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OBJECTIVE:Cement-augmentation pedicle screws have been widely used in spinal internal fixation surgery combined with osteoporosis in recent years,which can significantly improve the fixation strength,but compared with conventional methods,whether it has more advantages is still inconclusive of evidence-based medicine.To systematically evaluate the efficacy and safety of cement-augmented pedicle screw in the treatment of thoracolumbar degenerative diseases with osteoporosis. METHODS:Clinical controlled trials concerning the cement-augmented pedicle screw and the traditional pedicle screw placement for thoracolumbar degenerative diseases with osteoporosis were retrieved from the electronic databases such as CNKI,CBM,WanFang,VIP,PubMed,Cochrane Library,Web of Science and Embase.According to the unified criteria,we performed literature screening and quality evaluation.The meta-analysis was performed using RevMan 5.4 software. RESULTS:(1)Totally 20 articles were selected eventually,involving 2 randomized controlled studies and 18 retrospective cohort studies,totally 1 566 patients.Among them,789 cases were in the cement-augmented screw group and 777 cases in the conventional screw group.(2)Meta-analysis results showed that Japanese Orthopaedic Association score,intervertebral space height and fusion rate were higher in the cement-augmented screw group than those in the conventional screw group(MD=1.60,95%CI:1.14,2.07,P<0.000 01;MD=1.26,95%CI:0.62,1.90,P=0.000 1;OR=11.24,95%CI:2.86,44.14,P=0.000 5).Operation time was longer in the cement-augmented screw group than that in the conventional screw group(SMD=0.82,95%CI:0.42,1.23,P<0.000 1).Postoperative visual analog scale score,Oswestry dysfunction index score and incidence of screw loosening were lower in the cement-augmented screw group than those in the conventional screw group(MD=-0.50,95%CI:-0.78,-0.21,P=0.000 7;SMD=-0.49,95%CI:-0.88,-0.10,P=0.01;OR=0.08,95%CI:0.05,0.12,P<0.000 01).Hospitalization time,intraoperative blood loss,and postoperative drainage volume were not significantly different between the two groups(P>0.05). CONCLUSION:Compared with conventional pedicle screw placement,cement-augmented pedicle screw is more effective in the treatment of osteoporotic thoracolumbar degenerative disease by improving fusion rate and interbody height,reducing the incidence of screw loosening,and elevating long-term efficacy.
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BACKGROUND:Atlantoaxial dislocation,because of its high difficulty and high risk of surgery,has been regarded as the"surgical restricted area"by the international orthopedic community.However,with the rapid development of intelligent digitization in orthopedics,robot-assisted navigation screw placement technology has been widely used in clinical practice,which significantly reduces the difficulty and risk of surgery and improves the safety of surgery.However,there are few reports on the application of this technique in the treatment of atlantoaxial dislocation. OBJECTIVE:To explore the application value of robot-assisted pedicle screw internal fixation in the treatment of atlantoaxial dislocation. METHODS:The medical records of five patients with atlantoaxial dislocation treated with C1-C2 pedicle screw fixation under robot-assisted navigation in Zhuhai Hospital of Guangdong Provincial Hospital of Chinese Medicine from October 2021 to July 2022 were retrospectively analyzed.Operation time,length of neck incision,blood loss,postoperative drainage volume,and length of hospital stay were recorded.Attention should be paid to cerebrospinal fluid leakage,vertebral artery injury,nerve injury,operative area infection and other complications.The visual analog scale score of neck pain,the spinal cord injury grade of the American Spinal Injury Association,the cervical spine score of the Japanese Orthopaedic Association,and the imaging indicators were collected before surgery and at the last follow-up.Screw placement accuracy was assessed. RESULTS AND CONCLUSION:(1)Five patients were successfully completed surgery,without vascular,nerve injury or other complications,and were followed up for 12-20 months.(2)A total of 20 cervical pedicle screws were placed in 5 patients,including 9 type A screws,10 type B screws,and 1 type C screw.The accuracy of screw placement was 95%.(3)At the last follow-up,the visual analog scale score was(0.80±0.71)points,which was significantly lower than that before operation(4.00±2.83)points;the Japanese Orthopaedic Association score was(14.80±0.84)points,which was significantly higher than that before operation(8.00±0.71)points.Anterior atlantodental interval decreased from(7.86±3.25)mm to(2.82±0.93)mm;space available of the spinal cord increased from(6.74±1.99)mm to(12.10±3.51)mm;cervicomedullary angle increased from(133.32±13.55)° to(153.44±9.53)°;clivus-canal angle increased from(128.02±9.92)° to(143.25±12.99)°.The results of the last follow-up indexes were improved compared with those before operation,and the differences were significant(all P<0.05).(4)Postoperative imaging follow-up showed that all patients had bone fusion in the bone graft area,and no internal fixation loosening,fracture or pull-out occurred.(5)This method can avoid relying on the doctor's experience and hand feeling,ensure the accuracy of upper cervical screw placement,reduce the risk of surgery,and obtain satisfactory results in mid-term follow-up.
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Objective To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City. Methods Children with diarrhea under 5 years of age admitted to Guangzhou Children’s hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children’s Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants’ demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio (OR) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [OR = 4.221, 95% CI: (1.043, 17.087)], antibiotic use [OR = 0.125, 95% CI: (0.017, 0.944)] and chronic diarrhea [OR = 2.172, 95% CI: (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City. Conclusions B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.
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This study aimed to analyze aflatoxins content and fungal community distribution in the harvesting and processing of Platycladi Semen, and explore the key link that affects aflatoxins contamination. The related Platycladi Semen samples of different maturity periods(cone non-rupture period, early rupture, and complete rupture period) and different processing periods(before drying, during 2-d drying, during 7-d drying, before and after seed scale removal, before and after peeling, 1 d after color sorting, and 7 d after color sorting) were collected for identifying the fungal community composition on sample surface by ITS amplicon sequencing. Then the content of aflatoxins B_1, B_2, G_1 and G_2 was determined by HPLC-MS/MS. The results showed that during the harvesting of Platycladi Semen from cone non-rupture to complete rupture, aflatoxins were only detected in the seed scale and seed coat, with aflatoxin G_2 in the seed scale and aflatoxin B_1 in the seed coat. During the drying, with the prolongation of drying time, aflatoxins B_1 and G_2 were detected simultaneously in the seed scale, aflatoxin B_1 in the seed coat, and low-content aflatoxin B_1 in the seed kernel. During subsequent processing, the aflatoxin content in seed kernel during subsequent processing was slighted increased. As demonstrated by fungal detection, Aspergillus flavus was not present during the harvesting of Platycladi Semen, but present during the drying and processing. Its content in the seed coat during the drying process was relatively higher. In short, Platycladi Semen should be harvested as soon as possible after it becomes fully mature. Drying process is the key link of preventing aflatoxin contamination. It is advised to build a sunlight room or adopt similar settings, standardize the operations in other processes, and keep the surrounding environment clean to minimize aflatoxin contamination.
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Aflatoxins/analysis , Aspergillus flavus , Food Contamination/prevention & control , Mycobiome , Semen/chemistry , Tandem Mass SpectrometryABSTRACT
On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.
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Humans , China/epidemiology , Disease Eradication , Public Health , Schistosomiasis/prevention & control , World Health OrganizationABSTRACT
OBJECTIVE@#To predict the trends for fine-scale spread of Oncomelania hupensis based on supervised machine learning models in Shanghai Municipality, so as to provide insights into precision O. hupensis snail control.@*METHODS@#Based on 2016 O. hupensis snail survey data in Shanghai Municipality and climatic, geographical, vegetation and socioeconomic data relating to O. hupensis snail distribution, seven supervised machine learning models were created to predict the risk of snail spread in Shanghai, including decision tree, random forest, generalized boosted model, support vector machine, naive Bayes, k-nearest neighbor and C5.0. The performance of seven models for predicting snail spread was evaluated with the area under the receiver operating characteristic curve (AUC), F1-score and accuracy, and optimal models were selected to identify the environmental variables affecting snail spread and predict the areas at risk of snail spread in Shanghai Municipality.@*RESULTS@#Seven supervised machine learning models were successfully created to predict the risk of snail spread in Shanghai Municipality, and random forest (AUC = 0.901, F1-score = 0.840, ACC = 0.797) and generalized boosted model (AUC= 0.889, F1-score = 0.869, ACC = 0.835) showed higher predictive performance than other models. Random forest analysis showed that the three most important climatic variables contributing to snail spread in Shanghai included aridity (11.87%), ≥ 0 °C annual accumulated temperature (10.19%), moisture index (10.18%) and average annual precipitation (9.86%), the two most important vegetation variables included the vegetation index of the first quarter (8.30%) and vegetation index of the second quarter (7.69%). Snails were more likely to spread at aridity of < 0.87, ≥ 0 °C annual accumulated temperature of 5 550 to 5 675 °C, moisture index of > 39% and average annual precipitation of > 1 180 mm, and with the vegetation index of the first quarter of > 0.4 and the vegetation index of the first quarter of > 0.6. According to the water resource developments and township administrative maps, the areas at risk of snail spread were mainly predicted in 10 townships/subdistricts, covering the Xipian, Dongpian and Tainan sections of southern Shanghai.@*CONCLUSIONS@#Supervised machine learning models are effective to predict the risk of fine-scale O. hupensis snail spread and identify the environmental determinants relating to snail spread. The areas at risk of O. hupensis snail spread are mainly located in southwestern Songjiang District, northwestern Jinshan District and southeastern Qingpu District of Shanghai Municipality.
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Animals , Bayes Theorem , China/epidemiology , Ecosystem , Gastropoda , Supervised Machine LearningABSTRACT
In the WHO new road map for neglected tropical diseases 2021—2030, the disease-specific targets are classified into control, elimination as a public health problem, elimination and eradication, and taeniasis and cysticercosis are targeted for control. The overall prevalence of taeniasis and cysticercosis is low in China, and varies remarkably in regions and populations; however, there are many challenges for elimination of taeniasis and cysticercosis in China. Based on previous taeniasis and cysticercosis control programs, developing a sensitive taeniasis and cysticercosis surveillance-response system, updating criteria for diagnosis of taeniasis and cysticercosis, proposing a national guideline for treatment of taeniasis and cysticercosis, and strengthening interdisciplinary and intersectoral communications and collaborations are urgently needed under the One Health concept.
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Objective To systematically review the effects of exercise on systemic inflammation of chronic obstructive pulmonary disease (COPD) and skeletal muscle dysfunction. Methods The literature about the effect of exercise on COPD systemic inflammation and skeletal muscle dysfunction were retrieved from PubMed, Web of Science, CNKI, VIP and Wanfang data, until June, 2021, supplemented by reference review and manual retrieval. Results A total of 192 literatures were retrieved and eight were included, involving 245 subjects. The comprehensive results showed that exercise could decrease the level of pro-inflammatory factors and increase the level of anti-inflammatory factors. Exercise can improve the motor ability and skeletal muscle structure of patients with COPD. Exercise can improve systemic inflammation of COPD, which is related to the mode, intensity and duration of exercise. Exercise may affect ubiquitin-protease, insulin-like growth factors -1/phosphatidylinositol 3 kinase/Akt and other pathways by regulating the inflammatory response, and improve skeletal muscle dysfunction. Conclusion Exercise has certain effect on reducing systemic inflammation and improving skeletal muscle dysfunction.
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Objective To systematically review the effects of exercise on systemic inflammation of chronic obstructive pulmonary disease (COPD) and skeletal muscle dysfunction. Methods The literature about the effect of exercise on COPD systemic inflammation and skeletal muscle dysfunction were retrieved from PubMed, Web of Science, CNKI, VIP and Wanfang data, until June, 2021, supplemented by reference review and manual retrieval. Results A total of 192 literatures were retrieved and eight were included, involving 245 subjects. The comprehensive results showed that exercise could decrease the level of pro-inflammatory factors and increase the level of anti-inflammatory factors. Exercise can improve the motor ability and skeletal muscle structure of patients with COPD. Exercise can improve systemic inflammation of COPD, which is related to the mode, intensity and duration of exercise. Exercise may affect ubiquitin-protease, insulin-like growth factors -1/phosphatidylinositol 3 kinase/Akt and other pathways by regulating the inflammatory response, and improve skeletal muscle dysfunction. Conclusion Exercise has certain effect on reducing systemic inflammation and improving skeletal muscle dysfunction.
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Aim To observe the effects of sacubitril/valsartan (Sac/Val, LCZ696) on atrial remodeling and atrial fibrillation (AF) susceptibility in spontaneously hypertensive rats (SHR). Methods Twenty-four 7-week-old male SHR were randomly divided into SHR group, SHR + Val group (30 mg · kg
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Objective:To observe the clinical efficacy of Xiao Qinglongtang on chronic heart failure with cold phlegm in lung， and explore its mechanism of action. Method:A total of 87 patients with definite chronic heart failure were divided into observation group and control group by random number table method．The two groups received routine western medicine at the same time. Forty-two cases in observation group were treated with Xiao Qinglongtang based on western medicine， and 45 cases in control group received the same dose of placebo. Both groups were treated for 4 weeks， and then their cardiac function， traditional Chinese medicine （TCM） syndrome score and efficacy were compared before and after treatment. Left ventricular ejection fraction （LVEF） and N-terminal pro-brain natriuretic peptide （NT-proBNP） were measured in both groups before and after treatment. The changes of standard deviation of NN intervals （SDNN）， square root of the mean squared differences of successive NN intervals （RMSSD）， high frequency （HF） and low frequency （LF） that reflect autonomic nerve function indexes in heart rate variability （HRV） after treatment were compared between two groups. The changes of inflammatory indicators such as interleukin-6 （IL-6） and highly sensitive C reaction protein （hs-CRP） were detected. Result:After treatment， the total effective rate for cardiac function in observation group was higher than that in control group （P<0.05）. The TCM symptom scores were improved after treatment in both groups （P<0.05）， and the total effective rate in observation group was higher than that in control group （P<0.01）. After treatment， LVEF levels significantly increased （P<0.01） and NT-proBNP levels significantly decreased （P<0.01） in both groups， and the effect in observation group was more obvious （P<0.01）. After treatment， SDNN， RMSD， HF and LF indicators in HRV were all higher than those before treatment in both groups （P<0.01）， and the improvement in observation group was more significant than that in control group （P<0.01）. The levels of IL-6 and hs-CRP decreased after treatment in both groups （P<0.01）， and the level of observation group was significantly lower than that of control group （P<0.01）. Conclusion:Xiao Qinglongtang has certain clinical efficacy in treating chronic heart failure with cold phlegm in lung as it can improve the clinical symptoms of patients， regulate autonomic nervous balance， and inhibit inflammatory factors， providing new clinical ideas to treat chronic heart failure in TCM.
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Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 μmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.
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Animals , Rats , Down-Regulation , Heart Atria , Myocytes, Cardiac , Tumor Necrosis Factor-alpha , src-Family KinasesABSTRACT
Objective To study the effect of continuous nursing on the growth and development of extremely low birth weight preterm infants. Me thods 80 cases of extremely low birth weight preterm infants treated in the Dept. of Pediatrics, The Third People's Hospital of Yunnan Province from October 2015 to October 2016, were selected and divided into 2 groups: experimental group and control group, 40 cases in each group. The control group was given conventional nursing, the experimental group was given continuous nursing. Then the growth and development of infants in the two groups were compared. Re s ults The weight, body length, head circumference in the experimental group were significantly better than the control group, the difference was statistically significant (P ＜ 0.05). The readmission rate in 6 months of infants in the experimental group was lower and the parents satisfaction was significantly higher than that of control group, the difference was statistically significant (P ＜0.05). Conclus ion Conventional nursing has significant effect for extremely low birth weight preterm infants, it can improve the growth and development of infants, reduce the hospital readmission rate, and improve parents' satisfaction.
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<p><b>Background</b>In a small proportion of cases, spontaneous osteonecrosis of the knee (SONK) involves the medial tibial plateau (MT). Here, we introduced the clinical characteristics of spontaneous osteonecrosis of the MT and unicompartmental knee arthroplasty (UKA) as the favorable treatment for this situation based on a retrospective case study.</p><p><b>Methods</b>Patients with spontaneous osteonecrosis of the MT, confirmed by magnetic resonance imaging (MRI) at Guangdong Provincial Hospital of Chinese Medicine (China) from March 2015 to June 2016, were included as a case serial and analyzed retrospectively. All patients underwent Oxford Medial UKA. The characteristics of their lesions, corresponding treatment, and results of follow-up were presented. The lesion scores and grade were determined according to the criteria of Ficat and Arlet.</p><p><b>Results</b>In total, 22 patients (5 men, 17 women; mean age, 64.1 years) with spontaneous osteonecrosis of the MT were analyzed. The lesion stages assessment showed that 3 (14%) were Stage II, 10 (45%) were Stage III, 7 (32%) were Stage IV, and 2 (9%) were Stage V. In the sagittal plane, 7 (32%) were in the anterior region (MTa) and 15 (68%) were central (MTc). The lesion volume averaged 2.24 ± 0.79 cm (range: 1.57-3.08 cm). Seventeen patients (77%) had Level III posterior medial meniscus root tears (MMRTs). All the patients underwent UKA. Average follow-up was 30.0 ± 6.4 months with a range of 23.0-38.0 months. The visual analog scale score was 7.78 ± 0.67 before surgery while decreased to 2.22 ± 1.09 at the final follow-up (P < 0.001). The Hospital for Special Surgery scores of pre-/post-surgery were 65.67 ± 5.45 and 84.10 ± 4.20, respectively (P < 0.001).</p><p><b>Conclusions</b>SONK often occurs in the anterior and central tibial plateau due to abnormal stresses. Most of the patients had Level III posterior medial meniscus root tears. MRI is recommended for suspected cases to identify SONK at an early stage. The use of the Oxford Medial UKA for SONK of the MT is reliable both immediately and at follow-up.</p>
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AIM:To investigate the effect of angiotensin 1-7(Ang1-7)on the human glomerular endothelial cells(HGECs)injury induced by angiotensin Ⅱ(Ang Ⅱ)and its possible mechanism.METHODS: Cultured HGECs were divided into 6 groups randomly: control group, Ang Ⅱ group, Ang1-7 group, Ang Ⅱ +Ang1-7 group, Ang Ⅱ +Ang1-7+A779(an inhibitor of Mas receptor)group and A779 group.The apoptotic rate and reactive oxygen species (ROS)of HGECs were analyzed by flow cytometry and photographed by fluorescence microscopy.The levels of lactate de-hydrogenase(LDH),nitric oxide(NO),endothelin-1(ET-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α), transforming growth factor-β(TGF-β),monocyte chemoattractant protein-1(MCP-1)and intercellular adhesion molecule-1(ICAM-1)in the supernatant of cell cultures were measured.RESULTS:Compared with the control group,the apoptot-ic rate and the average fluorescence intensity of ROS were increased in the Ang Ⅱ group,IL-6,TNF-α,TGF-β,ICAM-1 and MCP-1 in cell supernatants were also increased in the Ang Ⅱ group(P<0.05).Compared with the Ang Ⅱ group,the apoptotic rate,ROS level, and the above inflammatory factors were decreased in Ang Ⅱ +Ang1-7 group(P<0.05). Compared with the Ang Ⅱ +Ang1-7 group,adding A779 increased the cell apoptotic rate,ROS production and the releases of the above inflammatory factors in cell supernatants(P<0.05).Compared with the Ang Ⅱ group,adding Ang1-7 inhibi-ted the LDH leakage, ET-1 secretion and promoted the release of NO in a dose-dependent manner(P<0.05).CON-CLUSION:Ang1-7 attenuates the HGECs injury induced by Ang Ⅱ by inhibiting the Mas receptor.
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<p><b>OBJECTIVE</b>To investigate the effect of sericin on the proliferation of human gastric cancer MKN45 cells and explore the underlying molecular mechanism.</p><p><b>METHODS</b>MKN45 cells were transfected by LC3 double fluorescent autophagic virus, and the positive cells screened by puromycin were divided into blank group, sericin group and sericin∓3-MA group. After incubation with sericin for 48 h, the cells were examined for proliferation, apoptosis and cell cycle using CCK-8 assay and flow cytometry. Cell autophagy was detected by transmission electron microscopy (TEM) and fluorescent inverted microscope, and the autophagy-related markers including LC3, p62 and Beclin proteins were detected with Western blotting. Nude mice bearing gastric cancer xenograft were treated with normal saline or sericin injections (n=5) and the changes in the tumor volume and weight were measured.</p><p><b>RESULTS</b>Compared with the blank group, MKN45 cells with sericin treatment showed significantly inhibited proliferation both in vitro and in nude mice. Autophagosomes were observed in sericin-treated cells under TEM and fluorescent inverted microscope. Sericin treatment of the cells significantly increased the cell apoptosis (P<0.01), caused obvious cell cycle arrest in G/M phase (P<0.01), up-regulated the expressions of both LC3-2 and Beclin, and down-regulated the expression of p62. The autophagy inhibitor 3-MA obviously antagonized the effects of sericin on cell apoptosis, cell cycle and autophagic protein expressions.</p><p><b>CONCLUSION</b>Sericin can inhibit the proliferation of human gastric cancer MKN45 cells by regulating cell autophagy to serve as potential anti-tumor agent.</p>
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Ezetimibe was reported to pharmacologically defend against oxidative stress.This study was designed to investigate whether ezetimibe can protect against the oxidative stress induced by oxidized low-density lipoprotein (oxLDL) in vitro and the underlying mechanism.Human umbilical vein endothelial cells (HUVECs) were pretreated with ezetimibe and then exposed to oxLDL for 24 h.TUNEL assay and detection for the protein levels of cleaved caspase-3,Bcl-xl and Bcl-2 were employed to assess the oxLDL-induced endothelial apoptosis.Intracellular reactive oxygen species (ROS) generation was evaluated by measuring dichlorofluorescein (DCF) fluorescence.The activities of endothelial antioxidant enzymes [superoxide dismutase (SOD) and catalase] were tested via an enzymatic assay.The mitochondrial membrane potential (MMP) was monitored by flow cytometry using JC-1 staining.Phosphorylation levels of glycogen synthase kinase-3β (p-GSK-3β) and Akt (p-Akt),as well as total GSK-3β and Akt were determined by Western blotting.The results showed that ezetimibe treatment inhibited HUVECs apoptosis,intracellular ROS production,and enhanced antioxidant enzyme activities elicited by oxLDL.HUVECs exposed to oxLDL alone had reduced mitochondrial function,while ezetimibe pre-intervention could significantly rescue the MMP.Furthermore,the protein levels of p-GSK-3β and p-Akt in ezetimibe-pretreated HUVECs were markedly increased as compared with those in oxLDL-induced HUVECs.However,no significant effect on total GSK-3β and Akt was found in ezetimibe-pretreated HUVECs.Taken together,it was concluded that ezetimibe protects against oxLDL-induced oxidative stress through restoring the MMP,which may be mediated by Akt-dependent GSK-3β phosphorylation.
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Ezetimibe was reported to pharmacologically defend against oxidative stress.This study was designed to investigate whether ezetimibe can protect against the oxidative stress induced by oxidized low-density lipoprotein (oxLDL) in vitro and the underlying mechanism.Human umbilical vein endothelial cells (HUVECs) were pretreated with ezetimibe and then exposed to oxLDL for 24 h.TUNEL assay and detection for the protein levels of cleaved caspase-3,Bcl-xl and Bcl-2 were employed to assess the oxLDL-induced endothelial apoptosis.Intracellular reactive oxygen species (ROS) generation was evaluated by measuring dichlorofluorescein (DCF) fluorescence.The activities of endothelial antioxidant enzymes [superoxide dismutase (SOD) and catalase] were tested via an enzymatic assay.The mitochondrial membrane potential (MMP) was monitored by flow cytometry using JC-1 staining.Phosphorylation levels of glycogen synthase kinase-3β (p-GSK-3β) and Akt (p-Akt),as well as total GSK-3β and Akt were determined by Western blotting.The results showed that ezetimibe treatment inhibited HUVECs apoptosis,intracellular ROS production,and enhanced antioxidant enzyme activities elicited by oxLDL.HUVECs exposed to oxLDL alone had reduced mitochondrial function,while ezetimibe pre-intervention could significantly rescue the MMP.Furthermore,the protein levels of p-GSK-3β and p-Akt in ezetimibe-pretreated HUVECs were markedly increased as compared with those in oxLDL-induced HUVECs.However,no significant effect on total GSK-3β and Akt was found in ezetimibe-pretreated HUVECs.Taken together,it was concluded that ezetimibe protects against oxLDL-induced oxidative stress through restoring the MMP,which may be mediated by Akt-dependent GSK-3β phosphorylation.
ABSTRACT
To investigate the effects of Fritillariae Cirrhosae Bulbus on airway remodeling and matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), tissue inhibitor-1 of metalloproteinase(TIMP-1) of a murine asthma model, and explore its mechanism in treatment of asthma. BALB/C murines were randomly divided into the normal group, model group, high dose group, low dose group, and positive control group. Except for the normal group, all the other groups received ovalbumin(OVA) to establish murine asthma model. After successful modeling, the murines in high dose group and low dose group were orally administered with Fritillariae Cirrhosae Bulbus powder at the dose of 18.0 mg•kg⁻¹ and 9.0 mg•kg⁻¹, respectively; the murines in positive control group were injected intraperitoneally with dexamethasone at the dose of 0.5 mg•kg⁻¹; while the murines in normal group and the model group were orally administered with the same volume of normal saline. All the drugs were given to murines per day for 28 d. The variations of airway responsiveness, variations of the total cell count and leukocyte differential count in bronchoalveolar lavage fluid(BALF), and the variations of thicknesses of bronchial wall and airway smooth muscle of each group were observed. The levels of MMP-2, MMP-9 and TIMP-1 were measured by ELISA; and the expression levels of MMP-2, MMP-9 and TIMP-1 mRNA were detected by RT-PCR. The results showed that as compared with the normal group, the airway responsiveness, the count of total cells, neutrophils, macrophage, lymphocytes, eosinophils in BALF, and the thicknesses of bronchial wall and airway smooth muscle were increased significantly in the model group(P<0.01); as compared with the model group, the above indicators were decreased significantly in the high dose group, low dose group and positive control group (P<0.05 or P<0.01). As compared with the normal group, the levels and expressions of MMP-2, MMP-9 and TIMP-1 mRNA were increased significantly in the model group(P<0.01); while as compared with the model group, these levels were decreased significantly in the high dose group, low dose group and positive control group(P<0.01). In conclusion, Fritillariae Cirrhosae Bulbus can improve airway remodeling in a murine asthma model, and its mechanisms may be related to down-regulating MMP-2, MMP-9 and TIMP-1 levels.
ABSTRACT
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality in part due to its high resistance to chemotherapeutic drugs. The anti-apoptotic Mcl-1 expression has been reported as a resistance factor in various types of tumors. Here, we investigated the expression of Mcl-1 in hepatoma cells and HCC tissues and its relationship with p53, and analyzed the possibility of the gene as a molecular target for HCC therapy. HCC specimens of 30 patients were examined by immunohistochemistry for Mcl-1 and p53 expression. Mcl-1 expression in hepatoma cell lines was measured by RT-PCR and Western blotting. The suppression of Mcl-1 by RNA interference or specific phosphatidylinositol-3 kinase (PI3K) inhibitor, LY294002, was evaluated as monotherapy, and it was combined with mitomycin C (MMC) in treating hepatoma cell line HepG2. Cell viability and apoptosis were assessed by MTT and FACS analysis. Finally, changes of Mcl-1 or p53 expression in various hepatoma cell lines were examined after transfection with Mcl-1 siRNA, the Mcl-1 expression plasmid, or the wide-type p53 expression plasmid, respectively. Mcl-1 protein was remarkably enhanced in HCC tissues as compared with adjacent non-tumor liver tissues. In addition, Mcl-1 was prominently expressed in HepG2 and Hep3B cells, weakly in SMMC7721 cells, and not in L02 cells. P53 protein was also overexpressed in HCC tissues and there was a significant correlation between the expression of p53 and Mcl-1. Silencing Mcl-1 by RNAi or LY294002 downregulated Mcl-1 expression and led to decreased cell viability and increased apoptosis. Combination of MMC and Mcl-1 RNAi or LY294002 exhibited a significant chemosensitizing effect. The expression of p53 was not influenced by Mcl-1 siRNA in HepG2 cells or transfection with the Mcl-1 expression plasmid in L02 cells. Furthermore, the expression of Mcl-1 in Hep3B cells was also not significantly changed after transfection with the wild-type p53 expression plasmid. It is concluded that Mcl-1 is overexpressed in HCC tissues. The mechanisms by which silencing Mcl-1 sensitizes hepatoma cells towards chemotherapy may be not attributed to the upregulated expression of p53 but the dysfunction of p53 through Mcl-1/p53 interaction. Mcl-1 may be a potential target of gene therapy for HCC.