A cross-sectional study on the relationship between 24-hour activities and depressive symptoms in vocational school students / 复旦学报（医学版）

Objective An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity(PA),sedentary behavior(SB),and sleep(SLP),and depressive symptoms among vocational school students with and without depressive symptoms.Methods Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022.Fourteen schools were selected using the convenience cluster sampling method.The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale(CES-D)scores.Results A total of 40 339 questionnaires were collected,of which 10 086 were able to clearly remember the time of physical activity in the past week,and 8 149 were valid after data cleaning.According to the valid questionnaires,5 496 students(67.44%)were in the non-depressive symptoms group and 2 653(32.56%)were in the depressive symptoms group.The mean age of the students were(16.70±1.19)years.In the non-depressive symptoms group,substituting moderate physical activity(MPA)for all the other behaviors was negatively associated with CES-D scores,while substituting vigorous physical activity(VPA)for MPA and SB was positively associated with CES-D scores.In the depressive symptoms group,substituting walking,SB,and SLP with MPA was negatively associated with CES-D scores,respectively.The associations of MPA substituted for walking,SB,and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group.Conclusion The detection rate of depressive symptoms was high among vocational students.Substituting MPA for walking,SB,and SLP were negatively associated with CES-D scores,with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.

Estamos prontos para múltiplas trocas entre produtos de referência e biossimilares? / Are we ready for multiple switches between reference products and biosimilars?

ABSTRACT Inflammatory bowel diseases (IBD) currently impose an immense social and economic burden on society in terms of both direct and indirect healthcare costs. Their incurable and progressive nature results in an unavoidable lifetime expense. The introduction of infliximab more than two decades ago had revolutionized IBD treatment. Nowadays, while biologic drugs comprise various vital therapeutic options for patients, they can be associated to significant costs to healthcare systems. The most crucial benefit of biosimilars is that they bring more significant cost reduction and increase access to advanced therapies. They also allow the treatment of newly diagnosed patients and dose optimization for those who need it. There is an inverse relationship between price and demand for treatment with biologics. For a more significant reduction in cost to be possible, greater use of biosimilars is necessary. For this to occur, it is imperative not only to use biosimilars in naïve patients but also to switch to biosimilars in those patients who have started therapy with reference biologics. At present, randomized and observational studies have demonstrated effectiveness and safety results in recommending a single switch between a reference product and a biosimilar, and vice versa. The purpose of this manuscript is to review the literature and discuss whether scientific evidence is enough to support multiple switches of biologics and biosimilars in IBD patients.

A Case of Aortoesophageal Fistula in Advanced Esophageal Cancer Treated with SB-Tube and TEVAR / 日本心臓血管外科学会雑誌

The patient is a 71-year-old man. After receiving chemoradiotherapy (CRTx) for an unresectable esophageal cancer, he developed sudden hematemesis during a follow-up examination. Subsequent imaging via contrast-enhanced computed tomography (CT) showed leakage of the contrast medium from the descending aorta into the esophagus. Consequently, an aortoesophageal fistula (AEF) was diagnosed and an emergency thoracic endovascular aortic stent graft repair (TEVAR) was scheduled. However, during the preparation for surgery, the patient vomited a large amount of blood and went into cardiopulmonary arrest. Following the administration of cardiopulmonary resuscitation, a Sengstaken-Blakemore tube (SB-tube) was inserted intranasally to control bleeding and TEVAR was performed to save his life. Although a gastrostomy was necessary after the surgery, the patient was transferred from the hospital on the 32nd day without any complications. Nonetheless, his general condition deteriorated as the cancer progressed and he died on the 103rd postoperative day. It is generally reported that the risk for esophageal perforation is 10-20% in CRTx for unresectable esophageal cancer. Although issues regarding the long-term prognosis of patients treated with TEVAR have been highlighted in recent years, there have also been reports of life-saving cases following its use; in this case, the patient was discharged home after SB-tube insertion and TEVAR with prompt treatment, resulting in his life being prolonged for an estimated 3 months.

Enhancing definitive hematopoiesis signals improves the efficiency of natural killer cell generation derived from human embryonic stem cells / 免疫学杂志

This study explores the effects of enhancing the definitive hematopoiesis(DH)signals during the differentiation of human embryonic stem cells(hESCs)into hematopoietic stem/progenitor cells on the generation efficiency and effector function of natural killer(NK)cells generated from hESCs(also known as hESC-NK cells).The hESC(H1)were transformed into embryoid bodies(Ebs)by centrifugation,and during the induction of K562,were used to analyze the efficiency of hematopoietic differentiation,the efficiency of NK cell generation from hESC,the in vitro effector functions,and the expression of effector function related surface receptors.Compared to the control group,the DH group had a significant increase in the number of arterial hematopoietic endothelial cells(CD34+DLL4+)and a significant decrease in primitive hematopoietic related cells(CD34-CD43+)on day 8 of hematopoietic differentiation(P<0.05).On day 28 of NK cell differentiation,the DH group demonstrated a significant increase in the number of NK cells(CD45+CD56+),while a slight increase in the expression of effector function-related molecules such as IFN-γ,Granzyme B,Perforin and CD107a without statistical significance.Furthermore,the activation receptors CD16a and CD69 were significantly increased,NKP46 was significantly decreased,the inhibitory receptor NKG2A was significantly increased,while CD96 was significantly decreased on hESC-NK cells of DH groups(P<0.05).Conclusively,enhancing the signals for definitive hematopoiesis during hESC differentiation into hematopoietic stem/progenitor cells significantly improves the yield of NK cells and the expression of CD16a without affecting their in vitro effector functions.Our study provides a new approach to improving the efficiency of hESC-NK cell or iPSC-NK cell generation.

Systematic biopsy combined with cognitive fusion targeted biopsy increases the detec-tion rate of clinically significant prostate cancer / 中国肿瘤临床

Objective:To investigate the ability of separate and combined biopsy methods to distinguish clinically significant prostate cancer(csPCa)from clinically insignificant prostate cancer(incsPCa),we assessed diagnostic positive rates for patients undergoing transperineal pro-state systematic biopsy(SB),cognitive fusion targeted biopsy(CF-TB),and combined biopsy(CB)(i.e.SB combined with CF-TB)under intra-venous anesthesia.Methods:We analyzed clinical data from 151 patients with prostate-specific antigen(PSA)≤50 ng/mL undergoing their first prostate biopsy in Cancer Hospital of Huanxing Chaoyang District Beijing and National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from January 2019 to November 2021.The 3.0 Tesla standard prostate multi-parametric magnetic resonance imaging(mpMRI)examinations found 161 lesions with prostate ima-ging reporting and data system(PI-RADS)scores≥3.With patients under intravenous anesthesia and indwelling catheter,2-4 needle CF-TB biopsies were performed using transperineal ultrasound guidance,followed by 12 needle SB.Patients who underwent SB,CF-TB,and CB were each analyzed by stratification for their respective csPCa and incsPCa detection rates,age,PSA,CF-TB needle count,PI-RADS score,and digital rectal examination results.Results:The median PSA value for all patients was 11.50(0.52-49.37 ng/mL).In total,161 lesions with PI-RADS score≥3 points were found.All 151 patients received 12 needles of SB,while 47,52,and 52 patients received 2,3,and 4 needles of CF-TB,respectively.The respective positivity rates of SB,CF-TB and CB in diagnosing csPCa were 54.3%(82/151),53.0%(80/151)and 58.9%(89/151).Statistical results indicate that the difference in positivity rate between CB and SB is significant(P=0.016)as is the difference between CB and CF-TB positivity rates(P=0.004).The respective positivity rates of SB,CF-TB,and CB in diagnosing incsPCa were 7.9%(12/151)、9.3%(14/151),and 11.3%(17/151).The positivity rate of CB was not significantly different than that of SB or CF-TB(all P>0.05).Stratification plane analysis with age,PSA value,number of CF-TB needles,PI-RADS score,and digital rectal examination results showed that the 2-needle CF-TB scheme was inferior to CB in diagnosing csPCa(P=0.031).There was no significant difference in the csPCa positivity rates of 3-needle and 4-needle CF-TB relative to CB.Conclusions:CB achieves a higher csPCa diagnosis rate without increasing de-tection of incsPCa under transperineal ultrasound guidance.CF-TB with 3-needles per lesion was highly effective in diagnosing csPCa.

Effect of SB431542 on retinal vascular endothelial cells under hypoxia / 中华眼底病杂志

Objective:To investigate the effect of Nodal protein on retinal neovascularization under hypoxia.Methods:In vivo animal experiment: 48 healthy C57BL/6J mice were randomly divided into normal group, oxygen-induced retinopathy (OIR) group, OIR+dimethyl sulfoxide (DMSO) group and OIR+SB431542 group, with 12 mice in each group. Retinal neovascularization was observed in mice at 17 days of age by retina flat mount. Counts exceeded the number of vascular endothelial nuclei in the retinal inner boundary membrane (ILM) by hematoxylin eosin staining. In vivo cell experiment: human retinal microvascular endothelial cells(hRMEC) were divided into normal group, hypoxia group, hypoxia+DMSO group and hypoxia +SB431542 group. The cell proliferation was detected by thiazolyl blue colorimetry (MTT). The effect of SB431542 on hRMEC lumen formation was detected by Matrigel three-dimensional in vitro molding method. Cell migration in hRMEC was detected by cell scratch assay. The Seahorse XFe96 Cell Energy Metabolism analyzer measured extracellular acidification rate (ECAR) of intracellular glycolysis, glycolysis reserve, and glycolysis capacity. One-way analysis of variance was used to compare groups.Results:In vivo animal experiment: compared with normal group, the neovascularization increased in OIR group ( t=41.621, P<0.001). Compared with OIR group, the number of vascular endothelial nuclei breaking through ILM in OIR+SB431542 group was significantly reduced, and the difference was statistically significant ( F=36.183, P<0.001). MTT test results showed that compared with normal group and hypoxia+SB431542 group, the cell proliferation of hypoxia group and hypoxia+DMSO group was significantly increased, and the difference was statistically significant ( F=39.316, P<0.01). The cell proliferation of hypoxia+SB431542 group was significantly lower than that of hypoxia+DMSO group, and the difference was statistically significant ( t=26.182, P<0.001). The number of intact lumen formation and migration cells in normal group, hypoxia group, hypoxia+DMSO group and hypoxia+SB431542 group were statistically significant ( F=34.513, 41.862; P<0.001, <0.01). Compared with the hypoxia+DMSO group, the number of intact lumen formation and migrating cells in the hypoxia+SB431542 group decreased significantly, and the differences were statistically significant ( t=44.723, 31.178; P<0.001,<0.01). The results of cell energy metabolism showed that compared with the hypoxia +DMSO group, the ECAR of intracellular glycolysis and glycolysis reserve in the hypoxia +SB431542 group was decreased, and the ECAR of glycolysis capacity was increased, with statistical significance ( t=26.175, 33.623, 37.276; P<0.05). Conclusion:SB431542 can inhibit the proliferation, migration and the ability to form lumens, reduce the level of glycolysis of hRMECs cells induced by hypoxia.

Activation of p38 MAPK and its effect on the expression of Bax and Bcl-2 after cerebral ischemia-reperfusion in hyperlipidemia rats / 解剖学报

Objective To detecte the expressions of phosphorylated p38 MAPK (p-p38 MAPK), Bax and Bcl-2 in the cerebral cortex of hyperlipidemia rats after cerebral ischemia-reperfusion (I/R) injury and the effect of SB203580 on the expressions of p-p38 MAPK, Bax and Bcl-2, to explore the effect of p38 MAPK activation on the expressions of Bax and Bcl-2 in hyperlipidemia cerebral I/R injury. Methods After the hyperlipidemia model was established, the rats were randomly divided into 3 groups: sham operation group, operation group (I/R) and SB203580 treatment group (SB+I/R), with 10 rats in each group. The focal cerebral I/R model in hyperlipemia rats was established with thread embolism of the left middle cerebral artery. The neurobehavioral score was used to observe the symptoms of neurobehavioral injury. The 2, 3, 5-triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction, and the TUNEL staining was used to observe apoptotic cells. The relative expression levels of p-p38 MAPK, Bax and Bcl-2 were analyzed by immunohistochemistry. Results Compared with the sham group, the infarct volume, apoptosis index and neurobehavioral score of rats in the I/R group increased significantly, and the expressions of p-p38 MAPK and Bax increased significantly, and the expression of Bcl-2 decreased significantly (P<0. 05). Compared with the I/R group, rats in the SB+I/R group had less brain damage, the infarct volume and the apoptosis index were significantly reduced, the expressions of p-p38 MAPK reduced significantly, Bax expression decreased while Bcl-2 expression increased. The differences were statistically significant (P<0. 05). Neurobehavioral scores were lower in SB+I/R group than in I/R group, but the difference was not statistically significant. Conclusion In the process of cerebral I/R injury in hyperlipidemiarats, activation of p38 MAPK can regulate the expression of Bax and Bcl-2.

The effect of inhibiting p38 MAPK on the expression of genes related to enamel development in mice / 口腔疾病防治

Objective@#To study the effect of p38 mitogen activated protein kinase (p38 MAPK) on the expression of genes related to enamel development in the enamel epithelium and to provide a basis for the study of the molecular mechanism of enamel development.@*Methods@#The p38 MAPK-specific inhibitor SB203580 dissolved in DMSO was added to the culture medium of mouse mandibular molar tooth germs in vitro as experiment group, and mouse mandibular molar tooth germs treated with the same amount of DMSO were used as control group. Western blot was used to detect the protein expression level of phosphorylated p38 (p-p38) in the enamel epithelium. Real-time PCR was used to detect the mRNA expression levels of runt-related transcription factor 2 (Runx2), osteoblast-specific transcription factor (Osx), ameloblast markers odontogenic ameloblast associated protein (ODAM), amelotin (AMTN), matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4) in the enamel epithelium. @*Results @# Western blot results showed that under the action of the inhibitor SB203580, the phosphorylation level of p38 MAPK in mouse enamel epithelium decreased, and the difference was statistically significant (P < 0.05). Real-time PCR results showed that the expression levels of the transcription factors Runx2 and Osx and the ameloblast markers ODAM, AMTN, MMP20, and KLK4 in the SB203580 group were lower than those in the control group, and the difference was statistically significant (P < 0.05).@*Conclusion@#The p38 MAPK signaling pathway can mediate enamel development by regulating the expression of the transcription factors Runx2 and Osx and the ameloblast markers ODAM, AMTN, MMP20 and KLK4 in the mouse enamel epithelium.

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective To investigate the effect and underlying mechanisms of p38 mitogenactivated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.Methods Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group,APILP group,and SB203580 treatment (SB) group.APILP model was induced by retrograde injection of 5％ sodium taurocholate into the biliary-pancreatic duct.SB203580 administration (10 mg/kg body weight,intraperitoneal injection) was performed 0.5 h before surgery.All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point.Animals were sacrificed at 12 h after the induction of APILP,then the blood and tissue samples were harvested.Serum levels of AMY and TNF-α were analyzed.Histopathological changes of maternal pancreas and fetal lung were observed and evaluated.The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence.The expression ofp-p38MAPK,p38MAPK,TNF-α and ICAM-1 was determined by Western blot.One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.Results The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7871.3±623.5) vs (1 915.3±452.3),(193.8±25.4) vs (107.0±±13.3),(P＜0.05)].Obvious pathological changes presented in matemal pancreas and fetal lung after the attack of APILP,and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56),(2.50±0.53) vs (0.88±0.64),(P＜0.05)].The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80),(53.38±8.30) vs (11.75±3.33);P＜0.05)].In addition,the expression and nuclear translocation were pervasive in fetal lungs in the APILP group.Furthermore,the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)],TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)],ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P＜0.05).However,with the pre-administration of SB203580,the pathological scores of matemal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P＜0.05),as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P＜0.05).The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P＜0.05) and fewer nuclear translocation was observed in the SB group.Interestingly,the expression levels of p-p38MAPK (0.2578±0.0170),TNF-α (0.3240±0.0326),ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P＜0.05).Conclusions P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury;SB203580 administration could significantly attenuate fetal lung injury induced by APILP,which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective@#To investigate the effect and underlying mechanisms of p38 mitogen-activated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.@*Methods@#Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group, APILP group, and SB203580 treatment (SB) group. APILP model was induced by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. SB203580 administration (10 mg/kg body weight, intraperitoneal injection) was performed 0.5 h before surgery. All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point. Animals were sacrificed at 12 h after the induction of APILP, then the blood and tissue samples were harvested. Serum levels of AMY and TNF-α were analyzed. Histopathological changes of maternal pancreas and fetal lung were observed and evaluated. The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence. The expression of p-p38MAPK, p38MAPK, TNF-α and ICAM-1 was determined by Western blot. One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.@*Results@#The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7 871.3±623.5) vs (1 915.3±452.3), (193.8±25.4) vs (107.0±13.3), (P<0.05)]. Obvious pathological changes presented in maternal pancreas and fetal lung after the attack of APILP, and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56), (2.50±0.53) vs (0.88±0.64), (P<0.05)]. The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80), (53.38±8.30) vs (11.75±3.33); P<0.05)]. In addition, the expression and nuclear translocation were pervasive in fetal lungs in the APILP group. Furthermore, the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)], TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)], ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P<0.05). However, with the pre-administration of SB203580, the pathological scores of maternal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P<0.05), as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P<0.05). The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P<0.05) and fewer nuclear translocation was observed in the SB group. Interestingly, the expression levels of p-p38MAPK (0.2578±0.0170), TNF-α (0.3240±0.0326), ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P<0.05).@*Conclusions@#P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury; SB203580 administration could significantly attenuate fetal lung injury induced by APILP, which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

Inhibition of the TGF-β/Smad3 signaling pathway by SB431542: A study of the intervention effect of SB431542 on silicotic fibrosis in rats / 中华劳动卫生职业病杂志

Objective@#To investigate the intervention effect of SB431542, which inhibits the TGF-β/Smad3 signaling pathway, on silicotic fibrosis in rats.@*Methods@#A total of 40 specific pathogen-free Sprague-Dawley rats were divided into normal saline control group, model group, SB431542 inhibitor group, and SB431542 inhibitor control group using a random number table, with 10 rats in each group. All rats except those in the normal saline control group were given non-exposed single intratracheal instillation of free silicon dioxide dust suspension 1 mL (50 mg/mL) ; the rats in the SB431542 inhibitor group were given intraperitoneal injection of SB431542 (5 mg/kg) on days 7 and 30 after dust exposure, those in the SB431542 inhibitor control group were given intraperitoneal injection of SB431542 cosolvent (5 mg/kg) on days 7 and 30 after dust exposure, and those in the normal saline control group were given intratracheal instillation of an equal volume of normal saline (5 mg/kg). On day 60 after dust exposure, the paraffin-embedded section of the right upper lobe of lung was collected for HE staining; the left upper lobe of lung was collected to measure the mRNA levels of fibronectin (FN) , collagen type I (COL-I) , and collagen type III (COL-III) by quantitative real-time PCR; the right inferior lobe of lung was collected to measure the protein levels of FN, COL-I, COL-III, phosphorylated Smad3 (p-Smad3) , and Smad3.@*Results@#Compared with the normal saline control group, the model group had nodules with various sizes in lung tissue, with rupture of some alveolar septa, emphysema changes, and pulmonary interstitial fibrosis, as well as significant increases in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 in lung tissue (P<0.05) . Compared with the SB431542 inhibitor control group, the SB431542 inhibitor group had a relatively complete structure of lung tissue without marked nodules and with a small amount of exudate in alveolar space and the lumen of bronchioles, as well as significant reductions in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 in lung tissue (P<0.05) . There were no significant differences in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 between the model group and the SB431542 inhibitor control group (P>0.05) .@*Conclusion@#SB431542 exerts an intervention effect on silicotic fibrosis by blocking the TGF-β/Smad3 signaling pathway and reducing the expression of the downstream fibrosis factors FN, COL-I, and COL-III.

The Application Methods of Mitogen-activated Protein Kinase Signal Pathway Inhibitors SP600125 and SB203580 in Long-term in Vivo Experiments / Métodos de aplicación de los inhibidores SP600125 y SB203580 de la vía de señalización de la proteína quinasa activada por mitógeno en experimentos in vivo a largo plazo

ABSTRACT Objective: To explore the application methods of mitogen-activated protein kinase signal pathway inhibitors SP600125 and SB203580 in long-term in vivo experiments. Methods: A total of 55 healthy New Zealand rabbits were randomly divided into blank control group, model control group, SP low dose group, SP high dose group, SP blank group, SB low dose group, SB high dose group, SB blank group, dimethyl sulfoxide (DMSO) control group, DMSO blank group, and positive control group. Since the first day of the experiment, each group was administered the corresponding treatment for four weeks continuously. Then, the myocardial c-Jun N-terminal kinase (JNK) and the total protein of p38, protein phosphorylation and its gene expression levels were detected. Results: After intravenous treatment with adriamycin, the myocardial phosphorylate-JNK (p-JNK) and phosphorylate-p38 (p-p38) levels in all groups were increased to varying degrees, of which the model control group increased the most significantly (p < 0.05). Compared with the model control group, the myocardial p-JNK and p-p38 increased more slowly in the SP low dose group, SP high dose group, SB low dose group, SB high dose group and positive control group (p < 0.05), of which the increase in the SP high dose group and the SB high dose group was the slowest (p < 0.05). After four weeks, the total protein and messenger ribonucleic acid of the myocardial JNK and p38 in all groups had no statistically significant difference (p > 0.05). Conclusion: The continuous intravenous injection of SP600125 and SB203580 for four weeks significantly reduced the protein phosphorylation levels of JNK and p38, which provides a practical avenue for the long-term study in vivo.

RESUMEN Objetivo: Explorar los métodos de aplicación de los inhibidores SP600125 y SB203580 de la vía de señalización de la proteína quinasa activada por mitógeno en experimentos in vivo a largo plazo. Métodos: Un total de 55 conejos sanos de Nueva Zelandia fueron divididos aleatoriamente en los grupos siguientes: grupo de control en blanco, grupo de control modelo, grupo de dosis baja SP, grupo de dosis alta SP, grupo en blanco SP, grupo de dosis baja SB, grupo de dosis alta SB, grupo en blanco SB, grupo de control dimetilsulfóxido (DMSO), grupo en blanco DMSO, y grupo de control positivo. Desde el primer día del experimento, a cada grupo se le administró el tratamiento correspondiente por cuatro semanas continuas. Entonces, se detectaron la quinasa c-Jun N-terminal (JNK) miocárdica y la proteína p38 total, así como la fosforilación proteica y sus niveles de expresión génica. Resultados: Después del tratamiento intravenoso con adriamicina, los niveles de fosfo-JNK (p-JNK) y fosfo-p38 (p-p38) del miocardio aumentaron en todos los grupos en diversos grados, siendo el aumento del grupo de control modelo el más significativo (p < 0.05). En comparación con el grupo de control modelo, p-JNK y p-p38 miocárdicos aumentaron más lentamente en el grupo de dosis baja SP, el grupo de dosis alta SP, el grupo de dosis baja SB, el grupo de dosis alta SB, y el grupo de control positivo (p < 0.05). De estos, el aumento en el grupo de dosis alta SP y el grupo de dosis alta SB fue el más lento (p < 0.05). Después de cuatro semanas, la proteína total y el ácido ribonucleico mensajero de JNK y p38 miocárdicos en todos los grupos, no tuvieron diferencias significativas (p > 0.05). Conclusión: La inyección intravenosa continua de SP600125 y SB203580 durante cuatro semanas redujo significativamente los niveles de fosforilación proteica de JNK y p38, lo que proporciona una vía práctica para el estudio a largo plazo in vivo.

Application of Flush Knife and SB Knife in Peroral Endoscopic Myotomy for Treatment of Achalasia / 胃肠病学

Background:Peroral endoscopic myotomy (POEM) has been widely used in treatment of achalasia,and the efficacy is satisfactory.However,POEM is associated with high level of technical difficulty and high incidence of complications.Aims:To investigate the efficacy and safety of Flush knife and SB knife in POEM for treatment of achalasia.Methods:A total of 111 achalasia patients who had undergone POEM from April 2013 to April 2017 at Renmin Hospital of Wuhan University were enrolled,and were divided into Flush knife group,SB knife group and Dual knife group.Procedure-related parameters,complications,and follow-up data were compared among the three groups.Results:All the 111 patients underwent POEM successfully.The mean procedure time,mean frequency of hemostasis and mean frequency of device exchange were significant different among Flush knife group,SB knife group and Dual knife group (P all ＜ 0.05).Further comparisons showed that the above-mentioned procedure-related indices were significantly lower in Flush knife group and SB knife group than in Dual knife group (P all ＜ 0.05).The incidence of complications was significant different among the three groups (P =0.005).Further comparisons showed that incidence of complications was significantly lower in SB knife group than in Dual knife group (P =0.011),however,no significant difference was found between Flush knife group and Dual knife group (P =0.056).No significant difference in surgery success rate was found among the three groups (P ＞0.05).Conclusions:Flush knife and SB knife in POEM can shorten the procedure time and achieve similar success rate when compared with conventional Dual knife.

Expression and clinical significance of B7-H3 and IL-21 in serum of patients with HBV associated hepatocellular carcinoma / 中国免疫学杂志

Objective:To investigate the expression and clinical significance of B7-H3 and IL-21 in serum of patients with HBV-related primary liver cancer.Methods: Gathering 121 cases of HBV-related patients,50 cases of primary hepatic carcinoma of them were considered as hepatic carcinoma group,71 cases of benign group including 12 cases with acute hepatitis,21 cases of chronic moderate to severe hepatitis,20 cases of compensatory phase cirrhosis,18 cases of decompensated cirrhosis and 20 cases of healthy persons in the same period as normal control.The content of serum B7-H3 and IL-21 were detected by ELISA.HBV DNA quantitative results were analyzed by Quantitative Real-time PCR.Results: The levels of B7-H3 and IL-21 in patients with primary hepatic carcinoma were (207.60±57.16)ng/ml and(2 357.28±805.01)pg/ml,respectively,which were significantly higher than those of the normal control subjects(P<0.001).Comparison with the normal control subjects,the content of B7-H3 and IL-21 in serum of patients with different clinical types in the benign group increased significantly(P<0.001).B7-H3 and IL-21 were positively associated with each other in serum of patients with HBV-related primary liver cancer.The expression of sB7-H3 was not significantly correlated with the degree of HBV DNA replication.The expression of IL-21 was correlated with HBV DNA replication in patients with HBV associated hepatocellular carcinoma,but was not significantly correlated with the degree of HBV DNA replication.Conclusion: HBV-related primary hepatic carcinoma express sB7-H3 and IL-21 with high level.The continuous high expression of sB7-H3 and IL-21 in the body may be related to the development and prognosis of the patients.

FlaA gene deletion of LM90 SB2 inducing sheep encephalitis and the influence on virulence / 中国人兽共患病学报

The flagellin of Listeria monocytogenes is encoded by flaA gene;there is no detail report about the influence of flaA gene on the virulence of LM90 SB2.FlaA gene-deleted strain was constructed successfully with recombination technology.The influence of FlaA on LM90 SB2 virulence was evaluated by motility,BF formation,LD50,etc.Results showed that the colony morphology did not change,gene-deleted strain still had good genetic stability,but its growth was slow and the motility was decreased in the environment at 25 ℃,the morphological structure of the mutant BF was looser and incomplete,LD50 was increased from 4.27 × 106 cfu to 1.62 × 107 cfu.Results indicated that the flaA gene affected the flagellar formation of LM90 SB2 significantly,the ability of the BF formation and the virulence of the flaA deleted strain were decreased obviously.

Mucosal Changes in the Small Intestines in Portal Hypertension: First Study Using the Pillcam SB3 Capsule Endoscopy System

BACKGROUND/AIMS: To evaluate patients with portal hypertension (PH) of varied etiologies for portal hypertensive enteropathy (PHE) using the PillCam SB3 capsule endoscopy (CE) system. METHODS: Consecutive patients with PH presenting with unexplained anemia and/or occult gastrointestinal bleeding were evaluated using the PillCam SB3 CE system. Abnormal findings were categorized as vascular or non-vascular. The patients with ongoing bleeding caused by PHE were treated. The correlation of the CE scores of PHE with the clinical, laboratory, and endoscopic features was determined. RESULTS: Of the 43 patients included in the study, 41 (95.3%) showed PHE findings. These included varices (67.4%), red spots (60.5%), erythema (44.2%), villous edema (46.5%), telangiectasia (16.3%), and polyps (16.3%). The CE scores varied from 0 to 8 (mean±standard deviation, 4.09±1.8). Five patients (11.6%) showed evidence of ongoing or recent bleeding due to PHE. Three of these five patients underwent endotherapy, and one patient underwent radiological coil placement. CONCLUSIONS: The PillCam SB3 CE system revealed a high prevalence of PHE in the patients with PH. Using this system, evidence of bleeding due to PHE was found in a small but definite proportion of the patients.

Effects of SB203580 on biological functions of human extravillous trophoblast cells under oxidative stress / 上海交通大学学报（医学版）

Objective · To investigate the effects of a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 on biological function changes of human extravillous trophoblast cells induced by hypoxia/re-oxygenation (H/R). Methods · In-vitro cultured early pregnancy villus explants and human extravillous trophoblast cell line HTR8/SVneo were assigned to 4 groups according to different interventions, i.e. control group, SB203580 group (p38 MAPK inhibition), H/R group (simulation of preeclampsia by the oxidative stress model), and SB203580+H/R group. The effects of SB203580 on biological functions of human extravillous trophoblast cells under oxidative stress in early pregnancy villus explants were observed. Protein expression and phosphorylation of p38 MAPK in HTR8/SVneo cells were measured with Western blotting. Cell migration and invasion were observed with Transwell migration and Matrigel invasion assay, respectively. Gelatin zymography was used to measure the activity of matrix metalloproteinase (MMP) -2/9 in supernatant. ELISA was used to detect the levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). Results · SB203580 could promote the exogenous migration of human extravillous trophoblast cells in early pregnancy villus explants under oxidative stress. H/R could decrease the migration and invasion of HTR8/SVneo cells , and increase the phosphorylation level of p38 MAPK in HTR8/SVneo cells and the secretion of sFlt-1 and sEng. SB203580 could increase the activity of MMP2/9 in supernatant and cell migration and invasion, decrease the phosphorylation level of p38 MAPK in HTR8/SVneo cells under oxidative stress and the secretion of sFlt-1 and sEng. Conclusion · SB203580 can protect biological functions of human extravillous trophobalst cells under oxidative stress.

Effect of P38MAPK pathway on autophagy in rat hippocampus following cerebral ischemic postcoditioning / 西安交通大学学报(医学版)

Objective To explore the mechanism of ischemic postconditioning in relieving cerebral ischemia reperfusion (IR) by regulating autophagy through P38MAPK pathway.Methods Cerebral ischemia reperfusion model was established by using modified Pulsinelli four-vessel occlusion (4-VO).Totally 128 male SD rats were divided into 4 groups randomly:control group (sham),cerebral ischemia reperfusion model group (CIR),cerebral ischemic postconditioning group (CIP),and cerebral ischemic postconditioning + P38MAPK inhibitor group (SB203580 group).Each group was subdivided into four time points:6 h,24 h,48 h,and 72 h.The morphological changes of the hippocampus CA1 area neurons at each time point and the number of surviving nerve cells were detected with HE staining.The expression of the hippocampus CA1 area phosphorylated P38MAPK and the autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with immunohistochemistry.The protein content of the hippocampus phosphorylated P38MAPK and autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with Western blotting.Results Compared with those in sham group,the damage of rats' hippocampal neuron structure and the survival rate of neurons at each time point decreased in CIR group,the expressions of p-P38MAPK,LC3-Ⅱ and Beclin-1 increased.Compared with those in CIR group,in CIP and SB203580 groups the structure of rats hippocampal neurons was improved,the survival rate of neurons increased,the expression of p-P38MAPK decreased and the expressions of LC3-Ⅱ and Beclin-1 increased at each time point.Compared with CIP group,SB203580 grouphad improved structure of rats' hippocampal neurons,increased survival rate of neurons,decreased expression of p-P38MAPK,and increased expressions of LC3-Ⅱ and Beclin-1 at each time point.Conclusion Cerebral ischemic postconditioning through inhibiting P38MAPK pathway can regulate autophagy and exert its nerve-protective effect.

Agreement between international classification of disease (ICD) and cause of death and associated conditions (CODAC) for the ascertainment of cause of stillbirth (SB) in the rural areas of north India.

International Classification of Diseases-10 th version (ICD-10) has been used to ascertain the cause of death but its use for stillbirths (SBs) is limited. Cause of Death and Associated Conditions (CODAC) as a detailed system expected to provide the exact cause of SB, so a community-based study was planned to study the level of agreement between ICD-10 and CODAC for ascertaining the cause of SB. A verbal autopsy (VA) tool was used to collect the information and then the cause of each SB was assigned using ICD-10 and CODAC separately. Each tool was used for 87 SBs and found that prolonged singleton labor, maternal pregnancy induced hypertension (PIH), and central nervous system (CNS) related congenital malformations were considered the top three causes. There was a significant agreement between ICD-10 and CODAC but the latter offers a scope to delineate the causes more precisely due to its hierarchal nature.

Expression and clinical signiifcance of sB7-H3 and cytokines in the bronchoalveolar lavage lfuid in children with refractory Mycoplasma pneumoniae pneumonia / 临床儿科杂志

Objective To explore the level of expression, clinical signiifcance of sB 7-H 3 in the bronchoalveolar lavage lfuid (BALF) of refractory Mycoplasma pneumoniae (MP) pneumonia (RMPP) in children and the relationship between sB7-H3 and various cytokines. Methods The BALF of forty-three hospitalized children with RMPP (RMPP group) were collected for the diagnosis and treatment. Thirteen cases were lavaged only once and the other thirty cases had collected the BALF twice. The BALF of iffteen hospitalized children with bronchial foreign body were collected as control group. The expression levels of sB 7-H 3 , IL-1β, IL-2 and IL-36 in the BALF were detected by enzyme-linked immunosorbent assay. The expression levels of sB 7-H 3 , IL-1β, IL-2 and IL-36 in the BALF at the acute phase were compared with control group and the group after treatment. Analyzed the correlation between the level of sB 7-H 3 and IL-1β, IL-2 , IL-36 in the BALF of RMPP children at acute stage. Results The levels of sB 7-H 3 , IL-1β and IL-36 in the BALF of the ifrst lavage group were higher than those of single lavage group and control group (all P0 . 05 ). The levels of sB 7-H 3 had positive correlation with the levels of IL-1β, IL-2 and IL-36 (all P<0 . 001 ). Conclusions sB 7-H 3 may control the secretion of IL-1β, IL-2 and IL-36 , and participate in immune response and lung injury after MP infection, which may lead to occurrence and development of RMPP.