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@#Objective To investigate the effect of caloric restriction(CR)on myocardial ischemia/reperfusion injury(MI/RI)in mice and its mechanism.Methods C57 mice were randomly divided into normal diet group(AL group,free feeding)and CR group(diet decreased by 10% every 2 weeks)for 8 weeks and monitored for weight changes.Each group was divided into sham operation group and MI/RI group,total 4 groups,AL + Sham group,AL + I/R group,CR + Sham group and CR + I/R group).The left anterior descending coronary artery was ligated for 30 minutes and then reperfused for 24 hours in mice of MI/RI group and mice in Sham group were only threaded but not ligated.The mice were determined for myocardial ischemia and infarct size by Evans blue/TTC staining,observed for the pathology of myocardium by HE staining,determined for the activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD)and the contents of creatine kinase-MB(CK-MB)and malondialdehvde(MDA)in myocardium by the corresponding kits,determined for serum levels of IL-1β and IL-18 by ELISA and detected for the expression of pyroptosis-associated proteins in myocardium by Western blot.Results After 8weeks,the weights of mice in CR group[(24.54 ± 0.41)g]were significantly lower than those in AL group[(31.46 ±0.25)g](t = 14.34,P<0.05).Compared with those in AL + I/R group,the area of myocardial ischemia in CR + I/R group showed no significant difference(t = 0.783 0,P>0.05),while the area of myocardial infarction decreased significantly(t = 7.250,P<0.01);The myocardial arrangement was relatively neat,and the degree of pathological changes was obviously reduced;LDH activity,CK-MB and MDA contents decreased significantly(t = 4.331,2.875 and 5.343 respectively,each P<0.05),while SOD activity increased significantly(t = 4.211,P<0.05);Serum levels of IL-1β and IL-18 decreased significantly(t = 3.375 and 4.266 respectively,each P<0.05);The expression levels of nod-like receptor protein 3(NLRP3),gasdermin D(GSDMD),apoptosis-associated speckle-like protein(ASC)and caspase-1 significantly decreased(t = 3.412,3.420,3.480 and 2.585 respectively,each P<0.05).Conclusion CR alleviated MI/RI in mice,and its mechanism was related to the inhibition of cardiac pyroptosis.
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AIM:To investigate the mechanism of curcumin inhibiting the choroidal neovascularization(CNV)of brown Norway(BN)rats.METHODS: CNV model of 36 BN rats was established through laser photocoagulation induction, and they were divided into 6 groups with 6 rats in each group. Normal group was fed normally with no intervention, while 532nm laser photocoagulation was used to establish a experimental CNV model in BN rats. Rats after modeling were respectively intervened for 14d and divided into model group, ranibizumab group, curcumin low [100mg/(kg·d)], medium [200mg/(kg·d)], and high [400mg/(kg·d)] dose group. The model group was given intragastric administration of saline for 14d, ranibizumab(10mg/mL, 0.2mL/dose)was injected at 2d after photocoagulation with 5μL once for rats in ranibizumab group, and different concentrations of curcumin were intragastrically administrated to the rats in low, medium and high groups for 14d. Fundus photography, fundus fluorescein angiography(FFA)and indocyanine green angiography(ICGA)examination were performed at 14d after photocoagulation. Ocular histopathological specimens of rats with CNV were made, and the central thickness of CNV were observed by HE staining. Ocular histopathological specimens were made, and the expressions of AKT/p-AKT/HIF-1α/VEGF signaling pathway-related proteins were observed by immunohistochemistry. The mRNA relative expressions of AKT/HIF-1α/VEGF factor in CNV tissues were detected by RT-qPCR, and the protein expressions of AKT/p-AKT/HIF-1α/VEGF factor in CNV tissues were detected by Western-blot.RESULTS: CNV generation rates in the model group, the ranibizumab group, and the low, medium and high-dose curcumin groups were 78.18%, 73.21%, 77.19%, 75.86%, 74.55%, respectively, which were higher than 70%. The average absorbance were 182.12±6.59, 119.22±8.03, 166.45±8.33, 164.34±5.69, 149.22±6.45, respectively; the ranibizumab group was significantly lower than the model group(P&#x003C;0.05); the low-dose, medium-dose and high-dose groups were significantly higher than the ranibizumab group(P&#x003C;0.05), and the curcumin high-dose group was significantly lower than the model group(P&#x003C;0.05). HE staining showed that the retinal tissue structure of BN rats in normal group was clear and neatly arranged. The central thickness of CNV in the ranibizumab group was significantly reduced at 14d after photocoagulation compared with the model group(P&#x003C;0.05); While the curcumin high-dose group was significantly reduced compared with the model group(P&#x003C;0.05), but increased when compared with ranibizumab group(P&#x003C;0.05). Immunohistochemistry results showed that AKT, p-AKT, HIF-1α, and VEGF factors were negatively expressed in the retinal tissue structure of BN rats in the normal group, and no brown-yellow reactants were found. The expression of AKT, p-AKT, HIF-1α, and VEGF factors in the model group were higher than that in the normal group at 14d after photocoagulation(P&#x003C;0.05); the ranibizumab group was lower than the model group(P&#x003C;0.05). While the expression of the curcumin high-dose group was significantly decreased compared with the model group(P&#x003C;0.05), but significantly increased when compared with ranibizumab group(P&#x003C;0.05). The mRNA results showed that the relative expression levels of AKT, HIF-1α and VEGF mRNA in the model group at 14d after photocoagulation were higher than those of the normal group(P&#x003C;0.05); the ranibizumab group was lower than the model group(P&#x003C;0.05). While curcumin high-dose group was significantly decreased compared with the model group(P&#x003C;0.05), but significantly increased when compared with ranibizumab group(P&#x003C;0.05). Western-blot results showed that there was no significant difference in the relative expression of AKT protein among each experimental groups at 14d after photocoagulation. The relative expression of p-AKT protein in the model group was significantly higher than that in the normal group(P&#x003C;0.05); the ranibizumab group was significantly lower than the model group(P&#x003C;0.05); the curcumin high-dose group was significantly lower than the model group(P&#x003C;0.05). The relative expression levels of HIF-1α protein were significantly higher in the model group than in the normal group(P&#x003C;0.05), and the ranibizumab group was lower than in the model group(P&#x003C;0.05). The relative expression levels of HIF-1α protein was lower in the curcumin high-dose group than in the model group(P&#x003C;0.05)but higher than ranibizumab group(P&#x003C;0.05). The relative expression level of VEGF protein was significantly lower in the curcumin medium/high-dose group than in the model group(P&#x003C;0.05).CONCLUSION: Curcumin at 400mg/(kg·d)has an inhibitory effect on CNV in BN rats. The mechanism may be closely related to inhibiting the activation of AKT/p-AKT/HIF-1α/VEGF signaling pathways.
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ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease（COPD）， and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups， including blank group， model group， fecal bacterial transplantation（FMT） group， dexamethasone group and low， medium and high dose groups of Bufeitang， 12 rats in each group. Except for the blank group， cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide（LPS） were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low， medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang（3.645， 7.29， 14.58 g·kg-1）， the FMT group was given fecal bacteria liquid enema（10 mL·kg-1）， dexamethasone group was given dexamethasone acetate tablet suspension by gavage（0.135 mg·kg-1）， the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin（HE） for pathomorphological observation， and enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in lung tissues. ResultCompared with the blank group， the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group， the extent of injury was significantly improved， and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group， the model group had severely abnormal colonic tissue structure， the epithelial cells in the mucosal layer were eroded and shed， the number of inflammatory cells increased， the submucosal layer was edematous and the gap was enlarged. Compared with the model group， the extent of damage was significantly improved in the medium and high dose groups of Bufeitang， the epithelial cells in the mucosal layer were neatly and closely arranged， with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group， the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased（P<0.01）. Compared with the model group， the TNF-α and IL-8 levels of lung tissues in the low， medium and high dose groups of Bufeitang were significantly decreased（P<0.01）. Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats， corrected the return of intestinal flora to normal abundance and diversity， and positively regulated 4 differential phyla（such as Firmicutes， Proteobacteria） and 13 differential genera（such as Turicibacter， Lactobacillus， Anaerobiospirillum， Intestinimonas） in COPD model rats with lung Qi-deficiency syndrome， and down-regulated 2 carbohydrate metabolic pathway functions， including the pentose phosphate pathway（non-oxidative branch） Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species， affect the function of metabolic pathways， repair the structure of lung and colon tissues， regulate the level of inflammatory factors， and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.
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Abstract Background: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. Methods: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and down-regulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR. Results: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain. Conclusion: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.
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Objective:To summarize the research progress of domestic nurses′ turnover intentions in the past ten years, and to provide references for related research on improving nurses′ turnover intentions.Methods:In May 2021, the documents related to nurses′ resignation intentions were retrieved in China National Knowledge Infrastructure (CNKI), Wanfang and VIP database and Citespace5.7.R5 software was used to perform keyword visualization analysis to form keyword clustering graphs and tables, emergent words, and corresponding time zones figure, the current research status and hot trends of nurses′ turnover intentions were analyzed.Results:A total of 2 029 valid documents were retrieved, the number of publications reached the highest peak in 2019. Among them, "nurse", "willingness to leave", "job satisfaction", "turnover intention" and "influencing factors" were the top 5 hot keywords and 23 emergent words were generated; research directions mainly included influencing factors and research objects and workplace related topics.Conclusions:Managers should actively play a leadership role to reduce nurses′ turnover intention through various effective intervention studies.
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Objective:To evaluate the safety and feasibility of double endoscopic bypass, namely endoscopic ultrasound-guided gastroenterostomy (EUS-GE) combined with endoscopic ultrasound-guided biliary drainage (EUS-BD), for malignant gastric outlet and biliary obstruction.Methods:A retrospective analysis was conducted on data of 10 patients with malignant gastric outlet and biliary obstruction who were not suitable for surgery or endoscopic retrograde cholangiopancreatography (ERCP) and treated by double endoscopic bypass in Nanjing Drum Tower Hospital from August 2017 to October 2020. The completion of therapy, clinical efficacy and post-procedure adverse events were analyzed.Results:Ten patients with different malignant cancer successfully underwent EUS-GE and EUS-BD, with procedure time of 60.5±22.3 min (30-100 min). There were no postoperative adverse events. EUS-GE was clinically successful in all 10 cases. Of the 10 EUS-BD cases, 9 were clinically successful, and 1 did not meet the criteria of clinical success. The median follow-up was 71 (37-120) days. None of the 10 patients had recurrent gastric outflow tract obstruction or biliary tract obstruction.Conclusion:Double endoscopic bypass is feasible and effective for patients with malignant gastric outlet and biliary obstruction and without surgery or ERCP opportunity.
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Procalcitonin, as a biological marker of bacterial infection, has been widely used in clinical diagnosis of various infectious diseases. With the development of basic and clinical research, it has been found that procalcitonin not only plays a cascading and amplifying role in systemic inflammatory response, but also exerts an important effect on assessment, diagnosis, and prognosis in some central nervous system diseases. In this article, "procalcitonin" "bacterial meningitis""marker" and "central nervous system diseases" were used to search the relevant literatures published from 1993 to 2021 in the databases of Pubmed, Wanfang Medicine and China Knowledge Network. The roles of procalcitonin in central nervous system diseases were systemically reviewed for assisting the diagnosis and treatment of central nervous system diseases.
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Objective:To analysis of clinical and imaging characteristics of pulmonary cryptococcosis.Methods:The clinical and imaging characteristics of 113 patients with pulmonary cryptococcosis who were admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to March 2019, were retrospectively analyzed.Results:Among 113 patients, 74 cases (65.5%) were males, and 71 cases (62.8%) were at a age of 40-60 years. The imaging manifestations showed a nodular-infiltrating patchy mixed type ( n=44,38.9%), accompanied by halo sign ( n=48, 42.5%) and bronchial air sign ( n=48, 42.5%). All patients were treated with fluconazole and the follow-up at 3 months after discharge showed their conditions were all improved. Subgroup analysis showed that patients with complications had older average age [(54.28±10.64)y vs. (46.52±12.12)y, t=-5.05, P<0.001], longer hospital stay [(10.42±6.11)d vs. (7.09±5.63)d, t=-4.28, P=0.007], lower white blood cell count [(6.02±2.16)×10 9/L vs. (6.96±2.29)×10 9/L, t=2.44, P=0.027]. The symptomatic group had fewer male patients [56.2% (45/80) vs. 87.9% (29/33), χ 2=19.54, P<0.001], and imaging was more likely to show infiltrative patchy [32.5%(26/80) vs. 9.1%(3/33), χ 2=18.25, P=0.031]. There was no significant difference in clinical and imaging manifestations between antigen positive group and antigen negative group(all P>0.05). Conclusions:Most of the patients with pulmonary cryptococcosis are middle-aged men, and have nodular-infiltrating patchy mixed type in imaging; the complications would prolong the length of hospital stay.
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ObjectiveThe law of fertilizer requirement serves as the basis for the fertilization of medicinal plants， development of special fertilizer， and high-quality medicinal materials. MethodThis study aims to explore the optimal potassium application rate for Panax ginseng to achieve high yield and quality of the medicinal material and targeted management of potassium fertilizer. To be specific， 6 concentration gradients （0， 2， 4， 8， 10， and 12 mmol·L-1） of potassium sulfate （potassium fertilizer） were designed and applied to the 4-year-old P. ginseng in CK， C1， C2， C3， C4， and C5 treatments， respectively. Thereby， the influence of potassium concentration on P. ginseng was observed. ResultWhen potassium sulfate was applied at 8 mmol·L-1， P. ginseng had the chlorophyll content of 32.13%， net photosynthetic rate of 2.548 8 µmol·m-2·s-1， and activities of superoxide dismutase （SOD）， peroxidase （POD）， and catalase （CAT） significantly higher than those in the CK， C1， C4， and C5 treatments （P<0.05）. The average fresh weight of P. ginseng roots was 6.25 g， 134% up from the CK， and the content of ginsenoside Rg1 （5.24 mg·g-1） and Re （4.17 mg·g-1） and total saponins （12.33 mg·g-1） was significantly higher than that in CK and other treatments （P<0.05）. Thus， 8 mmol·L-1 potassium sulfate was most favorable for the growth and effective component accumulation of four-year-old P. ginseng. ConclusionThis study expounds the effect of potassium fertilizer on the yield and quality of P. ginseng， which is expected to help guide the precise application of potassium fertilizer in P. ginseng production in the field and lay a theoretical basis for the development of special fertilizer for P. ginseng and the optimization of fertilization technology.
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Anxiety and depression are common comorbidities of coronary heart disease and are considered as independent risk factors in addition to traditional cardiovascular risk factors. Anxiety，depression and other mental abnormalities belong to the category of "depressive syndrome" of traditional Chinese medicine，which can lead to stasis of blood due to the lack of Qi flow. "Blood stasis" involves abnormal blood rheology， vascular endothelial dysfunction， chronic inflammatory response， abnormal lipid metabolism and other comprehensive pathological changes， and is the core pathogenesis of coronary heart disease in traditional Chinese medicine. "Depressive syndrome"can aggravate the development of coronary heart disease by promoting blood stasis in multiple ways. Prescriptions and herbs of promoting blood circulation and removing blood stasis can have a clinical effect by promoting blood circulation （improving physiological functions） and removing blood stasis （eliminating pathological changes）. In clinical practice， strengthening the screening of the mental and psychological status of patients with coronary heart disease and providing early and effective psychological interventions and combined Chinese and Western medicine drug treatment can significantly improve the clinical symptoms and prognosis of patients. This article was the first to put forward the academic view of "stasis caused by depression" for the first time，and discuss the modern biological research progress of "depression" in Chinese medicine that promotes blood stasis and aggravates coronary heart disease，in order to provide a basis for the subsequent development of Chinese medicine in the prevention and treatment of coronary heart disease. The aim is to provide a theoretical basis for the subsequent systematic research on the prevention and treatment of coronary heart disease with emotional abnormalities in Chinese medicine.
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"Four in one" is a research idea of identifying the classic prescriptions from the following four dimensions： "nature， location， tendency， and syndrome". The multi-dimensional analysis of the mechanism of classic prescription Zhigancao Tang in treating coronary heart disease helps to understand the syndrome differentiation and treatment thoughts of ZHANG Zhong-jing. The coronary heart disease results from deficiency. The efficacy of Zhigancao Tang in treating coronary heart disease can be elucidated from the "nature，location，tendency， and syndrome". In terms of nature， Zhigancao Tang is pungent and sweet in flavor and warm in property， with the sweet responsible for tonifying deficiency， the pungent for dispersing Yang， resolving Yin， and eliminating surplus pathogen， and the warm for moving Yangqi， nourishing blood， and promoting blood circulation. In terms of location， Zhigancao Tang mainly acts on vessels for restoring the normal circulation of blood in the vessels and improving coronary artery stenosis and the resulting ischemia and anoxia. In terms of tendency， Zhigancao Tang tends to affect the upper and inner parts of the body to tonify deficiency in Zangfu organs， promote fluid production， nourish nutrient blood， and dissipate cold simultaneously， thus alleviating chest impediment. In terms of syndrome， Zhigancao Tang is applicable to fluid exhaustion with blood dryness and Yin-yang-qi-blood deficiency syndrome， manifested as regularly or irregularly intermittent pulse and severe palpitation. Zhigancao Tang has been widely used for the treatment of over 70 diseases classified into 10 systems， especially the cardiovascular diseases， in traditional Chinese medicine （TCM） and western medicine. As the “one” of “four in one”， Zhigancao Tang is composed of multiple Chinese herbs and its therapeutic effect is superior to the sum of its parts. It ameliorates the coronary heart disease by resisting inflammation， protecting against ischemia-reperfusion injury， adjusting the ion channels of myocardial cells， and participating in atrial remodeling and hematopoiesis. Its mechanism and clinical efficacy in the treatment of coronary heart disease have been verified by clinical and experimental studies. The utilization of the thought of "four in one" to analyze classical prescriptions enables the combination of prescriptions with syndromes， which is of great significance to the clinical application and modern development of classical prescriptions.
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The present study investigated the pharmaceutical effect and underlying mechanism of Zexie Decoction(ZXD) on nonalcoholic fatty liver disease(NAFLD) in vitro and in vivo via the LKB1/AMPK/PGC-1α pathway based on palmitic acid(PA)-induced lipid accumulation model and high-fat diet(HFD)-induced NAFLD model in mice. As revealed by the MTT assay, ZXD had no effect on HepG2 activity, but dose-dependently down-regulated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver cell medium induced by PA, and decreased the plasma levels of ALT and AST, and total cholesterol(TC) and triglyceride(TG) levels in the liver. Nile red staining showed PA-induced intracellular lipid accumulation, significantly increased lipid accumulation of hepatocytes induced by PA, suggesting that the lipid accumulation model in vitro was properly induced. ZXD could effectively improve the lipid accumulation of hepatocytes induced by PA. Oil red O staining also demonstrated that ZXD improved the lipid accumulation in the liver of HFD mice. JC-1 staining for mitochondrial membrane potential indicated that ZXD effectively reversed the decrease in mitochondrial membrane potential caused by hepatocyte injury induced by PA, activated PGC-1α, and up-regulated the expression of its target genes, such as ACADS, CPT-1α, CPT-1β, UCP-1, ACSL-1, and NRF-1. In addition, as revealed by the Western blot and immunohistochemistry, ZXD up-regulated the protein expression levels of LKB1, p-AMPK, p-ACC, and PGC-1α in vivo and in vitro. In conclusion, ZXD can improve NAFLD and its mechanism may be related to the regulation of the LKB1/AMPK/PGC-1α pathway.
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AMP-Activated Protein Kinases/metabolism , Alanine Transaminase/metabolism , Animals , Diet, High-Fat , Liver/metabolism , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaABSTRACT
Objective:To analyze the incidence and risk factors of acute kidney injury (AKI) in patients undergoing neurosurgery.Methods:This study was a single center and retrospective research. The patients hospitalized in the general neurosurgery ward of Xuanwu Hospital, Capital Medical University, due to intracranial tumors and intracranial vascular diseases from January 1, 2017 to December 31, 2020 were enrolled. Demographic, clinical data and laboratory examination results of the selected patients were collected. The patients were divided into AKI group and non-AKI group according to AKI diagnosis criteria, and the differences of clinical parameters and medication between the two groups were compared. Logistic regression analysis method was used to analyze the risk factors of AKI in neurosurgical patients.Results:Among 4 509 patients undergoing neurosurgery with age of (51.93±16.03) years old, 2 361 males and 2 148 females, 152 patients (3.37%) had AKI. The incidence of AKI in patients undergoing intracranial tumor surgery was 3.69% (84/2 278), and the incidence of AKI in patients undergoing intracranial cerebrovascular surgery was 3.05%(68/2 231). The length of hospital stay ( t=4.897, P<0.001) and operation time ( t=5.496, P<0.001) in AKI group were significantly longer than those in non-AKI group. The proportions of diabetes mellitus, preoperative serum creatinine, blood urea nitrogen, glycosylated hemoglobin, lactic acid, fibrinogen, and systolic pressure levels in AKI group were significantly higher than those in non-AKI group (all P<0.05); the hemoglobin level in AKI group was significantly lower than that in non-AKI group ( P<0.05). The proportions of patients using angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists, cephalosporins, proton pump inhibitors, mannitol, and nonsteroidal anti-inflammatory drugs in AKI group were also significantly higher than those in non-AKI group (all P<0.05). Multivariate logistic regression analysis results showed that hemoglobin<110 g/L ( OR=4.252, 95% CI 1.569-11.527, P=0.004), elevated blood urea nitrogen ( OR=1.304, 95% CI 1.139-1.492, P<0.001) and application of nonsteroidal anti-inflammatory drugs ( OR=2.342, 95% CI 1.044-5.253, P=0.039) were independent risk factors of AKI in neurosurgical patients. Conclusions:The incidence of AKI in patients in neurosurgery general ward is 3.37%. Anemia, elevated blood urea nitrogen and application of nonsteroidal anti-inflammatory drugs are independent risk factors of AKI in patients undergoing neurosurgery.
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Objective:To explore the incidence, influencing factors and prognostic value of cardiac valve calcification (CVC) in chronic kidney disease (CKD) non-dialysis patients.Methods:The non-dialysis patients with CKD stage 1-5 who were hospitalized and underwent echocardiography in the Department of Nephrology, Xuanwu Hospital, Capital Medical University from January 1, 2018 to December 31, 2019 were retrospectively admitted. The patients were divided into CVC group and non-CVC group, and the clinical data were compared between the two groups. The deadline for follow-up was November 1, 2021, and the follow-up end point event was all-cause mortality. Logistic regression model was used to analyze the risk factors of CVC in patients with CKD, and Cox proportional hazards regression model was used to analyze the risk factors of all-cause mortality in patients with CKD.Results:A total of 563 patients with CKD were enrolled in the study, with age of (59.49±13.97) years old, and 352 males (62.52%). There were 325 patients (57.73%) with CKD stage 1-3 and 238 patients (42.27%) with CKD stage 4-5. The incidence of CVC in CKD stage 1-5 patients was 32.32%(182/563). Aortic valve calcification occurred in 30.73%(173/563), mitral valve calcification occurred in 9.77% (55/563), double valve (mitral and aortic valve) calcification occurred in 8.35% (47/563), and tricuspid valve calcification occurred in 0.18%(1/563). Age (t=12.223, P<0.001) and the proportions of CKD stage 4-5 ( χ 2=10.854, P=0.001), hypertension ( χ 2=7.811, P=0.005), diabetes ( χ 2=8.424, P=0.004), hyperlipidemia ( χ 2=9.331, P=0.002), and taking statins ( χ 2=4.868, P=0.027) in CVC group were significantly higher than those in non-CVC group. Total cholesterol (t=2.243, P=0.025), low density lipoprotein cholesterol (t=2.025, P=0.043), platelet count (t=2.230, P=0.026) and estimated glomerular filtration rate (t=8.630, P<0.001) in CVC group were lower than those in the non-CVC group. Logistic regression analysis results showed that age≥60 years old (≥60 years old/<60 years old, OR=7.412, 95% CI 4.514-12.170, P<0.001), CKD stage 4-5 (stage 4-5/stage 1-3, OR=2.791, 95% CI 1.730-4.505, P<0.001) and hyperlipidemia ( OR=5.241, 95% CI 3.283-8.367, P<0.001) were the independent influencing factors of CVC in patients with CKD. Five hundred and sixty-three patients were followed up for an average of 26 months, including 68 cases (12.08%) of death, 436 cases (77.44%) of survival and 59 cases (10.48%) of loss to follow-up. Multivariate Cox regression analysis results showed that age≥60 years old (≥60 years old/<60 years old, HR=2.157, 95% CI 1.127-4.127, P=0.020), serum albumin<30 g/L (<30 g/L/≥30 g/L, HR=1.923, 95% CI 1.037-3.568, P=0.038) and double valve calcification (double valve calcification/no valve calcification, HR=2.516, 95% CI 1.279-4.950, P=0.008) were the independent influencing factors of all-cause death in patients with CKD. Conclusions:CVC accounts for 32.32% in non-dialysis patients with CKD stage 1-5. Older age, worse renal function and hyperlipidemia are the independent risk factors of CVC in CKD patients. Older age, hypoproteinemia and double valve calcification are the independent risk factors of all-cause death in patients with CKD.
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Objective:To determine the mechanical properties of our self-designed novel cross-locking intramedullary nails and the impact of number of conical locking nails on the fixation through a finite element analysis and specimen experiments.Methods:Mimics 19.0 and SolidWorks 2014 were used to create transverse fracture models of the olecranon which were subjected to fixation with respectively K-wire tension band (KTB) and our self-designed novel cross-locking intramedullary nails (NIN). The strengths of KTB and NIN fixation were analyzed by Ansys. Fifteen human ulna specimens were used to construct a transverse fracture model of the olecranon; an Instron E10000 mechanical testing machine was used to determine mechanical properties in fixation respectively with KTB, one NIN (NIN-1) and 3 NINs (NIN-3).Results:In the finite element analysis, in simulation of the forearm flexed at 45° under a 100 N load, the deformation of the fracture surface of the olecranon in fixation with KTB, NIN-1 and NIN-3 was respectively 0.131 mm, 0.123 mm and 0.121 mm. In the specimen experiments, in simulation of the forearm flexed at 45°, the maximum failure loads for fixation with KTB, NIN-1 and NIN-3 were (313.38±27.68) N, (528.56±53.58) N and (871.04±94.95) N, respectively, showing significant differences among the 3 groups ( P<0.05). The maximum failure load for NIN-3 fixation was significantly greater than that for KTB or NIN-1 fixation, and the maximum failure load for NIN-1 fixation was significantly greater than that for KTB fixation ( P<0.05). Conclusions:Compared with KTB fixation, NIN fixation is more convenient in operation and has better mechanical properties. NIN-3 fixation has the best mechanical properties.
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Ferroptosis is a novel cell death mode proposed in recent years, which is characterized by intracellular iron-dependent lipid peroxidation. Its mechanisms include lipid peroxidation, iron accumulation and the imbalance of antioxidant system. The crosstalk between ferroptosis and asthma is gradually deepening. Elucidating the specific mechanism of ferroptosis in regulating asthma is helpful to broaden the understanding of the pathology of asthma. This paper expounds the role of ferroptosis in airway epithelial cells in the occurrence and development of asthma from three perspectives: lipid peroxidation, iron accumulation and the imbalance of antioxidant system, hoping to find new targets and strategies for asthma treatment.
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It is a common understanding that turbidity and precipitation of traditional Chinese medicine are easy to occur in the process of decocting. At present, our research group found that the cause of "multi-phase of traditional Chinese medicine decoction" mainly came from the interaction between the effective components of traditional Chinese medicine, especially the interaction of acid and base components. For example, the Liquorice and Rhizoma chinensis was a supramolecular system formed by a large number of active components in the decoction (>30%), and could stably exist in the decoction system. In this study, the supramolecular part was extracted, and the morphology of the supramolecular part was characterized by scanning electron microscopy and dynamic light scattering. It was observed that the supramolecular particles were uniform in size and regular in shape. The main components of supramolecular sites were identified by liquid mass spectrometry (LC-MSn). The results of UV and IR spectra showed that the chemical components of Liquorice and Rhizoma chinensis in the co-decocting process collided with each other, and weak bonds were formed between the functional groups of the molecules, which then induced the aggregation to form supramolecules. Thereafter, Through the diarrhea model of mice, sensory evaluation and antibacterial activity evaluation found that Liquorice and Rhizoma chinensis decocted together enhanced the antibacterial activity of Rhizoma, and compatibility "reconcile" Rhizoma "big bitter cold" property compared with single decoction group and interval administration group. All animal experiments were approved by the Animal Ethics Committee of Beijing University of Chinese Medicine, and the relevant regulations of Beijing University of Chinese Medicine on experimental animals were strictly followed. In this study, supramolecular chemistry method was used to preliminarily discuss the scientific connotation of "increasing efficiency and decreasing toxicity" of Liquorice and Rhizoma chinensis combined decoction from three perspectives of "property, efficacy and taste", and provide new ideas for the basic research of "reconcile" compatibility of Liquorice.
ABSTRACT
Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.
ABSTRACT
Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.
Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Biological Products/pharmacology , Indole Alkaloids/pharmacology , Porifera , Structure-Activity RelationshipABSTRACT
Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.