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ObjectiveTo observe the intervention effect of Huaiqihuang granules （HQH） on immunoglobulin A vasculitis nephritis （IgAVN） mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group， an IgAVN model group， a dexamethasone group （2.5 mg·kg-1·d-1）， a low-dose HQH group （4 g·kg-1·d-1）， and a high-dose HQH group （8 g·kg-1·d-1）. The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling， the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein （24 h UTP）， urine β2-microglobulin （β2-MG）， serum total protein， albumin， IgA， etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 （Th17） cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α （AMPKα）， phosphorylated AMPKα （p-AMPKα）， acetyl-CoA carboxylase 1 （ACC1）， and phosphorylated ACC1 （p-ACC1） in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group， the IgAVN model group showed significant increases in 24 h UTP， urine β2-MG， total cholesterol （P<0.05）， serum interleukin-17 （IL-17）， IgA， Th17 proportion in the spleen cell suspension， and IL-17 expression in the spleen tissue （P<0.01）， and significantly decreased serum total protein， albumin， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.01）. Compared with the IgAVN model group， in the 4th week， the 24 h UTP， urine β2-MG， serum IL-17， IgA levels， and renal IgA deposition were significantly reduced in each treatment group （P<0.01）， and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased （P<0.05， P<0.01）. Serum albumin levels significantly increased （P<0.05）. Compared with the IgAVN model group， the dexamethasone group and the high-dose HQH group showed increases in serum total protein （P<0.01）， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.05， P<0.01）. The high-dose HQH group showed a significant decrease in total cholesterol level （P<0.05）. Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway， correcting immune inflammatory disorders， and exerting therapeutic effects on IgAVN.
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The development of medical research is completed by the cooperation of sponsors, investigators, subjects, and ethics committees. Clinically, it mainly includes clinical trials of medical devices, clinical medicine and new technology research. This paper analyzed the game and the relationship between rights, responsibilities and interests of relevant parties in medical research, combined with the relevant costs and sharing principles involved in medical research, and found that the use of the word "free" in the informed consent is easy to cause misunderstanding and the lack of relevant compensation costs in the informed consent, while the compensation and insurance costs had some problems, such as the imperfect subject compensation mechanism and the insufficient insurance purchase by the sponsor, which can not protect the basic rights and interests of the subjects. Therefore, in order to standardize the cost management of clinical medical research, it is necessary to standardize the process and content of informed consent, strengthen the supervision of medical research process, establish medical research damage compensation fund and research damage insurance system, so as to better protect the rights and interests of subjects.
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As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.
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With the continuous progress of medical technology, some violations of ethical principles often occur in science experimental research targeting humans. Taking the type of human experimental research as the starting point, through ethical analysis and evaluation of different types of human experimental research, this paper concluded that in human experimental research, it was necessary to adhere to humanitarian principles of human experimental research, fully respect the research participants’ right to informed consent, select research participants fairly, fully protect the research participants’ rights and interests, and supervise the whole research process. So as to better regulate the behavior of medical researchers in human experimental research and protect the rights and interests of research participants.
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The development of medical research is completed by the cooperation of sponsors, investigators, subjects, and ethics committees. Clinically, it mainly includes clinical trials of medical devices, clinical medicine and new technology research. This paper analyzed the game and the relationship between rights, responsibilities and interests of relevant parties in medical research, combined with the relevant costs and sharing principles involved in medical research, and found that the use of the word "free" in the informed consent is easy to cause misunderstanding and the lack of relevant compensation costs in the informed consent, while the compensation and insurance costs had some problems, such as the imperfect subject compensation mechanism and the insufficient insurance purchase by the sponsor, which can not protect the basic rights and interests of the subjects. Therefore, in order to standardize the cost management of clinical medical research, it is necessary to standardize the process and content of informed consent, strengthen the supervision of medical research process, establish medical research damage compensation fund and research damage insurance system, so as to better protect the rights and interests of subjects.