Adenosine is an endogenous purine uncleoside released by cells as part of the normal metablic mechinary. During inflammation, massive ATP degradation increases the local adenosine concentration to the micromolar range, at the range, adenosine extert potent antiinflammatory rale. In vivo or in vitro experiments, the addition exogenious adenosine, its analogues and inhibition of its degradation attenuate injury of animal models of inflammation. Antiinflammatory mechinasms involve in;(1)Adenosine inhibites neutrophil function in vitro, including chemotaxiz, adhesion, phogocytosis, and oxygen radical generation. (2) Decrease the expression of collagenase, and reduce the amount of collagenase. (3)Blocking neutrophil adhesion to the endothelium mediated by L-selectin and ftrEategrin. (4)inhibition activated humanmonocytes and macrophage secreting cytokins. (5) Adenosine enhances IL-10 secretion by human monocytes. (6)inhibition of immune response and so on. Relation with nonsteroidal antiinflammatory drugs (NSALDs) includes:(1)MTX and SASP inhibit the activity of 5-aminoimidazole-4-carboxam-ide ribonucleotide (AICAR) transformylase resulting in increased local adenosine concentraton. (2) Azathioprine and its potential metabolite inhibits adenosine kinase, diminish AMP formation by adenosine. In conclusion, the existance of a novel class of antiinflammatory agents, affects adenosine metabolism and may be a useful antiinflammatory drug as well.

Objective To study the effect of extracellular signal-regulated kinase1/2 (ERK1/2)inhibitor U0126 on matrix metalloproteinase-9(MMP-9)in brain tissue after subarachnoid hemorrhage(SAH)in rats and to investigate the action mechanisms of ERK1/2 and M M P-9 in blood-brain barrier(BBB)injury and brain edema after SAH.Methods Seventy-two male Sprague-Dawley rats were randomly divided into four groups:SAH model,sham operation,U0126 intervention,and vehicle groups.A SAH model was induced by injection of autologous blood into cisterna magna once.The dry-wet weight method was used to detected brain tissue water content in order to evaluate cerebral edema.BBB permeability was evaluated by the Evans blue extravasation method.The immunohistochemical method was used to detect the expression of MMP-9 and phosphorylated ERK1/2.Results The expression of phosphorylated ERK1/2 and MMP-9 was lower in the sham operation group.The expression of both was up regulated at 24 hours after SAH.The brain water content and Evans blue content also increased.U0126 treatment decreased the phosphorylation of ERK1/2 and the expression of MMP-9,improved the BBB permeability,and alleviated brain edema.Conclusions MMP-9 is involved in the pathophysiological processes of early BBB injury and brain edema aft er SAH.ERK1/2 pathway may play a vital role in the expression of MMP-9.U0126 may protect BBB and reduce brain edema after SAH by inhibiting the phosphorylation of ERK1/2.

Aim To test the skin healing and repairing efficacy and the mechanism of Hibiscus rosa-sinensis L bud extract by using the animal models. Methods KM mice were randomly divided into three groups:the model group, the positive control group, and the n-bu-tyl alcohol extract ( HrBN) group. Using the boils and carbuncles model, the healing condition of all the animals were observed. KM mice were kept in the SPF condition room and divided into five groups: the model group, the positive control group, and the low, middle, high dose groups. Using the full-thickness loss model, the repairing results of all the mice were ob-served. Through the antimicrobial test, the results of MIC and inhibition zone were obtained. The carbon clearance test was used to collect the blood at the time 5min and 15min, and get the liver and spleen, and the results of K andαwere obtained. Results In vivo ex-periments showed there was significant difference be-tween groups;the HrBN extract had the outstanding ef-ficacy in healing and repairing skin boils and full-thickness loss models. It had higher recovery rate than other ethanol extract, such as ethyl acetate extract and chloroform extract. In vitro experiments showed that the HrBN extract, ethyl acetate extract ( HrBE) ,AB-8 macroporous resin 30% alcohol part and 60% alcohol part had obvious antimicrobial efficacy. The carbon clearance test showed HrBN had a good effect in im-proving immune function, and it can increase the K and α. Conclusion HrBN in animal models exerts good skin healing and repairing efficacy, which might be related to its antibacterial activity and immunologic enhancement function.

OBJECTIVETo explore whether bone marrow stromal cell line QXMSC1 (H-2(d)) engineered to secrete IL-3 (QXMSC1 IL-3) can improve the hematopoiesis post-allogeneic bone marrow transplantation (BMT) in mice.

METHODSThe stromal cell line QXMSC1 IL-3 was established by transfecting QXMSC1 (H-2(d)) cell with a recombined retrovirus vector PL3SN containing mice IL-3 gene cDNA. Lethally irradiated mice C57BL/6 (H-2(b)) were transplanted with T cell depleted allogeneic bone marrow (BALB/c, H-2(d), 1 x 10(7)/mice) and QXMSC1 IL-3 cells (5 x 10(5)/mice). The numbers of RBC and WBC in peripheral blood were counted 20 and 40 days after bone marrow transplantation. The marrow nucleated cells, CFU-S, CFU-GM, CFU-E and CFU-GEMM yields were measured in recipient mice.

RESULTQXMSC1 IL-3 cells could stably secrete IL-3 and increase the peripheral RBC and WBC counts as well as the number of marrow nucleated cells and CFU-GM, CFU-E, CFU-GEMM yields.

CONCLUSIONCotransplantation of QXMSC1 IL-3 cells with T cell depleted marrow grafts improve hematopoiesis post allogeneic BMT in mice.

Animals ; Bone Marrow Transplantation ; Erythrocytes ; cytology ; Female ; Hematopoiesis ; genetics ; physiology ; Interleukin-3 ; genetics ; Leukocytes ; cytology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Stromal Cells ; metabolism ; transplantation ; Time Factors ; Transfection

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.