Depending on the meaning and function of the liver in traditional Chinese medicine and modern medicine,this paper explores the important role of liver in the pathogenesis of DM (Diabetes Mellitus,DM).Combined with treatment based on syndrome differentiation and specific case report study,this paper has stressed the importance of treating DM from liver and so to set a sound basis for the systemic treatment based on syndrome differentiation from internal organs for DM.

AIM To observe the effect of sodium orthovanadate on glucose and maltose absorption and to reveal its mechanism. METHODS ① Normal Wistar rats were divided into 6 groups at random, 0 9% NaCl group, acarbose group(30 mg?kg -1 ) and sodium orthovanadate high dose(16 mg?kg -1 ), middle dose (4 mg?kg -1 ) and low dose (1 mg?kg -1 )groups. The values of blood glucose of all the groups were measured with oxidation enzyme method after administration of glucose and maltose. ② The ? glucosidase was abstracted from the upper small intestine and the inhibitory effect of sodium orthovanadate on ? glucosidase was examined. RESULTS ① Sodium orthovanadate could delay the peak values of plasma glucose induced by glucose, with AUC in these groups lower than that in controls, that is (8 42?0 63) mmol?h -1 ?L -1 ( P

Objective To explore the effects of morroniside on the expression of CD34 in ipsilateral cortex of rats after focal cerebral isch-emia-reperfusion. Methods 45 male Sprague-Dawley rats were divided into sham group (n=9), ischemia group (n=9), and morroniside groups (low, medium and high dosage groups, n=9). The middle cerebral artery were occluded for 30 minutes, and reperfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg, 270 mg/kg after operation. The expression of CD34 in the isch-emic ipsilateral cortex were detected with immunohistochemistry (n=6) and Western blotting (n=3) 7 days after operation. Results The ex-pression of CD34 increased in the ischemia group compared with the sham group, and further increased in the morroniside groups of high dos-age compared with the ischemia group (F>14.865, P<0.001). Conclusion Morroniside could increase the expression of CD34 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, which may promote the angiogenesis and neurogenesis after ischemia.

The unmet clinical needs of patients with rare diseases persist.Many rare diseases lack effec-tive treatments,and drug development for rare diseases faces greater challenges than that for common multiple diseases.In recent years,the concept of"patient-centered"drug development has been widely adopted.The Center for Drug Evaluation(CDE)of the National Medical Products Administration has successively issued a series of relevant guiding principles,such as the Technical Guidelines for the Implementation of Patient-Centered Clinical Trials,to promote a"patient-centered"drug development model.The implementation of the"patient-centered"approach in rare disease drug research and development,with a focus on patient perspectives and ac-tive engagement,can effectively facilitate a comprehensive understanding of rare diseases and patient needs among drug research and development enterprises,researchers,and regulatory agencies.This approach also en-hances the accuracy and efficiency of rare disease drug research and development.The CDE will continue to pri-oritize the integration of the"patient-centered"concept into rare disease drug research and development,effec-tively enhance the involvement of rare patients in the drug research and development process,and leverage the guiding role of patients'perspectives on drug research and development.

BACKGROUNDIntense exercise can cause injury and apoptosis, but few studies have reported its effect on the central nervous system (CNS). The initial reason for hippocampus injury is the excitotoxicity of glutamate and calcium overload. Intracellular free Ca(2+) ([Ca(2+)]i) overload may trigger the apoptosis pathway and neuron damage. The aim of this study was to investigate whether intense exercise could cause hippocampus apoptosis and neuron damage and then to determine which pathway was activated by this apoptosis.

METHODSWe used one bout of swimming exhaustion rats as models. Intracellular [Ca(2+)]i was measured to estimate the calcium overload by Fura-2/AM immediately after exhaustion; glial fibrillary acidic protein (GFAP) and synaptophysin (SYP) immunofluorescence were performed for estimating astrocyte activation and synapse plasticity 24 hours after exhaustion. Apoptosis cells were displayed using dUTP nick end labelling (TUNEL) stain; endoplasmic reticulum (ER) stress-induced apoptosis pathway and mitochondrial apoptosis pathway were synchronously detected by Western blotting.

RESULTSAn increasing level of intracellular [Ca(2+)]i (P < 0.01) was found in the hippocampus immediately after exhaustion. GFAP and SYP immunofluorescence showed that the astrocytes are activated, and the synapse plasticity collapsed significantly 24 hours after exhaustion. TUNEL stain showed that the number of apoptosis cells were notably raised (P < 0.01); Western blotting of the apoptosis pathway showed increasing levels of caspase-3 cleavage (P < 0.01), Bax (P < 0.01), caspase-12 cleavage (P < 0.01), C/EBP-homologous protein (CHOP) (P < 0.01), and phospho-Junaminoterminal kinases (p-JNK; P < 0.01) and decreasing level of Bcl-2 (P < 0.01). Our results proved that exhaustion can induce hippocampus injury and apoptosis by [Ca(2+)]i overload, with collapsed synaptic plasticity as the injury pattern and ER stress-induced apoptosis as the activated pathway.

CONCLUSIONIntense exercise can cause excessive apoptosis and synapse plasticity damage in the hippocampus with [Ca(2+)]i overload as the initial reason, and thus provides leads for therapeutic interventions in the brain health of athletes.

Animals ; Apoptosis ; physiology ; Blotting, Western ; Calcium ; metabolism ; Endoplasmic Reticulum Stress ; physiology ; Glial Fibrillary Acidic Protein ; metabolism ; Hippocampus ; metabolism ; In Situ Nick-End Labeling ; Male ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Synaptophysin ; metabolism

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

The incidence of each of the rare disease is very low. The complexity and diagnosis difficulty of the rare disease lead to the difficulties in the clinical research and development (R&D) of drugs for rare diseases. There is an urgent clinical need for the drug development of rare diseases in China. Encouraging R&D of new drugs, particularly the innovative drugs with China's own independent intellectural property is the basis for solving the predicament in drug shortage in China.. In order to further improve the efficiency of clinical R&D of drugs for rare diseases, the National Medical Products Administration (NMPA), Center for Drug Evaluation (CDE) issued Technical Guidance for Clinical Research and Development of Drugs for Rare Diseases. This is the first guidance for rare diseases in China that is drafted from the standpoint of the clinical technology research and development.The guidance is the scientifitc thinking and framework for the drug developing enterprises to research and develop drugs for rare disease efficiently and appropriately by following drug developing protocols and relating to the special features of rare disease.This paper presents the concepts and rationale in the guidance for the appraisal of rare disease drug research and development.