Effect of Yixintai on Mitochondrial Fission Proteins Fis1 and Mff in Rat Model of Chronic Heart Failure / 中国实验方剂学杂志

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg-1， respectively） Yixintai， and trimetazidine （10 mg·kg-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

Mechanism of Active Ingredients of Astragalus Membranacus in Treating Heart Failure： A Review / 中国实验方剂学杂志

Heart failure is one of the main cardiovascular system diseases at present， and it is a clinical syndrome caused by changes in cardiac structure and function， resulting in impaired ejection function or ventricular filling. Therefore， heart failure has become the most important cardiovascular disease in the 21st century. In recent years， the incidence of heart failure is increasing， and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine， more and more attention has been paid to the research， development， and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus， a traditional Chinese medicine， is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics， protecting myocardial muscle， and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure， yielding remarkable results. In recent years， it has been found that astragaloside， Astragalus polysaccharide， quercetin， calyx isoflavones， and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response， myocardial apoptosis， and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature， with a view to providing a reference for its further research， development， and application in the prevention and treatment of heart failure.

The Path Analysis of Integrating Sun Simiao’s Medical Ethics Thought into the Humanistic Spirit of Medical Students / 中国医学伦理学

Medicine is the subject of studying human and its inherent humanistic attribute endows medicine with the temperature it deserves. However, with the continuous improvement of medical testing technology and treatment technology, medical workers pay more attention to diseases and ignore humanistic care, which has become an important factor in the aggravation of patients’ burden and the tension relationship between doctors and patients. There are many virtues in Chinese traditional culture. Sun Simiao’s medical ethics thought of "great doctor with professionalism and sincerity" embodies the core value of the humanistic spirit of Chinese traditional medicine. In his medical ethics thought, the moral and ethics of "great doctor with professionalism and sincerity", the medical practice attitude of "being cautious and diligent", the values of "benevolence for the world" and the professional conduct of "honesty and truth" still have strong practical significance at present. It is the good material to cultivate the humanistic spirit of medical students. This is of great value to integrate Sun Simiao’s medical ethics thought into cultivate medical students with both "professionalism" and "sincerity", practice the original intention of medical and health undertakings, and carry forward cultural self-confidence.

Artificial intelligence cell image analysis technology can improve the accuracy of bone marrow cells / 中华检验医学杂志

Objective:To evaluate the screening efficacy of AI for bone marrow cell morphology.Method:Bone marrow specimens of patients attending the Second Hospital of Hebei Medical University from December 1,2019 to December 21,2020;(1) Selected from one hundred bone marrow specimens, The cases included chronic myeloid cell leukemia ( n=23), myelodysplastic syndrome ( n=4), chronic lymphocytic leukemia ( n=4), multiple myeloma ( n=5), 7 acute leukemia ( n=7), chronic anemia ( n=32), infection ( n=6) and healthy control ( n=15). Including 45 males and 55 females, with age 52(37,66)years old.The bone marrow smear prepared with Wright-Giemsa, The AI analysis system and manual audit were applied to classify 13 types of bone marrow nucleated cell, taking the results of manual audit as the gold standard, comparing the difference between the results of the two methods, using statistical software to draw the confusion matrix, The compliance between the manual audit results and the pre-classification results of the AI analysis system was calculated by the Kappa consistency test method; The consistency analysis between the pre-classification results of AI and those of the manual microscopic examination was performed by the Pearson test; (2)Statistics analyzed the blast cell differential count differences of AI and manual microscopy, to evaluate the clinical application value of AI analysis system, which soured from thirty bone marrow samples of patients diagnosed with MDS and AML. Results:76 630 images of 13 nucleated cells were obtained by AI analysis system; the weighted average experimental diagnostic efficiency parameters of 13 types of bone marrow nucleated cells, are as follows: sensitivity(%)=95.82, specificity(%)=99.19, accuracy(%)=98.89, false positive rate(%)=0.81, false negative rate (%)=4.18; the correlation results, between the pre-classification results of AI and manual microscopic classification results,showed that blast cell, promyelocytes, neutrophilic myelocyte, neutrophilic metamyelocyte, band neutrophil, segmented neutrophi,eosinophil, basophil, polychromatic erythroblast, orthochromatic erythroblast, and lymphocytes have good positive correlation ( r>0.70,all P<0.001), while basophilic erythroblast and monocytes have no obvious correlation ( r=0.32,0.30, all P> 0.001); the count results of the blast cells in bone marrow smears of MDS and AML, got by AI and manual microscopy respectively, showed that the average percentage of blast cells was 8.19% by AI and 8.68% by manual microscopy in MDS, there was no significant difference between the two methods ( P>0.05); the average percentage of blast cells was 48.52% by AI analysis system and 53.77% by manual microscopy in AML, and although there was a significant difference in blast cell count ( P<0.01), coincidence the classification diagnostic criteria for AML (blast cells ≥ 20%). Conclusion:The AI analysis system performed good sensitivity, specificity and accuracy for 13 types of bone marrow nucleated cells, which showed potential application value for the rapid classification and diagnosis of MDS and AML.

Association Between Plasma Homocysteine Level and Hyperuricemia in Elderly Patients With Hypertension / 中国医学科学院学报

Objective To explore the association between plasma homocysteine (Hcy) level and hyper-uricemia (HUA) in the elderly patients with hypertension.Methods From March to August in 2018,9902 hypertensive patients ≥ 60 years were routinely tested for blood biochemical indicators in Wuyuan county,Jiangxi province.The patients were assigned into a HUA group and a normal uric acid group.Multivariate Logistic regression was adopted to analyze the relationship between Hcy level and the risk of HUA.Results Compared with the normal uric acid group,the HUA group showed increased incidence of hyperhomocysteinemia (99.9% vs.98.7%,P<0.001) and elevated Hcy level[16.8 (13.8-21.5) μmol/L vs.14.4 (12.3-17.7) μmol/L,P<0.001].The multivariate Logistic regression analysis showed that after adjusting for influencing factors,the risk of HUA in the patients with hyperhomocysteinemia was 2.92 times of that in the patients with a normal Hcy level.The threshold effect analysis showed that the Hcy level was positively correlated with the occurrence of HUA in the case of Hcy<20 μmol/L (OR=1.05,95%CI=1.04-1.07,P<0.001).In the case of Hcy ≥ 20 μmol/L,there was no correlation between Hcy level and HUA (OR=1.00,95%CI=0.99-1.00,P=0.055),and the likelihood ratio test showed statistically significant results (P<0.001).Conclusion The elderly with hypertension should pay attention to control the Hcy level,which will be helpful to prevent the occurrence of HUA.

Perilla frutescens PfFUL Regulates the Flowering and Silique Development in Transgenic Arabidopsis thaliana / 中国生物化学与分子生物学报

The FRUITFULL (FUL) gene belongs to the AP1/ FUL subfamily of the plant MADS-box family and has functions in regulating flowering time, floral meristem differentiation and fruit development. PfFUL gene sequence was derived from the perilla transcriptome data, and the basic physicochemical properties of PfFUL were analyzed by bioinformatics methods. Evolutionary relationships of PfFUL with other species of FUL were analyzed by phylogenetic tree. Plant expression vector 35S::PfFUL was constructed and used to transform wild type Col-0 and mutant ful-7 Arabidopsis to obtain overexpression 35S::PfFUL/ Col-0 and complemented mutation 35S::PfFUL / ful-7 plants respectively. Comparative phenotypic analysis was performed to preliminarily clarify the function of PfFUL gene in plant flowering and fruit development. The functions of the PfFUL gene during flowering and angular fruit development of the plants were initially clarified. The CDS of PfFUL gene is 738 bp and encodes 245 amino acids. Phylogenetic tree showed that the perilla PfFUL was closely related to Solanum lycopersicum, Salvia splendens and Salvia hispanica, but far related to Arabidopsis thaliana, Nicotiana tabacum and Vitis vinifera. Compared to Col-0 and ful-7, the transgenic plants showed early flowering (P0. 05), and the amount of wrinkled seed was significantly reduced (P<0. 01). In addition, phenotypic observations revealed that the transgenic plants also exhibited increased internode length and narrowed and curled cauline leaves. In conclusion, this study confirmed that the PfFUL gene regulates early flowering and fruit development in plants and participates in nutritional growth.

Huazhi Rougan Granules attenuates steatosis in cell model of nonalcoholic fatty liver disease by inducing autophagy / 中国中药杂志

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.

Effect of Erxian Decoction-containing serum on H_2O_2-induced proliferation and osteogenic differentiation of MC3T3-E1 cells via BK channels / 中国中药杂志

This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.

The role of Keap1/Nrf2/HO-1 signal pathway in liver injury induced by rare earth neodymium oxide in mice / 中华劳动卫生职业病杂志

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1β and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.

Progress of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 in hematological malignancies / 白血病·淋巴瘤

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in the development of various tumors. Recent studies have shown that MALAT1 is highly expressed in hematological tumors and can participate in development, progression and prognosis of hematological tumors at transcriptional and post-transcriptional levels as a competitive endogenous RNA. Therefore, MALAT1 might be a novel marker as a valuable basis for the diagnosis, treatment and prognosis evaluation of hematological tumors.

Analysis of the implementation of health impact assessment of public policies in Zhejiang province / 中华医院管理杂志

The policy implementation model of G. C. Edwards was used to analyze the public policy health impact assessment in Zhejiang province, and summarize its practice and existing problems in four aspects of policy implementation standards, policy resources, policy executors′ intention and management organization structure, so as to provide reference for promoting the national health impact assessment pilot work. The analysis results showed that Zhejiang province has initially established the public policy health impact assessment mechanism and achieved phased results, but there were still some problems, including the imperfection of policy content and implementation strategy, the inadequacy of leadership decision-making and top-level design, the difference in attitude, understanding and implementation preference of policy implementation subjects, and the ambiguity of the authority and responsibility system of each department in cooperation. In order to further promote the smooth development of public policy health impact assessment, Zhejiang province should actively promote the top-level design to strengthen policy support, integrate and optimize policy resources, gradually establish and improve the health governance mechanism of multiple and overall coordination, and promote the high-quality development of public policy health impact assessment by taking cross departmental cooperation as the path of health co-construction.

Elabela alleviates diabetic kidney disease by regulating aquaporin 2 / 中华内分泌代谢杂志

Objective:To assess the renal-protective effect of Elabela (Ela) on diabetic kidney disease (DKD), and explore its potential mechanism.Methods:db/db mice were randomly divided into diabetic group and Ela intervention group, while db/m mice were taken as normal control group. The mice in the Ela intervention group were intraperitoneally injected with Ela-21 5 mg·kg -1·d -1 for 8 weeks. At the end of the experiment, urinary albumin/creatinine ratio (UACR) was measured. The renal pathological changes were observed by HE and PAS staining. The expression of aquaporin 2(AQP2) examined by immunohistochemistry. The level of collage Ⅳ(Col-Ⅳ) and AQP2 in renal tissue was analyzed by Western blot. The human renal tubular epithelial cells (HK-2) were incubated with high glucose medium and further interfered with apelin receptors (APJ)-siRNA. Western blot analysis was used to detect the effect of Ela intervention on Col-Ⅳ and AQP2 expression. Finally, to clarify the possible mechanism of Ela regulating AQP2, the interaction between Ela-induced APJ activation and arginine vasopressin (AVP)-evoked arginine vasopressin receptor 2 (AVPR2) activation was investigated by NanoBit ? technology. Results:(1) Without affecting blood glucose and body weight, Ela intervention significantly reduced the UACR in db/db mice, and attenuate pathological changes of the kidney, as well as expression of Col-Ⅳ and AQP2. (2) Ela treatment could remarkably inhibit the high glucose-induced the expression of Col-Ⅳ and AQP2, which was reversed by interfering with APJ. (3) AVP-induced downstream β-Arrestin-2 signaling transduction via AVPR2 was obviously antagonized by interaction of Ela and APJ, further suggesting that the inhibitory effect of Ela on AQP2 may be related to antagonizing AVP/AVPR2 signaling.Conclusion:Ela exerts renal protection by inhibiting the expression of AQP2 through APJ.

The Research on Ferritinophagy, Ferroptosis and Related Diseases / 中国生物化学与分子生物学报

Iron, an important cofactor for heme, mitochondrial respiratory chain complexes, and various biologically important enzymes, participates in biological processes including oxygen transport, redox reactions, and metabolite synthesis. Ferritin is an iron storage protein that maintains iron homeostasis in the body by sequestering and releasing iron. Ferritinophagy is a selective type of autophagy that mediates ferritin degradation, releasing free iron when increased intracellular iron level is needed. Moderate rates of iron autophagy maintain intracellular iron content homeostasis. Excessive ferritinophagy will release a large amount of free iron, causing lipid peroxidation and cell damage via reactive oxygen species (ROS) produced by the Fenton reaction. Therefore, ferritinophagy plays a vital role in maintaining cellular iron homeostasis. Nuclear receptor co-activator 4 (NCOA4) acts as a key regulator of ferritinophagy by targeting ferritin binding and delivery to lysosomes for degradation, leading to release of free iron. Thus, NCOA4-mediated ferritinophagy is an important contributor to iron metabolism. Recent research reveals that NCOA4 is regulated by factors including iron content, autophagy, lysosomes, and hypoxia. NCOA4-mediated ferritin degradation is related to ferroptosis (an autophagic cell death process) . Ferritinophagy acts as an upstream mechanism driving ferroptosis by regulating cellular iron homeostasis and ROS production, which are closely correlated with the occurrence and development of anemia, neurodegenerative diseases, cancer, ischemia / reperfusion injury, and other diseases. In this study, the functional characteristics of NCOA4-mediated ferritinophagy in ferroptosis and the role of NCOA4 in these diseases were reviewed, which may provide new avenues for the treatment of related diseases.

Progress on correlation between intestinal flora and mental diseases / 中国药理学通报

The impact of intestinal flora on human and animal health and diseases has attracted much attention both at home and abroad in recent years. The intestinal flora constitutes the intestinal microecosystem and plays an important role in physiological activities such as nutrition, metabolism, growth and development, barrier protection, and immunity. In this article, the relationship between intestinal dysbiosis and psychiatric diseases has been reviewed from two aspects:metagenomic characterization of intestinal microflora diversity in neurological diseases and validation of the relationship between intestinal flora and psychiatric diseases by fecal bacteria transplantation in germ-free mice. In addition, the microbial-gut-brain axis theory has been proposed in recent years, which links the nerve-endocrine-immune system to form a two-way signaling pathway. Intestinal flora plays an important role in regulating the central nervous system by promoting neurotransmitter release, endocrine, and immunity. The system plays an important role. Changes in intestinal flora mainly affect the host's nervous system through vagus nerve pathways, endocrine pathways, immune pathways, etc, thereby triggering or aggravating depression, autism, Alzheimer's disease, schizophrenia, Parkinson's disease, etc. This article reviews the relationships between host-related neurological abnormalities, intestinal flora imbalance and mental diseases, and discusses the research methods, research progress, and mechanism of the correlation between intestinal flora imbalance and mental diseases to research progress on microbe-gut-brain axis.

Effect of Wenyang Jieyu Decoction on Hippocampal Neuroplasticity in Depressed Rats Induced by Corticosterone / 中国实验方剂学杂志

ObjectiveTo observe the effect of Wenyang Jieyu decoction （WYJY） on the hippocampal structure of depressed rats with kidney-yang deficiency. MethodThe 105 SD rats were randomly divided into normal group， model group， fluoxetine group （4.17 mg·kg-1）， Xiaoyaosan group （1.88 g·kg-1）， and low-， medium- and high-dose （1.25，2.50，5.00 g·kg-1） WYJY groups，15 in each group. The depression model was induced by subcutaneous injection of corticosterone in rats except for those in the normal group and the rats were orally administered once a day for 28 days. The depression-like behaviors of rats were observed by sucrose preference test， novelty-suppressed feeding test， forced swimming test， and open field test. The morphology of hippocampal neurons was observed by hematoxylin-eosin（HE） staining， and the density of hippocampal neurons was detected by Nissl staining. The ultrastructure of hippocampal synapses was observed by transmission electron microscopy （TEM）. The expression of synaptophysin （SYP）， postsynaptic density-95 （PSD95）， and apoptosis-related protein Caspase-3 in hippocampal neurons was observed by immunohistochemistry， and bromodeoxyuridine （BrdU） and doublecortin （DCX） were used to observe the apoptosis and regeneration of hippocampal neurons. ResultWYJY could improve weight loss in depressed rats. As revealed by the behavioral tests， the model group showed depression-like behaviors， which were relieved in the WYJY groups and the positive drug groups. HE staining showed that the nuclei of hippocampal neurons in the model group were constricted， deeply stained， and sparsely arranged， while the neurons in the WYJY groups and the positive drug groups were significantly improved. Nissl staining demonstrated that the cell density of the model group was lower than that of the normal group （P<0.05）. Compared with model group， the groups with drug intervention showed increased cell density （P<0.05） and compact arrangement. According to the results in TEM， compared with normal group， the model group showed shortened synaptic active zone （P<0.05）， widened synaptic cleft （P<0.05）， and thinned tight zone （P<0.05）. Compared with model group， the groups with drug intervention showed shortened synaptic active zone （P<0.05）， narrowed synaptic cleft （P<0.05）， and thickened tight zone （P<0.05）. As displayed by the results of immunocytochemistry and immunofluorescence， compared with the normal group， the model group showed decreased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and increased protein expression of Caspase-3 （P<0.05）. Compared with the model group， the groups with drug intervention showed increased protein expression of SYP， PSD95， BrdU， and DCX in the hippocampus （P<0.05） and decreased protein expression of Caspase-3 （P<0.05）. ConclusionWYJY can promote the regeneration of hippocampal neurons in rats and improve the depression of rats.

Mechanism of Anti-tuberculosis Particles （Kanglao Granule） Based on Network Pharmacology and Experimental Research / 中国实验方剂学杂志

ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology. MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information （NCBI）， and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed. Finally， AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them. ResultA total of 29 important chemical components in the prescription were screened out， including β-sitosterol， sesamin， and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved， such as protein kinase B1 （Akt1）， epidermal growth factor receptor （EGFR）， hypoxia inducible factor-1A （HIF-1A）， proto-oncogene tyrosine-protein kinase （SRC）， and matrix metalloproteinase-9 （MMP-9）. Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism， nucleic acid transcription， and metabolic enzyme pathway， and 28 key KEGG pathways， including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1. ConclusionKanglao granule improved the sterilization level and immune response through multi-component， multi-target， and multi-pathway interactions， thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.

Controversy of subtalar arthroereisis in symptomatic flatfoot / 中国骨伤

Flatfoot could be divided into flexible flatfoot and rigid flatfoot. Flatfoot with symptoms is called symptomatic flatfoot, surgical treatment is required if conservative treatment is not effective. Subtalar arthroereisis is a minimally invasive procedure which has been used for many years with good results in flexible flatfoot, however, still has many controversial points. Controversial points focus on indications and contraindications, optimal age, subtalar arthroereisis alone or not, efficacy and safety of absorbable material implants, and implant removal. The paper reviewed and summarized the use and controversies of subtalar arthroereisis in symptomatic flatfoot as follows:the best indication for subtalar arthroereisis was pediatric flexible flatfoot syndrome and aged from 10 to 12 years old was optimal age for treatment;tarsal coalitions with flatfoot and adult flatfoot were relative indications. Stiff flatfoot, joint laxity, and subtalar arthritis were contraindications;obesity and neurogenic flexible flatfoot were relative contraindications. The correction ability of subtalar arthroereisis alone was limited, and it's combined with other procedures depending on patient's situation. The safety and efficacy of absorbable material implants had been reported. Routine removal of the implant was not necessary, the main reason of which was tarsal sinus pain.

Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome / 中国骨伤

OBJECTIVE@#To investigate the surgical skills and clinical curative results of arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome.@*METHODS@#From February 2019 to August 2020, 13 patients with ankle instability combined with anteromedial impingement were retrospectively analyzed. There were 10 males and 3 females with age of (40.0±15.1) years old. The course of disease was(44.1±33.2) months. All patients had history of ankle sprain. MRI showed the injury of anterior talofibular ligament. All patients had anteromedial pain and pressing pain when ankle dorsiflexion. All patients were treated with ankle debridement and Brostr?m-Gould surgery under ankle arthroscopic. Postoperative results were evaluated by VAS(visual analogue scale) and AOFAS-AH(American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, AOFAS-AH).@*RESULTS@#All 13 patients completed the surgery successfully with an operative time of 60 to 90 minutes. All the surgical incisions healed by first intention, and no complications such as incision infection, skin necrosis and neurovascular injury. Follow-up time was (18.1±4.7) months. At the latest follow-up, the VAS score was 1.2±1.1, which was significantly lower than the preoperative score 4.8±1.5 (P<0.05);the AOFAS-AH score 94.2±5.1 was significantly higher than the preoperative score 65.5±11.5 (P<0.05). The AOFAS-AH score at the final follow-up ranged from 84 to 100. All patients walked with normal gait without ankle instability or impingement recurrence.@*CONCLUSION@#Ankle anteromedial impingement syndrome combined with ankle instability is easy to be ignored clinically. Such kind of anteromedial impingement syndrome is mostly related to osteophyte at dorsal medial talar neck. Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome has satisfactory curative effect with safety and minimal injury.

Establishment of the method for simultaneous determination of levetiracetam and carbamazepine in human plasma / 中国药房

OBJECT IVE To e stablish the method for simultaneous determination of levetiracetam and carbamazepine concentrations in human plasma. METHODS After plasma samples were precipitated with methanol ，using carbamazepine-D 10 as the internal standard ，the concentrations of levetiracetam and carbamazepine were determined by high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. The determination was performed on XBridge BEH C 18 column with methanol-0.1％ formic acid as mobile phase （gradient elution ）at the flow rate of 0.35 mL/min. The column temperature was set at 40℃，and sample size was 2 μL. With electrospray ion source，a multiple reaction monitoring mode was used for positive ion scanning；the detected ion pairs for quantitative analysis were m/z 171.3→126.3（levetiracetam），m/z 237.1→194.1（carbamazepine）， 247.1→204.1（internal standard ）. RESULTS The linear range of the concentrations of levetiracetam and carbamazepine were 0.5-50 and 0.2-20 μg/mL（r＝0.997 3 and 0.998 5），respectively；the lower quantitative limits were 0.5 and 0.2 μg/mL，respectively. RSDs of intra-day and inter-day were all no more than 10.00％. RE of intra-day and inter-day were within ±4.00％；the average extraction recoveries rate were 95.60％-105.00％；the average internal standard correction matrix factors were 98.40％-110.00％； RSDs of stability tests were all not higher than 5.60％. The concentrations of levetiracetam and carbamazepine in the plasma of 22 patients measured by this method were 3.36-40.90 and 3.64-9.93 μg/mL，respectively. CONCLUSIONS The established method for determining the concentration of levetiracetam and carbamazepine in human plasma is f ast，sensitive，accurate and stable ，and can be used for the monitoring of plasma concentration and pharmacokinetic study in epilepsy patients.

Progress of the mechanism of Wnt signaling pathway in T-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

T-cell acute lymphoblastic leukemia (T-ALL) is derived from the malignant transformation and clonal proliferation of precursor T cells. T-ALL is usually associated with the genetic mutations and/or chromosomal translocation, thus causing the change of survival, proliferation and progenitor cell differentiation of T cells in T-cell development. Studies have shown that Wnt signaling pathway plays a key role in the regulation of hematopoietic stem cell and normal T-cell development, and it is also abnormally altered in T-ALL. This article reviews the research progress of the mechanism of Wnt signaling pathway in T-ALL development.