Objective To investigate the mechanism for rhein to improve the insulin sensitivity in diabetes mellitus. Methods Male Wistar rats were randomly divided into normal control group (NC,n=15) and diabetic group (DM,n=40) induced by STZ and high-fat diet.Diabetic rats were randomly divided into diabetic control group (DM-C,n=15) and diabetic group treated with rhein (DM-T,n=15).Then DM-T group was given intragastric administration with rhein at the dose of 100 mg/ (kg-1?d-1) for 11 weeks.FBG,fasting serum insulin (FIns),triglyceride (TG),total cholesterol (TC),insulin sensitivity index (ISI) and other biochemical parameters in each group were measured.The protein expressions of PPAR-? and GluT-4 were determined by immunohistochemistry and Western blot. Results At the end of the 17th week,compared with NC group,DM-C group showed higher FBG and TG,lower ISI,lower protein expressions of PPAR-? and GluT-4 in the adipose tissue.Compared with DM-C group,DM-T group showed lower FBG [(15.73?3.08 vs 22.57?3.23) mmol/l,P

ObjectiveTo investigate and analyze the current primary quality management situation in TCM clinical studies.Methods One sub-center unit from 39 projects of “Prevention and Treatment of Difficult and Complicated Disease of TCM” plan of the“11th Five-year National Key Technology R&D Program” was chosen. Executive condition of the primary quality control of each unit was under field investigation, and quality control quantitative evaluation indexes were used to conduct quantitative evaluation.Results Results were shown as the forms of statistical description and radar map. The average and median scores of primary quality management were 5.05 and 5.2, respectively. The best and preferable proportions of 39 units were 25.64% and 28.21%. Other 46.15% of these units performed poor. The problem mainly manifested on insufficient frequency and bad normalization of primary quality management, such as comprehensiveness and integrity of inspection contents, cases, problem recordings and problems timely feedback.ConclusionAlthough the primary quality management is widely conducted in TCM clinical studies, there are still some problems to be settled and improved.

This paper was aimed to analyze the correlation between quality evaluation and whole complete quality assessment in traditional Chinese medicine (TCM) clinical research progress,in order to discuss key steps and strategies in the clinical research progress.In accordance with the quality control indexes,all projects of Prevention and Treatment of Chronic Disease of TCM were given a research progress evaluation and complete condition.The scores were described with radar map method.The influence of research progress to whole complete quality was analyzed with correlation methods.The results showed that there was a significant correlation between research progress (including included cases and completed cases) and the total score of quality control (P ＜ 0.05).It was concluded that research progress was a key step to influence the entire clinical research level.It is necessary to strengthen the supervision on research progress to guarantee the whole research level.

Objective To predict the disease progression risks of healthy rhesus ( normal) and rhesus infected with simian immunodeficiency virus ( SIV) in the stages of long-term nonprogressor ( LTNP) , normal progressor ( NP) , rapid progressor ( RP) by discriminant analysis. Methods Five-year observation was carried out in SIV infected rhesus model without any intervention. The SIV infected rhesus model at the stages of LTNP, NP, RP were selected, 10 in each group, and T lymphocyte subsets and serum parameters for spleen-deficiency syndrome and kidney-deficiency syndrome in SIV infected rhesus were compared with 5 healthy monkey having the same survival time. The influence factors of different types of disease progression were screened from T cell subsets and Chinese medical syndrome indexes, and then the discriminant equation was established to predict the risks. Results White blood cell ( WBC) count and lymphocyte ( LYM) ratio were enrolled into the discriminant equation before infection, and T4 level and Log10RNA of set point were enrolled into the discriminant equation in the platform period. The test results for the uniform rate of the established discriminant function showed that the total coincidence rate of theoretic distinguish to the actual data was 57.1% , 91.2%respectively before infection and in the platform period. Conclusion The pre-infection WBC count and LYM ratio can be used as a reference for the evaluation of different types of disease progresson, and Log10RNA and T4 level at platform phase can be used as the predicting factors of different types of disease progression risk prediction.

Objective: To observe the effects of electroacupuncture (EA) pretreatment on motor function, cerebral blood flow, cerebral infarction volume, and vascular endothelial growth factor (VEGF) level in middle cerebral artery occlusion (MCAO) model rats. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into a normal group, a model group, and an EA group, with eight rats in each group. The middle cerebral artery ischemia-reperfusion model was established by the suture-occluded method in the model group and the EA group, while not in the normal group. The EA group was pretreated with EA at bilateral Fengchi (GB20) before model preparation, once a day for 30 min each time for a total of 7 d. The changes in the CatWalk gait parameters, modified Bederson neurological deficit score, cerebral blood flow, cerebral infarction volume after ischemia, and VEGF level in the brain tissue of rats in each group were observed. Results: Compared with the normal group, the modified Bederson neurological deficit score in the model group and the EA group increased after modeling (P<0.05), and the CatWalk gait parameters (one-leg stance duration, gait cadence, and gait cycle) were all changed (P<0.05). Compared with the model group, the modified Bederson neurological deficit score in the EA group decreased (P<0.05), and the CatWalk gait parameters improved (P<0.05). Immediately after ischemia, the cerebral blood flow in the normal group was greater than that in the model group and the EA group (P<0.05); after reperfusion, the cerebral blood flow in the EA group was greater than that in the model group (P<0.05). Compared with the normal group, the cerebral infarction volume in the model group and the EA group increased (P<0.05). Compared with the model group, the cerebral infarction volume in the EA group decreased (P<0.05). The expression level of VEGF-positive cells in the rat brain tissue in the model group was higher than that in the normal group (P<0.05), and was higher in the EA group than in the model group (P<0.05). Conclusion: EA pretreatment improves the limb motor function in MCAO model rats, alleviates the symptoms of neurological deficits, promotes the recovery of cerebral blood flow, reduces the cerebral infarction area after MCAO modeling, and increases the VEGF expression in the brain tissue.

Objective To investigate the effects of rhein on insulin sensitivity of diabetic rats induced by high fat feeding and low dose streptozotocin (STZ), and the possible mechanisms. Methods (1) Fifty-five Wistar rats were randomly divided into normal control group (NC,n=15) and diabetes group (DM, n=40). The NC rats were fed with regular chow and DM rats were fed with high fat diet. Five weeks later, the DM rats were injected with STZ 30 mg/kg once. The 30 diabetic rats were randomly divided into two subgroups, diabetic control group (DM-C) and diabetic group treated with rhein (DM-T). DM-T rats received intragastric administration of rhein and DM-C rats were given equal doses of solvent. All rats were sacrificed eleven weeks later, the blood sample was collected. The body weight, fasting blood glucose (FBG), HbA1C, triglycerides (TG), tolal cholesterol (TC), glycosylated serum protein (GSP) and Fasting insulin (FINS) concentrations were examined.The insulin sensitive index (ISI) and homeostasis model assessment for insulin resistance (HOMA-IR) werecalculated. (2) The PPART and GLUT-2 expression in hepatic tissue were detected by immunohistoehemistry and Western-blot. Results At the end of experiment the FBG [(22.57±3.23 vs 7.11±1.44) mmol/L,P<0.01],HbA1C[(12.49±1.96 vs 8.36±0.84)%, P<0.01], TG [(0.89±0.29 vs 0.58±0.17)nunoL/L,P<0.01],GSP [(57.29±4.14 vs 13.43±2.70)μmoL/L, P<0.01] and tumor necrosis factor-α [TNF-α,(1.365±0.133 vs 1.233±0.159) μg/L, P<0.05] and the liver weight index (0.032±0.004 vs 0.024±0.002, P<0.01) in DM-C rats were higher than those in NC rats. Besides, the ISI of DM-C rats decreased [In(ISI),-5.46±0.61 vs -4.81±0.75, P<0.05] and HOMA-IR elevated [In(HOMA-IR),2.34±0.64 vs 1.70±0.78,P<0.05]. The expression of PPARγ [11 131.7(5 723.1-18 979.4) vs 48 782.1(21 576.7-108 829.5), P<0.01] and GLUT-2 (0.98±0.35 vs 1.29±0.27, P<0.05) of DM-C rats decreased markedly compared with NC rats. Compared with DM-C rats, FBG [(15.94±3.16) mmol/L], HbA1C[(10.51±1.74)%], GSP[(47-31±6.09) μmol/L] in DM-T and the In (HOMA-IR), (1.86±0.30) rats decreased (P<0.05 or P<0.01), and In (ISI), of DM-T rats increased (-4.97±0.29, P<0.05). The expressions of PPARγ [35 156.3(24 554.3-86 660.9)] and GLUT-2 (1.55±0.55) of DM-T rats were up-regulated markedly compared with DM-C rats (P<0.05 or P<0.01). Conclusion Rhein decreased FBG, HbA1C and GSP, and improved the insulin sensitivity in diabetic rats, which might be related to the up-regulated expressions of PPARγ and GLUT-2 in hepatic tissue.

Objective:To investigate the effect of butyrate produced by bacterial metabolism on immune features of murine bone marrow-derived dendritic cells(BMDCs) and its potential mechanisms.Methods: BMDCs were prepared from bone marrow cells of C57BL/6 mice by being cultured with GM-CSF and IL-4.The expression of CD80,CD86,B7-DC and MHCⅡ on BMDCs and its pri-ming ability on the proliferation of OVA257-264 antigen specific CD8+T cell were analyzed by using Flow cytometry.The mRNA levels of IL-6 and IL-12 in BMDCs were detected by real-time fluorescence quantitative PCR(q-PCR).Simultaneously,Griess reaction and Western blot was used for analyzing the levels of NO2-in BMDCs culture supernatant and the ERK phosphortylation in BMDCs respectivly.Results:Butyrate could decrease the levels of CD80,CD86,MHCⅡand B7-DC,and downregulate the capability of BMDCs in priming the proliferation of CD8+T cells.Furthermore,the secretions of IL-6,IL-12,NO2-and the phosphorylation of ERK were sup-pressed.Conclusion:Butyrate down-regulats the immune functions of BMDCs via inhibition of ERK phosphorylation in TLR 4 signaling pathway.

Objective To explore the value of diffusion tensor imaging (DTI)-metrics (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, AD and radial diffusivity, RD) in assessing the neonatal neurobehavioral development. Methods From November 2010 to September 2017, 101 neonates (gestational age range, 30-42 weeks;male/female, 69/32) with no abnormalities on conventional MRI were retrospectively included. DTI scalar maps (FA, MD, AD and RD) were calculated by using FMRIB's diffusion toolbox. The tract-based spatial statistics (TBSS) was used to investigate the relationships between white matter (WM) DTI-metrics and neurobehavioral scores (i.e. behavioral and active tone). Automated fiber quantification (AFQ) was used to extract the CST (corticospinal tract), OR (optic radiation), AR (auditory radiation) and thal-PSC (thalamus-primary somatosensory cortex); Pearson correlation was further used to explore the relationships between neurobehavioral scores and DTI-metrics along the four tracts. Results TBSS results indicated that behavior scores showed significant correlations with DTI-metrics in almost the whole WM, e. g. corpus callosum, CST, OR, AR and etc (P<0.05, TFCE-FWE corrected). Significant correlations of active tone with MD, AD and RD were just observed in local WM regions, i. e. cerebral peduncle, anterior and posterior limb of internal capsule (P<0.05, TFCE-FWE corrected); while FA just showed boundary significant correlations in the above regions (P=0.055, TFCE-FWE corrected). AFQ results indicated that DTI-metrics along the almost entire CST, OR and thal-PSC showed significant correlations with behavior scores (P<0.05); while significant correlations mainly located in the initial and middle segments of AR (P<0.05). For active tone, significant correlations were only observed in the initial and middle segments of CST. Conclusions Neonatal brain WM DTI-metrics in specific sensorimotor regions, to a certain extent, could reflect the corresponding neurobehavior abilities, suggesting the potential value of DTI in assessing the neonatal neurodevelopment.

Objective:To summarize the clinical features of developmental epileptic encephalopathy children with DNM1 gene variants. Methods:The genotypes and clinical features of 15 children with DNM1 variants related epilepsy in the Department of Pediatrics, Peking University First Hospital from June 2017 to October 2021 were retrospectively analyzed. Results:A total of 8 male and 7 female epilepsy patients with DNM1 gene variants with the age of seizure onset ranging from 15 days to 22 months were recruited, median age was 8 months.All cases belonged to de novo heterozygous variants of the DNM1 gene, including 13 cases of missense variants, 1 case of frame shift variant and 1 case of nonsense variant, 8 cases of ectopic sites have not been reported.Multiple seizure types were observed, including epileptic spasms in 15 patients, focal seizure in 9 patients, atypical absence seizure in 2 patients and tonic seizure in 2 patients.There were various types of seizures in 7 children.Nine cases occurred as infantile spasm for the first time.All 15 patients showed varied degrees of development delay, among them, 11 cases had developmental retardation before epilepsy.Three patients had slow rhythm of electroencephalogram background activity, the electroencephalography showed hypsarrhythmia in 13 patients; clinical seizures were detected in 8 cases, among them, epileptic spasms were captured in 7 patients, tonic seizure was captured in 1 patient.Widened frontotemporal subarachnoid space, cerebral atrophy, and corpus callosum dysplasia were examined in 6, 2 and 3 patients by cranial magnetic resonance imaging, respectively.All 15 cases were diagnosed as developmental epileptic encephalopathy, of which 13 cases were consistent with infantile spasms.The age of the last follow-up ranged from 1 year old to 7 years old.After multi-antiepileptic drug treatment, 2 patients were remission, 1 patient(small size of identical twins) died of severe pneumonia at the age of 2 years, and 12 patients still had intermittent seizures, of which 1 patient was transformed from infantile spasms to Lennox-Gastaut syndrome. Conclusions:The onset age of developmental epileptic encephalopathy caused by the DNM1 gene variant usually begins in the infantile period, the peak onset age was 8 months.The main types of seizures include epileptic spasms and focal seizures, developmental retardation can occur before seizures.The clinical manifestations are mostly infantile spasms syndrome, and some children can be transformed into Lennox-Gastaut syndrome.

Objective To study the brain functional connectivity(FC)changes in patients with normal tension glau-coma(NTG)and healthy volunteers using FC technique of resting-state functional magnetic resonance imaging(rs-fMRI)based on V1 region seed point(ROI),so as to explore the pathogenesis and early diagnosis of NTG.Methods Fourteen NTG patients(NTG group)who met the inclusion criteria and 14 healthy controls(HCs group)were enrolled.The clinical data of all subjects were collected,and rs-fMRI was performed in both groups.The magnetic resonance data was pre-pro-cessed by software,and bilateral A1 regions were taken as the ROI to analyze their correction with the whole brain voxel time series and obtain the FC value between the ROI and the whole brain by comparison of FC values in resting state be-tween the groups.Pearson correlation analysis was used to explore the relationship between FC value in the brain regions with significant differences with the ROI and clinical variables in the NTG group.Results Compared with the subjects in the HCs group,there were no statistically significant differences in age,gender,body weight,cup-disc ratio and 24 h mean intraocular pressure of patients in the NTG group(all P＞0.05),and there were statistically significant differences in the best corrected visual acuity(BCVA)of both eyes and peripapillary retinal nerve fiber layer thickness(RNFLT)(all P＜0.05).The Pearson correlation analysis showed that FC value of the brain regions with abnormal FC to V1 region were cor-related with RNFLT in the NTG group(P＜0.05).ROI1-left superior frontal gyrus,ROI1-right superior frontal gyrus,ROI2-left cingulate gyrus and ROI2-right middle frontal gyrus were significantly positively correlated with RNFLT(all P＜0.05).Compared with the HCs group,the brain regions with reduced FC to the right ROI in the NTG group were the left superior frontal gyrus and right superior frontal gyrus;the brain regions with reduced FC to the left ROI were the left cingulate gyrus and right middle frontal gyrus.Conclusion Compared to healthy individuals,NTG patients have significant changes in the functional connections between certain specific brain regions and V1 region,including bilateral superior frontal gyrus,left cingulate gyrus,and middle frontal gyrus.The changes in brain functional activity may be caused by visual dysfunction caused by NTG,leading to functional impairment of the visual and cognitive emotion processing brain regions,which may be one of the potential neuropathological mechanisms in NTG patients.