[Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology].

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

[Application of carbon nanoparticles mapping lymph nodes in curative resection for colorectal carcinoma].

Objective: To investigate the clinical application of carbon nanoparticles mapping lymph nodes in curative resection for colorectal carcinoma. Methods: Patients diagnosed with colorectal cancer before operation and undergoing radical surgery with intact postoperative pathological data in the Sixth Affiliated Hospital, Sun Yat-sen University from March 2016 to March 2018 were included in this retrospective case-control study. Those who were diagnosed with ileus, recurrent carcinoma or underwent emergency operation were excluded. A total of 1421 cases were included, with 156 cases in the carbon nanoparticles mapping group and 1265 cases in the control group. Using 1∶3 case control matching based on gender, weight, TNM staging and neoadjuvant chemotherapy, 145 and 435 cases were finally recruited in the carbon nanoparticles mapping group and control group, respectively. Patients in the carbon nanoparticles mapping group underwent preoperative colonoscopy with carbon nanoparticles submucosal injection 2.4 (1.0 - 14.0) days before operation. Carbon nanoparticles of 0.25 ml was injected at 4 points (3, 6, 9 and 12 o'clock each) 0.5-1.0 cm around the tumor. The number of eliminated lymph node, number of positive lymph node and positive rate between the two groups were compared, and the number of eliminated lymph node in different subgroups of T stage, N stage, TNM stage and neoadjuvant chemotherapy was analyzed and compared. Results: After case control matching, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher than that in the control group (22.2±11.2 vs. 19.0±9.5, t=3.025, P=0.003). However, no statistically significant differences were found in the number of positive lymph node and lymph node positive rate between two groups (all P>0.05). Subgroup analysis showed that as compared to the control group, total number of eliminated lymph nodes in the carbon nanoparticles mapping group was significantly higher in T3 stage subgroup (median: 22 vs. 18, Z=2.435, P=0.015), N0 stage subgroup (median: 20.5 vs. 17.5, Z=2.772, P=0.006), TNM II stage subgroup (median: 23.5 vs. 19.0, Z=2.654, P=0.008) and neoadjuvant chemotherapy (median: 22.5 vs. 13.0, Z=3.287, P=0.001), while compared to the control group, the number of positive lymph node (median: 4.0 vs. 6.5, Z=-2.530, P=0.011) and the lymph node metastasis degree (median: 16% vs. 31%, Z=-2.862, P=0.004) were lower in the carbon nanoparticles mapping group in N2 subgroup. Conclusion: Carbon nanoparticles mapping lymph nodes can effectively enhance the number of eliminated lymph nodes in curative resection for colorectal cancer.

[Analysis of gene mutations and clinic features in 108 patients with myeloproliferative neoplasm].

Objective: To analyze the genetic mutations and clinical features of the subtypes of classical BCR-ABL-negative myeloproliferative neoplasm (MPN) . Methods: Mutations of 108 newly diagnosed BCR-ABL-negative MPN patients [including 55 patients with essential thrombocytopenia (ET) , 24 with polycythemia vera (PV) , and 29 with primary myelofibrosis (PMF) ] were identified using next-generation sequencing with 127-gene panel, and the relationship between gene mutations and clinical features were analyzed. Results: Total 211 mutations in 32 genes were detected in 100 MPN patients (92.59% ) , per capita carried (1.96±1.32) mutations. 85.19% (92/108) patients carried the driver gene (JAK2, CALR, MPL) mutations, 69.56% (64/92) of these patients carried at least 1 additional gene mutation. In descending order of mutation frequency, the highest frequency was for activation signaling pathway genes (42.2% , 89/211) , methylation genes (17.6% , 36/211) , and chromatin-modified genes (16.1% , 34/211) . There was a significant difference in the number of mutations in the activation signaling pathway genes, epigenetic regulatory genes, spliceosomes, and RNA metabolism genes among the three MPN subgroups. The average number of additional mutations in PMF patients was higher than that in ET and PV patients (1.69±1.39, 0.67±0.70, 0.87±1.22, χ(2)=13.445, P=0.001) . MPN-SAF-TSS (MPN 10 score) (P=0.006) and myelofibrosis level (P=0.015) in patients with ≥ 3 mutant genes were higher and the HGB level (P=0.002) was lower than in those with<3 mutations. Twenty-six patients (24.1% ) carried high-risk mutation (HMR) , and patients with HMR had lower PLT (P=0.017) , HGB levels (P<0.001) , and higher myelofibrosis level (P=0.010) and MPN10 score (P<0.001) . The frequency of ASXL1 mutations was higher in PMF than in PV patients (34.5% vs. 4.2% , P=0.005) . PMF patients with ASXL1 had lower levels of PLT and HGB (P=0.029 and 0.019) . Conclusion: 69.56% of MPN patients carry at least one additional mutation, and 24.1% patients had HMR. Each subgroup had different mutation patterns. PMF patients had a higher average number of additional gene mutations, especially a higher frequency of ASXL1 mutation; PLT and HGB levels were lower in ASXL1 mutation PMF patients.

Development, validity and reproducibility of a whole grain food frequency questionnaire in Malaysian children.

BACKGROUND: To date, there is no validated whole grain assessment tool for children in any Southeast Asian countries. Hence, there is a need for a valid tool to assess whole grain intake among Malaysian children. This study aimed to develop, validate and test the reproducibility of a food frequency questionnaire (FFQ) in estimating whole grain intake among Malaysian children. METHODS: A total of 392 children participated in the FFQ development and 112 children aged 9-12 years participated in the validation phase; with a subsample of 50 children participating in the reproducibility phase. Three-day diet record (3DR) as the reference method in validation phase. Spearman correlations, mean difference, Bland-Altman plot and cross-classification analyses were used to assess validity. The reproducibility was tested through a repeat administration of the FFQ, with 1 month time interval. Reproducibility analyses involved intra-class correlation coefficient (ICC), Cronbach's alpha and cross-classification analyses. RESULTS: The FFQ consisted of 156 whole grain food items from six food groups. Mean intake of whole grain in FFQ1 and 3DR were correlated well (r = 0.732), demonstrated good acceptance of the FFQ. Bland Altman plots showed relatively good agreement for both the dietary methods. Cross-classification of whole grain intake between the two methods showed that < 9.9% of children were grossly misclassified. Outcomes from ICC (0.989) and Cronbach's alpha (0.995) demonstrated excellent reliability. All the children were classified in the same or adjacent quartile of whole grain intake. CONCLUSIONS: Overall, the findings support the validity of the developed FFQ to appropriately estimate the whole grain intake in Malaysian children. This validated FFQ will be a valuable tool for future studies, to analyses the impact of whole grain consumption with disease relationship among Malaysian schoolchildren.

Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes.

PURPOSE: Immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes. PROCEDURES: We have assessed the ability of a fluorine-labelled peptide, [18F]AlF-mNOTA-GZP, targeting granzyme B, to stratify ICI response in two syngeneic models of colon cancer, CT26 and MC38. In vivo tumour uptake of [18F]AlF-mNOTA-GZP following ICI monotherapy, or in combination with PD-1 was characterised and correlated with changes in tumour-associated immune cell populations. RESULTS: [18F]AlF-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8+ T cells; however, overall uptake and response to monotherapy or combination therapies was very different in the CT26 and MC38 tumours, likely due to the immunostimulatory environment imbued by the MSI-high phenotype in MC38 tumours. CONCLUSIONS: [18F]AlF-mNOTA-GZP uptake correlates well with changes in CD8+ T cell populations and is able to stratify tumour response to a range of ICIs administered as monotherapies or in combination. However, tracer uptake can be significantly affected by preexisting phenotypic abnormalities potentially confusing data interpretation.

RMP promotes venous metastases of hepatocellular carcinoma through promoting IL-6 transcription.

Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), which are responsible for tumor relapse and metastases. Portal vein tumor thrombus (PVTT) is raised from HCC and strongly correlated to a poor prognosis. However, the mechanism underling the formation of PVTT is largely unknown. Herein, we provide evidence that RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) was progressively upregulated in PVTT and overexpressed RMP appeared to increase T-ICs self-renewal. Moreover, RMP promoted metastases of PVTT cells and HCC cells in vitro and in vivo. Knockdown of RMP attenuated T-ICs self-renewal and reversed epithelial-mesenchymal transition (EMT) in HCC and PVTT cells. The neutralizing assays suggested that interleukin-6 (IL-6) had an indispensable role in RMP regulating metastases and self-renewal of HCC cells. Furthermore, the transcription of IL-6 was verified to be modulated by RMP via interaction with p65 and RPB5, through which expanding the T-IC/cancer stem cell populations, as well as inducing EMT was promoted. These results suggested that RMP may promote PVTT formation by promoting IL-6 transcription. Thus, RMP serves as a potent factor contributed to develop PVTT and a promising therapeutic target for HCC patients.

Asparagine synthetase is an independent predictor of surgical survival and a potential therapeutic target in hepatocellular carcinoma.

BACKGROUND: Asparagine synthetase (ASNS) is associated with drug resistance in leukaemia, and the function of this enzyme in the context of hepatocellular carcinoma (HCC) is not clear. In this study, the relationship between ASNS expression and clinical outcomes after surgical resection was investigated, and the therapeutic value of ASNS was also evaluated. METHODS: The expression of ASNS was evaluated in HCC samples by real-time PCR and immunohistochemistry assays. The correlation between ASNS expression and clinicopathological features was investigated. Potential clinicopathological prognostic factors were examined by univariate and multivariate survival analysis. Asparagine synthetase was overexpressed and knocked down in HCC cell lines to assess the influence of the enzyme on cell proliferation, migration and tumourigenicity. L-asparaginase was used to treat HCC cells with high or low levels of ASNS in vitro and in vivo to examine the therapeutic efficacy. RESULTS: The expression of ASNS was higher in HCC tumour tissues and was closely correlated with the serum AFP level, tumour size, microscopic vascular invasion, tumour encapsulation, TNM stage and BCLC stage. Patients with low ASNS expression levels had a poor prognosis with respect to overall survival (OS). The multivariate survival analysis indicated that ASNS is an independent prognostic factor for OS. Furthermore, functional studies demonstrated that ASNS significantly inhibits the proliferation, migration and tumourigenicity of HCC cells. The knockdown of ASNS markedly increased sensitivity to L-asparaginase, indicating that cells with different ASNS protein levels have different sensitivities to L-asparaginase. CONCLUSION: The expression of ASNS is an independent factor affecting the survival of HCC patients, and low ASNS expression in HCC was correlated with worse surgical outcomes. The ASNS may be a promising therapeutic target for the treatment of HCC.

Dynamic variations of c-Fos expression in the spinal cord exposed to intramuscular hypertonic saline-induced muscle nociception.

BACKGROUND: Numerous studies focus on intramuscular (i.m.) injection of hypertonic saline-induced muscle pain and nociception. The spatio-temporal characteristics and dynamic variation of spinal neuronal activities elicited by i.m. hypertonic saline remain unknown. METHODS: The spatio-temporal variations of c-Fos expression in the lumbar spinal cord exposed to i.m. injection of 5.8% saline were investigated in male rats. RESULTS: After a unilateral i.m. 5.8% saline injection, c-Fos expression in dorsal horn of spinal L4-6 segments was significantly enhanced bilaterally (p < 0.05 and p < 0.001). These 5.8% saline-induced bilateral spinal Fos expression occurred rapidly 0.5 h following the i.m. injection, and reached the peak levels within 1 h, which declined gradually and returned to the control levels within 8 h. Compared with intact rats without i.m. insults, no significant influence of the spinalization on spinal c-Fos expression was found. However, the 5.8% saline-induced increases in Fos expression in intact and spinalized rats differed significantly. During muscle nociception, the c-Fos expression within the superficial layer (laminae I-II) and the deep layer (laminae V-VI) in spinalized rats were significantly lower and higher than that of in intact rats (p < 0.05 and p < 0.001). Fentanyl (20 µg/kg, intraperitoneal) completely attenuated the 5.8% saline intramuscularly induced increases in c-Fos expression in laminae III-VI (p < 0.001), but not laminae I-II. CONCLUSIONS: It is suggested that spinal nociceptive neuronal activities in superficial and deep layers may differently be modulated by endogenous descending facilitation and inhibition, respectively.

Hepatocyte nuclear factor 4alpha attenuates hepatic fibrosis in rats.

BACKGROUND AND AIMS: Hepatocyte nuclear factor 4alpha (HNF4alpha) is a central transcriptional regulator of hepatocyte differentiation and function. The aim of this study was to evaluate the effect of HNF4alpha on attenuation of hepatic fibrosis. METHODS: The adenoviruses carrying HNF4alpha gene or containing siRNA targeting HNF4alpha were injected through tail vein on two distinct hepatic fibrosis models either induced by dimethylnitrosamine or by bile duct ligation in rats. Moreover, HNF4alpha, epithelial-mesenchymal transition (EMT)-related and fibrotic markers in hepatocytes, hepatic stellate cells (HSCs) and liver tissues were detected by real time PCR, immunofluorescence or immunohistochemistry. RESULTS: We demonstrated that decreased expression of HNF4alpha and epithelial markers accompanied by enhanced expression of mesenchymal markers occurred in fibrotic liver. More importantly, forced expression of HNF4alpha remarkably alleviated hepatic fibrosis and improved liver function with suppression of EMT in both fibrosis models. In contrast, downregulation of HNF4alpha by siRNA aggravated hepatic fibrosis and decreased the expression of E-cadherin in association with the enhanced expression of vimentin and fibroblast-specific protein-1. In vitro study revealed that HNF4alpha could suppress the EMT process of hepatocytes induced by transforming growth factor-beta1 and increase the expression of liver-specific genes. A similar phenomenon of the EMT process was observed during the activation of HSCs, which was abrogated by HNF4alpha. Additionally, HNF4alpha deactivated the myofibroblasts through inducing the mesenchymal-to-epithelial transition and inhibited their proliferation. CONCLUSIONS: Our study suggests that HNF4alpha is critical for hepatic fibrogenesis and upregulation of HNF4alpha might present as an ideal option for the treatment of hepatic fibrosis.

Ro 31-8220 inhibits release of interleukin-1 and interleukin-6 from mouse peritoneal macrophages induced by fibrin fibrinogen degradation products.

AIM: To study the effect of fibrin fibrinogen degradation products (FFDP) on release of interleukin-1 (IL-1) and interleukin-6 (IL-6) from mouse peritoneal macrophages, and the effect of a new selectively potent protein kinase C inhibitor Ro 31-8220 (Ro). METHODS: IL-1 and IL-6 activities were measured by thymocyte proliferation assay and B9 cell proliferation methyl thiazolyl tetrazolium (MTT) colorimetric method, respectively. RESULTS: Ro 0.01-1 mumol.L-1 obviously inhibited FFDP-induced release of IL-1 and IL-6 from mouse peritoneal macrophages. CONCLUSION: Ro exerted inhibitory effects on FFDP-induced release of IL-1 and IL-6 in vitro.

Total body lipid and triglyceride response to energy deficit: relevance to body composition models.

Although the study of human body composition is advancing rapidly, confusion still prevails regarding the molecular-level lipid component. Most molecular-level body composition models are presently based on the overall hypothesis that nontriglyceride lipids constitute an insignificant proportion of total body lipid. A single lipid or "fat" component consisting of triglycerides is thus assumed in most molecular-level body composition models. To test this hypothesis, the present study, carried out in adult rats, was designed to examine two questions: 1) What is the proportion of total lipids as triglycerides? and 2) Is this proportion constant or does it change with negative energy balance and weight loss produced by calorie restriction and increased exercise? Results indicated that with negative energy balance and weight loss there were progressive losses of total body triglyceride and lipid. The proportion of total lipids as triglyceride was 0.83 +/- 0.08 (SD) in control animals, with reductions at 2 and 9 wk of energy restriction [0.82 +/- 0.04 (P = NS vs. control) and 0.70 +/- 0.15 (P = 0.05)] and at 9 wk for energy restriction plus exercise [0.67 +/- 0.09 (P = 0.003)]. Nontriglyceride lipids comprised 2.8% of carcass weight at baseline and decreased to 2.2% by 9 wk of energy restriction and exercise (P = NS). Substantial differences were observed between body composition ratios expressed as percentages of the lipid-free body mass (LFM) and triglyceride-free body mass (TGFM); (e.g., total body water/LFM and TGFM in controls = 72.7 +/- 0.7 and 70.4 +/- 2.2, respectively; P = 0.02). These observations strongly support the existence and importance of nontriglyceride lipids as a body composition component that responds independently from storage triglycerides, with negative energy balance produced by food restriction and exercise.

Levels of immunoreactive dynorphin A1-13 during development of morphine dependence in rats.

AIM: To study the relationship between the levels of immunoreactive dynorphin A1-13 (ir-dynorphin A1-13) and the degree of morphine dependence. METHODS: The levels of ir-dynorphin A1-13 in discrete brain regions, spinal cord, and plasma in rats were determined by radioimmunoassay, and the degree of morphine dependence was assessed by scoring withdrawal signs on d 3, d 6, and d 12. RESULTS: Morphine injection s.c. decreased the levels of ir-dynorphin A1-13 in spinal cord, pituitary, and plasma. The levels of ir-dynorphin A1-13 in hippocampus and hypothalamus were increased. No changes in cortex, midbrain, cerebellum, pons, and medulla were observed. With continuous injection of morphine, withdrawal signs scores were increased on d 6, but there was no difference between the scores of d 6 and d 12. CONCLUSION: The changes of the levels of endogenous ir-dynorphin A1-13 in pituitary, spinal cord, and plasma were compatible with the degree of morphine dependence.

New electrode system for rapid whole-body and segmental bioimpedance assessment.

Skeletal muscle is a clinically important body composition component which at present is difficult to quantify in vivo. Previous studies suggest that measured appendicular resistance at 50 kHz can be used to predict extremity skeletal muscle mass, although accurate technician placement of multiple gel electrodes is required. In the present study we developed a new bioimpedance analysis (BIA) electrode stand designed for rapid whole-body and segmental resistance and reactance measurements. The new system incorporates stainless steel hand and foot contact electrodes in place of gel electrodes and employs a previously reported lead placement algorithm for deriving extremity resistances without the need for placing conventional proximal limb gel electrodes. This report describes the new electrode system's design and examines the relationships between contact and gel electrode-measured resistance and between appendicular resistance measured with the recently reported lead placement algorithm and conventionally placed segmental electrodes. Results in healthy adults demonstrate high correlations between contact and gel electrodes (e.g., hand-to-hand, N = 12, r = 0.994, P < 0.001) and between segmental resistance measured by the recently reported approach and conventionally-measured segmental resistance (e.g., right arm, N = 13; r = 0.997, P < 0.001). These results strongly support the validity of the new electrode system's resistance measurements and suggests the feasibility of developing a BIA system for rapidly measuring extremity skeletal muscle mass.

[Effects of calcium inhibitor on hydrogen peroxide-induced damage and calcium influx in bovine aortic endothelial cells in culture].

Hydrogen peroxide(H2O2)-induced cell damage and Ca2+ influx into bovine aortic endothelial cells (BAEC) were investigated. Our data suggested that H2O2 could dose- and time-dependently induce damage in cultured BAEC assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay and increase malondialdehyde (MDA) production, which reflects the level of lipid peroxidation. Exposure of BAEC to H2O2 (100 mumol.L-1) caused significant increase in intracellular free calcium ([Ca2+]i) within 6 min, suggesting that the increase of [Ca2+]i might implicate in H2O2-induced cell damage. The calcium inhibitor nifedipine was found to dose-dependently decrease the increase of [Ca2+]i caused by H2O2 and protect BAEC against H2O2-induced damage reflected by significant decrease of MDA production and increase of MTT value. These results indicate that overload of calcium might be responsible to some extent causing oxidative damage to cells.

Protection of ebselen against anoxic damage of cultured neurons of cerebral cortex.

AIM: To study the protective effect of ebselen on anoxic damage of brain cells. METHODS: On d 10 after plating of the cortical neurons from 1-d-old rat, cultures were placed under 95% N2 + 5% CO2 for 2-6 h. Lactate dehydrogenase (LDH) in supernatant, thiobarbituric acid reactive substance (TBARS) and glutathione peroxidase (GSH-Px) activity of neurons were determined. RESULTS: Under anoxia, efflux of LDH and TBARS from cultured neurons increased while GSH-Px activity decreased. Ebselen reduced the efflux of LDH and TBARS in a dose-related manner and increased the total GSH-Px activity. CONCLUSION: Ebselen can protect neurons from anoxic damage.

[Protection of ebselen on oxygen free radical-induced lipid peroxidation damage of cultured rat cortical neuron and cortical mitochondria].

Ebselen (2-phenyl-1, 2-benzisoselenanzol-3 (2H) one, C13 H9NOSe) is a seleno-organic anti-oxidant compound. In this study, the effect of ebselen on lipid peroxidation damage induced by O2.- and .OH in vitro, of cultured rat cortical neuron and cortical mitochondria was studied. When neuron was exposed to hypoxanthine/xathine oxidase system and vitamin C/CuSO4 system, obvious damage was detected: lactic dehydrogenase(LDH) was released and TBARS content increased. Ebselen (10, 25, 50 mumol.L-1) reduced LDH efflux induced by O2.- and .OH in a dose-dependent manner. As for the TBARS content, from 5 mumol.L-1 to 50 mumol.L-1, ebselen negated its increase, also dose-dependently. Furthermore, ebselen lowered TBARS content of cortical mitochondria treated with O2.- and .OH in a dose-related manner. But ebselen showed no activity of scavenging O2.- and .OH. This suggests that ebselen has direct anti-oxidant activity on neuron and its activity is not achieved by scavenging oxygen free radical.

[Effects of inhibitor of protein kinase C on brain edema formation evoked by experimental cerebral ischemia in gerbils and rats].

Recent studies have suggested that protein kinase C (PKC) may be involved in the formation of brain edema. In this paper, the effects of two kinds of PKC inhibitors, H-7 and matrine, were examined on the brain edema formation in experimental models. The results showed that pretreatment with H-7 6.25 and 12.5 mg.kg-1 prevented the accumulation of water and certain electrolytes in the unilateral hemisphere of the brain evoked by ligation of a single common carotid artery in Mongolian gerbil; pretreatment with matrine 25 and 50 mg.kg-1 reduced the extent of cerebral edema formation evoked by ligation of a single common carotid artery in gerbil and by middle cerebral artery occlusion in Sprague-Dawley rats. These results present new evidence for the involvement of PKC in the formation of brain edema.

[Short-term energy and protein support in mechanically ventilated patients with acute exacerbation of cor pulmonale].

Twenty-one mechanically ventilated patients with acute exacerbation of cor pulmonale had received home made "Nutritient" via nasal gastric tube as energy and protein support for four weeks (energy supplement 37-45 kcal.kg-1.d-1, protein 1.40-1.67 g.kg-1.d-1). Anthropometry, serum albumin, serum prealbumin were measured on the 1st day and at the end of the 1st, 2nd, 4th week of ventilation. The results were compared with those in 15 age-matched ventilated patients who received routine hospital nasal gastric feeding (energy 24-29 kcal.kg-1.d-1, protein: 0.92-1.09 g.kg-1.d-1). All patients were in protein deficient type malnutrition. At the end of the 1st week of ventilation, serum albumin dropped significantly in both groups, resulting in a status of mixed type malnutrition. At the end of the 2nd week, however, serum prealbumin in the experimental group (24.31 +/- 4.80 mg/dl) returned nearly to normal level, being significantly higher than that in the control group (15.10 +/- 3.10 mg/dl, P < 0.01). At the end of the 4th week, both serum albumin (3.90 +/- 0.31 g/dl) and prealbumin (27.33 +/- 3.30 mg/dl) in experimental group returned to normal, being also significantly higher than those in the control group (3.00 +/- 0.23 g/dl, P < 0.05; 17.11 +/- 3.22 mg/dl, P < 0.01). Anthropometry showed no significant change between the two groups during ventilation. It is shown that nasal tube administration of "Nutritient" provides much higher energy and protein as compared with routine nasal feeding, and enables the patient to overcome protein deficiency and to reach positive nitrogen balance earlier.