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AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.
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AIM: To evaluate the accuracy of the formulas, including Haigis, SRK/T, Holladay 1, and Holladay 2, in predicting the diopter of the intraocular lens implanted in high myopia cataract patients.METHODS: Prospective study. A total of 168 cases(168 eyes)of age-related cataract with an axial length(AL)≥26 mm who were treated in our hospital from August 2017 to November 2021 were selected. According to the preoperative AL measured by IOL Master 700, the patients were divided into five groups, including 37 cases(37 eyes)in group A with 26 mm≤AL<27 mm, 34 cases(34 eyes)in group B with 27 mm≤AL<28 mm, 42 cases(42 eyes)in group C with 28 mm≤AL<29 mm, 28 cases(28 eyes)in group D with 29 mm≤AL<30 mm, and 27 patients(27 eyes)in group E with AL ≥ 30 mm. Subjective refraction was performed at 3 mo postoperatively, and the mean numerical error(MNE)and mean absolute error(MAE)of each formula for predicting diopters were calculated.RESULTS: The MNE and MAE of the Haigis and Holladay 2 formulas were relatively less in each group, and MNE and MAE did not significantly increase with the growth of the axial length. However, the MAE and MNE of the SRK/T and Holladay 1 formulas significantly increased with the growth of the axial length, with the MNE and MAE of the Holladay 1 formula increasing more significantly in groups C, D, and E.CONCLUSION: For patients with age-related cataract, with an axial length of ≥26 mm, the accuracy of predicting the diopter of the intraocular lens using the Haigis and Holladay 2 formulas were higher.
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Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
الموضوعات
Humans , Ischemic Stroke , Brain/metabolism , Macrophages , Brain Ischemia/metabolism , Microglia/metabolism , Gene Expression Profiling , Anti-Inflammatory Agents , Neuronal Plasticity/physiology , Infarction/metabolismالملخص
Objective To analyze the correlation between uric acid and coronary atherosclerotic heart disease in adults. Methods A total of 186 patients with hyperuricemia from January 2020 to October 2021 were selected as the observation group and 186 subjects with normal blood uric acid were selected as the control group . The levels of uric acid, hs-CRP, MCP-1, IL-6, RANTES and adropin protein were measured . The SYNTAX score was used to assess the risk of coronary heart disease and the incidence rate of coronary heart disease was recorded. The correlation between uric acid and inflammatory indexes was analyzed by linear regression model . The relationship between serum uric acid level and coronary atherosclerotic heart was tested by spearman correlation test. Results The levels of hs-CRP, MCP-1, IL-6, RANTES and adropin protein in the observation group were higher than the control group significantly (P<0.05) . The syntax score of the observation group was higher than the control group significantly (P<0.05) .The incidence rate of coronary heart disease in the observation group was significantly higher than that in the control group, and the difference was statistically significant (P<0.05). The level of uric acid was significantly positively correlated with hs-CRP, MCP-1, IL-6, RANTES and adropin . There was positive correlation between serum uric acid and syntax score and the incidence of coronary atherosclerotic heart disease (P<0.05). Conclusion The increase of uric acid level can predict coronary atherosclerotic heart disease. Patients with hyperuricemia should actively carry out uric acid lowering treatment to prevent the risk of coronary atherosclerotic heart disease.
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Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
الموضوعات
Humans , U937 Cells , RUNX1 Translocation Partner 1 Protein , Leukemia/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Oncogene Proteins, Fusion/genetics , Leukemia, Myeloid, Acute/geneticsالملخص
Ionic liquids(ILs) are salts composed entirely of anions and cations in a liquid state at or near room temperature, which have a variety of good physicochemical properties such as low volatility and high stability. This paper mainly reviewed the research overview of ILs in the application of traditional Chinese medicine(TCM) volatile oil preparation technology. Firstly, it briefly introduced the application of TCM volatile oil preparation technology and composition classification and physicochemical properties of ILs, and then summarized the application of ILs in the extraction, separation, analysis, and preparation of TCM volatile oil. Finally, the problems and challenges of ILs in the application of TCM volatile oil were explained, and the application of ILs in TCM volatile oil in the future was prospected.
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Ionic Liquids/chemistry , Oils, Volatile/analysis , Medicine, Chinese Traditional , Cations , Biological Products , Technologyالملخص
BACKGROUND@#Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown.@*METHODS@#We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines.@*RESULTS@#The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy.@*CONCLUSIONS@#The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
الموضوعات
Humans , Mendelian Randomization Analysis , Irritable Bowel Syndrome , Colorectal Neoplasms/genetics , Cholelithiasis/complications , Cholecystectomy/adverse effects , Genome-Wide Association Study , Polymorphism, Single Nucleotideالملخص
The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.
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Animals , Dogs , Mice , Cysts/genetics , Inositol 1,4,5-Trisphosphate Receptors/pharmacology , Kidney/metabolism , Polycystic Kidney Diseases/metabolism , Polycystic Kidney, Autosomal Dominant/drug therapy , Madin Darby Canine Kidney Cellsالملخص
ObjectiveTo understand the distribution characteristics of soil metal pollution around an abandoned rare earth ore in Jiangxi and the health impact on the surrounding residents. MethodsAccording to the distribution of abandoned rare earth ore, the village was divided into mining and non-mining areas. The prevalence of chronic diseases among residents over 15 years old in the village was collected through a self-designed questionnaire. Twenty-three soil samples were collected. The contents of rare earth metals (including lanthanum, cerium, praseodymium, and neodymium) and heavy metals (including arsenic (metalloids), cadmium, and lead) in the soil samples were determined by inductively coupled plasma mass spectrometry (ICP-MS). ResultsThe metal content showed a cumulative increasing trend. One of the23 sampling sites showed mild cadmium pollution. Compared with non-mining farmland, the metal content of farmland soil around the abandoned rare earth mine was relatively higher. The residents' top six self-reported chronic diseases were hypertension, chronic bronchitis, diabetes, stroke, hyperlipidemia, and cataract. The prevalence of hypertension in mining area was higher than non-mining area (χ2=4.141, P=0.042). The main related factors for hypertension in residents were the increase in age (OR=14.576, 95%CI: 2.773‒76.605) and body mass index (OR=3.147, 95%CI: 1.121‒8.835). ConclusionAbandoned rare earth ore may have a potential impact on the health of surrounding residents.
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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common complication after liver transplantation, which could prolong the length of postoperative intensive care unit stay, affect clinical efficacy of liver transplantation and even lead to the death of recipients. ALI/ARDS has attracted extensive attention from liver transplant surgeons in clinical practice. ALI/ARDS after liver transplantation may be directly caused by pulmonary factors (such as mechanical ventilation-related lung injury, lung infection and aspiration, etc.) or indirectly induced by non-pulmonary factors (such as severe infection outside the lungs, blood transfusion and ischemia-reperfusion injury, etc.). In this article, the diagnostic criteria, incidence, mechanism, risk factors, laboratory and clinical diagnostic approaches and treatment of ALI/ARDS after liver transplantation were reviewed, aiming to deepen the understanding and cognition of ALI/ARDS during the perioperative period of liver transplantation and provide reference for the diagnosis and treatment of ALI/ARDS following liver transplantation.
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Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.
الموضوعات
Male , Humans , Premature Ejaculation/surgery , Intraoperative Neurophysiological Monitoring/methods , Prospective Studies , Neurosurgical Procedures/methods , Penis/surgery , Retrospective Studiesالملخص
Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/therapeutic use , Daunorubicin/therapeutic use , Homoharringtonine/therapeutic use , Induction Chemotherapy , Leukemia, Myeloid, Acute/genetics , Nuclear Proteins , Prognosis , Remission Induction , Retrospective Studiesالملخص
Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
الموضوعات
Adult , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Cytarabine/therapeutic use , Hematopoietic Stem Cell Transplantation , Idarubicin/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Neutropenia , Prospective Studies , Recurrence , Retrospective Studiesالملخص
Objective:To investigate the influencing factors for anastomotic biliary stric-ture after liver transplantation.Methods:The retrospective case-control study was conducted. The clinical data of 428 recipients who underwent allogeneic orthotopic liver transplantation in the First Hospital of Jilin University from September 2014 to August 2021 were collected. There were 324 males and 104 females, aged (52±10)years. Observation indicators: (1) surgical conditions of recipients; (2) occurrence of anastomotic biliary stricture after liver transplantation and its treat-ment; (3) analysis of influencing factors for anastomotic biliary stricture after liver transplantation. Follow-up was conducted using outpatient examination to detect occurrence of anastomotic biliary stricture and treatment up to August 30, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers, and the chi-square test was used for comparison between groups. Logistic regression model was used for multivariate analysis. Results:(1) Surgical conditions of recipients: the operation time of 428 recipients was 465(420,520)minutes, the cold ischemia time was 368(320,450)minutes, and the volume of intraoperative blood loss was 2 500(1 500,4 000)mL. Of the 428 recipients, 142 cases were performed continuous biliary posterior wall anastomosis + interrup-ted anterior wall anastomosis by polygluconate sutures, 286 cases were anastomosed with polypro-pylene sutures, including 169 cases undergoing continuous biliary posterior wall anastomosis combined with interrupted anterior wall anastomosis, 73 cases undergoing completely interrupted biliary anterior and posterior wall anastomosis, and 44 cases undergoing completely continuous biliary anterior and posterior wall anastomosis. None of the 428 recipients had indwelling T tubes. (2) Occurrence of anastomotic biliary stricture after liver transplantation and its treatment:all the 428 recipients were followed up for 3 to 72 months, with a median follow-up time of 28 months. During the follow-up, 50 patients developed anastomotic biliary stricture, of which 41 patients were treated with endoscopic retrograde cholangiopancreatography, 8 patients were treated with percutaneous transhepatic cholangial drainage, and 1 patient was treated with surgery, showing no recurrence. (3)Analysis of influencing factors for anastomotic biliary stricture after liver transplanta-tion: results of univariate analysis showed that anastomosis method and donor liver cold ischemia time were related factors for postoperative anastomotic biliary stricture of recipients undergoing allogeneic orthotopic liver transplantation ( χ2=15.74, Z=-2.04, P<0.05). Results of multivariate analysis showed that completely interrupted biliary anterior and posterior wall anastomosis and donor liver cold ischemia time were independent influencing factors for postoperative anastomotic biliary stricture of recipients undergoing allogeneic orthotopic liver transplantation ( odds ratio=0.25, 1.00, 95% confidence interval as 0.08-0.85, 1.00-1.01, P<0.05). Conclusions:Suture type is not an influencing factor for postoperative anastomotic biliary stricture of recipients undergoing allogeneic orthotopic liver transplantation. Completely interrupted biliary anterior and posterior wall anastomosis and donor liver cold ischemia time were independent influencing factors.
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OBJECTIVE@#To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients.@*METHODS@#We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells.@*RESULTS@#The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells.@*CONCLUSION@#As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.
الموضوعات
Humans , Aldehyde Oxidoreductases , CA-19-9 Antigen , Carcinoembryonic Antigen , Gastrectomy , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/pathologyالملخص
Background@#and Purpose Patients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset. @*Methods@#This study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed. @*Results@#The onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD (n=16, 66.7%), AQP4-IgG-seropositive NMOSD (n=7, 29.2%), or multiple sclerosis (n=1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability. @*Conclusions@#Definite NMOSD may be preceded by LF-NMOSD, particularly isolated/ mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.
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Objective:To explore the feasibility and advantages of planned initiation of extracorporeal membrane oxygenation(ECMO)prior to liver transplantation.Methods:From November 2017 to July 2021, clinical data were retrospectively reviewed for 3 liver transplantation recipients assisted by ECMO.There were such preoperative symptoms of right ventricular dysfunction as fatigue, chest tightness and palpitations.In the first case, right heart catheterization was not performed due to patient refusal; another two patients were screened by transthoracic Doppler echocardiography(TDE)and diagnosed through right heart catheterization as portopulmonary hypertension(POPH)and pulmonary hypertension.Results:Three recipients with pulmonary hypertension received catheterization in right femoral artery and vein.After freeing of diseased liver and before blocking inferior vena cava, V-A ECMO support was performed.The dose of heparin was adjusted according to activated clotting time(ACT)and perioperative vital signs remained stable.They were ventilated for 54, 12 and 62 hours and supported by ECMO for 27, 61 and 14 hours.All were smoothly discharged.During a mean follow-up period of 26(9-22)months, liver functions were normal.Conclusions:Patients with end-stage liver disease with pulmonary hypertension should undergo routine TDE examinations during waiting period before liver transplantation.Those with pulmonary hypertension should undergo further right heart catheterization to confirm the diagnosis and severity of the disease.Planned application of ECMO through multidisciplinary consultations can expand surgical indications for liver transplantation, maintain intraoperative hemodynamic stability and facilitate smooth liver transplantation and postoperative patient recovery.
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Objective To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Methods We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers. Results The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Conclusions Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.
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Objective:To screen the active components of sovereign medicinal Achyranthis Bidentatae Radix in Rongjin Niantong formula based on bioinformatics and network pharmacology and observe their effects on therapeutic targets of osteoarthritis (OA) in <italic>in vivo</italic> and <italic>in vitro</italic> animal experiments. Method:The main active components and therapeutic targets of Achyranthis Bidentatae Radix were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the differentially expressed genes relevant to OA from the Gene Expression Omnibus (GEO) database for cross analysis. The effects of main active components in Achyranthis Bidentatae Radix on enriched therapeutic targets of rats with OA <italic>in vivo </italic>and <italic>in vitro</italic> were detected by real-time polymerase chain reaction (Real-time PCR) and Western blot. Result:There were 20 active components for Achyranthis Bidentatae Radix against OA, with quercetin being an important one. Among the three target genes, osteopontin (OPN) and plasminogen activator inhibitor-1(PAI-1) were the key ones in the network. Gene Ontology (GO) analysis yielded 227 related terms, involving the regulation of physiological response to trauma (GO: 1903034), negative regulation of trauma response (GO: 1903035), etc. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 12 related pathways, involving extracellular matrix receptor interaction (hsa04512) and so on. In animal experiments, compared with the normal group, the model group exhibited increased gene and protein expression of OPN and PAI-1. Compared with the model group, the quercetin group displayed decreased gene and protein expression of OPN and PAI-1 (<italic>P</italic><0.05). In cell experiments, the OPN and PAI-1 protein expression levels in the model group were increased as compared with those in the normal group, while the Collagen Ⅱ protein expression was decreased. The OPN and PAI-1 protein expression levels in the quercetin group and the inhibitor group were down-regulated in contrast to those in the model group, whereas the Collagen Ⅱ protein expression levels were up-regulated significantly (<italic>P<</italic>0.05). Conclusion:Achyranthis Bidentatae Radix<italic> </italic>inhibits cartilage degeneration and exerts the preventive and therapeutic effects against OA, which is possibly due to the efficacy of its active component quercetin in down-regulating the expression of OPN and PAI-1 in chondrocytes and up-regulating the Collagen Ⅱ protein expression.
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Objective:To investigate the effect of miR-141 down-regulation on the damage of renal tubular epithelial cell, and further to explore its mechanism.Methods:The renal tubular epithelial cell line HK-2 cells were divided into normal (5.5 mmol/L D-glucose) group, hypertonic group, high glucose (30 mmol/L D-glucose) group, negative control+high glucose group (transfected with NC inhibitor vector) and si-miR-141+high glucose group (transfected with miR-141 inhibitor vector) . Real time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-141. The production of reactive oxygen species (ROS) , cell viability and apoptosis were detected by DCFH-DA fluorescence staining, CCK-8 method and flow cytometry. The expression of Sirt1/Nrf2 signaling pathway related proteins was detected by Western blot. Luciferase reporter gene assay verified the targeting relationship between miR-141 and Sirt1 mRNA.Results:①Compared with the normal group, after transfection with si-miR-141, the relative expression of miR-141 decreased (1.00±0.03 vs 0.52±0.06) , the difference was statistically significant ( F=278.104, P<0.05) ; ② Compared with the normal group [DCFH-DA fluorescence intensity (7.18±0.59) %], the high glucose group [DCFH-DA fluorescence intensity (84.95±3.21) %] cell ROS level was significantly increased, and compared with the high glucose group [DCFH-DA fluorescence intensity (84.95±3.21) %] Compared with the si-miR-141+ high glucose group [DCFH-DA fluorescence intensity (45.10±4.29) %] cell ROS levels were significantly reduced, the difference was statistically significant (all P<0.05) ; ③compared with the normal group (5.13%±0.78) % Compared with the hypertonic group (5.96±0.81) %, the high glucose group (32.76±2.95) % cell apoptosis rate was significantly increased, while the si-miR-141+ high glucose group (17.54%± 2.79) % apoptosis rate was significantly lower in the higher glucose group and the negative control+ high glucose group (33.40%±3.14) %, the difference was statistically significant ( F=221.419, P<0.05) ; ④compared with the normal group (100±3.98) % Compared with the hypertonic group (95.68±5.14) %, the high glucose group (67.24±5.18) % HK-2 cell survival rate was significantly reduced; at the same time, compared with the high glucose group (67.24±5.18) % and Compared with the negative control+ high glucose group (65.33±3.10) %, the si-miR-141+ high glucose group (83.55±5.10) % cell survival rate increased significantly, and the difference was statistically significant ( F=93.008, P<0.05) ; ⑤ Compared with the normal group and the hypertonic group, the expression of Cleaved Caspase 3 protein in the high glucose group increased, while the expression of Sirt1, Nrf2 and HO-1 protein was down-regulated; however, compared with the high glucose group, si- In the miR-141+ high glucose group, Cleaved caspase 3 protein expression decreased, while Sirt1, Nrf2 and HO-1 protein expression increased, the difference was statistically significant (all P<0.05) . Conclusions:Down-regulation of miR-141 can ameliorate high glucose-induced renal tubular epithelial cell damage induced oxidative stress by activating Sirt1/Nrf2 signaling pathway.