Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_

Thyroglobulin(Tg)is a glycoprotein with large molecular weight,which is synthesized and secreted into the bloodstream by thyroid follicular cells.The concentration level of Tg in blood is one of the important biomarkers for diagnosis of thyroid diseases such as differentiated thyroid cancer(DTC),subacute thyroiditis,etc..Radioimmunoassay(RIA),immunoradiometric assay(IRMA),and immunochemiluminescence assay(ICMA)are the main clinical methods for detecting Tg.Recently,for meeting the requirement of detecting low concentration of Tg in blood after thyroid clearance surgery,researchers have developed various high-performance analysis methods for detecting Tg concentration in blood samples,providing new assays for thyroid disease screening and efficacy evaluation.This review summarized the analysis methods of Tg,especially the new progresses in the biosensors for monitoring low concentration of Tg in blood during the past five years.The current technical challenges of these methods in clinical applications were briefly discussed,which might provide useful information for developing new liquid biopsy methods of DTC.

OBJECTIVE: To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of FGA, FGB and FGG and their flanks were amplified by PCR and sequenced to search for gene mutations. RESULTS: The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of FGA gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were FGA gene g.9308A/G (p.AαThr331Ala) and FGB gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery. CONCLUSION Heterozygous mutation of 6233G/A (p.AαArg35His) of FGA gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Humans ; Child ; Female ; Fibrinogen/genetics* ; Pedigree ; Afibrinogenemia/genetics* ; Mutation ; Blood Transfusion

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.
Antihypertensive Agents ; Capsules ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Hypertension/drug therapy* ; Network Meta-Analysis ; Nonprescription Drugs

ObjectiveTo investigate the biological effect of circ_0036176 on myocardial fibrosis. MethodsLevels of circ_0036176 and its host gene Myo9a were determined by real-time quantitative polymerase chain reaction （RT-qPCR） assay in human myocardial tissue， including 22 healthy organ donors and 26 patients with heart failure （HF）. A cell model of angiotensin Ⅱ （Ang-Ⅱ）-induced fibrosis in human atrial fibroblasts （HAFs） was achieved. To test the typical ring structure of circ_0036176， actinomycin D treatment and RNase R exonuclease digestion were performed. The expression of fibrosis-related gene in HAFs with overexpression of circ_0036176 was detected at mRNA and protein level. To select miRNAs that can effectively bind to circ_0036176， dual luciferase reporter gene assay and RNA antisense purification assay （RAP） were conducted， respectively. The neonatal mouse cardiac fibroblasts （mCFs） were used to study whether mir-218-5p mediates the effect of circ_0036176 on myocardial fibrosis phenotype. ResultsThe expression of circ_0036176 was up-regulated in the myocardium of HF patients （P＜0.001）， and the expression of circ_0036176 and the host gene Myo9a was down-regulated in Ang-Ⅱ-induced HAFs （P＜0.01）. In response to actinomycin D treatment and RNase R exonuclease digestion， circ_0036176 was more stable than Myo9a mRNA. The expression of COL1A1， COL3A1， TGF-β1 and ACTA2 was down-regulated in HAFs with overexpression of circ_0036176 （P＜0.05）. Results of dual luciferase reporter gene assay and RAP assay confirmed the interaction between miR-218-5p and circ_0036176. Overexpression of miR-218-5p could promote the expression of fibrosis-related genes， and attenuate the inhibitory effect of circ_0036176 on cardiac fibrosis. ConclusionsCirc_0036176 is up-regulated in the myocardium of HF patients， and circ_0036176 inhibits the expression of fibrosis-related gene through sponging miR-218-5p in CFs.

ObjectiveTo investigate the effect of circ_0018478 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0018478 and its host gene of HECT and RLD domain containing E3 ubiquitin protein ligase 4 （HERC4） in the myocardium of patients with heart failure （HF） （n=28） and healthy donors （n=18） was analyzed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. The distribution of circ_0018478 was identified by fluorescence in situ hybridization （FISH） assay and RT-qPCR assay based on nucleocytoplasmic RNA in human AC16 cardiomyocytes. Actinomycin D and RNase R exonuclease digestion were used to test the stability of circ_0018478 in AC16 cells. RNA and protein expression of fibrosis-related genes was detected in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated over-expression of circ_0018478. EdU staining and transwell migration assay were performed to detect the effects of circ_0018478 on mCFs proliferation and migration activities. The potential circ_0018478-translated protein in mCFs was identified by mass spectrometry （MS） shot-gun assay. HERC4-193 was inhibited by small interfering RNA （siRNA）， and the effect of HERC4-193 knock-down on the fibrotic phenotype of mCFs with over-expression of circ_0018478 was studied. ResultsThe expression of circ_0018478 was up-regulated in the myocardium of HF patients， with no significant difference in its host gene of HERC4. The results of FISH and RT-qPCR assay showed that circ_0018478 was mainly in the cytoplasm of AC16 cardiomyocytes. The characteristic RNA stability of circ_0018478 was verified by Actinomycin D and RNase R assay， respectively. The enforced expression of circ_0018478 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The results of MS shot-gun assay and Western blotting showed that circ_0018478 could translate protein HERC4-193. Overexpression of the circ_0018478 and protein HERC4-193 could consistently inhibit the fibrotic phenotype of mCFs. Knock-down of HERC4-193 could attenuate the inhibitory effect of circ_0018478 on fibrosis-related gene expression in mCFs （P<0.05）. ConclusionsCirc_0018478 inhibits the fibrotic phenotype of cardiac fibroblasts via translating HERC4-193 protein.

OBJECTIVE: To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients. METHODS: The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR. RESULTS: There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months. CONCLUSION For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.
Adult ; Dasatinib ; Female ; Fusion Proteins, bcr-abl/genetics* ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Male ; Middle Aged ; Protein Kinase Inhibitors ; Young Adult

To analyze the domestic clinical application of vascular dementia scales, and provide the basis for the refinement of clinical scales. VIP, SinoMed, Wanfang and CNKI databases were searched by computer to analyze the clinical application of vascular dementia scales published in Chinese Core Periodicals in Library of Peking University, CSSCI and CSCD, with time limit from database establishment to August 31, 2020. According to the inclusion or exclusion criteria, the combination of Note Express software and manual search was used to complete the literature duplicate detection and screening. According to the research needs, the relevant data were extracted and a new database was established. In this study, a total of 4 246 related literatures were initially searched, 2 048 repetitive literatures were eliminated, 1 484 literatures were manually screened out, and finally 714 literatures and 44 scales were included. The total using frequency of scales was 2 660. The results of descriptive analysis showed that there were many kinds of clinical scales for vascular dementia. In order to avoid the repeated use of scales with similar functions, it is correct to include the possible influences such as the purpose of use, way, frequency and function of the scales into reference factors of scale selection according to the disease diagnostic criteria. It is necessary to develop the scales with traditional Chinese medicine characteristic for objective clinical evaluation of traditional Chinese medicine.
Dementia, Vascular/diagnosis* ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome