A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

The predictive value of small densed low-density lipoprotein cholesterol and HbA 1C for cardiovascular and cerebrovascular events in elderly patients with type 2 diabetes mellitus / 中华检验医学杂志

Objective:To investigate the serum level of low density lipoprotein cholesterol (sdLDL-C) in elderly patients (age≥65 years) with type 2 diabetes mellitus (T2DM) and the its predictive value in evaluatingthe risk of cardiovascular and cerebrovascularevents in elderly patients with T2DM.Methods:In this retrospective study,386 elderly patients with T2DM were collected from December 2014 to December 2016, the averageage was (72.7±5.4) years old, including 269 males and 117 females; 92 of whom had cardiovascular events during follow-up, the averageage was (72.9 ± 5.2) years old, including 65 males and 27 females, and serum sdLDL-C level was detected. Meanwhile, biomarkers such as lipoprotein (a), apolipoprotein B, apolipoprotein AI and hypersensitive c-reactive protein were analyzedin all the patients.Univariate and multivariate factors were used to analyze the relationship between each variable and the occurrence of cardiovascular and cerebrovascular events. The correlation between LDL-C, sdLDL-C of all subjects with age and other lipid indexes were analyzed. ROC curve was used to determine the predictive value of sdLDL-C elevation for cardiovascular and cerebrovascular events in elderly patients with T2DM.Results:The levels of LDL-c, sdLDL-C, non-HDL-C, GLU, HbA1c and ApoB were significantly higher in theCardio-cerebral vascular event group ( t=3.26, 3.46, 2.91, 2.47, 4.03, 3.00, P<0.05). While the levels of apolipoprotein AI was significantly lower than those in theNon-cardio-cerebral vascular event group ( t=-2.39, P<0.05). Cox regression analysis showed that sdLDL-C per 10 mg/dl was independently correlated with the risk of cardiovascular and cerebrovascular events( HR 1.281, 95 %CI 1.225-16.032, P<0.01)after adjusted for age. SdLDL-C was positively correlated with TG, non-HDL-C and ApoB ( r=0.323, 0.588, 0.623, P<0.01) and was negativelycorrelated correlation with age, HDL-C and apolipoprotein AI ( r=-0.363, -0.301, P<0.01), ROC curve analysis showed that sdLDL-C had a strong ability to predict the occurrence of cardiovascular and cerebrovascular events (AUC=0.736, 95 %CI 0.554 9-0.918 2, P=0.003), while HbA1c also had a strong ability to predict the occurrence of cardiovascular and cerebrovascular events(AUC=0.725, 95 %CI 0.524 3-0.927 3, P=0.006). Combined sdLDL-C with HbA1had the strong ability to predict the occurrence of cardiovascular and cerebrovascular events (AUC=0.837, 95 %CI 0.711 4-0.973 5, P=0.001). Conclusions:The elevation of serum sdLDL-C in elderly patients with T2DM wasa significantly independentrisk factorof cardiovascular and cerebrovascular events. Serum sdLDL-C had a higher clinical value than LDL-C, which was expected to be the most effective predictor of lipid profile in riak assessment of cardiovascular and cerebrovascular events in elderly patients with T2DM.

Effect of LGR5 knockdown by shRNA on the proliferation and drug resistance of HeLa cells / 西安交通大学学报(医学版)

Objective To investigate the effect of leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5 )on the proliferation and drug resistance of HeLa cells and its possible mechanism.Methods LGR5 expression was interfered using shRNA,and LGR5 knockdown HeLa cells were constructed.The effect of LGR5 on the proliferation and drug resistance of HeLa cell was evaluated by cell count,clone formation and MTT;the expressions of LGR5 and β-catenin in HeLa cells were detected by Western blot method.Results LGR5 knockdown HeLa cell line was successfully constructed;the cell growth rate and clone formation rate in shLGR5 group were markedly decreased compared to those in shCon group (P<0 .01 ).Drug resistance of HeLa to cisplatin differed significantly between shLGR5 group and shCon group (P<0.01 ).Moreover,the LGR5 knockdown inhibited the expression ofβ-catenin in HeLa cells.Conclusion LGR5 plays an important role in cell proliferation and drug resistance of HeLa cells,and its mechanism is related to Wnt/β-catenin signaling pathway.

Arthroscopic treatment of ulnar impaction syndrome / 中华骨科杂志

Objective To investigate ulnar impaction syndrome imaging characteristics and wrist arthroscopy in the diagnosis and treatment effects.Methods From September 2006 to April 2014,41 patients with ulnar impaction syndrome were treated.Of all 41 patients,28 were male and 13 female with an average age of 34.5±3.9 years old (ranging from 15 to 52 years old).The preoperative values of wrist range of motion (ROM) were 44.17°±6.22° at volar flexion,42.72°±3.37° at dorsal extension,17.45°±4.11° at radial deviation,19.12°±3.70° at ulnar deviation,66.81°±4.28° at pronation,and 70.27°±5.30° at supination.Arthroscopic exploration was conducted in all patients,aiming to observe the ulnar variance,wrist osteonecrosis,articular cartilage damage and triangular fibrocartilage complex tear.Arthroscopic synovectomy were performed in all cases;33 cases of articular cartilage injury were treated with arthroscopic chondroplasty;16 cases of osteonecrosis were treated with arthroscopic drilling decompression;30 cases with tear of TFC were treated with arthroscopic repair;26 cases with ulna positive mutation were treated with arthroscopic distal ulna resection.Patients were followed at 3,6,and 12 months after operation.At 12 months follow-up,the values of wrist range of motion was evaluated for volar flexion,dorsal extension,radial deviation,ulnar deviation,pronation,and supination.GreenO'Brien method was used to evaluate the function of wrist joint.Results Primary healing was presented in all patients without neurovascular injury and joint infection.All patients were followed up 12-36 months (mean,17.5 months).At 12 months followup,the values of ROM compared with that preoperative increased with significant difference,49.13° ±3.47° at volar flexion,47.13°±2.39° at dorsal extension,19.33°±3.29° at radial deviation,25.17°±4.89° at ulnar deviation,75.73°±7.66° at pronation,and 77.22°±4.89° at supination.According to Green-O'Brien standard,the results were excellent in 21 case,good in 17 cases and fair in 3 case,with 93％ excellent and good rate.Conclusion Wrist arthroscopy dose not only contribute to the diagnosis in ulnar impingement syndrome but also can be used in treating inflammatory synovium and cartilage lesions,bone drilling decompression,TFC repair and arthroscopic distal ulna resection with improvement in the range of motion of the wrist joint and function.

Updates on the relationship between vitamin D and epilepsy / 国际儿科学杂志

Vitamin D adjusts the body′s absorption and utilization of calciumand phosphorus. Vitamin D deficiency is closely related to incidence of many disease. Several disorders,both systemic and those of the nerv-ous system,have been linked with vitamin D deficiency. Neurological disorders with a vitamin D link include but are not limited to multiple sclerosis,Alzheimer and Parkinson disease,as well as cerebrovascular disorders. In re-cent years,studies have found that the vitamin D may play a critical role in the pathogenesis of epilepsy and pos-sess certain anticonvulsant effects. This article summarized the role of vitamin D in the nervous system and epi-lepsy,the level of serum vitamin D and the correlation of the polymorphism of its receptor genes with epilepsy. The review also summarizes the interaction between antiepileptic drugs and vitamin D.

The arthroscopic diagnosis and treatment of acute patellofemoral joint impingement syndrome / 中华骨科杂志

Objective To explore the mechanism and characteristics of MRI of acute patellofemoral joint impingement syndrome as well as its arthroscopic diagnosis and treatment.Methods There were a total of 46 cases (9 males and 37 females)with acute patellofemoral joint impingement syndrome from September 2005 to October 2012 in our department,and their average age was 21.6 years old (ranging from 15 to 31 years old).The Q angle,lateral patellofemoral angle (LPA) and lateral shift distance (LSD) of all cases were measured by X-ray and MRI preoperatively.MRI checked the medial patellar retinaculum injury by 4 degrees:15 cases of degree Ⅰ,18 cases of degree Ⅱ,8 cases of degree Ⅲ,and 5 cases of degree Ⅳ.All operations were monitored under arthroscopy.Firstly,the hemarthrosis was cleared,and secondly arthroscopy was used to explore all around inside joints,the free cartilage and osteochondral fragment were taken out,and the impaired surface of cartilage was repaired.Medial patellar retinaculum was treated arthroscopically with radio frequency ablation in degree Ⅰ injury.Lateral patellar retinaculum was released when the time of injury was longer than 2 weeks (9 cases),and medial capsule and retinaculum structure were reefed with modified arthroscopy assistance for patients with medial patellar retinaculum injury of degree Ⅱ to Ⅲ with obvious patellar shift.The medial capsule and retinaculum structure were strengthened by open surgical method for patients with degree Ⅳ injury.Results Constant findings under arthroscopy were haemarthrosis (46 cases),chondral lesions involved in the lateral femoral condyle and medial marginal of patella (37 cases),osteochondral fragments (28 cases),and tear of the medical retinaculum (46 cases).All patients were available at follow-up,the average duration of follow-up was 18.2 months (ranging from 12-36 months).No infection,nerve and blood vessel injury,redislocation or other complications happened.Lysholm,Tegner and AAOS scores were used both preoperatively and postoperatively,and LPA and LSD were compared.Statistically,the difference between these two scores was significant (P＜0.05).The sport ability was improved among all patients.Conclusion Acute patellofemoral joint impingement syndrome can be treated effectively by modified suture of medial capsule and retinaculum structure combined with release of lateral retinaculum.The function of knee joint recovered well after operation with satisfactory objective and subjective effects.

Effect of bone marrow mesenchymal stem cells transplantation on the expression of CD163 and interleukin-10 in rats with acute hepatic liver failure / 中国组织工程研究

BACKGROUND:Studies have shown that bone marrow mesenchymal stem cells have the ability to persistently generate hepatocytes and biliary cells, and thus in the repair process of liver injury, replenish the reduced number of hepatocytes due to damage and participate in damaged liver structure. OBJECTIVE:To investigate the effect of bone marrow mesenchymal stem cells transplantation on acute liver failure and the expression of CD163 and interleukin-10 in rat serum and liver tissue. METHODS:D-galactose and lipopolysaccharidewere used to make acute liver failure models in 60 Sprague-Dawley rats. Then, the rats were divided into control group and transplantation group. Bone marrow mesenchymal stem cells at passage 3 were injected through tail vein in the transplantation group, and normal saline was injected in the control group. After transplantation 24, 120, 168 hours, serum samples and liver tissues were col ected. RESULTS AND CONCLUSION:After transplantation 120 and 168 hours, the serum alanine transaminase and aspartate aminotransferase activities of the transplantation were significantly lower than those of the control group (P<0.05). In the transplantation group the apoptotic index was stil lower compared with the control group, and the difference was significant (P<0.05). The levels of CD163 and interleukin-10 in the serum and liver tissue in the transplantation group were decreased significantly compared with the control group (P<0.05). The results suggested that there were highly significant correlations between CD163 and interleukin-10 (P<0.01). Bone marrow mesenchymal stem celltransplantation has a therapeutic effect on acute liver failure rats. CDl63 and interleukin-10 play a very important role in the pathogenesis of acute liver failure, which can be used as sensitive serum marker proteins for diagnosis and prognosis of acute liver failure.

Effect of total alkaloids of Rubus alceaefolius on oxidative stress in rats with non-alcoholic fatty liver disease / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of total alkaloids of Rubus alceaefolius (RAP) on non-alcoholic fatty liver disease (NAFLD) rats and explore its possible mechanisms.</p><p><b>METHOD</b>Sixty SD rats were randomly divided into six groups: control group, model group, compound methionine and choline bitartrate tablets (CMCB)group and three RAP groups treated respectively with low, middle and high dose of RAP. The NAFLD model was induced by feeding fat-rich food. NAFLD rats were administrated with 0.35 g x kg(-1) CMCB and 0.36, 0.72, 1.44 g x kg(-1) RAP for 4 weeks respectively. The weight index of liver was measured. Hepatic histolog ical changes were observed. The concentration in serum of aspartate amino transferase (AST), alanine amino tranferase (ALT), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined. The mRNA expressions of SOD, MDA, TNF-alpha and IL-6 in hepatic tissue were detected.</p><p><b>RESULT</b>Compared with the model group, degree of steatosis of hepatic lobule was improved, the weight index of liver was decreased, serum levels of ALT, AST, TNF-alpha and IL-6 were significantly lower in the high and middle dose RAP group (P < 0.05 or P < 0.01). The levels of SOD and MDA in hepatic tissue were lower in the high dose RAP group (P < 0.05). The mRNA expressions of TNF-alpha and IL-6 in hepatic tissue were decreased (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>RAP can protect liver in experimental NAFLD, and its possible mechanisms may be concerned with clearing the oxygen free radical, reducing the product of lipid peroxidation, inhibiting the release of inflammatory cytokines and reducing nflammatory response.</p>

Application of misoprostol combined with fentanyl and propofol in visualization of artificial abortion / 中国基层医药

Objective To study the feasibility and security about misoprostol combined with fentanyl and propofol applied in visualization of artificial abortion.Methods 1270 cases of pregnant women who requested termination of pregnancy and voluntarily accepted abortion were selected.In the observe group,634 cases of pregnant women received oral misoprostol about 600 mg 90 minutes before surgery.After anesthetized by fentanyl and propofol,painless artificial abortion using visual abortion instrument was carried out.In the control group,636 cases of pregnant women anesthetized by fentanyl and propofol via the venous were carried out artificial abortion.The degree of cervical relaxation,loss of blood,total dose of propofol,surgical time,recovery time,the incidence of abortion complications and so on were observed.Results In the observation group and the control group,the average dosage of propofol are( 14.15 ± 2.37) ml and (16.90 ± 4.52) ml respectively;The average time required for surgery are ( 146.1 ± 38.2) s and ( 199.7 ± 37.3 ) s respectively;the average time required for awakening are ( 6.01 ± 1.90 ) min and ( 8.81 ± 2.02 )in;In the observation group,there are 405 ( 63.9% ) cases of cervical laxity markedly,in the control group,including 145 ( 22.8% ) cases of cervical laxity markedly,there is statistical significance ( P ＜ 0.05 ) between the observation group and the control group.There are no abortion syndrome in both groups.Conclusion Misoprostol combined with fentanyl and propofol was the first choice for painless artificial abortion using ultrasound visualization.

Ultrastructure and TUNEL staining on inhibition of Rubus alceaefolius total alkaloids for apoptosis of liver in rat models of acute hepatitis / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the anti-apoptosis effects of Rubus alceaefolius total alkaloids in rats with hepatic injury.</p><p><b>METHOD</b>The hepatic injury model of rat was induced by intraperitoneal injection with CCl4. Sixty SD rats were randomly divided into the normal group, the model group, the R. alceaefolius total alkaloids intervened group, and the bifendate intervened group. The expressions of the levels of liver cell apoptosis were determined by TUNEL. Ultrastructures of the liver cells were observed with transmission electron microscope.</p><p><b>RESULT</b>Compared with the model group, the degree of hepatic injury and the positive expressions of apoptosis in liver tissues in the R. alceaefolius total alkaloids intervened groups and the bifendate intervened group were significantly lower.</p><p><b>CONCLUSION</b>R. alceaefolius total alkaloids could reduce the pathological changes and degree of hepatic injury in rats, which may be partially through inhibiting the expressions of apoptosis in liver tissue.</p>

A Simple Reliable Fluorescent Assay Method for Histone Acetyltransferase (HAT) Inhibitors / 生物化学与生物物理进展

Histone acetyltransferases (HATs) are involved in the regulation of gene transcription in eukaryotic cells and their inhibitors could be a promising class of drugs due to their ability to modulate transcription and exert antiviral, anti-inflammatory as well as antioxidant effects. Nonradioactive spectrophotometric HAT assay is an alternative method to the widespread radioactive assay but suffers from drawbacks as lack of sensitivity and accuracy. A simple, non-radioactive fluorescent assay that measures the production of CoASH was established by its facile reaction with O-phthalaldehyde and 2-amino-ethanol. This method gives much higher accuracy compared to spectrophotometric assay, and allows screening of various compounds with potential HAT inhibition. The novel assay should be a valuable tool in transcriptional research and especially drug discovery.

Metabolic syndrome and hepatocellular carcinoma:an advance in epidemiology study / 第二军医大学学报

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third cause of cancer-related death worldwide;meanwhile,it is also one of the fastest growing malignancies.The causes of HCC are multiple;HBV is the most important cause in China,with about 25%-30% of HBV infection patients finally develop hepatic cirrhosis and liver cancer.At present,large scale epidemiological studies revealed that the metabolic syndrome(MS) was closely related to liver cancer,and it even served as an independent risk factor for the occurrence and progression of liver cancer.Non-alcoholic fatty liver disease is a metabolic syndrome clinically manifested in the liver;recently it has been indicated to be closely related with HCC development and progression.This paper reviews the recent researches on metabolic syndrome and liver cancer,so as to provide literature for preventive and therapeutic studies on non-virus-related liver cancer.