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Objective To explore the role of endothelial cells in angiogenesis and myocardial remodeling in heart failure based on MAPKs pathway mediated by tumor endothelial marker 1(TEM1).Methods Sixty-four mice were equally randomized into four groups:sham operation,myocardial infarction(MI),MI+sh-NC and MI+ sh-TEM1.On the 7th day after MI,the changes of EndMT in the infarct border area were detected by immunofluo-rescence staining,and the cardiac function of mice was evaluated by echocardiography on the 28th day.Mouse aortic endothelial cells(MAECs)were divided into three groups:control,Vector and rTEM1.In addition,MAECs were pretreated with MAPK inhibitor SB203580,and the cells were treated with rTEM1 for 48 h.The changes of EndMT and MAPKs signaling pathways in endothelial cells were evaluated by Western blot.Results In the myocardium at the border of infarction,the level of TEM1-1 increased slightly on the 1st day after MI,reached the peak on the 7th day,and then decreased on the 28th day.Compared with Vector group,the expression of VE-Cadherin protein in the rTEM1 group decreased significantly(P<0.05),and the levels of α-SMA and vimentin,relative migration distance,the number of invading cells,and the number of branching formation increased signifi-cantly(P<0.05).SB203580 reversed these changes of MAECs induced by rTEM1.Compared with the MI group,the co-staining level of CD31+Vimentin+ in the MI+sh-TEM1 group decreased significantly(P<0.01).On the 28th day,the LVEF and LVFS in the MI+sh-TEM1 group were significantly higher than those in MI group(P<0.05).Compared with the MI group,the expressions of p-P38/P38 and p-JNK/JNK in the endothelial cells of the MI+sh-TEM1 group decreased.Conclusion EndMT and angiogenesis induced by TEM1 participate in the pathogenesis of cardiac fibroblasts induced by MI,which may be mechanically related to the activation of MAPKs signaling pathway.
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BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.
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BACKGROUND:Establishing a nomogram prediction model for postoperative pulmonary infection in hip fractures and taking early intervention measures is crucial for improving patients'quality of life and reducing medical costs. OBJECTIVE:To construct a nomogram risk prediction model of postoperative pulmonary infection in elderly patients with hip fracture,and provide theoretical basis for feasible prevention and early intervention. METHODS:Case data of 305 elderly patients with hip fractures who underwent surgical treatment at Wuxi Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine between January and October 2020(training set)were retrospectively analyzed.Using univariate and multivariate logistic regression analysis and Hosmer-Lemeshow goodness of fit test,receiver operating characteristic curve was utilized to analyze the diagnostic predictive efficacy of independent risk factors and joint models for postoperative pulmonary infections.Tools glmnet,pROC,and rms in R Studio software were applied to construct a nomogram model for predicting the risk of postoperative pulmonary infection in elderly patients with hip fractures,and calibration curves were further drawn to verify the predictive ability of the nomogram model.Receiver operating characteristic curves,calibration curves,and decision curves were analyzed for 133 elderly patients with hip fractures(validation set)receiving surgery at the same hospital from November 2022 to March 2023 to further predict the predictive ability of the nomogram model. RESULTS AND CONCLUSION:(1)The postoperative pulmonary infection rate in elderly patients with hip fractures in this group was 9.18%(28/305).(2)Single factor and multivariate analysis,as well as forest plots,showed that preoperative hospitalization days,leukocyte count,hypersensitive C-reactive protein,and serum sodium levels were independent risk factors(P<0.05).The Hosmer-Lemeshow goodness of fit test showed good fit(χ2=4.57,P=0.803).Receiver operating characteristic curve analysis was conducted on the independent risk factors and their joint models mentioned above,and the differentiation of each independent risk factor and joint model was good,with statistical significance(P<0.05).(3)The graphical calibration method,C-index,and decision curve were used to validate the nomogram prediction model.The predicted calibration curve was located between the standard curve and the acceptable line,and the predicted risk of the nomogram model was consistent with the actual risk.(4)The validation set used receiver operating characteristic curve,graphic calibration method,and decision curve to validate the prediction model.The results showed good consistency with clinical practice,indicating that the model had a good fit.The nomogram risk prediction model constructed for postoperative pulmonary infection in elderly patients with hip fractures has good predictive performance.The use of the nomogram risk prediction model can screen high-risk populations and provide a theoretical basis for early intervention.
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ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） 1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.
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Objective:To discuss the efficacy of pelvic lymph node dissection (PLND) on the patients undergoing radical cystectomy (RC).Methods:The clinicopathological data of bladder cancer patients who did not receive neoadjuvant chemotherapy and underwent RC in our center from November 2013 to December 2019 were collected. The average age of the patients was (67.4±10.9) years, including 284 males and 55 females. Postoperative pathology showed that 171 cases of MIBC and 168 cases of NMIBC. In the MIBC group, 124 patients received PLND. In the NMIBC group, 118 patients received PLND. There was no statistical difference of the PLND ratio between the two groups(72.5% vs. 65.5%, P=0.643). The average number of lymph nodes(LNs)in patients receiving PLND was(13.7±7.1). Explore the prognostic factors in NMIBC and MIBC respectively. The Kaplan-Meier method was used to analyze the effect of PLND on the prognosis of patients in MIBC and NMIBC group. Results:In MIBC group, 26 patients showed positive LNs, while 98 had negative LNs. 144 cases were high-grade urothelial carcinoma, and 47 cases received adjuvant treatment. In NMIBC group, 4 patients exhibited positive LNs, while 114 had negative LNs. 99 cases were high-grade urothelial carcinoma, and 15 cases received adjuvant treatment. After a median follow-up of 24(13, 43)months, Kaplan-Meier survival analysis showed that the 5-year overall survival(OS)of 395 patients was 63.6%. MIBC had a 5-year OS rate of 47.5%, while NMIBC had a rate of 79.1%. Univariate Cox regression showed that age≥65 years( HR=2.07, 95% CI 1.21-3.54, P=0.009), high tumor grade( HR=9.76, 95% CI 2.39-39.90, P<0.01), and positive lymph nodes( HR=2.47, 95% CI 1.27-4.78, P=0.008)were risk factors for the prognosis of MIBC.PLND ( HR=0.37, 95% CI 0.23-0.60, P<0.01) and adjuvant therapy ( HR=0.21, 95% CI 0.10-0.46, P<0.01) were protective factors of MIBC. However, the only risk factor of NMIBC was high tumor grade ( HR=6.66, 95% CI1.51-29.50, P=0.012). PLND had no effect on the prognosis of NMIBC patients following RC( HR=1.32, 95% CI 0.37-4.75, P=0.667). Multivariate COX regression analysis revealed that high tumor grade( HR=6.38, 95% CI 1.54-26.50, P=0.011) was independent risk factor of MIBC, PLND( HR=0.59, 95% CI 0.35-0.99, P=0.047), as well as adjuvant therapy ( HR=0.30, 95% CI 0.13-0.68, P=0.004) were independent protective factors of MIBC. Further analysis discovered that MIBC patients with negative LNs had a better prognosis than those with no PLND (62.4% vs. 16.1%, P<0.01)and positive LNs(62.4% vs.32.3%, P=0.005). However, there was no difference in prognosis between the negative LNs and no PLND group in NMIBC patients (81.3% vs. 66.6%, P=0.764). Conclusions:This study found that PLND was an independent predictive factor for MIBC patients receiving radical cystectomy.
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Objective:Comprehensively review national and provincial policies related to centralized procurement of Chinese Patent Medicines(CPM)and to compare the grouping rules and methods of centralized procurement in different regions,with the goal of providing guidance for enhancing the grouping rules for CPM.Methods:Through literature analysis and comparative analysis,the 22 policies included in the study were analyzed in depth,and the progress of centralized volume-based procurement of CPM in national and inter-provincial alliances was compared and summarized.Results:National and inter-provincial alliances'centralized volume-based procurement of CPM divides procurement groups according to functional indications,route of administration,and market conditions.The grouping rules are not closely related to drug dosage forms and quality.Dividing bidding groups based on the market competition pattern ignores the innovative value of some CPM,and does not take into account the unique brand value of the company and its drugs.The completeness of the grouping rules needs to be improved.Conclusions:There are many dosage forms of CPM and complex quality control indicators.The existing grouping rules follow the idea of grouping chemical drugs and lack a top-level design oriented to the value of CPM.It is recommended to adopt a diversified grouping method and advance the technical evaluation link in the existing shortlisting rules.This means that factors such as drug dosage form,quality and innovation value should be considered when formulating grouping rules.At the same time,it is necessary to improve and refine the current grouping rules.
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Objective:To explore the application value of quality detection technology in the acceptance process of new medical injection pump equipment.Methods:75 sets of medical injection pumps newly purchased by the hospital were selected,and quality inspection and acceptance were carried out by using quality inspection techniques in accordance with the requirements of the Technical Specifications for Quality Inspection of Infusion Pumps and Injection Pumps(Trial).The unqualified equipment was calibrated by a combination of precision calibration,system version upgrade and data import and then the quality inspection was conducted again.Results:The appearance,blocking alarm and alarm prompt function of 75 newly purchased medical injection pumps were all in line with the regulatory requirements.In the flow parameter detection,16 sets were initially detected,11 sets were unqualified,with a failure rate of 68.75%,and 3 of 5 qualified equipment showed a relative error of less than-4.0%.After the equipment was calibrated,the flow parameters were tested again.All 75 medical injection pumps met the regulatory requirements.The absolute value of the relative error of the indication value of 69 medical injection was less than 2.5%,and the absolute value of the relative error of the indication value of only 6 was more than 2.5%.Conclusion:The quality detection technology and calibration method can ensure the safety of clinical use of medical equipment and protect the life and health of patients.
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Objective:To explore the feasibility of mismatch of amide proton transfer weighted (APTw) imaging with diffusion weighted imaging (DWI) in evaluating ischemic penumbra (IP) in patients with wake-up stroke.Methods:A prospective study was performed; 96 patients with wake-up stroke and unilateral middle cerebral artery territory infarction admitted to Emergency Stroke Department, Affiliated Hospital of Jining Medical University from September 2020 to January 2023 were chosen. All patients underwent routine MRI, DWI, APTw imaging and 3D arterial spin labeling (3D-ASL) before treatment and 90 d after treatment. IP presence was defined as changes of abnormal signal on T2-fluid-attenuated inversion recovery (FLAIR) 90 d after treatment greater than 20% of high signal range on DWI before treatment, and it was used as the gold standard to compare the efficacy in evaluating whether the patients had IP based on mismatch of 3D-ASLwith DWI and mismatch of APTw imaging with DWI before treatment. The infarct core (IC) region, mismatch region of APTw imaging with DWI, mismatch region of 3D-ASL with APTw imaging were delineated on the fusion images in patients with IP based on mismatch of 3D-ASLwith DWI and mismatch of APTw with DWI, and the differences of APTw values in different regions were compared.Results:According to the 90-d follow-up results, 50 patients had IP and 46 patients did not have IP. Specificity, accuracy and sensitivity evaluating whether the patients had IP based on mismatch of 3D-ASL with DWI were 86.9%, 93.7% and 100.0%, respectively; specificity, accuracy and sensitivity evaluating whether the patients had IP based on mismatch of APTw imaging with DWI were 100.0%, 95.8% and 92.0%, respectively. The APTw max, APTw min and APTw ave values of the IC region were significantly lower than those of mismatch region of APTw with DWI, and the APTw max-min values of mismatch region of APTw imaging with DWI were significantly higher than those of mismatch region of 3D-ASL with APTw imaging ( P<0.05). Conclusion:APTw imaging can reflect the acidosis status of different brain regions in patients with wake-up stroke; specificity and accuracy evaluating whether the patients have IP based on mismatch of APTw imaging with DWI are higher than those based on mismatch of 3D-ASL with DWI.
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OBJECTIVE@#To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism.@*METHODS@#Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines.@*RESULTS@#A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis.@*CONCLUSION@#Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.
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Humans , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Network Pharmacology , Data Mining , Gastroesophageal Reflux/drug therapyABSTRACT
Objective: To analyze the prevalence and the trend of the disease burden of chronic respiratory diseases and relevant risk factors in Jiangsu province from 1990 to 2019 and provide evidence for the prevention and treatment of chronic respiratory diseases. Methods: The data from the 2019 Global Burden of Disease Study (GBD2019) were used to calculate the prevalence rate, mortality rate and disability-adjusted life year (DALY) rate. Software Joinpoint was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of the standardized prevalence rate, standardized mortality rate and standardized DALY rate. The population attributable fractions (PAF) were used to estimate the proportion of chronic respiratory disease caused by different risk factors. Results: In 1990 and 2019, the prevalence rates of chronic respiratory diseases were 4.83% and 5.45%. The mortality rates were 134.91/100 000 and 80.99/100 000 respectively, and the DALY rates were 2 678.52/100 000 and 1 534.31/100 000 respectively. From 1990 to 2019, the age-standardized prevalence rate, mortality rate and DALY rate in Jiangsu showed a significant downward trend (AAPC values were -0.90%, -5.28% and -4.70% respectively, P<0.05). Tobacco use was the leading cause of chronic respiratory diseases, followed by air pollution, occupational exposure, suboptimal temperature and high BMI. Compared with 1990, the proportion of DALYs of chronic respiratory diseases attributable to tobacco use and high BMI increased in 2019. Conclusion: The overall burden of chronic respiratory diseases in Jiangsu shows a downward trend. Prevention and health education should be focused on the population with a smoking history and high BMI. At the same time, environmental management, attention to suboptimal temperature and control of occupational exposure factors should also be adopted as important means to prevent and control chronic respiratory diseases.
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Humans , Global Burden of Disease , Respiratory Tract Diseases/mortality , Risk Factors , China/epidemiology , PrevalenceABSTRACT
Objective: To analyze the prevalence and the trend of the disease burden of chronic respiratory diseases and relevant risk factors in Jiangsu province from 1990 to 2019 and provide evidence for the prevention and treatment of chronic respiratory diseases. Methods: The data from the 2019 Global Burden of Disease Study (GBD2019) were used to calculate the prevalence rate, mortality rate and disability-adjusted life year (DALY) rate. Software Joinpoint was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of the standardized prevalence rate, standardized mortality rate and standardized DALY rate. The population attributable fractions (PAF) were used to estimate the proportion of chronic respiratory disease caused by different risk factors. Results: In 1990 and 2019, the prevalence rates of chronic respiratory diseases were 4.83% and 5.45%. The mortality rates were 134.91/100 000 and 80.99/100 000 respectively, and the DALY rates were 2 678.52/100 000 and 1 534.31/100 000 respectively. From 1990 to 2019, the age-standardized prevalence rate, mortality rate and DALY rate in Jiangsu showed a significant downward trend (AAPC values were -0.90%, -5.28% and -4.70% respectively, P<0.05). Tobacco use was the leading cause of chronic respiratory diseases, followed by air pollution, occupational exposure, suboptimal temperature and high BMI. Compared with 1990, the proportion of DALYs of chronic respiratory diseases attributable to tobacco use and high BMI increased in 2019. Conclusion: The overall burden of chronic respiratory diseases in Jiangsu shows a downward trend. Prevention and health education should be focused on the population with a smoking history and high BMI. At the same time, environmental management, attention to suboptimal temperature and control of occupational exposure factors should also be adopted as important means to prevent and control chronic respiratory diseases.
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Humans , Global Burden of Disease , Respiratory Tract Diseases/mortality , Risk Factors , China/epidemiology , PrevalenceABSTRACT
ABO incompatible(ABO-I) liver grafts will affect the prognosis of liver transplantation. With the improvement of perioperative treatment,including plasma exchange,rituximab,splenectomy,etc.,the prognosis of ABO-I liver transplantation has been greatly improved. Because children's immune systems are not fully developed,the perioperative management of ABO-I pediatric liver transplantation is significantly different from that of adults. Reducing the perioperative anti-donor ABO antibody titer is the key to the perioperative management of ABO-I liver transplantation. This article summarizes literatures on the perioperative management of ABO-I pediatric liver transplantation, including the perioperative anti-rejection regimen in pediatric recipients of different ages, splenectomy, postoperative monitoring and postoperative complications, etc.
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Adult , Humans , Child , Liver Transplantation , Postoperative Complications , SplenectomyABSTRACT
Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.
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Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.
Subject(s)
Mice , Animals , Colitis, Ulcerative/metabolism , Powders , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Metabolomics , Colon , Disease Models, Animal , Biomarkers , Dextran Sulfate/therapeutic useABSTRACT
The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Subject(s)
Humans , Network Pharmacology , Vascular Endothelial Growth Factor A , NF-kappa B , Interleukin-6 , Lipopolysaccharides , Molecular Docking Simulation , Respiratory Distress Syndrome, Newborn , Tumor Necrosis Factor-alpha , Sepsis/genetics , NLR ProteinsABSTRACT
According to the traditional Chinese medicine(TCM) theory, Qi is the essential component maintaining life. Mitochondria are the cellular organelles that generate energy. Qi exhibits abundant common characteristics in bioenergetics compared with mitochondria which control the cellular energy through fusion and fission. Studies have proven that the qi-tonifying function of Chinese medicinal plants and their components facilitates mitochondrial fusion, therefore enhancing ATP synthesis. These studies provide a framework for deciphering the pharmacological mechanisms of Qi-tonifying herbs. This article introduces the common source and function shared by Qi and mitochondria and the regulatory effects of herbal remedies on energy from mitochondria dynamics. This review aims to interpret the connotation of tonifying qi in TCM theory based on the modern biomedical theory.
Subject(s)
Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Qi , Mitochondrial Dynamics , Plants, MedicinalABSTRACT
Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.
ABSTRACT
ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae， and provide clinical experience for the diagnosis and treatment of this rare spinal infection. MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months， which aggravated for more than 1 week， was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission， the symptoms became acutely aggravated， and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points， and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed， and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture. ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation， and the patient was cured during the follow-up of half a year after the operation. ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain， the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.
ABSTRACT
The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.
ABSTRACT
A multifunctional moxibustion treatment machine is designed and developed to assist the heat-sensitive moxibustion therapy. Through the motion control of the stepping motor by programmable logic controller (PLC), the automatic control is obtained for the acupoint detection of heat-sensitive moxibustion therapy and the manual operation of moxibustion. The skin temperature is monitored in real-time, using infrared non-contact temperature measurement technology. Based on the deviation of the temperature set value and the monitoring one, the distance between the moxibustion device and the exerted region is adjusted automatically by PLC so that the temperature is controlled practically. The multifunctional moxibustion treatment machine based on the heat-sensitive moxibustion therapy is capable of the operation control of mild moxibustion, circling moxibustion, sparrow-pecking moxibustion and along-meridian moxibustion techniques, as well as real-time monitoring of skin temperature. The temperature change curve of this machine is coincident with that obtained by the manual operation of heat-sensitive moxibustion. This multifunctional moxibustion treatment machine assists the delivery of heat-sensitive moxibustion therapy and it is satisfactory in temperature control and precise in operation.