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Inflammatory bowel disease(IBD)is a group chronic inflammatory gastrointestinal diseases with unknown etiology, which includes Crohn′s disease, ulcerative colitis and indeterminate colitis.The number of pediatric IBD patients increases year by year and the disease causes a huge burden on patients, families and society.Infliximab(IFX) is an effective and important drug, but more and more patients don′t respense to it.The reason for non-respense is complex and unclear.This review discussed the factors that may cause failure to respond to IFX, in order to find a suitable method to improve the therapeutic effect of IFX on children with IBD.
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Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.
الموضوعات
Rats , Animals , Glucocorticoids/metabolism , Rats, Sprague-Dawley , Nicotine/metabolism , Hydrocortisone/metabolism , Muscle, Smooth, Vascular , Dexamethasone/metabolism , Vascular Calcification/metabolism , Myocytes, Smooth Muscle/metabolism , Cells, Culturedالملخص
Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.
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Medical education reform mainly focused on the reform of the form and method of teaching but neglected the reform of the teaching concept that has truly penetrated into all aspects of teaching. With reference to the reflection on the teaching goal of physiology and the need of the cultivation of "post competency", the core concepts of physiological teaching are summarized into the following four aspects: "Three Outlooks" must be positive to help students establish a balanced view, a dialectical view, and a holistic view; "Three Fundamentals" should be solid to help students master basic knowledge structure system, cultivate basic knowledge acquisition ability, and improve basic operation skills; students should attach importance to learning and use; humanistic quality should be strengthened. The above core concepts have been widely recognized by students in teaching practice , and clinical medical students have significantly better evaluation of the core concepts than nursing students . Future direction of the subsequent teaching reform should be how to refine the contents of lectures under the guidance of the teaching concepts to adapt to the increasingly detailed specialities.
الملخص
Medical education reform mainly focused on the reform of the form and method of teaching but neglected the reform of the teaching concept that has truly penetrated into all aspects of teaching. With reference to the reflection on the teaching goal of physiology and the need of the cultivation of "post competency", the core concepts of physiological teaching are summarized into the following four aspects: "Three Outlooks" must be positive to help students establish a balanced view, a dialectical view, and a holistic view; "Three Fundamentals" should be solid to help students master basic knowledge structure system, cultivate basic knowledge acquisition ability, and improve basic operation skills; students should attach importance to learning and use; humanistic quality should be strengthened. The above core concepts have been widely recognized by students in teaching practice, and clinical medical students have significantly better evaluation of the core concepts than nursing students. Future direction of the subsequent teaching reform should be how to refine the contents of lectures under the guidance of the teaching concepts to adapt to the increasingly detailed specialities.
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Abstract: A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).
الموضوعات
Humans , Male , Female , Adult , Psoriasis/blood , Uric Acid/blood , Metabolic Syndrome/blood , Hyperuricemia/blood , Body Mass Index , Cross-Sectional Studies , Multivariate Analysisالملخص
Objective To evaluate the treatment effect of the arthroscopic incomplete removal of calcifications of the supraspinatus tendinitis without acromioplasty.Methods The clinical data of 20 patients of calcified supraspinatus tendinitis with Ellman Ⅰ or Ⅱ in general hospital of Shenyang military area command from January 2014 to February 2016 were retrospectively analyzed.Of the 20 patients,4 males and 16 females,the age ranged from 45 to 62 years old,with average age (50.2 ± 6.3) years old.All the patients received removal incomplete of calcification without acromioplasty.Pre-and postoperative 3,6,9 months general situation were evaluated by the VAS score,Constant-Murley score,University of California Los Angeles (UCLA) score,X-Radiographs and CT.Results The shoulder function was evidently improved in all 20 patients.The average VAS pain score was (8.2 ± 1.4) preoperatively and (0.8 ± 0.6) at the 6 months follow-up.The average Constant-Murley score was (44.6 ± 7.4) preoperatively and (95.4± 3.4) at the 6 months follow-up.The average UCLA score was (12.2 ± 3.6) preoperatively and (33.1 ± 1.4) at the 6 months follow-up.Conclusion The arthroscopic incomplete removal of calcifications of the supraspinatus tendon without acromioplasty can lead to good results with less iatrogenic injury.
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Objective To investigate the effect and mechanism of high-dose sirolimus (rapamycin) upon protecting the hepatic ischemia-reperfusion injury (HIRI) in aged mice. Methods Twenty C57BL/6 aged mice were randomly and evenly divided into the ischemia-reperfusion injury group (IRI group), low-dose rapamycin pretreatment group (rpm group), high-dose rapamycin pretreatment group (RPM group) and control group (Sham group) using the random number table method (5 mice in each group). In the Sham group, abdominal cavity was incised and sutured alone. In the other three groups, aged mouse 70% HIRI models were established. The ischemia time was 60 min. At preoperative 1 h, rapamycin at a dose of 1 mg/kg and 5 mg/kg was administered via intraperitoneal injection in the rpm and RPM groups. At 12 h post-reperfusion, hematoxylin-eosin (HE) staining was performed to observe the histological changes in the mouse liver. Suzuki grading method was adopted to evaluate the pathological score. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), tumor necrosis factor (TNF)-α and interleukin (IL)-10 and the LC3B-Ⅱ protein level in the liver tissues were quantitatively measured and statistically compared among different groups. Results HE staining of the liver tissues revealed normal liver tissues in the Sham group, severe liver cellular injury accompanied with a large quantity of inflammatory cellular infiltration in the IRI and rpm groups. Mild sinusoidal congestion and slight inflammatory cellular infiltration were observed in the RPM group. The pathological score was 5 (4-6) in the RPM group, significantly lower than 7 (5-8) and 8 (7-10) in the rpm and IRI groups (Z=-2.554 and -2.731, both P<0.05). In terms of postoperative liver function parameters, the AST level was (691±207) U/L in the RPM group, significantly lower compared with (2032±575) U/L and (1817±777) U/L in the IRI and rpm groups (t=4.90 and 3.13, both P<0.05). In the RPM group, the ALT level was measured as (996±584) U/L, considerably lower than (2992±992) U/L and (2373±687) U/L in the IRI and rpm groups (t=3.86 and 3.41, both P<0.05). The AST and ALT levels did not significantly differ between the IRI and rpm groups (both P>0.05). No statistical significance was identified in the TNF-α and IL-10 levels among different groups (all P>0.05). Western blot analysis revealed that the relative expression level of LC3B-Ⅱ protein in the liver tissue of the RPM group was significantly higher than those in the Sham, IRI and rpm groups (all P<0.05). Conclusions Administration of high-dose rapamycin exerts a protective effect upon HIRI probably through promoting cellular autophagy in aged mice.
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Objective Inflammatory bowel disease is an important chronic gastrointestinal disease of childhood and adolescence.Intestinal mucosa barrier damage plays an important role in its pathogenesis.This study attempts to use IL-1β stimulating Caco-2 cell monolayer simulates inflammatory intestinal epithelial barrier in vitro,provides the basis for studying the pathogenesis and treatment of IBD.Methods Caco-2 cells were cultivated in vitro until the 21st day to simulate intestinal epithelial cell monolayer barrier.The cells of inflammation group one were disposed with IL-1β for 2 h since the 5th day and detected TEER every other day until the 21st day.The cells of inflammation group two were disposed with IL-1 β at the 18th day for 0,12,24,48,72h, and detected TEER respectively.Normal control group cells were cultured with common medium and detected TEER at the corresponding time point.Results The TEER of Caco-2 cells gradually increased from the 5th to 15th days,reached 600Ω·cm2 in the 15th day of a plateau until to the 21st day.Since the 5th day,the TEER of inflammation group one were all lower than normal group,and still to the 21st day < 500Ω·cm2.Inflammation group two shows the time dependence TEER gradually reduce,peaked at 48 hours,then a slight increase in 72 hours.Conclusion The Caco-2 cells cultured for 2 ~ 3 weeks can form intestinal epithelial monolayer barrier with polarity,then treated with IL-1 β can manufacture inflammatory intestinal epithelial barrier model in vitro.
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Objective Intestinal epithelial barrier damage is closely related to a variety of gastrointestinal disease,how to maintain its function effectively is the key to treat all these diseases.This research attempts to explore the protective effect and its mechanism of toll-like receptor 2 (Toll-like receptor,TLR2)on permeability of intestinal epithelial barrier by experiments in vitro,to lay a foundation for new treatment methods.Methods We cultured non-transfected Caco-2 cells,TLR2-deficiency Caco-2 cells,TLR2-overexpressed Caco-2 cells in normal control group until the 21 st d,then tested transepithelial electrical resistance(TEER) which reacts the permeability of epithelial barrier.We cultured 3 types of cells in inflammation group until the 19th d treated with 10 ng/ml IL-1 beta for 48 h,then tested TEER values at the 21st d.We treated 3 types of cells in inhibition group with PI3K/Akt pathway inhibitor for 1h befor IL-1 beta,then tested TEER values at the 21st d.Results TEER value of TLR2-deficiency Caco-2 cell monolayer significantly reduced (P < 0.01),whereas TEER value of TLR2-overexpressed Caco-2 monolayer raised,but without statistically significant.TLR2 can prevent IL-1 beta caused TEER decreasing (P < 0.01),but the effect disappeared after given PI3K/Akt pathway inhibitor.Conclusion TLR2 can regulate the permeability of intestinal epithelial barrier.In addition,TLR2 can protect permeability increasing caused by inflammation,this effect mediated by PI3 K/Akt pathway.
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Objective To evaluate the efficacy and safety of bicyclol tablet on hepatic lesions caused by Epstein-Barr virus( EBV) infection in children.Methods A single-center controlled retrospective study was conducted in 121 children with hepatic lesions caused by EBV infection for evaluating safety,tolerability, and efficacy of treatment with bicyclol tablets or Glycyrrhizin capsules.Childer n in bicyclol group ( n=63 ) were treatedw ith bicyclol at blets and cotn rol group ( n =58 ) were treated with Glycyrrhizin capsules.The course of the treatment were both 8 weeeks for two groups.The level of the EBV load pretreatment and plas-ma aminotransferase,blood routine,urine routine pretreatment and 1 week,4 weeks and 8 weeks after treat-mentw ere analyzed er trospectively.Rse ults (1) The pal smaA LT level sigin ficantly decreased in theb icy-clol group compared with that in the contro l group(P<0.01), se pecai lly the levle after 8 weeks treatm ent. (2) Bicycol l was more effce tive in the bicyclol group than Glycyrrhizin capslu se in the control group( P<0.01).(3) Both grousp had no significantlya dvesr e events.Conclusion Bicyclol tablet can derc ease plas-ma aminotransferase level,espce ially ALT,inc hildren caused by EBV infection with better efficiency and safety.
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Objective To investigate and compare the clinical values of serum procalcitonin (PCT)and high sensitivity C-reac-tive protein (hs-CRP)levels for predicting the blood culture positivity in the patients with sepsis.Methods 132 adult patients with sepsis were enrolled in this study.Blood cultures were performed before the antibacterial therapy.The white blood cell (WBC) count,absolute neutrophil count(ANC),levels of PCT and hs-CRP were determined.The application value of PCT and hs-CRP for predicting the positive blood culture results were evaluated.Results The median serum PCT levels in the blood culture positive group and the blood culture negative group were 7.92 ng/mL and 0.95 ng/mL respectively,the difference had statistical signifi-cance(P <0.01).The receiver operating characteristic (ROC)curves showed that PCT had a higher predictive accuracy for blood culture positivity compared with hs-CRP,the area under the curve (AUC)was 0.810(P =0.001)and 0.690(P =0.274),respec-tively.The combined detection of PCT and hs-CRP for predicting the blood culture positive results was similar to the performance of PCT alone,AUC as 0.885 (P =0.001 ).The median cut point of PCT was 0.91 ng/mL,the sensitivity of PCT for predicting blood culture positivity was 90%.This sensitivity remained unchanged when PCT cut point was1.14ng/mL.Using the PCT cut points of 0.91 and 1.14 enabled reducing the submitted blood cultures by 51% and 56% respectively.Conclusion Compared with hs-CRP,serum PCT level could better predict the blood culture positivity in the patients with sepsis.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of infliximab in the treatment of Crohn's disease in children.</p><p><b>METHODS</b>Thirteen children who were diagnosed with Crohn's disease and received routine comprehensive treatment and infliximab (5 mg/kg) between January 2011 and December 2014 were enrolled. The changes in their clinical manifestations, laboratory indices, and Pediatric Crohn's Disease Activity Index (PCDAI) after the 30-week treatment were analyzed retrospectively. Meanwhile, endoscopy was performed to evaluate therapeutic effects.</p><p><b>RESULTS</b>The symptoms such as abdominal pain, diarrhea, and bloody stool were relieved soon after infliximab treatment, with no recurrence observed; after the 30-week treatment, the white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and the PCDAI decreased, while the hemoglobin increased significantly compared with those before treatment (P<0.05). After infliximab treatment, two children underwent endoscopy. The endoscopy showed that one child was cured, and the other child failed to respond to the treatment. No adverse drug reactions were seen in all patients.</p><p><b>CONCLUSIONS</b>Infliximab treatment has significant clinical effects in children with Crohn's disease, with no obvious adverse reactions, and therefore, it can be applied as one of the preferred alternatives for treatment of Crohn's disease in children.</p>
الموضوعات
Adolescent , Child , Child, Preschool , Female , Humans , Male , Crohn Disease , Blood , Drug Therapy , Pathology , Infliximab , Therapeutic Usesالملخص
Aim To confirm the inhibitory effect of chronic intermittent hypobaric hypoxia ( CIHH) on my-ocardial apoptosis induced by metabolism syndrome ( MS) , and to investigate its mechanism. Methods A rat model of MS induced by fructose was used. The blood pressure and the plasma content of glucose, tri-glyceride, cholesterol, and insulin after 12 h fasting were detected. HE stain were used to detect the cardi-ac structure. The TUNEL staining and activity of caspase-3 were used to detect the apoptosis of myocar-dium. The protein expression of Bcl-2 and Bax was detected by Western blot . Results Compared with the control rats, the blood pressure and the plasma content of glucose, triglyceride, cholesterol, and insu-lin were all increased in rats with MS. In rats with MS, the impairment of cardiac structure and the increase of apoptosis were also observed. The protein expression of Bcl-2 was significantly down-regulated, and that of Bax was significantly up-regulated in MS rats. The ratio of Bcl-2/Bax was also significantly decreased. Interest-ingly, CIHH could ameliorate all of the above issues. There was no significant difference between control group and CIHH group. Conclusion CIHH may im-prove the increased apoptosis in rats with MS via inhib-iting the mitochondrial pathway of apoptosis. This stud-y might provide new targets for therapy and the preven-tion of MS patients.
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Objective To investigate the association of hepatitis B virus ( HBV) precore ( preC) /C mutations with the pro-gression of liver disease .Methods The HBV genes of 50 chronic hepatitis B , including 30 HBV e-antigen ( HBeAg)-negative and 20 HBeAg-positive patients, were detected with real-time quantification polymerase chain reaction (RT-PCR) and the direct sequencing method.Results The mutations T1762/A176, T1766/A1768, A1896 , and the levels of HBV viral loads significantly correlated with the disease progression .The HBeAg-negative patients had a higher frequency of mutations at T 1762/A1764 , T1766/A1768 , and A 1896 relative to HBeAg-positive patients .Conclusions Patients with advanced liver diseases and with HBeAg-negativity possibly had multi-mutations at T1762/A1764, T1766/A1768, and A1896 in HBV genomes.
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The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day. The rats in control group were kept in the same environment as CIHH rats except no hypoxia exposure. The relaxation of thoracic aorta rings was recorded by organ bath perfusion technique, and expression of opioid receptors was measured by Western blot. Results are shown as follows. (1) The acetylcholine (ACh)-induced endothelium-dependent relaxation of thoracic aorta in CIHH rats was increased obviously in a concentration-dependent manner compared with that in control rats (P < 0.05). (2) This enhancement of ACh-induced relaxation in CIHH rats was abolished by naloxone, a non-specific opioid receptor blocker (P < 0.05). (3) The expressions of δ, μ and κ opioid receptors in thoracic aorta of CIHH rats were up-regulated compared with those in control rats (P < 0.05). (4) The enhancement of CIHH on relaxation of thoracic aorta was reversed by glibenclamide, an ATP-sensitive potassium channel (KATP) blocker (P < 0.05). The results suggest that opioid receptors are involved in CIHH-enhanced ACh-induced vasorelaxation of thoracic aorta through KATP channel pathways.
الموضوعات
Animals , Male , Rats , Acetylcholine , Pharmacology , Altitude , Aorta, Thoracic , Glyburide , Pharmacology , Hypoxia , KATP Channels , Rats, Sprague-Dawley , Receptors, Opioid , Metabolism , Vasodilationالملخص
Objective To explore the risk factors of adhesive small bowel obstruction for the influence of the long-term therapeutic effects.Methods 218 case of adhesive small bowel obstruction in patients were treeted with a long follow-up and retrospective analysis.Results Among the 218 admissions in 235 patients,192 admissions (81.7.%) were surgical treated and 43 admissions(18.3%) were performed conservative treatment.The mean recovery time was 65.7 months and the accumulative incidence of surgical recurrence in 5 years was 19.0% in surgical group and those in conservative group were 50.4 months and 34.0% respectively.There was significant difference between two groups (P < 0.05).Conclusion The long-term efficacy of risk factors was related to the treatment before the operation site and times,the last operation to the incidence of admissions.No other independent risk factor of recurrence was found.Surgical treatment serves as a better way in the prevention of later recurrences in patients with adhesive intestinal obstruction under certain conditions.
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Objective To analyze the risk factors that influence prognosis of pancreatic injury.Methods The clinical data of 73 patients with pancreatic injury were analyzed retrospectively.Univariate analysis and multivariate Logistic regression were performed to analyze the clinical parameters.Results Complications occurred in 27 patients with the overall incidence rate of 36.9%.6 patients died with the mortality of 8.2%.Result of univariate analysis indicated that the volume of blood loss,systolic blood pressure,injury grade by American Association surgery of Trauma (AAST),pancreatic leakage,time on admission were significant factors that influence the incidence rate of complications (P < 0.05).The results of Multivariate Logistic regression indicated that the volume of blood loss,systolic blood pressure,injury grade by AAST,time on admission were independent predictors for prognosis in pancreatic injury (OR =3.764,0.940,7.315,1.501,all P < 0.05).Conclusion It should pay attention to all the factors that influence the prognosis of pancreatic injury in clinic.Exact judgment and appropriate treatment plan are helpful to increase achievement ratio of pancreatic injury.
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<p><b>OBJECTIVE</b>Glutamine has protective effects against renal injuries. This study was designed to explore the possible mechanism underlying the protections by examining the effects of glutamine on extracellular signal regulated kinase (ERK) and p38MAPK expression in the kidney in rats with endotoxemia.</p><p><b>METHODS</b>One hundred and twenty-one 18-day-old Wistar rats were randomly injected with LPS (4 mg/kg; n=55), LPS (4 mg/kg)+glutamine (1 mL/kg) (n=55), or normal saline (control group; n=11). The two LPS groups were subdivided into five groups sacrificed at 2, 4, 6, 24 and 72 hrs after administration (n=11 each). ERK-2 and p38MAPK mRNA and protein expression in the kidney were measured by RT-PCR and immunohistochemistry.</p><p><b>RESULTS</b>Compared to the control group, the mRNA and protein expression of both ERK-2 and p38MAPK in the LPS group significantly increased 2, 4, 6, 24 and 72 hrs after administration (P<0.01), and reached a peak at 6 hrs (P<0.01). In the LPS+glutamine group, the trend of ERK-2 and p38MAPK expression was similar to the LPS group but their expression levels were significantly lower than those in the LPS group at all time points (P<0.05 or 0.01).</p><p><b>CONCLUSIONS</b>Both ERK-2 and p38MAPK expression increased in young rats with LPS-induced endotoxemia. Glutamine alleviates renal injuries possibly by decreasing the expression of both.</p>
الموضوعات
Animals , Female , Male , Rats , Endotoxemia , Pathology , Extracellular Signal-Regulated MAP Kinases , Genetics , Glutamine , Pharmacology , Immunohistochemistry , Kidney , Lipopolysaccharides , Toxicity , RNA, Messenger , Rats, Wistar , p38 Mitogen-Activated Protein Kinases , Geneticsالملخص
<p><b>OBJECTIVE</b>To compare therapeutic effects of acupuncture plus massage therapy and western medicine on infantile diarrhea.</p><p><b>METHODS</b>A total of 120 cases of infantile diarrhea were randomly divided into a treatment group of 80 cases and a control group of 40 cases. The treatment group were treated by acupuncture and massage therapy, and the control group by smecta.</p><p><b>RESULTS</b>The cured rate of 55.0% in the treatment group was better than 35.0% in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Acupuncture plus massage therapy has obvious therapeutic effect on infantile diarrhea.</p>