Objective:To explore the effects of multimodal imaging on the performance of automatic segmentation of glioblastoma targets for radiotherapy based on a deep learning approach.Methods:The computed tomography (CT) images and the contrast-enhanced T1 weighted (T1C) sequence and the T2 fluid attenuated inversion recovery (T2- FLAIR) sequence of magnetic resonance imaging (MRI) of 30 patients with glioblastoma were collected. The gross tumor volumes (GTV) and their corresponding clinical target volumes CTV1 and CTV2 of the 30 patients were manually delineated according to the criteria of the Radiation Therapy Oncology Group (RTOG). Moreover, four different datasets were designed, namely a unimodal CT dataset (only containing the CT sequences of 30 cases), a multimodal CT-T1C dataset (containing the CT and T1C sequences of 30 cases), a multimodal CT-T2-FLAIR dataset (containing the CT and T2- FLAIR sequences of the 30 cases), and a trimodal CT-MRI dataset (containing the CT, T1C, and T2- FLAIR sequences of 30 cases). For each dataset, the data of 25 cases were used for training the modified 3D U-Net model, while the data of the rest five cases were used for testing. Furthermore, this study evaluated the segmentation performance of the GTV, CTV1, and CTV2 of the testing cases obtained using the 3D U-Net model according to the indices including Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and relative volume error (RVE).Results:The best automatic segmentation result of GTV were achieved using the CT-MRI dataset. Compared with the segmentation result using the CT dataset (DSC: 0.94 vs. 0.79, HD95: 2.09 mm vs. 12.33 mm, and RVE: 1.16% vs. 20.14%), there were statistically significant differences in DSC ( t=3.78, P<0.05) and HD95 ( t=4.07, P<0.05) obtained using the CT-MRI dataset. Highly consistent automatic segmentation result of CTV1 and CTV2 were also achieved using the CT-MRI dataset (DSC: 0.90 vs. 0.91, HD95: 3.78 mm vs. 2.41 mm, RVE: 3.61% vs. 5.35%). However, compared to the CT dataset, there were no statistically significant differences in DSC and HD95 of CTV1 and CTV2 ( P>0.05). Additionally, the 3D U-Net model yielded some errors in predicting the upper and lower bounds of GTV and the adjacent organs (e.g., the brainstem and eyeball) of CTV2. Conclusions:The modified 3D U-Net model based on the multimodal CT-MRI dataset can achieve better segmentation result of glioblastoma targets and its application potentially benefits clinical practice.

Antibody-mediated rejection (AMR) is one of the major causes of graft loss after transplantation. Recently, the regulation of B cell differentiation and the prevention of donor-specific antibody (DSA) production have gained increased attention in transplant research. Herein, we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin (FK228) on DSA. The survival of grafted skins was monitored daily. The serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow cytometry. Then, we isolated and purified B cells from B6 mouse spleens in vitro by magnetic bead sorting. The B cells were cultured with interleukin-4 (IL-4) and anti-clusters of differentiation 40 (CD40) antibody with or without FK228 treatment. The immunoglobulin G1 (IgG1) and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the corresponding levels of messenger RNA (mRNA) and protein expression in cultured cells and the recipient spleens. The results showed that FK228 significantly improved the survival of allogeneic skin grafts. Moreover, FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1 (HADC1) and HDAC2 and the upregulation of the acetylation of histones H2A and H3. It also inhibited the differentiation of B cells to plasma cells, decreased the transcription of positive regulatory domain-containing 1 (Prdm1) and X-box-binding protein 1 (Xbp1), and decreased the expression of phosphorylated inositol-requiring enzyme 1 α (p-IRE1α), XBP1, and B lymphocyte-induced maturation protein-1 (Blimp-1). In conclusion, FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling pathway. Thus, FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.
Animals ; Depsipeptides ; Endoribonucleases ; Hematopoietic Stem Cell Transplantation ; Histone Deacetylase Inhibitors/pharmacology* ; Mice ; Protein Serine-Threonine Kinases ; Skin Transplantation

【Objective】 To investigate the molecular mechanism of long non-coding RNA (lncRNA) TDRG1 in facilitating the malignant progression and poor prognosis of patients with cervical cancer. 【Methods】 Cervical cancer cell lines and normal cervical cell Ect1/E6E7 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of TDRG1. Cervical cancer cell lines were transfected with TDRG1-siRNA, and the proliferation of cancer cells was detected by CCK-8 method and cell plate cloning experiment. The invasion and migration of cancer cells were measured by Transwell experiment. The apoptosis of cancer cells was examined by flow cytometry, and the expressions of relevant proteins were tested by Western blot. 【Results】 Compared with Ect1/E6E7, cervical cancer cell lines showed relatively increased expression of TDRG1. Downregulation of TDRG1 expression inhibited the proliferation and colony formation (162±21 vs. 411±33, P<0.05), as well as the invasion and migration (invasion: 86±13 vs. 315±38, P<0.01; migration: 177±22 vs. 406±41, P<0.01) of Hela cells. Meanwhile, the apoptosis of Hela cells increased [(28±1.5)% vs. (16±1.2)%, P<0.05] and the expression of Bcl-2 protein reduced. In addition, TDRG1 knockdown also decreased the activity of autophagy in Hela cells. 【Conclusion】 TDRG1 facilitates the malignant biological progression of cervical cancer by inhibiting the apoptosis and providing a protective autophagy in cervical cells.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Objective:To describe the COVID-19 epidemic and its characteristics in Heilongjiang province, and provide evidence for the further prevention and control of COVID-19 in the province.Methods:The information of COVID-19 cases and clusters were collected from national notifiable disease report system and management information system for reporting public health emergencies of China CDC. The Software’s of Excel 2010 and SPSS 23.0 were applied for data cleaning and statistical analysis on the population, time and area distributions of COVID-19 cases.Results:On January 22, 2020, the first confirmed case of COVID-19 was reported in Heilongjiang. By March 11, 2020, a total of 482 cases domestic case of COVID-19, The incidence rate was 1.28/100 000, the mortality rate was 2.70% (13/482) in 13 municipalities in Heilongjiang. There were 81 clusters of COVID-19, The number of confirmed cases accounted for 79.25% (382/482) of the total confirmed cases and 12 cases of deaths. The family clusters accounted for 86.42% (70/81). Compared with the sporadic cases, the mortality rate, proportion of elderly cases aged 60 or above and severe or critical cases of clinical classification were all higher in the clusters especially the family clusters, but the differences were not significant ( P>0.05). There were 34 clusters involving more than 5 confirmed cases accounted for 41.98% (34/81) of the total clusters, the involved cases accounted for 68.31% (261/382) of the total cases of clusters. There were significant differences in age distribution of the cases among the case clusters with different case numbers. In the clusters involving 6-9 cases, the proportion of cases aged 65 years or above was more (26.53%, 39/147). Conclusions:The incidence rate of COVID-19 was relatively high and the early epidemic was serious in Heilongjiang, The number of cases was large in clusters especially family clusters.

OBJECTIVE: To investigate the efficacy of image-guided radioactive 125I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121–0.718), lesion volume (HR=2.898; 95% CI=1.139–7.372), D 90 (HR=0.332; 95% CI=0.130–0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136–44.176) and recurrence site (HR=0.358; 95% CI=0.136–0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D 90 (128.5±47.4 Gy), D 100 (50.4±23.7 Gy) and V 100 (86.7%±12.9%). When D 90 ≥105 Gy or D 100 ≥55 Gy or V 100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive 125I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.
Brachytherapy ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Radiometry ; Radiotherapy* ; Radiotherapy, Image-Guided ; Recurrence ; Salvage Therapy* ; Tumor Burden ; Uterine Cervical Neoplasms*

Objective To evaluate the efficacy and adverse effects of 125I seeds implantation for pelvic recurrence of cervical cancer (PRCC) after radiotherapy.Methods From July 2005 to October 2015,36 PRCC patients (median 44 years) after radiotherapy in Peking University Third Hospital were enrolled in this retrospective study.All patients underwent 125I seeds implantation under ultrasound or CT guidance.Treatment planning was performed before implantation to estimate the number and activity of 125I seeds.The seed numbers ranged from 10-140 (median:62.5),and the activity ranged from 18.5-29.6 (median:25.9) MBq.Postoperatively,the median dose delivered to 90％ gross tumor volume (D90) was 127.3 Gy.Kaplan-Meier method was used to calculate local progress free survival (LPFS) rate and overall survival (OS) rate,and log rank test and Cox regression were used for univariate and multivariate analyses.Results The median follow-up time was 11.5 months.The local control rate was 88.89％(32/36).The 1-year LPFS rate was 34.9％ and the 1-year OS rate was 52.0％.Thirty-one patients died,of which 22 (70.97％,22/31) died from cancer.Univariate analysis showed that the location of recurrence (x2=5.195),volume of lesion (hazard ratio (HR)=1.012) and D90(HR=0.988) were significantly correlated with LPFS (all P＜0.05).Multivariate analysis showed that the location of the recurrence was significantly related with LPFS (HR =0.215,P＜0.05).The 1-year LPFS rates of pelvic wall recurrence and central recurrence were 41.6％ and 26.7％ (x2 =5.195,P＜0.05),and 1-year OS rates were 54.7％ and 49.5％ (x2 =2.535,P＞0.05),respectively.Vaginal fistula,which may be caused by the treatment,occurred in 1 case.No other sever adverse effects were observed.Conclusions 125I seeds implantation is a safe and effective treatment for PRCC after radiotherapy.With the treatment of 125I seeds implantation,patients with pelvic wall recurrence may achieve better therapeutic effects than those with central recurrence.

Objective To evaluate the outcomes and prognostic factors of image-guided 125I seed implantation for locally recurrent soft tissue sarcoma(RSTS).Methods A total of 60 patients with RSTS who received image-guided 125I seed implantation in Peking University Third Hospital,from September 2002 to December 2015,were retrospectively analyzed.The enrollment criteria: KPS ＞60 points,refused or could not tolerate surgery or radiotherapy,the expecting survival time ＞3 months,relapsed after multiple treatment of soft tissue sarcoma,and underwent CT or ultrasound guided 125 I seed implantation treatment.In all,the median activity of seeds was 25.9×106Bq(range,11.1×106-29.6×106Bq),median number of implanted seeds was 58(range,3-133),and the median D90was 120 Gy(range,36.50-460.97 Gy).The local progression-free survival(LPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.The log-rank test and Cox regression model were used for the univariate and multivariate analyses.Results The median follow-up was 18.75 months(range,1-146).The median OS was 18.5 months(95％CI 13.1-23.9).The 1-,3-and 5-year OS rate were 63.3％,33.0％and 29.5％,respectively.The 1-,3-and 5-year LPFS rate were 72.5％,63.7％and 59.7％,respectively.The general rate of pain relieving was 100％(6/6).8.3％(5/60)presented grade Ⅳskin toxicity.No fatal complications ocurred.The univariate analysis suggested that tumor size,tumor volume,KPS score,D90were prognostic factors of OS and LPFS.The multivariate analysis demonstrated that previous chemotherapy history and distant metastases were independent prognostic factors of survival.Conclusions Image-guided 125I seed implantation for recurrent soft tissue sarcoma is a safe treatment option with high efficacy and low morbidity.Tumor size and D90were the prognostic factors of OS and LPFS.

Objective To study blood type B antigen elimination with α-galactosidase in human liver tissue,and discuss the feasibility of blood type conversion in human liver.Methods The liver specimens from patients with blood type B in liver transplantation were collected,and an in vitro liver perfusion model was established.The in vitro livers were perfused with UW solution +/-α-galactosidase.The effect of enzyme in B antigen of human liver were analyzed by immunofluorescence.Results With UW solution containing α-galactosidase to perfuse the in vitro livers,immunohistochemistry showed the level of blood type B antigen in liver was significantly reduced after hypothermic perfusion and preservation.The B antigen level in 1 h perfusion was reduced to approximate 58％ of this figure prior to perfusion,in 2 h was 10％,and in 4 h was 4％.Among the different intervals,the blood group antigen levels showed significant differences (P ＜ 0.05).In the control group,the blood group antigen levels showed no obvious change on statistical analysis.Conclusions α-galactosidase was effective to clear blood type B antigen in isolated liver tissue.In the experimental group,Although the B antigen did not fall to a undetectable level,liver blood type conversion from B→O remains a promising potential which has been meaningful for related researches on blood type conversion of human organs.

Objective To evaluate the efficacy of computed tomography ( CT ) image?guided 125 I radioactive seed implantation for locally recurrent rectal cancer ( LRRC ) , and to analyze the relationship between the dosimetry and prognosis. Methods A retrospective analysis was performed on the clinical data of 36 patients with LRRC who received CT image?guided 125 I seed implantation in our hospital from 2003 to 2011. Dosimetric verification was performed using CT scan immediately after 125 I seed implantation. The D90 , D100 , V100 , and V150 values were evaluated. In all the patients, the median activity of seeds was 0?7 mCi (0?4?0?8 mCi) and the median number of implanted seeds was 74(33?137). The local control (LC) and overall survival ( OS ) rates were calculated using the Kaplan?Meier method. The log?rank test and Cox regression model were used for the univariate and multivariate analyses, respectively. Results The median OS time was 16?2 months ( 95% CI= 13?5?18?9 months ) . The median LC time was 10?0 months (95% CI=6?2?13?8 months). The D90 and V100 values were (118.6±25?1) Gy and (90.0±0?3)%, respectively. The univariate analysis suggested that D90 was correlated with the LC time ( P=0?048) and V100 was correlated with the OS time ( P=0?035) . The multivariate analysis showed that a V100 value higher than 90% was a prognostic factor of OS (P=0?044). Conclusions In the treatment of LRRC using CT image?guided 125 I radioactive seed implantation, a D90 value larger than 140 Gy and a V100 value higher than 90% in the postoperative verification plan help improve the LC and OS rates. The D90 and V100 values in the postoperative verification plan may predict treatment outcomes in patients.