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OBJECTIVE: To evaluate the protective effects of Chang'an decoction (, CAD) on colitis, and investigate the potential mechanisms underlying these effects from the perspectives of endoplasmic reticulum (ER) stress induced by mitofusin 2 (MFN2). METHODS: The composition of CAD was identified by liquid chromatography-mass spectrometry technology. A mice model of dextran sulfate sodium (DSS) induced colitis was established and therapeutic effects of CAD were determined by detecting body weight, disease activity index, colon length and histopathological changes. Then, the expression levels of MFN2, ER stress markers and Nucleotide-binding domain and leucine-rich repeat protein3 (NLRP3) relevant proteins were detected by polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence staining. Subsequently, knockdown and overexpression cell model were constructed to further investigate the underlying mechanism of MFN2 mediating ER stress and energy metabolism by PCR, Western blot, electron microscopy and reactive oxygen species (ROS) staining. Finally, inflammatory indicator and tight junction proteins were measured by PCR and immunofluorescence staining to evaluate the protective effects of CAD. RESULTS: Results showed that the indispensable regulatory role of MFN2 in mediating ER stress and mitochondrial damage was involved in the protective effects of CAD on colitis in mice fed with DSS. Network pharmacology analysis also revealed CAD may play a protective effect on colitis by affecting mitochondrial function. In addition, our data also suggested a causative role for MFN2 in the development of inflammatory responses and energy metabolic alterations by constructing a knockdown and overexpression cell model whereby alter proper ER-mitochondria interaction in Caco-2 cells. Furthermore, relative expression analyses of ER stress markers and NLRP3 inflammasome showed the onset of ER stress and activation of NLRP3 inflammasome, which is consistent with the above findings. In contrast, intervention of CAD could improve the mucosal barrier integrity and colonic inflammatory response effectively through inhibiting ER stress response mediated by MFN2. CONCLUSION: CAD could alleviate ER stress by regulating MFN2 to exert therapeutic effects on DSS-induced colitis, which might provide an effective natural therapeutic approach for the treatment of ulcerative colitis.
Assuntos
Colite , Medicamentos de Ervas Chinesas , Estresse do Retículo Endoplasmático , GTP Fosfo-Hidrolases , Animais , Masculino , Camundongos , Colite/tratamento farmacológico , Colite/metabolismo , Colite/genética , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , GTP Fosfo-Hidrolases/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The clinical data of two children with refractory/relapsed acute B-lymphoblastic leukemia (ALL-B)treated with Blinatumomab in Department of Pediatrics, Peking University People′s Hospital from September 2019 to May 2021 were retrospectively analyzed.After 1 course of Blinatumomab infusion, both children achieved complete hematologic remission.During the infusion process, grade 2 cytokine release syndrome (CRS) was observed, and there were no fatal adverse reactions.One case underwent bridging hematopoietic stem cell transplantation after remission and achieves disease-free survival currently.The other case is still alive after subsequent consolidation chemotherapy.As a novel bispecific antibody, Blinatumomab has a good response rate to refractory/relapsed ALL-B and induces fewer adverse events, so it can be used as a candidate immunotherapy for patients with high tumor burden.
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In view of the pain points and difficulties in the current stroke service system, the Internet-plus model is merged into the stroke service process for exploration and practice. Mobile Internet technology bridged the process before and after the patient arrives at the hospital, thus extending the green path. This green path is under refined management by mobile applications and 2-dimensional bar code technologies, supporting sustained improvement of data-driven clinical quality. Benefited by"Internet-plus"stroke service management, the efficiency and key performance indicator of the stroke center are significantly elevated.
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OBJECTIVE:To strengthen the supervision of clinical antibiotics use through establishing electronic consultation system. METHODS:Based on hospital information system(HIS)and antibiotic management system,consultation system for anti-biotics of special use(ASU)was established,and the effects of the system after used(Jan. 2014)were also evaluated. RESULTS:Real-time consultation of ASU medical orders and related consultation results inquiry and statistics could be achieved through de-signing ASU consultation application form,establishing consultation experts and confirming their working content,adding statistics function,etc. The consultation have been finished 8275 times from 2014 to 2015. The inspection rate for pathogenic microbes in ASU patients rose from 78.68% in 2013 to 83.90% in 2015. CONCLUSIONS:The establishment and application of ASU consulta-tion system can improve consultation efficiency and quality,so as to promote rational use of antibiotics in the clinic.
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Objective To investigate the correlation between hypoglycemia and brain injury of newborns.Methods Medical records and follow-up data of 110 newborns with hypoglycemia (blood glucose level≤2.2 mmol/L) who admitted into neonatal department of Peking University First Hospital from December 2006 to December 2009 were studied.All patients were divided into 3 groups:no brain injury group,mild and severe brain injury group according to their clinical manifestation,cerebral radiological characteristics and cerebral functional tests.By using receiver operating characteristic (ROC) curve and x2 test,the potential optimal blood glucose level and duration of hypoglycemia for predicting brain injury were confirmed.Multivariate Logistic regression was taken to determine independent predictors for brain injury.The analyzed factors included gender,preterm/small for gestational age,hyperbillirubinemia,fetal distress,asphyxia,infection,seizures and maternal hypertensive disorder complicating pregnancy and hyperglycemia.Results Among the 110 hypoglycemia newborns,33 (30.0%) infants suffered from brain injury,of which 23 were mild and 10 were severe.Blood glucose ≤1.7 mmol/L had high specificity (73%) and sensitivity (60%)for predicting brain injury.When blood glucose≤ 1.7 mmol/L,the incidence of brain injury and severe brain injury was 43.6% (24/55) and 18.2% (10/55),which was higher than those [16.4%(9/55) and 0.0% (0/55)] of patients whose glucose level >1.7 mmol/L(x2 =9.74 and 11.00,P<0.01 respectively).Blood glucose ≤ 1.2 mmol/L had high specificity (100%) and sensitivity (81%) for predicting severe brain injury.When blood glucose ≤1.2 mmol/L,the incidence of severe brain injury was higher than that of the patients whose glucose level was higher than 1.2 mmol/L [34.5% (10/29) vs 0.0% (0/81),x2 =30.72,P<0.01].Duration of hypoglycemia ≥12 h had specificity (100%) and sensitivity (36 %) for predicting brain injury.When duration of hypoglycemia <12 h,the incidence of brain injury was lower than that of the patients whose duration of hypoglycemia≥12 h [21.4% (21/98) vs 6/6,x2 =27.69,P<0.01].Multivariate Logistic regression showed that fetal distress (OR=4.69,95%CI:1.47-14.97,P=0.009),glucose level≤1.2 mmol/L (OR =5.16,95%CI:1.56-17.03,P=0.007),duration of hypoglycemia≥12 h (OR=8 885 220 297.12,95%CI:0.00-∞,P =0.000) and maternal hyperglycemia (OR =3.34,95%CI:1.01-11.02,P=0.048) were independent risk factors for neonatal brain injury.Conclusions Low blood glucose level and prolonged hypoglycemia might induce injury of neurol system.Fetal distress and maternal hyperglycemia might increase the incidence of brain injury in newborns with hypoglycemia.