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@#This paper summarized the clinical experience of AI Rudi in the treatment facial hormone-dependent dermatitis with the method of clearing heat and protecting yin. It is believed that the key pathogenesis is the heat toxin accumulation， yin depletion and collaterals obstruction. The clinical treatment should focus on “heat exuberance” and “yin depletion”. It is advocated that “half treatment is from heat and half from yin” is the general principle， and the treatment is staged. In the acute phase， the treatment is half from cooling blood and dispersing wind to dispel heat pathogen， and half from protecting fluid and moisturizing skin to strengthen yin； and the modified Liangxue Xiaofeng Powder （凉血消风散） could be used. In the chronic phase， half treatment is from clearing residual toxin to eliminate heat pathogen， and half from nourishing yin and unblocking collaterals to strengthen yin， for which Xuanmai Ganju Decoction and Erzhi Pills （玄麦甘桔汤合二至丸） can be used and modified according to the symptoms. At the same time， we should pay attention to the simultaneous internal and external treatment， and emphasize the importance of daily protection in the treatment of the disease.
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Objective @#To observe the clearance of smear layer on the root canal wall in different action time by scanning electron microscope (SEM), and to determine the optimal amount of time using sonically activated irrigation to wash root canal in clinic. @*Methods@# Fifty-six ex vivo human anterior teeth with single straight root canal were selected. After routine mechanical preparation, they were divided into two experimental groups according to different irrigating agents: saline group and EDTA group. Each group was assisted by VDW sonic activation EDDY. The saline group was divided into three subgroups according to the irrigating time: 5 s, 30 s and 50 s; EDTA group was divided into six subgroups according to the irrigating time: 5 s, 10 s, 20 s, 30 s, 40 s and 50 s. The control group did not undergo root canal irrigation. After irrigation, the root was cut longitudinally. The smear layer of crown, middle and apical of root canal wall was observed by SEM.@* Results@# After irrigating for 30 seconds, there was a significant difference between the normal saline group and the control group and the 5 second group (P<0.05), and there was no difference in the middle and apical part (P>0.05). After 50 seconds, there was a significant difference in the score of the smear layer between the apical area and the other groups (P<0.05). After irrigating for 5 seconds or 10 seconds in EDTA group, there was a significant difference between the scores of the crown and middle area of the root canal and the control group (P<0.05), and there was no significant difference in the apical area (P>0.05). There was a significant difference between the 20-40 second group and the first two groups (P<0.05). There was a significant difference between the 50 second group and the other groups (P<0.05). Comparing the cleaning effect on the smear layer after 50 seconds of irrigating between the two experimental groups, the whole root canal showed significant statistical difference (P<0.05). @*Conclusion @#The EDTA-assisted sonic activated device used for 50 seconds has the best cleaning effect.
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This paper summarized the clinical experience of AI Rudi in the treatment facial hormone-dependent dermatitis with the method of clearing heat and protecting yin. It is believed that the key pathogenesis is the heat toxin accumulation， yin depletion and collaterals obstruction. The clinical treatment should focus on “heat exuberance” and “yin depletion”. It is advocated that “half treatment is from heat and half from yin” is the general principle， and the treatment is staged. In the acute phase， the treatment is half from cooling blood and dispersing wind to dispel heat pathogen， and half from protecting fluid and moisturizing skin to strengthen yin； and the modified Liangxue Xiaofeng Powder （凉血消风散） could be used. In the chronic phase， half treatment is from clearing residual toxin to eliminate heat pathogen， and half from nourishing yin and unblocking collaterals to strengthen yin， for which Xuanmai Ganju Decoction and Erzhi Pills （玄麦甘桔汤合二至丸） can be used and modified according to the symptoms. At the same time， we should pay attention to the simultaneous internal and external treatment， and emphasize the importance of daily protection in the treatment of the disease.
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ObjectiveTo investigate the effect and mechanism of Shenling Baizhusan on the treatment of oligoasthenospermia with hyperuricemia （HUA）. MethodThirty-two male Kunming （KM） mice were randomly divided into blank group （n=6）， model group （n=6）， high-dose Shenling Baizhusan group （n=7）， low-dose Shenling Baizhusan group （n=7）， and febuxostat group （n=6）. Except for the blank group， all other groups received intraperitoneal injection of potassium oxazinate suspension （600 mg·kg-1） for 7 days. After modeling， the high-dose Shenling Baizhusan group and the low-dose Shenling Baizhusan group were orally administered with 20.14 g·kg-1 and 10.07 g·kg-1 of Shenling Baizhusan， respectively. The Febuxostat group was orally administered with 0.25 g·kg-1 of Febuxostat， while the blank group and model group were orally administered with the same volume of physiological saline. Oral administration was performed once a day for 14 consecutive days， after which samples were collected. Biochemical methods were used to measure serum uric acid （UA）， superoxide dismutase （SOD） and malondialdehyde （MDA） in testicular tissue. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in testicular tissue and evaluate the spermatogenesis function. Automated sperm analyzer was used to measure sperm density and motility. Single-cell gel electrophoresis （SCGE） was used to assess sperm DNA integrity. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） was used to detect testicular cell apoptosis rate. Western blot analysis was performed to measure the protein expression levels of Kelch-like ECH-associated protein 1 （Keap1）， nuclear factor E2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and Caspase-3 in testicular tissue. Real-time polymerase chain reaction （PCR） was conducted to evaluate the mRNA expression levels of Keap1， Nrf2， and HO-1 in testicular tissue. ResultCompared with the blank group， the model group showed elevated serum UA level （P<0.01）， decreased testicular spermatogenesis function， sperm density， and motility （P<0.01）， and increased sperm trailing rate and testicular cell apoptosis rate （P<0.01）. Compared with the model group， the high-dose Shenling Baizhusan group showed significant improvements in the above-mentioned indicators （P<0.05， P<0.01）. Additionally， the expression levels of Keap1， Bax， and Caspase-3 in testicular tissue were reduced， while the expression levels of Nrf2， HO-1， and Bcl-2 increased （P<0.05， P<0.01）. The mRNA level of Keap1 decreased （P<0.05， P<0.01）， while the mRNA levels of Nrf2 and HO-1 increased （P<0.05， P<0.01）. ConclusionShenling Baizhusan can significantly improve HUA oligoasthenospermia， and its mechanism may be related to the Nrf2/antioxidant response element （ARE） signaling pathway.
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italic>γ-Aminobutyric acid (GABA) is a crucial inhibitory neurotransmitter found in various cells in the human body. While the GABAergic system is typically associated with the nervous system, recent research has revealed that immune cells and tumor cells also express components of this system. In the tumor microenvironment (TME), GABA is secreted to act extracellularly on other cells. GABA is metabolized via the GABA shunt and is involved in the tricarboxylic acid (TCA) cycle by generating succinate, which can provide energy for tumor cells. Activation of GABA receptors (GABARs) is a major pathway through which GABA participates in the regulation of antitumor immune responses. The activation of GABA type A receptors (GABAARs) can inhibit the activation and proliferation of T cells, elicit anti-inflammatory macrophages, and promote tumor cell growth and migration, while activation of GABA type B receptors (GABABRs) is generally considered to inhibit cancer cell migration and induce cancer cell apoptosis. In general, receptor activation inhibits immune cells, but the effect on tumor cells varies. Additionally, the downregulation of the expression levels of GABA transporters (GATs) is involved in tumor progression. Although antagonists of GABA metabolism and drugs that act on GABA receptors are considered therapeutic drugs for tumors, there have been few clinical studies conducted on them.
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Depressive disorder seriously affects people's physical and mental health.Acupuncture is a safe and effective treatment for depression,yet,its mechanism is unclear.Therefore,acupuncture's action mechanism in intervening depression was summarized from several perspectives,including morphology and ultrastructure of neurons in depression-related brain areas,function and structure of glial cells,brain functional and structural connectivity,and neuroelectrophysiology.It's discovered that acupuncture can repair the morphological and ultrastructural damage of neurons in the hippocampus and prefrontal lobe,mitigate the functional and structural injuries of glial cells in the hippocampus and prefrontal lobe,strengthen functional connectivity and heal structural connection,and promote neuroelectrophysiological activities,which possibly are the principal mechanisms of how acupuncture works in intervening depressive disorder.
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Comprehensive geriatric assessment(CGA), one of the core approaches of geriatrics, is a strategy and option for the management of common clinical problems in the elderly.It has a guiding role in surgery, radiotherapy, chemotherapy, endocrine therapy and anti-tumor clinical research for elderly breast cancer patients, and can be used to evaluate treatment tolerance, monitor intervention effects, adjust treatment plans and strategies, and improve patients' quality of life and life satisfaction.This article reviewed the clinical application of CGA in elderly patients with breast cancer.
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It is quiet rare that transient high level of elevated antiphospholipid (aLP) antibodies are triggered by infective endocarditis(IE). We report a young woman who went to hospital because of fever was diagnosed with IE, she was suffering from lower and upper arterial thrombosis, tests showed that anticardiolipin and anti-beta2-glycoprotein(GP)-1 IgM antibodies elevated highly. She had mitral valve replacement surgery, echocardiography detected vegetation on mitral valve, multiple blood culture showed negative, after treatment of antibiotics,the second cardiac surgery and warfarin, the patient got stable condition and the upper limb arterial thrombosis disappeared. Three months later, aLP antibodies tests came back negative. This case illustrate that IE could lead to transient high level of elevated aLP antibodies, does that increase the risk of thrombosis of IE patient is unknown, what if we find that phenomenon earlier and prescribe anticoagulant drugs, that need more observation.
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Pyroptosis is a newly discovered way of proinflammatory programmed cell death. Pyroptosis is mediated by caspase-1 (Caspase-1). Through the cleavage and activation of GSDM family proteins, small pores are formed on the cell membrane, thus rapid lysis of the cell membrane process, and then leads to intracellular inflammatory content release thereby causing inflammatory response. The three pyroptosis pathways are the classical pathway of Caspase-1, the non-classical pathway of Caspase-4, 5, and 11, and the special pathway of Caspase-3 or Hela cells. Pyroptosis plays an important role in the occurrence, invasion, and metastasis of breast cancer, and is closely related to the prevention and treatment of breast cancer. This article reviews the biological mechanism of pyroptosis and its research progress in breast cancer, to provide a new idea for clinicians in the treatment of breast cancer.
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ObjectiveTo observe the effects of Sinisan on behaviors and NOD-like receptor protein 3 （NLRP3） inflammasomes of depressed rats induced by chronic unpredictable mild stress （CUMS） and further explore the anti-depressant mechanism of Sinisan. MethodFifty male rats were randomly divided into a normal group， a model group， an NLRP3 inhibitor （MCC950） group （10 mg·kg-1）， and low- （2.5 g·kg-1） and high-dose （5 g·kg-1） Sinisan groups， with 10 rats in each group. The depression model was induced by 42 d CUMS in rats except for those in the normal group. Drug intervention was performed on the 22nd day of modeling by gavage in the Sinisan groups and by intraperitoneal injection in the MCC950 group. Except for the MCC950 group， the remaining four groups received 10 mg·kg-1 physiological saline by intraperitoneal injection， while the rats in the model group， the normal group， and the MCC950 group were administered with 3 mL of physiological saline by gavage. Twenty-one days later， the sucrose preference test and open field test were performed. Western blot was used to detect the protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， ionized calcium-binding adapter molecule 1 （Iba1）， and CD68 in the hippocampus of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the hippocampus of rats. Nissl staining and TUNEL were used to assess the pathological changes and apoptosis level in the hippocampal CA1 region of rats， respectively. ResultThe sucrose preference rate and consumption volume in the sucrose preference test， the total distance， the percentage of central movement distance， and the percentage of residence time in the open field test of rats in the model group were lower than those in the normal group （P<0.01）. Compared with the model group， the Sinisan groups and the MCC950 group showed improved depression-like behaviors， apoptosis level in the hippocampal CA1 region， and neuron loss to varying degrees. Sinisan could reduce the levels of IL-1β， IL-18， Bax， Iba1， and CD68 in the hippocampus （P<0.05， P<0.01）， increase the level of Bcl-2 （P<0.05， P<0.01）， and inhibit the protein expression of NLRP3， ASC， and Caspase-1 related to NLRP3 inflammasomes （P<0.05， P<0.01）. ConclusionSinisan can improve the depression-like behaviors and pathological damage of hippocampal neurons in CUMS-induced rats， and the mechanism may be related to the inflammatory response mediated by the NLRP3 inflammasome signaling pathway.
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@#Objective To investigate the relationship between gait spatiotemporal parameters and balance function in stroke hemiplegic patients. Methods From September, 2018 to March, 2020, 76 stroke hemiplegic patients (38 in Brunnstrom Ⅳ and V, respectively) were assessed balance function with Active Balancer EAB-100 and Star Excursion Balance Test (SEBT), and gait parameters of speed, cadence and asymmetry, named step length asymmetry ratio (SLA), swing time asymmetry ratio (SWTA), stance time asymmetry ratio (STA), maximum flexion angle ratio (MFA) of hip and knee. The correlation among gait parameters and balance function was analysed. Results The balance and gait parameters were better in those in Brunnstrom V than in Brunnstrom Ⅳ (|t| > 2.268, P < 0.05). The speed and cadence correlated with the most balance indexes (|r| > 0.335, P < 0.05). SLA correlated with SEBT in Brunnstrom Ⅳ patients (r = -0.467~-0.613, P < 0.01), while it correlated with medial-lateral (M-L) stability limits in Brunnstrom V patients (r = -0.356, P = 0.028). SWTA correlated with stability limit of Anterior-Posterior (A-P) (r = -0.335, P = 0.040) and M-L (r = 0.510, P = 0.001), and most of SEBT (r = -0.330~ -0.445, P < 0.05) in Brunnstrom Ⅳ patients. MFA of hip and knee correlated with balance indexes in Brunnstrom Ⅳ patients (|r| > 0.326, P < 0.05), while MFA of knee correlated with most balance indexes in Brunnstrom V patients (r > 0.329, P < 0.05), and MFA of hip correlated with A-P stability limit (r = 0.369, P = 0.023). Conclusion Both speed and cadence of steps can well respond to the balance function in stroke hemiplegic patients. For the asymmetry, it is related with balance in patients with poorer recovery.
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Objective:To explore a new method of diagnosing and identifying renal transplantation clinical almost tolerance through a diagnostic model using plasma proteomics.Methods:From November 2011 to November 2012, plasma samples from 43 subjects were collected and divided into the groups of clinical almost tolerance(18 cases), rejection(12 cases)and healthy control(13 cases). Protemic analysis of plasma samples was performed by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS). Differential mass spectrometry peaks were screened and diagnostic model was established by Biomarker Wizard and Biomarker Pattern software. Identification of mass spectrometric peaks of nodes in the diagnostic model was carried out by searching the databases of SWISS-PROT and TrEMBL using ExPASy's TagIdent tool.Results:A total of 21 differential proteins peaks were obtained( P<0.05). Diagnostic model was composed of five mass spectrum peaks of 2 565.15, 1 966.28, 6 674.78, 1 103.27, 1 716.69 and 1 966.28.The sensitivity, specificity and area under the ROC curve of model were 83.3%, 92.0% and 0.951 respectively for diagnosing clinical almost tolerance.Bioinformatic identification results of mass spectrometric peaks of nodes in model were proteins of ANFB, MCH, TFF1, PDYN and PSME3. Conclusions:Establishing a diagnostic mode by plasma proteomics may be effectively employed for diagnosing clinical almost tolerance in kidney transplant.
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Objective:To analyze the risk factors of systemic inflammatory response syndrome (SIRS) caused by wasp stings.Methods:A prospective case-control study was conducted to analyze the clinical data of 225 patients with wasp stings admitted to Taihe hospital of Shiyan City and Ankang Central Hospital from January 2014 to December 2018, including 131 males and 94 females, with the age of 49 (41, 60) years. The patients were divided into SIRS group ( n=62) and non-SIRS group ( n=163) according to the SIRS diagnostic criteria. The data were collected including gender, age, sting in the head, sting in waist and back, sting in the abdomen, sting in the limbs, number of stings, admission time, hospitalization day, and mortality. The plasma levels of interleukin(IL)-6 and IL-8 in peripheral blood of the patients were analyzed by ELISA method. The whole genome DNA was extracted from white blood cells, and the IL-6: -174G/C, -572G/C, -597G/A, -634C/G and IL-8: -251A/T, -738T/A, -845T/C, + 396T/G were selected for research. The PCR method was used to perform bidirectional sequencing and comparison after amplification, and record the genotyping and frequency. The risk factors of SIRS caused by wasp stings were investigated by univariate analysis and multivariate Logistics regression analysis. Results:(1) The two groups showed significant differences in sting in the limbs, sting in waist and back, sting in the abdomen, number of stings, hospitalization day and mortality ( P<0.01), while there were no significant differences in gender, age, sting in the head and admission time ( P>0.05). (2) ELISA test showed the plasma levels of IL-6 and IL-8 in SIRS group were higher than those in non-SIRS group ( P<0.01). (3) Three genotypes of CC, GC and GG were observed in IL-6-572G/C. There were significant differences in the frequencies of genotypes and alleles between SIRS group and non-SIRS group ( P<0.01). Three genotypes of AA, AT and TT were observed in IL-8 -251A/T. There were significant differences in the frequencies of genotypes and alleles between SIRS group and non-SIRS group ( P<0.01). (4)Univariate analysis showed sting in waist and back, sting in the abdomen, sting in the limbs, number of stings, IL-6-572G allele, IL-8-251T allele were related to SIRS caused by wasp stings ( P<0.01). (5)Multivariate Logistics regression analysis showed limb stings ( OR=2.15), number of stings ≥10 ( OR=11.10), IL-6-572G allele ( OR=3.91) and IL-8-251T allele ( OR=3.97) were significantly related to SIRS caused by wasp stings ( P<0.05 or 0.01). Conclusions:The plasma levels of IL-6 and IL-8 are increased in patients with SIRS after wasp stings. The limbs stings, number of stings ≥10, IL-6 -572G and IL-8 -251T are all independent risk factors for SIRS caused by wasp stings.
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Objective:To explore the clinical features, diagnosis and differential diagnosis of splenic marginal zone lymphoma.Methods:The clinical diagnosis and differential diagnosis processes of 3 cases of CD5 - CD10 - B cell non-Hodgkin lymphoma with splenomegaly and cytopenia who were admitted to Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology in 2019 were retrospectively analyzed, and the relevant literature was reviewed. Results:The 3 cases were all elderly patients with varying degrees of splenomegaly and cytopenia. CD5 - CD10 - monoclonal B lymphocytes were found in the bone marrow or lymph nodes. Based on the patient's clinical characteristics, peripheral blood and bone marrow morphology, immunophenotype and genetic characteristics, 2 patients were diagnosed as splenic marginal zone lymphoma, and 1 patient was diagnosed as diffuse large B-cell lymphoma. Conclusions:The diagnosis of splenic marginal zone lymphoma requires comprehensive analysis of clinical characteristics, peripheral blood and bone marrow morphology, immunophenotype and genetic characteristics. Careful differentiation from other CD5 - CD10 - small B-cell lymphomas is also needed. The next-generation gene mutation high-throughput sequencing and mutational spectrum analysis will help the accurate diagnosis of atypical and difficult cases.
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The potential effect mechanism of acupuncture for perimenopausal syndrome is analyzed and summarized from five aspects, i.e. the influence on reproductive endocrine system, the regulation on nervous system, the improvement of immune function, the intervention on free radical metabolism and the regulation of adverse emotions. It is believed the mechanism research of acupuncture in the treatment of perimenopausal syndrome should be deepened in terms of acupoint specificity and the influence of acupoint compatibility based on the characteristics of acupuncture therapy itself. In clinic, the research on therapeuticmethods and treatment frequency should be enhanced.
Subject(s)
Acupuncture , Acupuncture Points , Acupuncture Therapy , Emotions , PerimenopauseABSTRACT
To systematically evaluate the efficacy and safety of Ningxinbao Capsules in treatment of arrhythmia by Meta-analysis. Randomized controlled trial(RCT) or quasi-randomized control trial(Quasi-RCT) on Ningxinbao Capsules treating arrhythmia were obtained by computer-based retrieval in CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and EMbase as well as manual retrieval, with time limit from database establishment to April 7, 2020. According to the inclusion and exclusion criteria of trials, all RCTs were screened and evaluated. Then the effective data were collected and RevMan 5.3 Meta-analysis software was used for analysis. Thirteen trials were included, involving 1 379 patients in total. Ningxinbao Capsules combined with anti-arrhythmia Western medicine were adopted as the intervention, and the patients in control group were treated with the anti-arrhythmia Western medicine alone. Meta-analysis results showed that as compared to control group, Ningxinbao Capsules combined with anti-arrhythmia Western medicine group was superior in clinical efficacy, dynamic electrocardiogram and average heart rate in patients with bradycardia, with indicated statistically significant differences. Ningxinbao Capsules had fewer adverse reactions and could relieve the toxic and side effects of anti-arrhythmia medicine possibly. The study showed that Ningxinbao Capsules played a role in treatment of arrhythmia and was relatively safe. However, due to the limited quality of the included studies, high-quality clinical trials are needed to verify the conclusions.
Subject(s)
Humans , Bradycardia , Capsules , Drugs, Chinese Herbal/adverse effects , Treatment OutcomeABSTRACT
Objective:To explore the mechanism of Bushen Huoxue prescription in regulating the related factors in phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt）/ mammalian target of rapamycin （mTOR） pathway and improving ovarian reserve function of rats with diminished ovarian reserve （DOR）. Method:Sixty DOR model rats were duplicated by Ataya method （intraperitoneal injection of cyclophosphamide） and then randomized into the model group， estradiol valerate （0.000 9 g·kg<sup>-1</sup>） group， and high- （33 g·kg<sup>-1</sup>）， middle- （16.5 g·kg<sup>-1</sup>） and low-dose （8.25 g·kg<sup>-1</sup>） Bushen Huoxue prescription groups， with 12 rats in each group. Another 12 healthy rats were classified into the blank control group. The rats in each group were given the corresponding drugs by gavage， while those in the blank control group and model group received the same volume of normal saline， once per day， for 14 successive days. After treatment， the ovarian tissue was stained with hematoxylin-eosin （HE） for observing the changes in quantities of primary follicles， mature follicles， and total follicles under a light microscope， followed by the detection of vascular endothelial growth factor （VEGF） expression in the ovarian tissue by immunohistochemistry. The protein expression levels of PI3K， Akt， mTOR， and cysteine-dependent aspartate-directed protease-3 （Caspase-3） in the ovarian tissue were assayed by Western blot， whereas the mRNA expression levels of PI3K， Akt， and mTOR were measured by Real-time polymerase chain reaction （Real-time PCR）. Result:As revealed by comparison with the blank control group， the quantities of mature follicles and total follicles in the ovarian tissue of model group were significantly reduced （<italic>P</italic><0.05， <italic>P</italic><0.01）. The protein expression levels of VEGF and Caspase-3 in the ovarian tissue were increased （<italic>P</italic><0.05）， while the protein and mRNA expression levels of PI3K， Akt， and mTOR were decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， Bushen Huoxue prescription at the high and middle doses elevated the quantities of mature follicles and total follicles to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）， and VEGF increased most significantly in the middle-dose Bushen Huoxue prescription group （<italic>P</italic><0.05）. Caspase-3 in the low-， middle-， and high-dose Bushen Huoxue prescription groups and the western medicine group declined. The protein and mRNA expression levels of PI3K， Akt， and mTOR were up-regulated in the middle- and high-dose Bushen Huoxue prescription groups （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the levels in the middle-dose Bushen Huoxue prescription group were closer to those in the blank control group. Conclusion:Bushen Huoxue prescription effectively improves the ovarian reserve function of rats with DOR and increases the number of follicles possibly by up-regulating VEGF expression in the ovarian tissue， activating the PI3K/Akt/mTOR signaling pathway， and regulating the content of Caspase-3.
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Objective:To observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 （APP/PS1） dementia mice on cognitive and memory impairment and to explore its mechanism. Method:The 40 APP/PS1 mice were divided into model group （given Physiological saline）， low and high-dose modified Shuyuwan （14，64 g·kg<sup>-1</sup>）group， and donepezil group （1 mg·kg<sup>-1</sup>） and 10 wild mice were set as the blank control group （given Physiological saline）. All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze， the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of <italic>β </italic>amyloid 1-42（A<italic>β</italic><sub>1-42</sub>） in mouse hippocampus was detected by immunohistochemistry， and the expression of ionized calcium-binding adapter molecule 1（Iba1）， a marker of hippocampal microglia （MG） and Nitric oxide synthase（iNOS）， a marker of actived MG， were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3（Nlrp3）， Apoptosis-associated speck-like protein containing a Caspase-recruitment domain （ASC）， cysteine protease-1（Caspase-1）and interleukin-1 beta （IL-1<italic>β</italic>） were detected by Western blot， and the expression of IL-1<italic>β</italic>， tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>）and interleukin-18 （IL-18） mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the blank control group， the memory and space exploration ability of the model group were significantly reduced （<italic>P</italic><0.05）， the number of hippocampal neurons decreased， the deposition of A<italic>β</italic><sub>1-42</sub> increased， the markers of actived MG Iba1，iNOS increased， the protein expression of Nlrp3， ASC， Caspase-1， IL-1<italic>β</italic> increased significantly （<italic>P</italic><0.05）， and the mRNA expression of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> increased significantly （<italic>P</italic><0.05）. Compared with model group， the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability （<italic>P</italic><0.05）， increase the number of hippocampal neurons， reduce A<italic>β</italic><sub>1-42</sub> deposition， reduce the activation of MG， and reduce the protein expression of Nlrp3， ASC， Caspase-1 and IL-1<italic>β</italic> （<italic>P</italic><0.05）， and reduced the expression of IL-1<italic>β</italic> mRNA （<italic>P</italic><0.05）. Conclusion:Modified Shuyuwan can reduce the expression of IL-1<italic>β</italic> and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway， and relieve nerve inflammation and pathological injury of AD.
ABSTRACT
Objective:To observe the effect of Jinxiangdan （JXD） on NOD-like receptor pyrin domain-containing-3 （NLRP3）/cysteine-dependent aspartate-directed protease-1 （Caspase-1）/interleukin-1<italic>β</italic> （IL-1<italic>β</italic>） signaling pathway in myocardium of rats with myocardial ischemia-reperfusion injury （MIRI） and explore the protective effect and mechanism of JXD against MIRI. Method:Fifty male SD rats were randomly divided into the sham operation group， model group， high- and low-dose JXD groups， and positive drug （Di'ao Xinxuekang） group， with 10 rats in each group. Seven days before modeling， rats in the JXD groups were separately treated with intragastric administration of 0.72 and 0.18 g·kg<sup>-1</sup> JXD tablets， the ones in the sham operation group and model group with the same volume of normal saline， and those in the positive drug group with 1.29 g·kg<sup>-1</sup> Di'ao Xinxuekang. Twelve hours after the last intragastric administration， the anterior descending branch of the left coronary artery was ligated for 30 min and then re-perfused for 60 min for inducing MIRI. ST segment elevation was detected by electrocardiogram（ECG） for model evaluation. The contents of creatine kinase （CK） and lactate dehydrogenase （LDH） in cardiac tissue were measured by colorimetry. Hematoxylin-eosin （HE） staining was conducted for observing myocardial histopathological changes， followed by the detection of cardiomyocyte apoptosis by DNA in situ nick end-labeling （TUNEL） assay. The protein and mRNA expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> were detected by Western blot and real-time polymerase chain reaction （Real-time PCR）， respectively. Result:Compared with sham operation group， the model group exhibited obviously elevated ST segment （<italic>P</italic><0.01）， enhanced CK and LDH activities in the myocardium （<italic>P</italic><0.01）， increased apoptotic cardiomyocytes （<italic>P</italic><0.01）， and up-regulated NLRP3， Caspase-1， and IL-1<italic>β</italic> protein and mRNA expression （<italic>P</italic><0.01）. Compared with model group， JXD at both the high and low doses and Di'ao Xinxuekang significantly lowered the ST segment （<italic>P</italic><0.05，<italic>P</italic><0.01）， diminished the CK and LDH activities in myocardial tissue （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved the apoptosis of cardiomyocytes （<italic>P</italic><0.05，<italic>P</italic><0.01）， and down-regulated the mRNA and protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> in myocardial tissue （<italic>P</italic><0.05，<italic>P</italic><0.01）. The ST segment of ECG in the low-dose JXD group was increased as compared with that in the Di'ao Xinxuekang group （<italic>P</italic><0.05）， while the ST segment in the high-dose JXD group was obviously elevated （<italic>P</italic><0.05）. Besides， the green fluorescence intensities in the low- and high-dose JXD groups and the Di'ao Xinxuekang group remarkably declined （<italic>P</italic><0.05，<italic>P</italic><0.01）. The mRNA and protein expression levels of NLRP3， Caspase-1， and IL-1<italic>β</italic> in the high-dose JXD group were down-regulated （<italic>P</italic><0.05）. Conclusion:JXD alleviates MIRI possibly by lowering NLRP3 and IL-1<italic>β</italic> expression and inhibiting cardiomyocyte apoptosis.
ABSTRACT
Objective:To investigate the mechanism of Shugan Bushen Yulin decoction in inhibiting voltage-dependent anion-selective channel protein 2 （VDAC2） gene methylation， affecting sperm mitochondrial function， and improving sperm motility through the cyclic adenosine monophosphate/protein kinase A （cAMP/PKA） pathway. Method:Forty male SD rats were randomly divided into the blank group， model group， high- and low-dose Shugan Bushen Yulin decoction groups， and L-carnitine group， with eight rats in each group. Adenine （0.05 g·kg<sup>-1</sup>） was administered by gavage for 14 d for inducing oligospermia and asthenospermia. Rats in the Shugan Bushen Yulin decoction groups were treated with intragastric administration of 32.4， 8.1 g·kg<sup>-1 </sup>Shugan Bushen Yulin decoction， respectively， while those in the L-carnitine group received 0.27 g·kg<sup>-1</sup> L-carnitine by gavage. Following the measurement of sperm motility using an automatic sperm analyzer， the pathological changes in testicular tissue were observed by hematoxylin-eosin （HE） staining. Sperm mitochondrial membrane potential was detected by flow cytometry. The expression of VDAC2 in the testicular tissue was determined by immunofluorescence assay. Real-time polymerase chain reaction （Real-time PCR） was conducted for detecting VDAC2 mRNA expression in testicular tissue. The methylation of VDAC2 gene was examined using bisulfite sequencing. The cAMP expression in testicular tissue was detected by enzyme-linked immunosorbent assay （ELISA）， and the PKA protein expression in testicular tissue by Western blot. Result:Compared with the blank group， the model group exhibited significantly decreased sperm density and motility （<italic>P</italic><0.01）， increased mitochondrial membrane potential （<italic>P</italic><0.01）， down-regulated VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in testicular tissue （<italic>P</italic><0.01）， and elevated VDAC2 gene methylation （<italic>P</italic><0.01）. Compared with the model group， L-carnitine and Shugan Bushen Yulin decoction at the high and low doses all remarkably increased the sperm density and motility and mitochondrial membrane potential （<italic>P</italic><0.01）， up-regulated VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in the testicular tissue （<italic>P</italic><0.01）， and lowered the methylation of VDAC2 in testicular tissue （<italic>P</italic><0.01）. The comparison with the L-carnitine group showed that the sperm density and motility and mitochondrial membrane potential in the low-dose Shugan Bushen Yulin decoction group declined significantly （<italic>P</italic><0.01）. The VDAC2 mRNA and protein expression， PKA protein expression， and cAMP content in the testicular tissue were significantly down-regulated （<italic>P</italic><0.01）， while the methylation of VDAC2 was significantly enhanced （<italic>P</italic><0.01）. Conclusion:Shugan Bushen Yulint decoction may inhibit VDAC2 gene methylation， increase VDAC2 expression， regulate cAMP/PKA pathway， and change mitochondrial membrane potential to enhance the sperm motility.