Dosimetric comparison of intensity-modulated photon radiotherapy and intensity-modulated proton radiotherapy for non-small cell lung cancer / 肿瘤研究与临床

Objective:To investigate the difference of dose distribution between intensity-modulated photon radiotherapy (IMRT) and intensity-modulated proton radiotherapy (IMPT) in patients with non-small cell lung cancer.Methods:The clinical data of 8 patients with stage Ⅱ-Ⅲ non-small cell lung cancer who received radiotherapy in Ion Medical center of the First Affiliated Hospital of University of Science and Technology of China from November 2020 to April 2022 were retrospectively analyzed. IMRT and IMPT radiotherapy plans were created for each patient separately, the main evaluation indicators were targeted area dose distribution parameters [homogeneity index (HI), conformity index (CI) and the percent volume of volume wrapped by 95% and 100% of prescription dose profile in the targeted area (V 95% and V 100%)], and the average dose (D mean) to the organ at risk and the percent volume of a certain relative biological effect (RBE) dose exposure [D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of ipsilateral lung, D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of bilateral lung, D mean, V 30 Gy(RBE) and V 40 Gy(RBE) of heart, maximum dose (D max) of spinal cord, and D mean of esophageal]. Results:In comparison with IMRT, IMPT reduced the levels of dose parameters in bilateral lung, ipsilateral lung, spinal cord, esophagus, and heart with statistically significant differences (all P < 0.05), especially in D mean of bilateral lung [(4.1±1.8) Gy (RBE) vs. (6.9±1.9) Gy (RBE)], V 5 Gy(RBE) [(15.9±7.1) % vs. (28.5±8.6)%], V 20 Gy(RBE) [(7.4±3.5)% vs. (10.1±3.5)%], and D mean of ipsilateral lung [(9.1±4.5) Gy (RBE) vs. (11.9±3.3) Gy (RBE)], all decreased significantly (all P < 0.001), but the differences in the levels of targeted area dose distribution parameters between them were not statistically significant (all P > 0.05). Conclusions:For patients with non-small cell lung cancer, IMPT is superior to IMRT in the protection of bilateral lung, ipsilateral lung, spinal cord, esophagus and heart.

Application of endoscopic complete areola approach in the resection of parathyroid adenoma / 中华内分泌外科杂志

The most common cause of primary hyperparathyroidism (PHPT) is parathyroid adenoma. Surgery is the most effective method to treat PHTP. The data of 10 patients who underwent endoscopic complete areola approach for parathyroid adenoma resection in our hospital from Jan. 2018 to Oct. 2021 were reviewed. It is considered that this method is feasible and has certain advantages compared with traditional surgery.

Impact of radiotherapy-related factors on survival in non-small cell lung cancer complicated with malignant pleural effusion based on propensity score matching / 中华放射肿瘤学杂志

Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.

Targeting context-cpecific dependent transcriptional addiction in bone and soft tissue sarcoma: advance and future / 中华骨科杂志

High heterogeneity of bone and soft tissue sarcomas limits the development of molecular-targeted therapy but in turn provides an important clue to inner genomic and regulomic diversityof driver pathways that define molecular subtypes associated with patient outcome. The importance of malignant biological behaviorshave been re-emphasized, since tumor arises from the collaborative interplay of oncogenic events acquired the tissue-specifying gene expression programs to survive cancer cells and benefit multi-step tumorigenesis and neoplastic progression. Differ from most epithelial carcinomas that harbor clinically operative mutation sites, sarcomas are characterizedpredominantly by chromosomal alterations and copy-number changes, with low mutation loads. Sarcoma-specific fusion proteins produced by chromosomal translocations are common significant transcription factors, driving tumor cells exhibit an absolute dependence on "transcription addiction". It has been confirmed that cyclin-dependent kinase-7 (CDK7) plays a key role in transcriptional regulation such as cell growth and proliferation, invasion and metastasis. The dysregulated transcriptional regulation acquired during tumor development strictly depends on the essential regulation of CDK7. Targeted inhibition of CDK7 is an effective strategy to suppress tumors, especially those with specific genomic backgrounds (oncogene or fusion-gene driven) which are highly sensitive to CDK7 intervention. Emerging studies have shown that CDK7 is closely related to the malignant behaviors of bone and soft tissue sarcomas, and is expected to become a potential target for the treatment of sarcoma.

Effect of CD 4+ T cells and CD 4+/CD 8+ in peripheral blood on survival of patients with stage Ⅳ non-small cell lung cancer—Establishment of a Nomogram prediction model / 中华放射肿瘤学杂志

Objective:To explore the possibility of CD 4+ T cells and CD 4+ /CD 8+ ratio in peripheral blood to predict the survival of patients with stage Ⅳ non-small cell lung cancer (NSCLC), and to establish a Nomogram prediction model. Methods:The influence of CD 4+ T cells and CD 4+ /CD 8+ ratio on the clinical factors and survival of 682 patients pathologically diagnosed with stage Ⅳ NSCLC with no history of cancer treatment was retrospectively analyzed and the Nomogram prediction model was established. Combined with the changes of immune cells levels in 110 patients after treatment, the prognostic and predictive values of CD 4+ T cells and CD 4+ /CD 8+ ratio were verified. Countable data were analyzed by t-test. The survival rate was calculated by Kaplan-Meier method, log-rank test or univariate analysis. The multivariate analysis was performed by Cox regression model. Results:Univariate analysis demonstrated that CD 4+ > 43.15% before treatment significantly prolonged the survival. By multivariate analysis of Cox regression model, CD 4+ >43.15% was an independent prognostic factor to prolong survival for stage Ⅳ NSCLC. The Nomogram model was established and verified that the predicted and actual overall survivals were highly consistent. Further analysis showed that 43.15% as the critical value of CD 4+ T cell level significantly prolonged survival when CD 4+ expressed at a high-level before treatment, after treatment, before and after treatment, or combined with CD 4+ /CD 8+ >1.65. Conclusions:The baseline level of CD 4+ T cells before treatment in peripheral blood is an independent prognostic factor for stage Ⅳ NSCLC. The CD 4+ /CD 8+ ratio before treatment has limited value in predicting the prognosis.

Study of volume change and radioherapy timing in patients with stage Ⅳ non-small cell lung cancer by targeted therapy / 中华放射肿瘤学杂志

Objective:To investigate the primary tumor volume change and timing of radiotherapy for patients with stage Ⅳ non-small cell lung cancer with EGFR mutation during molecular targeted therapy.Methods:Simulated CT scanning measurement and analysis were performed to observe the volume changes of primary tumors before and after treatment with a time interval of 10 days in this prospective study. Positioning and volume measurement were terminated when the volume change was 5% or less between two time points before and after treatment or 90 days after treatment. Primary tumor radiation therapy was then performed, acute radiation-induced injury was recorded, and the implementation and simulation of related parameters of radiotherapy plans were compared.Results:Twenty-nine of 30 cases were included in the analysis (1 case dropped off). After EGFR-TKIs treatment, the volume of all primary tumors was decreased, but the shrinking rate was inconsistent with the speed. Until the last simulated CT scanning, the maximum and minimum shrinking rates were 90% and 28%, respectively. There was no case of termination within 30 days of treatment, and the average tumor volume was significantly decreased within 40 days and the average tumor volume significantly differed every 10 days ( P<0.001). After 40 days, the volume shrinking rate of primary tumors ≤5% gradually appeared, and one patient presented with a volume shrinking rate of >5% on 90 days. During this time, the average volume shrinking rate slowed down and became stable, ranging from 49.15% to 54.77%. Moreover, the average volume continued to gradually shrink after slight increase at 70 days. There was no significant difference in the average volume every 10 days ( P>0.05). After the termination of simulated CT scanning, the dose of primary tumor was (69±7) Gy for patients receiving radiotherapy. Two patients had grade 2 acute radiation-induced pneumonitis and 3 patients had grade 3 acute radiation-induced pneumonitis. In addition, 1 patient had grade 2 radiation-induced esophagitis. According to the technology and dose parameters of radiotherapy plan, simulated radiotherapy plans before and 40 days after EGFR-TKIs treatment were designed. The timing of implementation plan was significantly better than that before EGFR-TKIs treatment (all P<0.05), whereas it was similar to that at 40 days after EGFR-TKI treatment ( P>0.05). Conclusions:The primary tumor shrinking rate is gradually slowed down over time after EGFR-TKIs treatment in patients with stage Ⅳ non-small cell lung cancer. The average tumor volume is significantly decreased within 40 days and then the shrinking rate becomes slow. The tumor shrinking rate of each case is inconsistent. Radiotherapy at 40 days after treatment is probably the optimal timing to obtain high dose and control radiation-induced injury.

Clinical outcome of radiotherapy for primary tumors in stage Ⅳ non-small cell lung cancer complicated with malignant pleural effusion / 中华放射肿瘤学杂志

Objective:To retrospectively analyze the clinical efficacy and safety of three-dimensional radiotherapy for the primary tumors in patients with stage Ⅳ non-small cell lung cancer complicated with malignant pleural effusion (MPE-NSCLC).Methods:A total of 198 patients who were initially pathologically diagnosed with MPE-NSCLC from January 2007 to April 2018 were enrolled and divided into the untreated group ( n=45), drug group ( n=57) and radiotherapy group ( n=96), respectively. The short-term efficacy, overall survival (OS) and adverse events in the drug and radiotherapy groups were analyzed. The OS rate was analyzed by Kaplan-Meier method and log-rank test. Clinical prognosis was evaluated by multivariate Cox′s regression model. Results:In the radiotherapy group, the objective response rate and non-response rate was 54% and 46%, significantly better than 25% and 75% in the drug group ( P=0.007). In the radiotherapy group, the 1-, 2-, 3-, 5-year OS and median survival was 47%, 18%, 6%, 1% and 12 months, remarkably higher than 15%, 3%, 2%, 0% and 5 months in the drug group, respectively (all P<0.001). Multivariate Cox′s regression analysis showed that radiotherapy for the primary tumors was an independent prognostic factor to prolong the OS ( P<0.001). Radiotherapy at a dose of ≥63 Gy and 4-6 cycles of chemotherapy tended to prolong the OS ( P=0.063 and 0.071). The OS of patients with EGFR mutation receiving radiotherapy combined with molecular target therapy was significantly better than that of those with unknown EGFR status treated with radiotherapy and chemotherapy ( P=0.007). Addition of radiotherapy for the primary tumors did not significantly increase the incidence of adverse events ( P>0.05). Conclusion:Addition of three-dimensional radiotherapy for the primary tumors in MPE-NSCLC patients may prolong the OS and yield tolerable adverse events.

Recombinant human endostatin reduces radiation-induced myocardial fibrosis in rats / 中华放射医学与防护杂志

Objective:To assess the effects of recombinant human endostatin (rh-ES) on radiation-induced myocardial fibrosis.Methods:Totally 40 SD rats were randomly divided into 4 groups, including A group as normal control, B group receiving rh-ES with a dosage of 6 mg·kg -1·d -1, in traperitoneal injection, for 14 consecutive days, C group with local heart irradiation delivered to the precordial region of rats in five fractions with a dose of 25 Gy, D group receiving rh-ES as the same as B group and local heart irradiation as C group. At 1 and 3 months after irradiation, five rats were killed under anesthesia. Mason staining was used to observe myocardial injury and fibrosis. Western blotting was used to detect the expression of TGF-β1, CTGF and COL-I in myocardium. Results:Masson staining showed that no obvious myocardial fibrosis was found in group B at 1 month and 3 months after irradiation, while collagen fibers were distributed in myocardium in groups C and D. One month after irradiation, the result of semi-quantitative analysis showed that the CVF in group A was (5.20 ±0.75)%, which was significantly lower than that in group C (10.12 ±2.17)% ( t=4.74、4.93, P<0.01) and the CVF in group D (10.32 ±1.36), and the CVF of group C was similar to that of group D ( P<0.01). Three months after irradiation, CVF in group C (13.17±2.67)% was still higher than that in group A (5.23 ±1.32)% ( t=4.49, P<0.01), but lower than that in group D (16.92 ±3.58)% ( t=3.19, P<0.05). One month after irradiation, the expression of TGF-β1 in group A was 0.441 ±0.063, lower than that in group C (0.817 ±0.079, t=5.81, P<0.01). Three months after irradiation, the expression of TGF-β1 in group A was 0.501 ±0.110, lower than that in group C (0.832 ±0.150, t=4.19, P<0.01), and the expression of TGF-β1 in group D was 1.403 ±0.133, which was significantly higher than that in group C ( t=7.24, P<0.01). Conclusions:Radiation can cause the formation of myocardial fibrosis, and recombinant human endostatin may aggravate the formation of late radiation fibrosis.

Investigation on iodine nutrition level and prevalence of thyroid nodules in Harbin / 中华地方病学杂志

Objective To investigate the iodine intake level and the prevalence of thyroid nodules in Harbin City,and to study the correlation between the concentration of urinary iodine and the prevalence of thyroid nodules.Methods In Harbin,18 communities were randomly selected and specimens were collected from fasting morning urine from 2015 to 2017.The urine iodine concentration (UIC) was detected by arsenic cerium catalytic spectrophotometry,and the thyroid nodule was examined by B ultrasound.Results A total of 2 552 residents aged (45.79 ± 12.06) years old agreed to participate in the study,including 371 males and 2 181 females.The median UIC in all participants was 159.8 μg/L,there was a significant difference in urine iodine frequency distribution among age groups (x2 =40.097,P ＜ 0.01).Furthermore,the median UIC in male was 166.6 μg/L,and in female was 156.2 μg/L.There was a significant difference in UICs between male and female (U =2.122,P ＜ 0.05).The prevalence of total thyroid nodules in all participants was 48.75％ (1 244/2 552),and the standardized rate was 40.55％.Significant difference in the detection rate of thyroid nodules was observed among age groups (x2 =114.922,P ＜ 0.01),and there was a positive and significant correlation between the detection rate of thyroid nodules and increasing age (xtrand =111.746,P ＜ 0.01).Furthermore,in male,41.24％ (153/371) had thyroid nodules,with standardized prevalence rate of 41.13％,and in female,50.02％ (1 091/2 181) had thyroid nodules,with standardized prevalence rate of 49.20％.Likewise,there was a significant difference in the detection rate of thyroid nodules between male and female(x2 =9.790,P ＜ 0.01).The detection rate of thyroid nodules in the iodine deficient population (urinary iodine was 0-＜ 100 μg/L) was 55.58％ (244/439),and the incidence of thyroid nodules in the iodine adequate or optimal population (urinary iodine was 100-＜ 200 μg/L) was 46.68％ (591/1 266).Conclusions The total iodine level of the population in Harbin City of Heilongjiang Province is at adequate level.The detection rate of thyroid nodules is high and it is increased with age.The detection rate of thyroid nodules is higher in female than male.Regular detection of urine iodine and adjusting iodine nutrition will help prevent thyroid nodules.

CT diagnosis of nutcracker syndrome / 实用放射学杂志

Objective To investigate the diagnostic value of some measured values of CT for nutcracker syndrome(NCS).Methods 28 patients with NCS confirmed by clinical diagnosis and other 81 normal controls were enrolled in the study.The angle between the superior mesenteric artery and the abdominal aorta,and the diameter and the area of left renal vein before/within this angle were measured on enhanced CT and MPR reconstruction images.The ratios of the diameter and the area before the angle to those within the angle were calculated.ROC curve was established to calculate the cut-off value and to evaluate the sensitivity,specificity,positive predictive value and negative predictive value of these parameters.Results In patient group,the mean aortomesenteric angle was 22.4°± 7.16°,mean diameter ratio was 5.10 ± 1.76 and the mean area ratio was 4.07 ± 2.10.In control group,the mean aortomesenteric angle was 61.32°± 22.82°,mean diameter ratio was 1.38 ± 0.40 and mean area ratio was 1.29 ± 0.49.The area under the ROC of the aortomesenteric angle,and the diameter ratio and area ratio were 0.979,1.000 and 0.989 respectively with corresponding cut-off values of 32.5°,2.63 and 2.06,sensitivity of 92.8%,100% and 96.4%,specificity of 95.1%,100% and 92.6%,positive predictive value of 86.7%, 100% and 81.8%,and negative predictive value of 97.5%,100% and 98.7%,respectively.Conclusion The aortomesenteric angle, the diameter and area ratios of left renal vein before/within the aortomesenteric angle have significant diagnostic value in the patients with NCS,and the value of diameter ratio is the highest.

CD137 signaling promotes the formation of plaque calcification via inhibiting the fusion of autophagy and lysosomal in Apo E-/- mice / 中华心血管病杂志

Objective@#To investigate whether CD137 signaling promoted the formation of atherosclerotic plaque calcification by inhibiting the fusion of autophagosome and lysosome.@*Methods@#(1) In vivo, CD137 agonist antibody and anti-CD137 antibody were used to stimulate and inhibit the CD137 signaling, respectively. Fifteen Apo E-/- mice were randomly divided into three groups: control group (intraperitoneal injection of IgG2b 200 µg) , CD137 agonist group (intraperitoneal injection of CD137 agonist antibody 200 µg) , anti-CD137 group (pretreatment with 200 µg anti-CD137 antibody for 24 hours, then injection of CD137 agonist antibody) . (2) In vitro, primary culture of mouse aortic VSMCs obtained through adherence methods for tissues explants. The cells was divided into three groups: control group, agonist-CD137 group (CD137 agonist antibody 10 μg/ml) , and anti-CD137 group (pretreatment with 10 μg/ml anti-CD137 antibody for 60 minutes, then incubated with 10 μg/ml CD137 agonist antibody) . Von kossa staining was used to detect the calcification in the cell and plaque. Immunohistochemical staining was used to observe the expression of LC3B, Beclin 1 and p62 which are associated with autophagy. The levels of autophagy related protein (LC3) , Beclin 1, p62, and the expression of Runx2 and bone morphogenetic protein 2, which is associated with osteogenic differentiation in the VSMCs, were determined by Western blot. The autophagy flow of each group was detected by fluorescence microscopy. The autophagy was observed by transmission electron microscope in vivo and in vitro.@*Results@#(1) In vivo, the calcified plaque area in CD137 agonist group was significantly larger than that in the control group (3.01%±0.45% vs. 0.27%±0.06%, P<0.01) , and calcified plaque area in anti-CD137 group was significantly smaller compared with that in the CD137 agonist group (1.23%±0.39% vs. 3.01%±0.45%, P<0.05) . Immunohistochemical staining showed that the expression of early autophagy marker protein LC3B and Beclin 1 were significantly upregulated in CD137 agonist group and anti-CD137 group than in control group, and the highest expression was observed in CD137 agonist group (P<0.05) . The expression of advanced autophagy marker protein p62 was higher in the CD137 agonist group than in the anti-CD137 group (P<0.05) . (2) In vitro, the ratio of autophagy related protein LC3 Ⅱ/Ⅰ and p62 protein expression were significantly higher in CD137 agonist group and anti-CD137 group than in control group (P<0.01) , while the expression of p62 protein was significantly higher in CD137 agonist group than that in anti-CD137 group (P<0.05) . In the cell calcification inducing experiment, the expression of BMP-2 and Runx2 protein was significantly higher in CD137 agonist group than that in control group (P<0.01) , but the levels of BMP-2 and Runx2 protein were lower in anti-CD137 group than in CD137 agonist group (P<0.05) .@*Conclusion@#Our results indicate that activation of CD137 signaling can promote the formation of atherosclerotic plaque calcification by inhibiting the fusion of autophagosome and lysosome.

Impact of CD137-CD137L signaling mediated exocytosis of autophagosome within vascular smooth muscle cells on the formation of atherosclerotic calcification / 中华心血管病杂志

Objective@#To explore whether CD137-CD137L signaling mediated exocytosis of autophagosome within vascular smooth muscle cells (VSMCs) could influence the formation of atherosclerotic calcification.@*Methods@#Fifteen 8-week-old male ApoE-/-(C57BL/6J-KO) mice fed with high fat diet for 5 weeks were randomly divided into three groups by using stochastic indicator method as follows: control group, n=5; agonist-CD137 group: agonist-CD137 antibody 200 μg/2 weeks for 4 weeks, ip, n=5; anti-CD137 group: 200 μg anti-CD137 antibody+ 200 μg agonist-CD137 antibody/2 weeks for 4 weeks, ip, n=5. Von Kossa staining was applied to observe the calcification of the thoracic aortic atherosclerotic plaque in each group. Immunohistochemistry was used to detect the expression of LC3 and Beclin1 which were the autophage markers of early-to-mid stage; Western blot was adopted to quantify protein level of microtubule-associated proteins 1 light chain 3B(LC3B) and mammalian ortholog of the yeast autophagy-related gene 6 (Beclin1). Transmission electron microscope (TME) was used to observe the formation of autophagosome in plaque. C57BL/6J mouse VSMCs were cultured by using tissue piece inoculation method. Groups of in vitro studies were the same as in vivo study: control group, agonist-CD137 group, anti-CD137 group, the agonist-CD137 groups was treated with agonist-CD137 antibody (10 μg/ml) and anti-CD137 group was treated with anti-CD137 antibody (10 μg/ml) for 30 minutes, followed by agonist-CD137 antibody (10 μg/ml). Von Kossa staining and osteogenesis phenotypic alkaline phosphatase (ALP) activity detection were adopted to observe calcification in VSMCs. Autophagosomes were separated from the supernatant of the agonist-CD137 group with density gradient centrifugation method. VSMCs were divided into two groups: positive group (containing complete medium with above autophagosomes to a final concentration 15 μg/ml) and negative group (only complete medium) after being pretreated with mixed inflammatory cytokines (IL-1β、IFN-γ and TNF-α, final concentration was 25 ng/ml respectively) for 24 hours and calcium deposition and osteogenesis phenotypic marker bone morphogenetic protein 2(BMP2) were then detected.@*Results@#(1) Compared with the control group, activation of the CD137-CD137L signal significantly increased the formation of calcification area in thoracic aortic atherosclerotic plaque of ApoE-/- mice((1.82±0.15)×104 μm2 vs. (0.34±0.08)×104 μm2, P<0.01), this effect was significantly attenuated by inhibiting this signal ((0.83±0.30)×104 μm2 vs. (1.82±0.15)×104 μm2, P<0.05); positive autophagy makers LC3B and Beclin1 were detected in both agonist-CD137 group and anti-CD137 groups and the expression of LC3B and Beclin1 was substantially higher in anti-CD137 group. Western blot analysis indicated that the expression of LC3B and Beclin1 in agonist-CD137 group was significantly upregulated compared with the control group (0.17±0.01 vs. 0.03±0.08, P<0.05, and 0.12±0.02 vs. 0.06±0.02, P<0.05), which could be significantly downregulated in anti-CD137 group (0.28±0.09 vs. 0.17±0.01, P<0.05 and 0.17±0.02 vs. 0.12±0.02, P<0.05). TME showed that the number (QTY /HP) of autophagosome of agonist-CD137 group and anti-CD137 group in plaque were both increased (14.67±2.52 vs. 3.67±1.53, P<0.01, and 15.33±2.08 vs. 3.67±1.53, P<0.01), while in the agonist-CD137 group, the number of extracellular autophagosome within thoracic aortic atherosclerotic plaque of ApoE-/- mice increased more substantially (5.33±1.53 vs. 1.33±0.58, P<0.01). (2) In vitro study showed that activating CD137-CD137L signal could promote calcium deposition in extracellular matrix and the activity of osteogenesis phenotypic ALP((6.73±0.02) μmol/mg protein vs. (1.07±0.03) μmol/mg protein, P<0.05), and ((563.20±0.72) U/mg protein vs. (117.50±0.64) U/mg protein, P<0.05), while these effects were significantly blunted in anti-CD137 group ((1.94±0.05) μmol/mg protein vs. (6.73±0.02) μmol/mg protein, P<0.05, and (236.10±0.14) U/mg protein vs. (563.20±0.72) U/mg protein, P<0.05). TME showed that the number of intracellular autophagosome in agonist-CD137 group and anti-CD137 group was both significantly higher than in control group ((21.65±1.34) μg/ml vs. (8.32±1.58) μg/ml, P<0.01, and (15.42±1.65) μg/ml vs. (8.32±1.58) μg/ml, P<0.05). After the density gradient centrifugation, exocytotic autophagosome in the medium of agonist-CD137 group was markedly higher than in control group ((14.67±1.53) μg/ml vs. (2.33±1.15) μg/ml, P<0.01). (3) Compared with the control group, autophagosomes isolated from culture supernatant (final concentration: 15 μg/ml) could significantly stimulate calcium deposition((2.30±0.10) μmol/mg protein vs. (0.15±0.40) μmol/mg protein, P<0.05) and enhance the expression of bone morphogenetic protein 2 (2.10±0.04 vs. 0.30±0.01, P<0.05).@*Conclusion@#CD137-CD137L signaling could mediate exocytosis of autophagosome within VSMCs, thus influence the formation of atherosclerotic calcification.

Clinical assessment of combination serum miR-21 and CA199 for pancreatic cancer diagnosis / 中华检验医学杂志

Objective To investigate the diagnostic value of serum miR-21 andCA199 for pancreatic cancer,and aim to provide a potential diagnostic method for the diagnosis of pancreatic cancer in clinical practice.Methods Detect the levels of CA199 and the relative expression of miR-21 in 134 pancreatic cancer patients,97 benign pancreatic disease patients and 106 healthy subjects from January 2014 to December 2015 in Clinical Laboratory of 263 Clinical Department of Army General Hospital,Evaluate the diagnostic value of single and combined detection of CA199 for pancreatic cancer.The diagnostic values were evaluated by receiver operating characteristic curve,sensitivity and specificity.The area under the receiver operating characteristic curve was compared by the z-score test.Results Compared with healthy control group,CA199 and miR-21 in benign pancreatic disease group and pancreatic cancer group showed significantly increased.Compared with benign pancreatic disease group,CA199 and miR-21 alsoshowed significantly increased in pancreatic cancer group.For discriminating the healthy control group and pancreatic cancer group,the sensitivity and specificity were 77.61％and 69.81％respectively when combination CA199 and miR-21.The AUC of combination CA199 and miR-21 was0.85,it showed significantly higher when compared with CA199 and miR-21 alone(P=0.021,P=0.036).For discriminating the benign pancreatic disease group and pancreatic cancer group,the sensitivity and specificity were 69.40％and 65.98％respectively when combination CA199 and miR-21.The AUC of combination CA199 and miR-21 was 0.78,it showed significantly higher when compared with CA199 and miR-21 alone(P=0.017,P=0.023).Conclusions miR-21 showed certain diagnostic value for pancreatic cancer.Combined with CA199,miR-21 may provide a potential assistant diagnostic method for the diagnosis of pancreatic cancer.

Therapeutic effect analysis for open resection in osteoid osteoma around lesser trochanter of femur / 中南大学学报(医学版)

To evaluate the radiological features of osteoid osteoma around lesser trochante of femur, and to analyze the outcomes of treatment with open surgery.
 Methods: From July 2013 to August 2015, 14 patients (9 males, 5 females) with osteoid osteoma around lesser trochanter were retrospectively reviewed. The ages of patients were 9-44 (average 20) years old. The duration of symptom was 3-36 (average 8) months. After the X-ray plain radiography, CT and MR, all patients underwent open resection. No intense exercise was allowed in the first three months after the operation.
 Results: There were 9 cases of cortical type, and 5 cases of subperiosteal type. The niduses were found by plain radiographs in 9 patients. By CT scan, the niduses were found in all 14 patients. The average pre-operative visual analogue scale (VAS) without NSAIDs was 6.5. One month after the operation, the average VAS was 0 for all patients. The follow up time for all patients was 9-34 (average 20) months. No recurrence, infection, neurovascular injury or fracture was found during the follow up.
 Conclusion: Open resection is a feasible method for osteoid osteoma around lesser trochanter of femur with satisfied outcome and low complication rate.

Efficacy of reconstruction with modular endoprosthesis after resection of periacetabular malignant tumors / 中南大学学报(医学版)

OBJECTIVE@#To explore the efficacy of the resection of periacetabular malignant tumors and the reconstruction with modular endoprosthesis.
@*METHODS@#From August 2006 to December 2012, 22 patients with periacetabular malignant tumors, who received the resection and reconstruction with modular prosthesis, were retrospectively reviewed. There were 11 males and 11 females, and the average age was 44 (16-65) years old. Pathological results showed there were 13 cases of chondrosarcoma, 5 cases of osteosarcoma, 2 cases of Ewing's sarcoma, 1 case of maligant fibrous histiocytoma, and 1 case of giant cell tumor. According to the classification system by Enneking, there were 11 cases of Type II+III resection, 5 cases of Type I+II+III resection, 3 cases of Type I+II resection, and 3 cases of Type II resection.
@*RESULTS@#All patients were followed up. The average time for follow-up was 49 (11-103) months. At the last time of follow-up, 13 patients (59%) were still alive, 9 patients (41%) died due to their primary disease. Metastasis occurred in 8 patients (36%), and local recurrence occurred in 5 patients (23%). The mean Musculoskeletal Tumor Society (MSTS) score for 13 cases of alive patients at the latest time of follow-up was (18.5±5.7) months. The mean score for 11 patients, whose limb salvage were successful, was 20.7±2.0.
@*CONCLUSION@#Reconstruction with modular prosthesis after wide resection for periacetabular malignant tumor can achieve satisfied outcome.

Effect of class 10000 laminar flow ward on the incidence of healthcare-as-sociated infection in patients with initial occurrence of acute leukemia dur-ing induction chemotherapy period / 中国感染控制杂志

Objective To evaluate the effect of class 10000 laminar flow ward on the incidence of healthcare-asso-ciated infection (HAI)in patients with initial occurrence of acute leukemia during induction chemotherapy period. Methods Patients with initial occurrence of acute leukemia admitted to a hematological department of a hospital be-tween October 2013 and June 2014 were investigated retrospectively,patients in class 10000 laminar flow ward was as trial group,in general ward was as control group. All patients received standard induction chemotherapy and the same nursing measures,the incidence of HAI between two groups of patients,and ward air cleanliness were com-pared.Results A total of 79 patients with initial acute leukemia were received (trial group,n= 39;control group, n= 40). The average air cleanliness value in rooms and corridors of laminar flow wards were both significantly dif-ferent with general ward (3.57×106/m3 vs 149.36×106/m3 ,t= 45.80,P<0.001;24.46×106/m3 vs 15854.38 ×106/m3 ,t= 108.70,P<0.001). Incidence of HAI between trial group and control group was significantly differ-ent (23.08% [9/39]vs 45.00% [18/40],χ2= 4.219,P= 0.040). The main infection site in trial group was gastro-intestinal tract (n= 5 ),in control group was lower respiratory tract (n= 8 ). The duration of fever,duration and cost of antimicrobial use in trial group were (6.20±2.10)d,(9.35±2.12)d,and (27113.79±1559.03)yuan re-spectively,in control group were (10.20±2.90)d,(14.15±3.14)d,and (58566.29±2217.54)yuan respectively, difference in duration of fever and cost of antimicrobial use between two groups were all significant(t= 1.021, 1377.45,both P<0.05).Conclusion Laminar flow ward can reduce the incidence of HAI in patients with initial occurrence of acute leukemia,and decrease cost of antimicrobial use.

Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC-MS/MS: Rg1 excretion in rat bile, urine and feces

Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile, urine, and feces after oral administration (25 mg/kg). Calibration curves offered satisfactory linearity (>0.995) within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80-120%. The excretion recoveries of Rg1, ginsenoside Rh1 (Rh1), and protopanaxatriol (Ppt) in bile, urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were 40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile. Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.

Correlation between the TNF-αGene Promoter-308G/A Polymorphism and the Chronic Hepatitis B / 现代检验医学杂志

Objective To investigate the association between the single nucleotide polymorphisms (SNP)in-308 loci of tumor necrosis factor-α(TNF-α)gene promoter region and chronic hepatitis B (CHB).Methods Genotypes of-308 loci of the TNF-αpromoter were examined by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)in 142 patients with chronic hepatitis B (CHB group)and 150 healthy controls (HC group).The indexes for evalua-ting the curative effect were the ALT,AST,HBeAg,HBV-DNA and the viral load weight,HBV-LP and HBV-PreS1,mean-while,the correlations between related indexes and SNP in TNF-α308 loci were explored as well.Results There was no sta-tistical significance in frequency distribution difference of the genotypes and alleles of-308 loci between CHC and HC groups (P>0.05),the protective factors of TNF-α308 allele A may be not associated with CHB (OR=1.529,OR95%CI:0.872~2.684).There was no association between TNF-αgene promoter-308G/A polymorphism and the positive rates of AST, ALT,HBV-LP and HBV-PreS1 (P>0.05),however,TNF-α-308G/A polymorphism associates with the positive rates of HBeAg and HBV-DNA,and A-allele of 308 loci may increase the risk of HBeAg and HBV-DNA positive expression (HBeAg:OR=3.256,OR95%CI=1.105~9.594;HBV-DNA:OR=2.847,OR95%CI=1.059~7.655).Furthermore,A-allele compared with Gallele,statistically significant differences were observed in the certain HBVDNA viral load range of104~107 copies/ml (P <005).Conclusion TNFαgene promoter308G/A polymorphism would not be associated withCHB,but the TNFα308 gene G mutation of Aallele,which was associated with HBVDNA viral load,may be the susceptible factors of HBV infection.

Effects of jejunal infusion of amino acids on secretion of gastrointestinal hormone in dog model / 中华临床营养杂志

Objective To investigate the effect of jejunal infusion of amino acids on secretion of gastrointestinal hormone in healthy dogs.Methods Six healthy adult dogs were treated with jejunal fistulas and femoral vein intubation.Twenty-four hours after the operation,solution of 8 different amino acid monomers (experimental group) or normal saline (control group) were infused into the jejunum of the dogs every 24hours.The levels of cholecystokinin (CCK),motilin,and gastrin in the peripheral plasma were measured using radioimmunoassay at the start of infusion (0 minute),and 30,60,90,and 120 minutes after infusion.Results Compared with the control group,the serum CCK level in the phenylalanine group was significantly higher 30 and 60 minutes after infusion [(1.25 ±0.19) ng/L vs.(0.66 ±0.14) ng/L,(1.23 ±0.12) ng/L vs.(0.80 ± 0.03) ng/L,both P ＜ 0.01],while that in the tryptophan group was significantly higher 30 minutes after infusion [(1.08 ±0.26) ng/L vs.(0.66 ±0.14) rig/L,P ＜0.01].The other measurement results showed no statistically significant differences.Conclusions Jejunal infusion of phenylalanine or tryptophan may stimulate the secretion of gastrointestinal hormone to some extent.Aromatic amino acids (phenylalanine and tryptophan) is more potent in triggering the release of CCK than aliphatic (leucine,isoleucine,and methionine) and charged amino acids (aspartic acid,arginine,and glutamate).The mechanism may be related to the properties of the amino acids.

Analysis of indicators in 2 521 patients before blood transfusion / 中国医师杂志

Objective To investigate the infection status of infectious diseases for 2 521 patients before blood transfusion in a Hospital in Changsha.Methods A total of 2 521 patients who would be transfused were selected,and six kind of serum hepatitis B virus indicators,hepatitis C virus antibody (antiHCV),human immunodeficiency virus antibody (anti-HIV/1 + 2),and treponema pallidum antibody (antiTP) of nine common infectious disease targets were detected with enzyme-linked immunosorbent assay (ELISA).Results Among 2 521 patients,HBsAg-positive cases were 8.33％,anti-HCV positive were 0.59％,anti-HIV positive [confirmed by the Provincial Center for Disease Control (CDC)] was 6 cases,and TP-positive were 2.301％.A total of 289 patients were tested positively,with a total positive rate of 11.46％.Conclusions Detection before transfusion may reduce infection risk and decrease the risk of occupational exposure,strengthen medical staff self-protection,and reduce medical malpractice caused by blood transfusion.