The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Abnormal Metabolic Connectivity in Rats at the Acute Stage of Ischemic Stroke / 神经科学通报·英文版

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.

Innovative Analysis on KY3H Health Care Service Model / 世界科学技术-中医药现代化

Vigorously development of the health service industry has received great attention,but the health service industry faces many difficulties.By analyzing the current predicament,this paper put forward the KY3H health care service model and systematically analyzed its six innovations:from "disease as the center" to "health as the center",from "homogenized group health service" to "Personalized and Humanized Health Service",from "Extensive Health Service"to "Precise Intervention of Individual Health Status",from "Single Health Service" to "Trinity Service of Health,Culture,Health Management and Health Insurance",from the "seeking medical" service model to "seeking one's own"service model,as well as from the "fixed (fixed-time,fixed-point,fixed-mode) service" to "anytime,anywhere full-time service".This model has achieved initial success in practice.It is an important way to solve the dilemma.

The Key Problems and Technology Strategies of KY3H Health Care Service Model / 世界科学技术-中医药现代化

KY3H is a traditional Chinese medicine health care service mode based on the existing problem,focusing on an interconnected and continuous integration of four key technological innovation,which promotes the service model transformation from passive "doctor-searching" to "asking yourself ".There are four features on KY3H mode.First,based on traditional Chinese medicine meridian and viscera theory,it can accurately identify the health status and take risk assessment of individuals through digital quantitative model.Then,the mode realizes the personalized health status recognition and precisious intervention through integrated technology products of dynamic monitoring and identification,assessment and intervention with independent intellectual property rights.The third is to improve the intelligence,realtime and accessibility of KY3H health care services through developing the Chinese-western medicine informationalized software system about health status identification,assessment and intervention.The last one is formulating traditional Chinese medicine health care standards,industry standards and service package design,which drive KY3H health service model spreading effectively and practical applying,achieving remarkable social and economic benefits.

Construction of KY3H Health Care Service Model / 世界科学技术-中医药现代化

This paper systematically summarized the core problems in the field of medical and health services and did the root analysis.It is concluded that the current domestic and international related medical service modes deviated from the essence of health services and led to difficulties in the idea and method,bringing people to new problems and new crises.KY3H health care service model,set innovative ideas,innovative technical methods,innovative products,innovative processes,standards and standards into one,by providing a full range and the whole cycle of people-oriented,self-help,"diagnosis and treatment of security" integration of health careservice,improve people's health status,fundamentally change the traditional passive "seeking medical treatment" service mode,to active "seeking one's own" health service mode,so as to achieve "health status continues to rise,the medical costs continue to decline,"which is the social development aims.The paper systematically analyzes the idea,operational logic,goal,mode structure,characteristics of the model,and its significance to individuals,industries,society,countries and even the international community in order to make a positive contribution to the healthy development strategy in China and provide a Chinese case for global Health.

Researches of Electroacupuncture for Cognitive Function and Histopathology in Alzheimer's Disease Model (review) / 中国康复理论与实践

@#With the development of aging population, the morbidity of Alzheimer's disease (AD) is increasing. Electroacupuncture on several acupoints, especially Baihui (GV20), may improve the cognitive function, brain morphology, and reduceβ-amyloid deposition and tau protein phosphorylation, in AD models.

Learning and Memory Deficit and Demyelination of Corpus Callosum in APP/PS1 Transgenic Mice / 中国康复理论与实践

Objective To investigate the relationship between learning and memory deficit and demyelination of the corpus callosum in twelve-month old APP/PS1 transgenic mice. Methods Twelve twelve-month old APP/PS1 transgenic mice were as AD group, and age-matched wild type (WT) littermates were as WT group. Learning and memory ability was tested with Morris water maze, and the mor-phology of nerve fiber of corpus callosum was detected with Luxol Fast Blue staining. Immunohistochemistry was used to detect myelin ba-sic protein (MBP) in the corpus callosum. Thioflavine S staining was used to detect amyloid plaque in the corpus callosum. Results Com-pared with WT group, the latency increased (Z>2.873, P<0.01) and the times crossing the location of the platform decreased (t=-7.339, P<0.001) in AD group. The nerve fibers were sparse and disorganized, with a lot of vacuoles in the corpus callosum of AD group. The positive expression of MBP in the corpus callosum was significantly decreased (t=-4.481, P<0.001) in AD group compared with WT group. There were amyloid plaques in the corpus callosum of AD group. Conclusion Twelve-month old APP/PS1 transgenic mice exhibit learning and memory deficit, which may be attributed to the deposition of the amyloid plaque mediated demyelinated injury of the corpus callosum.

Effects of Electroacupuncture at Baihui and Shenting on Learning-memory Function and Ultrastructure in Hip-pocampal CA1 in Cerebral Ischmeia-reperfusion Rats / 中国康复理论与实践

Objective To observe the effect of electroacupuncture at Baihui (GV20) and Shenting (GV24) on learning-memory function and ultrastructure in hippocampal CA1 region of rats after cerebral ischmeia-reperfusion. Methods A total of 25 male Sprague-Dawley rats were randomly divided into sham group (n=6) and operation group (n=19). The operation group was occluded the left middle cerebral arter-ies with modified Longa's methods for 90 minutes and reperfused, and twelve qualified rats of them were randomly divided into model group (n=6) and electroacupuncture group (n=6), the later accepted electroacupuncture at Baihui and Shenting for seven days. They were as-sessed with Longa's scores, and tested with Barnes maze. Their cerebral infarct volume was tested with magnetic resonance imaging T2-weighted image. The ultrastructure of synapse in hippocampal CA1 region was observed with transmission electron microscope. Results Compared with the model group, the Longa's score improved (P<0.05), the infarct volume decreased (P<0.01), the average escape latency decreased (P<0.01) and the times entering the wrong hole decreased (P<0.001) in the electroacupuncture group. Under the transmission elec-tron microscope, the number of synapse decreased in the model group, with the structure damage and vesicles sparse;compared with the model group, the number of synapse increased in the electroacupuncture group, with clear and complete structure and rich vesicles. Conclu-sion Electroacupuncture at Baihui and Shenting can improve the learning-memory function in rats after cerebral ischmeia-reperfusion, which may relate to improvement of synaptic plasticity and ameliorating ultrastructure in hippocampal CA1 region.

Effects of Electroacupuncture on Nerve Bundle of Motor Cortex and Striatum in Rats with Ischemic Stroke:Observed with Diffusion Tensor Imaging / 中国康复理论与实践

@#Objective To explore the effect of electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on motor behaviors, the axonal integrity and nerve bundle of motor cortex and striatum in rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) using diffusion tensor imaging (DTI). Methods Thirty-six adult male Sprague-Dawley rats were randomly assigned to sham opera-tion group (sham group), ischemia control group (model group) and electroacupuncture treatment group (EA group) with twelve rats in each group. The later two groups were occluded their middle cerebral arteries for two hours. Twenty-four hours after modeling, EA group re-ceived electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on the paralyzed limb, once a day, for 14 days. They were assessed with modified Neurological Severity Scores (mNSS) and Rota-rod test, and scanned with small animal magnetic resonance imaging system for T2-weighted image (T2WI) and DTI, the infarct size, related fractional anisotropy (rFA) and related number of tracks of motor cortex and striatum were recorded. Results Compared with the sham group, the score of mNSS increased in the model group and EA group after model-ing, and was lower in EA group than in the model group seven days and 14 days after intervention (P<0.05). Rota-rod test showed that the retention time was significantly longer in EA group than in the model group (P<0.05). T2WI showed that the infarct size was smaller in EA group than in the model group (P<0.05). DTI showed that rFA in motor cortex and striatum was higher in EA group than in the model group (P<0.05), as well as the related number of tracks (P<0.05) in motor cortex. Conclusion Electroacupuncture at Quchi and Zusanli acupoints could improve the motor function in rats with ischemic stroke, which may be related to the recovery of nerve bundle of motor cortex and stri-atum in ischemic side.

White Matter Damages in Alzheimer's Disease Found with Diffusion Tensor Imaging (review) / 中国康复理论与实践

Diffusion tensor imaging (DTI) can detect the integrity of white matter in vivo, through which various white matter damages of the brains have been found in patients with Alzheimer's disease (AD), even mild cognitive impairment. These damages of white matter may relate to the impairment of cognitive function, otherwise, damages in various area may result in various clinical features. DTI may fur-ther be used in the study of AD development and therapeutic evaluation.

Role of Microglia Polarization in Alzheimer's Disease and Association to Electroacupuncture (review) / 中国康复理论与实践

There are two phenotypes of microglia, M1 and M2. Microglia in M2 polarization may associate with the phagorytosis of be-ta-amyloid and inhibition of Tau hyperphosphorylation, as well as in other pathology. Electroacupuncture can impact the phenotypes of mi-croglia, which may play a role in the treatment for Alzheimer's disease.

Effects of acupuncture on the expression of P2X receptors in the hippocampus of mice with a telomerase gene knocked out / 中华物理医学与康复杂志

Objective To observe the expression of P2X receptors in the hippocampus of telomerase gene knockout mice after acupuncturing the bilateral ST36 acupoints.Methods Eighteen telomerase gene knockout homozygous mice were randomly divided into a blank control group (group A),a manual acupuncture group (group B) and an electric acupuncture group (group C),each of 6.Group A was not given any intervention,while groups B and C were provided with manual or electric acupuncture at point ST36 for 7 days.The expression of P2X receptors and cAMP response element bound protein (CREB) in the hippocampus were observed and compared among the 3 groups.Results The expression of P2X4 in the hippocampus was not significantly different among the 3 groups in groups B and C decreased significantly compared with group A,but there were no significant differences between group Bs and C.The expression of CREB in group C decreased significantly compared with groups A and B.Conclusion EA inhibits the expression of P2X4 receptor and CREB the hippocampus.The signaling pathway may play an important role in the mechanism of action of acupuncture in neurodegenerative diseases.

Effects of Electroacupuncture on Differentiation of Neural Stem Cells after Cerebral Ischemia-reperfusion in Rats / 中国康复理论与实践

Objective To explore the effect of electroacupuncture at Quchi (LI11), Zusanli (ST36) on differentiation of neural stem cells after cerebral ischemia-reperfusion in rats. Methods Thirty-six male Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and electroacupuncture group (n=12). The latter two groups were occluded the left middle cerebral arteries for 90 min-utes and reperfused. The electroacupuncture group received electroacupuncture at Quchi and Zusanli acupoints for 21 days. They were evalu-ated with modified Neurological Severity Scores 7, 14 and 21 days after electroacupuncture. Their infarct volumes were tested with MRI T2WI 21 days after electroacupuncture, while the differentiation of neural stem cells was observed with double-immunopositive BrdU/Dcx and BrdU/NeuN. Results Compared with the model group, the neurological deficits score improved in the electroacupuncture group in all the time points (P<0.05). The infarct volumes decreased in the electroacupuncture group (P<0.05), with less number of BrdU+/Dcx+cells in subventricular zone (P<0.001) and more number of BrdU+/NeuN+ cells in peri-infarct cortex (P<0.001) 21 days after electroacupuncture. Conclusion Electroacupuncture at Quchi and Zusanli acupoints can improve neurological function and decrease the infarct volumes in rats after cerebral ischemia-reperfusion, which may be associated with promoting differentiation of neural stem cells to neurons.

Mechanism of unilateral spatial neglect after stroke based on functional magnetic resonance imaging technique / 实用医学杂志

Objective To explore the mechanism of brain function connection (FC) by observing the changes of unilateral spatial neglect (USN) and non-USN patients, using functional magnetic resonance imaging technique (fMRI). Methods 8 USN and 8 control patients participated in the study and fMRI data were collected. The data was analyzed by independent component analysis method. Results USN group showed increased FC in the left frontal/temporal lobeas well and decreased FC in the right cingulate gyrus, precuneus, temporalgyrus compared with control group. These were highly related to behavioral scores. Conclusions Abnormal brain function connection may be related to USN. The findings were helpful for understanding the potential mechanism underlying of USN.

Relationship between Injury Sites, Pathological Types and Attention in Post Stroke Cognitive Impairment / 中国康复理论与实践

Objective To study the relationship between injury site (right or left) or pathological type (hemorrhage or infarct) and atten-tion impairment in post stroke cognitive impairment (PSCI). Methods June, 2014 to June 2015, 49 patients with PSCI were assessed with Test of Attentional Performance (TAP) within 1 week of admission. The reaction time and the numbers of correct response were recorded. Results The reaction time of alertness (with or without alarm) was shorter in the patients with left infarction (Z=-2.32, t=-3.76, P2.32, t=-3.10, P<0.05). Conclusion A trend of lateralization was found in patients with PSCI, rather than in the pathology.

Effects of Electroacupuncture at Shenting and Baihui on Learning and Memory, and Expression of Cyclic AMP Response Element Binding Protein and Phosphorylation in Rats with Cerebral Ischemia-reperfusion / 中国康复理论与实践

@#Objective To explore the effects of electroacupuncture at Shenting (DU24) and Baihui (DU20) on cognitive dysfunction after stroke. Methods Forty-five Sprague-Dawley rats were randomly divided into control group (n=15), model group (n=15) and electroacupuncture group (n=15). The latter two groups were occluded their middle cerebral artery for two hours and reperfused. The electroacupuncture group accepted electroacupuncture at Shenting and Baihui 24 hours after modeling for seven days. They were assessed with Morris water maze once a day since the second day of intervention. Their brains were stained with TTC staining to measure cerebral infarction volume after treatment, while the expression of cyclic AMP response element binding protein (CREB) and phosphorylation (p-CREB) in hippocampal CA1 area were detected with immunohistochemistry. Results The escape latency and swimming distance of place navigation shortened in the electroacupuncture group compared with those in the model group (P<0.05) from the fourth day of intervention. The number of cross platform of spatial probe increased (P<0.05). The infarction volume was less in the electroacupuncture group than in the model group (P< 0.05), with increased expression of CREB and p-CREB in hippocampal CA1 area (P<0.05). Conclusion Electroacupuncture at Shenting and Baihui can increase the expression of CREB and phosphorylation in hippocampal CA1 area in rats after cerebral ischemia-reperfusion, to protect the neurons from ischemia and improve the learning and memory function.

Effects of Electroacupuncture at Baihui (DU20) on Learning and Memory and Expression of Brain-derived Neu-rotrophic Factor in APP/PS1 Double-transgenic Mice / 中国康复理论与实践

Objective To explore the effects of electroacupuncture at Baihui (DU20) acupoint on learning and memory and its possible mechanism through the expression of brain-derived neurotrophic factor (BDNF) in APP/PS1 double-transgenic mice. Methods 30 female APP/PS1 double transgenic mice were randomly divided into model group, DU20 group and non-acupoint group, and 10 wild type mice con-sisted of wild group. DU20 group received electroacupuncture at Baihui and the non-acupoint group received electroacupuncture at non-acu-point for 28 days. Learning and memory was tested by Morris water maze. Deposition ofβ-amyloid (Aβ) peptide was determined by immu-nohistochemical staining. The expression of BDNF in cortex was examined by RT-PCR and Western blotting. Results Compared with the model group, DU20 group ameliorated the learning and memory ability of APP/PS1 double-transgenic mice (P0.05). Conclusion Electroacupuncture at DU20 acupoint could ameliorate learning and memory in APP/PS1 double-transgenic mice. The mechanism may be related to increase the expression of BDNF and decrease the deposition of Aβ.

Effects of Electroacupuncture on Learning and Memory Ability and RhoA expression in Rats after Cerebral Ischemic-reperfusion / 中国康复理论与实践

Objective To explore the effects of electroacupuncture at Shenting (DU24) and Baihui (DU20) on learning and memory abil-ity in the cerebral ischemia-reperfusion rats and its possible mechanism. Methods 45 male Sprague-Dawley rats were randomly divided into sham group (n=15), ischemia group (n=15) and electroacupuncture group (n=15). The latter 2 groups were modeled as focal cerebral isch-emia-reperfusion injury, and the electroacupuncture group received electroacupuncture at Shenting (DU24) and Baihui (DU20) for 7 days. They were tested with Morris Water Maze, observed with Nissl's staining. The protein expression of RhoA was detected with Western blot-ting. Results The learning and memory ability improved in the electroacupuncture group (P<0.05), the injury of the neurons reduced (P<0.05) and the expression of RhoA in hippocampus decreased compared with the ischemia group (P<0.05). Conclusion Electroacupuncture could ameliorate the learning and memory ability in ischemia-reperfusion rats, which may relate with the inhibition of the expression of RhoA in hippocampus.

Advance in Cerebellum's Involvement in Cognition (review) / 中国康复理论与实践

@#Cognitive function is an important part of non-motor function of the cerebellum. The cerebellum is involved in cognition and has a variety of cognitive functions, including working memory function, language function, spatial cognitive function (spatial processing and spatial memory), and temporal cognitive function (time perception and time processing), etc. This article reviewed recent advances in these aspects of cognitive function of the cerebellum.

Effects of Electroacupuncture on Activation of Microglia in Peri-infarct Cortex of Cerebral Ischemia-reperfusion Injury Rats / 中国康复理论与实践

@#Objective To explore the effect of electroacupuncture on activation of microglia in peri-infarct cortex after cerebral isch-emia-reperfusion in rats. Methods 36 male Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and electroacupuncture group (n=12). The latter two groups were occluded the left middle cerebral arteries with modified Longa's method for 2 hours and reperfused. The electroacupuncture group received electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints for 3 days. The nerve cell damage in peri-infarct cortex was observed with HE staining, while the expression of ED1 was determined with immunohisto-chemical staining, and the expression of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and IL-6 were determined with Western blotting. Results The neurological deficits score improved significantly in the electroacupuncture group (P<0.05), with less nerve cell dam-age, less number of ED1 positive microglia (P<0.05) and less levels of TNF-α, IL-1βand IL-6 (P<0.05), compared with the model group. Conclusion The electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints can protect brain from ischemia-reperfusion injury, which might be associated with inhibiting the microglial activation and proinflammatory response in peri-infarct cortex.