Objective To study the anti-inflammatory effects of idazoxan (IDA) on endotoxin lipopolysaccharide (LPS) challenged mice in vivo and activated macrophages in vitro,and explore its potential molecular mechanisms.Methods To do the experiments in vivo,30 adult male C57BL/6 mice were randomly divided into control group,model group,and low,medium and high doses IDA groups (IDA-L,IDA-M,and IDA-H groups),n =6 in each group.The inflammatory model was reproduced by intraperitoneal injection of LPS 10 mg/kg,and the control group was injected with the same amount of normal saline.The IDA groups received LPS (10 mg/kg) and IDA 0.3,1.0 and 3.0 mg/kg,respectively.The blood samples of mice in each group were collected at 6 hours after the reproduction of the model.For the in vitro experiments,primary peritoneal macrophages were collected from 20 adult male C57BL/6 mouse cells and they were divided into control group,LPS group (10 mg/L) and LPS+IDA-L,IDA-M,IDA-H groups (10 mg/L LPS + 5,25,100 μmol/L IDA,respectively).Cell culture supernatants were collected at 24 hours after the reproduction of the model.Detection methods:enzyme linked immunosorbent assay (ELISA) was used to determine the levels of serum tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO).Western Blot was used to determine the effect of IDA on the expression levels of nuclear factor-κB (NF-κB) in macrophages.Results ① For the in vivo experiment,the serum levels of TNF-α and IL-6 were significantly elevated in the model group as compared with those in the control group [TNF-o (ng/L):403.96 ± 40.98 vs.17.50 ± 8.68;IL-6 (ng/L):61 400.31 ± 7 826.61 vs.2 436.30 ± 448.89;both P ＜ 0.01].IDA treatment could inhibit the elevation of inflammatory cytokines in a dose-dependent manner,with the most significant decrease in LPS+IDA-H group [TNF-α (ng/L):170.09 ± 28.53 vs.403.96 ± 40.98,IL-6 (ng/L):16 570.81 ± 1 083.65 vs.61 400.31± 7 826.61;both P ＜ 0.01].② For the in vitro experiment,the levels of TNF-α,IL-6,MCP-1,and NO secreted by LPS-stimulated macrophages were distinctly higher in the LPS group than those in the control group [TNF-α (ng/L):7 259.14 ± 320.70 vs.28.50±27.08,IL-6 (ng/L):14809.60±5852.73 vs.1 113.47±465.53,MCP-1 (ng/L):20847.37± 1 788.33 vs.447.37± 395.69,NO (μmol/L):1 900.00 ± 144.31 vs.603.03 ± 102.18;all P ＜ 0.01].However,IDA intervention could lower the secretion of TNF-α,IL-6,MCP-1 and NO in a dose-dependent manner,with the most notable decrease in the LPS+IDA-H group [TNF-α (ng/L):784.40±281.90 vs.7259.14±320.70,IL-6 (ng/L):1 802.96± 1 534.18 vs.14 809.60± 5 852.73,MCP-1 (ng/L):2005.26± 1 534.28 vs.20847.37 ± 1 788.33,NO (μ mol/L):654.54± 150.21 vs.1 900.00 ± 144.31;all P ＜ 0.05].In addition,IDA at the concentration of 100 μmol/L could promote the translocation of NF-κBp65 in macrophages into the nucleus 15 minutes early and lead to increased NF-κBp65 expression (gray value:18.70 ± 2.29 vs.1.09 ± 0.36,P ＜ 0.05),hut significantly reduce the expression levels of NF-κBp50 in the nucleus at 45 minutes after treatment (gray value:1.99 ± 0.14 vs.2.94 ± 0.54,P ＜ 0.05).Conclusions IDA could significantly reduce inflammation of mice challenged with LPS and inhibit inflammatory cytokines and mediators secreted by macrophage in a dose-dependent manner.High concentration of IDA (100 μmol/L) exhibited the greatest anti-inflammatory effects.The anti-inflammatory effect of IDA may be worked through NF-κB signaling pathway.

Objective To evaluate the correlation between serum procalcitonin (PCT) level and severity of diseases caused by different kinds of stress factors, and to identify the prognostic value of PCT on the prognosis in non-sepsis critically ill patients. Methods A retrospective case control study was conducted. The clinical data of non-sepsis critically ill patients with age of ≥ 18 years admitted to surgery intensive care unit (ICU) of China-Japan Friendship Hospital from August 2013 to December 2015 and stayed for more than 3 days were enrolled. The PCT level in the first 24 hours, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score and 28-day mortality were recorded. Patients were divided into different groups by the original injury, including trauma stress group, stroke stress group and non-infection inflammation stress group. According to PCT level, patients were divided into PCT normal group, low level group, medium level group and high level group. Furthermore, patients were divided into survival group and non-survival group according to 28-day prognosis. The clinical data of patients were compared among the groups, and the correlations among different markers were analyzed with Pearson or Spearman correlation analysis. The predictive value of PCT on prognosis of non-sepsis critically ill patients was evaluated with receiver operating characteristic curve (ROC). Results Ninety-four non-sepsis critical ill patients were enrolled, with 28 patients in trauma stress group, 30 in stroke stress group, and 36 in non-infection inflammation stress group, as well as 32 patients in PCT normal group, 18 in low level group, 18 in medium level group, and 26 in high level group. Of them, 78 survivors and 16 non-survivors were found. ① The PCT level of non-sepsis critically ill patients was significantly positively correlated with APACHE Ⅱ score and SOFA score (r1 = 0.688, r2 = 0.771, both P = 0.000). ② The PCT level in trauma stress group was significantly higher than that in stroke stress group and non-infection inflammation stress group [μg/L: 4.43 (0.86, 11.72 ) vs. 0.28 (0.16, 5.85), 2.39 (0.13, 4.11), both P < 0.01]. APACHE Ⅱ score (13.9±7.5, 13.9±7.0 vs. 9.4±4.4), SOFA score [7.0 (4.0, 9.0), 5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0)], and 28-day mortality [21.4% (6/28), 33.3% (10/30) vs. 0 (0/36)] in trauma stress group and stroke stress group were significantly higher than those of non-infection inflammation stress group (all P < 0.05). The abnormal rate of PCT in trauma stress group was significantly higher than that of stroke stress group and non-infection inflammation stress group [100.0% (28/28) vs. 33.3% (10/30), 66.7% (24/36), both P < 0.01]. ③ Non-survivors had significantly higher PCT level [μg/L: 6.02 (4.43, 18.34) vs. 0.76 (0.16, 4.11)], APACHE Ⅱ score (22.5±3.8 vs. 10.1±5.1) and SOFA score [9.0 (7.0, 11.0) vs. 4.0 (2.0, 8.0)] as compared with those of survivors (all P < 0.01). ④ APACHE Ⅱ score (7.8±2.8, 9.3±4.3, 13.7±6.2, 18.7±5.8, F = 22.495, P = 0.000), SOFA score [3.0 (1.2, 4.8), 4.0 (3.5, 4.5), 6.0 (3.5, 8.0), 10.0 (8.8, 12.0), Z = 51.040, P = 0.000], and 28-day mortality [0 (0/32), 11.1% (2/18), 22.2% (4/18), 38.5% (10/26), χ2 = 15.816, P = 0.001] were gradually increased as PCT level elevated. ⑤ The area under ROC curve (AUC) of PCT for evaluating prognosis of non-sepsis critically ill patients was 0.799 [95% confidence interval (95%CI) = 0.709-0.889, P = 0.000], when the cut-off value was 4.2 μg/L, the sensitivity was 87.5%, and the specificity was 77.6%. Conclusions Serum PCT level was positively correlated with severity of illness in non-sepsis critically ill patients, which had predicted value on prognosis. Trauma stress can lead to higher PCT level than stroke stress and non-infection inflammation stress can.

OBJECTIVE: To explore the microsurgical techniques for insular glioma without damaging its surrounding normal structures. METHODS: We retrospectively analyzed 54 patients with insular gliomas who underwent microsurgical operation by trans-syvian fissure approach between May, 2003 and August, 2008 in Xiangya Hospital. We discussed the techniques in the operation and summarized how to protect the key blood vessels, distinguish and protect the surrounding normal structures. RESULTS: There were 36 complete removals,14 secondary complete removals, and 4 partial removals.Six patients had complications after the craniotomy who had temporal speech disorder (aphasia mostly began to recover about 10 days after the craniotomy),4 patients had opposite side paralysis worsening (3 recovered normally and 1 improved after 6 months),4 had light paralysis, and another 3 had paralysis and speech disorder. CONCLUSION The microsurgery by means of trans-syvian fissure approach can well expose the anatomical relation between tumor and its surrounding structures,so that we can remove the tumor and protect the surrounding normal tissues as much as we can.
Adolescent ; Adult ; Brain Neoplasms ; pathology ; surgery ; Cerebral Cortex ; pathology ; surgery ; Female ; Glioma ; pathology ; surgery ; Humans ; Male ; Microsurgery ; methods ; Middle Aged ; Neurosurgical Procedures ; methods ; Retrospective Studies ; Young Adult

OBJECTIVE: To explore the pathogenetic mechanism of cystic meningioma and the key to its diagnosis and operation. METHODS: Clinical data of 8 patients with cystic meningioma were analyzed retrospectively. The occuring position and cure rate of cystic meningioma were compared with those of solid meningioma in the corresponding period. RESULTS: All patients were subjected to total resection of tumor parenchyma and cystic wall. No operative death and severe complications occurred. The incidence of uppertentorial region of cystic meningioma was higher than that of solid meningioma, and the difference was significant (χ(2)=2.618, P<0.05). The cure rate was not significantly different between cystic meningioma and solid meningioma (χ(2)=0.010, P>0.05). CONCLUSION Removing tumor totally is the key to preventing its recurrence.
Adult ; Aged ; Arachnoid Cysts ; complications ; diagnosis ; surgery ; Female ; Humans ; Male ; Meningeal Neoplasms ; diagnosis ; surgery ; Meningioma ; classification ; complications ; diagnosis ; surgery ; Middle Aged ; Retrospective Studies

The liver reserve function refers to the compensatory ability to maintain liver function after damage, providing implication for the resection of hepatic malignant tumor. Hepatobiliary scintigraphy imaging can provide quantitative evaluation of liver blood perfusion, and has advantages on the evaluation of liver reserve function and the prediction of postoperative complications. 99Tc m-galactosyl serum albumin (GSA) and 99Tc m-mebrofenin are commonly used imaging agents for hepatobiliary scintigraphy imaging assessment of liver reserve function. This article reviews the application and progress of hepatobiliary scintigraphy in liver reserve function assessment.

Objective:To investigate the short term outcomes and postoperative respiratory complications of patients with chronic thromboembolic pulmonary hypertension(CTEPH) treated by pulmonary endarterectomy(PEA).Methods:45 consecutive CTEPH patients underwent PEA between December 2017 and January 2020 in our institution were enrolled, including 25 females and 20 males. The mean age of operation was 51.2(25-70) years old. 24(53.5%) patients were in New York Heart Association(NYHA) functional class Ⅲ-Ⅳ. The mean PVR before operation was 923(461-2 711) dyn·s·cm -5. All patients’ data were entered in a prospective database, divieded into patients with respiratory complications group(WRC)and without respiratory complications group(WORC). To assess risk factors for postoperative respiratory complications and its effect on short term outcomes. Results:There was a significant reduction in mPAP(from 37 mmHg to 20 mmHg) and PVR(from 923 dyn·s·cm -5 to 293 dyn·s·cm -5) in the entire group. The in-hospital mortality rate was 4.4%(2 cases), died due to postoperative cardiogenic circulatory failure, even with VA-ECMO treatment and mediastinal infection, respectively. Postoperative respiratory complications occurred in 32 patients(71.1%). The most common complications were reperfusion pulmonary edema 44.4%(20 cases) and residual pulmonary hypertension 11.1%(5 cases). The WRC group showed a tendency to have longer periods of mechanical ventilation, longer ICU stays and more ICU costs. Independent predictors of postoperative respiratory complications were time from symptom onset to PEA>36 months( OR=12.2, 95% CI: 2.1-70.7, P=0.005)and six-minute walking distance<300 m( OR=12.6, 95% CI: 1.1-138.0, P=0.0038). Conclusion:Pulmonary endarterectomy is an effective and safe treatment for CTEPH. Postoperative respiratory complications were mainly determined by symptom onset time and pre-operative status. Patients with CTEPH should consider PEA surgery early.

Objective:To investigate the relationship between antibacterial treatment scheme and prognosis, and to analyze the mortality risk factors of bloodstream infection with carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods:A retrospective case-control study was conducted. The CRKP isolated from clinical venous blood samples in the First Medical Center, Chinese PLA General Hospital between January 1, 2013 and December 31, 2018(not included from January 1, 2016 to December 31, 2017) was collected. According to relevant standards, a total of 50 patients with bloodstream infection with CRKP were included. The patients were divided into death (19 cases) or survival (31 cases) group according to their hospitalization outcomes, and clinical data and antibacterial treatment scheme after infection were collected. The clinical features of the two groups and the correlation between different antibacterial treatment regimens and prognosis were compared. Logistics regression model was used to analyze the risk factors for death in CRKP-infected patients.Results:The all-cause mortality rate of patients with CRKP bloodstream infection during hospitalization was 38%(19/50). The age ((66.89±18.13) vs. (55.06±14.39) years old, t=2.555, P=0.014), charlson's comorbidity index ((6.11±2.87) vs. (3.19±1.97), t=4.256, P<0.001) of the death group was higher than that of the survival group. The proportion of patients with chronic obstructive pulmonary disease (42.1%(8/19) vs. 3.2%(1/31), χ2=9.574, P=0.002), Charlson's comorbidity index ≥5 (68.4%(13/19) vs. 22.6%(7/31), χ2=10.314, P=0.001), septic shock (36.8%(7/19) vs. 6.5%(2/31), χ2=5.456, P=0.020), source of lung infection (36.8%(7/19) vs. 9.7%(3/31), χ2=3.868, P=0.049) was higher in death group than those in survival group. Kaplan-meier survival curve showed that the 30-day mortality of appropriate targeted treatment was lower than that of inappropriate targeted treatment ( χ2=8.138, P=0.004). Multivariate analysis showed that septic shock ( OR=56.363, 95% CI: 4.309-737.273, P=0.002) and charlson's comorbidity index ≥5 ( OR=18.605,95% CI: 1.813-190.896, P=0.014) were independent risk factors for mortality in patients with bloodstream CRKP infection. Conclusion:Appropriate targeted therapy can reduce 30-day mortality in patients with CRKP bloodstream infection. In order to reduce the risk of mortality, we should prevent the occurrence of septic shock and strengthen the diagnosis and treatment of patients with Chalson's comorbidity index ≥5.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans ; Cell Membrane ; Mutation, Missense ; Phosphates/metabolism* ; Sodium-Phosphate Cotransporter Proteins, Type III/genetics*