ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective:To explore the clinical utility of bronchoscopy and transbronchial cryotherapy in children with tracheobronchial tuberculosis (TBTB).Methods:Retrospective study was conducted to collect the clinical data of 10 hospitalized children who underwent bronchoscopy and were diagnosed as TBTB and in the Department of Pediatrics of Peking University First Hospital and the Department of Pediatric Respiratory Medicine of the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University from January 2011 to October 2019. The clinical characteristics of TBTB in children, and the efficacy and safety of bronchoscopy and transbronchial cryotherapy were summarized through descriptive analysis.Results:The onset age of 10 children (6 males and 4 females) ranged from 1-14 years. The clinical manifestations included fever (8/10), cough (7/10) and hemoptysis (2/10). Purified protein derivative test and interferon-γ release assay were performed in 9 and 10 patients respectively, the results were all positive. Chest CT examination was performed in all patients, and 8 patients had hilar and mediastinal lymphadenopathy. All patients underwent pediatric bronchoscopy in time, in 9 patients bronchus was found to be blocked in varying degrees by granulation tissue and caseous necrosis and in the remaining patient, obvious congestion and edema in bronchial mucosa. The bronchoscopic manifestations included 8 cases of lymph node fistula type, 1 case of granulation proliferative type and 1 case of inflammatory infiltration type. Pathological biopsies were performed in 7 cases, the findings were consistent with the pathological characteristics of tuberculosis. Nine patients were treated by pediatric bronchoscopic intervention, with 8 transbronchial cryotherapy by flexible bronchoscopy, and among them, 2 patients were treated by simultaneous rigid bronchoscopy. After 1-3 times of transbronchial cryotherapy, the blocked bronchial lumina in 8 cases were all recanalized, and the curative effect was significant without any serious complications.Conclusions:Bronchoscopy plays an important role in the diagnosis of TBTB in children and is helpful for its classification. Also, transbronchial cryotherapy has good efficacy and safety for TBTB in children, especially for the granuloproliferative type or lymph node fistula type.

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Objective The aim of this study was to establish a PM2.5air pollution-induced mouse model of pulmo-nary inflammation and investigate its pathogenetic mechanism. Methods 150 specific pathogen-free BALB/c mice were subjected to intratracheal instillation of 2.5,5,or 10 mg/kg PM2.5suspension to construct airborne inflammation models. The blank group and saline group were taken as a control group. Mice were euthanized after 3rd,7th,21st,35th and 49th days to assess the pathological changes in lung tissues using HE staining and ELISA. Results The success rate of tracheal instillation was 96%. With the time prolongation and increasing doses of intratracheal PM2.5instillation,the histopathologi-cal scores of lung tissue increased gradually,showing alveolar macrophages with engulfed particles and lymphocyte accumu-lation in bronchiole and widened inter-alveolar space. The levels of BALF IL-6 and TNF-α of lung tissue homogenate were significantly increased in the high dose PM2.5(10 mg/kg)group, compared with the control groups. Conclusions A mouse model of PM2.5air pollution-induced lung inflammation is successfully established by intratracheal instillation of PM2.5suspension.This method is proved to be simple,safe and reliable,and is useful for further study of air pollution-in-duced and other inflammatory mechanisms.

Objective To investigate the clinical features,pathogenic distribution and drug susceptibility of patients with infective endocarditis (IE).Methods Clinical data of IE patients were collected,who were admitted to Capital Medical University Affiliated Beijing Anzhen Hospital from January 2012 to March 2015.Results Three hundred and three IE patients were enrolled with age of (43 ± 16)years old.Fever (85.5％)and cardiac murmur (62.4％)were the most common clinical presentations.Congenital heart diseases was the leading underlying diseases in IE patients.Non rheumatic valve diseases (13.5％) followed.Vegetations were found in 90.4％ (274/303) patients.Streptococcus which accounted for 44.2％ was the major pathogen of IE.Staphylococcus (28.9％) was the second common pathogen.Gramnegative bacteria were diversified in categories.Gram-positive cocci were consistently sensitive to vancomycin and linezolid.Conclusions Congenital heart disease is the main underlying disease related to IE.Streptococcus is still the primary pathogen.Gram-positive cocci keep good sensitivity to vancomycin and linezolid.

Objective To investigate the effect of aging on the sleep apneas syndrome in Sprague-Dawley (SD) rats.Methods 18 male SD rats in a SPF grade were divided into three groups:young (3-month-old rats,n=6),middle-aged(12-14-month-old rats,n=6) and old group (18-20-month-old rats,n=6).The rats were implanted with EEG and ECG electrodes and underwent sleep monitoring.Results During non-rapid eye movement (NREM),the spontaneous apnea index (SPAI) in young,middle-aged and old groups were increased with aging [0.41 (0.00-1.14)times/h,0.76(0.00-6.28)times/h,2.13(1.44-3.87)times/h respectively,(x2=8.801,P=0.012)].There were significant differences in the average time of post sigh apnea in NREM between the three groups [(3.51±0.18)sec vs.(3.84±0.57)sec vs.(4.36±0.57) sec,F=4.729,P=0.026].SPAI in NREM and the average time of post-sigh apnea in rapid eye movement (REM) as well as NREM showed an increase trend with aging,but there was no significant difference between groups (both P ＞0.05).Conclusions The apnea index,total time of sleep apneas and the average time of postsigh apnea are increased with aging,which is similar to that in human.

BACKGROUNDRecent studies showed the central Na+/H+ exchanger type 3 (NHE3) has a close relationship with ventilation control. The objective of the study is to investigate the role of NHE3 in sleep apnea in Sprague-Dawley (SD) rats.

METHODSA sleep study was performed on 20 male SD rats to analyze the correlation between the sleep apneic events and total NHE3 protein content and inactive NHE3(pS552) in the brainstem measured by Western blotting. Another 20 adult male SD rats received 3 days of sleep and respiration monitoring for 6 hours a day, with adaption on the first day, 0.5% DMSO microinjection into the fourth ventricle on the second day, and AVE0657 (specific inhibitor of NHE3) microinjection on the third day. Rats were divided into two groups with injection of 5 µmol/L or 8 µmol/L AVE0657 before the sleep study. The effects of AVE0657 on sleep apnea and sleep structure of rats were analyzed through self-control.

RESULTSThe total post-sigh apnea index (TPSAI) and post-sigh apnea index in non-rapid eye movement (NREM) sleep (NPSAI) and total apnea index (AI) in NREM sleep (NAI) were negatively correlated with NHE3(pS552) protein contents in the brainstem (r = -0.534, -0.547 and -0.505, respectively, P < 0.05). The spontaneous apnea index in REM sleep (RSPAI) was positively correlated with the level of NHE3(pS552) protein expression in the brainstem (r = 0.556, P < 0.05). However, the sleep AI had no relationship with total NHE3 protein. Compared with the blank control and microinjection of 0.5% DMSO, 5 µmol/L AVE0657 significantly reduced the total AI and NPSAI (both P < 0.05) without a significant effect on sleep architecture. In contrast to blank control and microinjection of 0.5% DMSO, injection of 8 µmol/L AVE0657 significantly reduced the AI and PSAI in NREM and REM sleep (all P < 0.05).

CONCLUSIONSThe severity of sleep apnea was negatively correlated with central inactive NHE3. A specific inhibitor of NHE3 decreased the sleep AI. Thus, our results indicate that central NHE3 might be a molecular target for sleep apnea treatment, whose inhibitors may be potential therapeutic drugs for sleep apnea.

Animals ; Male ; Rats ; Rats, Sprague-Dawley ; Sleep Apnea Syndromes ; metabolism ; physiopathology ; Sleep, REM ; physiology ; Sodium-Hydrogen Exchanger 3 ; Sodium-Hydrogen Exchangers ; antagonists & inhibitors ; metabolism

BACKGROUNDVery recent studies revealed that obstructive sleep apnoea (OSA) is a contributor of the increased incidence and mortality of cancer in humans, but mechanisms of how OSA promotes tumorigenesis remains largely unknown. We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.

METHODSFirst, Sprague-Dawley (SD) male rats (12 weeks old) were subjected to different hypoxia exposures: intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air. The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour. Then routine blood tests were performed and the levels of brain derived neurotrophic factor (BDNF) and miR-34a were examined.

RESULTSIn contrast to intermittent hypoxia with hypercapnia, both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments. Compared to normoxia, intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and, miR-34a in the lower brainstem, while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.

CONCLUSIONSThe exposure of intermittent hypoxia with or without hypercapnia, mimicking the situations in severe OSA patients, was associated with, or even promoted tumorigenesis.

Animals ; Brain Stem ; metabolism ; Brain-Derived Neurotrophic Factor ; blood ; metabolism ; Cell Transformation, Neoplastic ; Hypercapnia ; blood ; complications ; Hypoxia ; blood ; complications ; Male ; MicroRNAs ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction