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OBJECTIVE To explore the material basis and mechanism of expectorant and cough relief effects of the fruits of Phellodendron chinense var. glabriusulum Schneid. METHODS The expectorant and cough relief effects of volatile oil and water decoction of the fruits of P. chinense var. glabriusulum Schneid. were studied by ammonia water cough induction and drug expectorant model mice experiments； GC-MS and UPLC-MS technologies were used to identify its volatile oils and non-volatile components of the fruits of P. chinense var. glabriusulum Schneid. The active ingredients， core targets and pathways of expectoration and cough relief were analyzed by network pharmacology. RESULTS The volatile oil （0.8， 0.2 g/kg， calculated by volatile oil） and water decoction （12， 3 g/kg， calculated by crude drug） of the fruits of P. chinense var. glabriusulum Schneid. both had obvious expectorant and cough relief effects， and showed obvious dose-dependent relationship. A total of 38 volatile oil components were identified from the medicinal herbs， and the relative percentage contents of 8 components were greater than 1%， such as α -pinene， myrcene， β -caryophyllene， germanene D， isospathulenol； a total of 69 non-volatile oil components were identified， mainly including phenolic compounds， alkaloids， and flavonoids. The active ingredients screened from the identified components included 13 compounds such as α-pinene， myrcene， chlorogenic acid， luteolin， berberine. There were a total of 55 intersection targets with diseases， and the core targets were tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， vascular endothelial growth factor A （VEGFA）， serine/threonine kinase proteins （AKT1） and Toll-like receptor 4 （TLR4）. The molecular docking results showed that the active ingredients and the core targets had good binding ability. GO functional analysis found that the targets were significantly enriched in biological processes such as the reaction affecting lipopolysaccharides， the positive regulation of peptidyl serine phosphorylation， and the positive regulation of the biosynthesis process of nitric oxide. KEGG pathway enrichment analysis found that the targets were significantly enriched in the signaling pathways such as cancer， non-small cell lung cancer， proteoglycans in cancer. CONCLUSIONS Fruits of P. chinense var. glabriusulum Schneid. have obvious expectorant and cough relief effects， and its material basis may be α-pinene， myrcene， chlorogenic acid， luteolin， berberine， etc.， and mainly act on TNF， EGFR， VEGFA， AKT1， TLR4 and its significantly enriched signaling pathway.
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【Objective】 To investigate the effect of optimized preoperative hemoglobin (Hb) level on clinical outcome in patients undergoing coronary artery bypass grafting (CABG). 【Methods】 Retrospective analysis was performed on patients who were selected to receive CABG from April 2020 to August 2021 in our hospital. Preoperative basic data, perioperative blood transfusion volume, blood transfusion rate, acute liver function impairment, renal function impairment (AKI), ICU stay, length of hospital stay, and in-hospital mortality of patients, meeting the inclusion criteria, were collected. According to the perioperative red blood cell transfusion, the optimal preoperative Hb threshold was calculated by receiver operating characteristic curve (ROC). According to the threshold, all patients were divided into two groups, and the blood transfusion volume and clinical outcomes of the two groups were compared to evaluate the predictive value of the optimal threshold of Hb. 【Results】 A total of 915 patients who met the inclusion criteria were enrolled in the study. The optimal threshold for predicting red blood cell transfusion rate by calculating preoperative Hb value by ROC curve was 118 g/L for males and 116g/L for females. Group A: Hb≤ threshold (n=293) was divided into the red blood cell transfusion group A1 and the red blood cell non-transfusion group A2. Group B: Hb>threshold (n=622) was divided into the red blood cell non-transfusion group B1 and no red blood cell non-transfusion group B2. The risk factors for perioperative red blood cell transfusion were age (OR=1.033 874, 95%CI 1.000 4-1.068 3, P<0.01), gender (female) (OR=3.268 5, 95%CI 2.353 1-4.540 0, P<0.01), BMI (OR=0.927 8, 95%CI 0.883 3-0.974 4, P<0.01), chronic renal insufficiency (CKD) (OR=2.041 1, 95%CI 1.347 8-3.091 0, P<0.01). Preoperative Hb≤ threshold (OR=3.517 4, 95%CI 2.502 1-4.944 7, P<0.01) was an independent risk factor for perioperative red blood cell transfusion. Perioperative red blood cell transfusion in patients with preoperative anemia further increases the incidence of postoperative complications (acute liver injury, AKI) and length of ICU stay. 【Conclusion】 Preoperative Hb≤ threshold can effectively predict perioperative red blood cell transfusion in patients with CABG, and increase the risk of postoperative acute liver injury, AKI, prolonged ICU stay and hospital stay. Optimizing the preoperative Hb level in CABG patients, increasing the Hb level to 118 g/L in males and 116 g/L in females can reduce the incidence of perioperative red blood cell transfusion and postoperative complications.
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Objective@#To investigate the prevalence and types of maternal near miss in Hangzhou City from 2015 to 2020, so as to provide insights into early identification and interventions for maternal near miss.@*Methods@#The data of maternal near miss in 5 hospitals of Hangzhou City from 2015 to 2020 were collected from China's National Maternal Near Miss Obstetrics Surveillance System, and the incidence and mortality of maternal near miss, types of pregnancy-related complications/comorbidities and types of critical illness were descriptively analyzed.@*Results@#Totally 230 490 pregnant and lying-in women were recruited in 5 hospitals in Hangzhou City from 2015 to 2020, and there were 182 514 live births, 177 428 women with pregnancy-related complications/comorbidities, and 1 790 cases of maternal near miss with a 0.98% annual incidence rate. The incidence of maternal near miss was high in 2019 (1.18%). The hospital mortality and death index were respectively 3.29/105 and 0.33% among pregnant and lying-in women from 2015 to 2020, and there was no death found among pregnant and lying-in women from 2018 to 2020. The main pregnancy-related complications/comorbidities included anemia (79.33%), obstetric hemorrhagic disorders (69.83%), and gestational hypertension (16.65%). The main critical illness among maternal near miss included coagulation dysfunction (87.23/104), cardiovascular dysfunction (20.44/104), and respiratory dysfunction (9.70/104).@*Conclusions@#The incidence of maternal near miss was high and the hospital mortality appeared a reduction tendency among pregnant and lying-in women in Hangzhou City from 2015 to 2020. Coagulation dysfunction is the primary critical illness among maternal near miss, and the management of anemia and hemorrhagic diseases requires to be improved.
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Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.
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Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.
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Animals , Mice , Imaging, Three-Dimensional , Neural Networks, Computer , Spinal Cord/diagnostic imaging , Synchrotrons , X-Ray MicrotomographyABSTRACT
Objective To explore the expression of tiny RNA-25 (microRNA-25, miR-25) in the plasma、tissues of triple-negative breast cancer(TNBC) patients and cell lines, to investigate the potential molecular mechanisms of miR-25 on migration and invasion of TNBC. Methods Real-time fluorescent quantitative PCR was used to detect the expression of miR-25 in the plasma of TNBC patients. Linked omics web platform was used to analyse miR-25 level in samples of TNBC and non-TNBC. Real-time fluorescent quantitative PCR was also used to detect the miR-25 level in TNBC cell lines. The wound healing and transwell assay was applied to assess the effects on migration and invasion of TNBC cell lines which transfected with miR-25 inhibitor or the negative control. The luciferase reporter assay was used to validate the relationship between miR-25 and the sphingosine-1-phosphate phosphatase 1 (SGPP1) in HEK293T cell. The wound healing and transwell assay was used to detect the migration and invasion ability of TNBC cell lines when cotransfected with pCMV6-SGPP1 and miR-25. Furthermore, Western blot was performed to detect the SGPP1 level in TNBC cell lines. Results The expression of miR-25 was significantly elevated in the plasma of 86 TNBC patients compared with the healthy controls (P value was 0.031). LinkedOmics web platform analysis showed that miR-25 expression was significantly higher in TNBC samples than in non-TNBC samples with Luminal A or Luminal B (P value was<0.001 and 0.006). The level of miR-25 was also elevated in TNBC cell lines HS578T, HCC1806, MDA-MB-231 and BT549(P value was 0.006, 0.01, 0.029 and 0.046). The MDA-MB-231 and HS578T cells which transfected with miR-25 inhibitor exhibited a significant slower wound healing rate than control (P value was 0.035 and 0.001). At the same time, when transfected with miR-25 inhibitor, MDA-MB-231 and HS578T both exhibited a decreased invasion ability compared with the control group(P value was 0.002 and 0.001). LinkedOmics web platform analysis showed that sphingosine-1-phosphate phosphatase 1 (SGPP1) gene level was negatively correlated with miR-25 in the tissues of TNBC patients (P value was 0.037). The luciferase reporter assay validated that SGPP1 was a directed target of miR-25. The western blot assay indicated that the SGPP1 level was increased in MDA-MB-231 and HS578T after transfection with miR-25 inhibitor. Over-expression of SGPP1 could abrogate the positive effects of miR-25 on migration and invasion when pCMV6-SGPP1 was cotransfected with miR-25 (P value was all 0.002). Conclusions MiR-25 was elevated in both plasma and tissues of TNBC patients and also increased in TNBC cell lines. Transfection of MDA-MB-231 and HS578T cells with miR-25 inhibitor resulted in reduced migration and invasion. Moreover, SGPP1 was identified as a novel target of miR-25. The ability of miR-25 to promote TNBC cell migration and invasion is attributable to its effect on SGPP1 suppression.
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OBJECTIVE@#To investigate the clinical efficacy and feasibility of surgical treatment for thoracic spinal tuberculosis with intraspinal abscesses by internal fixation, unilateral vertebral lamina limited decompression, debridement, together with interbody and posterior fusion via a posterior only approach. @*METHODS@#A total of 37 pantients (24 males and 13 females) with thoracic spinal tuberculosis complicated with intraspinal abscess lesions were admitted to our hospital, with age 13-68(39.7 ± 9.1) years old. Spinal lesions of segmental kyphosis Cobb angle was 8°-62° (29.6° ± 3.6°). Frankel grade system was used to assess neurological function. According to the system, there were 3, 7, 19 and 8 cases for grade B, C, D and E, respectively. All 37 cases were treated with internal fixation, unilateral vertebral lamina limited decompression, debridement, together with interbody and posterior fusion via a posterior only approach. @*RESULTS@#The mean duration for follow-up was 24-90 (53.0 ± 15.7) months. Intraoperative dural tear occurred in 1 cases with cerebrospinal fluid leakage after operation; 2 cases showed postoperative neurological complications; delayed wound healing occurred in 2 cases. The postoperative kyphotic angle was 5°-21° (8.3° ± 1.3°). The kyphotic angle was 8°-26° (10.1° ± 1.9°) at the last follow-up. By the time of the last follow-up, all patients with preoperative neurological symptoms improved at different degree. According to Frankel classification, 2 cases recovered from grade B to D, 1 case from grade B to E, 3 cases from grade C to D, 4 cases from grade C to E, 13 cases from grade D to E. No failure in fixation and pseudarthrosis. All patients obtained satisfactory bone graft fusion. @*CONCLUSION@#Posterior internal fixation, unilateral vertebral lamina limited decompression, debridement, together with interbody and posterior fusion might be a effective and feasible method for treatment of thoracic spinal tuberculosis with intraspinal abscess lesions.
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Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Abscess , Pathology , General Surgery , Bone Transplantation , Debridement , Decompression, Surgical , Fracture Fixation, Internal , Kyphosis , Pathology , Postoperative Complications , Spinal Fusion , Thoracic Vertebrae , General Surgery , Treatment Outcome , Tuberculosis, Spinal , Pathology , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture (EA) on cochlea morphology and expression of aquaporin 1 (AQP1) in guinea pigs with endolymphatic hydrops, so as to explore the possible mechanism of EA on endolymphatic hydrops.</p><p><b>METHODS</b>Forty guinea pigs were randomly divided into a blank group, a model group, a medication group and an EA group, 10 guinea pigs in each one. Model of endolymphatic hydrops was established by using intraperitoneal injection of aldosterone. Guinea pigs in the blank group and model group were treated with identical immobilization as EA group but no treatment was given; guinea pigs in the medication group were treated with intragastric administration of hydrochlorothiazide at a dose of 5 mg/kg, once a day for consecutive 10 days; guinea pigs in the EA group were treated with' EA at "Baihui" (GV 20) and "Tinggong"(SI 19), once a day for consecutive 10 days. The serum ionic concentration in each group was tested by turbidimetric method; hematoxylin-eosin staining was used to measure the severity of cochlea hydrops; immunohistochemical method was used to observe the expression of AQP1 in the cochlea.</p><p><b>RESULTS</b>(1) There was no endolymphatic hydrops in the blank group, moderate-severe endolymphatic hydrops in the model group and slight endolymphatic hydrops in the EA group and medication group. (2) The concentration of K+ and Ca2+ in the EA group was higher than that in the model group and medication group (all P<0. 01); the concentration of Na+ was lower than that in the model group (P< 0. 01) but higher than that in the medication group (P<0. 01); the concentration of Cl- was higher than that in the medication group (P<0. 01), but not significantly different from the model group (P>0. 05). (3) The ratio of expression area of AQP1 in the model group was lower than that in the blank group (P<0. 01); the ratio of expression area of AQP1 in the EA group was higher than that in the model group (P<0. 01), and lower than that in the medication group without significant difference (P>0. 05).</p><p><b>CONCLUSION</b>EA could relieve the endolymphatic hydrops in guinea pigs; the mechanism is likely to be related with up-regulating the expression of AQP1 in cochlea and ion concentration might be an important factor involved.</p>
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Animals , Humans , Male , Aquaporins , Genetics , Metabolism , Cochlea , Metabolism , Disease Models, Animal , Electroacupuncture , Endolymphatic Hydrops , Genetics , Metabolism , Therapeutics , Guinea PigsABSTRACT
A sensitive method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of folic acid (FA) and its active metabolite, 5-methyltetrahydrofolic acid (5-M-THF), in human plasma. The analytes were extracted from plasma with methanol solution containing 10 mg/mL of 2-mercaptoethanol and 0.025% (v/v) ammonium hydroxide. FA and 5-M-THF were more stable after the addition of 2-mercaptoethanol and ammonium hydroxide in the sample preparation procedures of this study than they were in the previously published methods. Chromatographic separation was performed on a Hedera ODS-2 column using a gradient elution system of acetonitrile and 1 mM ammonium acetate buffer solution containing 0.6% formic acid as mobile phase. LC-MS/MS was carried out with an ESI ion-source and operated in the multiple reaction monitoring (MRM) mode. The assay was linear over the concentration ranges of 0.249-19.9 ng/mL for FA, and 5.05-50.5 ng/mL for 5-M-THF. The developed LC-MS/MS method offers increased sensitivity for quantification of FA and 5-M-THF in human plasma and was applicable to a pharmacokinetic study of FA and 5-M-THF.
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Objective To evaluate the efficiency and toxicities of Gemcitabine combined with S -1 cap-sule in the treatment of advanced esophageal cancer .Methods Twenty-nine patients with advanced esophageal cancer were treated with S-1 capsule 80 mg/m2 ,twice daily for 14 days and Gemcitabine (1 000 mg/m2 ) was in-travenously administrated on day 1 and 8.The chemotherapy was repeated every 21 days.After two consecutive treatment circles ,the short term efficacy ,adverse effects and follow -up condition were evaluated .Results One case showed complete remission (CR),11cases showed partial remission (PR),9 cases showed stable disease (SD),8 cases showed progressive disease(PD).The responsive rate(CR+PR)was 41.4%;the illness control rate(CR+PR+SD)was 72.4%.The major adverse events were myelosuppression ranging from grade Ⅰto Ⅲ, hand-foot syndrome,disgusting and the damage of liver function .Some patients displayed the damage of liver function.The median time to progress ( mTTP) was 6.9 months.The median 1-year survival rate was 64.3%. Conclusion The combination of Gemcitabine and S -1 capsule is an effective and well -tolerated method for the patients with advanced esophageal cancer .
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The study aims to solve the instability problem of methylphenidate (MPH) in plasma, and establish a LC-MS/MS method for simultaneous determining of MPH in human plasma. The stabilities of MPH in different media were studied, and the degradation characteristics of MPH in these media were also investigated by HPLC and LC-MS/MS. To a 200 microL aliquot of freshly collected plasma sample, 10 microL 2% formic acid was added immediately to prevent the hydrolysis of MPH in human plasma samples. Chromatographic separation was performed on a Sapphire C18 column using the mobile phase of methanol - 5 mmol.L-1 ammonium acetate buffer solution containing 0.1% formic acid (46 : 54). MPH was quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring. The detection used the transitions of protonated molecules at m/z 234.2-->84.1 for MPH and m/z 260.3-->183.1 for propranolol (IS), separately. The intra- and inter-assay precisions were all below 5.0%. The accuracies were all in standard ranges. The linear calibration curve was obtained in the concentration range of 0.035-40 ng.mL-1. The methods fulfilled the demand. The method was used to determine the concentration of MPH in human plasma after a single dose of 36 mg MPH tablet to 6 healthy Chinese volunteers. The method is suitable for the precisely determination of MPH and for pharmacokinetic study of MPH in human plasma.
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Aim To study the inhibitory effect of NO donating-aspirin derivative Ⅱ_6 on thrombosis and its mechanism of nitric oxide release. Methods Inferior vena cava thrombosis and cerebral thrombosis model in rats were used to investigate the antithrombotic activities of Ⅱ_6.TXB_2 and 6-Keto-PGF_(1?)in rat serum、rat aortic strip and in ECV304 cells were determined by radioimmunosay.NO content in the serum of rats and extracellular fluid of the ECV304 cells were tested with Griess reagent.Results Ⅱ_6 inhibited the thrombosis in inferior vena cava and brain,and it reduced the concentration of TXB_2.but increased NO production.Conclusion Ⅱ_6 has an inhibitory effect on thrombosis and increases NO content in vivo and vitro.