Objective To observe effect of intra-and post-operative mild hypothermia using an ice blanket on patients with severe traumatic brain injury (sTBI).Methods Twenty sTBI patients with Glasgow Coma Scale (GCS) of 3-8 points were included and were assigned to either ice bag cooling (Bag group) or ice blanket cooling (Blanket group) (n =10 each) according to random number table.Patients in Bag group had temperature reduction by placing ice bag over great vessels,whereas in Blanket group an ice blanket (temperature was set as the nasopharyngeal temperature of 33℃-34℃) was employed to have temperature reduction.Hypothermia therapy in the two group groups was initiated from the beginning of operation and continued for 48 hours after operation.Intracranial pressure,cerebral perfusion pressure (CPP) and GCS in both groups were recorded respectively at 10 minutes before operation (T0) and at 8,12,24,48 and 72 hours after operation (T1,T2,T3,T4 and T5).Venous blood of the two groups was harvested to assay the serum concentration of neuronspecific enolase (NSE),myelin basic protein (MBP)and S-100β at T0,T3,T4,-Ts and at 96 hours after operation (T6) by ELISA method.Glasgow Outcome Scale (GOS) was evaluated at postoperative six months.Results In Bag group,body temperature (T1-T5) of the patients had no significant decrease (P ＞ 0.05) and NSE (T3-T6),S-100β (T3-T6) and MBP (T4-T6) were increased (P ＜ 0.05 or 0.01) when compared with those in T0 ; intracranial pressure (T2-T5) was increased (P ＜ 0.05) and CPP (T3-T5) was lowered (P ＜ 0.05) when compared with those in T1.In Blanket group,body temperature (T1-T6) of the patients presented was decreased significantly (P ＜ 0.01) and NSE (T3-T6),MBP (T5-T6) and S-100β (T4-T6) were increased (P ＜ 0.05 or 0.01) when compared those in T0 ; intracranial pressure (T2-T6) was increased (P ＜ 0.05) and CPP had no significant changes (P ＞0.05) when compared with those in T1.By contrast with those in the same time points in Bag group,lower body temperature (T1-T5) (P ＜ 0.001),lower intracranial pressure (T2-T5),higher CPP (T3-T5) as well as lower NSE (T4-T6),MBP (T4-T6) and S-100β(T6)were observed in Blanket group (P ＜0.05 or 0.01).Changes of GCS and GOS in the two groups were no significance (P ＞0.05).Conclusion Intraoperative and postoperative mild hypothermia therapy using an ice blanket may alleviate the degree of brain injury in sTBI patients.

Objective To investigate the effects of remifentanil in painless bronchoscopic examination of elderly panents.Methods One hundred and twenty elderly patients undergoing painless bronchoscopic examination were randomly divided into 4 groups (n=30),the group A was administered with propofol and the groups B,C and D were administered with propofol and remifentanil(remifentanil dose:0.05 μg · kg-1 · min-1 in the group B,0.10μg · kg-1 · min-1 in the group C and 0.15 μg · kg-1 · min-1 in the group D).The body moving response,hemodynamic changes,propofol dose,examination time,wake-up time,departure time and adverse reactions in each group were observed during the examination process.Results During the examination process,the body moving response and bucking of the group A were significantly higher than those of the other three groups(P＜0.05);in hemodynamics,the group A fluctuated greatly,while the group B,C and D were relatively stable,but the incidence rate of hypotension,bradycardia and transient respiratory depressionof the group D were higher than those of the other three groups(P＜0.05);propofol dose of the group A was significantly higher than that of the other three groups (P＜0.05)and the group B was higher than the group C and D(P＜0.05).In wake-up time and departure time,the groups B,C,D were significantly better than the group A(P＜0.05),while the group C and D were better than the group B(P＜0.05).Conclusion Remifentanil can be used in painless bronchoscopic examination for elderly patients,and the effect is better by using propofol combined with remifentanil at a dose of 0.1 μg · kg-1 · min-1.

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p< 0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p< 0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.
Animals ; Apoptosis ; Blotting, Western ; Humans ; In Situ Nick-End Labeling ; Ischemia ; JNK Mitogen-Activated Protein Kinases ; Male ; Myocardial Ischemia* ; Myocytes, Cardiac ; Naloxone* ; Rats* ; Rats, Sprague-Dawley ; Reperfusion Injury* ; Reperfusion*

Microspheres are a novel drug delivery system,which provides a new approach for cancer therapy.Anti-cancer agents loaded in microspheres can be released in a controlled and sustained pattern,thereby enhancing the therapeutic efficacy and reducing the side effects and toxicity.The preparation methods for drug delivery microspheres include solvent evaporation,phase separation,spray drying,and microfluidic technology,each of these have advantages and limitations.Based on the preparation materials,drug delivery microspheres can be categorized into natural polymer microspheres,synthetic polymer microspheres and bioceramic microspheres.Natural polymer micro-spheres have good biocompatibility and degradability;synthetic polymer microspheres exhibit superior mechanical properties;bioceramic microspheres have good biocompatibility and specific biological functions,which are widely used in bone tissue engineering.Drug delivery microspheres are used for cancer treatment in various modalities,including photothermal therapy,photodynamic therapy,radioembolization,and immunotherapy,as well as chemotherapy.This article reviews the recent progress of microspheres as nano drug delivery system in cancer treatment to provide a reference for further clinical and translation research.

Objective: To explore clinical features and the effect of treatment of neuromyelitis optica spectrum disorders (NMOSD) in childhood. Methods: Children who were hospitalized in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2018 and meeting diagnostic criteria of NMOSD proposed by the International Panel for NMOSD Diagnosis in 2015 were summarized and followed up. The basic information, symptoms of each attack, locations and patterns of new lesions, features of cerebrospinal fluid, serologic markers, treatments and outcomes in these patients were analyzed. Thirty-three children were included in the study, with 13 males and 20 females. The median age of onset was 6.83 (4.25, 8.75) years. Compared aquaporin-4 immunoglobulin G (AQP4-IgG) associated NMOSD with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated NMOSD. Mann-Whitney U test was used for continuous variables and Fisher test for categorical variables in comparison between AQP4-IgG and MOG-IgG associated NMOSD. Wilcoxon test was used for annualized relapse rate (ARR) before and after adding disease-modifying drugs. Results: Optic neuritis (39% (13/33) in initial attacks and 49% (62/127) in total attacks) and myelitis (36% (12/33) in initial attacks and 26% (33/127) in total attacks) were the top two symptoms in both the initial attacks and all 127 attacks during follow-up. There was 42% (37/89) of brain magnetic resonance imaging (MRI) scans in acute phase showing new lesions in supratentorial white matter, with 43% (16/37) showing acute disseminated encepha lomyelitis (ADEM)-like or leukodystrophy-like patterns. AQP4-IgG was detected in 30% (10/33) patients, and MOG-IgG was detected in 55% (11/20) patients, with no combined positive case. In 20 patients treated with rituximab, two were treated after the initial attack. In the other 18 patients, the median annualized relapse rate decreased from 1.86 (1.52, 2.60) before treatment to 0.28 (0, 1.13) during treatment (Z=-3.376, P=0.001). Compared with AQP4-IgG associated NMOSD (10 cases), fever of unknown origin (8/40 vs. 0/33, P=0.007) was more common, area postrema syndrome (0/40 vs. 4/33, P=0.038) was fewer, cell count of cerebrospinal fluid (49.0 (17.5, 115.0) ×10⁶/L vs. 5.5 (3.0, 15.8)×10⁶/L, Z=-3.526, P=0.000) was higher in MOG-IgG associated NMOSD (11 cases). Conclusions In childhood-onset NMOSD, optic neuritis and myelitis were top two symptoms. Childhood-onset NMOSD has high proportion of positive MOG-IgG. Lesions in supratentorial white matter are common. Rituximab could significantly decrease ARR of NMOSD in childhood. However, more studies should be conducted to explore the optimal treatment strategy in different antibody associated NMOSD.

Objective To observe the effect of excretory/secretory products from Trichinella spiralis adult worms(AES)on cecal ligation and puncture(CLP)?induced sepsis in mice. Methods Forty?eight BALB/c mice were randomly divided into 3 groups:a sham operation group(PBS+sham group,Group A),a CLP?induced sepsis group(PBS+CLP group,Group B)and an AES treatment group(AES+ CLP group,Group C). The mice of each group were intraperitoneally injected with 25 μg of AES or PBS only as a control in a total volume of 200μl. Eight mice from each group were selected randomly for survival analy?sis of 96 hours. The other 8 mice in each group were observed for pathological changes in the lung,liver and kidney tissues by HE staining 12 h after CLP,and then determined for the detection of cytokines including TNF?α,IL?1β,IL?6,IL?10 and TGF? βin the sera by ELISA. Results The difference among the survival rates of mice in the 3 groups was statistically significant (χ2=21.16,P<0.05). Compared to Group A(100%),the survival rate of mice in Group B(0)decreased significantly(P<0.05),and also the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group B increased signifi?cantly after CLP. Compared with the mice in group B,the survival rate of those in Group C(70%)increased significantly(P<0.05),and the pathological damage degrees in the lung,liver and kidney tissues of the mice in Group C decreased significantly after the treatment with AES. The differences among the levels of pro?inflammatory cytokines TNF?α(F=27.11,P<0.05),IL?1β(F=18.75,P<0.05)and IL?6(F=100.93,P<0.05)in the sera of the mice in the three groups were statistically signifi?cant. Compared with the mice in Group A,the levels of the 3 cytokines of those in Group B increased significantly(all P <0.05). However,after the treatment with AES,the levels of the pro?inflammatory cytokines of those in Group C decreased signifi?cantly(all P<0.05). The differences among the levels of immunoregulatory cytokines IL?10(F=10.88,P<0.05)and TGF?β(F=11.37,P<0.05)in the sera of the mice in the three groups were also statistically significant. Compared with the mice in Group B,the levels of IL?10 and TGF?β of those in Group C were higher after treatment with AES(both P<0.05). Conclu?sion T. spiralis AES has a therapeutic potential for alleviating sepsis induced by CLP in mice.

Objective To predict the risk of in-hospital death in patients with chronic heart failure(CHF)complicated by lung infections using interpretable machine learning.Methods The clinical data of 1415 patients diagnosed with CHF complicated by lung infections were obtained from the MIMIC-IV database.According to the pathogen type,the patients were categorized into bacterial pneumonia and non-bacterial pneumonia groups,and their risks of in-hospital death were compared using Kaplan-Meier survival curves.Univariate analysis and LASSO regression were used to select the features for constructing LR,AdaBoost,XGBoost,and LightGBM models,and their performance was compared in terms of accuracy,precision,F1 value,and AUC.External validation of the models was performed using the data from eICU-CRD database.SHAP algorithm was applied for interpretive analysis of XGBoost model.Results Among the 4 constructed models,the XGBoost model showed the highest accuracy and F1 value for predicting the risk of in-hospital death in CHF patients with lung infections in the training set.In the external test set,the XGBoost model had an AUC of 0.691(95%CI:0.654-0.720)in bacterial pneumonia group and an AUC of 0.725(95%CI:0.577-0.782)in non-bacterial pneumonia group,and showed better predictive ability and stability than the other models.Conclusion The overall performance of the XGBoost model is superior to the other 3 models for predicting the risk of in-hospital death in CHF patients with lung infections.The SHAP algorithm provides a clear interpretation of the model to facilitate decision-making in clinical settings.

Objective To predict the risk of in-hospital death in patients with chronic heart failure(CHF)complicated by lung infections using interpretable machine learning.Methods The clinical data of 1415 patients diagnosed with CHF complicated by lung infections were obtained from the MIMIC-IV database.According to the pathogen type,the patients were categorized into bacterial pneumonia and non-bacterial pneumonia groups,and their risks of in-hospital death were compared using Kaplan-Meier survival curves.Univariate analysis and LASSO regression were used to select the features for constructing LR,AdaBoost,XGBoost,and LightGBM models,and their performance was compared in terms of accuracy,precision,F1 value,and AUC.External validation of the models was performed using the data from eICU-CRD database.SHAP algorithm was applied for interpretive analysis of XGBoost model.Results Among the 4 constructed models,the XGBoost model showed the highest accuracy and F1 value for predicting the risk of in-hospital death in CHF patients with lung infections in the training set.In the external test set,the XGBoost model had an AUC of 0.691(95%CI:0.654-0.720)in bacterial pneumonia group and an AUC of 0.725(95%CI:0.577-0.782)in non-bacterial pneumonia group,and showed better predictive ability and stability than the other models.Conclusion The overall performance of the XGBoost model is superior to the other 3 models for predicting the risk of in-hospital death in CHF patients with lung infections.The SHAP algorithm provides a clear interpretation of the model to facilitate decision-making in clinical settings.

CaMKII is essential for long-term potentiation (LTP), a process in which synaptic strength is increased following the acquisition of information. Among the four CaMKII isoforms, γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons (LTP_E→I). However, the molecular mechanism underlying how γCaMKII mediates LTP_E→I remains unclear. Here, we show that γCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10-30 Hz range. Following stimulation, γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95. Knocking down γCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors (AMPARs) in putative inhibitory interneurons, which are restored by overexpression of γCaMKII but not its kinase-dead form. Taken together, these data suggest that γCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Hippocampus/metabolism* ; Interneurons/physiology* ; Long-Term Potentiation/physiology* ; N-Methylaspartate/metabolism* ; Receptors, AMPA/physiology* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Synapses/physiology*

DNA damage response (DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modifications play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring finger protein 126 (RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner. RNF126 directly interacted with and ubiquitinated another E3 ligase, RNF168. Overexpression of wild type RNF126, but not catalytically-inactive mutant RNF126 (CC229/232AA), diminished ubiquitination of H2A histone family member X (H2AX), and subsequent bleomycin-induced focus formation of total ubiquitin FK2, TP53-binding protein 1 (53BP1), and receptor-associated protein 80 (RAP80). Interestingly, both RNF126 overexpression and RNF126 downregulation compromised homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs). Taken together, our findings demonstrate that RNF126 negatively regulates RNF168 function in DDR and its appropriate cellular expression levels are essential for HR-mediated DSB repair.
Carrier Proteins ; metabolism ; Cell Line, Tumor ; DNA Breaks, Double-Stranded ; DNA Repair ; genetics ; DNA-Binding Proteins ; metabolism ; Genomic Instability ; HeLa Cells ; Histones ; metabolism ; Humans ; Nuclear Proteins ; metabolism ; RNA Interference ; RNA, Small Interfering ; genetics ; Signal Transduction ; Tumor Suppressor p53-Binding Protein 1 ; metabolism ; Ubiquitin ; Ubiquitin-Protein Ligases ; genetics ; metabolism ; Ubiquitination