[A clinical study of high dependency units to reduce ICU readmission rates in patients with severe liver disease].

Objective: To investigate the real-world difference in the ICU readmission rate between the high-dependency unit (HDU) and the general ward so as to reflect the role of HDU in the diagnosis and management of patients with SLD. Methods: Patients with severe liver disease who were consecutively enrolled were step-downed to HDU and general wards in the ICU of the Fifth Medical Center of the People's Liberation Army General Hospital between July 2017 and December 2021. The main liver function indicators, MELD scores, and other were compared between the two groups. SLD severity, ICU readmission rates, and others differences were analyzed among the patients transferred to different wards. The HDU role was clarified for SLD patients' grade management. The area under the curve of the receiver operating characteristic curve (AUROC) was used to calculate and explore the feasibility of a baseline Model for End-Stage Liver Disease (MELD) score to define the treatment scope of HDU. Results: The SLD group of patients who were transferred to HDU had significantly higher levels of the international normalized ratio, bilirubin, alanine aminotransferase, MELD score, and other factors compared to those in the general ward (P < 0.05). 70.7% of SLD patients in the HDU group had a MELD score > 17, while 61.9% of SLD patients in the general ward group had a MELD score ≤ 17. The overall ICU readmission rate in this cohort was 11.4%. The ICU readmission rate was significantly higher with a MELD score of > 23 (20.0%) than that with a MELD score of ≤ 23 (8.6%) in patients with SLD, according to the MELD score quartile P75 (P = 0.020). The ICU readmission rate was 8.2% when MELD score ≤ 23, and 9.1% when MELD score>23 in the HDU group, with no statistically significant difference (P = 1.000). However, in the general ward group, the ICU readmission rate in patients with a MELD score ≤ 23 was 8.8%, and when the MELD score was >23, the ICU readmission rate significantly increased to 36.4% (P = 0.001). The optimal cut-off value of the MELD score for predicting ICU readmission in patients with SLD in the general ward group was 23.5. Conclusion: The high-dependency unit can better undertake ICU step-down patients with SLD and significantly reduce the ICU readmission rate with MELD scores > 23 in practice. Additionally, ICU step-down SLD patients with a MELD score > 23 are suitable for transfer to HDU treatment.

[Comparison of off-pump coronary artery bypass grafting alone or combined with mitral valve plasty for coronary heart disease with moderate ischemic mitral insufficiency].

Objective: To compare the efficacy of off-pump coronary artery bypass grafting (CABG) or CABG plus mitral valve plasty (MVP) in patients with coronary heart disease complicated with moderate ischemic mitral insufficiency. Methods: The clinical data of 1 050 patients with coronary heart disease complicated with moderate ischemic mitral insufficiency who underwent surgical procedures from January 2009 to December 2020 were analyzed retrospectively. There were 733 males and 317 females, aging (63.3±9.0) years (range: 31 to 83 years). Patients were divided into CABG+MVP group and CABG group according to surgical methods, and the two groups of patients were matched for 1∶4 by the propensity score matching method. There were 107 patients in the CABG+MVP group and 406 patients in the CABG group after matching. The t test, Mann-Whitney U test, χ2 test, Fisher's exact probability method and repeated measures anova were used to compare the surgical outcomes and overall survival in the two groups. Results: There were no significant differences in perioperative death and postoperative complications between the two groups (all P>0.05). Compared with CABG group, CABG+MVP group had longer operation time ((5.6±1.2) hours vs. (4.2±1.0) hours, t=11.528, P<0.01), ICU stay(M(IQR))(43.0(47.3) hours vs. 25.0(33.6) hours, Z=2.483, P=0.013), and postoperative hospital stay (8(4) days vs. 7(5) days, Z=2.143, P=0.032). The amount of erythrocyte and platelet used in CABG+MVP group was significantly increased (2.0(6.5) U vs. 0(2.0) U, Z=7.084, P<0.01; 0(0.5) U vs. 0(0) U, Z=5.210, P<0.01). A total of 463 cases (93.9%) were followed up. Median follow-up was 32(31) months (range: 3 to 105 months). There was no significant difference in overall survival and no major adverse cardic and cerebrovascular events survival between CABG group and CABG+MVP group (P=0.196,P=0.305). Echocardiography showed that there was no significant difference in ejection fraction left ventricular end-diastolic diameter between the two groups (F=0.322, P=0.571; F=0.681, P=0.410). However, CABG+MVP improved mitral regurgitation better than CABG (F=160.222, P<0.01). Conclusions: For patients with coronary heart disease with moderate ischemic mitral insufficiency, the rates of all-cause mortality and major adverse cardiac and cerebrovascular events are similar between the two surgeries. Although CABG+MVP improves mitral regurgitation better than CABG, it increases the duration of surgery, ICU stay, postoperative hospital stay, and blood transfusion requirement.

Effects of edaravone combined with Oxiracetam on neuronal apoptosis in rats with cerebral infarction through targeting SIRT1/NF-κB inflammatory pathway.

OBJECTIVE: The objective of this study was to investigate the effects of edaravone combined with oxiracetam on neuronal apoptosis in rats with cerebral infarction (CI) and to explore the potential molecular mechanism. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham-operation group (n=12), model group (n=12) and treatment group (n=12). Only the external carotid artery was exposed in sham-operation group, while the models of CI were established using suture method in the other two groups. After modeling, the rats in sham-operation group and model group were intraperitoneally injected with normal saline, and those in treatment group were administered with edaravone and oxiracetam solutions via intraperitoneal injection. Then, the specimens were obtained at 2 weeks after intervention. The cognitive function of the rats was evaluated using a water maze, Nissl staining was applied to observe the neuronal morphology, and the relative protein expressions of silent information regulator 1 (SIRT1) and NF-κB were measured by means of Western blotting. Furthermore, quantitative polymerase chain reaction (qPCR) was performed to determine the messenger ribonucleic acid (mRNA) expressions of interleukin-1 beta (IL-1ß) and IL-6, the content of IL-1ß and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was conducted to examine the cell apoptosis. RESULTS: Model group displayed a significantly longer escape latency and significantly fewer times of crossing the original platform than sham-operation group (p<0.05), whereas treatment group had a significantly shorter escape latency but significantly more times of crossing the original platform than model group (p<0.05). The relative protein expression level of SIRT1 was lowered significantly, while that of NF-κB was elevated significantly in model group in comparison with those in sham-operation group (p<0.05), and the opposite results were observed between model group and treatment group (p<0.05). Besides, the content of IL-1ß and IL-6 in brain tissues was increased significantly in model group compared with that in sham-operation group (p<0.05), but it was decreased significantly in treatment group in comparison with that in model group (p<0.05). The relative mRNA expression levels of IL-1ß and IL-6 were significantly higher in model group than those in sham-operation group (p<0.05). Moreover, model group exhibited more positive apoptotic cells and a significantly higher apoptosis rate than sham-operation group (p<0.05) and treatment group (p<0.05). No apparent abnormalities of neuronal morphology and structure were detected in sham-operation group, with many Nissl bodies. The neurons were damaged, with abnormal morphology and structure, and there were a small number of Nissl bodies in model group. The neurons were damaged in treatment group, but their morphology and structure were improved evidently compared with those in model group. CONCLUSIONS: Edaravone combined with oxiracetam can inhibit the neuronal apoptosis in CI rats by regulating the SIRT1/NF-κB signaling pathway, thereby exerting a neuroprotective effect.

[The application of Voriconazole in 76 patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection].

Objective: To investigate the safety and efficacy of voriconazole in the patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection(IFI). Methods: A retrospective collection of medical records of 76 patients with cirrhosis at Child-Pugh C stage complicated by IFI who were admitted to our hospital, from August 2014 to August 2017 was carried out. All the 76 patients who used voriconazole to treat IFI were divided into recommended dose group for hepatic insufficiency(56 cases) and routine dose group(20cases). The two groups were observed and compared in terms of the voriconazole's plasma concentrations, the outcomes of IFI and the rate of untoward reactions. The liver functional indicators were also compared between before and after treatment each group. We used Student's t test, Z test, chi-square test, or Fisher's exact test, as appropriate, for statistical analysis. Results: Both groups had good performance and low frequencies of side effects in the treatment of IFI, but there were also significant differences in the plasma concentrations of voriconazole and the incidence of untoward reactions between the two groups(P = 0.008 and P = 0.022). There commended dose group for hepatic insufficiency had lower adverse effect rate. The levels of direct bilirubin, alanine aminotransferase and aspartate aminotransferase were significantly lower after treatment of IFI in the recommended dose group for hepatic insufficiency(P < 0.05). Conclusion: In our research, it is relatively safe and effective to use voriconazole to treat IFI in the patients with cirrhosis at Child-Pugh C stage if according to the recommended dose regimen for cirrhosis at Child-Pugh A,B stage.

Myocardial motion-corrected phase-sensitive inversion recovery late gadolinium enhancement in free breathing paediatric patients: a comparison with single-shot coherent gradient echo ("TrueFISP") phase-sensitive inversion recovery.

AIM: To investigate the value of motion-corrected (MOCO) phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) compared with single-shot balanced steady-state gradient echo ("TrueFISP", Siemens) PSIR in free breathing paediatric patients. MATERIALS AND METHODS: In this retrospective study, 238 paediatric patients underwent clinical contrast-enhanced cardiovascular magnetic resonance imaging (CMRI). Both the single-shot TrueFISP PSIR and MOCO PSIR sequences were performed on each child. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Two radiologists rated the quality of the images on a scale of 1-5 (1 = poor, 5 = very good). Bland-Altman, linear regression, and intraclass correlation coefficient were used to compared the extent of LGE of the single-shot TrueFISP PSIR and MOCO PSIR. Imaging artefacts were described and compared. RESULTS: Children ranged in age from 60 days to 17 years with an average age of 8.1 ± 3.8 years. MOCO PSIR had higher SNR and CNR than the single-shot TrueFISP PSIR (p<0.001). Mean quality ratings for short-axis imaging were 4 (interquartile range, 3-4) for single-shot TrueFISP PSIR and 4 (interquartile range, 4-5) for MOCO PSIR (p<0.001). The scan time was faster for single-shot TrueFISP PSIR than for MOCO PSIR. The myocardial LGE results were similar with high agreement between the single-shot TrueFISP PSIR and MOCO PSIR (ICC = 0.955-0.986). CONCLUSION: The MOCO PSIR sequence is feasible in children. MOCO PSIR is robust at high heart rates and can be performed without breath-holding with higher image-quality ratings than the single-shot TrueFISP PSIR.

[Analysis of treatment modalities and prognosis of patients with gallbladder cancer in China from 2010 to 2017].

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

[Respiratory support for severe 2019-nCoV pneumonia suffering from acute respiratory failure: time and strategy].

Respiratory support is a very important technique for saving severe 2019-nCoV pneumonia patients who suffering respiratory failure, which can improve oxygenation, reduce mortality. Therefore, how to reasonable using respiratory support technique is the key point that relating success or failure. In this paper, the authors introduce their experience on treating severe 2019-nCoV pneumonia, it is hopeful for current fighting against 2019-nCoV in China.

[Respiratory support for severe 2019-nCoV pneumonia suffering from acute respiratory failure: time and strategy].

Respiratory support is a very important technique for saving severe 2019-nCoV pneumonia patients who suffering respiratory failure, which can improve oxygenation, reduce mortality. Therefore, how to reasonable using respiratory support technique is the key point that relating success or failure. In this paper, the authors introduce their experience on treating severe 2019-nCoV pneumonia, it is hopeful for current fighting against 2019-nCoV in China.

[Protective effects of oligomeric proanthocyanidins in mice exposed to paraquat].

Objective: To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice. Methods: An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD(50)) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1ß (IL-1ß) , and transforming growth factor-ß1 (TGF-ß1) using enzyme-linked immunosorbent assay. Results: The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD(50) values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-ß1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1ß (P<0.05) . After 48 hours, the expression of TNF-α, TGF-ß1, and IL-1ß in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) . Conclusion: OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.

[Comparison of external fixation with or without limited internal fixation for open knee fractures].

Objective: To explore the characteristics and methods of different fixation methods and prevention of open knee joint fracture. Methods: The data of 86 cases of open knee joint fracture admitted from January 2002 to December 2015 in Department of Orthopaedics, Affiliated Hospital of Chengdu University were analyzed retrospectively.There were 65 males and 21 females aged of 38.6 years. There were 38 cases treated with trans articular external fixation alone, 48 cases were in the trans articular external fixation plus auxiliary limited internal fixation group. All the patients were treated according to the same three stages except for different fixation methods. Observation of external fixation and fracture fixation, fracture healing, wound healing and treatment, treatment and related factors of infection control and knee function recovery. χ(2) test was used to analyze data. Results: Eleven patients had primary wound healing, accounting for 12.8%. Seventy-five patients had two wounds healed, accounting for 87.2%. Only 38 cases of trans articular external fixator group had 31 cases of articular surface reduction, accounting for 81.6%; Five cases of trans articular external fixator assisted limited internal fixation group had 5 cases of poor reduction, accounting for 10.4%; There was significant difference between the two groups (χ(2)=44.132, P<0.05). Take a single cross joint external fixation group, a total of 23 cases of patients with infection, accounted for 60.5% of external fixation group; trans articular external fixation assisted limited internal fixation group there were 30 cases of patients with infection, accounting for the assistance of external fixator and limited internal fixation group 62.5%; There was significant difference between the two groups(χ(2)=0.035, P>0.05). Five cases of fracture nonunion cases of serious infection, patients voluntarily underwent amputation. The Lysholm Knee Scale: In the external fixation group, 23 cases were less than 50 points, accounting for 60.5%, 15 cases were more than 50 points, accounting for 39.5%, external fixation and limited internal fixation group 20 cases were less than 50 points, accounting for 41.7%, 28 cases were more than 50 points, accounting for 58.3%; There was significant difference between the two groups(χ(2)=1.279, P>0.05). Conclusions: Prevention and control of infection is a central link in the treatment of open fracture of the knee. Trans articular external fixator plus limited internal fixation is an important measure to treat open fracture of the knee-joint.

[Mechanism of action for oligomeric proanthocyaniclins in pava qnat-induced acute lung injury].

Objective: The present study was designed to evaluate the protective effects of oligomeric proanthocyanidins (OPC) in mice exposed to paraquat (PQ) , and to explore the molecular mechanism. Methods: Four experimental groups were designed. CONTROL GROUP: 10 BALB/c mice were intraperitoneally injected with normal saline) . PQ group: 10 BALB/c mice were intraperitoneally injected with PQ (100 mg/kg) . PQ+OPC group: 10 BALB/c mice were administered with OPC (100 mg/kg) for 1 h before PQ (100 mg/kg) expo-sure. OPC group: 10 BALB/c mice were intraperitoneally injected with OPC (100 mg/kg) . The peripheral blood samples or lung tissue samples were collected at the designed time points for measuring the levels of oxi-dative stress indicators, the related protein levels of nuclear factor-kappa B (NF-κB) pathway and nuclear fac-tor erythroid related factor-2 (Nrf2) pathway. Results: Compared with the control group, the level of reactive oxygen species (ROS) , the content of malondialdehyde (MDA) in the PQ group were significantly induced, and the activity of superoxide dismutase (SOD) in the PQ group was decreased in the peripheral blood. As com-pared with the PQ group, the level of ROS and the content of MDA in the PQ+OPC group were significantly re-duced, the activity SOD in the PQ+OPC group was increased in the peripheral blood; the level of ROS and the content of MDA were also reduced in lung tissues in the PQ+OPC group. Moreover, compared with the con-trol group, the phosphorylation of IκBα and the expression of NF-κB p65 were increased in lung tissues in the PQ group. The phosphorylation of IκBα and the expression of NF-κB p65 were decreased in lung tissues in the PQ+OPC group as compared with the PQ group. In addition, compared with the control group, the expressions of HO-1 and Nrf2 were increased in lung tissues in OPC group, and these were decreased in lung tissues in PQ groups. Furthermore, the expressions of HO-1 and Nrf2 were also increased in lung tissues in PQ+OPC as com-pared with the PQ group. Conclusion: OPC could alleviate PQ-induced systemic toxicity in mice by regulating oxidative stress via NF-κB and Nrf2 pathway.

[Application value of combination of 18F-FDG pet and ultrasound cardiogram in the assessment of patients with severe coronary heart diseases].

Objective: To investigate the application value of combination of 18F-FDG PET and ultrasound cardiogram in the assessment of patients with severe coronary heart diseases. Methods: A total of 38 patients with severe coronary heart diseases who were admitted to Beijing Anzhen Hospital from January 2015 to November 2015 were enrolled.There were 32 men and 6 women in this study, and the mean age was 33-73(59±10)years.All patients underwent coronary angiography, PET myocardial metabolic imaging, and echocardiography to evaluate the degree of myocardial ischemia, percentage of infarcted myocardium, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD). On the basis of the clinical experience of Beijing Anzhen Hospital, the study allocated these 38 patients to a CABG group (n=20), who underwent CABG, and a non-CABG group treated by medical therapy alone (n=18). Results: A significantly smaller amount of abnormal myocardium was seen in the CABG group (28.9%±6.3% vs 43.3%±4.5%; P<0.01). The percentage of infarcted myocardium was significantly smaller in the CABG group (13.0%±4.1% vs 24.2%±5.5%) (P<0.01). LVEF was significantly greater (45.3%±3.8% vs 36.1%±6.3%, P<0.01) and LVEDD significantly smaller (54.2 mm±7.1 mm vs 65.1 mm±5.8 mm) in the CABG group (P=0.003). Percentage of abnormal myocardium was moderately negatively correlated with LVEF (r=-0.603, P=0.006). Percentage of infarcted myocardium was mildly negatively correlated with LVEF (r=-0.477, P=0.039). CABG was performed without complications.The LVEF of A1 group before and after operation were 45.3%±3.8% vs 51.6%±9.3%(P=0.043). The cardiac function of the patients was improved obviously after operation.All patients were followed for 1-10 months after discharge.The cure rate was 100%. Conclusion: In patients with severe coronary heart diseases undergoing CABG, 18F-FDG PET myocardial metabolic imaging combined with echocardiography have great value, they can assist in preoperative evaluation.

Several time indicators and Barthel index relationships at different spinal cord injury levels.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To compare different injury levels in spinal cord injury (SCI) patients with respect to operation intervention time (OIT), rehabilitation intervention time (RIT), average length of hospital stay (ALOS) and Barthel Index (BI) on admission and discharge. SETTING: China. METHODS: We retrospectively analyzed data from 95 SCI cases who received treatment in our rehabilitation center from 2010-2013. RESULTS: SCI resulted from high falls (55.79%), traffic accidents (28.42%), diseases (8.42%) and low falls (7.37%). We found no correlations between OIT, RIT, ALOS and discharge BI for all spinal segments (P>0.05). The OIT of thoracic SCI and lumbar SCI correlated negatively with RIT (P<0.01). The OIT of lumbar SCI correlated negatively with ALOS (P<0.05). CONCLUSION: BI had no correlation with OIT, RIT or ALOS for all spinal segments; the OIT of thoracic and lumbar SCI correlated negatively with RIT; and the OIT of lumbar SCI correlated negatively with ALOS.

Diagnostic value of cytological and microbiological methods in cryptococcal meningitis.

The aim of this study was to investigate diagnostic methods for cryptococcal meningitis (CM). A retrospective analysis was conducted for 31 patients with CM confirmed by etiologic detection of cerebrospinal fluid in our hospital in the past 5 years. Nineteen cases in 31 patients were confirmed with CM in the first diagnosis, with a misdiagnosis rate of 38.7%. The positive rates of cryptococcus detection in cerebrospinal fluid with May-Grünwald-Giemsa (MGG)-, ink-, and Alcian blue-staining methods were 86.9, 70.9, and 80.6%, respectively. The misdiagnosis rate of CM is high during the early stage of disease. The total positive rate of cryptococcus diagnosis using the MGG-staining method was significantly higher than that using the ink-staining method. These results are important for diagnosing CM.

Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGB1-RAGE axis.

High mobility group box B1 (HMGB1)-receptor for advanced glycation end products (RAGE) axis has been previously known to be involved in carcinogenesis and development of multiple malignancies. Some studies have confirmed that Ethyl pyruvate (EP), a potent inhibitor of HMGB1, exerts the therapeutic effects on metastatic live tumor from gastric cancer. However, the effects and possible molecular mechanisms of EP on gallbladder cancer (GBC) need to be further explored. In the present study, human GBC cell lines (GBC-SD and SGC-996) were treated with different concentrations of EP. Then, the expression levels of HMGB1, RAGE and some transcription factors were identified by Real-time PCR and Western blot assays. Cell proliferative activities indicated by MTT assay, invasive potential by Transwell assay and cell apoptosis and cycle distribution were performed for functional analysis of GBC cell lines in vitro. As a result, EP decreased the expression of HMGB11, RAGE, PCNA and matrix metallopeptidase-9 (MMP-9), while it increased the expression of p53. Moreover, EP administration decreased GBC cell proliferation, inhibited the invasive potential, and induced apoptosis and cycle arrest in S phase in GBC cells. In conclusion, EP administration inhibits growth and invasion of gallbladder cancer cells possibly via down-regulation of the HMGB1-RAGE axis, suggesting that EP may play a critical role in the treatment of cancer in conjunction with other therapeutic agents.

N-desulfated non-anticoagulant heparin inhibits leukocyte adhesion and transmigration in vitro and attenuates acute peritonitis and ischemia and reperfusion injury in vivo.

OBJECTIVE: Heparin, a highly sulfated proteoglycan, is known to have strong anticoagulant and anti-inflammatory activities. Here we sought to generate a heparin derivative, which had a significantly lower anticoagulant activity while retaining its strong anti-inflammatory activity. MATERIALS AND METHODS: Heparin was chemically modified and this discrete set of the heparin derivatives was tested for their anticoagulant activities, such as activated partial thromboplastin time (APTT), and anti-inflammatory activities, such as leukocyte adhesion and transmigration in vitro and acute peritonitis and ischemia and reperfusion injury in vivo. RESULTS: We found that an N-desulfated heparin had 188-fold (compared to heparin) and 32-fold (compared to low molecular weight heparin; LMWH) reductions of APTT. The N-desulfated heparin inhibited adhesion of human promyeloid HL-60 cells to the stimulated human umbilical vein endothelial cells (HUVECs) under a physiological shear stress. It also prevented the transmigration of human neutrophils through the monolayers of the stimulated HUVECs. Further, intravenous administration of this compound attenuated the peritoneal infiltration of neutrophils in a mouse model of acute peritonitis, and reduced tissue edema and leukocyte deposition in a rabbit ear model of ischemia and reperfusion injury. CONCLUSION: It is to our best knowledge that the N-desulfated heparin has the lowest anticoagulant activity among LMWH and chemically modified heparin derivatives, while preserving a potent anti-inflammatory activity. These combined properties appear to suggest it as a safer medicine for treatment of inflammation.

Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats.

Brain-derived neurotrophic factor (BDNF) is abundantly expressed in the hippocampus and cerebral cortex and is involved in synaptic plasticity and long-term potentiation (LTP). The present study was under taken to investigate whether endogenous BDNF was required for spatial learning and memory in a rat model. Antibodies to BDNF (anti-BDNF, n=7) or control immunoglobulin G (control, n=6) were delivered into the rat brain continuously for 7 days with an osmotic pump. The rats were then subjected to a battery of behavioral tests. The results show that the average escape latencies in the BDNF antibody treated group were dramatically longer than those of the control (F=13.3, p<0.001). The rats treated with control IgG swam for a significantly longer distance in the P quadrant (where the escape plane had been placed) compared with the other three quadrants (p<0.05). In contrast, anti-BDNF-treated rats swam an equivalent distance in all four quadrants. The average percentage of swimming distance in the P quadrant by anti-BDNF-treated rats was much less than that by control IgG treated rats (p<0.001). These results suggest that endogenous BDNF is required for spatial learning and memory in adult rats.