Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.

T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

[Experimental Study of Ginsenoside Rg1 Combined with Antibiotics in the Treatment of Acute Lung Injury in Mice with Sepsis].

OBJECTIVE: To observe the effect of ginsenoside Rg1 on the acute lung injury of sepsis in combination with the antibiotic imipenem in a mouse model of sepsis that induced by cecal puncture. METHODS: C57BL/6 mice were used to establish the model of sepsis. The model mice were randomly divided into model group, imipenem group, ginsenoside Rg1 group, and ginsenoside Rg1+imipenem group, 10 mice in each group. Another 10 mice were set as control group. Sham operation was performed in the mice of control group. Each mice was intraperitoneally injected the corresponding drug in 2 h, 26 h and 50 h after surgery for three times. They were 2 h after surgery, 26 h after surgery and 50 h after surgery. 2 h after the last administration, the oxygenation index of the arterial blood was measured, the lung tissue was taken to measure lung wet/dry ratio (W/D), and HE staining was used to observe the lung inflammation. The ELISA kits were used to detect the levels of interleukin (IL)- 1ß, IL-6, tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) inalveolar lavage fluid. Western blot and immunohistochemical staining were used to detect NF-κB p65 expression in lung tissues. RESULTS: The drug-administered groups significantly reduced the W/D of the lungs in the septic mice and increased the oxygenation index in the blood ( P<0.01), and decreased the inflammation in lung and the levels of IL-1ß, IL-6, TNF-α and NF-κB in the alveolar lavage fluid ( P<0.01), and decreased the expression of NF-κB p65 in lung tissue ( P<0.01). When ginsenoside Rg1 was combined with imipenem, the above indicators were closer to the control group than that in the ginsenoside Rg1 and imipenem groups. CONCLUSION: Rg1 can significantly inhibit lung inflammation in septic mice. It has a better therapeutic effect when combined with antibiotics.

Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China.

Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses. Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles. Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues. Conclusion:  Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.

Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China.

BACKGROUND: We investigated whether BCMO1 variants and dietary patterns are associated with lung cancer risk. METHODS: Case-control study including 1166 lung cancer cases and 1179 frequency matched controls was conducted for three BCMO1 variants (rs6564851, rs12934922, and rs7501331) and four dietary patterns were investigated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The rs6564851, rs12934922, and rs7501331 were not found to be associated with lung cancer risk (P > 0.05). In multivariable-adjusted models, compared to the lowest quartile of the score on the "fruits and vegetables" pattern, the highest quintile was associated with a 78.4% decreased risk (OR Q4 vs. Q1 = 0.216; 95% CI, 0.164-0.284; P for trend < 0.001). Other patterns were not found the association. The "fruits and vegetables" pattern was associated with a reduced risk of lung cancer with all 3 SNPs irrespective of genotypes (all P for trend< 0.001). The association for the "Frugal" pattern was associated with increased risk of lung cancer among smokers (P for interaction = 0.005). The protective effects of the "cereals/wheat and meat" pattern was more evident for squamous cell carcinoma and other histological type. CONCLUSIONS: We did not observe associations of BCMO1 variants and lung cancer. Diets rich in fruits and vegetables may be protective against lung cancer.

The association between human papillomavirus infection and lung cancer: a system review and meta-analysis.

To estimate the global attributable fraction of human papillomavirus (HPV) in lung cancer, we provided updated information through a system review and meta-analysis. We did a literature search on PubMed, Ovid and Web of Science to identify case-control studies and cohort studies that detected HPV in lung carcinomas. We included studies that tested 30 or more cases and were published before Feb 28, 2017. We collected information about gender, smoking status, HPV detection methods, HPV types, materials and clinical features. If it was not possible to abstract the required information directly from the papers, we contacted the authors. A meta-analysis was performed to calculate the pooled effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0 software. 36 case-control studies, contributing data for 6,980 cases of lung cancer and 7,474 controls from 17 countries and one cohort study with 24,162 exposed and 1,026,986 unexposed from China were included. HPV infection was associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60-5.08), calculated with the random-effects model. Pooled OR for allogeneic case-control studies, self-matched case-control studies and nested case-control studies were 6.71 (95% CI: 4.07-11.07), 2.59 (95% CI: 1.43-4.69) and 0.92 (95% CI: 0.63-1.36), respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07-4.76) and 2.25 (95% CI: 1.49-3.40), respectively. We also found that HPV infection may be associated with squamous cell carcinoma, adenocarcinoma and small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and HPV 18 infection, significantly increase the risk of lung cancer. Future research needs to focus attention toward whether an HPV vaccine can effectively reduce the incidence of lung cancer.

The relationship of lung cancer with menstrual and reproductive factors may be influenced by passive smoking, cooking oil fumes, and tea intake: A case-control study in Chinese women.

The aim of this study was to investigate the association of menstrual and reproductive factors with risk of lung cancer in women. Potential etiological clues related to lung cancer in women are identified to inform preventive strategies.Case-control study of 477 newly diagnosed women with lung cancer and 479 age-matched (±2 years) controls. Data on menstrual and reproductive factors and history of oral contraceptive use were obtained on personal interviews using a structured questionnaire. Risk factors were analyzed by unconditional logistic regression analysis.Maternal age ≥25 years at first birth appeared to protect against female lung cancer [odds ratios (ORs): 0.511, 95% confidence interval (CI), 0.376-0.693]. Age at menopause > 50 years and use of contraceptives was associated with an increased risk of lung cancer in women (OR: 1.471, 95% CI, 1.021-2.119 and OR: 1.844, 95% CI: 1.111-3.061, respectively). Age ≥13 years at menarche was associated with a decreased risk of lung adenocarcinoma (OR: 0.563, 95% CI, 0.317-0.997). There was significant heterogeneity in the levels of cooking oil fume (COF) exposure (Pheterogeneity = .015). Higher levels of exposure to passive smoking, COF, and lack of tea intake were associated with an increased risk of lung cancer.Menstrual and reproductive factors are considered to play a role in the development of lung cancer in women. Exposure to passive smoking, COF, and lack of tea intake appeared to significantly modify the relationship.

A case-control study of the association between self-reported occupational and recreational physical activity and lung cancer.

This case-control study with a Fujian population investigated whether self-reported occupational and recreational physical activity may be associated with lung cancer.The population comprised 1622 patients with newly diagnosed primary lung cancer and 1622 age- and gender-matched healthy controls.High-intensity occupational physical activity was associated with significantly higher risk of lung cancer (OR = 1.354, 95% CI: 1.068-1.717), especially nonsmall cell lung carcinoma (OR = 1.384, 95% CI: 1.087-1.762). Moderate or low intensity recreational physical activity was associated with reduced risk of lung cancer. The protective effect of recreational physical activity was observed in current or former smokers, but not never-smokers, and in subjects with normal or high BMI, but not low BMI, as well as people without a history of chronic lung disease. The frequency of recreational physical activity was associated with a linear reduction in the risk of lung cancer (P < .001), and also specifically nonsmall cell lung cancer (P < .001).Occupational and recreational physical activity was associated with different effects on the risk of lung cancer in a Fujian population. While recreational physical activity was associated with decreased risk of lung cancer, occupational physical activity was associated with increased risk of lung cancer.

Phase I clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma.

AIM: To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC). METHODS: A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. RESULTS: Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects. CONCLUSION: Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.

MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality in China and the third leading cause worldwide. A number of microRNAs (miRNAs) have been implicated in cell cycle progression, growth, apoptosis, angiogenesis and metastasis in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect the levels of miR-302d expression in the tissues of 30 patients with HCC. Cell cycle, growth, apoptosis and migration were analyzed using a cell counting kit, flow cytometry and a Transwell migration assay. Dual-luciferase reporter assays and western blotting were also used to analyze the expression levels of transforming growth factor beta type II receptor (TGFBR2) in HCC cells. The present study evaluated the role of miR-302d in the development and progression of HCC. Abnormally high expression of miR-302d was observed in 80% of HCC specimens. Moreover, patients with lower levels of miR-302d expression experienced a longer survival time than those with higher levels of miR-302d expression. It was demonstrated that miR-302d promoted HCC cell growth and migration, suppressed cell apoptosis and affected cell cycle distribution in vitro, and augmented tumorigenicity in vivo. Furthermore, TGFBR2, which is a tumor suppressor, was confirmed as a target of miR-302d in HCC cells. Dual-luciferase reporter assays indicated that TGFBR2 expression was negatively regulated by miR-302d. Taken together, the results of the present study suggest that miR-302d may serve as a valuable tool for predicting the prognosis of patients with HCC.

Role of autophagy in acute myeloid leukemia therapy.

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain.

ETHNOPHARMACOLOGICAL RELEVANCE: Oxymatrine is extracted from the traditional Chinese herb Sophora flavescens Ait, possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, and has been used for the treatment of chronic viral hepatitis and many other diseases. AIMS OF THE STUDY: This study aimed to investigate the effects of oxymatrine on inflammatory response mediated by Toll-like receptor4 (TLR4) and nuclear factor kappa-B (NF-κB), oxidative injury induced by 12/15 lipoxygenase (12/15-LOX), phosphorylated p38 mitogen activated protein kinase (phosphor-p38 MAPK) and cytosolic phospholipase A2 (cPLA2), and neuronal cell apoptosis in rat brain with intracerebral hemorrhage (ICH). MATERIALS AND METHODS: Wistar rats were treated intraperitoneally with 60 or 120mg/kg of oxymatrine daily for 5 days following ICH. The rats were sacrificed at hour 2, 6, 12, 24, 48, 72, and 120 after ICH. The gene expressions of TLR-4 and NF-κB, the levels of TNF-alpha, interleukin-1beta, interleukin-6, 12/15-LOX, phospho-p38 MAPK and cPLA2, and the number of apoptotic neuronal cells in rat brain were determined. RESULTS: Oxymatrine at 120mg/kg significantly suppressed gene expressions of TLR-4 and NF-κB, decreased levels of TNF-alpha, interleukin-1beta and interleukin-6, inhibited synthesis of 12/15-LOX, phospho-p38 MAPK and cPLA2 protein, and mitigated apoptotic neuronal changes following ICH in rat. CONCLUSION: Oxymatrine at 120mg/kg following ICH inhibits inflammatory responses, oxidative injury, and neuronal cell apoptosis in rats.

High hospital occupancy is associated with increased risk for patients boarding in the emergency department.

BACKGROUND: Boarding admitted patients in the emergency department due to high hospital occupancy is a worldwide problem. However, whether or not emergency department-boarded patients managed by emergency department providers subjects them to increased serious complications needs further clarification. METHODS: A multivariate logistic regression analysis was used to examine the relationship of patient's age, sex, arrival hours, diagnostic category, triage category, daily emergency department visits, and daily hospital occupancy to the occurrence of serious complications within 24 hours for 20,276 emergency admissions in a 4-year period. RESULTS: A vast majority of study days (86.5%) saw very high occupancy ≥90%. Serious complications incidence was 13.62 per 1000 patient days when hospital occupancy was ≤90%, and it increased significantly to 17.10 and 22.52 per 1000 patient days for occupancy at 90%-95% and ≥95%, respectively. In the multivariate analysis, significant risk factors for serious complications included daily occupancy ≥95% (adjusted odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.39), triage category (adjusted OR 0.20; 95% CI, 0.17-0.24), and specific diagnoses (injury and poisoning [adjusted OR 1.62; 95% CI, 1.22-2.84], respiratory [adjusted OR 2.48; 95% CI, 1.37-4.49], and circulatory [adjusted OR 3.24; 95% CI, 1.80-5.80]). CONCLUSION: High hospital occupancy was associated with an increased incidence of serious complications within 24 hours for patients admitted but still boarded in the emergency department and managed by emergency department providers.

Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgolide B (GB) is one of the ginkgolides that have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L. (Ginkgoaceae), and is a specific and potent antagonist of platelet activating factor. There is a large body of data showing that GB possesses a markedly neuroprotective property against ischemia-induced impairment in vivo and in vitro. Recently it has been found that GB can inhibit the inflammation in the rat brain tissues with ischemia/reperfusion injury and in the astrocytes treated with lipopolysaccharide, as well as protect neurons against beta-amyloid 25-35 and ischemia-induced apoptosis. However, there have been few reports on the influence of GB on intracerebral hemorrhage (ICH). This study was to investigate the effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines and Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway after ICH. MATERIALS AND METHODS: Wistar rats obtained an intraperitoneal injection of 5, 10 and 20mg/kg GB after ICH once a day till day 5. Rats were sacrificed by decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene expressions of TLR-4 and NF-κB, concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) as well as number of apoptotic neuronal cells in hemorrhagic rat brain tissues were determined. RESULTS: The administration of 10 and 20mg/kg GB could significantly suppress gene expressions of TLR-4 and NF-κB, lessen concentrations of TNF-α, IL-1ß and IL-6 as well as reduce number of apoptotic neuronal cells in hemorrhagic rat brain tissues by Least-significant Difference test (P<0.05), but the administration of 5mg/kg GB not (P>0.05). However, a clear concentration-response relationship was not found. CONCLUSIONS: GB may inhibit TLR4/NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after ICH, which may support the use of G. biloba extracts for the treatment of ICH.

Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with (L)-serine ligand on septic pigs.

A novel adsorber, polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser), was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfusion. Endotoxin adsorption efficiency (EAE) of the adsorber was firstly measured in vitro. The biocompatibility and hemodynamic changes during extracorporeal circulation were then evaluated. One half of 16 pigs receiving lipopolysaccharide (Escherichia coli O111:B4, 5 µg/kg) intravenously in 1 h were consecutively treated by hemoperfusion with the new adsorber for 2 h. The changes of circulating endotoxin and certain cytokines and respiratory function were analyzed. The 72 h-survival rate was assessed eventually. EAE reached 46.3% (100 EU/ml in 80 ml calf serum) after 2 h-circulation. No deleterious effect was observed within the process. The plasma endotoxin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were decreased during the hemoperfusion. Arterial oxygenation was also improved during and after the process. Furthermore, the survival time was significantly extended (>72 h vs. 47.5 h for median survival time). The novel product PVDF-Ser could adsorb endotoxin with high safety and efficacy. Early use of extracorporeal hemoperfusion with the new adsorber could reduce the levels of circulating endotoxin, IL-6, and TNF-α, besides improve respiratory function and consequent 72 h-survival rate of the septic pigs. Endotoxin removal strategy with blood purification using the new adsorber renders a potential promising future in sepsis therapy.

Current recognition and management of intra-abdominal hypertension and abdominal compartment syndrome among tertiary Chinese intensive care physicians.

This survey was designed to clarify the current understanding and clinical management of intra-abdominal hypertension (IAH)/abdominal compartment syndrome (ACS) among intensive care physicians in tertiary Chinese hospitals. A postal twenty-question questionnaire was sent to 141 physicians in different intensive care units (ICUs). A total of 108 (76.6%) questionnaires were returned. Among these, three quarters worked in combined medical-surgical ICUs and nearly 80% had primary training in internal or emergency medicine. Average ICU beds, annual admission, ICU length of stay, acute physiology and chronic health evaluation (APACHE) II score, and mortality were 18.2 beds, 764.5 cases, 8.3 d, 19.4, and 21.1%, respectively. Of the respondents, 30.6% never measured intra-abdominal pressure (IAP). Although the vast majority of the ICUs adopted the exclusively transvesicular method, the overwhelming majority (88.0%) only measured IAP when there was a clinical suspicion of IAH/ACS and only 29.3% measured either often or routinely. Moreover, 84.0% used the wrong priming saline volume while 88.0% zeroed at reference points which were not in consistence with the standard method for IAP monitoring recommended by the World Society of Abdominal Compartment Syndrome. ACS was suspected mainly when there was a distended abdomen (92%), worsening oliguria (80%), and increased ventilatory support requirement (68%). Common causes for IAH/ACS were "third-spacing from massive volume resuscitation in different settings" (88%), "intra-abdominal bleeding", and "liver failure with ascites" (52% for both). Though 60% respondents would recommend surgical decompression when the IAP exceeded 25 mmHg, accompanied by signs of organ dysfunction, nearly three quarters of respondents preferred diuresis and dialysis. A total of 68% of respondents would recommend paracentesis in the treatment for ACS. In conclusion, urgent systematic education is absolutely necessary for most intensive care physicians in China to help to establish clear diagnostic criteria and appropriate management for these common, but life-threatening, diseases.

[Protective effect of Xingnaojing and Xuesaitong injections on cerebral ischemic reperfusion injury in rats].

OBJECTIVE: To investigate the mechanism of protective effect of Xingnaojing and Xuesaitong injections on cerebral ischemic reperfusion injury in rats. METHODS: The focal cerebral ischemia & reperfusion model was established by middle cerebral artery occlusion (MCAO). A total of 152 male SD rats were randomly assigned into 19 groups: sham operated group, Xingnaojing group, Xingnaojing plus Xuesaitong group and control group according to different reperfusion durations: 2, 4, 8, 24, 48, 72 h. Each group had 8 rats. Rats in Xingnaojing group received the ip injections of Xingnaojing (1 ml x 100 (-1) x d(-1)) until an onset of ischemia; Xingnaojing plus Xuesaitong group received the ip injections of Xingnaojing (1 ml x 100 g(-1) x d(-1)) and Xuesaitong (1 ml x 100 g(-1) x d(-1)) until an onset of ischemia; In the meantime, rats in control group received the same ip dose of saline. The levels of SOD and MDA were detected. The number of apoptotic neurons was detected by terminal-deoxynucleotidyl transferase medicated nick end labeling (TUNEL). RESULTS: During ischemic reperfusion, the MDA content of brain homogenate increased while the SOD activity decreased (P < 0.05). Xingnaojing could significantly inhibit the increase of MDA after cerebral ischemic reperfusion (P < 0.05) and the decrease of SOD activity in rats. The changes of SOD and MDA were smaller in the Xingnaojing plus Xuesaitong group than those in the Xinnaojing group (P < 0.01). The number of apoptotic neurons in the Xingnaojing group was significantly lower than that in control group (P < 0.05). And the number of apoptotic neurons in the Xingnaojing plus Xuesaitong group was even lower than that in the Xingnaojing group(4,8 h: P < 0.05, 24, 48, 72 h: P < 0.01). CONCLUSION: The Xingnaojing plus Xuesaitong injection has protective function after cerebral ischemic reperfusion.

Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury.

OBJECTIVE: To explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier (BBB) in rats following traumatic brain injury (TBI). METHODS: A total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups: sham-operation, TBI and Xingnaojing injection groups (10 ml/kg/d, intraperitoneal injection). TBI in rats was set up by the improved device of Feeney's weight-dropping model with the impact of 600 g.cm. Brain water content and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery. RESULTS: In sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%+/-1.22% and 5.13 microgram+/-0.71 microgram. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days (83.49%+/-0.54%, 82.74%+/-0.72%, 80.22%+/-0.68%, 79.21%+/-0.60%), being significantly higher than that in sham operation group (P less than 0.05). Evans blue content was increased in TBI group (16.54 microgram+/-0.60 microgram, 14.92 microgram+/-0.71 microgram, 12.44 microgram+/-0.92 microgram, 10.14 microgram+/-0.52 microgram) as compared with sham-operation group(P less than 0.05). After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group (81.91%+/-1.04%, 80.38%+/-0.72%, 79.54%+/-0.58%, 78.60%+/-0.77%, P less than 0.05). Xingnaojing injection also reduced the leakage of BBB as compared with TBI group (15.11 microgram+/-0.63 microgram, 13.62 microgram+/-0.85 microgram, 10.06microgram+/-0.67 microgram, 9.54 microgram+/-0.41 microgram, P less than 0.05). CONCLUSION: Xingnaojing injection could alleviate cerebral edema following TBI via reducing permeability of BBB.

Effect of increased intra-abdominal pressure and decompressive laparotomy on aerated lung volume distribution.

Increased intra-abdominal pressure (IAP) is common in intensive care patients, affecting aerated lung volume distribution. The current study deals with the effect of increased IAP and decompressive laparotomy on aerated lung volume distribution. The serial whole-lung computed tomography scans of 16 patients with increased IAP were retrospectively analyzed between July 2006 and July 2008 and compared to controls. The IAP increased from (12.1+/-2.3) mmHg on admission to (25.2+/-3.6) mmHg (P<0.01) before decompressive laparotomy and decreased to (14.7+/-2.8) mmHg after decompressive laparotomy. Mean time from admission to decompressive laparotomy and length of intensive-care unit (ICU) stay were 26 h and 16.2 d, respectively. The percentage of normally aerated lung volume on admission was significantly lower than that of controls (P<0.01). Prior to decompressive laparotomy, the total lung volume and percentage of normally aerated lung were significantly less in patients compared to controls (P<0.01), and the absolute volume of non-aerated lung and percentage of non-aerated lung were significantly higher in patients (P<0.01). Peak inspiratory pressure, partial pressure of carbon dioxide in arterial blood, and central venous pressure were higher in patients, while the ratio of partial pressure of arterial O(2) to the fraction of inspired O(2) (PaO(2)/FIO(2)) was decreased relative to controls prior to laparotomy. An approximately 1.8 cm greater cranial displacement of the diaphragm in patients versus controls was observed before laparotomy. The sagittal diameter of the lung at the T6 level was significantly increased compared to controls on admission (P<0.01). After laparotomy, the volume and percentage of non-aerated lung decreased significantly while the percentage of normally aerated lung volume increased significantly (P<0.01). In conclusion, increased IAP decreases total lung volume while increasing non-aerated lung volume. Decompressive laparotomy is associated with resolution of these effects on lung volumes.

Aquaporin-4 and traumatic brain edema.

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.

Diagnosis and treatment of organotin poisoned patients.

BACKGROUND: With the development of industry and agriculture, organotin compounds have been widely used in China. Organotin compounds cause a common occupational poisoning. The toxicity of organotin was reported in animal studies; however the reports about human organotin intoxication are very rare. In this study we retrospectively analyzed the clinical manifestations of 15 organotin-poisoned patients who had been treated at our hospital from 2002 through 2007. METHODS: Fifteen patients with organotin poisoning were admitted to Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from 2002 to 2007. They were 9 males and 6 females, aged from 25 to 52 years. Clinical manifestations and Glasgow Coma Scales showed that the poisoning was mild in 4 patients, moderate in 6 and severe in 5. The severe patients were given glucocorticoid after hospitalization by intravenous guttae of 500 mg methylprednisolone for the first day, followed by 160 mg methylprednisolone per day for three days, and then 80 mg methylprednisolone per day for another three days. Potassium glutamate and sodium glutamate were intravenously dripped to reduce blood ammonia; intravenous guttae plus oral administration of potassium 9 g/day was used to correct intractable hypokalemia; sodium bicarbonate was used to correct metabolic acidosis, and sedatives were used to control spasm and twitch; mechanical ventilators were used in 4 patients with dyspnea. RESULTS: Most of the patients showed elevated level of blood ammonia, decreased level of blood potassium and metabolic acidosis, but some had demyelination changes shown by CT and MRI. Treatments included correction of metabolic acids, blood potassium and ammonia, and mechanical ventilation when necessary. For patients with injuries of the nervous system, glucocorticoids were given immediately after hospitalization. These patients showed intractable hypokalemia and metabolic acidosis during the treatment. Forteen patients recovered completely without long-term side-effect. One patient in the aphasiac stage restored the linguistic capacity during a 6-month follow-up. CONCLUSIONS: Elevated level of blood ammonia, decresed level of blood potassium, and metabolic acidosis are common in patients with organotin poisoning. Demyelination can be observed in patients with severe poisoning. The abnormalities of the patients are reversible after suitable treatments.