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Objective To apply ultrasound to monitor cardiac function changes after anthracycline exposure in children with acute leukemia,in order to obtain the indicators of early changes in their cardiac function.Methods Children with acute leukemia from 2018 March to December 2020 in the Children's Hospital of Kunming Medical University were enrolled according to the inclusion and exclusion criteria,their routine cardiac ultrasound and tissue Doppler condition were recorded,and the changes in systolic function were evaluated by Tei index including TeiS,TeiRL,TeiM and TeiT.Results The mean values of LVEF in the normal and the experimental group were both above 60%.FS,SV,and EDV were all in the normal range.While common indicant,the index of TDI or Tei was not statistically significant(P>0.05).The levels of TeiM,TeiRL and TieT in the groups that received a total dose of 200 mg/m2 anthracyclines and 250 mg/m2 were significantly different from that before treatment(P<0.05).Conclusion Tei index can be utilized as a sensitive indicator for early changes in left and right heart function after children with acute leukemia are exposed to anthracyclines.
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Objective·To investigate the effect of ceria nanoparticles-polyethylene glycol(CeNP-PEG)on scavenging reactive oxygen species(ROS)and alleviating disease activity in dextran sulphate sodium(DSS)-induced colitis mice.Methods·CeNP was synthesized with the hydrates of cerium acetate,oleamine,and xylene,which was modified with polyethylene glycol-stearyl phosphatidylethanolamine(mPEG-DPSE)to obtain CeNP-PEG.Then CeNP-PEG was purified.The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy(TEM)and dynamic light scattering(DLS).Mouse macrophages(Raw264.7)were cultured in vitro and induced to a pro-inflammatory phenotype(M1 phenotype).M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG,respectively,and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB(NF-κB)signaling pathway.DSS-induced colitis mice models were constructed,and CeNP-PEG(1.0 mg/mL)was intravenously administrated for 3 times via tail vein during the modeling period.Meanwhile,the body weight,fecal characteristics,and frequency of rectal bleeding in mice were monitored in the normal control group(Normal group),the model group(DSS group),and the CeNP-PEG treatment group.The disease activity index(DAI)was calculated to evaluate the intestinal inflammation.The level of ROS in mouse intestinal tissues was detected by dihydroethidine(DHE)staining and the mRNA expression levels of inflammatory cytokines interferon-γ(Ifn-γ),interleukin-6(Il-6),Il-1β and tumor necrosis factor-α(Tnf-α)were detected by real-time quantitative PCR(RT-qPCR).Results·The hydrated particle size of synthesized CeNP-PEG was(6.96±0.27)nm,and the average zeta potential was(-6.02±1.31)mV.Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group.The expression of NF-κB inhibitor-α(IκB-α)decreased,and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG.In the DSS-induced colitis models,mice in the CeNP-PEG treatment group lost less weight than those in the DSS group(P= 0.000)and had lower DAI scores(P=0.000).The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ,Il-1β,Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group(P=0.000),and all of them significantly decreased in the CeNP-PEG treatment group.The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group,and the fluorescence intensity decreased in the CeNP-PEG treatment group.Conclusion·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages,eliminate intestinal ROS,improve the intestinal inflammatory microenvironment,and alleviate the disease activity of DSS-induced colitis in mice.
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Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.
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The World Health Organization has declared that the outbreak of coronavirus disease 2019(COVID-19) is a global pandemic. As mutations occurred in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the global epidemic still needs further concern. Worryingly, the effectiveness and neutralizing activity of existing antibodies and vaccines against SARS-CoV-2 variants is declining. There is an urgent need to find an effective antiviral medication with broad-spectrum inhibitory effects on novel coronavirus mutant strains against the SARS-CoV-2 infection. Neutralizing antibodies play an important role in the prevention and treatment of COVID-19. The interaction of spike-receptor-binding domain (Spike-RBD) of SARS-CoV-2 and human angiotensin-converting enzyme 2 (ACE2) is the first and critical step of SARS-CoV-2 infection. Hence, the SARS-CoV-2 Spike-RBD is a hot target for neutralizing antibodies development. Evusheld, the combination of Tixagevimab and Cilgavimab monoclonal antibodies (mAbs) targeting Spike-RBD exhibits neutralizing activity against BA.2.12.1, BA.4 and BA.5, which could be used as pre-exposure prophylaxis against SARS-CoV-2 infection. The nucleocapsid (N) protein is a conservative and high-abundance structural protein of SARS-CoV-2. The nCoV396 monoclonal antibody, isolated from the blood of convalescent COVID-19 patients against the N protein of SARS-CoV-2. This mAb not only showed neutralizing activity but also inhibits hyperactivation of complement and lung injury induced by N protein. The mAb 3E8 targeting ACE2 showed broadly neutralizing activity against SARS-CoV-2 and D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1 variants in vitro and in vivo, but did not impact the biological activity of ACE2. Compared with neutralizing antibodies, small molecule inhibitors have several advantages, such as broad-spectrum inhibitory effect, low cost, and simple administration methods. Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Known drugs such as chloroquine and hydroxychloroquine could also block the infection of SARS-CoV-2 by interacting with residue Lys353 in the peptidase domain of ACE2. The transmembrane protease serine 2 (TMPRSS2) inhibitors Camostat mesylate and Proxalutamide inhibit infection by blocking TMPRSS2 mediates viral membrane fusion. The main protease inhibitor Paxlovid and RNA-dependent RNA polymerase inhibitor Azvudine have been approved for treatment of COVID-19 patients. This review summarizes the current research status of neutralizing antibodies and small molecule inhibitors and prospects for their application. We expect to provide more valuable information for further studies in this field.
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In the 18th century, the trade of medicinal materials in East Asia showed a trend of rapid development, and by the second half of the 18th century, it became the largest commodity category in East Asia's international trade. The growth of medicinal material trade during this period was not a simple trade issue, but was closely related to a series of changes in economic fields, such as the market network, trade balance and production. The changes in the international trade environment from the 17th to the 19th centuries greatly increased the demand for medicinal materials. It also affected the production of medicinal materials. The medicinal material industries in East Asian countries were characterised by specialisation and marketisation, and provided the market with abundant and high-quality medicinal materials. In turn, the development of the medicinal material industry promoted international trade, making medicinal materials the largest traded commodity in East Asia. In the 18th century, the development of medicinal material trade promoted the recalibration of international trade, and changed the commodity structure of East Asian trade. It is a result of the transformation of international trade and economic relations, and an important participant in the development of East Asian economy. Trade of medicinal materials in the 18th century expanded the market network and formed a positive interaction between trade and production, and reshaped the international trade structure of East Asia.
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OBJECTIVE To investigate the effects and mechanism of curcumin （Cur） solid lipid nanoparticles （SLN） loaded with flower-shaped lactose （Cur-SLN-FL） for lung inhalation on lung inflammation in chronic obstructive pulmonary disease （COPD） model mice. METHODS Firstly， the irritation of Cur-SLN-FL to lung tissue was investigated， and the local safety of inhalation materials was determined. Then， 10 mice were randomly selected and injected with normal saline through the trachea， and the other 50 mice were all injected with porcine trypsin solution （concentration of 33.3 mg/mL， dosage of 1.0 mL/kg） to induce the COPD model. After normal feeding for 28 days， the mice were divided into sham operation group， model group， budesonide group （20 mg/kg）， Cur-SLN-FL high-dose and low-dose groups （100， 50 mg/kg）， with 10 mice in each group. The corresponding drugs were given to each group， once a day， for 14 consecutive days. Twenty-four hours after the last administration， the bronchoalveolar lavage fluid （BALF） of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin （HE） staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 （NLRP3）， caspase-1 and interleukin-1β （IL-1β） in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3， caspase-1 and nuclear factor of kappa B（NF-κB） in lung tissue. RESULTS Cur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group， the total number of white blood cells， neutrophils and eosinophils in BALF of the model group increased significantly， while the number of lymphocytes decreased significantly （P＜0.05）； ciliated columnar epithelium proliferated， thickened and exfoliated in the trachea， mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue；the deposition of collagen fibers in lung tissue increased significantly， the positive expressions of NLRP3， caspase-1 and IL-1β in lung tissue increased significantly， and the expressions of NLRP3， caspase-1 and NF-κB protein in lung tissue all increased significantly （P＜0.05）. After giving Cur-SLN-FL， the above indexes were all improved to certain extent. CONCLUSIONS Cur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice，and its mechanism may be through regulating the NLRP3 signaling pathway， inhibiting the expressions of caspase-1， NF-κB and IL-1β， thus alleviating the process of pulmonary fibrosis in COPD model mice.
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Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
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Animals , Rats , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/genetics , Reactive Oxygen Species , Tumor Suppressor Protein p53/genetics , Signal Transduction , Liver , Aging , Cell Cycle Proteins , Interleukin-6ABSTRACT
In recent years， with the changes of population structure and the aggravation of aging， the prevalence of osteoporosis is increasing year by year. Osteoporosis poses great impacts on the body and family life of the patients and increases the burden on the society. Therefore， the research on osteoporosis is urgent and significant. The imbalance between osteoblasts， osteocytes， and osteoclasts causes abnormal bone metabolism， which destroys the fine structure of bone and increases bone fragility， thus increasing the risk of fracture. Although the pathogenesis of osteoporosis is complex， researchers have confirmed that the imbalance of the endocrine system directly or indirectly promotes the occurrence and development of osteoporosis. Traditional Chinese medicine （TCM） is a treasure of Chinese traditional culture and plays a key role in safeguarding the public health. With unique therapeutic effects and advantages， TCM has been widely accepted. Chinese medicines， moxibustion， acupuncture and other TCM therapies have play a unique role in the treatment of osteoporosis. Particularly， TCM prevention and treatment of osteoporosis by regulating the endocrine system has received extensive attention. By reviewing relevant literature， this paper introduces the research progress in the TCM modulation of bone metabolism and alleviation of bone loss by regulating estrogen， calcitonin， and parathyroid hormone in the endocrine system and affecting the hypothalamus capable of regulating these hormones， aiming to provide ideas for the TCM treatment of osteoporosis.
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Objective:To identify the risk factor for prolonged post-anesthesia care unit (PACU) stay in elderly patients after painless gastrointestinal endoscopy.Methods:The elderly patients received painless gastrointestinal endoscopy from March to June 2021 in our hospital were included in this study. The information such as preoperative interview, patient′s general condition, current and past medical history, intraoperative conditions, and conditions in the PACU was collected. Patients were divided into non-prolonged group (group N) and prolonged group (group D) based on whether PACU stay was prolonged, and the risk factors for prolonged PACU stay were identified by logistic regression analysis.Results:There were 257 patients in group D and 716 cases in group N, and the incidence of prolonged PACU stay was 26.4%. Compared with group N, the proportion of preoperative frailty, smoking, intraoperative hypotension, and ratio of hypotension, somnolence and dizziness in PACU were significantly increased in group D ( P<0.05). The results of logistic regression analysis showed that preoperative frailty, smoking, intraoperative hypotension, and hypotension, somnolence and dizziness in PACU were independent risk factors for prolonged PACU stay( P<0.05). Conclusions:Preoperative frailty, smoking, intraoperative hypotension, and hypotension, somnolence and dizziness are independent risk factors for prolonged PACU stay in elderly patients after painless gastrointestinal endoscopy.
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Objective:To develop and validate a predictive model for post-anesthesia care unit (PACU) hypotension in elderly patients undergoing painless gastrointestinal endoscopy.Methods:The medical records of elderly patients of both sexes, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing painless gastrointestinal endoscopy at the Endoscopy Center of Subei People′s Hospital from March to June 2021, were retrospectively collected. The patients were randomly divided into training and validation sets according to the ratio of 3∶1. In the training set, the characteristic variables associated with PACU hypotension were screened by Lasso regression, and the independent risk factors for PACU hypotension were identified by multivariate logistic regression analysis of the characteristic variables, according to which a nomogram model predicting the risk for PACU hypotension was established.The discrimination, calibration and accuracy of the model were evaluated by calibration curve and receiver operating characteristic(ROC)curve. And the clinical practicability of the model was determined by decision curve analysis and further assessed by external validation.Results:Of the 973 patients ultimately included, 378 patients experienced PACU hypotension, with an incidence of 38.8%. Multivariate logistic regression analysis showed that age, prolonged preoperative water deprivation time, increased percentage of changes in SBP before and after induction, and intraoperative MAP <65 mmHg were independent risk factors for hypotension in the PACU, and intraoperative use of norepinephrine was a protective factor. The nomogram model was then developed based on the results. The area under the ROC curve was 0.710 (95% confidence interval [ CI] 0.672-0.748) in training set and 0.778 (95% CI 0.720-0.837) in validation set. In training and validation sets, the calibration curves were tested by Hosmer-Lemeshow good of fit test, the P values were 0.590 and 0.950, respectively. The decision curve analysis curve showed that the risk threshold of the prediction model in the training and validation sets were between 20% and 82% and between 18% and 92%, respectively, in the external validation. Conclusions:The nomogram model for prediction of PACU hypotension is successfully established based on age, prolonged preoperative water deprivation, percentage of change in SBP before and after induction, intraoperative MAP <65 mmHg and use of norepinephrine in elderly patients undergoing painless gastrointestinal endoscopy, and the model can visually and individually predict the risk of PACU hypotension.
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Objective:To investigate the feasibility of anthocyanins(C3G)antioxidant inhibition of autophagy to al-leviate epilepsy.Methods:Seventy-five SD rats were randomly divided into 5 groups:Control group,pentetrazole(PTZ)group,hydrogen peroxide(H2O2)intervention group,3-methyladenine(3-MA)intervention group,and C3G intervention group.The seizure grade,latency,and frequency were documented.Electroencephalography was employed to detect abnormal electrical discharges in the brain across.Patch clamp technique was utilized to measure action poten-tials in hippocampal neurons for each group.The concentration of 4-hydroxynonenoic(4-HNE)hippocampus was deter-mined using a specific kit.Ultrastructural alterations in hippocampal neurons were examined through electron microsco-pyissl staining was performed to assess neuronal damage within the hippocampus.Immunohistochemical staining and Western Blot were conducted to evaluate expression levels of 15-LOX,GPX4,and LC3 proteins within the hippocampus of rats.Results:Compared with the control group,the PTZ group was completely ignited and the modeling was success-ful.Compared with other epilepsy groups,the seizure grade of C3G group decreased,abnormal discharge decreased,latency increased,hippocampal neuron excitability decreased,nishi content increased,4-HNE content,15-LOX expression and LC3Ⅱ/LC3Ⅰ ratio decreased,but GPX4 expression increased(P＜0.05).Conclusion:The oxidative stress induced by epilepsy can induce excessive autophagy of neurons,and C3G can alleviate the occurrence and devel-opment of epilepsy by anti-oxidation and inhibition of autophagy.
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Objective:To evaluate the effect of berberine (BBR) on morphine-induced activation of BV2 microglial cells.Methods:The BV2 microglial cells were divided into 3 groups ( n=12 each) using a random number table method: control group (C group), morphine group (Mor group)and morphine+ BBR group (Mor+ BBR group). The Mor group was treated for 24 h with a final concentration of 200 μmol/L morphine, while C group was treated for 24 h with an equal volume of PBS buffer. Mor+ BBR group was first treated for 2 h with a final concentration of 20 μmol/L berberine, followed by treatment with a final concentration of 200 μmol/L morphine for another 24 h. The viability of BV2 microglial cells was determined using the CCK-8 assay, the concentrations of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-10 in supernatant were measured using enzyme-linked immunosorbent assay, and the expression of CD86 and NF-κB proteins in microglial cells was detected using Western blot. Results:Compared with group C, the BV2 microglial cell viability and concentrations of IL-1β and TNF-α were significantly increased, the concentrations of IL-10 were decreased, and the expression of CD86 and NF-κB in microglial cells was up-regulated in Mor group ( P<0.05). Compared with Mor group, the BV2 microglial cell viability and concentrations of IL-1β and TNF-α were significantly decreased, the concentrations of IL-10 were increased, and the expression of CD86 and NF-κB in microglial cells was down-regulated in Mor+ BBR group( P<0.05). Conclusions:BBR can inhibit morphine-induced activation of BV2 microglial cells.
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OBJECTIVE To study the tissue distribution characteristics of curcumin solid lipid nanoparticles （Cur-SLN） in rats. METHODS Cur-SLN was prepared with microemulsion. SD rats were randomly divided into Cur raw material group and Cur- SLN group， with 45 rats in each group. The rats of two groups were injected with the corresponding drugs （by Cur， 25 mg/kg） by single intravenous injection. The heart， lung， kidney and liver tisse were separated at 0.25， 0.5， 1， 2， 4， 6， 8， 12 and 24 h after administration. The contents of Cur in different tissues were determined by high-performance liquid chromatography method. Their tissue distribution was analyzed. RESULTS The linear range of detected mass concentration of Cur in heart， lung， kidney and liver tissues were 0.064 75-129.50， 0.064 75-64.75， 0.064 75-129.50， 0.064 75-129.50 μg/mL， respectively （all r＞0.99）. The lower limits of quantitation were all 0.064 75 μg/mL， and the limit of detection were all 0.012 95 μg/mL. The intra-day and inter-day precision， accuracy and extraction recovery were in line with the requirements of quantitative analysis. Compared with Cur raw material group， the contents of Cur in heart， kidney， lung （at each time point of 0.25-24 h） and liver tissue （at each time point of 0.25-1 h， 12-24 h） of samples were significantly increased in the Cur-SLN group （P＜0.05 or P＜0.01）， while the contents of Cur in liver tissue （at each time point of 2-8 h） were significantly decreased （P＜0.01）. CONCLUSIONS After Cur was prepared into solid lipid nanoparticles， its distribution in heart， kidney and lung tissues is increased.
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Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.
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Humans , Rats , Animals , Diabetic Nephropathies/drug therapy , Abelmoschus , Flavones/pharmacology , Podocytes , Tumor Necrosis Factor-alpha/metabolism , Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Fibrosis , Threonine/pharmacology , Collagen/metabolism , Serine/pharmacology , Diabetes Mellitus/drug therapyABSTRACT
With the aging of population， osteoporosis has become one of the main diseases endangering the health of the elderly in China. Therefore， the research on osteoporosis has become a hot spot. Since Chinese medicines demonstrate significant therapeutic effects on osteoporosis， this issue is attracting increasing attention from researchers， especially in the deciphering of the molecular mechanism. This paper introduces the mechanism of the prevention and treatment of osteoporosis by Chinese medicines via the mitogen-activated protein kinase （MAPK） signaling pathway， aiming to provide a theoretical basis for deciphering the mechanism of Chinese medicines in the treatment of osteoporosis and promoting their clinical application. MAPK signaling pathway mainly involves p38 MAPK， extracellular signal-regulated kinase 1/2 （ERK1/2）， c-Jun N-terminal kinase （JNK）， and extracellular signal-regulated kinase 5 （ERK5）. Studies have shown that these proteins play a role in the progression of osteoporosis by regulating cell proliferation， differentiation， and apoptosis. Chinese medicines as a unique therapy with Chinese characteristics has definite efficacy， high safety， and mild side effects. Researchers have proved by experiments that the extracts or compounds of Chinese medicines can significantly mitigate osteoporosis by regulating the proteins involved in the MAPK signaling pathway. Therefore， this article reviews the relevant studies with focus on these proteins.
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OBJECTIVE@#To explore the characteristics of infection in patients with myelodysplastic syndromes (MDS), risk factors of serious infection, and their correlation with curative effect.@*METHODS@#The clinical data of 92 newly diagnosed MDS patients with nosocomial infection from January 2016 to June 2020 in our hospital were retrospectively analyzed.@*RESULTS@#A total of 306 courses of treatment were completed in 92 newly diagnosed MDS patients. The infection rate was the highest in the first course of treatment (84.8%, 78/92), and then decreased gradually. The top three infection sites were lung, upper respiratory tract, and gastrointestinal tract. A total of 90 strains of pathogenic bacteria were detected, of which 33.4% (30/90) were gram-negative bacilli, 23.3% (21/90) were gram-positive cocci, 23.3% (21/90) were fungi, and 20.0% (18/90) were viruses. The serious infection rate among 92 patients with MDS was 22.8% (21/92). Multivariate analysis showed that neutrophil deficiency>7 days (OR=10.875, 95%CI: 2.747-43.051, P=0.001) was an independent risk factor for serious infection in MDS patients. Compared with non-severe infection group, the total effective rate of severe infection group was lower (90.9% vs 63.6%, χ2=4.393, P<0.05).@*CONCLUSION@#The infection rate of MDS patients is high in the first course of treatment, and the most common infection site is the lung. Gram-negative bacteria is the most common pathogen. MDS patients with neutrophil deficiency>7 days have a high risk of serious infection and poor efficacy.
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Humans , Cross Infection , Gram-Negative Bacteria , Myelodysplastic Syndromes , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVE@#To establish a deep learning algorithm that can accurately determine three-dimensional facial anatomical landmarks, multi-view stacked hourglass convolutional neural networks (MSH-CNN) and to construct three-dimensional facial midsagittal plane automatically based on MSH-CNN and weighted Procrustes analysis algorithm.@*METHODS@#One hundred subjects with no obvious facial deformity were collected in our oral clinic. Three-dimensional facial data were scanned by three-dimensional facial scanner. Experts annotated twenty-one facial landmarks and midsagittal plane of each data. Eighty three-dimensional facial data were used as training set, to train the MSH-CNN in this study. The overview of MSH-CNN network architecture contained multi-view rendering and training the MSH-CNN network. The three-dimensional facial data were rendered from ninety-six views that were fed to MSH-CNN and the output was one heatmap per landmark. The result of the twenty-one landmarks was accurately placed on the three-dimensional facial data after a three-dimensional view ray voting process. The remaining twenty three-dimensional facial data were used as test set. The trained MSH-CNN automatically determined twenty-one three-dimensional facial anatomical landmarks of each case of data, and calculated the distance between each MSH-CNN landmark and the expert landmark, which was defined as position error. The midsagittal plane of the twenty subjects' could be automatically constructed, using the MSH-CNN and Procrustes analysis algorithm. To evaluate the effect of midsagittal plane by automatic method, the angle between the midsagittal plane constructed by the automatic method and the expert annotated plane was calculated, which was defined as angle error.@*RESULTS@#For twenty subjects with no obvious facial deformity, the average angle error of the midsagittal plane constructed by MSH-CNN and weighted Procrustes analysis algorithm was 0.73°±0.50°, in which the average position error of the twenty-one facial landmarks automatically determined by MSH-CNN was (1.13±0.24) mm, the maximum position error of the orbital area was (1.31±0.54) mm, and the minimum position error of the nasal area was (0.79±0.36) mm.@*CONCLUSION@#This research combines deep learning algorithms and Procrustes analysis algorithms to realize the fully automated construction of the three-dimensional midsagittal plane, which initially achieves the construction effect of clinical experts. The obtained results constituted the basis for the independent intellectual property software development.
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Humans , Algorithms , Deep Learning , Face , Neural Networks, Computer , SoftwareABSTRACT
Small renal cell carcinoma refers to a renal malignant tumor with a maximum diameter of 4 cm.Due to the small size, its diagnosis and differential diagnosis have been difficult points in clinical work. CT texture analysis is an emerging technique, it determines the tumor heterogeneity by analyzing the distribution and relationship of pixel or voxel gray-scale levels in the CT images, it acts to more accurately predict the benign and malignant tumors and the classification of tumors.This paper reviews CT texture analysis on the diagnosis and differential diagnosis of small renal cell carcinoma, in order to guide the correct diagnosis of doctors and effectively clinical treatment.
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Cyclic thrombocytopenia (CTP) is a rare hemorrhagic disorder characterized by cutaneous and mucosal bleeding and periodic fluctuations platelet count. The clinical characteristics and treatment response of a patient with CTP were analyzed. The patient is a 30-year-old male with recurrent cutaneous and mucosal bleeding for 5 years. Skin petechiae, oral blood blister, conjunctival hemorrhage, by tracing the history, monitoring changes in blood routine diagnosis of CTP, further testing of reticulocyte platelets and platelet hormone, and periodically promoting bone marrow megakaryocyte with changes of platelet, confirmed that the patient's periodic reduction in bone marrow hematopoiesis, was causing more damage. Periodic changes of reticulocyte, erythropoietin and erythroid hematopoiesis in bone marrow were also observed. The patient had normal Treg levels, no significant telomere length shortening in peripheral blood nucleated cells, and no clear pathogenic gene mutation was found by whole exon gene sequencing. Recombinant human thrombopoietin(rhTPO) treatment shortened the time of thrombocytopenia and increased the minimum platelet value. The average age of onset of CTP was 35 years old, some patients had severe bleeding, and more than half of the patients were misdiagnosed as primary immune thrombocytopenia. At present, the pathogenesis of CTP has not been clarified and there is no effective treatment. The experience of this patient suggests that rhTPO may be effective. This case of CTP complicated with periodic anemia is the first report. The exploration of its pathogenesis provides important information for understanding CTP.
ABSTRACT
OBJECTIVE：To study the effects of Cu rcumin solid lipid n anoparticels （Cur-SLN） on cardiac ，renal and pulmonary functions ，the expression of autophagy related factors in cardiorenal syndrome model rats. METHODS ：The rats were divided into sham operation group ，model group ，rapamycin group （positive control ，2 mg/kg），Cur-SLN low-dose and high-dose groups（5，10 mg/kg），except for 13 rats in the model group （3 of which are used to judge whether modeling is successful ），10 rats in the other groups. Except for sham operation group ，cardiorenal syndrome of other groups were induced by abdominal aortic coarctation combined with acute renal ischemia-reperfusion injury. After successful modeling ，rats in each administration group were injected with corresponding drugs through caudal vein ，and rats in sham operation group and model group were injected with equal volume normal saline ，once a day for 4 weeks. Twenty-four hours after the last administration ，the contents of angiotensin converting enzyme （ACE），free triiodothyronine （FT3） and arginine vasopressin （AVP） in rat serum were detected. The pathological morphology of rat heart ，kidney and lung were observed. The distribution and expression of LC 3 and Beclin- 1 protein in rat heart ，kidney and lung were detected. RESULTS ：Compared with sham operation group ，the contents of ACE and FT 3 in serum，the indexes of heart and kidney ，the expression of LC 3（except in renal tissue ）and Beclin- 1 protein in heart ，kidney and lung were significantly increased （P＜0.01），and the contents of AVP and lung index were decreased significantly （P＜0.01）； myocardial cells in the non-infarcted area of the heart were obviously hypertrophic ，the arrangement of myocardial fibers was disordered ； the structure of renal tubules in the non-infarcted area of the kidney was disordered ；and there was cystic expansion and obvious inflammatory cell infiltration llittls- in the alveoli ；positive expression of LC 3 and Beclin- 1 protein nows@126.com in heart ，kidney and lung increased ，mainly distributed in the cytoplasm of cardiomyocytes ，distal renal tubular epithelial cells ，alveolar macrophages and epithelial cells. Compared with model group，the above indexes of rats in each dose group of Cur-SLN were mostly significantly reversed ；the pathological changes of heart，kidney and lung tissues were reduced ，the infiltration of inflammatory cells was reduced ；and the positive expression of LC 3 and Beclin- 1 protein were reduced ，which were mainly distributed in the cytoplasm of cardiomyocytes and proximal renal tubular epithelial cells ，and a few in distal renal tubular epithelial cells ，alveolar macrophages and epithelial cells. CONCLUSIONS ： Cur-SLN can improve the heart ，kidney and lung functions of rats with cardiorenal syndrome ，and its mechanism may be related to regulating the distribution or expression of LC 3 and Beclin- 1 protein in heart ，kidney and lung.