A dosimetric study on off-target isocenter plans for stereotactic body radiotherapy of lung cancer / 中华放射医学与防护杂志

Objective:To investigate the effects of off-target isocenter plans with different off-target distances on the plan quality and delivery accuracy of stereotactic body radiotherapy (SBRT) for lung cancer, aiming to provide a reference for the clinical plan design of SBRT for lung cancer.Methods:For 10 lung cancer patients treated with SBRT, isocenter reference plans were designed by setting the plan isocenters at the mass centers of tumors and 60 off-target isocenter plans by setting the isocenters at distances of 1, 3, 5, 8, and 10 cm from the mass centers of tumors. The dosimetric differences between the off-target isocenter plans and the reference plans. Subsequently was analyzed, under different positional errors (0-5 mm). The gamma pass rates (GPRs) of these plans were measured using the Octavius 4D high-resolution dose verification system, and 240 verifications of these plans were completed. The robustness of the delivery accuracy of the reference plans and off-target isocenter plans were analyzed under different positional errors.Results:The off-target isocenter plans yielded slightly worse dose gradient indices than the isocenter reference plans, but there was no statistically significant differences. With an increase in the off-target distance, the mean lung dose (MLD), V20 of normal lungs, as well as the Dmax of bronchi, showed slight upward trends. Compared with the isocenter reference plans, the MLD of the off-target isocenter plans increased by 0.8%, 0.8%, and 1.9% at off-target distances of 1, 3, and 10 cm, respectively, with statistically significant differences ( z = -2.34 to -1.99, P < 0.05), and the V20 of the off-target isocenter plans increased by 2.0%, 2.5%, and 3.7% at off-target distances of 1, 5, and 10 cm, respectively, with statistically significant differences ( z =-2.11 to -1.99, P < 0.05). In the case of a positional error of up to 5 mm, the GPRs of plans with off-target distances of 5 cm and above decreased by more than 1.0% on average and up to a maximum of 3.5%, showing statistically significant differences ( z = 2.13-2.75, P < 0.05). Conclusions:Compared to the reference plans, the off-target isocenter plans showed slightly lower dosimetric quality and less robust delivery accuracy under different positional errors. Therefore, it is necessary to avoid the plans and treatment with too large off-target distances (≥ 5 cm) as far as possible for SBRT of lung cancer.

A metaheuristics-based automatic planning method for intensity-modulated radiation therapy / 中华放射医学与防护杂志

Objective:To establish a metaheuristics-based automatic radiotherapy treatment planning method (ATP-STAR) and verify its effectiveness.Methods:The main process of the ATP-STAR method was as follows. First, the optimization parameters were vectorized for encoding and corrected using Gaussian convolution. Then, the candidate optimization parameter vector set was selected through simulated annealing. Finally, the optimal combination of optimization parameters was determined by combining the field fluence optimization to achieve automatic trial-and-error. Twenty cases with large individual differences in tumors were selected for testing. Clinical physicists with more than five years of experience were invited to perform manual planning. Both the manual and ATP-STAR plans were made utilizing the matRad open source software for radiation treatment planning, with the fields and prescribed doses consistent with those of the clinical treatment plans. The dosimetric differences of target volumes and organs at risk between the ATP-STAR and manual plans for different diseases were analyzed.Results:For the target volumes, the ATP-STAR plans showed superior homogeneity compared with the manual plans (brain tumors: z = 2.28, P = 0.022; lung cancers: z = 2.29, P = 0.022; liver cancers: z = 2.11, P = 0.035). The conformability of the ATP-STAR plans was comparable to that of the manual plans for brain tumors and liver cancer and was slightly lower than that of the manual plans for lung cancer ( z = 2.29, P = 0.022). The comparison result of doses to organs at risk (OARs) between the manual plans and STAR plans were as follows. For OARs of brain tumors, the ATP-STAR plans decreased the mean left lens Dmean from 2.19 Gy to 1.76 Gy ( z = 2.28, P = 0.022), decreased left optic nerve Dmean from 11.36 Gy to 10.22 Gy ( z = 2.28, P = 0.022), decreased right optic nerve Dmax from 32.92 Gy to 29.97 Gy ( z = 2.10, P = 0.036), and decreased pituitary Dmax from 39.53 Gy to 35.21 Gy ( z = 2.29, P = 0.022). For OARs of lung cancer, the ATP-STAR plans decreased the mean spinal cord Dmax from 38.00 Gy to 31.17 Gy ( z = 2.12, P = 0.034), decreased the bilateral lungs Dmean from 8.51 Gy to 8.07 Gy ( z = 2.29, P = 0.022), and decreased cardiac Dmean from 3.21 Gy to 2.69 Gy ( z =2.29, P = 0.022). For OARs of liver cancer, the ATP-STAR plans decreased spinal cord Dmax from 18.19 Gy to 14.76 Gy ( z = 2.11, P = 0.035), decreased liver Dmean from 15.61 Gy to 14.45 Gy ( z = 2.11, P = 0.035), and decreased kidneys Dmean from 4.76 Gy to 4.04 Gy ( z = 2.10, P = 0.036). Conclusions:The proposed ATP-STAR method relies little on the experience of manual planning and thus is easy to be widely applied. This method is expected to improve the quality and consistency of IMRT plans and save clinical labor and time costs.

Effect of dwell time deviation constraint on the three-dimensional brachytherapy plans for cervical cancer / 中华放射肿瘤学杂志

Objective:To investigate the effect of dwell time deviation constraint of inverse optimization on the quality and position error robustness of three-dimensional (3D) brachytherapy plans for cervical cancer.Methods:A total of 20 patients with cervical cancer receiving 3D brachytherapy treatment in Xiangya Hospital Central South University from August 2020 to August 2021 were retrospectively selected. All plans were designed using the Eclipse treatment planning system, and the dwell time deviation constraint parameter smooth value in the system were set to 0.00, 0.25, 0.50, 0.75, and 1.00, respectively. An inverse dose volume optimization algorithm was used to generate plans with various smooth values, and the optimization conditions were the same as the original clinical plans. Key dosimetric metrics and total dwell time differences were comparatively analyzed. The applicators were intentionally subjected to position errors (0.2-1.0 cm) in 6 directions (left-right, anterior-posterior, head-foot), and the effect of various smooth values on plan quality and robustness was assessed. There were 133 plans per case and 2 660 plans for 20 patients. The results were statistically analyzed using the Wilcoxon signed-rank nonparametric test.Results:As the smooth value was increased, the modulation factor was gradually decreased and the D 2 cm3 of the bladder and rectum was increased. Plans with smooth values of 0.25, 0.50, 0.75, 1.00 had modulation factors of 0.72±0.09, 0.63±0.08, 0.55±0.08, 0.51±0.06, respectively, lower than 0.75±0.05 of the plan with the smooth value of 0.00, and all differences were statistically significant ( P=0.004, 0.002, 0.002, 0.002). The bladder D 2 cm3 of plans with smooth values of 0.50, 0.75, 1.00 were (475.4±41.0) cGy, (483.7±46.2) cGy, and (489.0±46.8) cGy, respectively, higher than (469.8±41.8) cGy of the plan with the smooth value of 0.00, with statistically significant differences (all P=0.002). The rectum D 2 cm3 of plans with smooth values of 0.50 and 0.75 plans were (413.2±93.3) cGy and (418.6±96.4) cGy, both higher than (410.2±91.5) cGy of the plan with the smooth value of 0.00, with statistically significant differences ( P=0.006, 0.010). When positional errors were introduced, the high risk clinical target volume (HR-CTV) D 90% was close for different smooth plans at most positional errors, and the differences were not statistically significant. The organs at risk D 2 cm3 of plans with the smooth value of 0.00 was lower than those of plans with other smooth values, and for the bladder and rectum, the differences were statistically significant at most positional errors (all P<0.01). Conclusions:The dwell time deviation constraint parameter exerts significant effect on the plan quality, and the smaller the value of the constraint parameter, the higher quality of the plan. The dwell time deviation constraint parameter has slight impact on the positional error robustness of dosimetric indices of targets and key organs at risk.

Research progress of traditional external preparations and novel nanoformulations of Arnebiae Radix / 中国药房

Arnebiae Radix is used widely in TCM external treatment. It has obvious curative effect on skin diseases， wound infection and local inflammation， and is used to treat water and fire burns， skin ulcers， eczema， psoriasis， vitiligo and atopic dermatitis， etc. The clinical and commercial preparations mainly include ointment， liniment and suppository. Modern research has proved that microcapsules， nano-micelles， nanofiber membranes， nanogels and other novel nanoformulations can significantly improve the stability of drug-effective substances， improve local drug concentration and targeting， and perform sound drug release properties in vitro. This paper reviews the variety and application of Arnebiae Radix traditional preparations for external use and the research progress of novel nanoformulations of Arnebiae Radix， from which we prospect to provide some valuable references for the future application and development of Arnebiae Radix external preparations.

Quality difference of wild Lysimachiae Herba in the source areas of Sichuan, Chongqing and Guizhou / 国际中医中药杂志

Objective:To determine the contents of quercetin, kaempferol, total flavonoids and extracts in 52 samples of Lysimachiae Herba collected from different origins; To analyze the quality differences of Lysimachiae Herba among different producing areas. Methods:The quercetin and kaempferol contents of the Lysimachiae Herba from Guizhou Province, Sichuan Province and Chongqing were determined by HPLC, and the total flavonoids were determined by Symergy HTX microplate reader. Results:The total content of quercetin and kaempferol in 52 samples was among 0.146 2-2.517 0 mg/g, with an average content of 0.872 6 mg/g, among which the average content of Sichuan was 1.073 2 mg/g, that of Guizhou was 0.705 4 mg/g, and that of Chongqing was 0.865 1 mg/g. Among them, 20 samples reached the standard of the Chinese Pharmacopoeia. The average content of the samples that met the standard was 1.439 7 mg/g. The compliance rate of samples collected in Guizhou, Sichuan and Chongqing reached 12.5%, 62.5%, and 38.8% respectively. The total flavonoid content of 52 samples was among 0.994 2- 3.866 4 mg/g, and 52 samples were in conformity with the ethanol hot extract standard of the Chinese Pharmacopoeia. Conclusions:The total contents of quercetin and kaempferol from different sources in Sichuan, Guizhou and Chongqing are quite different, and the total contents of quercetin and kaempferol collected from the same district and county are also quite different, and the compliance rate is low. There are great differences in total flavonoids in different producing areas and different populations of Lysimachiae Herba samples collected in the field.

Assessment of left ventricular diastolic dyssynchrony and its influencing factors early after acute myocardial infarction by SPECT gated myocardial perfusion imaging: an experimental study / 中华核医学与分子影像杂志

Objective:To evaluate the left ventricular diastolic dyssynchrony (LVDD) and its influencing factors early after acute myocardial infarction (AMI) using phase analysis of SPECT gated myocardial perfusion imaging (GMPI).Methods:Bama miniature swines ( n=16) were subjected to establish AMI models. GMPI was performed before and 1 d after AMI to obtain the extent of myocardial perfusion defect (Extent, %) and left ventricular systolic dyssynchrony (LVSD)/LVDD parameters, namely the phase histogram bandwidth (PBW) and phase standard deviation (PSD). Meanwhile, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and the ratio of early to late peak mitral diastolic flow (E/A) were obtained by echocardiography. Independent-sample t test, paired t test and Pearson correlation analysis were used to analyze the data. Results:Sixteen AMI swines were successfully created. Compared to baseline, Extent, LVEDV and LVESV significantly increased on 1 d after AMI ( t values: -11.14, -4.55, -6.12, all P<0.001), while LVEF and E/A significantly decreased ( t values: 10.16, 2.18, P<0.001, P=0.046). GMPI showed that the LVDD parameters PBW and PSD increased significantly on 1 d after AMI when compared to those at baseline((142.25±72.06)° vs (33.06±8.98)°, (56.15±26.71)° vs (12.51±5.13)°; t values: -6.11, -6.60, both P<0.001). There were significant differences between LVSD parameters and LVDD parameters (PBW: (109.06±62.40)° vs (142.25±72.06)°, PSD: (44.40±25.61)° vs (56.15±26.71)°; t values: -2.73, -2.20, P values: 0.016, 0.044). LVDD parameters PBW, PSD were negatively correlated with E/A after AMI ( r values: -0.569, -0.566, P values: 0.021, 0.022), and positively correlated with the Extent ( r values: 0.717, 0.634, P values: 0.002, 0.008). The phase analysis of SPECT GMPI to evaluate LVDD showed good intra-observer and inter-observe reproducibility (intraclass correlation coefficient (ICC): 0.953-0.984, all P<0.001). Conclusions:LVDD occurs early on 1 d after AMI, and can reflect left ventricular diastolic dysfunction. The Extent is correlated with LVDD significantly. Phase analysis of SPECT GMPI is an accurate method to evaluate LVDD and left ventricular diastolic function.

Research on KBP model refining method using multi-criterion optimization technology / 中华放射肿瘤学杂志

Objective:Utilizing multi-criterion optimization (MCO) technology to improve plan design quality based on knowledge-based planning (KBP) model.Methods:Fifty-five patients with nasopharyngeal carcinoma (NPC) who had completed radiotherapy were selected, and fixed-field intensity-modulated radiotherapy (IMRT) technology was used in each case. Among them, 40 cases were randomly selected as training set 1. Then, IMRT plans in training set 1 were preprocessed by MCO technology to construct a new training set 2. With the initial training set 1 and the processed training set 2 as training samples, the traditional KBP model and the MCO-KBP model refined by MCO technology were trained, respectively. Among the remaining 15 cases, 5 cases were randomly selected as the validation set, and the remaining 10 cases were used as the test set. After verification, the test set was used to statistically analyze the plan quality of the initial manual plan and the automatic plan generated by the traditional KBP model and the MCO-KBP model.Results:The target dose (D 95%) of plans generated by the traditional KBP model and the MCO-KBP model met the clinical requirements. Conformity index (CI) and homogeneity index (HI) were almost the same ( P>0.05), and the doses of organ at risk (OAR) of the automatic plans generated by the MCO-KBP model were lower than those of the traditional KBP model. For example, compared with the traditional KBP model, the average D max of the brainstem in the automatic plans generated by the MCO-KBP model was lower by 2.13 Gy, the average D mean of the left parotid gland was lower by 1.39 Gy, the average D mean of the right parotid gland was lower by 1.59 Gy, and the average D max of the left optic nerve was lower by 1.42 Gy, the average D max of the right optic nerve was lower by 1.16 Gy, and the average D max of the pituitary gland was lower by 1.88 Gy. All of the above-mentioned dosimetry indexes were statistically significant. Conclusion:Compared with the traditional KBP model, the IMRT plans designed by the refined MCO-KBP model have obvious advantages in the protection of OAR, which proves the feasibility of utilizing MCO technology to improve the plan design quality of the KBP model.

Research progress on mechanism of comorbid alcohol use disorder and depressive disorder / 四川精神卫生

In this paper， the latest research progress on the mechanism of comorbid alcohol use disorder and depressive disorder at home and abroad is elucidated from genetic， neurochemical， neuroendocrine and neuroimmunologic perspectives. It aims to identify the gaps in current research and predict future research directions， providing a further basis for the clinical management of comorbid alcohol use disorder and depressive disorder.

Advances of research on oxygen-enhancing nano-delivery system for photodynamic therapy / 中国药科大学学报

@#Photodynamic therapy, a new type of non-invasive treatment, is based on the principle that the photosensitizer excited by laser can transfer energy to oxygen, which generates cytotoxic singlet oxygen and thus induce tumor cell apoptosis or necrosis. As an oxygen-dependent therapy, the antitumor effect of photodynamic therapy is obviously limited by hypoxia environment of solid tumor tissue. Therefore, reversing and improving the hypoxia of tumor tissue can significantly enhance the efficacy of photodynamic therapy. This review focuses on the progress of tumor oxygenation strategy mediated by nano-delivery system, including direct oxygen delivery strategies, catalytic oxygen production strategies, responsive material in situ oxygen supply strategies and microorganism oxygen supply strategies, aiming to improve the antitumor effect of photodynamic therapy. It provides new ideas and new approaches for further study of oxygen-enchancing nano-delivery system for photodynamic therapy.

Efficacy of liraglutide combined with enpagliflozin in the treatment of obesity complicated by type 2 diabetes mellitus / 中国基层医药

Objective:To investigate the efficacy of liraglutide combined with enpagliflozin in the treatment of obesity complicated by type 2 diabetes mellitus.Methods:A total of 160 obesity patients with type 2 diabetes mellitus who received treatment in Yuyao People's Hospital, China between October 2018 and October 2019 were included in this study. They were randomly assigned to receive repaglinide, insulin detemir and metformin in combination (control group, n = 80) or liraglutide, enpagliflozin and metformin in combination (treatment group, n = 80). After 3 months of treatment, fasting blood glucose, glycosylated hemoglobin, 2-hour postprandial blood glucose, body mass index, tumor necrosis factor-alpha, C-reactive protein, interleukin-6, leptin, adiponectin, and vaspin as well as the incidence of adverse reactions were compared between the control and treatment groups. Results:After treatment, fasting blood glucose, glycosylated hemoglobin, 2-hour postprandial blood glucose and body mass index were reduced in each group. They were (7.89 ± 1.02) mmol/L, (8.10 ± 1.25) %, (11.10 ± 1.59) mmol/L, (23.18 ± 2.19) kg/m 2, respectively in the observation group, which were significantly lower than those in the control group [(9.88 ± 1.27) mmol/L, (11.20 ± 1.85)%, (13.67 ± 2.01) mmol/L, (27.80 ± 2.51) kg/m 2, t1 = 10.927, t2 = 12.418, t3 = 8.969, t4 = 12.405, all P < 0.001). After treatment, tumor necrosis factor-alpha, C-reactive protein and interleukin-6 levels were reduced in each group. Their levels in the observation group were [(51.19 ± 3.19) pg/L, (2.14 ± 0.31) mg/L, (4.07 ± 0.67) pg/L, respectively, which were significantly lower than those in the control group [(62.18 ± 4.10) pg/L, (3.66 ± 0.58) mg/L, (5.96 ± 0.81) pg/L, t1 = 18.922, t2 = 20.672, t3 = 8.969, all P < 0.001). After treatment, leptin and vaspin levels were reduced in each group, and their values in the observation group were (5.48±0.94) μg/L, (1.62 ± 0.37) μg/L, respectively, which were significantly lower than those in the control group [(6.59 ± 0.82) μg/L, (1.99 ± 0.52) μg/L, t1=7.959, t2=10.323, both P < 0.001]. Adiponectin level increased in each group, and it was significantly higher in the observation group than in the control group [(7.13 ± 1.52) mg/L vs. (5.12 ± 0.85) mg/L, t3 = 5.185, P < 0.001]. There was no significant difference in the incidence of adverse reactions between control and observation groups ( χ2 = 0.313, P > 0.05). Conclusion:Liraglutide combined with enpagliflozin for the treatment of obesity complicated by type 2 diabetes mellitus is highly effective. It can effectively lower blood glucose level, reduce body mass and inflammatory reactions, further regulate serum vaspin, leptin and adiponectin levels and is highly safe. Therefore, this method can be widely used in the clinic.

Application values of multiple detection methods of bone marrow in newly diagnosed multiple myeloma / 白血病·淋巴瘤

Objective:To investigate the application values of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and cytogenetic testing in newly diagnosed multiple myeloma.Methods:A total of 280 patients with multiple myeloma who were newly diagnosed in Tianjin KingMed Diagnosis Center from September 2018 to August 2019 were collected. The bone marrow biopsy was carried out according to the routine method, and bone marrow morphology, bone marrow immunohistochemistry, flow cytometry immunophenotyping, FISH and cytogenetic testing were performed. The detection results of each method were compared.Results:In 280 patients, the bone marrow immunohistochemistry results showed that the median ratio of plasma cells was higher than those of bone marrow morphology (20 cases, 0.675 vs. 0.300) and flow cytometry (47 cases, 0.650 vs. 0.147), and the differences were statistically significant ( Z = -3.883, P < 0.01; Z = -5.947, P < 0.01). Flow cytometry results showed that the positive rates of CD38, CD138, κ, λ, CD56 and CD19 were 100.0% (280/280), 100.0% (280/280), 57.5% (161/280), 42.5% (119/280), 62.1% (174/280) and 19.3% (54/280); bone marrow immunohistochemistry results showed that the positive rates of CD38, CD138, κ, λ and CD56 were 98.9% (277/280), 98.2% (275/280), 57.5% (161/280), 42.5% (119/280) and 62.1% (174/280); there was no statistical difference between the two detection methods in the detection coincidence rate of the same detection index (all P > 0.05). Among patients who underwent FISH detection, the detection rate of gene abnormalities was 69.9% (93/133); the detection rate of abnormalities by direct fluorescence in situ hybridization (D-FISH) was 42.9% (57/133); the detection rate of abnormalities by CD138 immunomagnetic sorting myeloma cells (MACS)-FISH was 82.7% (110/133). Among patients who underwent G-band karyotyping, the detection rate of abnormal karyotype was 38.5% (85/221). FSIH, especially MACS-FISH, had a higher detection rate of cytogenetic abnormalities than G-band karyotyping, and the difference was statistically significant ( χ2 = 65.697, P < 0.05). Conclusion:The comprehensive application of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, FISH (especially MACS-FISH), cytogenetic testing and other detection methods is more helpful for the diagnosis of multiple myeloma, and may be useful for prognostic judgment.

Diagnostic efficacy of three test kits for SARS-CoV-2 nucleic acid detection / 浙江大学学报·医学版

OBJECTIVE@#To compare the diagnostic efficacy among three RT-PCR test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection.@*METHODS@#The throat swab samples from 40 hospitalized patients clinically diagnosed as coronavirus disease 2019 (COVID-19) and 16 hospitalized non-COVID-19 patients were recruited. The SARS-CoV-2 nucleic acid was detected in throat swab samples with RT-PCR test kits from Sansure Biotech ("Sansure" for short), Jiangsu Bioperfectus Technologies ("Bioperfectus" for short) and BGI Genomics ("BGI" for short). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa value were analyzed. The viral nucleic acid was extracted from the throat swab samples by one-step cleavage and magnetic bead methods, and the efficacy of two extraction methods was also compared. The results of magnetic bead method for nucleic acid extraction by two different extractors (Sansure Natch CS S12C Fully Automated Nucleic Acid Extraction System vs. Tianlong NP968-C Nucleic Acid Extractor) were also compared.@*RESULTS@#The sensitivity, specificity, PPV, NPV and kappa value were 95.00%, 87.50%, 95.00%, 87.50%and 0.825 for Sansure kit; 90.00%, 87.50%, 94.74%, 77.78%and 0.747 for the Bioperfectus kit, and 82.50%, 81.25%, 91.67%, 65.00%and 0.593 for the BGI kit, respectively. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by one-step cleavage and magnetic bead methods were 95.24%, 100.00%, 96.43%and 0.909, respectively, but the one-step cleavage method took only 25 min, while the magnetic bead method required 180 min. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by the two different nucleic acid extractors were 85.00%, 100.00%, 89.29% and 0.764, respectively.@*CONCLUSIONS@#The detection efficacy for SARS-CoV-2 nucleic acid by the Sansure kit is relatively higher and the one-step cleavage method has advantages of convenient operation and less time consuming.

Baeyer-Villiger monooxygenases in the biosynthesis of microbial secondary metabolites / 生物工程学报

Baeyer-Villiger monooxygenases, a well-studied class of flavin-dependent enzymes, catalyze the conversion of ketones to lactones or esters and the oxygenation of heteroatoms, which possesses great practical prospect in synthetic chemistry and biocatalysis. In this review, we focus on Baeyer-Villiger oxidations involved in biosynthesis of microbial secondary metabolites and discuss the characteristics of these Baeyer-Villiger oxidations and Baeyer-Villiger monooxygenases, to provide reference for the protein engineering of Baeyer-Villiger monooxygenases.

Effect of polylactic-co-glycolic acid/graphene oxide nanofibers combined with brain derived neurotrophic factor on spinal cord injury repair / 中华创伤杂志

Objective To investigate the effect of polylactic-co-glycolic acid (PLGA)/graphene oxide (GO) nanofibers combined with brain derived neurotrophic factor (BDNF) on neural stem cells (NSCs) proliferation and differentiation as well as on the spinal cord injury repair.Methods PLGA/GO nanofibers were manufactured and absorbed with BDNF,and the microstructure of PLGA/GO nanofibers was observed by scanning electron microscope.The loading efficiency and release curve of BDNF on PLGA/GO nanofibers were measured by ELISA.NSCs were implanted on the surface of PLGA/GO and PLGA/GO/BDNF nanofibers.The absorbance values of each group were measured by MTT method,and the expression of Tuj-1 was observed by immunofluorescence and PCR.A total of 30 female SD rats were divided into control group (n =10),PLGA/GO group (n =10) and PLGA/GO/BDNF group (n =10) according to random number table.T9 spinal cord tissue was cut by Venus scissors to establish spinal cord hemisection injury model of rats.PLGA/GO and PLGA/GO/BDNF nanofibers were implanted onto the surface of injury site.BBB score was used to assess the motion functional recovery of the rats at 1,7,14 and 28 days after operation.Immunofluorescence staining of neuron specific nucleoprotein (NeuN)and glial fibrillary acidic protein (GFAP) were performed to observe the expressions of neurons and astrocytes at the injured site respectively one month after injury.Results The PLGA/GO nanofibers showed an irregular smooth fiber-like structure,and the average fiber diameter was (987.5 ± 176.3)nm.NSCs could differentiate into neurons on the nanofibers.The result of ELISA showed loading rate of BDNF on PLGA/GO nanofibers was about 47.5％.The release curve showed that BDNF was first released about 30％ on the first day and then about 60％ on the 21st day.The results of MTT and PCR showed that optical density value and Tuj-1 gene expression in the PLGA/GO/BDNF group were significantly higher than those in the PLGA/GO group (P ＜ 0.05).The animal experiment results showed that the BBB score of PLGA/GO/BDNF group was (15.3 ±0.7) points at 28 days after injury,which was significantly higher than that of the injury control group [(11.8 ± 0.8) points] and that of PLGA/GO group [(12.7 ±0.8) points] (P ＜ 0.05).Immunofluorescence results showed that the expression of NeuN in PLGA/GO/BDNF group was 13.7 ± 2.2,significantly higher than that in injury control group (4.3 ± 2.9) (P ＜0.05),and the expression of GFAP in PLGA/GO group was (25.6 ± 4.3) ％ significantly lower than that in injury control group [(38.5 ± 6.2) ％] and PLGA/GO group [(36.7 ± 7.3) ％] (P ＜ 0.05).Conclusion PLGMGO nanofibers combined with BDNF can effectively promote the proliferation and neuron differentiation of NSCs in vitro and repair spinal cord injury in vivo through orthotopic transplantation at the injury site.

Study of the optimal thresholds of gamma passing rate in VMAT plan verification for cervical cancer / 中华放射肿瘤学杂志

Objective To investigate the optimal thresholds of the passing rate with different gamma measurement criteria (percent dose difference/DTA) based on the Delta 4 three-dimensional dosimetric verification system in the verification of volumetric modulated arc-therapy (VMAT) plan for cervical cancer.Methods Thirty clinically-approved dual-arc VMAT plans using the RapidArcTM (Varian Medical Systems Inc.) for cervical cancer were randomly selected.The gamma analysis and dose-volume histogram (DVH) evaluation were performed using Delta 4.All the plans were classified according to the following two criteria:1.If the absolute percentage dose errors of all specific dosimetry indices on the DVH were less than 5％,the plan was regarded as clinically acceptable.2.If the gamma passing rate was 90％ or 95％ under the criteria of 2％/2 mm and 3％/3 mm,the plan was regarded as acceptable.The sensitivity and specificity analyses were conducted based on the classification results and the receiver operating characteristic (ROC) curve was plotted.By calculating the Youden Index,the optimal thresholds under different Gamma criteria (global and local 2％/2 mm and 3％/3 mm) were investigated.Finally,the ability of distinguishing the plan was clinically acceptable or not between the conventional and optimal thresholds was quantitatively compared according to the sensitivity and specificity analyses.Results The optimal thresholds under the global 3％/3 mm and 2％/2 mm criteria were 98.3％ and 87.05％;and 97.55％ 、86.05％ for the local gamma analysis.Compared with the conventional thresholds,the sensitivity of the optimal thresholds was 0.93 by using the global and local gamma analyses under the 3％/3 mm criterion.Under the 2％/2 mm criterion,the sensitivity of the optimal thresholds was 0.65 and the specificity was 0.49 by using the global gamma analysis.The sensitivity was 0.7 and the specificity was 0.46 by using the local gamma analysis,suggesting that the sensitivity and the specificity were more balanced under the 2％/2 mm criterion.Conclusions Application of the optimal thresholds in the verification of VMAT plans can maintain the balance between the sensitivity and specificity,prevent the harm of clinically unacceptable plans to patients to certain extent and reduce the probability of increasing the daily work load for physicists due to the misjudgement of clinically acceptable plans.

Clinical report of testicular hypoplasia combined with 21-hydroxylase deficiency / 中华医学遗传学杂志

OBJECTIVE To investigate the correlation of 21-hydroxylase deficiency (21-OHD) with male testicular dysplasia. METHODS Clinical data of 8 infertile males with congenital adrenal hyperplasia due to 21-OHD was retrospectively analyzed. In addition, potential mutations of the CYP21A2 gene was detected. RESULTS All patients were referred because of azoospermia or severe oligospermia and had small testis with averaged testicular volume of 6.1 mL. Three patients had testicular adrenal rest tumors. Endocrinologic examinations revealed low levels of leutinizing hormone and follicular stimulating hormone, normal or elevated testosterone, elevated progesterone, elevated or normal adrenocoticotropic hormone, and low or normal cortisol. All patients had adrenal cortical hyperplasia, 5 with adrenal adenoma, 1 case associated with bilateral adrenal myelolipoma. All patients were given glucocorticoid replacement therapy for 3 to 6 months, which successfully improved the seminal status of 6 patient and resulted pregnancies in 5 couples. Seven pathogenic mutations of the CYP21A2 gene among the 8 patients. CONCLUSION 21-OHD can cause testicular hypoplasia and spermatogenic failure. Glucocorticoids and operations can obtain good result and improve spermatogenesis. Our results have shown a good genotype/phenotype correlation in these cases. All patients have carried the p.Ile172Asn mutation, which is associated with simple virilizing form.

The optimal gamma passing rate thresholds of IMRT dosimetric verification in the treatment of esophageal cancer / 中华放射医学与防护杂志

Objective To investigate the optimal gamma passing rate of intensity-modulated radiotherapy (IMRT) dosimetric verification in the treatment of esophageal cancer using a three-dimensional dose verification system EDoseTM.Methods Twenty five esophageal cancer patients treated by 7-field IMRT were retrospectively reviewed.Measured dose distribution were reconstructed on CT image and evaluated by gamma analysis and DVH metrics using the EDoseTM system.Plans with DVH metrics dose difference ＜ 5％ or with gamma passing ＞ 90％ under 3％/3 mm criteria were accepted.The optimal gamma passing rate for criteria of 5％/3 mm,3％/3 mm,2％/2 mm were investigated by drawing the receiver operating characteristic (ROC) curves and calculating the Youden Index.The sensitivity and specificity of the these optimal thresholds in the plan verification were also analyzed.Results The optimal thresholds for global gamma indices with 5％/3 mm,3％/3 mm,2％/2 mm were 98.66％,94.84％,78.56％,respectively.In the 90％ common threshold,The sensitivity and specificity for common 90％ threshold and optimal threshold under 3％/3 mm criteria were 0.17 vs.0.85 and t 0.84 vs.0.27,respectively.The sensitivity and specificity were 0.89,0.65 and 0.23,0.47 for optimal thresholds under 5％/3 mm and 2％/2 mm criteria,respectively.Conclusions The sensitivity of optimal threshold gamma passing rate improved significantly compared with the common threshold (90％) at 3％/3 mm criteria.,The sensitivity and the specificity were more balanced at the 2％/2 mm criteria compared with those at 3％/3 mm criteria.

Effect of oxycodone on function of GABAA receptors in dorsal root ganglion neurons of rats with neuropathic pain / 中华麻醉学杂志

Objective To evaluate the effect of oxycodone on function of GABAA receptors in dor-sal root ganglion ( DRG ) neurons of rats with neuropathic pain ( NP ) . Methods Thirty-six adult male Sprague-Dawley rats, weighing 180-220 g, aged 10 weeks, were allocated into 3 groups ( n=12 each) u-sing a random number table method: sham operation group ( group S ) , group NP and oxycodone group ( group O) . The sciatic nerve was only isolated but not ligated in group S. NP was induced by chronic con-striction injury. The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut. Oxycodone 15μg∕kg was intraperitoneally injected once a day for 14 con-secutive days from ligating the sciatic nerve to satisfaction in group O. The thermal paw withdrawal latency( TWL) was measured at 1 day before establishing the model ( T0 ) and 3, 5, 7, 10 and 14 days after es-tablishing the model ( T1-5 ) . The rats were sacrificed after measurement of pain threshold at T5 , and DRG neurons were acutely isolated for recording the amplitude of GABAA receptors-activated currents using whole-cell patch-clamp technique. Results Compared with group S, the TWL was significantly shortened at T1-5, and the amplitude of GABAA receptors-activated currents in DRG neurons was decreased in NP and O groups (P<0. 05). Compared with group NP, the TWL was significantly prolonged at T1-5, and the ampli-tude of GABAA receptors-activated currents in DRG neurons was increased in group O ( P<0. 05) . Conclu-sion Oxycodone can enhance the function of GABAA receptors-activated currents in DRG neurons and thus enhance GABAA receptors-mediated presynaptic inhibition, which may be related to the mechanism of oxyc-odone-induced reduction of NP in rats.

Inhibitory effect of Chlamydia trachomatis plasmid-encoded protein pORF5 on HeLa cell apoptosis induced by tumor necrosis factor-alpha / 中华皮肤科杂志

Objective To evaluate inhibitory effect of Chlamydia trachomatis plasmid-encoded protein pORF5 on HeLa cell apoptosis induced by tumor necrosis factor-alpha(TNF-α). Methods The recombinant lentiviral expression vector containing pORF5 gene and helper plasmids were co-transfected into 293T cells to prepare the recombinant lentivirus. Then, the lentivirus particles were collected and concentrated, and used to infect HeLa cells. Flow cytometric screening identified stable pORF5-expressing HeLa (pORF5-HeLa) cells. Meanwhile, the empty plasmid was transfected into HeLa cells to prepare control HeLa cells. The two cell lines were both divided into two subgroups to be treated with 20μg/L TNF-αand fresh culture medium respectively for 6 hours. Then, Hoechst 33258 staining was performed to observe morphological changes of apoptotic cells, flow cytometry to detect cell apoptosis, real-time PCR to measure the mRNA expression of Caspase3, Bax and Bcl-2, and Western blot analysis to determine the protein expression of Bax and Bcl-2. Results After 6-hour treatment with TNF-α, Hoechst 33258 staining showed variable degrees of karyopyknosis and karyorrhexis, and highly-refractive blue apoptotic bodies in the pORF5-HeLa cells and control HeLa cells. The pORF5-HeLa cells and control HeLa cells both showed significantly higher apoptosis rate in the treated subgroup than in the untreated subgroup (pORF5-HeLa cells:35.5%± 4.5%vs. 9.5%± 1.5%, t=13.53, P<0.01;control HeLa cells:63.6%± 5.8%vs. 7.9%± 0.9%, t=32.36, P<0.01). Compared with treated control HeLa cells, treated pORF5-HeLa cells showed significant decreases in mRNA expression of Bax(72.8%)and Caspase 3(84.5%)(t = 35.29, 42.25, respectively, both P < 0.01), as well as in Bax protein expression(t = 17.58,P < 0.01), but significant increases in Bcl-2 mRNA and protein(6.8 times)expression(t = 87.12, 18.93, respectively, both P <0.01). Conclusion pORF5 plasmid protein can inhibit TNF-α-induced HeLa cell apoptosis likely by increasing the expression of anti-apoptotic protein bcl-2 and decreasing the expression of pro-apoptotic proteins Caspase-3 and Bax.

Expression and clinical significance of protein disulfide-isomerase A3 in a rabbit model of spinal cord ischemia/reperfusion injury / 中国组织工程研究

BACKGROUND:At present, spinal cord ischemia/reperfusion injury is considered as the main reason for secondary paralysis after spinal decompression, and to control the levels of stress-related proteins and excitatory amino acids plays an important role in the treatment of spinal cord ischemia/reperfusion injury. OBJECTIVE:To investigate the expression level of protein disulfide-isomerase A3 (PDIA3) after spinal cord ischemia/reperfusion injury in rabbits. METHODS:Thirty-six New Zealand white rabbits were enrolled, the models of spinal cord ischemia/reperfusion injury were established using Zivin's method, and were then randomized into six groups (n=6 per group). The rabbit abdominal aorta in control group was exposed without vascular occlusion and then the abdominal cavity was closed 30 minutes later. In experimental groups, the abdominal aorta was blocked for 30 minutes, followed by 0, 6, 12, 24 and 48 hours of reperfusion, and then the abdominal cavity was closed. The neurological function was evaluated with a modified Tarlov score. The L3-5lumbar vertebrae were removed, and PDIA3 was screened by two-dimensional fluorescence differential gel electrophoresis combined with mass spectrometry, and then its temporal and spatial changes in the spinal cord were detected by western blot assay and immunohistochemistry. RESULTS AND CONCLUSION:The function of hind limbs was improved in all the experimental groups after spinal cord ischemia/reperfusion injury, and the modified Tarlov scores reached the peak at 24 hours after schemia/reperfusion injury, and decreased slightly at 48 hours. The expression of PDIA3 in the control group showed clear imprinting, which was slightly strengthened at 0 hour, became more strengthened at 6-12 hours, significantly reduced to the minimum level at 24 hours, and returned to the level of 6-12 hours at 48 hours after ischemia/reperfusion. Immunohistochemical results showed that there was visible PDIA3 in the cytoplasm of neurons, and the expression level in the interneurons was significantly higher than that in the motor neurons. These results suggest that upregulated PDIA3 appears in the development and progression of spinal cord ischemia/reperfusion injury, indicating that PDIA3 is closely related to spinal cord ischemia/reperfusion injury, which can be used as a new diagnosis and treatment target.