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Objective:To investigate the correlation between cognitive function and addiction, impulsivity, and anhedonia in adolescent depressive disorder patients with self-injury behavior.Methods:From September 2021 to October 2022, adolescents with depressive disorders who visited the outpatient department of the Qingdao Mental Health Center were enrolled and divided into self-injury group and non self-injury group based on the presence or absence of self-injury behaviors, each with 60 participants.A self-compiled general information questionnaire, the 17 items Hamilton depression rating scale (HAMD-17), the Ottawa self-injury inventory (OSI), the Chinese version of the Barratt impulsiveness scale (BIS-11), and the temporal experience of pleasure scale(TEPS) were used to evaluate both groups.The Chinese brief cognitive test(C-BCT) was used to assess cognitive function in both groups.SPSS 26.0 software was used for statistical analysis, including t-test, χ2 test, Pearson correlation analysis, and multiple linear regression analysis. Results:The self-injury group had higher scores for OSI addiction factors (9.43±8.29) and BIS-11 (67.09±11.48) compared to the non self-injury group (OSI addiction factor scores: 0, BIS-11 scores: 53.70±7.12, t=6.22, 5.91, both P<0.05). TEPS score and C-BCT scores in various dimensions were lower in the self-injury group than those in the non self-injury group ( t=-2.93, -2.01, -2.88, -2.20, -5.35, all P<0.05). Information processing speed was negatively correlated with BIS-11 score ( r=-0.296, P<0.05), and attention score were negatively correlated with OSI addiction factor score and BIS-11 score ( r=-0.303, -0.561, both P<0.05) and positively correlated with TEPS score ( r=0.364, P<0.05), including a positive correlation with the scale of anticipatory anhedonia score ( r=0.318, P<0.05). Working memory score was negatively correlated with OSI addiction factor score and BIS-11 score ( r=-0.312, -0.416, both P<0.05). Comprehensive ability and executive function scores were negatively correlated with OSI addiction factor score and BIS-11 score ( r=-0.308, -0.679, both P<0.05), and positively correlated with TEPS score ( r=0.304, P<0.05). Multiple linear regression analysis showed that BIS-11 scores were influencing factors of C-BCT dimensions ( β=-0.260, -0.592, -0.557, -1.797, t=-2.150, -3.314, -2.285, -5.165, all P<0.05). Conclusion:In adolescent depressive patients with self-injury, cognitive function is correlated with addiction, impulsivity and anhedonia, among which impulsivity is a risk factor for cognitive function.
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Objective:To explore the effects of knocking down glycine cleavage system H protein (GCSH) on proliferation, apoptosis, oxidative stress and migration of gastric cancer SNU-1 cells in vitro. Methods:SNU-1 cells were cultured in vitro and divided into control group (no transfection) , negative control group (transfection of negative control siRNA) and GCSH knockdown group (transfection of GCSH siRNA) . Quantitative PCR was used to detect the knockdown effect. Immunofluorescence was used to observe the morphology of cells in each group. CCK-8 was used to test the proliferation of SNU-1 cells. Flow cytometry was used to detect the apoptosis and oxidative stress level, and scratch test was used to detect the cell migration. Results:Quantitative PCR experiment showed that the relative expression levels of GCSH in the control group, negative control group and GCSH knockdown group were 1.29±0.16, 1.36±0.17 and 0.32±0.04, respectively ( F=90.32, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.497) . Compared to the negative control group, the GCSH knockdown group was significantly decreased ( P<0.001) . Immunofluorescence experiment showed no significant difference in the morphology of cells among the groups. The CCK-8 experiment results showed that the cell proliferation activities of the control group, negative control group and GCSH knockdown group were 2.63±0.12, 2.61±0.14, 2.45±0.14, respectively ( F=6.35, P=0.005) . There was no significant difference between the control group and negative control group ( P=0.751) , and the GCSH knockdown group significantly decreased compared to the negative control group ( P=0.011) . The results of flow cytometry showed that the early stage apoptosis rates of SNU-1 cells in the control group, negative control group and GCSH knockdown group were (13.38±0.45) %, (12.86±0.65) %, (20.04±3.61) %, respectively ( F=15.37, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.559) . Compared to the negative control group, the GCSH knockdown group significantly increased ( P=0.002) . The late stage apoptosis rates of the three groups were (2.21±0.25) %, (2.68±0.45) %, (5.67±1.67) %, respectively ( F=18.24, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.356) . Compared to the negative control group, the GCSH knockdown group showed a significant increase ( P=0.024) . The reactive oxygen species positive rates in the control group, negative control group and GCSH knockdown group were (26.98±8.79) %, (28.27±5.63) %, (48.41±0.94) %, respectively ( F=22.56, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.950) . Compared to the negative control group, the GCSH knockdown group significantly increased ( P<0.001) . The cell migration rates of the control group, negative control group and GCSH knockdown group were (48.29±5.79) %, (51.66±2.29) %, (14.01±1.56) %, respectively ( F=148.80, P<0.001) . There was no significant difference between the control group and negative control group ( P=0.328) . Compared with the negative control group, the GCSH knockdown group significantly decreased ( P<0.001) . Conclusion:Knock down of GCSH gene can inhibit the proliferation and migration, increase cell apoptosis rate and oxidative stress of SNU-1 cells in vitro. GCSH gene may be a potential target for the treatment of gastric cancer.
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OBJECTIVE To investigate the effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats. METHODS SD rats were randomly divided into 4 groups according to single-dose administration and multiple-dose administration， with 6 rats in each group. Groups A and B were given olanzapine （5 mg/kg） or olanzapine （5 mg/kg）+Yiru tiaojing granules （0.972 g/kg） in a single gavage， and groups C and D were administered with the same method once a day for 14 d. Blood was collected from the orbital venous plexus before administration and 5， 15， 30 min and 1， 2， 3， 6， 8， 12， 24 h after the last administration， respectively. The blood concentration was determined by LC-MS， and the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS Compared with group A， group B showed a significant decrease in AUC0－24 h， AUC0－∞ and cmax （P＜0.05）， and a significant prolongation of MRT0－24 h， MRT0－∞ and CLz/F （P＜0.05）； there was no statistically significant difference in the pharmacokinetic parameters between group C and group D （P＞0.05）. CONCLUSIONS A single administration of Yiru tiaojing granules can inhibit the absorption of olanzapine in rats， and long-term administration of Yiru tiaojing granules does not have a significant effect on the pharmacokinetic process of olanzapine.
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OBJECTIVE To identify the chemical components of Changtong oral liquid （CTOL），and to provide reference for the basic research and secondary development of its pharmacological substances. METHODS UHPLC-Orbitrap HRMS technique was adopted. CTOL sample was separated on a Hypersil Gold column with mobile phase consisted of 0.1% formic acid （containing 5 mmol/L ammonium formate）-acetonitrile （gradient elution）. The eluent was detected in positive and negative ion modes using an electrospray ionization source. The data was processed by Xcalibur 4.3 and Compound Discoverer 3.3 software. The primary and secondary mass spectra data of each compound were collected. The unknown compounds were identified according to the mass spectrometry library of the instrument and the network databases mzCloud，mzVault，etc. Through matching with the pharmacology database and analysis platform of the traditional Chinese medicine system，the chemical components could be attributed to the traditional Chinese medicine. RESULTS Fifty-three chemical components were identified and analyzed from CTOL，such as 24 flavonoids，8 quinones，5 phenylpropanoids，4 sugars and glycosides，5 organic acids，3 amino acids，1 alkaloid，1 phenolic and 2 other compounds. Among them，12 components were derived from Salvia miltiorrhiza，9 from Citrus aurantium，7 from Rheum palmatum，4 from Angelica sinensis，1 from Magnolia officinalis，16 from Glycyrrhiza uralensis，and 4 from many kinds of medicinal materials. CONCLUSIONS CTOL mainly contains flavonoids，quinones and phenylpropanoid compounds，and its chemical components mainly come from G. uralensis，S. miltiorrhiza and C. aurantium.
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Acute respiratory distress syndrome(ARDS)is one of the most common complications of sepsis, resulting in the high risk of death in patients with sepsis.By comparison with non-septic ARDS, sepsis-associated ARDS is characterized by high morbidity, heterogeneity and mortality.It is vital to early identify the occurrence of ARDS, accurately assess the severity, as well as effectively implement the individualized treatment.Based on the genome-wide association study, mass cytometry, and multiple omics data analysis, the molecular signatures of sepsis-associated ARDS have been elucidated, which were related to genetic susceptibility, inflammatory reaction pathway, and metabolic characteristics.The development of novel biomarkers is helpful to molecular classifier, risk stratification, early recognition and assessing severity, implement early intervention, then improving the prognosis.
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Biomarkers of sepsis play critical roles in diagnosis, early recognition of organ dysfunction, risk stratification, prognostication, and therapeutic strategy.The dysregulated inflammatory response is reflected drastic changes in pathogen-associated molecular patterns and damage-associated molecular patterns, presented the changes of gene expression and epigenetic modification, metabolic reprogramming and immune dysfunction of immune cells.Sepsis is classified into hyperinflammatory phenotype and immunosuppression phenotype.Biomarker exploration is also conductive to understand the heterogeneity of sepsis and developing the individualized treatment strategies.This issue focused on novel immune-associated biomarkers for prognostic prediction that could be useful to optimize patient management.
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Neurogenic bowel dysfunction is one of the common complications after spinal cord injury. Long-term constipation and fecal incontinence can cause great troubles in the daily life of patients and seriously affect their quality of life. The key to the solution is effective intestinal intervention, including the establishment of defecation patterns, dietary interventions, and drug interventions, enema, electromagnetic stimulation, and enterostomy, etc. At the same time, a personalized bowel management plan is formulated based on the specific conditions of the patient to better manage the bowel and improve the patient′s quality of life.
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Objective:To explore the critical issues in the construction of management and supporting system of Investigator-Initiated trials (IIT) in pediatrics.Methods:Through summarizing related literature and considering the current status of pediatric clinical research, the critical issues in the construction of management and support system, for instance, the responsibility, training model, and performance evaluation in Europe and U. S. were evaluated, decision-making suggestions were put forward based on domestic pediatric IIT management system.Results:Besides IIT, clinical trials on children′s drugs are also supported by the pediatric clinical research management system in Europe and U. S.. The supporting service covers research consultation, ethical review, research design, trial implementation, patient education, risk control, and investigator training. The organizational structure and management system are relatively mature. Clinical trials are the majority of clinical research in children′s hospitals in China. Main issues identified in the construction of the management and supporting system include ethical review for pediatric clinical research, professional investigator training, multicenter cooperation scheme, performance assessment, and incentive strategies.Conclusions:Taking account into the current status of pediatric IIT in China, it is urgent to accelerate the training of pediatric investigators, set up standard IIT project management team, build the professional project management platform and Electronic Data Capture System, and promote the transformation of research outcomes. Finally, the whole process management of pediatric IIT will be developed to facilitate the development of pediatric medicine.
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The occurrence, development and prognosis of sepsis are closely related to immune regulation.Immunometabolism has been the research hotspot of immune intervention in sepsis in recent years.AMP-activated protein kinase(AMPK)and mammalian target of rapamycin(mTOR)are star molecules involved in metabolic regulation.As an important way of immunometabolic regulation in sepsis, AMPK-mTOR is involved in the process of chemotaxis of neutrophils, the polarization of macrophages, the development and differentiation of natural killer cells and dendritic cells, and the development and functional regulation of T cells.This article reviewed the research progress of AMPK-mTOR signaling pathway on regulating metabolic reprogramming in immune cells, which contributes to immunoregulation in sepsis.
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Objective:To evaluate the predictive value of lung ultrasound on mortality in children with severe acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation (ECMO) support.Methods:A prospective observational study was used to enroll patients with severe ARDS who met the Berlin criteria in the Pediatric Intensive Care Unit of Children’s Hospital of Shanghai Jiao Tong University from January 2016 to December 2019. Patients with ECMO support <3 d, lack of appropriate acoustic windows, with severe pneumothorax, and secondary to congenital heart disease or chronic lung disease were excluded. ECMO parameters, respiratory mechanics parameters and outcome were collected and analyzed. Lung ultrasound score (LUS) was measured at the initiation of ECMO as LUS-0 h, then at 24 h, 48 h, 72 h, and 7 d after ECMO support as the value of LUS-24 h, LUS-48 h, LUS-72 h, LUS-7 d, as well as after weaning ECMO as LUS-w. The patients were divided into survivors and non-survivors according to hospital survival status. Receiver operating characteristic (ROC) curve and Kaplan-Meier survival analysis curve were performed to explore the predictive value of lung ultrasound on mortality in patients with severe ARDS undergoing ECMO.Results:A total of 26 patients were enrolled in this study, of which 18 patients survived and 8 died. There were no significant differences in PRISM Ⅲ, dynamic pulmonary compliance (Cdyn), oxygenation index, PaO 2/FiO 2, and PaCO 2 on PICU admission between the two groups (all P>0.05). The values of LUS-72 h and LUS-w in non-survivors were significantly higher than those in survivors [26 (24, 29) vs16 (13, 19), P<0.01] and [30 (26, 35) vs11 (10, 13), P<0.01]. The values of Cdyn-72 h, Cdyn-7 d and Cdyn-w in survivors were significantly higher than those in non-survivors [0.48 (0.42, 0.54)mL/cmH 2O·kg vs 0.36 (0.29, 0.40) mL/cmH 2O·kg, P<0.01; 0.60 (0.52, 0.67) mL/cmH 2O·kg vs 0.27 (0.13, 0.30) mL/cmH 2O·kg, P<0.01, and 0.66 (0.62, 0.70) mL/cmH 2O·kg vs 0.30 (0.13, 0.35) mL/cmH 2O·kg, P<0.01]. ROC curve analysis showed that an area under ROC curve (AUC) of LUS-72 h for predicting PICU mortality was 0.955 (95% CI: 0.864-1.000; P<0.01). The cutoff value of LUS-72 h was 24 with a sensitivity of 87.5% and a specificity of 100.0%. Kaplan-Meier survival analysis showed that PICU mortality of patients with LUS-72 h≥24 was significantly higher than that in patients with LUS-72 h < 24 ( P<0.01) . Conclusions:Lung ultrasound is an effective tool for monitoring progress of children with severe ARDS received ECMO support. LUS-72 h >24 is an index to predict the worsen outcome in children with severe ARDS under ECMO support.
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Objective:To summarize the clinical features, imaging changes, treatment, and prognosis of children with severe autoimmune encephalitis (AE).Methods:A retrospective study was conducted on patients with severe AE admitted to PICU of Shanghai Children’s Hospital from June 2017 to May 2020. Clinical features, treatment protocols and follow-up data were collected.Results:A total of 27 children were included, among which 18 cases (66.7%) were girls. The on-set age was (7.9±3.2) years. Eighteen cases were diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Fever (77.8%), headache (40.7%) and vomiting (44.4%) were most of prodromal symptoms in children with severe AE. Patients’ neurological symptoms showed seizures (88.9%), mental behavior abnormalities (81.5%), speech disorders (70.4%) and dyskinesia (70.4%). Moreover, epileptic discharge and slow wave activity were critical feature of electroencephalogram (EEG) abnormalities, and the abnormal signal changes on T2-weighted and FLAIR sequence of head MRI were in the posterior horn of the lateral ventricle. In addition, the main comorbidities included refractory status epilepticus (RSE), cardiovascular dysfunction, central hypoventilation syndrome and acute intracranial hypertension syndrome. For patients with central respiratory failure, the median duration of mechanical ventilation was 19.8 (14.8, 29.1) days. According to treatment protocol, the first-line immune treatment included the combination therapies of methylprednisolone, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE). Eighteen cases were given with methylprednisolone [10-30 mg/(kg. d), 3-5 d] + IVIG (2 g/kg, within 2 d) + TPE, 1 case was treated with methylprednisolone [10-30 mg/(kg·d), 3-5 d] + TPE and 8 cases were given with[10-30 mg/(kg·d), 3-5 d] + IVIG (2 g/kg, within 2 d). Sequential therapy was given with methylprednisolone (1-2 mg/kg), gradually reduced from 3 to 6 months. Finally, 16 children (59.3%) had neurological damages at the first discharge, among which 8 cases (29.6%) were with dyskinesia, 5 cases (18.5%) were with speech disturbance, and 5 cases (18.5%) were with abnormal mental behaviors.Conclusions:The most of first clinical symptom is epileptic seizures in pediatric severe AE, and most of these patients are diagnosed with Anti-NMDA receptor encephalitis. RSE, cardiovascular dysfunction, central respiratory and acute intracranial hypertension syndrome constitute to main organ dysfunctions.
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Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.
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Objective:To investigate the clinical significance of the expression of oxidized α1-antitrypsin (ox-AAT) and neutrophil elastase (NE) in the peripheral blood and fetal membrane tissues of pregnant women with premature rupture of membranes (PROM).Methods:The clinical data of 95 cases of PROM pregnant women admitted to Binhai County People′s Hospital from April 2019 to April 2020 were analyzed. According to combination of histological chorioamnionitis (HCA), they were divided into PROM combined with HCA group ( 31 patients) and PROM without HCA group (64 patients). Besides, 50 normal pregnant women were collected during the same period as a healthy control group. The expression levels of ox-AAT and NE in the peripheral blood and fetal membrane tissues of the three groups were compared and analyzed.Results:The levels of peripheral blood ox-AAT and NE in the PROM combined with HCA group were higher than those in PROM without HCA group and healthy control group: (2.34 ± 0.02) ng/L vs. (1.50 ± 0.12), (0.32 ± 0.04) ng/L; (0.48 ± 0.08) ng/L vs. (0.13 ± 0.06), (0.11 ± 0.05) ng/L;the level of peripheral blood ox-AAT in PROM without HCA group was higher than that in healthy control group: (1.50 ± 0.12) ng/L vs. (0.32 ± 0.04) ng/L, and the differences were statistically significant ( P<0.05). The levels of fetal membrane tissues ox-AAT and NE in the PROM combined with HCA group were higher than those in PROM without HCA group and healthy control group: (0.031 ± 0.005) ng/L vs. (0.015 ± 0.002), (0.009 ± 0.003) ng/L; (0.020 ± 0.002) ng/L vs. (0.003 ± 0.001), (0.002 ± 0.001) ng/L; the level of fetal membrane tissues ox-AAT in PROM without HCA group was higher than that in the healthy control group: (0.015 ± 0.002) ng/L vs. (0.009 ± 0.003) ng/L, and the differences were statistically significant ( P<0.05). There was a positive correlation between ox-AAT and NE in peripheral blood and fetal membrane tissues ( r = 0.879, 0.875, P<0.05). The incidence of placental abruption in the PROM combined with HCA group and PROM without HCA group was higher than that in the healthy control group: 32.26%(10/31), 20.31%(13/64) vs. 4.00%(2/50), the incidence of neonatal pneumonia in the PROM combined with HCA group was higher than that in the PROM without HCA group and healthy control group: 25.81%(8/31) vs. 9.38%(6/64), 2.00%(1/50), and the differences were statistically significant ( P<0.05). Conclusions:The level of ox-AAT is overexpressed in peripheral blood and fetal membrane tissues of pregnant women with PROM, the level of NE is overexpressed in peripheral blood and fetal membrane tissues of PROM combined with HCA, and the increase of ox-AAT and NE expression is closely related to adverse perinatal outcomes.
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Objective To estimate the key epidemiological parameters, including the serial interval (SI), basic reproduction numbers (R0), and time-dependent reproduction numbers (Rt) based on the case data of COVID-19 published on the official website of Shaanxi Provincial Health Commission. Methods The method of maximum likelihood estimation was used to fit the probability distribution of SI, and three parametric models including Gamma, Weibull, and Lognormal distributions were adopted to estimate the distribution of SI. The optimal model was selected by the corrected Akaike information criterion (AICc). Based on nonlinear regression model the cumulative number of confirmed cases was fit to the growth rate r of the Richard growth model to estimate R0. The Rt was calculated based on the Bayesian framework. Results A total of 49 transmission chains were discovered from 245 local confirmed cases in Shaanxi Province. The Gamma distribution was the optimal model to fit the SI here by AICc. Using the Gamma distribution, the mean SI was estimated to be 6.3 days (95%CI:5.98 - 6.43) with a standard deviation (SD) of 3.94 days (95%CI: 3.01 - 5.03). Using the Richard growth model, the growth rate was estimated to be 0.23 (95% CI: 0.21 - 0.24) and the basic reproduction number in Shaanxi to be 3.11 (95%CI: 2.91 - 3.40). Rt showed an overall downward trend, and fell below 1 on February 10 (Rt=0.95（95%CI: 0.76-1.16)), and stabilized at around 0.35 on February 18. Conclusion The SI of COVID-19 is relatively shorter than that of MERS and SARS, while the R0 is relatively larger, and Rt is on a downward trend, which suggests COVID-19 is a highly transmissible infectious disease. The control measures including the isolation and treatment of confirmed patients, quarantine and observation of suspected cases, contact tracing, improvement of public awareness, and adoption of self-protection measures can effectively reduce the COVID-19 outbreak.
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The pathology of sepsis is extremely complex. Pathogen invasion, inflammatory factors secretion, coagulation disorder and microcirculation disturbance lead to metabolic disorder and organ dysfunction. In recent years, immunometabolism has aroused continuous attention in aspect of nutrition therapy and immune intervention for sepsis. Nutrition metabolites include amino acids, fatty acids, and glucose metabolites, which are not only the nutritional ingredients, but also the regulators of innate immune and adaptive immune. Fatty acids and glucose metabolites are involved in regulation of immune response mainly via free fatty acid receptors and AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Here, we summarized the research progress on the roles of nutrition metabolites in nutrition therapy and immune regulation during sepsis, which could provide a new direction for the development of metabolic therapy for sepsis.
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Objective:To investigate the effect of respiratory rehabilitation training combined with bailing capsule on the efficacy and lung function of patients with chronic obstructive pulmonary disease (COPD) through RhoA/Rho-kinase signaling pathway.Methods:One hundred patients with COPD from February 2016 to September 2017 in the Eighty-Eleventh Army Hospital of Hebei Army were randomly divided into control group (50 cases) and bailing capsule + respiratory rehabilitation training group (50 cases). At the same time, 50 healthy people were selected as blank group. The patients in the control group were treated with bailing capsule, and patients in the combined treatment group were treated with respiratory rehabilitation training combined with bailing capsule. The pulmonary function (FEV 1, FVC, FEV 1/FVC%) and clinical efficacy were analyzed. The expression of RhoA, Rock Ⅰ/Ⅱ protein and mRNA were detected by immunoblotting and qRT-PCR. Results:After treatment, the indexes of pulmonary function in the combined group were significantly higher than those in the control group: (2.34 ± 0.91) L vs. (1.91 ± 0.83) L, (2.98 ± 0.83) L vs. (2.34 ± 0.86) L, (79.63 ± 9.95)% vs. (76.13 ± 6.97)% ( P < 0.05). Compared with the blank group, RhoA mRNA and Rock Ⅰ/Ⅱ mRNA in the combined treatment groups were significantly higher than those in the control group ( P < 0.05), and RhoA mRNA and Rock Ⅰ/Ⅱ mRNA in the combined group were significantly lower than those in the control group ( P < 0.05). Compared with the blank group, the RhoA mRNA and Rock Ⅰ/Ⅱ proteins combined treatment groups were significantly higher than those in the control group ( P < 0.05), and the RhoA mRNA and Rock Ⅰ/Ⅱ proteins in the combined group were significantly lower than those in the control group (2.46 ± 0.18 vs. 4.38 ± 0.21, 1.72 ± 0.11 vs. 2.36 ± 0.24, 1.79 ± 0.24 vs. 3.34 ± 0.21) ( P < 0.05). After treatment, the 6MWD and the total clinical effective rate in the combined group were significantly better than those in the control group: 92.00% (46/50) vs. 78.00% (39/50) ( P < 0.05). Conclusions:Respiratory rehabilitation training combined with bailing capsule can significantly improve the pulmonary function of COPD patients, improve the clinical efficacy, and can down-regulate the expression of RhoA, Rock Ⅰ/Ⅱ protein and mRNA through RhoA/Rho-kinase signaling pathway.
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Specialized pro-resolving mediators(SPMs)are lipid mediators derived from essential fatty acids, which have anti-inflammatory/pro-resolution effects.SPMs mainly include lipoxin, resolvin, protectin, and maresin.Different SPMs can bind to different receptors[formyl peptide receptor 2(ALX/FPR2), G protein-coupled receptor 32(DRV1/GPR32), G protein-coupled receptor 18(DRV2/GPR18), or chemokine-like receptor 1(ERV1/CMKLR1)], through nuclear factor-κB, signal transducer and activator of transcription or mitogen-activated protein kinase signal pathways to proresolve inflammation by limiting neutrophil migration and infiltration, regulating inflammatory cytokine expression, and enhancing macrophage phagocytosis.SPMs have potential clinical value in severe disease severity, prognosis prediction and clinical intervention efficacy.This article focused on the role and potential clinical value of SPMs in immune-inflammatory response to severe infection.
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Severe infection and sepsis are the main causes of mortality in pediatric intensive care units(PICU). Severe infection in critically illness is characterized by acute onset, rapid progression, associated with multiple organs dysfunction, and several pathogens involved.It is critical to distinguish the main pathogen as soon as possible for clinical decision-making.Up to date, precision diagnosis and individualized strategy attract more attention in the field of critical care medicine.The improvements of molecular biology, the combination of multi-omics, and metagenomics sequencing, etc may yield many new insights into precision diagnosis of etiology.Inflammatory response biomarkers are defined as conventional inflammatory factor, acute phase protein(APP), blood RNA biosignature, metabolic molecules, immune cell markers and so on, which are promising indicators for identification of pathogenic microorganisms in severe infection.
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ObjectiveTo investigate the clinical significance of highly sensitive nucleic acid detection in precise antiviral therapy for patients with liver cirrhosis and its association with aminotransferase level. MethodsA total of 377 patients with hepatitis B cirrhosis who were hospitalized or attended the outpatient service from May 2013 to April 2019 were enrolled and tested by both domestic HBV DNA detection and highly sensitive Cobas HBV DNA detection. All patients underwent biochemical examination, four blood coagulation tests, routine blood test, and upper abdominal computed tomography or ultrasound. Sensitivity of different HBV DNA detection reagents was compared in liver cirrhosis patients with a low viral load, and the correlation between alanine aminotransferase (ALT) level and viral load was analyzed. The paired t-test was used for comparison of continuous data before and after treatment. The receiver operating characteristic (ROC) curve was used to screen out the optimal predictive values of ALT at different cut-off values of HBV DNA. ResultsAmong the 377 patients with hepatitis B cirrhosis, 215 tested positive and 162 tested negative by domestic HBV DNA, and among these 162 patients, 104 (64.2%) tested positive by Cobas HBV DNA detection, with a mean level of 267.5±42.3 IU/ml. After 24 weeks of antiviral therapy, the 104 patients with hepatitis B cirrhosis had significant improvements in viral replication level, ALT, and Child-Pugh score for liver function; HBV DNA decreased from 267.5±32.2 IU/ml before treatment to 59.6±7.7 IU/ml after treatment (t=3.486, P=0.002), ALT decreased from 871±10.8 U/L before treatment to 36.5±7.6 U/L after treatment (t=3.235, P=0.020), and the Child-Pugh score decreased from 6.5±0.7 before treatment to 5.7±0.5 after treatment (t=2.928, P=0.041). The ROC curve analysis of ALT in predicting HBV DNA decision point showed that an ALT level of 29 IU/L was the most sensitive cut-off value for predicting HBV DNA ＜20 IU/ml, with an area under the ROC curve of 0.904, a sensitivity of 1.0, and a specificity of 0.237. ConclusionPrecise detection helps to guarantee the precise clinical treatment of patients with hepatitis B cirrhosis and improve their treatment outcome and prognosis. An ALT level of 29 IU/L is a sensitive indicator for predicting patients with negative Cobas HBV DNA, so as to achieve individualized precise screening and treatment.
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Objective@#To explore the protective effect and mechanism of the dihydromyricetin (DHM) on cognitive dysfunction in Alzheimer’s disease (AD) rat model.@*Methods@#The AD model of rats was established by injecting Aβ1-42 oligomolymer into the hippocampus. According to the random number table, 30 successfully constructed AD model rats were divided into AD group, AD+ DHM1 group and AD+ DHM2 group, with 10 in each group.And the rats in the three groups were intraperitoneally injected with normal saline, 100 mg/kg DHM and 200 mg/kg DHM for 21 days, respectively.Another 10 rats with body mass matching were taken as the control group.Morris water maze was used to evaluate the spatial learning and memory ability of rats in each group, the expression of inflammatory cytokines were detected by Elisa, and the expressions of AMPK and SIRT1 proteins were detected by Western blot.@*Results@#Compared with the control group, the escape incubation period of rats in AD group was prolonged, and the difference was statistically significant (day 5 : (10.36±2.80)s, (22.40±2.98)s; t=-18.63, P<0.05). Compared with AD group, the escape latency of rats in AD+ DHM1 group and AD+ DHM2 group were shortened (day 5: AD+ DHM1 group (15.68±3.06) s, AD+ DHM2 group (18.85±3.22) s; t=10.65, 4.13, both P<0.05). Compared with AD group, rats in AD+ DHM1 group and AD+ DHM2 group had more crossing times ((1.87±0.76), (2.75±0.63) and (3.78±0.71); t=-6.86, -9.83, both P<0.05), and the target quadrant residence time were extended ((17.08±1.99) s, (16.33±4.33) s, (22.59±4.21) s; t= 28.5, 8.63, both P<0.05). Compared with the control group, the levels of IL-1β, IL-6 and TNF-α in the serum and hippocampus of the AD group were significantly increased (serum: t=4.98, 7.87, 5.43, all P<0.05; hippocampus: t=11.13, 30.50, 23.38, all P<0.05). Compared with the AD group, the levels of IL-1β, IL-6 and TNF-α in the serum and hippocampus of the AD+ DHM1 group and the AD+ DHM2 group were significantly decreased, the difference was statistically significant(serum: AD+ DHM1 group t=-4.13, -10.70, -9.22, AD+ DHM2 group t=-1.75, -3.63, -18.75, all P<0.05; hippocampus: AD+ DHM1 group t=-69.13, -15.13, -6.50, AD+ DHM2 group t=-10.25, -39.00, -8.00, all P<0.05). Compared with the control group, the expression of p-AMPK/AMPK protein and SIRT1 protein in the AD group were decreased.The expression of the two proteins in the AD+ DHM1 group and the AD+ DHM2 group were increased, comparing with those of AD group, and the difference was statistically significant(all P<0.05).@*Conclusion@#DHM exerts protective role in AD model rats, which may be related to the activation of AMPK/SIRT1 pathway and the inhibition of inflammatory response.