OBJECTIVE To investigate the protective effect proanthocyanidin B2(PC-B2) on oxidative damage and apoptosis of mouse astrocytes(AS) induced by hydrogen peroxide(H2O2) and its mechanism. METHODS AS were isolated and cultured from neonatal C57BL/6 mice(1−3 d). The optimal concentration of H2O2 and PC-B2 was divided into four groups: normal group, normal+PC-B2 group(100 μg·mL‒1 PC-B2 treated for 24 h), H2O2 model group(200 μmol·L‒1 H2O2 treated for 24 h), PC-B2 group(200 μmol·L‒1 H2O2 and 100 μg·mL‒1 PC-B2 treated for 24 h). The cell viability of each group was detected by CCK-8 method. Cytotoxicity was detected by LDH method. The antioxidant capacity was detected by ABTS and DPPH. The content of MDA and the activity of SOD, CAT and GSH-Px were detected by ELISA kit. Detection of apoptosis in each group was done by TUNEL staining. The mRNA and protein expression levels of Bax, Bcl-2, Caspase-3, Akt/Stat3, p-Akt, p-Stat3 and Nrf2/HO-1 in AS were detected by RT-PCR and Western blotting, respectively. RESULTS PC-B2 could significantly enhance cell viability and inhibit AS apoptosis. Compared with the H2O2 model group, PC-B2 intervention could significantly reduce the content of LDH and MDA in AS, and increase the activity of SOD, CAT and GSH-Px. PC-B2 intervention could inhibit the mRNA and protein expression of Bax and Caspase-3, and up-regulate the mRNA and protein expression of Akt/Stat3, Bcl-2, Nrf2/HO-1. CONCLUSION PC-B2 can enhance the antioxidant capacity of AS through Akt/Stat3 and Nrf2/HO-1 pathways, therefore reduce H2O2-induced AS oxidative damage and apoptosis.

Objective To investigate the effect of ethanolic extract of Cichorium glandulosum Boiss.et Huet.on fecal bile acid profiles in high-fat-diet-induced obese mice.Methods Twenty-four 6-week-old C57 BL/6 male mice were divided randomly into normal,model,drug-administration,and metformin groups.Mice in the normal group were fed a regular diet and mice in the other three groups were given high-fat diets.The drug-administration group was gavaged with 10 mL/kg ethanol extract of Cichorium glandulosum Boiss.et Huet.daily,and the metformin group was gavaged with 10 mL/kg metformin daily.After 10 weeks,livers were collected to measure hepatic total triglycerides(TG),total cholesterol(TC),low-density lipoprotein-cholesterol(LDL-C),and high-density lipoprotein(HDL)-C.Feces were collected and analyzed.Results Body weight(P＜0.0001),liver TG(P＜0.05),and TC(P＞0.05)were all significantly higher in model mice compared with normal mice,while LDL-C(P＞0.05)and HDL-C(P＜0.001)were significantly lower,indicating abnormal weight gain and lipid metabolism.Alcoholic extract of Cichorium glandulosum Boiss.et Huet.significantly reduced body weight(P＜0.0001),liver TG(P＜0.0001),serum TG(P＜0.05),TC(P＜0.01),and LDL-C(P＜0.05)in mice.Methodsological validation showed that the current method could accurately quantify 52 bile acids in feces.Analysis of the concentration of each type of bile acid revealed that alcoholic extract of Cichorium glandulosum Boiss.et Huet.significantly increased the secondary/primary bile acid ratio(P＜0.05).Multivariate analysis showed that the bile acid metabolic pattern was significantly altered in all groups.Eight differential bile acids were screened in the drug-administration group relative to the model group using variable importance of projection＞1 and P＜0.05.A search of the Kyoto Encyclopedia of Genes and Genomes database revealed that the differential bile acids were mainly involved in the secondary bile acid biosynthesis pathway.Correlation analysis showed that four differential bile acids,deoxycholic acid(r,=0.6445,P＜0.001),isolithocholic acid(r,=0.5879,P＜0.01),3β-deoxycholic acid(r,=0.6649,P＜0.001),and ω-rhamnoglutaric acid(rs=0.5387,P＜0.01),in feces were strongly positively correlated with body weight.Conclusions Cichorium glandulosum Boiss.et Huet.alcoholic extract may play a role in weight reduction and amelioration of dyslipidemia by modulating secondary bile acid biosynthesis and altering fecal bile acid metabolic profiles.

Objective:To assess the clinical value of helium-free magnetocardiography(MCG) in the diagnosis of coronary artery disease(CAD).Methods:A total of 213 patients with suspected CAD undergoing MCG in Beijing Anzhen Hospital were enrolled in the study. All patients underwent coronary CT angiography/invasive coronary angiography(CCTA/ICA) within 48 hours after MCG scanning. The parameters of MCG, including magnetic field multipolarization, magnetic field unipolarization, T-wave flattened, change in magnetic field distribution at TT segment, abnormal T-peak amplitude ration of maximum to minimum, significant movement of poles, magnetic field angle deviation and abnormal distribution of positive pole were used for the evaluation of the stenosis of coronary arteries.Results:Among 213 patients, MCG scanning was completed in 193 cases(90.6%), while 20 cases were excluded for various reasons. The CCTA/ICA results were taken as gold standard, the total coincidence rate of MCG with the degree of stenosis was 88.60%(95% CI: 83.25%-92.72%), the sensitivity and specificity of MCG in the diagnosis of CAD was 89.63%(95% CI: 83.21%-94.21%) and 88.23%(95% CI:78.12%-94.78%), respectively; the positive and negative predictive value were 93.80%(95% CI:88.72%-96.68%) and 81.08%(95% CI:72.15%-87.64%), respectively. Conclusion:MCG is highly accurate in the diagnosis of CAD, it may be widely used clinically as an non-invasive method free of radiation or contrast agent.

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alterna-tives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

【Objective】 To evaluate the efficacy and safety of early interventions by traditional Chinese medicine oral liquid combined with plasma exchange in the treatment of pregnant women with high titer of ABO/Rh antibodies. 【Methods】 156 pregnant women with serum antibodies presenting high titer (ABO ≥512, Rh ≥ 64) in our hospital from May 2018 to April 2021 were randomly divided into traditional Chinese medicine group(group Ⅰ, n=68), traditional Chinese medicine combined with plasma exchange group(group Ⅱ, n=57) and control group (n=31). The control group were given VC, VEand oxygen uptake. Group Ⅰ were further given oral administration of traditional Chinese medicine liquid on the basis of treatment of the controls. GroupⅡwas further treated with plasma exchange on the basis of group I treatment(for 20 days every month). The biochemistry, serum antibody titer and foetus intrauterine growth were monitored. The the efficacy of treatment, as well as pregnancy and neonatal conditions in the three groups were observed. 【Results】 The decrease time of antibody titer and IgG subtype titer in groupⅠ and Ⅱ, relative to the controls, were significantly better(P<0.05). The effective rate of group Ⅰ(72.59%, 49/68) and group Ⅱ(92.98%, 53 /57) were significantly higher than the controls(18.52%, 5/27, with 4 cases excluded). No HDN occurred in group II, indicating superior treatment outcome to group I and the controls. 【Conclusion】 The oral administration of traditional Chinese medicine liquid combined with plasma exchange, with good therapeutic efficacy and maternal-fetal safety, was effective for the early interventions of ABO/Rh incompatible HDN and worthy of clinical application.

Objective: To investigate the correlation between Traditional Chinese medicine (TCM) constitution classification and clopidogrel-related CYP2C19 gene polymorphism of acute cerebral infarction patients. Methods: A cross-sectional method was used in this study. Patients with acute cerebral infarction were screened and enrolled according to our inclusion and exclusion criteria. TCM constitution were evaluated in patients with acute cerebral infarction. Digital fluorescence hybridization Technology was used to test genotypes of CYP2C19 and Hardy-Weinberg’s equilibrium was used to examine CYP2C19 gene polymorphism of the patients. Binary logistic regression analysis method was used to explore the relationship between TCM constitution types and clopidogrel-related CYP2C19 gene polymorphism in acute cerebral infarction. Results: Among the 100 patients with acute cerebral infarction, 18 belong to Yang-deficiency constitution (18 cases, 18%), 30 Yin-deficiency (30 cases, 30%), 18 belong to Qi-deficiency constitution (18 cases, 18%), 51 belong to phlegm-dampness constitution(51 cases, 51%), 14 belong to damp-heat constitution (14 cases, 14%), 2 belong to special constitution (2 cases, 2%), blood-stasis constitution (27 cases, 27%), Qi stagnation constitution (4 cases, 4%), and normal constitution (11 cases, 11%). The CYP2C19*2 gene polymorphism distribution: CYP2C19*2 (A/A, mutant homozygous) (21 cases, 21%), CYP2C19*2 (A/G, mutant heterozygote) (33 cases, 33%), CYP2C19*2 (G/G) (normal homozygous) (46 cases, 46%). The mutant allele frequency was 0.375. Binary logistic regression analysis showed that compared with A/A genotype, the G/G genotype of CYP2C19*2 in acute cerebral infarction was correlated with phlegm-dampness constitution (OR=5.105, 95% CI: 1.308-19.928, P<0.05) and blood-stasis constitution (OR=12.557, 95% CI: 1.741-90.558, P<0.05). Conclusions The proportion of phlegm-dampness constitution is the highest in patients with acute cerebral infarction. The mutation rate of clopidogrel-related CYP2C19*2 was significantly higher than that of CYP2C19*3 clopidogrel-related CYP2C19*2 gene polymorphism might be related to phlegm-dampness constitution and blood-stasis constitution.

Accelerated forgetting has been identified as a feature of Alzheimer's disease (AD), but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTPase, has been shown to regulate active forgetting in Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models. Moreover, amyloid-beta 42 could induce Rac1 activation in cultured cells. The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice. A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model. Moreover, inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models. Finally, two novel compounds, identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models, were found to be capable of inhibiting Rac1 activity. Thus, multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.

Objective: To explore the value of nanoparticles (CN) in lateral cervical lymph node mapping in papillary thyroid carcinoma using carbon. Methods: Thyroid cancer patients with suspicious lymph node metastasis but without typical signs of metastatic disease from March 2016 to November 2017 in Fudan University Shanghai Cancer Center were prospectively included in the cohort. Neck dissection was performed in all patients (compartmentsⅡ-Ⅴ). Suspicious lateral lymph node metastasis was identified using pre-operative ultrasound or computed tomography. CN were used for lymph node mapping during surgery. Results: A total of 70 surgeries were performed in 67 patients, among which 57 were found to have lateral lymph node metastasis (81.4%). The median number of CN-dyed lateral lymph nodes was 6. Compartment IV had the highest number of CN-dyed positive lymph nodes as well as the highest rate of metastasis, followed by compartmentⅢ. In compartmentsⅢandⅣ, the incidence of lymph node metastasis was significantly higher in the CN-dyed group than in the CN-undyed group (P<0.001). When the final pathology of neck dissection was set as the gold standard, lateral CN-dyed lymph node biopsy was found to have a sensitivity of 86.0%; its negative predictive value was 61.9% and its overall accuracy was 88.6%. Conclusions:Injection of CN during surgery was a potential method of mapping lateral lymph nodes in papillary thyroid carcinoma. CompartmentⅢ-ⅣCN-dyed lymph node biopsy had a satisfactory sensitivity and thus, served as a reasonable range for lymph node biopsy.

The correct thoughts and principles of diagnosis and treatment of chronic refractory wounds need to be formulated. Through the relevant domestic and international consensus and based on clinical experience, the Thoughts and principles of diagnosis and treatment of chronic refractory wounds in China is proposed. It is considered that in the diagnosis and treatment of chronic refractory wounds, in the case of fully understanding the patient′s medical history, the following thoughts and principles should be complied in order. (1) Pay attention to the cleanliness of the wound after being cleaned. (2) Reasonably perform debridement to avoid being " excessive" or " not thorough". (3) Reasonably perform examination, diagnosis, and differential diagnosis of pathogenic factors. (4) Treat according to etiology. (5) Find comorbidities and prevent adverse outcomes. (6) Select the correct wound treatment method reasonably and timely. When the conservative wound care treatment is considered, pay attention to embodying the concept of etiological treatment, treat the wound according to the principles of safety, phase, selectivity, and effectiveness, and make a reasonable choice of continuing conservative treatment or surgical treatment in time after completing the preparation of the wound bed. When surgical treatment is considered, pay attention to the selection of reasonable surgical method and donor site, pay attention to the healing rate of surgical wound site and the outcome of donor site, and give reasonable protection to the wound site after surgery. (7) Carry out rehabilitation treatment after wound healing and related health education.

Stanniocalcin (STC) was ifrst found as a calcium- and phosphate-regulating hormone produced in bony ifsh by the corpuscles of Stannius. In mammals, the homolog STC-1 displays a relative high amino acid sequence identity (nearly 50%) with ifsh STC, and STC-2 has a lower identity (nearly 35%) with STC-1 and ifsh STC. Both STC-1 and STC-2 are expressed in a variety of tissues. The functions of STC have not been understood. But some ifndings have been reported on their cellular localization, gene structure, and expression in different physiological and pathological conditions, which will be clues in elucidating the functions of STC in mammals. Moreover, STC-1 and STC-2 are expressed in many tumor cell lines, suggesting other biological functions of STC in mammals other than mineral metabolism.