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OBJECTIVE@#To investigate the efficacy and clinical results of total internal protection technique in anterior cruciate ligament reconstruction.@*METHODS@#A total of 56 patients undergoing anterior cruciate ligament reconstruction treated from January 2018 to December 2019 were selected. According to the different surgical methods, they were divided into total internal reconstruction group and standard bone tunnel group. There were 21 patients in the total internal reconstruction group, including 15 males and 6 females, aged from 20 to 48 with an average of (35.6±6.7) years old, and 35 patients in the standard tibial tunnel group, including 26 males and 9 females, aged 22 to 51 years old with an average of (33.7±9.6) years old. Preoperative examination of Lachman test was positive, magnetic resonance indicated anterior cruciate ligament rupture. There were no significant differences between the two groups in age, sex, body mass index, time from injury to ACL reconstruction, combined meniscus injury and operation method, operation time, ligament diameter, ligament length and other general information. Postoperative evaluation included operation duration, length and diameter of transplanted tendon after braid. International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner score and perioperative complications 2 years after surgery.@*RESULTS@#Both groups were followed up, ranging from 24 to 30 months with an average of (26.9±3.4) months. Postoperative incision healing was good, and no failure or joint infection occurred at the last follow-up. There was no statistically significant difference between the two groups in IKDC score, Lysholm score and Tegner score before, 1 year and 2 years after surgery. However, IKDC score, Lysholm score and Tegner score at 1 year and 2 years after surgery.@*CONCLUSION@#The same postoperative function and stability of knee joint can be obtained by both the residual whole technique and the standardized reconstruction technique. In the residual whole group, only the semitendinosus muscle is taken, and the femoral thin muscle is retained, with greater tibial bone mass preserved, which is safe and effective in clinical practice.
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Male , Female , Humans , Adult , Young Adult , Middle Aged , Anterior Cruciate Ligament/surgery , Retrospective Studies , Treatment Outcome , Arthroscopy/methods , Knee Joint/surgery , Anterior Cruciate Ligament Injuries/surgeryABSTRACT
"MS/MS spectrum to structure"plays a critical role in the confirmative identification of complicated matrices and is currently regarded as an extremely challenging endeavor.MS/MS information provides vital clues to structural identification.In this study,a strategy was proposed to facilitate unambiguous identification through matching MS3 with MS2 spectra.Initially,MS3 spectra of the featured ions(c-and y-type ions)generated by the decomposition of ester functional group in esters and the MS2 spectrum of the structural unit([M-H]-)were all captured on the Qtrap-MS platform equipped with two tandem-in-space collision cells,including the second quadrupole cell(q2)and linear ion trap(LIT)chambers(actually the third quadrupole unit).Subsequently,the MS/MS spectrum matching between MS3 spectra of the ester compound and MS2 spectra of the structural unit(s)were achieved.As a result,the findings corresponding to MS3 and MS2 spectra matching were summarized.Finally,based on HR-MS/MS information of total salvianolic acid derivatives(TSA),36 kinds of compounds were preliminarily identified through matching with literature information and database retrieval.The applicability of MS3 and MS2 spectra matching strategy was further justified by the confirmative identification of phenolic acid compounds(Rosmarinic acid and salvianolic acid B)in TSA.Above all,MS3 and MS2 spectra matching strategy was quite meaningful towards advancing"MS/MS spectrum to structure"analysis through recognizing and identifying featured fragment ions,and also provided inspiration and new insights for the structural characterization.
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Objective To investigate the effect of right stellate ganglion block(SGB)on postoper-ative shoulder pain in patients receiving laparoscopic cholecystectomy(LC).Methods A total of 104 pa-tients scheduled for LC from April to August 2022,32 males and 72 females,aged 18-64 years,ASA phys-ical status Ⅰ orⅡ,were selected and randomized into two groups:the stellate ganglion block group(group S,n = 51)and the control group(group C,n = 53).Immediately after intubation,0.2%ropivacaine 4 ml was used for ultrasound-guided right SGB in group S,and saline 4 ml was injected at the same site in group C.The number of cases of post-laparoscopic shoulder pain(PLSP)and the duration of PLSP were re-corded within 48 hours after operation.The VAS pain scores of PLSP were recorded to assess the level of PLSP immediately after operation(T1),2 hours after operation(T2),6 hours after operation(T3),12 hours after operation(T4),24 hours after operation(T5),and 48 hours after operation(T6).The number of effective compressions of the PCIA pump and the salvage analgesia were recorded.The adverse reactions such as nausea,vomiting,and abdominal distension were recorded.Results The incidence of PLSP and the rate of patients with PLSP lasting more than 10 hours in group S was significantly lower than those in group C(P<0.05),and the degree of PLSP in group S was significantly lower than that in group C at T3-T5(P<0.05).The number of effective compressions of the PCIA pump and the salvage analgesia rate in group S was significantly lower than those in group C(P<0.05).The incidence of nausea in group S was significantly lower than that in group C(P<0.05).Conclusion Right stellate ganglion block can reduce the incidence of PLSP in patients receiving LC,relieve the pain degree of PLSP,and reduce the incidence of adverse reactions.
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BACKGROUND:Traditional 3D dental segmentation methods usually utilize predefined spatial geometric features,such as curvature and normal vectors,as the reference information for tooth segmentation. OBJECTIVE:To propose an algorithm for complex 3D dental segmentation and deeply explore the correlation between segmentation results and application scenarios. METHODS:A 3D dental segmentation algorithm based on dual stream extraction of structural features and spatial features was established,and the modular design of split flow was used to avoid feature confusion.Among them,the attention mechanism on the structural feature flow was used to capture the fine-grained semantic information required for tooth segmentation,and the Tran Net based on the spatial feature flow was used to ensure the robustness of the model to complex tooth and jaw segmentation.This algorithm verified its effectiveness and reliability based on clinical datasets including healthy dental jaws and complex dental jaws such as missing teeth,malocclusion and dentition crowding.The segmentation performance of the model was measured in terms of overall accuracy,mean intersection over union,and directional cut discrepancy. RESULTS AND CONCLUSION:The overall segmentation accuracy of this algorithm in the clinical data set is 97.08%,and the segmentation effect is superior to that of other competitive methods from the qualitative and quantitative perspectives.It is verified that the structural feature flow designed in this paper can extract more precise local details of tooth shape from coordinate and normal information by constructing an attention aggregation mechanism,and the spatial feature flow designed in this paper can ensure the robustness of the model to complex teeth such as missing teeth,dislocated teeth,and crowded dentition by constructing a transformation network(Tran Net).Therefore,this tooth segmentation algorithm is highly reliable for clinicians'practical reference.
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Objective:To explore the rehabilitation effect of Cox health behavior interaction mode in elderly patients with valvular heart disease(VHD)and its impact on their quality of life(QOL).Methods:A total of 120 elderly VHD patients enrolled from Jun 2020 to Jun 2022 were divided into routine nursing group(n=60)and Cox group(n=60,received Cox health behavior interaction mode intervention)according to random number table method.Both groups were intervened for six months.General data,cardiac function,6min walking distance(6MWD),QOL,sleep quality and disease percep-tion before and after intervention were compared between two groups.Results:Compared with routine nursing group after six months,there were significant rise in left ventricular ejection fraction(LVEF)[(48.87±4.41)%vs.(51.94± 4.04)%],6MWD[(353.20±4.83)m vs.(424.93±4.40)m],scores of China questionnaire of quality of life in pa-tients with cardiovascular diseases(CQQC)[(84.67±4.05)scores vs.(134.46±4.58)scores]and control attitude scale-revised(CAS-R)[(22.13±3.21)scores vs.(34.98±3.39)scores],and significant reductions in left ventricular end-systolic diameter(LVESd)[(54.99±6.07)mm vs.(49.01±5.48)mm],left ventricular end-diastolic diameter(LVEDd)[(59.20±7.16)mm vs.(54.05±6.14)mm]and Pittsburgh sleep quality index(PSQI)[(14.53±2.42)scores vs.(9.31±1.10)scores]in Cox group,P=0.001 all.Conclusion:The Cox health behavior interaction mode plays a role in the treatment and rehabilitation of elderly patients with valvular heart disease,which can observably improve their cardiac function,physical endurance and quality of life.
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Objective:To investigate the role of 24-dehydrocholesterol reductase(DHCR24)in doxorubicin-induced senescence-related dysfunction of vascular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were induced with 0.05 μM doxorubicin for 48 h to establish a stress-triggered premature senescence model.The lentiviral transfection method was employed to achieve DHCR24 overexpression in HUVECs.Cell senescence was evaluated by β-galactosidase staining and Western blot to detect the expression of the senescence-related molecules cyclin-dependent kinase inhibitor 1A(P21)and nicotinamide adenine dinucleotide dependent histone deacetylase 1(SIRT1).Western blot was performed to detect DHCR24 and endothelial nitric oxide synthase(eNOS)expression during endothelial senescence.DAF-FM DA(an NO fluorescent probe)was used to detect intracellular NO production.Results:In the stress-triggered premature senescence model of HUVECs induced by doxorubicin, the expression of the senescence marker P21 was up-regulated( t=19.44, P<0.01), SIRT1 was down-regulated( t=10.10, P<0.01, and the expression of DHCR24 was down-regulated( t=5.946, P<0.01), compared with the control group.Meanwhile, eNOS and NO expression was inhibited( t=11.26, P<0.01; t=10.83, P<0.01).After DHCR24 overexpression, compared with the control stimulation group, the overexpression stimulation group showed that DHCR24( F=72.10, P<0.01)was up-regulated.DHCR24 overexpression alleviated the doxorubicin-induced decrease in eNOS and NO( F=5.797, P<0.05; F=45.12, P<0.01), compared with the control group. Conclusions:DHCR24 may mitigate doxorubicin-induced senescence-related vascular endothelial dysfunction by modulating the eNOS/NO signaling pathway.
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Objective:To investigate the predictive value of serum uric acid/albumin ratio (sUAR) for acute kidney injury (AKI) after cardiac valve surgery.Methods:The clinical data of adult patients undergoing cardiac valve surgery under cardiopulmonary bypass from January 2021 to December 2021 from the Heart Center of Henan Provincial People's Hospital were collected retrospectively, and the sUAR was calculated. All patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac valve surgery, and the differences of clinical data between the two groups were compared. Multivariate logistic regression model was used to analyze the independent correlation factors of AKI after cardiac valve surgery. The receiver operating characteristic (ROC) curve was used to evaluate the performance of relevant indicators.Results:A total of 422 patients were enrolled, including 194 females (46.0%), 141 hypertension patients (33.4%) and 172 atrial fibrillation patients (40.8%). They were 57 (50, 65) years old. Their sUAR was 8.13 (6.57, 9.54) μmol/g, and hemoglobin was 135 (125, 145) g/L. There were 142 cases in AKI group and 280 cases in non-AKI group, and the incidence of AKI after cardiac valve surgery was 33.6%. Age, atrial fibrillation rate, baseline serum creatinine, N terminal pro B type natriuretic peptide, serum urea,serum uric acid, blood glucose and sUAR were higher in the AKI group than those in the non-AKI group (all P<0.05), and estimated glomerular filtration rate, lymphocyte count,hemoglobin and serum albumin were lower in the AKI group than those in the non-AKI group (all P<0.05). The median cardiopulmonary bypass time of patients in the AKI group was slightly longer than that in the non-AKI group, but the difference was not statistically significant [159 (125, 192) min vs. 151 (122, 193) min, Z=-0.797, P=0.426], and there were no statistically significant differences in other indicators between the two groups. The results of multivariate logistic regression analysis showed that sUAR ( OR=1.467, 95% CI 1.308-1.645, P<0.001), age ( OR=1.045, 95% CI 1.020-1.072, P<0.001), atrial fibrillation ( OR=2.520, 95% CI 1.580-4.020, P<0.001), hemoglobin ( OR=0.984, 95% CI 0.971-0.997, P=0.015) were the independent correlation factors. ROC curve analysis showed that the area under the curve ( AUC) of sUAR predicting AKI after cardiac valve surgery was 0.710 (95% CI 0.659-0.760, P<0.001) with a sensitivity of 85.2% and specificity of 45.0% for the sUAR cut-off point of 7.28 μmol/g. The AUC for the diagnosis of AKI after cardiac valve surgery was 0.780 (95% CI 0.734-0.825, P<0.001) with a sensitivity of 72.5% and specificity of 71.8% for the combination of sUAR with age, hemoglobin and atrial fibrillation. Conclusions:For patients undergoing cardiac valve surgery under cardiopulmonary bypass, preoperative high sUAR is an independent risk factor for postoperative AKI, and sUAR has a certain predictive value for postoperative AKI.
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Traditional Chinese Medicine (TCM) is an indispensable carrier of traditional culture for China to embrace the world. During the 14th Five-Year Plan period, the state proposed to "comprehensively promote the building of a healthy China, attach equal importance to TCM and western medicine, and vigorously develop the cultural industry of TCM". Promoting the development of TCM cultural industry needs scientific and innovative approaches. This paper explored how to realize the communication path of TCM culture from the perspective of "Industry-University-Research". Based on the analysis of the current situation of TCM culture communication, taking Shandong University of Traditional Chinese Medicine as an example, this paper integrated technology, human resources, resources, environment and information and other collaborative innovation elements to effectively gather, and explored a new way for the collaborative development of TCM communication with enterprises, schools, scientific research institutions and et al, aiming to further help TCM culture go abroad.
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Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60%participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10%participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.
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ObjectiveTo investigate the detoxification mechanism of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Prepared Aconiti Kusnezoffii Radix Cocta, and their effective components ellagic acid, liquiritin and aconitine based on cardiac cytochrome P450 (CYP450) system. MethodIn in vivo experiments, rats were randomly divided into control group, prepared Aconiti Kusnezoffii Radix Cocta group (0.25 g·kg-1), Chebulae Fructus group (0.252 g·kg-1), Glycyrrhizae Radix et Rhizoma group (0.25 g·kg-1) and combination group (0.25 g·kg-1 Chebulae Fructus+0.25 g·kg-1 Glycyrrhizae Radix et Rhizoma+0.25 g·kg-1 prepared Aconiti Kusnezoffii Radix Cocta, with prepared Aconiti Kusnezoffii Radix Cocta as standard). After 8 days of administration, creatine kinase (CK) and lactate dehydrogenase (LDH) in rats were detected to observe the pathological changes of heart tissue. Real-time PCR and Western blot were performed to detect the mRNA and protein expressions of CYP2J3, respectively. In in vitro experiments, control group, aconitine group, ellagic acid group, liquiritin group and combination group (aconitine+ellagic acid+liquiritin) were set, and their effects on cell number, DNA content, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by high content analysis. The changes in the mRNA and protein expressions of CYP2J3 were also observed. ResultIn vivo experiments, compared with the control group, the prepared Aconiti Kusnezoffii Radix Cocta group had increased CK and LDH in serum (P<0.05, P<0.01), while the combination group had decreased activities of CK and LDH. Additionally, pathological staining results showed that Chebulae Fructus and Glycyrrhizae Radix et Rhizoma reduced the cardiac toxicity caused by prepared Aconiti Kusnezoffii Radix Cocta. Real-time PCR found that compared with the control group, prepared Aconiti Kusnezoffii Radix Cocta down-regulated the mRNA level of CYP2J3 (P<0.05), while up-regulated that expression when used in combination with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma (P<0.01). The protein and mRNA translation levels were basically consistent. In vitro experiments, high content analysis revealed that there was a decrease in the cell number, DNA content and MMP fluorescence value of the aconitine group (P<0.01) and the combination group (P<0.05, P<0.01), and the fluorescence value of the combination group was higher than that of the aconitine group. Moreover, aconitine down-regulated the mRNA level of CYP2J3 (P<0.05), but the down-regulating ability of aconitine was reversed in the combination group (P<0.05). ConclusionThe detoxification mechanism of combined Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and prepared Aconiti Kusnezoffii Radix Cocta is mainly that the combination of ellagic acid, liquiritin and aconitine can up-regulate the expression of CYP2J3, and promote the metabolism of arachidonic acid (AA) to produce epoxyeicosatrienoic acids (EETs), thus reducing the cardiac toxicity, and this effect may start from the transcriptional link.
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The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.
Subject(s)
Animals , Mice , Adipose Tissue, Brown/metabolism , PPAR alpha/pharmacology , Diet, Ketogenic , Uncoupling Protein 1/metabolism , Blood Glucose/metabolism , Temperature , Mice, Inbred C57BL , Liver , Adipose Tissue/metabolismABSTRACT
The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Subject(s)
Rats , Mice , Animals , Rats, Sprague-Dawley , Angiotensin II/pharmacology , Fibroblasts , Mice, Inbred C57BL , Fibrosis , Collagen/pharmacology , Collagen Type I/metabolism , RNA, Messenger/metabolism , Myocardium/pathologyABSTRACT
This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.
Subject(s)
Osteogenesis , Core Binding Factor Alpha 1 Subunit/pharmacology , Large-Conductance Calcium-Activated Potassium Channels/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Calcium/metabolism , Cell Differentiation , RNA, Messenger/metabolism , Cell Proliferation , OsteoblastsABSTRACT
Objective To explore the risk factors of clopidogrel resistance (CR) in the elderly patients with atherosclerotic cardiovascular disease and to provide evidence for the antiplatelet therapy. Methods A total of 223 elderly patients (≥80 years old) with atherosclerotic cardiovascular disease treated in the Department of Geriatrics in the Peking University People's Hospital from January 18,2013 to November 30,2019 and meeting the inclusion criteria were enrolled in this study.The clinical data and laboratory test results were collected,including clinical disease,drug use,physical examination,complete blood cell analysis,biochemical indicators,and thromboelastogram (TEG).The rate of platelet inhibition induced by adenosine diphosphate was calculated according to the TEG.We assigned the patients into a CR group (n=84) and a control group (n=139) to analyze the incidence and influence factors of CR in the elderly patients with atherosclerotic cardiovascular disease. Results The incidence of CR was 37.7% in the elderly patients with atherosclerotic cardiovascular disease.The CR group had lower hemoglobin (t=3.533,P=0.001) and higher hypertension prevalence rate (χ2=6.581,P=0.006),proportion of multiple drugs (χ2=3.332,P=0.048),body mass index (BMI) (t=-2.181,P=0.030),total cholesterol (t=-2.264,P=0.025),triglycerides (Z=-2.937,P=0.003),low-density lipoprotein cholesterol (LDL-C) (t=-2.347,P=0.020),and proportion of women (χ2=5.562,P=0.014) than the control group.The results of multivariate Logistic regression showed that hemoglobin (OR=0.962,P<0.001),BMI (OR=1.154,P=0.003),and LDL-C (OR=1.688,P=0.018) were the factors influencing CR in the elderly patients with atherosclerotic cardiovascular disease. Conclusion Hemoglobin,BMI,and LDL-C may be independent factors associated with the occurrence of CR in the elderly patients with atherosclerotic cardiovascular disease.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Atherosclerosis , Cardiovascular Diseases , Cholesterol, LDL , Clopidogrel/therapeutic use , Risk FactorsABSTRACT
Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
Subject(s)
Humans , Mice , Animals , Dysbiosis , Anti-Bacterial Agents/pharmacology , Virulence , Microbiota , Periodontitis/chemically induced , CytokinesABSTRACT
This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA_07227 and circRNA_11464 in the aorta of AS model and circRNA expression(such as circRNA_11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS_00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.
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Animals , Male , Mice , Atherosclerosis/genetics , Lipids , Mice, Inbred C57BL , Myocardial Infarction/genetics , RNA, Circular/genetics , RNA, Long Noncoding/geneticsABSTRACT
Objective:To investigate the effects of Guiling Gao on body temperature, gastrointestinal motility, gastrointestinal hormones, Th1/Th2 cytokines and water metabolism in rats with damp-heat syndrome.Methods:Totally 60 SD rats were randomly divided into control group, model group, mosapride group, Guiling Gao low dose group (3.4 g/kg), medium dose group (6.8 g/kg) and high dose group (13.6 g/kg) according to random number table method, with 10 rats in each group. Except for the blank group, the other groups adopted the method of "environmental factors + fat and sweet diet + biological factors" to prepare the rat model of damp heat syndrome of febrile diseases. After modeling, they were administered by gavage for 7 days. During the experiment, the general state, body weight and body temperature were observed, the gastric residue rate of rats was calculated by weighing method, the intestinal propulsion rate of rats was calculated by charcoal propulsion method, and the levels of serum motilin (MTL), gastrin (GAS), somatostatin (SS), substance P (SP),IL-4 and interferon-γ (IFN-γ) were detected by ELISA, and the changes of aquaporin 3 (AQP3) mRNA transcription level were detected by real-time PCR.Results:Compared with the model group, the weight of rats in Guiling Gao high dose group increased after experiment of 22 days ( P<0.05), and body temperature of rats in Guiling Gao medium and high dose group decreased in 19-20 day ( P<0.01); and the gastric emptying rate and the small intestine propulsion rate of small intestine in Guiling Gao medium and high dose group increased significantly ( P<0.01 or P<0.05); the serum MTL, GAS and SP levels increased ( P<0.01 or P<0.05), and SS decreased ( P<0.01 or P<0.05) in the Guiling Gao medium and high dose groups; The levels of IL-4, IFN-γ and IFN-γ/IL-4 ratio decreased ( P<0.01); The expression of AQP3 mRNA (1.16 ± 0.25 vs. 0.23 ± 0.01) in the Guiling Gao high dose group was up-regulated ( P<0.01). Conclusions:Guiling Gao can effectively improve the activity state of damp-heat syndrome model rats caused by complex factors. This mechanism may be related to enhancing gastrointestinal movement, increasing gastrointestinal hormone secretion, restoring the dynamic balance of immune system Th1/Th2 and promoting the transport of water from intestinal cavity.
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Objective:To develop a formula for estimating the insertion length of orogastric (OG) tube for preterm infants based on growth indicators and gestational age (GA).Methods:From January 2020 to December 2021, preterm infants admitted to the neonatal intensive care unit of our hospital were retrospectively reviewed. OG tubes were inserted within 24 h of admission and the lengths of OG tubes were adjusted according to chest and abdominal X-ray results. The formula for OG tube placement was developed using stepwise regression analysis method with GA, body weight (BW) and body length (BL) as the independent variables and the corrected length of OG tube as the dependent variable. The weight-based formula developed by Freeman et al. were compared.Results:A total of 180 preterm infants were included, with 90 cases GA<32 weeks, 84 cases GA 32~35 weeks and 6 cases GA 36 weeks. No significant differences ( P>0.05) existed in the incidences of misplacement of OG tube and the specific types of misplacement among GA groups. For infants with GA≤35 weeks, the insertion length of OG tube was positively correlated with BW and BL and for preterm infants with GA 36 weeks, the insertion length of OG tube was positively correlated with BW only. Stepwise regression analysis showed the formula as OG tube length (cm)=11.8+2.1×BW (kg) or OG tube length (cm)=9.5+1.6×BW (kg)+0.091×GA (week). Comparing with the formula developed by Freeman et al., the differences of OG tube length estimated using our formula were more prominent as BW increased. Conclusions:The length of OG tube is positively correlated with BW and GA with BW shows more influence.
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Objective:To explore the anti-aging effects of berberine hydrochloride and underlying mechanism.Methods:Twelve 4-week-old C57BL6/J mice were divided into aging group (fed with normal chaw), aging+ BBR intervention group(fed with normal chaw containing 1 g/kg berberine hydrochloride). At the age of 64 weeks, all the experimental mice were executed. The liver tissues were made into paraffin sections for HE staining to observe the morphological and structural integrity of liver parenchymal cells for pathological evaluation. Immunofluorescence was used to detect p16 protein expression levels in liver. The expression levels of malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px) were detected by colorimetry. The expression levels of interleukin(IL)-1β, IL-6, and tumor necrosis factor-α(TNF-α) in liver tissues and IL-8 in serum were detected by enzyme linked immunosorbent assay(ELISA) technique. The p16, p21, nuclear factor erythroid-2 related factor 2(Nrf2), nuclear factor-κB(NF-κB), phospho(p-)NF-κB, inhibitory κB(IκB)α, p-IκBα, and p38 mitogen-activated protein kinase(MAPK) protein expression levels in liver were detected by Western blotting. The same indices were tested in the 16-week-old mice as the young control group.Results:Compared with the young control group, the liver tissue in the aging control group exhibited morphological aging and antioxidant capacity were reduced( P<0.01), and inflammatory factors were increased( P<0.05 or P<0.01). Compared with the aging group, the liver tissues in the aging+ BBR intervention group were still maintain regular arrangement of hepatocytes, the p16 and p21 protein expression levels were significantly increased( P<0.05 or P<0.01), the antioxidant capacity were increased( P<0.05 or P<0.01), the level of inflammatory factors were decresed( P<0.05 or P<0.01), and the p38 MAPK/NF-κB pathway and Nrf2 pathway were inhibited( P<0.001). Conclusion:Berberine hydrochloride improves the aging morphology of the liver, potentially by suppressing the p38 MAPK/NF-κB pathway to reduce inflammation levels and inhibiting the Nrf2 pathway to ameliorate oxidative stress.
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Objective The transcriptome sequencing results of brain tissues of olanzapine-treated mice were analyzed to screen out differentially-expressed genes and explore potential targets of atypical antipsychotics leading to body weight gain.Methods Twenty female C57BL/6 mice were randomly divided into control group (Ctrl) and Olanzapine administration group (Olz), which were given saline and Olanzapine solution by gavage, respectively. The whole brain tissues were collected 8 weeks later for Transcriptome sequencing (RNA-Seq). The possible targets of olanzapine-induced body weight gain were identified by the Gene Ontology (GO) functional annotation analysis, the Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Differential expression levels of mRNAs were further verified by real-time quantitative fluorescence PCR (RT-qPCR).Results Compared with Ctrl group, 591 differentially expressed genes were screened in Olz group, including 251 up-regulated genes and 340 down-regulated genes. GO analysis showed that differential genes were widely involved in transcriptional process, among which the expression of genes related to the regulation of digestive system and cold-induced thermogenesis were significantly enriched. KEGG analysis showed that differential genes were widely involved in the interaction between neuroactive ligands and receptors, and the differential genes were significantly enriched in oxytocin signaling, fat digestion and absorption, and cholesterol metabolism pathways. RT-qPCR were performed to verify the expression levels of genes enriched in feeding regulation, gastric kinesis, thermogenesis, fat metabolism and other processes (Oxt, Trpv1, Adipoq, Phox2b, Abcg5, Mogat2, Dbh, Plac8 and Neurog1) as well as hub genes in PPI network (Fos, Dusp1 and Egr2), and the results were consistent with the trend of RNA-Seq.Conclusion Olanzapine administration resulted in changes in central feeding regulation, gastrointestinal motility, thermogenesis and other physiological processes in mice, which might be involved in body weight gain induced by olanzapine.