OBJECTIVETo investigate the effect of ethyl pyruvate on barrier function of intestinal mucosa in dogs with septic shock.

METHODSTwenty dogs with septic shock induced by lipopolysaccharides(LPS) were randomly divided into two groups. Dogs randomly received placebo (Ringer's solution, control group, n=8) or ethyl pyruvate in lactated Ringer's solution (0.05 g/kg loading dose over 10 mins, thereafter 0.05 g.kg(-1).h(-1) for 12 hours, EP treatment group, n=12). The diamine oxidase(DAO) activity and D-lactate content were detected at the 0, 8 th, 12 th and 24 th hour of septic shock. Animals were sacrificed at the 24 th hour after septic shock and the jejunal tissue was taken for histopathological examination.

RESULTSThe levels of plasma DAO and D-lactate were significantly elevated in both groups after septic shock than those before septic shock. The changes in intestinal parameters of hemoperfusion and permeability in EP treatment group were significantly lowered than those in control group. Inflammation of small intestinal mucosa was more severe in control group than that in EP group, and the pathologic score was significantly lower in EP group(2.33+/-0.25) than that in control group(3.39+/-0.38)(P<0.05).

CONCLUSIONEthyl pyruvate can lessen intestinal permeability and protect intestinal barrier function in dogs with septic shock.

Animals ; Dogs ; Intestinal Mucosa ; drug effects ; pathology ; Intestine, Small ; Male ; Pyruvates ; therapeutic use ; Shock, Septic ; drug therapy ; pathology

This study was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on immune function of sensitized mice', and provide the evidences of acquired immune tolerance for allogeneic bone marrow transplantation. The mice sensitized on 7 day before transplant were divided into 4 groups: (1)CTLA4Ig+ anti-CD154 isotype control IgG; (2)anti-CD154 +CTLA4Ig isotype control IgG; (3)CTLA4Ig and anti-CD154; (4)isotype control IgG of CTLA4Ig and anti-CD154. CTLA4Ig and anti-CD154 used in normal BALB/c mice as isotype control IgG. Each mouse in all groups received CTLA4Ig and anti-CD154 (or corresponding isotype control IgG) 500 µg respectively, and was injected via tail vein on 7 day before transplant. There were 5 mice in each group. The mice were sacrificed on day 0, then the number of CD19(+)CD69(+)B cells, CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- T cells were measured by flow cytometry. Changes of cytokines and sensitized antibody were tested by ELISA or flow cytometry. The results showed that the numbers of CD19(+)CD69(+)B cells were significantly increased in comparison with the normal group (P < 0.01) , whereas the numbers of cells were significantly decreased when blocking B7/CD28 or /and CD40/CD154 co-stimulatory signals (P < 0.01) . Blocking these 2 signals together displayed a synergistic effect (P < 0.01) . The central memory and effector T cells were defined as CD44(high)/CD62L(high) and CD44(high)/CD62L(low)/- respectively, those increased significantly after sensitized in comparison with those in normal group, whereas their numbers decreased when blocking B7/CD28 or/and CD40/CD154 co-stimulatory signals. Blocking these two signals together, displayed a synergistic effect (P < 0.01). Cytokines, IgG and IgM in all groups were not significantly different. Sensitizing antibody test showed that the fluorescence intensity of sensitized group significantly increased as compared with normal group, whereas fluorescence intensity of CTLA4Ig or/and anti-CD154 treated groups significantly decreased as compared with sensitized group (P < 0.01) . It is concluded that blocking the B7/CD28 or/and CD40/CD154 co-stimulatory signal can inhibit the cellular and humoral immune function, whereas blocking these two signals together displays a synergistic effect.
Animals ; B7-1 Antigen ; metabolism ; Bone Marrow Transplantation ; CD28 Antigens ; metabolism ; CD40 Antigens ; metabolism ; CD40 Ligand ; metabolism ; Immune Tolerance ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Signal Transduction ; Transplantation, Homologous

The aim of this study was to investigate the effects of CD4(+)CD25(+) regulatory T cells (Treg) on allogeneic hematopoietic stem cell transplantation (HSCT) in sensitized mice so as to provide experimental evidence for clinical treatment of allogeneic HSCT rejection in sensitized recipients. The BALB/c mice were divided into 5 groups: group A - mice were sensitized with injection of splenocytes; group B - mice were sensitized with splenocytes and treated with >5×10(5) Treg on day 7 before transplantation; group C - mice were sensitized with splenocytes and treated with 5×10(5) Treg on day 13 and 7 before transplantation; group D - mice were not sensitized, but treated with equal volume of PBS as control; group E - blank control. Each group had 15 mice. On day 0 of transplantation, mice in each group were irradiated lethally with 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were intravenously injected via the tail vein. The fluorescent cells in peripheral blood and organ tissue were detected by flow cytometry on different time points for homing assessment. Survival rates and hematopoietic reconstitution were also recorded and monitored. The results showed that on 12 and 24 hours after transplantation, as compared with the sensitized group, the number of fluorescence homing cells in different tissue of the applied Treg groups increased significantly and the differences were statistically significant (P < 0.05). The mice in sensitized group and blank control group all died on the 6-13 day, whereas the median survival time of mice in applied Treg once and twice were 15 days and 16 days respectively. Comparing with sensitized group, the difference was statistically significant (P < 0.001), but there was no significant difference between these two groups applied regulatory T cell (P > 0.05). It is concluded that applying Treg can induce immune tolerance of sensitized recipient to allogeneic HSCT and inhibit immune destruction and prolong the survival time, but can not induce full immune tolerance and at last sensitized mice died of rejection of hematopoietic stem cells.
Animals ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; methods ; Immune Tolerance ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; immunology ; Transplantation, Homologous

OBJECTIVETo investigate the effect of CVVH on the plasma levels of TNF-alpha, IL-1, IL-6, IL-8 in patients with multiple organ dysfunction syndrome (MODS).

METHODSTwenty-two patients with MODS were treated with continuous veno-venous hemofiltration (CVVH), venous and arterial blood samples were taken at 0, 1, 4, 8 hour following CVVH and ultrafiltration fluid samples were taken at 8 hour following CVVH. Arterial blood samples were used for blood gas analysis, venous blood samples and ultrafiltration fluid were used to measure the levels of cytokines by ELISA.

RESULTSThe plasma levels of TNF-alpha and IL-1 were significantly decreased following CVVH (P < 0.05). The IL-1, IL-6, IL-8 were detected in the ultrafiltration fluid and TNF-alpha was not. Heart rate decreased and mean arterial pressure (MAP) increased significantly 4 hrs after CVVH (P < 0.05). PaO(2)/FiO(2) increased significantly (P < 0.05). The APACHE II scores reduced after CVVH (P < 0.05). The reduction of APACHE II score and the elimination of cytokines were positively correlated with ultrafiltration flow rates

CONCLUSIONSCVVH can remove some cytokines in plasma, reduce APACHEII score and improve hemodynamics and oxygenation in MODS. Moreover, higher volume hemofiltration has better effect on the elimination of cytokines and can further improve the prognosis of MODS.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Cytokines ; blood ; Female ; Hemofiltration ; methods ; Humans ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Male ; Middle Aged ; Multiple Organ Failure ; blood ; therapy ; Retrospective Studies ; Tumor Necrosis Factor-alpha ; metabolism

This paper introduced an experimental study of the preparation of polylacticacid (PLA) nanoparticles of cucurbitacin (CuC) using a precipitation method. The residual acetone, ratio of CuC PLA precipitates, and the relationships between the ratios of two precipitates and drug incorporation rates were measured. It appeared that the nanoparticles with 60% of PLA incorporated with 5.5% of CuC were formed when acetone was injected into the aqueous phase. As the acetone gradually evaporated, drug incorporation/encapsulation continued, with most of CuC (about 70%) formed new crystalline cores and suspended in the form of microcrystals in the medium, resulting a suspension containing both nanoparticles and microcrystals. We also concluded that this system may not necessarily be suitable for all lipophilic drugs to be prepared to PLA nanoparticles with good incorporation rate. The drug incorporation depended on the interactions among drug, PLA, and organic solvents, in addition to the solubility of the drug.
Antineoplastic Agents, Phytogenic ; administration & dosage ; Chemical Precipitation ; Cucurbitaceae ; chemistry ; Cucurbitacins ; Delayed-Action Preparations ; Drug Compounding ; methods ; Drug Delivery Systems ; Lactic Acid ; Microspheres ; Nanotechnology ; Particle Size ; Plants, Medicinal ; chemistry ; Polyesters ; Polymers ; Triterpenes ; administration & dosage ; isolation & purification

OBJECTIVETo investigate the imaging feature of primary malignant fibrous histiocytoma of the bone (PBMFH) by the conventional radiography, CT and MRI, and to evaluate these different imaging methods in its diagnosis.

METHODSThe imaging data of conventional radiography, CT and MRI of 35 patients with pathologically confirmed PBMFH were retrospectively analyzed.

RESULTSThough the imaging appearance of PBMFH varied in different cases, all the imaging findings of malignant bone tumors were revealed. The common imaging appearance on the conventional radiography and CT were eccentric, aggressive, osteolytic destructions of various types located at the ends of extremities with extraosseous soft tissue masses, but periosteal reaction was rare. Heterogeneous signal intensities on T(1)WI and T(2)WI were common MRI changes but not specific.

CONCLUSIONPrimary malignant bone fibrous histiocytoma, a rare primary malignant bone tumor, is most frequently located in the long bone. Conventional radiography is still the first and main choice and is taken as an essential means of diagnosis. CT and MRI are quite important in demonstrating the details and extent of the disease such as soft tissue, cortical destruction, periosteal reaction, calcification and necrosis. The imaging characteristics may be of value in differentiating MFH from the other malignant bone tumors. Furthermore, MRI may also be valuable in assessing the efficacy of chemotherapy and/or radiation therapy, as well as in distinguishing recurrence from postoperative or post-radiation changes.

Adolescent ; Adult ; Aged ; Bone Neoplasms ; diagnosis ; diagnostic imaging ; Female ; Histiocytoma, Malignant Fibrous ; diagnosis ; diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo compare the thermal conductivity of the related tissues along meridian line and non-meridian area.

METHODSForty healthy volunteers were observed with a infrared thermal imaging system.

RESULTSDuring heating the acupoint or the non-acupoint along the meridian line, the velocity of spreading of the temperature-increasing response along the meridian line was more easy and rapid, with a definite direction. However, during heating the non-meridian spots, the change of temperature was confined to the local area, with no definite direction. The spreading of skin temperature response along the meridian line was more rapid than the non-meridian area during both the two were heated simultaneously, and finally, 3 infrared radiant tracks along the meridian courses conformed basically with that of the classical three yin- meridians of the hand appeared.

CONCLUSIONThe thermal conductivity of the related tissues along the meridian line is better than that of non-meridian area and has definite direction, with differences in physical characteristics between them.

Acupuncture Points ; Hand ; Humans ; Meridians ; Skin Temperature ; Thermal Conductivity

BACKGROUND/OBJECTIVES: The association between tea consumption and risk of coronary heart disease (CHD) remains controversial. This study aimed to determine whether tea consumption has an effect on CHD risk in Chinese adults. SUBJECTS/METHODS: In this hospital-based case-control study, 267 cases of CHD and 235 non-CHD controls were enrolled. Blood samples from all cases were examined. Cardiac function indices (left ventricular ejection fraction, left ventricular end-diastolic dimension, lactate dehydrogenase, and creatine kinase of the muscle or brain type), blood lipid index (high-density lipoprotein cholesterol), and blood coagulation function indices (fibrinogen and activated partial thromboplastin time) were recorded. Tea consumption of study participants was assessed by a specifically designed questionnaire. The baseline characteristics of the study populations were recorded, and CHD-related biomarkers were detected. Differences in baseline characteristics of the study participants were examined using t-tests for continuous variables and chi-squared tests for categorical variables. Unconditional logistic regression was used to measure the association between tea and CHD. RESULTS: There were significant differences in cardiac function indices, blood lipid index, and blood coagulation indices between CHD cases and controls (P < 0.05). We found tea consumption reduced CHD risk in female participants (adjusted odds ratio (OR) = 0.484, 95% CI: 0.242–0.968, P = 0.0403). Regarding the type of tea consumed, the risk of CHD was reduced in women who drank partially fermented tea (adjusted OR = 0.210, 95% CI: 0.084–0.522, P = 0.0008). Analytic results for the amount of tea consumed per unit time showed CHD risk was reduced in women who consumed 1–2 cups of tea per day (adjusted OR = 0.291, 95% CI: 0.131–0.643, P = 0.0023). A tea-drinking frequency of > 6 days/week was beneficial for CHD prevention (adjusted OR = 0.183, 95% CI: 0.049–0.679, P = 0.0112). When analyzed according to the duration of tea consumption, the risk of CHD was reduced in participants who had been drinking tea for 10–20 years (adjusted OR = 0.360, 95% CI: 0.137–0.946, P = 0.0382). CONCLUSIONS: Tea consumption is associated with a reduced risk of CHD in female but not male populations in Guangzhou.

This research was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on engraftment of hematopoietic stem cell in the sensitized recipient so as to provide the experimental evidence for the treatment of sensitized recipient's immune rejection after clinical allogeneic hematopoietic stem cell transplantation (HSCT). The BALB/c mice were divided into 4 groups: (1)mice sensitized on 7 day before transplant; (2)mice were sensitized on 7 day before transplant, and injected CTLA4Ig+anti-CD154 applied; (3)normal mice injected by corresponding isotype control IgG of CTLA4Ig and anti-CD154; (4)normal blank control mice. Each group had 15 mice. On day 0, mice of each group were irradiated lethally 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were injected via the tail vein. The fluorescent cell level in peripheral blood and organ tissue at different time points were detected by flow cytometry (FCM) for homing assessment. Survival rates and hematopoietic reconstitution were also monitored and recorded. The results showed that application of CTLA4Ig anti-CD154 could promote implantation of allogeneic HSC in sensitized recipients, induce the immune tolerance, prolong their survival time and accelerate the hematopoietic reconstitution within 28 days, compared with the sensitized group. It is concluded that applying CTLA4Ig and anti-CD154 can enhance the engraftment of HSCT and induce immune tolerance in the sensitized recipient after allogeneic HSCT and accelerate the hematopoietic reconstitution.
Abatacept ; Animals ; B7 Antigens ; antagonists & inhibitors ; CD28 Antigens ; antagonists & inhibitors ; CD40 Antigens ; antagonists & inhibitors ; CD40 Ligand ; antagonists & inhibitors ; Graft Rejection ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Immune Tolerance ; Immunoconjugates ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous

Objective: To investigate surgical strategies and the corresponding benefits for patients with perihilar cholangiocarcinoma(pCCA). Methods: A total of 81 patients with pCCA who underwent radical excision in the Department of Biliary and Pancreatic Surgery of Sun Yat-Sen Memorial Hospital between January 2014 and December 2021 were retrospectively collected.The cohort consisted of 50 male and 31 female patients,with an age of (62.5±11.5)years(range:26 to 83 years).Seventy-five cases were diagnosed with jaundice,60 of whom received preoperative biliary drainage,while 20 patients received portal vein embolization.Their serum bilirubin level within one week before the operation(M(IQR)) was 44.3 (41.9) μmol/L(range:8.0 to 344.2 μmol/L).Preoperative imaging examinations were performed to evaluate the Bismuth-Corlette type of pCCA,showing 3,6,21,27,and 24 cases of Bismuth-Corlette type Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ,respectively.The primary outcome was overall survival (OS),and the secondary outcomes were relapse-free survival (RFS),90-day postoperative morbidity and 90-day postoperative mortality.OS and RFS were estimated using the Kaplan-Meier method and compared by the Log-rank test.Significant prognostic factors were determined using univariate and multivariable Cox proportional hazard regression analyses. Results: In the cohort of 81 pCCA patients,67 cases(82.7%) underwent major hepatectomy while 3 cases received major hepatectomy combined with pancreaticoduodenectomy.Thirty-four patients underwent hepatectomy combined with vascular resection and reconstruction(18 cases of portal vein resection and reconstruction alone;9 cases of hepatic artery resection and reconstruction alone;7 cases of combination of portal vein and hepatic artery resection and reconstruction).Margin negative(R0 excision) were achieved in 53.1%(43/81) of these patients.The operation duration was (627±136)minutes(range:565 to 940 minutes),and the intraoperative blood loss was 400(455)ml(range:200 to 2 800 ml).The 90-day postoperative mortality was 3.7%(3/81).Grade 3-4 postoperative morbidity was 23.4% (19/81) according to the Clavien-Dindo classification of surgical complications.Up to the last follow-up at September 2022,the follow-up time was 34.0(24.2)months (range:0.4 to 103.6 months).Three patients who died within 90 days after surgery were excluded from the survival analysis.The median OS was 36.10 months (95%CI:18.23 to 42.97 months) and the 1-,3-and 5-year OS rates were 85.3%,46.8% and 27.3%,respectively.The median OS of 41 patients with negative margins was 47.83 months(95%CI:36.90 to 58.80 months) and that of 37 patients with positive margins was 20.47 months(95%CI:10.52 to 30.58 months).The median RFS of 70 patients with R0 and R1 resection was 24.50 months(95%CI:12.15 to 31.85 months)and the 1-,3-and 5-year RFS rates were 65.2%,45.7% and 29.9%,respectively.The median RFS of 41 patients with R0 resection was 38.57 months(95%CI:21.50 to 55.63 months) and that of 29 patients with R1 resection was 10.83 months(95%CI:2.82 to 19.86 months). Conclusions: The primary therapy for pCCA is radical surgical resection.A precise preoperative evaluation and sufficient preparation can reduce postoperative morbidity.Surgical treatment can achieve a better survival outcome by increasing the radical resection rate.