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Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a group of persistent organic pollutants among environmental endocrine disruptors, are widely used in industrial production and daily life. PFASs are widely and persistently present in the environment and organisms due to their bioaccumulation, long half-life, and low degradability properties. Published studies have proved that PFASs have immunotoxicity, endocrine toxicity, neurotoxicity, reproductive toxicity, and hepatotoxicity. At present, several epidemiological studies have been conducted on the effects of PFASs on allergic diseases, the research endpoints include asthma, allergic rhinitis, atopic dermatitis, and the expression of allergic biomarkers such as serum immunoglobulin E (IgE), but no consistent results have been observed yet. PFASs have the potential to activate several signaling pathways, including the peroxisome proliferator-activated receptor (PPAR), nuclear factor-κB (NF-κB), and JAK/STAT pathways. These mechanisms, along with increasing mast cell calcium influx and sex hormone synergistic effects, may contribute to immunomodulation in allergic diseases. At present, the exact human effect of PFASs exposure on allergic diseases and the related mechanisms are still uncertain. This review focused on the impacts of PFASs on asthma, allergic rhinitis, and atopic dermatitis and their possible mechanisms, so as to provide research ideas for the prevention, diagnosis, and treatment of allergic diseases.
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Objective:To systematically evaluate the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) plus surgery versus neoadjuvant chemotherapy (NCT) plus surgery in the treatment of advanced esophageal squamous cell carcinoma.Methods:Clinical controlled trials of comparing the treatment of NCRT plus surgery with NCT plus surgery for esophageal squamous cell carcinoma were electronically searched from the databases including PubMed, The Cochrane Library, EMbase, CBM, CNKI, WanFang and VIP from the inception of databases to January, 2019. Two reviewers independently screened the literatures, extracted data and assessed the risk of bias of the included studies. And then, a meta-analysis was performed by using RevMan 5.3 software.Results:A total of 8 clinical control studies were included, including 995 patients with esophageal squamous cell carcinoma. Meta-analysis results showed that compared with the NCT group, the R 0 resection rate was significantly higher ( OR=2.14, 95% CI: 1.03-4.45, P=0.040) and the pathological complete response (pCR) rate was significantly higher ( OR=4.19, 95% CI: 1.71-10.28, P=0.002) in the NCRT group. The incidence of postoperative complications ( OR=1.37, 95% CI: 0.76-2.48, P=0.300) and the risk of perioperative death ( OR=1.28, 95% CI: 0.58-2.83, P=0.54) were not significantly different between two groups. The long-term survival of patients with esophageal squamous cell carcinoma in the NCRT group was significantly better compared with that in the NCT group ( HR=0.77, 95% CI: 0.64-0.92, P=0.005). Conclusions:Compared with NCT plus surgery for advanced esophageal squamous cell carcinoma, NCRT plus surgery has higher R 0 resection rate and pCR rate, does not significantly increase the risk of perioperative complications or perioperative death, and significantly improves the long-term survival of esophageal squamous cell carcinoma patients.
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Objective@#To explore the effect of 18β-sodium glycyrrhetinic acid on thymic stromal lymphopoietin (TSLP) in nasal mucosa of allergic rhinitis (AR) rats.@*Methods@#One hundred Wistar rats,half male and half female,were randomly divided into 5 groups by random number table method: control group, AR model group,budesonide group,18β-sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg groups, with 20 rats in each group. AR animal models were established by ovalbumin (OVA) sensitization in the other four experimental groups. After successful modeling, budesonide and 18β-sodium glycyrrhetinic acid were given in each group,and the detection time points were 2 weeks and 4 weeks. The distribution of TSLP in rat nasal mucosa was detected by immunohistochemistry,and the expression of TSLP in rat nasal mucosa was determined by Western blot at the protein level. The expression of TSLP-mRNA in rat nasal mucosa was detected and compared by real-time fluorescence quantitative PCR (RT-PCR) at mRNA level. The concentrations of IL-4 and OVA-sIgE in rat serum were measured and compared by ELISA. One-way analysis of variance and the least significant difference method were used for the comparison among groups, LSD t test was used for the comparison between the two groups,and the difference was statistically significant (P<0.05).@*Results@#Immunohistochemistry confirmed existence of TSLP in rat nasal mucosa, especially in epithelial cells,endothelial cells and epithelial cilia. Western blot and RT-PCR suggested that the expression of TSLP and TSLP-mRNA in nasal mucosa of AR model group was significantly higher than that of control group (2 weeks TSLP: 1.795 9±0.131 4 vs 0.990 5±0.164 2, 4 weeks TSLP: 1.809 7±0.253 4 vs 0.870 3±0.124 4; 2 weeks TSLP-mRNA:4.582 9±0.697 7 vs 1.108 7±0.081 1, 4 weeks TSLP-mRNA:4.814 4±0.662 8 vs 1.001 0±0.155 3; all P<0.05). After 2 weeks and 4 weeks of drug intervention,the expression of TSLP and TSLP-mRNA was inhibited in nasal mucosa of budesonide group,18β-sodium sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg group,which was significantly different from that of AR model group (2 weeks TSLP: (0.897 8±0.081 8)/(1.072 1±0.113 6)/(1.396 6±0.133 9) vs 1.795 9±0.131 4; 4 weeks TSLP: (1.191 0±0.161 3)/(1.141 0±0.152 3)/(1.200 5±0.189 6) vs 1.809 7±0.253 4; 2 weeks TSLP-mRNA: (1.175 6±0.100 9)/(1.254 4±0.078 2)/(2.037 2±0.559 2) vs 4.582 9±0.697 7; 4 weeks TSLP-mRNA: (1.158 3±0.104 3)/(1.224 0±0.034 0)/(1.275 2±0.099 6) vs 4.814 4±0.662 8; all P<0.05), and not significantly different from control group. With the inhibition of TSLP, the concentrations of IL-4 and OVA-sIgE in rat serum were also decreased.@*Conclusion@#18β-sodium glycyrrhetinic acid has obvious inhibitory effect on TSLP in nasal mucosa of AR rats, which can control Th2 type immune inflammatory reaction.
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BACKGROUND: Bone marrow mesenchymal stem cells improve neurological functional recovery from cerebral infarction, but they are a rare population in the bone marrow with difficulty in cell separation and purification. OBJECTIVE: To investigate the neuroprotective effects and the potential mechanisms of human placenta-derived mesenchymal stem cell transplantation for cerebral infarction in rats. METHODS: Totally 120 rats subjected to middle cerebral artery occlusion were randomized into treatment group and control (n=60 per group). The rats were intravenously treated with human placenta-derived mesenchymal stem cells in the treatment group or the phosphate buffer saline in the control group. Then, a modified neurological severity score was assessed at 1, 3, 7, 14 days post transplantation, and measurement of infarct volume in the ischemic brain was performed using 2,3,5-triphenyltetrazolium chloride staining at 14 days post transplantation. The anti-human specific immunostain for mitochondria in the ischemic brain was performed and the mitochondria-positive cells were counted; TUNEL immunostaining was performed and TUNEL positive cells were counted. ELISA assays for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also performed in the ischemic brain. RESULTS AND CONCLUSION: At 1, 3, 7 and 14 days after treatment, the modified neurological severity score in the treatment group was significantly lower than that in the control group (P < 0.05). At 14 days after treatment, the infarct volume in the treatment group was significantly lower than that in the control group (P < 0.05), only few mitochondria-positive cells were present in the ischemic brain, and the number of TUNEL positive cells in the treatment group was significantly less than that in the control group (P < 0.05). At 3 and 14 days after treatment, BDNF expression levels in the treatment group were significantly higher than those in the control group (P < 0.05). At 7 and 14 days after treatment, VEGF expression levels in the treatment group were significantly higher than those in the control (P < 0.05). At 7 days after treatment, HGF expression level in the treatment group was significantly higher than that in the control group (P < 0.05). To conclude, intravenous administration of human placenta-derived mesenchymal stem cells can promote neuroprotective effects against cerebral infarction. These effects may be related to the increase of BDNF, VEGF and HGF expression and the decrease of apoptosis in the ischemic brain.
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<p><b>OBJECTIVE</b>To investigate the effects of metformin on proliferation and apoptosis in multiple myeloma cell line RPMI8226 and U266, and to clarify the molecular mechanism of proliferation inhibition and apoptosis induced by metformin.</p><p><b>METHODS</b>RPMI8226, U266 cells were treated with 0, 5, 10, 20, 40, 80 mmol/L of metformin for 24, 48 and 72 hours, then the inhibition rate was detected by CCK-8; RPMI8226 cells were treated with 0, 10, 20, 40 mmol/L of metformin for 48 hours, the apoptosis rates were detected by flow cytometry with Annexin-V-FITC/PI double staining; RPMI8226 cells were treated with 0, 5, 10, 20 mmol/L of metformin for 48 hours, the expressions of Caspase-3, PARP, STAT3, p-STAT3, BCL-2, Cyclin D1 and P21 were detected by Western blot.</p><p><b>RESULTS</b>The inhibition rate increased in RPMI8226 and U266 cells treated with metformin in the dose- (r=0.982, r=0.967, P<0.05) and time-dependent (r=0.956, r=0.962, P<0.05) manner; the apoptosis rate increased(r=0.976, P<0.05) in RPMI8226 cells treated with metformin; it also was found that procaspase-3 was degraded and PARP was cleaved when treated with metformin. Proliferation inhibition and apoptosis of RPMI8226 cells were related with inhibition of STAT3 phosphorylation, down-regulation of BCL-2 and Cyclin D1, and up-regulation of P21.</p><p><b>CONCLUSION</b>Metformin can inhibit the proliferation and induce apoptosis of RPMI8226 and U266 cell lines, which may be related to down-regulation of STAT3 signal transduction pathway.</p>
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To investigate the effect of methyleugenol on expression of MUC5AC in nasal mucosa of rats with allergic rhinitis (AR).Seventy-two Wistar rats were randomly divided into 6 groups:normal control group, AR group, loratadine group, low-dose methyleugenol group, middle-dose methyleugenol group and high-dose methyleugenol group with 12 rats in each group. AR was induced by intraperitoneal injection of ovalbumin in latter 5 groups. 10 mg loratadine q.d was given to rats in loratadine group by gavage; and 10 mg/kg, 20 mg/kg and 40 mg/kg methyleugenol were given by gavege q.d to rats in low-, middle-and high-dose methyleugenol groups, respectively. Nasal mucosa samples were obtained from rats at 1, 2, 4 and 6 weeks after drug intervention. The expression of MUC5AC protein and mRNA in nasal mucosa was detected by immunohistochemistry and real-time fluorescence quota PCR (RT-PCR), respectively.Compared with AR, the percentage of cells staining positively for MUC5AC protein and the relative quantity of MUC5AC mRNA in middle-and high-dose methyleugenol groups were significantly decreased after 2 and 4 weeks of drug intervention (<0.05), but no such decrease was observed in low-dose methyleugenol group at all time points (>0.05). The percentage of cells with positive expression of MUC5AC protein and mRNA in loratadine group were significantly decreased after 1 week of administration (<0.05). The percentage of cells with positive MUC5AC protein in middle-dose methyleugenol group was higher than that in loratadine group (<0.05) after 6 week of drug intervention, but the difference was not seen in high-dose group (>0.05). There was no significant difference in relative quantities of MUC5AC mRNA after 4 weeks of administration between high-and middle-dose methyeugenol groups and loratadine group (>0.05).Methyleugenol can attenuate AR through inhibiting the expression of MUC5AC mRNA and protein in nasal mucosa of AR rats.
Subject(s)
Animals , Rats , Dose-Response Relationship, Drug , Down-Regulation , Eugenol , Pharmacology , Loratadine , Mucin 5AC , Physiology , Nasal Mucosa , Chemistry , Ovalbumin , Rats, Sprague-Dawley , Rats, Wistar , Rhinitis, Allergic , Drug TherapyABSTRACT
OBJECTIVE@#To investigate 18β-sodium glycyrrhetinic acid impact on nasal mucosa epithelial cilia in rat models of allergic rhinitis (AR).@*METHOD@#AR models were established by ovalbumin-induction. Wister rats were randomly divided into groups as normal group, model group, budesonide (0.2 mg/kg) group and sodium glycyrrhetinic acid (20 mg/kg and 40 mg/kg) group after the success of AR models. At 2 weeks and 4 weeks after treatment, the behavioral changes of rats were observed and recorded, and nasal septum mucosae were collected after 2 week and 4 week intervention, and the morphological changes of nasal mucosae were observed by electron microscope.@*RESULT@#Model group developed typical AR symptoms, the total score in all animals was > 5. With budesonide and sodium glycyrrhetinic acid treatment, the AR symptoms were relieved, and the total scores were reduced significantly (P < 0.01). Compared with the model group: after 2 weeks' intervention, thick mucous secretions on the top of columnar epithelium cilia in rat nasal mucosa was significantly reduced, and cilia adhesion, lodging, shedding were relieved in budesonide group and sodium glycyrrhetinic acid group, the relieve in budesonide group was slightly better than that in sodium glycyrrhetinic acid group; after 4 week intervention, Cilia adhesion, lodging, shedding were completely vanished, and the cilia were ranged in regular direction in budesonide group and sodium glycyrrhetinic acid group. Cilia in sodium glycyrrhetinic acid (20 mg/kg) group was more orderly, smooth than that in budesonide group and sodium glycyrrhetinic acid group (40 mg/kg), and the condition of cilia in sodium glycyrrhetinic acid group (20 mg/kg) was similar to the normal group.@*CONCLUSION@#18β-sodium glycyrrhetinic acid is effective to restrain the pathological changes of nasal mucosa cilia in rat models of AR.
Subject(s)
Animals , Rats , Budesonide , Pharmacology , Cilia , Disease Models, Animal , Glycyrrhetinic Acid , Pharmacology , Nasal Mucosa , Ovalbumin , Random Allocation , Rhinitis, Allergic , Drug TherapyABSTRACT
OBJECTIVE:To discuss the feasibility of the development of pharmaceutical care by clinical pharmacist based on micro letter public platform. METHODS:The content and method of pharmaceutical care based on micro letter public platform were introduced by registering micro letter public platform public number,building reasonable medication guidance team,releasing reasonable medication information regularly. RESULTS:40 pieces of reasonable medication information had been pushed by micro letter public platform of our department during Aug.-Nov. 2014,and 350 users added our public platform. The pushed information was mainly about reasonable drug use(57.5%),read by 18 585 persons,and read by 465 person per time in average. Reposted or collected 2 190 times in total,reposted or collected 55 times in average,each piece of information was read by 4 219 person per time at the most. CONCLUSIONS:The pharmaceutical care by pharmacists depending on micro letter public platform contribute to put pharmacist team together,build professional image and provide pharmaceutical care for the public in the information age.
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<p><b>OBJECTIVE</b>To explore the effect of 18-β glycyrrhetinic acid (GA) on the endoplasmic reticulum of nasal epithelial cells in allergic rhinitis (AR) model rats.</p><p><b>METHODS</b>Totally 96 Wistar rats were randomly divided into the blank group, the AR model group, the loratadine group, the GA group, 24 in each group. AR models were established by peritoneally injecting ovalbumin (OVA). Morphological scoring was performed. GA at 21. 6 mg/kg was intragastrically administered to rats in the GA group. Nasal mucosal tissues were taken for electron microscopic examinations at the second, fourth, sixth, and tenth week after drug intervention.</p><p><b>RESULTS</b>The overlapping score was 2.10 ± 0.45 in the blank group, 5.10 ± 0.56 in the loratadine group, 5.10 ± 0.56 in the AR model group, 5.20 ± 0.78 in the GA group, showing statistical difference when compared with the blank group (P < 0.01). Results under transmission electron microscope showed that the number of the endoplasmic reticulum increased in the AR model group, with obvious cystic dilatation, a lot of vacuole formation, and degranulation. A large number of free ribosomes could be seen in cytoplasm. With persistent allergen exposure, changes mentioned above was progressively aggravated in the endoplasmic reticulum of nasal mucosal epithelium in the AR model group. But the dilation of endoplasmic reticulum, vacuole formation, and degranulation were relieved in the GA group, and got close to those of the blank group.</p><p><b>CONCLUSION</b>18-β GA could improve the expansion, vacuolization, and degranulation of the endoplasmic reticulum of nasal epithelial cells in AR model rats.</p>
Subject(s)
Animals , Rats , Anti-Inflammatory Agents , Pharmacology , Therapeutic Uses , Endoplasmic Reticulum , Epithelial Cells , Glycyrrhetinic Acid , Pharmacology , Therapeutic Uses , Nasal Mucosa , Rats, Wistar , Rhinitis, Allergic , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of electric acupuncture (EA) on the Nogo receptors (NgR) protein expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral ischemia-reperfusion (I/R) stroke-prone renovascular hypertensive rats (RHRSP) with middle cerebral artery occlusion (MCAO) at different time points, and to investigate its possible mechanisms for remote-organ injury of acute cerebral infarction (ACI).</p><p><b>METHODS</b>The RHRSP model was duplicated in male SPF grade SD rats. Then the MCAO model was prepared by a thread stringing method. Rats were divided into the hypertension group,the sham-operation group, the MCAO group, the EA group, and the sham-acupoint group by random number table method, 60 in each group. Rats in the MCAO group only received MCAO reperfusion treatment. Those in the sham-operation group only received surgical trauma. Baihui (DU20) and Dazhui (DU14) were needled in the EA group, once daily for a total of 28 days.The needles were acupunctured at the skin one cun distant from Baihui (DU20) and Dazhui (DU14) and then the same EA treatment was performed in the sham-acupoint group. At day 1, 7, 14, 28 after treatment, six rats were executed from each group, and their right cortex and medulla oblongata, and the left spinal cord were isolated. The infarct volume was detected by Nissl's staining method. The NgR expression was detect by Western blot.</p><p><b>RESULTS</b>(1) In the cortex area: compared with the hypertension group,the NgR expression increased in the MCAO group at day 1,7,14,and 28 after MCAO (P < 0.05). Compared with the MCAO group, the NgR expression of the EA group and the sham-acupoint group were equivalent at 1 day af ter MCAO (P > 0.05). At day 7, 14,and 28 after MCAO, the NgR expression decreased in the EA group (P < 0.05), it was quite similar to that in the sham-acupoint group (P > 0.05). (2) In the medulla oblongata area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group. the MCAO group,the EA group, and the sham-acupoint group at 1 day after MCAO (P > 0.05). At day 7.14, and 28 after MCAO, the NgR expression increased in the MCAO group (P < 0.05). Compared with the MCAO group,the NgR expression decreased in the EA group at day 7, 14, and 28 after MCAO (P < 0.05), whereas it was similar in the sham-acupoint group (P > 0.05). (3) In the spinal cord area: compared with the hypertension group, the NgR expression was equivalent in the sham-operation group, the MCAO group,the EA group, and the sham-acupoint group at day 1 and 7 after MCAO (P > 0.05). At day 14 and 28 after MCAO, the NgR expression increased in the MCAO group (P < 0.05). Compared with the MCAO group, the NgR expression decreased in the EA group at day 14 and 28 after MCAO (P < 0.05), whereas it was equivalent in the sham-acupoint group (P > 0.05).</p><p><b>CONCLUSIONS</b>Increased NgR expression in the cerebral cortex, the medulla oblongata, and the spinal cord of cerebral infarct rats was an important reason for involving remote-organ injury of ACI. The protective effect of EA on hypertensive I/R cerebral injury rats might be closely related to down-regulating central nervous system myelin growth inhibition mediated factors Nogo-A receptor NgR protein expression.</p>
Subject(s)
Animals , Male , Rats , Cerebral Infarction , Metabolism , Therapeutics , Disease Models, Animal , Electroacupuncture , GPI-Linked Proteins , Metabolism , Hypertension, Renal , Metabolism , Therapeutics , Medulla Oblongata , Metabolism , Myelin Proteins , Metabolism , Nogo Receptor 1 , Rats, Sprague-Dawley , Receptors, Cell Surface , Metabolism , Spinal Cord , MetabolismABSTRACT
OBJECTIVE@#To observe 18β-glycyrrhetinic acid (GA) impact on ultrastructure of tight junctions (TJs) of nasal mucosa epithelial cells in rats models of allergic rhinitis (AR).@*METHOD@#Ninety-six Wistar rats were randomly divided into control group, model group, loratadine group, and 18β-glycyrrhetinic acid group, and each group had 24 rats. Ovalbumin was used to establish a rat AR model. The behavioral changes and the tight junctions of nasal epithelial were observed and compared in different groups after 2,4,6 and 10 weeks intervention.@*RESULT@#The length of TJs in allergic rhinitis model became shorter, electron-high-density plasma membrane became thicker, number of the integration loci reduced and gap of TJs widened or even ruptured. With the consistent effect of allergens,the changes of TJs in the model group aggravated gradually,and the changes of ultrastructure of TJs in 18β-glycyrrhetinic acid group was relieved apparently compared to model group and even were close to the control model with time.@*CONCLUSION@#18β-glycyrrhetinic acid can recover the ultrastructure of the tight junctions of AR rat nasal epithelial cells.
Subject(s)
Animals , Rats , Cell Count , Epithelial Cells , Glycyrrhetinic Acid , Pharmacology , Nasal Mucosa , Cell Biology , Ovalbumin , Rats, Wistar , Rhinitis, Allergic , Drug Therapy , Tight JunctionsABSTRACT
<p><b>OBJECTIVE</b>To compare changes of blood clotting state after initial trauma fractures and twice trauma fractures, investigate the effect of fracture history to the state of the blood clotting after secondary trauma fractures.</p><p><b>METHODS</b>Thirty New Zealand rabbits were selected, aged 5-6 months, males and females unlimited, weighted 2.4-2.6 kg, non-pregnant. Postoperative model of initial trauma fractures was established, and then postoperative model after twice trauma fractures was built. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fiber fibrinogen (FIB) and D-dimer (DD) were detected by venous blood at 1 day and 5 days after surgery. Changes of indicators were compared between after twice fractures at the same time.</p><p><b>RESULTS</b>Comparing with 1 day after the secondary trauma fracture and initial trauma fracture surgery, PT, APTT values showed no significant difference (P > 0.05), TT, FIB, DD values were increased, and the difference was statistically significant (P < 0.05); Comparing with 5 days after the secondary trauma fracture and initial trauma fracture surgery, PT values showed no significant difference (P < 0 .05), APTT, TT, FIB, DD values were increased, and the difference was statistically significant (P< 0.05).</p><p><b>CONCLUSION</b>Blood after the secondary trauma fractures is in hypercoagulable state after fracture surgery.</p>
Subject(s)
Animals , Female , Humans , Male , Blood Coagulation , Fibrinogen , Metabolism , Fractures, Bone , Blood , General Surgery , Prothrombin TimeABSTRACT
Mental health has emerged an outstanding problem in public health and a social problem as welL Early warning and intervention mechanism for mental health of community residents serves an effective mechanism to combat mental problems for such a population. Recommendation: Emphasize and build mental health service institutions in communities, and improve their functionality, establish an effective early warning and intervention mechanism for community mental health services in communities, enhance health education, health promotion and mental health knowledge education, and carry out the tertiary prevention and tertiary functionality principles for mental health. These measures can prevent community residents from mental illness, improve their mental health, and promote the development of mental health services in Chinas communities.