ObjectiveTo explore the effects and mechanisms of Naotai Formula （脑泰方） against white matter lesions associated with cerebrovascular disease via Wnt/β-catenin pathway. MethodsTen WKY rats were used as sham surgery group， and 30 spontaneously hypertensive rats （SHRs） were randomly divided into model group， low-and high-dose Naotai Formula group， with 10 rats in each group. In addition to the sham surgery group， rats in each group were modelled by dorsum subcutaneous injection of D-galactose for 56 days， by performing bilateral common carotid artery stenosis on the 29th day of modelling with low perfusion for 28 days to construct the rat models of cerebral small-vessel disease with composite risk factors. The rats in the low- and high-dose Naotai Formula groups were given 9 and 27 g/（kg·d） of Naotai Formula by gavage on the day after surgery， and 10 ml/（kg·d） of pure water by gavage in the sham surgery group and the model group， with all rats in each group gavaged for 4 weeks. Blood pressure of rats was monitored weekly before and after medication administration； water maze experiments were performed for 6 consecutive days from the 50th day of modelling； and changes in cerebral blood flow were detected by laser scattering preoperatively， postoperatively， and after medication administration. The samples were taken on the next day after the last gavage， and the extent of myelin damage in the rat corpus callosum was observed by Lucas fast blue （LFB） and transmission electron microscopy， and the levels of interleukin 1β （IL-1β）， tumour necrosis factor α （TNF-α）， interleukin 10 （IL-10）， and tumour necrosis factor β （TNF-β） were detected by ELISA， and the levels of expression of myelin basic protein （MBP） and ionized calcium binding adaptor molecule 1 （IBA1）， neuroglial antigen 2 （NG2）， cell proliferation marker Ki67 antigen （MBP）， and cell proliferation marker Ki67 antigen （Ki67A）/NG2， 2'，3'- cyclic-nucleotide 3'-phosphodiesterase （CNPase） expression were measured by immunofluorescence. MBP in the corpus callosum， wingless MMTV integration site family member 3a （Wnt3a）， phosphorylated glycogen synthase kinase 3β （p-GSK-3β）， glycogen synthase kinase 3β （GSK-3β）， phosphorylated β-catenin （p-β-catenin）， β-catenin expression were detected by western blotting， and GSK-3β， β-catenin mRNA expression in the corpus callosum were detected by RT-qPCR. ResultsCompared with the sham surgery group， rats in the model group had elevated systolic blood pressure at all time points， decreased the number of traversing platforms and the percentage of time spent in the target quadrant in the water maze experiments， significantly prolonged the evasion latency on days 4 and 5， and decreased cerebral blood flow in the postoperative period and after medication administration （P＜0.05 or P＜0.01）； significant myelin sheath damage in the corpus callosum was seen by LFB staining and transmission electron microscopy； the callus had significantly higher levels of TNF-α and IL-1β content increased， TNF-β content decreased， MBP fluorescence intensity and protein expression decreased， the number of IBA1-positive cells increased， Wnt3a and p-GSK-3β/GSK-3β values increased， p-β-catenin/β-catenin values decreased， GSK-3β mRNA expression decreased， and β-catenin mRNA expression increased （P＜0.05 or P＜0.01）. Compared with the model group， the myelin sheath damage of corpus callosum in rats in the high-dose Naotai Formula groups was significantly improved， and all of the above indexes were significantly improved （P＜0.05 or P＜0.01）. Compared with the low-dose Naotai Formula group， myelin damage in the corpus callosum of the high-dose Naotai Formula group was improved， systolic blood pressure reduced， cerebral blood flow and MBP fluorescence intensity and protein expression in the corpus callosum， the number of positive cells for NG2 and CNPase， the values of p-β-catenin/β-catenin and GSK-3β mRNA expression increased， and the expression of Wnt3a， p-GSK-3β/ GSK-3β values and β-catenin mRNA expression decreased （P＜0.05 or P＜0.01）. ConclusionsHigh-dose Naotai Formula can significantly improve white matter lesions in cerebral small vessel disease， and the mechanism may be related to the inhibition of the Wnt/β-catenin signalling pathway， reducing the inflammatory microenvironment in the brain， and promoting the differentiation of oligodendrocyte precursor cells into oligodendrocytes.

Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

Objective: To explore the molecular mechanism of Taoren-Honghua herb pair (THP) on syndrome of bloodstasis based on the network pharmacology. Methods: We collected THP's compounds from traditional Chinese Medicinedatabases and input them into Pharm Mapper to get their potential targets, and collected the known targets of compoundsby Scifinder. Then we did KEGG-pathway analysis by DAVID database. Finally draw and analyze the network byCytoscape by information above. Results: Seventeen compounds of THP acquired 74 known targets, which was associatedwith four modules: improving the hemodynamics, anticoagulation, anti-inflammation, regulating apoptosis andproliferation. We also got 317 potential targets through PharmMapper and got 128 signaling pathway through pathwayenrichment including 39 disease-related pathways, 25 endocrine-related pathways, 11 immune-related pathways and soon. Conclusion: The four modules of the known target are exactly related to the four characteristics of the syndrome ofblood stasis. The potential targets and the 128 signal pathways involve a variety of pathophysiological processes of thesyndrome of blood stasis. These reflect the molecular mechanism of THP intervention in the syndrome of blood stasis

Intracerebral Hemorrhage (ICH) is a common cerebrovascular disease with high disability rate and high mortality rate.A large number of clinical and experimental studies have shown that the abnormal metabolism of iron in the brain tissue around the hematoma after ICH is an important cause of secondary brain damage such as brain edema and neuronal apoptosis.It is an important factor affecting the outcome of patients.This article reviews the abnormal metabolism of iron and its significance after ICH.

Objective To understand the cognition of patients with anxiety disorder and their inner experience and disease,and provide reference and basis for making more perfect health education. Methods A group of 38 patients with hospitalized anxiety were interviewed by collective focus interview. The interview was conducted by using the team skill training model to create a pleasant atmosphere. Results Five subjects of periods were identified, including the denial period of disease, the period of inner pain,the period of worrying about side effects of drugs,and the expectation period of disease cure. Conclusions The lack of awareness of disease and the desire for disease-related knowledge are very urgent. Through this study, we understand the psychological characteristics and needs of some patients with anxiety, and explore a set of patients who are suitable for anxiety of the mission model to provide some reference.

Aim To investigate the effects of Naotai formula extract(NTE)on the expression of heme oxygenase-1(HO-1) and hephaestin(Heph) in hippocampus of rats after cerebral ischemia/reperfusion by Keap1-Nrf2/ARE signaling pathway.Methods Eighty rats were randomly divided into five groups as follows: sham operation group(Sham), cerebral ischemia/reperfusion group(I/R), low dose group of NTE(4.5 g·kg-1), middle dose group of NTE (9 g·kg-1) and high dose group of NTE(18 g·kg-1).Rats were pretreated by intragastric administration for three consecutive days, and then subjected to middle cerebral artery occlusion (MCAO) 2 hours before reperfusion.The rats were administered with intragastric administration for two days.After cerebral ischemia reperfusion 72 hours, the behavioral activity of rats was recorded by Zea Longa neurological score, and the infarct volume was measured by TTC staining.The expressions of Nrf2, HO-1 and Heph in hippocampus of cerebral ischemia reperfusion rats were observed by real-time quantitative PCR and Western blot, respectively.Results Compared with model group, the neurobehavioral scores significantly decreased in NTE high-dose and middle-dose groups (P<0.01);the infarct volume of NTE groups markedly decreased (P<0.01);the expression of HO-1 mRNA apparently increased (P<0.05) in NTE groups;the expression of Heph mRNA significantly increased in NTE middle-dose and high-dose groups (P<0.05);the expression of Nrf2 and Heph protein evidently increased in the NTE middle and high dose groups (P<0.05, P<0.01);and the expression of HO-1 protein also increased in NTE groups(P<0.01).Conclusions Naotai formula can relieve cerebral ischemia-reperfusion injury.The mechanism might be associated with activating Keap1-Nrf2/ARE signaling pathways, promoting HO-1 generation, advancing the expression of Heph, and then reducing brain iron deposition, to achieve the protection of neurons after cerebral ischemia-reperfusion.

Objective: To establish a method for determining the content of dracorhodin as an indicator in the quality control with methodological studies to provide basis for the preparation process study of Qilisan gel. Methods: An HPLC method was used with a DiamonsilR C18 (250 mm ×4. 6 mm, 5 μm) column, the detection wavelength was set at 440 nm and the column temperature was 30 ℃. Acetonitrile-0. 05 mol·L-1 sodium dihydrogen phosphate solution (45 ∶ 55) was used as the mobile phase, and the flow rate was l. 0 ml·min-1 . Results: The content of dracorhodin was in a good linear relationship (r =0. 999 6) within the range of 1. 632-64. 250 μg·ml-1 , and the average recovery was 99. 02%(RSD =0. 77%, n =6). The number of theoretical plates was calculated as 7 100 according to the dracorhodin perchlorate peak without any interference from the negative sample. Conclusion: The method is objective, accurate and sensitive with high reliability, easy operation and fast process. The measurement results can be used as the quality control basis for the preparation process study of Qilisan gel.

Objective To observe the regularities of distribution of TCM syndrome types and correlation between TCM syndrome types and cardiovascular prognosis risk factors of elderly hypertensive patients in three different urban and rural communities.Methods Totally 299 elderly hypertensive patients who conformed to the hypertensive diagnostic criteria from 896 respondents which participated in the health monitoring questionnaire drafted by health management team of China Academy of Chinese Medical Sciences were screened. The syndrome types were differentiated according to Guiding Principle of Clinical Research on New Drugs of Traditional Chinese Medicine (for Trial Implementation). The levels of some risk indicators, such as blood glucose, blood lipid, CREA, ET, Hcy and mALB were measured by radioimmunoassay, enzymatic cycling assay and other methods. Age, gender, BMI and pulse pressure were recorded.Results The TCM syndrome types of 299 elderly hypertensive patients were deficiency of yin and yang type (74 cases), hyperactivity of yang due to yin deficiency type (65 cases), blood stasis syndrome type (62 cases), stagnation of phlegm-dampness type (61 cases), hyperactivity of liver-fire type (37 cases). Single factor analysis showed that there existed statistical significance among BMI, FBG, GHbA1c, CREA, TC, LDL-C, ET, Hcy and mALB in the 5 TCM syndromes (P<0.05,P<0.01), and the statistical significance was more apparent in the stagnation of phlegm-dampness type, blood stasis syndrome type and hyperactivity of yang due to yin deficiency type. Discriminant analysis showed BMI and Hcy have certain reference value for the diagnosis of TCM syndrome types in elderly hypertensive patients. Binary-Logistic regression analysis showed that the course of disease had a positive correlation with syndrome of deficiency of yin and yang.Conclusion Compared with other types of elderly hepertensive patients, stagnation of phlegm-dampness type and blood stasis syndrome type are more closely related to hypertension cardiovascular prognosis risk factors.

This systematic review was aimed to evaluation the effectiveness and safety of supplementingqi and activating blood circulation prescriptions in the treatment of cerebral ischemic stroke. Dtabases both at home and abroad were electronically searched for randomized controlled trials (RCTs) on supplementingqi and activating blood circulation prescriptions in the treatment of cerebral ischemic stroke. And meta-analyses were performed using RevMan 5.0 software. The results showed that 27 studies were included, which contained 2 908 cases. There were 1 490 cases in the treatment group, and 1 418 cases in the control group. The results of meta-analyses indicated that supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had significant differences in the effective rate for cerebral ischemic stroke compared with the single using of routine treatment of modern medicine with significant difference (OR = 5.39, 95%CI (4.03, 7.22),P < 0.000 01). The treatment of supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had better treatment effect on neurological function defects for cerebral ischemic stroke compared with the single using of routine treatment of modern medicine with significant difference (WMD = -2.99, 95%CI (-3.26, -2.72),P < 0.000 01). In addition, the treatment of supplementingqi and activating blood circulation prescriptions combined with routine treatment of modern medicine had better treatment effect on improving the activity of daily living (WMD = 9.65, 95%CI (8.36, 10.93),P < 0.000 01). Adverse reaction and event was mild in 2 included research reports. It was concluded that the treatment of supplementingqi and activating blood circulation prescription or it combined with routine treatment in modern medicine was quite effective in the treatment of cerebral ischemic stroke by the existed limited evidences. It can also improve the nerve dysfunction and the ability of daily living. Due to the limited quantity of the included studies and the evidence with limited strength, further high-quality RCTs were needed to verify the forementioned conclusion.

Objective To observe effects of Naotaifang on MMP-9, NF-κB and TIMP-1 after focal cerebral ischemia in rats. Methods The rats were randomly divided into sham operation group, model group, and Naotaifang low- (3 g/kg), medium- (9 g/kg), high- dose (27 g/kg) group. After 3 days of corresponding therapy by intragastric administration once a day, the regional cerebral ischemia model was made by middle cerebral artery occlusion (MCAO) with suture method. Following 3 days, the rats were treated with previous method. On the third day, hippocampal C2 region of ischemic tissue was detected by HE dyeing. And the contents of MMP-9, NF-κB and TIMP1 proteins in hippocampal C2 region were measured by immunohistochemical method. Results The number of normal brain cells in high dose group of Naotaifang was more than that of the model group, and only a few cells appeared nucleus pycnosis. The MMP-9 expression of all dose groups of Naotaifang were significantly decreased than model group (P<0.05). The NF-κB expression of high and medium dose groups of Naotaifang were significantly decreased (P<0.05). The TIMP1 expression of all dose groups of Naotaifang were significantly increased compared with sham operation group (P<0.05). Conclusion The mechanism of Naotaifang protecting blood brain barrier against injury of cerebral ischemia may be involved in ameliorating MMP, NF-κB and increasing TIMP1 expression.