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OBJECTIVES@#To classify bladder cancer based on immune cell infiltration score and to construct a risk assessment model for prognosis of patients.@*METHODS@#The transcriptome data and data of breast cancer patients were obtained from the TCGA database. The single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells. The classification of breast cancer patients was realized by unsupervised clustering, and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed. The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis (WGCNA), and the key genes in the modules were extracted. A risk scoring model and a nomogram for risk assessment of prognosis for bladder cancer patients were constructed and verified.@*RESULTS@#The immune cell infiltration scores of normal tissues and tumor tissues were calculated, and B cells, mast cells, neutrophils, T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer. Breast cancer patients were clustered into two groups (Cluster 1 and Custer 2) based on immune cell infiltration scores. Compared with patients with Cluster 1, patients with Cluster 2 were more likely to benefit from immunotherapy (P<0.05), and patients with Cluster 2 were more sensitive to Enbeaten, Docetaxel, Cyclopamine, and Akadixin (P<0.05). WGCNA screened out 35 genes related to key immune cells, and 4 genes (GPR171, HOXB3, HOXB5 and HOXB6) related to the prognosis of bladder cancer were further screened by LASSO Cox regression. The areas under the ROC curve (AUC) of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-, 3- and 5-year survival of patients were 0.735, 0.765 and 0.799, respectively. The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-, 3-, and 5-year overall survival of bladder cancer patients.@*CONCLUSIONS@#According to the immune cell infiltration score, bladder cancer patients can be classified. And the bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.
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Objective To explore the mechanism of Nuanxinkang Powder(aka.NXK,composed of Ginseng Radix et Rhizoma Rubra and Ilex Pubescens Radix)on improving ventricular remodeling in post-infarction mice based on the"metabolic-inflammatory"network regulating macrophage polarization.Methods ①Thirty C57BL/6J male mice were randomly divided into three groups:sham-operation group,model group,and NXK group(1.65 g·kg-1),with 10 mice in each group;the mouse model of myocardial infarction was replicated using left anterior descending coronary artery ligation;and the drug was administered by gavage once a day for 4 consecutive weeks.Masson staining was used to detect collagen deposition in myocardial tissue;ultrasound was used to detect cardiac function in mice:left ventricular ejection fraction(LVEF),left ventricular anterior wall thickness at end-systole(LVAWS)and left ventricular anterior wall thickness at end-diastole(LVAWD);flow cytometry was used to detect distribution of cardiac macrophages in mice;qPCR was used to detect mRNA expressions of lactate dehydrogenase A(LDHA),carnitine palmitoyltransferase 1(CPT-1),glucose transport protein 4(GLUT4),isocitrate dehydrogenase(IDH),and succinate dehydrogenase(SDHa)in heart tissue.②NXK was given 1.15 g·kg-1 NXK suspension to rats by gavage twice a day for 5 consecutive days to prepare NXK-containing serum.Lipopolysaccharide(LPS)-induced RAW 264.7 cells were used to construct a pro-inflammatory macrophage model.The cells were grouped into the following groups:blank serum control group(medium containing 5%blank serum+5%fetal bovine serum),NXK drug-containing serum group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum),lipopolysaccharide group(medium containing 5%blank serum+5%fetal bovine serum+200 μg·mL-1 lipopolysaccharide),NXK drug-containing serum+ lipopolysaccharide group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum+200 μ g·mL-1 lipopolysaccharide),all the groups were intervened for 16 hours.Glycolysis stress test was used to detect the level of glycolysis in RAW 264.7 cells;qPCR was used to detect the mRNA expression of mitochondrial pyruvate carrier(MPC1)in RAW 264.7 cells;and MitoSox Red fluorescent staining was used to detect the level of oxidative stress damage in mitochondria of RAW 264.7 cells.Results ①Compared with the sham-operation group,the blue-stained area of cardiac collagen fibres in mice of the model group was significantly increased,accompanied by thinning of the ventricular wall and enlargement of the left ventricular cavity;cardiac function indexes,such as LVEF,LVAWS,LVAWD,etc.,were all significantly reduced(P＜0.01,P＜0.001);the mRNA expressions of LDHA and CPT-1 were significantly up-regulated in the cardiac tissues of mice(P＜0.05),and the mRNA expressions of GLUT4,IDH and SDHa were significantly down-regulated(P＜0.05,P＜0.01),and CD86 staining positive cell was significantly increased(P＜0.001).Compared with the model group,mice in the NXK group showed a significant decrease in cardiac collagen fiber deposition and an increase in the thickness of the ventricular wall;cardiac function indexes such as LVEF,LVAWS and LVAWD were significantly increased(P＜0.05,P＜0.01,P＜0.001);and the mRNA expressions of LDHA and CPT-1 in the cardiac tissues of the mice were significantly down-regulated(P＜0.01,P＜0.001),mRNA expressions of GLUT4,SDHa and IDH were significantly up-regulated(P＜0.01),and the number of CD86 positive cells was significantly reduced(P＜0.001).②Compared with the blank serum control group,the cytosolic glycolysis level and ROS level of macrophages in the NXK serum-containing group did not change significantly(P＞0.05),whereas the glycolysis level and ROS level of macrophages in the lipopolysaccharide group were significantly increased(P＜0.01),and the mRNA expression of MPC1 was significantly down-regulated(P＜0.001).Compared with the lipopolysaccharide group,the macrophage glycolysis level and ROS level were significantly reduced in the NXK serum-containing + lipopolysaccharide group(P＜0.05,P＜0.01),and mRNA expression of MPC1 was significantly up-regulated(P＜0.001).Conclusion NXK can reduce myocardial fibrosis and ventricular remodeling after myocardial infarction and improve cardiac function in mice,and its mechanism may be related to the down-regulation of mRNA expression of LDHA in cardiac tissues,the up-regulation of mRNA expression of GLUT4,the improvement of cardiac glucose uptake after myocardial infarction,the inhibition of pro-inflammatory macrophage glycolysis,the increase in the expressions of SDHa and IDH to alleviate the accumulation of succinate and citrate,and the reduction of reactive oxygen species(ROS)generation,thereby reducing pro-inflammatory macrophage hyperpolarisation.
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ObjectiveThrough the correlation analysis between intestinal absorption profile and inhibition of macrophage foaming， the pharmacodynamic components of Zhuriheng dripping pills（ZRH） were explored to provide a basis for establishing its quality standard. MethodIntestinal absorption fluids with 0， 5， 10， 15， 20 times clinical equivalent doses were prepared by a rat everted gut sac（EGS）， and the oxidized low density lipoprotein（ox-LDL）-induced RAW264.7 macrophage foaming model was used to investigate the effect of intestinal absorption fluid with different doses on the accumulation of lipids in RAW264.7 cells by oil red O staining and cholesterol content determination， and to screen for the optimal dose. Ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify intestinal absorption fractions of ZRH intestinal absorption fluids， and partial least squares-discriminant analysis（PLS-DA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on different doses of ZRH intestinal absorption fluids using SIMCA 13.0 with peak area as the independent variable and the pharmacodynamic indicators as the dependent variables to screen the compounds with variable importance in the projection（VIP） value>1.0 as contributing components， and Pearson correlation analysis was used to determine the spectral effect relationship， determined the compounds and positive correlation with pharmacodynamic were as active ingredients. Molecular docking was used to verify the binding energy of peroxisome proliferator-activated receptor α（PPARα）， PPARγ， PPARβ， human retinoid X receptor α（RXRA） and nuclear transcription factor-κB（NF-κB） with the active ingredients in ZRH intestinal absorption fluids. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to detect the mRNA levels of PPARγ， scavenger receptor A1（SRA1） and adenosine triphosphate-binding cassette transporter A1（ABCA1） in RAW264.7 cells， Westen blot was used to detect the expression level of PPARγ protein in RAW264.7 cells， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of interleukin（IL）-1β and NF-κB in RAW264.7 cells. ResultAccording to the results of oil red O staining and cholesterol content determination， the ZRH intestinal absorption fluids could significantly reduce macrophage foaming， and intestinal absorption fluids with 15， 20 times clinical equivalent doses had the best effect， the 15-fold ZRH intestinal absorption fluid was finally determined as the study subject. Spectral effect relationship showed that 52 corresponding peaks in the ZRH-containing intestinal fluid were positively correlated with the efficacy， including organic acids， phenylpropanoids， iridoids， flavonoids， bile acids， coumarins and chromones. Target validation results showed that 86.9%-96.2% of the total components processed good binding activities with the key targets of PPARα， PPARγ， PPARβ， RXRA and NF-κB， and the docking energy values were all less than -6.0 kcal·mol-1（1 cal≈4.19 J）. The results of validation showed that， compared with the normal group， the model group showed a significant increase in the levels of SRA1 and PPARγ mRNA expression， a significant decrease in ABCA1 mRNA expression， a significant increase in the level of PPARγ protein expression， and a significant increase in the levels of IL-1β and NF-κB（P<0.01）， compared with the model group， the 15-fold intestinal absorption fluid group showed a significant decrease in the levels of SRA1 and PPARγ mRNA expression（P<0.05， P<0.01）， ABCA1 mRNA expression level was significantly up-regulated， the levels of IL-1β and NF-κB were significantly reduced（P<0.01）， and PPARγ protein expression level was significantly reduced（P<0.05）. ConclusionThis study identifies 52 components and their metabolites in ZRH intestinal absorption fluid that are positively correlated with the inhibition of macrophage foaming， which may be related to the regulation of the PPARs pathway in cells and the reduction of the levels of inflammatory factors， and can provide a reference for the quality control and clinical application of ZRH.
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This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.
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Rats , Animals , AMP-Activated Protein Kinases/metabolism , Nerve Growth Factor/metabolism , Diabetes Mellitus, Experimental/drug therapy , TRPM Cation Channels/metabolism , GAP-43 Protein/metabolism , Signal Transduction , Diabetic Neuropathies/genetics , Fibrosisالملخص
A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).
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Male , Humans , Aged , Pancreatic Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adenocarcinoma , Neoplasm Recurrence, Local/surgery , Immunotherapy , Liver Neoplasms/therapy , Pancreatectomyالملخص
OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group， model group， Gushukang group， E. sphaerocephalus high-dose， medium-dose and low- dose groups， with 6 rats in each group. Except for blank group， other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection， E. sphaerocephalus high-dose， medium-dose and low-dose groups were given drugs intragastrically at dose of 878， 439， 219.5 mg/kg， respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically， once a day， for consecutive 8 weeks. After last administration， blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline （HYP）， alkaline phosphatase （ALP）] and oxidative stress indexes [total antioxidant capacity （TAOC）， superoxide dismutase （SOD）， malondialdehyde （MDA）] in serum of rats. Positron emission tomography/computedtomography （PET/CT） was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile， metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group， HYP， ALP， MDA， ratio of bone surface to bone volume （BS/BV）， and trabecular separation （Tb·Sp） in model group were significantly increased （P＜0.05）， while TAOC， SOD， bone mineral density （BMD）， bone volume fraction （BVF）， trabecular E-mail：Xpfdc153@163.com thickness （Tb·Th） and trabecular number （Tb·N） were significantly decreased （P＜0.05）. Compared with model group， above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus， 18 metabolites such as arachidonic acid， phenylalanine， tyrosine， tryptophan， isoleucine and uric acid in the serum of rats changed significantly， involving 15 metabolic pathways such as arachidonic acid， phenylalanine and tyrosine， of which arachidonic acid metabolism， phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure， which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.
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Human epidermal growth factor receptor 2 (HER2) -positive breast cancer is prone to metastasis and has a poor prognosis. In the context of the booming development of anti-HER2 targeted therapy, HER2-positive breast cancer has reduced recurrence and metastasis and improved prognosis. However, there are still some HER2-positive breast cancer patients who cannot benefit from anti-HER2-targeted therapy and continue to develop recurrent metastasis. Neoadjuvant therapy, surgical treatment, and the full range of adjuvant and palliative therapies enable HER2-positive breast cancer to benefit from them. Scholars from home and abroad have explored the treatment of HER2-positive breast cancer and have achieved some results. In this article, we review the current status and development of HER2-positive breast cancer treatment.
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In view of the problems existing in the probation teaching of obstetrics and gynecology, such as patients' non-cooperation, few cases and few practical opportunities. This study discusses the application effect of case teaching based on "Rain Classroom" and standardized patients in the obstetrics and gynecology probation course. The teaching is carried out by carefully selecting cases, refining pre-class preparation, adopting various teaching forms, and carrying out evaluation after class. In order to evaluate the teaching effect, an anonymous survey was carried out among 330 undergraduate interns majoring in clinical medicine, prevention, and forensic medicine in Batch 2015. The results showed that 210 (93.8%) of 224 (67.9%) students who participated in the survey believed that this method could promote learning enthusiasm and 200 students (89.3%) thought it could activate classroom atmosphere more than traditional teaching; most students thought it improved students' communication ability (163, 72.8%), clinical practice ability (189, 84.4%), and ability to analyze and solve problems (171, 76.3%) and deepening the understanding, mastery and application of knowledge (158, 70.5%). It shows that this method can improve the teaching effect of obstetrics and gynecology probation course to a certain extent.
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@#Objective To systematically evaluate the safety and efficacy of percutaneous closure of atrial septal defect (ASD) guided by echocardiography alone versus fluoroscopy. Methods The databases of PubMed, The Cochrane Library, EMbase, VIP, Wanfang Data and CNKI from January 2000 to October 2021 were searched by computer for relevant research literature. Two reviewers independently screened the literature, extracted the data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Results A total of 19 cohort studies and 1 randomized controlled study were collected, including 2 825 patients. The Newcastle-Ottawa Scale score for cohort studies was≥7 points. Meta-analysis showed that there was no statistical difference in the operative success rate (RR=1.01, 95%CI 1.00 to 1.02, P=0.17), incidence of occluder displacement/shedding (RR=0.77, 95%CI 0.26 to 2.27, P=0.63), incidence of arrhythmia (RR=0.50, 95%CI 0.21 to 1.14, P=0.10), incidence of pericardial effusion (RR=0.98, 95%CI 0.32 to 2.98, P=0.97), operative time (MD=–0.23, 95%CI –7.56 to 7.10, P=0.95) or cost (SMD=–0.39, 95%CI –1.09 to 0.30, P=0.27) between the two groups. The echocardiography group reduced the incidence of total postoperative complications (RR=0.42, 95%CI 0.30 to 0.60, P<0.001) and residual shunt (RR=0.70, 95%CI 0.50 to 0.98, P=0.04), and shortened length of hospital stay (MD=–0.43, 95%CI –0.77 to 0.09, P=0.01). Conclusion Compared with traditional fluoroscopy-guided percutaneous closure of ASD, echocardiography guidance alone is equivalent in terms of operative success rate, major postoperative complications, operative time and total cost, but it reduces the incidence of total postoperative complications and residual shunt, and has a shorter length of hospital stay.
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Objective:To evaluate the effect of preventive application of PEG-rhG-CSF on the prevention of neutropenia during concurrent chemoradiotherapy in patients with lung cancer.Methods:A total of 149 patients with lung cancer who received concurrent chemoradiotherapy at Peking University Cancer Hospital from April 2020 to April 2021 were retrospectively analyzed. There were 79 cases in the prevention group, including 48 cases of primary prevention group (preventive application of PEG-rhG-CSF in all concurrent chemoradiotherapy cycles) and 31 cases of secondary prevention group (preventive application of PEG-rhG-CSF in the concurrent chemoradiotherapy cycles after neutropenia occurred). There were 70 cases in non-prevention group. The incidence of grade 3-4 neutropenia, the completion rate of concurrent chemoradiotherapy, the rate of chemoradiotherapy dose reduction and treatment delay, and the rate of hematological toxicities related hospitalization were compared between the prevention group and the non-prevention group.Results:The incidence of grade 3-4 neutropenia in the whole group was 32.2% (48/149), including 6.3% (3/48) in the primary prevention group, 9.7% (3/31) in the secondary prevention group, and 35.7% (25/70) in the non-prevention group. The difference was statistically significant ( χ2=17.81, P<0.001) in the incidence of grade 3-4 neutropenia. The incidence of febrile neutropenia was 3.4% (5/149) in the whole group, but none of them occurred in the primary prevention group. The full completion rate of concurrent chemotherapy was 96.2% (76/79) in the prevention group, which was significantly higher than 82.9% (58/70) in the non-prevention group ( χ2=7.30, P=0.007). The incidence of treatment delayed and dose reduction of chemoradiotherapy was 19.0% (15/79) in the prevention group and 40.0% (28/70) in the non-prevention group, and the difference was statistically significant ( χ2=7.98, P=0.005). Conclusions:The preventive application of PEG-rhG-CSF can effectively reduce the incidence of neutropenia and better ensure the concurrent chemoradiotherapy in lung cancer patients on schedule.
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Objective:To explore the diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 (MCP-1) for ICU-acquired weakness (ICU-AW) in patients with sepsis.Methods:A prospective observational study was conducted. Patients with sepsis admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from April 2021 to October 2021 were enrolled. The demographic data were collected. The enrolled patients were evaluated with Medical Research Council (MRC) score every day until discharged from ICU. During this period, patients with total MRC score < 48 (for two consecutive times and a time interval of 24 hours) were divided into ICU-AW group, those with total MRC score ≥ 48 were served as non-ICU-AW group. On the 1st, 4th and 7th day following admission into ICU, ultrasound was used to measure the muscle linear thickness of the rectus femoris (RF-MLT), the cross sectional area of the rectus femoris (RF-CSA) and the muscle linear thickness of the vastus intermedius muscle (VI-MLT). And meanwhile, the plasmas samples of patients were collected to measure MCP-1 concentration by enzyme-linked immunosorbent assay (ELISA). The difference of each index was compared between the ICU-AW group and the non-ICU-AW group. The risk factors of ICU-AW in patients with sepsis were analyzed by binary Logistic regression. Besides, receiver operator characteristic curve (ROC curve) was plotted, the diagnostic value of ultrasound parameters and plasma MCP-1 level for ICU-AW in patients with sepsis was analyzed.Results:A total of 99 septic patients were enrolled, with 68 patients in the ICU-AW group and 31 patients in the non-ICU-AW group. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group tended to be older, and had higher sequential organ failure assessment (SOFA) score, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, higher rates of septic shock, higher blood lactic acid and lower Glasgow coma score (GCS). Binary Logistic regression analysis showed that APACHEⅡ score and septic shock were the risk factors of ICU-AW for septic patients [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.310 (1.138-1.509) and 0.232 (0.072-0.746), respectively, both P < 0.05]. The RF-MLT, RF-CSA and VI-MLT on the 1st, 4th and 7th ICU day was falling over time. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group had smaller RF-MLT on the 7th day [cm: 0.32 (0.22, 0.47) vs. 0.45 (0.34, 0.63), P < 0.05] and higher 7-day RF-CSA atrophy rate [25.85% (10.37%, 34.28%) vs. 11.65% (2.28%, 22.41%), P < 0.05]. According to ROC curve analysis, 7-day RF-MLT had diagnostic value for ICU-AW of septic patients. Area under ROC curve (AUC) was 0.688 (95% CI was 0.526-0.849); when the cut-off value was 0.41 cm, the sensitivity and the specificity were 66.7% and 68.4%. The levels of plasma MCP-1 in the ICU-AW group were significantly higher than those in the non-ICU-AW group on the 1st, 4th and 7th day. ROC curve analysis showed that the plasma MCP-1 levels on the 1st, 4th and 7th day played a significant role to diagnose ICU-AW for septic patients, the AUC and 95% CI were 0.732 (0.629-0.836), 0.865 (0.777-0.953), 0.891 (0.795-0.986), respectively. When the cut-off values were 206.3, 410.9, 239.5 ng/L, the sensitivity was 87.1%, 64.0%, 82.4%, and the specificity was 54.4%, 96.1%, 86.2%, respectively. Conclusion:The muscle mass parameters on the 7th day of bedside ultrasound and plasma MCP-1 levels had certain diagnostic values for ICU-AW in patients with sepsis.
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Coronary artery disease is the leading cause of death worldwide, the coronary artery stenosis or occlusion caused by atherosclerosis leads to myocardial ischemia, hypoxia, or necrosis, that is main histopathological features of coronary artery disease. Atherosclerosis relates closely to abnormal lipid regulation, chronic inflammation, and endothelial dysfunction. Cardiac enzymes and high, low-density lipoprotein are currently used to diagnose a variety of coronary artery diseases, but the evidence is inadequate. Thus, new cardioprotective therapies are required to explore sensitive molecular markers for the prediction of cardiovascular events. Lipids have an important role in maintaining the myocardial cell structure as well as cardiac function. Lipidomics is a newly emerged discipline that studies lipids on a large scale. Recent advancements in lipidomics on coronary artery disease have shown that certain lipids, such as ceramide, sphingosine, lysophosphatidic acid, oxidized lipids, and so on, are associated with the clinical classification and characteristics of coronary artery disease. In addition, recent studies of lipid profiles of the cardiac, fat, liver, and other tissue samples in animal models also have provided a novel viewpoint. Given the increasing application of lipidomics techniques for coronary artery disease, we provide a review of lipidomics technology, sensitive lipid markers, recent studies of therapeutic targets, and drug discovery for coronary artery disease.
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OBJECTIVE To optimize the extraction technology of modified Tabusen- 2（MT-2），and to investigate inhibitory effects of the extract obtained by the optimal technology on osteoclast differentiation. METHODS The index components of MT- 2 process optimization were selected by using network pharmacology. Based on single factor tests ，the extraction technology of MT- 2 was optimized by Box-Behnken design-response surface methodology according to the comprehensive score of contents of above index components ，and then validated. RAW 264.7 cells were induced by receptor activator of nuclear factor-κB ligand（100 ng/mL） to prepare osteoclast differentiation model. Inhibitory effects of MT- 2 extract（18.6，37.2，74.4 ng/mL）obtained by the optimal technology on osteoclast differentiation were investigated. RESULTS The index components screened by network pharmacology included chlorogenic acid ，terpineol diglucoside ，isochlorogenic acid A ，1，5-dicaffeoylquinic acid ，hydroxysafflower yellow A ， ginsenoside Rg 1 and ginsenoside Rb 1. The optimal extraction technology of MT- 2 was ethanol volume fraction of 60％ ，the solid-liquid ratio of 1 ∶ 14（g/mL），extraction time of 94 min and extraction times of twice. The average comprehensive score obtained by the three validation experiments was 95.50，and the relative error with the predicted value （95.75）was －0.26％. Compared with osteoclastic differentiation model cells ，the cells treated with MT- 2 extract prepared by the optimal technology were mostly mononuclear round cells ，and the number of osteoclasts decreased significantly （P＜0.05），its inhibitory effects tended to strengthen with the increase of drug concentration. CONCLUSIONS The optimal extraction technology of MT- 2 is stable and feasible. Obtained extract can inhibit osteoclast differentiation.
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The paper summarizes professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia. Professor LIN Guo-hua adheres to "essence and marrow deficiency and primary yang decline" as the pathogenesis and "conducting yin from yang " as the treating principle. By regulating the conception vessel and the governor vessel and focusing on yang meridians, in association with meridian differentiation and the location differentiation, professor LIN provides the staging treatment for post-stroke dysphagia. At the oral phase, yangming is dysfunction, manifested as facial paralysis and flaccid tongue. In treatment, reducing method is predominated at yangming meridian specially. At the pharyngeal phase, shaoyang is invaded by pathogens, manifested as pivoting dysfunction. The treatment focuses on communicating the exterior with the interior and promoting shaoyang meridian. At the esophageal phase, yangming meridian is deficiency and the turbid qi fails to descend, thus the reinforcing method is dominated to promote and tonify yangming. Additionally, the kinesiotherapy of acupuncture is assisted and the Lingnan fire needling therapy is used particularly. All of the summaries above provide the reference for the clinical treatment of post-stroke dysphagia.
الموضوعات
Humans , Acupuncture , Acupuncture Points , Acupuncture Therapy , Deglutition Disorders/therapy , Meridiansالملخص
【Objective】 To compare the clinical efficacy of unilateral biportal endoscopic （UBE） and microscopic discectomy in the treatment of lumbar disc herniation （LDH） and to explore the safety and effectiveness of this operation. 【Methods】 A total of 87 LDH patients from July 2018 to July 2021 were analyzed retrospectively， including 42 cases of unilateral biportal endoscopic discectomy and 45 cases of microscopic discectomy. Analysis was based on comparison of perioperative metrics， operation time， and estimated blood loss. Clinical outcomes were evaluated using visual analogue scale （VAS）， Oswestry disability index （ODI） and modified Macnab criterion. 【Results】 All patients were followed up for 13.3±1.18 months. In UBE group， operation time （57.12±6.35） min was shorter than that in the microscope group （62.21±7.09） min and estimated blood loss （29.31±3.62） mL was smaller than that in the microscope group （51.77±8.43） mL， with a significant difference （P0.05）. Dural sac tear occurred in 2 cases in UBE group and 3 cases in the microscope group； the incidence was not statistically significant （P>0.05）. Modified MacNab criterion evaluation at the last follow-up showed that 32 cases were excellent in UBE group， 7 cases were good， and 3 cases were fair， with the excellent and good rate of 92.9% （39/42）. The microscope group was excellent in 31 cases， good in 10 cases， and fair in 4 cases， with the excellent and good rate of 91.1% （41/45）. 【Conclusion】 UBE for LDH has a satisfactory short-term clinical efficacy， with the advantages of less trauma， greater efficiency， clear vision， and large operating space. Both UBE and microscopic discectomy can achieve good clinical results in treating LDH， but the former has the advantages of less trauma， high efficiency， and quick postoperative recovery.
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Aim To evaluate the therapeutic effect of apigenin on liver fibrosis in mice anrl the pharmacologi¬cal mechanism.Methods Carbon tetrachloride ( CC14) -induced liver fibrosis mouse model was estab¬lished.The mice were divided into six groups of con¬trol, model, silibinin(55 mg • kg 1 • d 1 ) , apigenin in high dosage (60 mg • kg 1 • d 1 ) , apigenin in mid¬dle dosage( 30 mg • kg 1 • d 1 ) and apigenin in low dosage( 15 mg • kg 1 • d 1 ).The general life status, body weight and liver coefficient of the mice in every group were recorded.HE staining, Masson staining, immunohistochemistry and Western blot were used to e- valuate the effect of apigenin on the pathological chan¬ges, the markers related to epithelial-mesenchymal transition and signaling pathways of liver tissues.Re¬sults In CCI4-induced liver fibrosis mice, middle and high-dosage of apigenin could improve the general life status, increase body weight, decrease liver coeffi¬ cient, and significantly improve liver lesions.Middle and high-dosage of apigenin significantly increased the expression of the epithelial marker protein E-cadherin and significantly decreased the expression of the mes¬enchymal marker protein Vimentin in liver tissues of mice with the disease.The further results showed that middle and high-dosage apigenin could significantly in¬hibit the expression of phosphorvlated PDK1 and phos- phorvlated AKT protein in liver tissues of model mice.Conclusions Apigenin can inhibit EMT by inhibiting PDK1/AKT signaling pathway, which plays an anti-fi- brosis role.The apigenin has the potential to be further developed as a drug to protect the liver and treat liver fibrosis.
الملخص
The advancement of the next generation sequencing (NGS) technology has promoted the development of ancient DNA research. Ancient DNA has made outstanding contributions in various fields such as human origin, animal evolution, etc. How to effectively extract and mine the genetic information from fossil and sub-fossil remains excavated from specific locations is a prerequisite for optimizing their important roles in many fields. In this study, we correlated the two main indicators of DNA damage (terminal base replacement rate, average fragment length) with the possible factors such as the burial time, geological epochs, tissue types, and sequencing library construction methods. The results show that the end base replacement rate of ancient DNA from Northeastern China is positively correlated with the water content of the environment and the ages of the samples. Among samples of different geological epochs, ancient DNA end base replacement rates have significant differences. On the contrary, different tissue types of the remains have no significant effects on the end base replacement rate of ancient DNA. The average fragment size of the molecules has no obvious correlation with the factors mentioned above. The results provide both solid data for investigating the characteristics of ancient DNA from specimens collected in Northeastern China, and valuable information for collecting appropriate samples from different geographical locations and the downstream storage before wet lab procedures after excavation.
الملخص
Talents constitute key resources for the development of healthcare sector, and studying abroad is an important and effective means for their training. Based on the analysis of the current status of China′s international talents training project of hospitals, this study summarized existing problems in such training. The authors covered such six aspects as lawful standardization of project management methods, selection of trainees by levels and by types, innovation of the process tracking management mechanisms and strengthened full-process assessment, all dimensional institutional support, consolidation of the responsibilities by individual disciplines in talent team building, and measures to cope with the impact of COVID-19. In accordance with the research results, the study analyzed the exploration and practice of the international training project under the " Elite Talents Cultivation Project" of the Affiliated Hospital of Qingdao University, and raised targeted recommendations on attention to the strategic and forward-looking planning, precise setup of training goal categories, classified evaluation of study results, and lawful management among others.
الملخص
Although the guiding principles for molecular identification of traditional Chinese medicines (TCM) using DNA barcoding have been recorded in the Chinese Pharmacopoeia, there is still a lack of systematic research on its application to commercial TCM decoctions. In this study, a total of 212 commercial TCM decoctions derived from different medicinal parts such as root and rhizome, fruit and seed, herb, flower, leaf, cortex, and caulis were collected to verify applicability and accuracy of the method. DNA barcodes were successfully obtained from 75.9% (161/212) of the samples, while other samples failed to be amplified due to genomic DNA degradation. Among the 161 samples, 85.7% of them were identified as recorded species in the Chinese Pharmacopoeia (2020 edition). In addition, 14 samples could be identified as species recorded in the Chinese Pharmacopoeia and their closely related species in the same genus. Morphological identification for the unconfirmed samples showed that eight were genuine species and three were adulterants, while the other three were unidentifiable due to lack of morphological characteristics. Furthermore, the DNA barcodes of seven samples accurately mapped to the sequences of adulterants. Remarkably, counterfeit products were detected in two samples. These results demonstrate that DNA barcoding is suitable for the identification of commercial TCM decoctions. The method can effectively detect adulterants and is appropriate for use throughout the industrial chain of TCM production and distribution, and by the supervisory agencies as well.
الملخص
Objective:The standard treatment for inoperable locally advanced esophageal cancer is concurrent chemoradiotherapy, but the survival was not satisfied. Nituzumab is a humanized IgG monoclonal antibody against EGFR. The purpose of this study is to investigate the toxicity and efficacy of concurrent chemoradiotherapy combined with nituzumab for locally advanced esophageal cancer.Methods:We retrospectively reviewed the clinical data of locally advanced esophageal cancer who were treated with concurrent chemoradiotherapy combined with nituzumab in Peking University Cancer Hospital from June 2015 to June 2020. Kaplan- Meier method was used for analysis. Results:Thirty Patients were enrolled this study.After a median follow-up of 22.5 months, The objective response rate was 93%. The 1-year, 2-year, 3-year overall survival rates were 83%, 57% and 41%, with the progression-free survival rates 75%, 47% and 32%, with the local-recurrence free survival rates 83%, 53% and 37%, with the metastasis-free survival rates 75%, 51% and 36%, respectively.The incidence of grade≥3 hematological toxicity was 32%. There were 16% patients experiencing grade≥3 esophagitis.Conclusion:The preliminary result of concurrent chemoradiotherapy combined with nituzumab is effective and safe for patients with locally advanced esophageal cancer.