This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Signal Transduction/drug effects* ; Glucose/metabolism* ; Caveolin 1/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; YAP-Signaling Proteins ; Oxygen/metabolism* ; Endothelial Cells/metabolism* ; Cell Line ; Adaptor Proteins, Signal Transducing/genetics* ; Neovascularization, Physiologic/drug effects* ; Cell Hypoxia/drug effects* ; Angiogenesis

Objective:To investigate the association between albumin-corrected anion gap(ACAG)and short-to long-term death out-comes in patients with acute pancreatitis(AP).Methods:This retrospective study was based on the Medical Information Mart for Inten-sive Care-IV database,and the adult patients who were diagnosed with AP and were admitted to the intensive care unit were enrolled in this study.Cox regression risk analysis,receiver operating charac-teristic(ROC)curve analysis,Kaplan-Meier survival curve analy-sis,restricted cubic spline,and subgroup analysis were used to in-vestigate the value of ACAG in predicting the death outcome of AP patients.Results:A total of 444 patients were enrolled in this study,and according to the death status of the patients on day 28 after ad-mission,the patients were divided into survival group with 412 pa-tients and death group with 32 patients,with a mortality rate of 7.2%on day 28 after admission.The multivariate Cox regression analysis showed that ACAG was an independent predictive factor for all-cause mortality rate on day 28 after admission in AP patients(hazard ratio[HR]=1.18,95%CI=1.05-1.32),while it was not an in-dependent predictive factor for death outcome on days 90(HR=1.05,95%CI=0.97-1.14)and 180(HR=1.01,95%CI=0.94-1.09)and at 1 year(HR=1.02,95%CI=0.95-1.10).The ROC curve analysis showed that ACAG had an area under the ROC curve(AUC)of 0.732(95%CI=0.632-0.832)in predicting 28-day death outcome,which was better than that of AG(AUC=0.665,95%CI=0.550-0.781)and serum albumin(Alb)(AUC=0.655,95%CI=0.550-0.761)and was similar to that of Sequential Organ Failure Assessment(SOFA)score(AUC=0.745,95%CI=0.651-0.838).The ROC curve showed that the optimal cut-off value of ACAG was 21.375.Based on the cut-off value of ACAG of 21.375,the patients were divided into high-value group and normal-value group,and the Kaplan-Meier curve analysis showed that the patients with a high level of ACAG had a significantly higher mortality rate than those with normal ACAG(P<0.001).The subgroup analysis showed that the results were stable.Conclusion:ACAG can be used as an independent pre-dictive factor for all-cause mortality rate on day 28 after admission in AP patients,with a better efficacy than AG and Alb and a similar efficacy to SOFA.However,it is not significantly associated with 90-day,180-day,and 1-year death outcomes in AP patients.

Objective:To investigate the protective mechanism of cerium oxide nanoparticles(CeO2 NPs)against acute pancreatitis(AP),with a focus on their antioxidant and anti-inflammatory properties.Methods:CeO2 NPs were characterized by transmission elec-tron microscopy(TEM)and dynamic light scattering.In in vitro experiments,cell counting Kit-8(CCK-8)assay,flow cytometry,and Western blotting were used to validate the role of CeO2 NPs in preventing the apoptosis of pancreatic acinar cells.In in vivo experi-ments,C57BL/6 mice were divided into control group,AP group,AP+CeO2 group,SAP group,and SAP+CeO2 group to investigate the mechanism of action of CeO2 NPs in alleviating inflammation and oxidative stress in AP mice.Results:CeO2 NPs demonstrated rela-tively good stability and biocompatibility,with a particle size of(50±4)nm on TEM.In vitro experiments showed that CeO2 NPs sig-nificantly reduced the apoptosis of pancreatic acinar cells by alleviating lipid peroxidation and maintaining mitochondrial membrane potential.In vivo experiments showed that CeO2 NPs could reduce the serum levels of amylase,lipase,and inflammatory cytokines(in-terleukin-6 and tumor necrosis factor-α).This result might be related to the regulation of the IKK/P53/Bcl-2 pathway.CeO2 NPs re-duced the production of reactive oxygen species and enhanced anti-oxidant response by regulating the Nrf-2 signaling pathway.Con-clusion:CeO2 NPs exert anti-inflammatory and antioxidant effects by regulating the IκB kinase/tumor protein p53/B-cell lymphoma 2(IKK/P53/bcl-2)and nuclear factor erythroid 2-related(Nrf-2)signaling pathways,thereby showing promising potential for the treatment of AP.

Patients with severe tumors do not refer to the patients with end-stage tumors,but rather to the patients with a performance status(PS)score between 2 and 4 in certain stages due to various reasons,such as acute or chronic comorbidities,tumor itself,or treatment-related adverse events.To these patients,there is a high probability of achieving survival benefit and/or improvement in PS scores after synergistic management of available life-support technologies and anti-tumor therapies based on dynamic and precise testing.Elderly patients with tumors frequently present with one or more chronic illnesses and have poor toler-ance and compliance to treatment.Moreover,their treatment regimens often lack high-quality clinical evidence,making them more susceptible to developing severe tumors.The management of severe tumors in the elderly is based on three basic diagnosis and treatment technologies:dynamic and precise detection,powerful life support technologies,and skillful application of current anti-tumor treatments.In specific clinical practice,the following 7 flexible and individualized treatment strategies should be adopted for different tumor types:1.concurrent management of cancer and comorbidities,2.upgrading and downgrading of anti-tumor drugs based on PS score,3.dynamic accurate detection,4.skillful combinations for increasing efficacy and reducing toxicity,5.complete overview,paying equal attention to systemic therapy and local therapy,6.safety first in medication for the elderly,7.multi-discipli-nary participation,individualized and comprehensive treatment.This article introduced the concept of severe tumors in the elderly and the associated management strategies,to increase awareness and provide feasible guidance for clinical practice.

Objective To explore the mediating role of depression between uremic toxins and cognitive function in end-stage renal disease(ESRD)patients,so as to provide a basis for early clinical intervention.Methods A retrospective study involved 49 predialysis ESRD patients diagnosed in the Nephrology Department of The First Affiliated Hospital of Xi'an Jiaotong University between August 2018 and October 2021,along with 50 healthy controls(HC).General information of the two groups was collected.Montreal Cognitive Assessment(MoCA),Auditory Verbal Learning Test-Huashan Version(AVLT-H),Trail Making Test A(TMT-A),Beck Depression Inventory(BDI),and Beck Anxiety Inventory(BAI)were used to collect data on cognitive function,anxiety,and depression in both groups.Serological indicators in the ESRD group were used to clarify the impact of uremic toxins on cognitive function.PROCESS v3.4.1 was applied to explore the relationship between uremic toxins,depression,and cognitive function,as well as the mediating effect of depression.Results Significant differences were found between the ESRD group and the HC group in MoCA total score(P＜0.001),AVLT-H(word learning;short-term delay;long-term delay,P＜0.001;word recognition,P=0.001),TMT-A(P＜0.001),BDI(P＜0.001),and BAI(P=0.009).Cystatin C was a negative influencing factor for short-term delay in AVLT-H(B＝-0.834,P=0.019),while BDI was a negative influencing factor for long-term delay in AVLT-H(B=-0.102,P=0.002),word recognition in AVLT-H(B=-0.071,P＜0.001),and MoCA total score(B=-0.135,P=0.002).BDI partially mediated the effect of cystatin C on short-term delay in AVLT-H(total effect,c=-0.3346;direct effect,c'=-0.223 5;mediating effect,a×b=-0.111 0;and mediating effect proportion,33.2％)and long-term delay in AVLT-H(total effect,c=-0.318 7;direct effect,c'=-0.218 8;mediating effect,a×b=-0.099 9;and mediating effect proportion,31.3％).Conclusion ESRD patients experience cognitive decline as well as anxiety and depression.Cystatin C and depression are both negative influencing factors for cognitive decline in ESRD patients.Cystatin C indirectly affects cognitive function in ESRD patients through depression.

Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.

Objective:With the advancement of science and technology, there are a series of new ethical issues in scientific research. How to improve the standardization of ethical review for clinical researchers deserves attention. This study summarized the challenges faced by researchers in conducting ethical reviews in a standardized manner, introduced the practice of A hospital in promoting researchers to conduct ethical reviews in a standardized manner using a paper management platform, and put forward related thoughts.Methods:In the first stage, after negotiation between the Ethics Committee and the scientific research management department, the key management nodes of researchers in the process of clinical research were sorted out. Combined with the regulations on paper management, the standardization of research behavior was forced by taking paper management as the starting point. In the second stage, a multiple-department collaboration was carried out in which the Ethics Committee coordinated communication and cooperation among various departments to ensure the standardization of clinical research.Results:After more than 3 years of practice, the proportion of papers rejected due to lack of ethical review approval decreased, and the number of retrospective and interventional research papers rejected showed a downward trend overall. Nursing and technician/pharmacist groups need to be paid special attention to.Conclusions:The government should improve the supervision mechanism and perfect the evaluation system; journals should play a role in ″passing″ ethical review; hospitals should strengthen multi-department collaboration and continuously optimize processes and publicity; researchers should consciously enhance their ethical awareness.

Objective To explore the application of regional cerebral oxygen saturation(rSO2)-bispectral index(BIS)monitoring anesthesia in children undergoing surgery for supracondylar fractures of the humerus.Methods A total of 60 children with supracondylar fractures of the humerus undergoing surgery in Department of Orthopedi,Jiangxi Provincial Children's Hospital were chosen and randomly number table method segmented into control group and observation group from January 2020 to December 2022,30 cases in each group.After anesthesia,children in observation group were carried out with rSO2-BIS monitoring,while children in control group were given routine anesthesia management.Results The dosage of propofol and long chain fat emulsion/remifentanil injection in observation group were significantly lower than those in control group(P＜0.05),while there was no difference in heart rate,blood oxygen saturation and mean arterial pressure at various time points during awakening(P＞0.05);The recovery rate of postoperative analgesics of observation group was lower than that of control group,and the extubation time of observation group was shorter than that of control group(P＜0.05);The incidence of postoperative adverse reactions and behaviors in observation group were lower than those in control group(P＜0.001).The dosage of propofol and long chain fat emulsion/remifentanil injection,as the independent risk factors inducing the occurrence of postoperative adverse reactions and adverse behaviors were proved by multivariate analysis.rSO2-BIS monitoring is a key factor in reducing postoperative adverse behaviors and reactions in pediatric patients(P＜0.05).Conclusion The use of rSO2-BIS monitoring during surgery for supracondylar fractures of the humerus in children can reduce the incidence rate of postoperative adverse behaviors and adverse reactions,thereby improving postoperative efficacy.

Objective:To investigate the effect of Fu-Fang-Yu-Jie(FFYJ)granules on LPS-induced inflammation model in bone marrow-derived macrophages(BMDM)and its intervention of FFYJ on nucleotide-bound oligomeric domain-like receptor protein 3(NLRP3)inflammatory signaling pathway in macrophages.Methods:Primary cells were extracted and isolated from the leg bone mar-row of C57BL/6 mice and BMDM macrophages were obtained after 7 days of induction with 50 ng/ml M-CSF.Groups included control group(Control),model group(LPS+ATP),FFYJ low dose group(FFYJ 50 μg/ml),FFYJ medium dose group(FFYJ 100 μg/ml),FFYJ high dose group(FFYJ 200 μg/ml)and positive drug dexamethasone group(DEX).BMDM in FFYJ treatment group and posi-tive drug group were pretreated for 1 hour before modeling.Lactate dehydrogenase(LDH)release assay was used to detect the level of LDH in the supernatant of each group of cells;ELISA was used to detect the level of inflammatory factors TNF-α,IL-6 and IL-1β in the supernatant of each group of cells;qRT-PCR was used to detect the levels of TNF-α,IL-6 and IL-1β in each group of cells;protein levels of NF-κB,p-NF-κB,NLRP3,Caspase-1 p45,Caspase-1 p20 and GSDMD-N in each group of cells were detected by Western blot;inverted fluorescence microscope was used to observe the cell pyroptosis of each group after Hoechst-PI staining.Results:Compared with control group,the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of the model group were signifi-cantly higher(P<0.000 1);the mRNA levels of TNF-α,IL-6 and IL-1β in the model group were significantly higher(P<0.000 1);the protein levels of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N were significantly higher(P<0.05);and the number of PI-posi-tive cells was significantly higher(P<0.05).Compared with the model group,FFYJ and DEX significantly reduced the levels of LDH,TNF-α,IL-6 and IL-1β in the supernatant of BMDMs(P<0.05);down-regulated the mRNA levels of TNF-α,IL-6 and IL-1β in the cells(P<0.05);and inhibited the expressions of p-NF-κB,NLRP3,Caspase-1 p20 and GSDMD-N protein expressions(P<0.05);and significantly reduced the number of PI-positive cells(P<0.05).Conclusion:FFYJ exerts anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in BMDM macrophages.