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OBJECTIVE To investigate the ameliorative effects and mechanism of Sanwei ganlu on hepatic fibrosis in rats. METHODS The rats were randomly divided into normal group， model group， silibinin group （positive control， 50 mg/kg）， and Sanwei ganlu low-dose， medium-dose， and high-dose groups （80， 250， 800 mg/kg）. Except for normal group， hepatic fibrosis rat models were established by intraperitoneal injection of CCl4 in the other groups of rats. Starting from the 6th week of modeling administration， they were given normal saline or corresponding drugs intragastrically at the same time. At the end of the ninth-week experiment， liver and spleen indexes of rats were calculated； the pathological structure and fibrosis changes of liver tissue were observed by HE， Masson and Sirus Red staining. The contents of alanine transaminase （ALT）， aspartate transaminase （AST）， procollagen type Ⅲ （PC Ⅲ）， collagen type Ⅳ （COL-Ⅳ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and IL-1β in serum， and hyaluronic acid （HA） and laminin （LN） in liver tissue were all detected. RESULTS Compared with the model group， the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group； the contents of ALT， AST， PC Ⅲ， COL-Ⅳ， IL-6， TNF-α and IL-1β in serum as well as the contents of HA and LN in liver tissue significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Sanwei ganlu can alleviate the progression of hepatic fibrosis in rats， possibly by inhibiting the synthesis of collagen fiber， reducing transaminase content， down-regulating the levels of HA， LN， PC Ⅲ and COL-Ⅳ， and reducing the inflammatory response.
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Objective:To explore the correlation between fibular head height and varus knee osteoarthritis occurrence and severity.Methods:A retrospective analysis was performed on 618 participants (618 knees, 184 males and 434 females, mean age 61.12±10.98 years) who underwent standard weight-bearing full-leg radiographs and were diagnosed as non-knee osteoarthritis or varus knee osteoarthritis from January 2019 to June 2019. Knee osteoarthritis was diagnosed according to Kellgren-Lawrence grading: 0-I grades were diagnosed as non-osteoarthritis, II-IV grades were diagnosed as osteoarthritis. Joint line convergence angle (JLCA), medial proximal tibial angle (MPTA) and hip-knee-ankle angle were measured on X-rays to reflect varus deformity. The fibular head height was defined as the vertical distance from upper edge of fibular head to lateral tibial plateau. Patients were divided into 5 groups according to Kellgren-Lawrence grading. Differences of age, gender, height, weight, body mass index, varus deformity (JLCA, MPTA and hip-knee-ankle angle) between Kellgren-Lawrence 0-IV grades were compared. Ordinal logistic regression was performed to analyze the correlation between fibular head height and Kellgren-Lawrence grades. Pearson's correlation analysis was used for the correlation among fibular head height, JLCA, MPTA and hip-knee-ankle angle, and the main factor of JLCA, MPTA and hip-knee-ankle angle was extracted by factor analysis. Multiple linear regressions were used to analyze the correlation between fibular head height and varus deformity score.Results:There were 68, 66, 97, 98, 289 participants in Kellgren-Lawrence grades 0-IV respectively that was 134 participants were diagnosed as non-osteoarthritis and 484 participants were diagnosed as osteoarthritis. Fibular head height and MPTA showed a decreasing trend ( F=129.076, 24.875; P<0.001) while JLCA and hip-knee-ankle angle showed an increasing trend ( F=414.346, 105.996; P<0.001) with the increase in Kellgren-Lawrence grading. Age, body mass index and fibular head height are influencing factors of Kellgren-Lawrence grading with OR(95%CI) were 1.116(1.093, 1.141), 1.363(1.060, 1.754), 0.617(0.575, 0.662) . Fibular head height was negatively correlated with JLCA and hip-knee-ankle angle ( r=-0.641, -0.478; P<0.001) , respectively, and positively correlated with MPTA ( r=0.320, P<0.001). There were significant correlations between age, fibular head height and the varus deformity score ( β=0.274, -0.457; P<0.001). Conclusion:Fibular head height of patients with varus knee osteoarthritis is lower than that of non-osteoarthritis. In addition to age and body mass index, fibular head height is a risk factor for varus knee osteoarthritis occurrence. The smaller the fibular head height is, the more serious the osteoarthritis severity and varus deformity are.
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Diabetic patients with poor glycemic control are exposed to media containing mold spores, and spores enter the body, which may lead to refractory infections. This article combines case and literature reviews, proposes the diagnosis and treatment method of mold infection, and provides some guidances for subjects who long-term exposure to mold groups such as farmers and immunocompromised people.
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Diabetic patients with poor glycemic control are exposed to media containing mold spores, and spores enter the body, which may lead to refractory infections. This article combines case and literature reviews, proposes the diagnosis and treatment method of mold infection, and provides some guidances for subjects who long-term exposure to mold groups such as farmers and immunocompromised people.
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Objective To explore the inhibitory effects of miR-15 b-5 p on choroid melanoma cell line proliferation by targeting CDK4.Methods Dual-luciferase assay was used to verify the direct binding site between miR-15 b-5 p and CDK4 3'-UTR. MUM-2 B cells were cultured in vitro and transfected with negative control RNA, miR-15 b-5 p mimics, inhibitor normal control (nc) RNA, and miR-15 b-5 p inhibitor. qRT-PCR was used to detect miR-15 b-5 p expression, Western blotting was used to measure the expression levels of CDK4 in the cells, CCK-8 assay was used to detect proliferation capacity, and flow cytometry was used to detect cell cycle. Results Dual-luciferase assay verified that miR-15 b-5 p could bind to CDK4 mRNA 3'-UTR successfully. Compared to the negative control group, the mimics group showed significantly increased miR-15 b-5 p expression, decreased CDK4 levels, decreased cell proliferation rate, and increased proportion of G1-phase cells. Compared to the inhibitor nc group, the inhibitor group showed significantly decreased miR-15 b-5 p expression (t = 25.01, P ＜ 0.000 1), increased CDK4 protein level, increased cell proliferation rate, and decreased proportion of G1-phase cells.Conclusion miR-15 b-5 p can target CDK4, induce G1 phase arrest in cells, and thus, reduce the proliferation rate of choroid melanoma cells.
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Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.
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Humans , Axons , Blotting, Western , Brain Injury, Chronic , Brain , Cell Body , Cerebral Cortex , Craniocerebral Trauma , Cytoskeletal Proteins , Gray Matter , Immunohistochemistry , Neurodegenerative Diseases , Neurons , Neuropathology , Neuropil , Oligodendroglia , tau Proteins , White MatterABSTRACT
Objective To investigate the effect of berberine on proliferation of neural stem cells(NSCs)induced by hydrogen peroxide(H2O2). Methods NSCs from Sprague-Dawley rats were isolated and purified by suspension culture. Cells were divided into a control group,H2O2group(NSCs exposed to H2O2injury),berberine group(NSCs were incubated with berberine concentrations ranging from 0.5 to 20 μmol/L and exposed to H2O2), and DAPT(a blocker of the Notch signaling pathway)group. Cell viability was evaluated using the Cell Counting Kit-8 assay. Proliferation of NSCs was evaluated by a neurosphere formation assay and Ki67 protein expression. Expression of key proteins in the Notch signaling pathway(including notch1 and hes1)in response to berberine treatment or DAPT(a Notch inhibitor)was determined by Western blotting. Results Cell viability of NSCs was significantly increased by berberine compared with the H2O2group. The neurosphere growth assay showed that 5 or 10 μmol/L berberine increased NSC proliferation. The ratio of Ki67 +/DAPI cells and notch1 and hes1 protein expression increased significantly compared with the H2O2group. Conclusions Berberine treatment upregulates Notch signaling in NSCs,whereas DAPT attenuates these effects. Berberine is a drug that promotes NSC proliferation and exerts a protective effect on NSCs via the Notch signaling pathway.
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Objective To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients undergoing selective surgeries.Methods The traumatic patients undergoing selective surgeries from November 2016 to January 2017 at our department were selected for this prospective cohort study.They were divided into an intervention group (69 patients) and a control group (121 patients) according to the wards where they stayed.The intervention group was fasted for solids 6 hours prior to surgery and received oral solution with maltodextrin 2 hours prior to surgery.After surgery,they were allowed to drink liquids as soon as they were awakened.Normal food was allowed 2 hours later.The control group was fasted for either liquids or solids the night before surgery.After surgery,the patients who had received brachial plexus block only were allowed liquids with no limitation while the other patients were allowed liquids 6 hours after surgery and then were free for solids and liquids if no discomfort was observed.The time periods for preoperative liquids and solids fasting and for postoperative intake of liquids and solids were recorded and compared between the 2 groups.The perioperative well-beings (including anxiety,thirst,hunger,nausea,fatigue,dizziness,sweating and stomach discomfort) and serum glucose levels were compared between the 2 groups.Adverse reactions were observed.Results The preoperative fasting time for liquids for the intervention group (4.5 ± 2.9 hours) was significantly shorter than that for the control group (14.3 ±3.9 hours) (P ＜ 0.05).The preoperative fasting time for solids for the intervention group (17.6 ± 3.0 hours) were significantly longer than that for the control group (16.1 ±3.8 hours) (P ＜ 0.05).The postoperative fasting time periods for both liquids [1 (0,3) h] and solids [2 (1,4) h] for the intervention group were significantly shorter than those for the control group [6(6,6) h] hours and [6(6,6) h] (P ＜ 0.05).Compared with the control group,the perioperative anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort were significantly improved in the intervention group (P ＜ 0.05).The average serum glucose level was similar in both groups upon admission (P ＜ 0.05);it was significantly higher in the intervention group immediately before surgery (P ＜ 0.05) but was gradually decreased after surgery until there was no significant difference between the 2 groups (P ＞ 0.05).No major adverse reaction was observed in either group.Conclusion The protocol of perioperative fasting abbreviation may be safe and feasible in traumatic patients for selective surgeries,showing benefits of decreased anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort.
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Objective To establish a high-throughput evaluation model for anaphylactic reactions; To screen and identify potential anaphylactogens from TCM monomeric compounds.MethodsCell model of stably expressed MrgX2 was established. Recombinate plasmid pmCherry-C1-MrgX2 was transfected to HEK293 to establish cell line for screening model. MrgX2 agonist and antagonist were used to identify the validation and stability of the cell line. A small library consisting of 180 compounds was profiled by using a cell-based calcium mobilization assay to find novel compounds targeting the MrgX2 receptor. EC50 test, IC50 test, specificity validation and cytotoxicity evaluation were carried out to detect the function of the positive agonist.ResultsThe EC50 of C48/80 to MrgX2 model was 2.7 μg/mL and the IC50 of 2-APB (evoked by 10 μg/mL C48/80) was 46.29 μmol/L. The first generation cell model of MrgX2 was similar to the 20th generation, and the Z factor of MrgX2 cell model was 0.78. In the primary screening for agonist, isoliensinine was identified as a novel agonist targeting receptor MrgX2 with an EC50 of 4.5 μmol/L and IC50 of39.47 μmol/L. Moreover, isoliensinine was validated to activate MrgX2 receptor specifically without cytotoxicity. Conclusion A high-throughput evaluation method for anaphylactic reactions can be established in vitro through calcium mobilization assay. A potential anaphylactogen isoliensinine is identified and validated.
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Objective To investigate risk factors of the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS).Methods From May 2012 to July 2014,17 cases of severe fever with thrombocytopenia syndrome in Renmin Hospital of Wuhan University were treated.Clinical data including history of epidemiology,clinical manifestations,complications,physical examination and laboratory test results on admission and the third day after admission were retrospectively analyzed and compared with the death group and recovery group by application of Spearman correlation analysis.Results Elderly male patients with neuropsychiatric symptoms,or abnormal liver function,or abnormal blood clotting function had higher risk of the poor prognosis.In SFTS patients,AST,ALT was significantly increased,AST 539 U/L (229.73,545.4) U/L (r =0.597,P =0.015) was a risk factor affecting prognosis.Elevated blood ammonia indicated serious liver dysfunction and neurological dysfunction which were manifested as irritability,delirium,and trembling limbs.In SFTS patients,platelets were significantly decreased accompanied with mouth ulcers / bleeding gums,gastrointestinal bleeding.PLT 24.88 × 10 9/L-1 (12.75,35.00) ×10 9/L-1 (r=0.557,P=0.005) or APTT 86.06 s (66.88,114.18) (r=0.798,P=0.001) or D-dimmer 9.79 mg / L (4.09,16.51) mg/L (r =0.597,P =0.015) are risk factors affecting poor prognosis.Conclusions On the third days after admission,AST,WBC,PLT,APTT,Ddimmer are risk factors for prognosis of patients with severe fever with thrombocytopenia syndrome infected by a novel bunyavirus.
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Objective To investigate fracture patients' perception about pain and analgesic.Methods In-depth interview for 30 min was done for 20 fracture patients within 12 h after their admission.Data were analyzed based on Colaizzi phenomenological research method.Results Fracture patients underestimated the influence that pain had dosne to them.When they were suffering from pain,most of them chose to endure until they couldn't endure anymore.For analgesics,most of them chose to avoid from using them unless they couldn't endure anymore.Conclusions Pain management education should be done to help patients correct their bias about pain,know more about analgesics according to their personal conditions,and help them self-report their pain and manage their pain timely and properly.
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Objective To evaluate the diagnostic and predict value of procalcitonin (PCT) levels in patients diagnosis of sepsis with immune system defect in the intensive care unit (ICU).Methods This is a retrospective analysis.We enrolled 278 patients diagnosis of sepsis in Emergency ICU,general ICU and Respiratory ICU in Renmin Hospital of Wuhan University from October 2011 to September 2012.Among them,122 patients have normal immune function and 156 patients have auto-immune system diseases or/and requiring corticosteroids or chemotherapy.According to the APACHE Ⅱ score,patients were divided into low-risk group,middle-risk group and high-risk group,and their PCT levels were compared.Logistic regression analysis of the multiple factors was used to screen independent risk factors for predicting 7 days' mortality.The predictive ability was also evaluated and compared between the first time of PCT concentration after admission and dynamic change of PCT within the first week with area under receiver operator's characteristic curve (ROC curve,AUC).Result The results of Spearman correlation analysis showed that there was a significant positive correlation between the patients' PCT concentration and APACHE Ⅱ score (r =0.979,P ＜ 0.05).And there was a positive correlation between the first PCT concentration after admission and 7 days' mortality in-hospital (r =0.826,P ＜ 0.05).Multiple factors logistic regression analysis indicated that both the first time PCT concentration after admission and APACHE Ⅱ score of patients were independent risk factors for predicting 7 days' mortality (PCT OR =1.77,95％ CI =1.28-3.83,P =0.0023).The warning value of 7 days' mortality for patients with normal immune function was PCT≥7.18 ng/ml and for those with abnormal immune function was PCT ≥ 3.52 ng/ml.Compared to dynamic monitoring of PCT,there was no significant difference in sensitivity but specificity is less than the dynamic monitoring of PCT.Conclusions The diagnostic and predict value of procalcitonin (PCT) levels were not affected by the immuno-suppressive therapy.The first time PCT concentration after admission was an independent risk factor for predict of 7 days' mortality in ICU patients with sepsis.The PCT warning value of the sepsis patients with abnormal immune function was much lower compared to those with normal immune function.
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Objective To investigate the diagnostic and predict vaIue of procalcitonin (PCT) in ICU patients with sepsis and the correlation between PCT concentration and positive results of bacterial culture.Methods A total of 278 patients with sepsis were admitted into emergency ICU,general ICU and respiratory ICU from October 2011 to September 2012.Of them,193 patients had definite microbial infection evidence.Serum PCT levels among groups of different pathogens were compared.The analysis of correlation between the PCT concentration of the first assay was got after admission and short-term prognosis was evaluated.The correlation between PCT level and positive results of bacterial culture was also evaluated.Results Spearman correlation analysis showed that serum PCT levels of bacterial infections in patients with sepsis were significantly higher than those of the non-bacterial infections in patients with sepsis (P =0.001).And there was a positive correlation between the PCT concentration of the first specimen after admission and 7-day in-hospital mortality in patients with sepsis due to bacterial infections (r =0.277,P =0.004).The patients with PCT levels greater than 2 ng/ml had high vulnerability to bacterial infection Conclusions The PCT concentration of the first assay after admission was positively correlated to 7-day mortality in ICU patients with sepsis due to bacterial infections.The serum PCT concentration indicated the severity of host response to the bacterial infection.And etiological evidence directly showed pathogenic factors.Both of PCT and etiological evidence related to bacterial infection,reflected different aspects of bacterial infection.
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AIM: To explore the role of extracellular signal-regulated kinases ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H2O2 preconditioning in PC12 cells.METHODS: In PC12 cells,the experimental model of cytoprotection by H2O2 preconditioning against oxidative stress-induced injury was set up.The morphological changes in the apoptotic cells were observed by using of chromatin dye Hoechst 33258.The percent of apoptotic cells was determined by flow cytometry(FCM) with propidium iodide staining.The levels of p-ERK1/2 and p-STAT3 expression were detected by Western blotting assay.RESULTS: Preconditioning with H2O2 at concentration of 100 ?mol/L for 90 min obviously inhibited apoptosis induced by 300 ?mol/L H2O2,and both ERK1/2 and STAT3 were activated.UO126(10 ?mol/L,an inhibitor of ERK1/2) or AG-490(10?mol/L,an inhibitor of JAK2) significantly blocked the cytoprotection effect of H2O2 preconditioning.Moreover,UO126(10 ?mol/L) also markedly inhibited the up-regulation of p-STAT3 expression by H2O2 preconditioning.CONCLUSION: H2O2 preconditioning activates ERK1/2-STAT3 signal pathway,which may be one of the mechanisms underlying H2O2 preconditioning-induced cytoprotection.