targeted drug delivery system will be reviewed, including positive-targeting, negative-targeting, and physicochemical-targeting used as anticancer drug carriers.

Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

DNA G-quadruplex and its potential as anticancer drug target

G-quadruplex secondary structures are four-stranded globular nucleic acid structures form in the specific DNA and RNA G-rich sequences with biological significance such as human telomeres,oncogene-promoter regions,replication initiation sites,and 5′and 3′-untranslated(UTR)regions.The non-canonical G-quadruplex secondary structures can readily form under physiologically relevant ionic conditions and are considered to be new molecular target for cancer therapeutics.This review discusses the essential progress in our lab related to the structures and functions of biologically relevant DNA G-quadruplexes in human gene promoters and telomeres,and the opportunities presented for the development of G-quadruplex-targeted smallmolecule drugs.

Therapeutic radionuclides in nuclear medicine: current and future prospects

The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131（^131I）, phosphorous-32（^32P）, strontium-90（^90Sr）, and yttrium-90（^90Y）, have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

Co-delivery of paclitaxel and gemcitabine via folic acid-conjugated polymeric multi-drug nanoparticles (FA-PMDNPs) for the treatment of breast cancer

Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA-PMDNPs)consisting of poly-L-lysine(PLL)and poly glutamic-conjugated PTX/GEM(PGA-PTX and PGA-GEM)for FA receptor-targeted synergistic breast cancer therapy.The carboxyl-rich structure of PGA provided plenty reaction sites and negative charge for drug loading.Transmission electron microscopy(TEM)results showed that FA-PMDNPs had uniform particle size and spherical morphology.The hemolysis study proved that FA-PMDNPs had good biocompatibility.In vitro cell viability and in vivo studies showed that FA-PMDNPs more effectively inhibited the proliferation of FA receptor(FR)-overexpressing breast cancer cells(4T1)than the pure drugs.Consequently,these results demonstrated that FA-PMDNPs could be effectively targeted at cancer cells compared with free drugs,indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.