Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis / 中西医结合学报

OBJECTIVE@#To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms.@*METHODS@#A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation.@*RESULTS@#FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation.@*CONCLUSION@#BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.

Comparison of hidden blood loss between minimally invasive percutaneous locking plate fixation and intramedullary nail fixation in the treatment of tibial shaft fracture / 中国骨伤

OBJECTIVE@#To analyze and compare the hidden blood loss of minimally invasive percutaneous plate osteosynthesis(MIPPO) combined with locking plate fixation and intramedullary nail fixation in the treatment of tibial shaft fracture.@*METHODS@#One hundred and ninety-one cases of tibial shaft fracture treated from January 2017 to January 2019 were analyzed retrospectively. The patients were all treated with closed reduction and divided into two groups:group A (110 cases) and group B (81 cases). In group A, 78 males and 32 females were treated with MIPPO combined with locking plate. The age ranged from 19 to 74 (45.32±11.79) years old. According to AO classification, 42cases were type 42-A, 45 were type 42-B and 23 were type 42-C fractures. Group B was treated with intramedullary nail, including 65 males and 16 females, aged 19 to 84 (45.44± 14.32) years old. According to AO classification, there were 39 cases of type 42-A, 29 cases of type 42-B and 13 cases of type 42-C. The operation time, intraoperative blood loss and hidden blood loss were observed and compared between the two groups.@*RESULTS@#On the first day, the hidden blood loss was (155.27±47.89) ml in group A and (160.43±131.42) ml in group B, the difference was statistically significant (0.05).@*CONCLUSION@#In the treatment of tibial shaft fracture with intramedullary nail, there is obvious hidden blood loss, which is much higher than expected.

Clinicopathological features of gastric mixed adenoneuroendocrine carcinoma / 中国肿瘤临床

Objective:To explore the clinicopathologic characteristics of gastric mixed adenoneuroendocrine carcinoma (MANEC). Methods:From January 2011 to December 2016, the clinical and pathological data of 35 patients with gastric MANEC who were diagnosed and surgically treated in Tianjin Medical University Cancer Institute and Hospital were analyzed retrospectively. Results:The average age of the 32 men and 3 women in this study was 61.6±7.5 years. Tumor locations were as follows:17 related to gastric cardia, 9 related to gastric body, 8 related to gastric antrum, and 1 related to gastric stump. Clinical symptoms were non-specific and the diagnosis relies on post-operative pathological examination. Using the histological microscope, the affected structures were detected in neuroendocrine systems and tissue linings. Immunohistochemical staining showed that carcinoembryonic antigen (CEA) and cytokeratins 8 and 18 (CK8/18) were expressed in 32 and 33 adenocarcinoma-related cases, respectively, whereas synaptophysin (Syn) and chromogranin A (CgA) were revealed in 33 and 27 neuroendocrine-related cases, respectively. Al patients received surgical resection. A total of 17 incidents of death were reported at three years after the operation, and most of the patients were at clinical stageⅢorⅣ. Conclusion:Gastric MANEC is a rare neoplasm and is often diagnosed at its advanced stage and mainly occurs in the aged population. Neuroendocrine structures and glandular tissues are the most frequent location of such condition. Diagnosis relies on both immunohistochemical and histological examinations. Surgical resection is the most effective treatment, but the prognosis of this condition remains poor.

Relationship between fluorodeoxyglucose uptake and overexpression of glucose transport protein 1 and hexokinase-Ⅱ in early-stage nasopharyngeal carcinoma / 中华核医学杂志

Objective To discuss the molecular mechanism of 18F-fluorodeoxyglucose (FDG) uptake in tumor and to assess its value to identify pathologic type and cancer staging in patients with earlystage nasopharyngeal carcinoma.Methods Forty patients with nasopharyngeal carcinoma of early-stage,including 12 cases with T1 stage and 28 cases with T2 stage, underwent FDG PET imaging.The maximum standardized uptake value ( SUVmax ) and mean standardized uptake value ( SUVmean ) of FDG uptake of each patient were measured and compared between T1 and T2 stage by t-test.The expression of glucose transport protein 1 ( Glut1 ) and hexokinase- Ⅱ ( HK- Ⅱ ) of each case was measured in paraffin sections by streptavidin-perosidase (SP) immunohistochemistry.The positive expression rate of Glut1 and HK- Ⅱ was calculated and compared between T1 and T2 by x2 test.Meanwhile, the correlation between the expression of Glut1 or HK-Ⅱ and the SUVmax was tested by Pearson analysis.Results The SUVmax and SUVmean in 40 patients were 9.45 ± 1.87 and 6.04 ± 1.09, respectively.The SUVmax of patients with T1 stage (8.95 ± 1.91 ) was significantly lower (t =4.46, P＜0.001 ) than that of patients with T2 stage (11.55 ± 1.70), and the SUVmean of patients with T1 stage (5.61 ± 1.08) was significantly lower ( t = 6.76, P ＜ 0.001 ) than that of patients with T2 stage (7.98 ± 1.10) too.Among 40 patients, all patients showed positive expression of Glut1 and HK-Ⅱ , and the positive expression rate of Glut1 and HK-Ⅱ was ( 45.2 ± 10.9 )% and ( 68.3 ±9.5)%, respectively.The positive expression rate of Glut1 was (38.4 ±8.1)% in T1 stage and (49.7 ±12.6)% in T2 stage, which displayed no difference (x2 =40.58, P＞0.05), but the HK-Ⅱ positive expression rate showed significant difference (x2 =58.71, P＜0.05) between T1 stage (60.1 ±11.1)% and T2 stage (77.9 ± 14.7 )%.The correlation analysis indicated that there was low-degree positive correlation (r =0.369, P=0.019) between the SUVmax and Glut1 expression, and there was medium-degree positive correlation (r = 0.549, P = 0.001 ) between the SUVmax and HK-Ⅱ expression.Conclusion Expression of Glut1 and HK-Ⅱ was positively correlated with FDG uptake in patients with early-stage nasopharyngeal carcinoma.

In vivo and in vitro stability of ¹³¹I-Herceptin and its form of existence in the blood of rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the in vivo and in vitro stability of (131)I-Herceptin and its form of existence in the blood.</p><p><b>METHODS</b>Herceptin was labelled with iodine-131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by high performance liquid chromatography (HPLC). Five rabbits received injections of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection, blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and the radio count of the serum and blood cells was calculated.</p><p><b>RESULTS</b>The baseline RCP of (131)I-Herceptin was (94.9±2.7)%. The RCP was stable after placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was significantly lowered to (82.6±2.8)% after preservation for over 72 h (t=9.971, P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I-Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered to (75.4±3.9)% (t=6.564, P<0.001).</p><p><b>CONCLUSION</b>Storage at 4 degrees celsius for no more than 72 h does not obviously affect the activity of (131)I-Herceptin in terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the serum and its radiochemical purity remains stable within 24 h, after which obvious degradation occurs.</p>

Analysis of radioactive distribution in the sacrum in whole-body bone scanning / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the radiogenic distribution in the sacrum in whole-body bone scanning.</p><p><b>METHODS</b>A total of 212 patients receiving whole-body bone scanning without any explicit bone metastases were divided into different age and gender groups. The radioactive distribution in the sacrum in whole-body bone scanning was analyzed statistically.</p><p><b>RESULTS</b>Of these cases, 31.1% presented with thin radioactive distribution in the sacrum and 11.3% exhibited increased radioactive distribution. Normal radioactive distribution in the sacrum was found in 57.6% of the cases. In both male and female elderly patients (>70 years), the rate of normal radioactive distribution in the sacrum was obviously reduced with increased rate of thin radioactive distribution. The female elderly patients showed higher rate of increased radioactive distribution in the sacrum than male elderly patients.</p><p><b>CONCLUSION</b>The radioactive distribution in the sacrum is similar between female and male patients. Elderly male patients over 70 years have generally thin radioactive distribution in the sacrum due to the presence of osteoporosis, which is also associated with latent fracture of the sacrum to result in increased radioactive distribution in the sacrum in whole-body bone scanning.</p>

Relationship between fluorodeoxyglucose uptake and vascular endothelial growth factor in early-stage nasophygeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the overexpression of vascular endothelial growth factor (VEGF) and fluorine-18 fluorodeoxyglucose (FDG) uptake in early-stage nasopharyngeal carcinoma (NPC) and evaluate their relationship.</p><p><b>METHODS</b>FDG positron emission tomography (PET) was performed in forty patients with stage I and stage II NPC. The maximum and mean standard uptake values (SUVmax and SUVmean, respectively) were measured in each patient, and the expression of VEGF was measured on paraffin sections using immunohistochemistry.</p><p><b>RESULTS</b>The FDG uptake in the patients were 9.45-/+1.87 (SUVmax) and 6.04-/+1.09 (SUVmean), 8.95-/+1.91 (SUVmax) and 6.04-/+1.09 (SUVmean) in stage I patients, and 11.55-/+1.70 (SUVmax) and 7.98-/+1.1 (SUVmean) in stage II patients. The FDG uptake of stage II patients was higher than that of stage I patients. The FDG uptake of non-keratinizing differentiated carcinoma was 9.74-/+1.82 (SUVmax) and 6.82-/+1.23 (SUVmean) and 10.44-/+2.16 (SUVmax) and 6.68-/+1.35 (SUVmean) in non-keratinizing undifferentiated carcinoma, showing no significant differences between them (SUVmax: t=1.230, P>0.05; SUVmean: t=0.346, P>0.05). The VEGF-positive cells were 60.80% in the tumor. A correlation between VEGF expression and FDG uptake in he tumor was noted (r=0.460, P=0.03).</p><p><b>CONCLUSION</b>VEGF overexpression is correlated to FDG uptake in patients with early-stage NPC. The SUV value reflects the glucose metabolism of NPC, and also shows the degree of oxygen insufficiency in the tumor tissue.</p>

Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin radioimmunoimaging / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the mechanism of cardiotoxicity associated with Herceptin.</p><p><b>METHODS</b>Herceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues.</p><p><b>RESULTS</b>The O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172).</p><p><b>CONCLUSION</b>Myocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.</p>

Effects of wrist-ankle acupuncture on functional states of the vegetative nerve in the recruit / 中国针灸

<p><b>OBJECTIVE</b>To observe effects of wrist-ankle acupuncture on functional states of the vegetative nerve in the recruit.</p><p><b>METHODS</b>Sixty recruits with the vegetative nerve balance index y > +0.56 determined with "Wenger-Chong Zhong Zhong Xiong"'s vegetative nerve balance factor assay were randomly divided into a treatment group and a control group. The treatment group were treated with wrist-ankle acupuncture and the control group with nothing.</p><p><b>RESULTS</b>After treatment, 24 cases with y < +0.56 was found in the treatment group and 16 cases in the control group with a significant difference between the two groups (P < 0.05).</p><p><b>CONCLUSION</b>Wrist-ankle acupuncture can better improve functional state of the vegetative nerve in the recruit.</p>

Hypoxia responsive element regulated herpes simplex virus-thymidine kinase system enhances killing effect of gancyclovir on Ewing's sarcoma cell line under hypoxic condition / 中华儿科杂志

<p><b>OBJECTIVE</b>To find out a possible approach to improve the effectiveness of radiotherapy and chemotherapy for Ewing's sarcoma by constructing a eukaryotic expression vector expressing herpes simplex virus-thymidine kinase (HSV-TK) regulated by hypoxia responsive element (HRE) under hypoxia and to evaluate the effects of this HRE regulated HSV-TK system on killing effect of gancyclovir (GCV) on Ewing's sarcoma cell line SK-ES under hypoxic condition.</p><p><b>METHODS</b>The HRE was synthesized according to the literature and cloned into the enhancer site of pIRES(2)-EGFP vector to obtain the pHRE recombinant plasmid. The HSV-TK was amplified by PCR and cloned into the multiple clone site of pIRES(2)-EGFP and pHRE to obtain pTK and pHRE-TK recombinant plasmid. The human Ewing's sarcoma cell line SK-ES was transfected by pTK or pHRE-TK recombinant plasmid with liposome and then was exposed to normoxic (21% oxygen) or hypoxic (3% oxygen) condition. The expression of enhanced green fluorescent protein (EGFP) was monitored by fluorescent microscopy. The sensitivity of human Ewing's sarcoma cell line SK-ES transfected with pTK or pHRE-TK recombinant plasmid to the anti-tumour drug GCV was determined with the method of tetrazolium (MTT) after treating with GCV for five days.</p><p><b>RESULTS</b>(1) The result of sequencing showed that the recombinant plasmid pHRE contained HRE, and that the recombinant plasmid pTK and pHRE-TK contained HSV-TK gene in the sense direction. (2) Comparison of fluorescent optical density (FOD) showed that (1) the EGFP FOD value of pHRE and pHRE-TK group cells exposed to hypoxia was significantly higher than those exposed to normoxia (P < 0.01); (2) when the cells were exposed to hypoxia, the EGFP FOD value of pHRE and pHRE-TK group cells was significantly higher than that of pTK and empty vector group (P < 0.01); (3) there was no significant difference among the four groups of cells when they were exposed to normoxia (P > 0.05). (3) Comparison of the sensitivity of four groups of cells to GCV showed that (1) the cells in pHRE-TK and pTK groups were much more sensitive to GCV than the cells in pHRE group under hypoxia condition (P < 0.01), the higher the GCV concentration, the greater the difference; (2) the cells of pHRE-TK group were more sensitive to GCV than those in pTK group under hypoxic condition (P < 0.01), but was almost equally sensitive under normoxic condition (P > 0.05); (3) the pHRE-TK group cells had higher sensitivity to GCV under hypoxia than normoxia (P < 0.01) while the pTK group cells had almost the same sensitivity to GCV under hypoxia and normoxia (P > 0.05).</p><p><b>CONCLUSION</b>(1) The eukaryotic expression vector expressing herpes simplex virus-thymidine kinase (HSV-TK) regulated by hypoxia responsive element (HRE) under hypoxia was constructed successfully. (2) HRE could up-regulate expression of EGFP by SK-ES cells under hypoxia condition. (3) HRE could enhance the killing effect of HSV-TK/GCV system on human Ewing's sarcoma cell line SK-ES under hypoxic condition.</p>

ISOLATION AND IDENTIFICATION OF PSEUDOMONAS AERUGINOSABACTERIOPHAGE AND DETERMINATION OF PHAGE-RSISTANCEMUTATION FREQUENCE / 微生物学通报

Three bactreiophages of Pseudomonas aeruginosa were isolated from sewage and named as PaP1, PaP2 and PaP3. All belong to double-strand DNA phages, their genome is about 47kb, 34kb and 24kb respectively. The titre (pfu/mL) of three phages is respectively 109, 1011 and 1011, PaP1 is lytic phage, both PaP2 and PaP3 are lysogenic. Under electron microscope, All show icosahedral heads with diameter of 70nm, 55nm and 65nm respectively. PaPl belongs taxonomically to Myoviridae, and both of PaP2 and PaP3 belong to Pedoviridae. The phage-re-sistance and substitution phenomenon of the resistant flora for the sensitive were observed, and the mutation frequence of Pseudomonas aeruginosa resistant to the phage is about 1.4 ? 10-7 ~ 7.9 ?10-7 determined by end-point -titer method.