ObjectiveTo investigate the survival and adverse reactions of patients with unresectable cholangiocarcinoma after stereotactic body radiation therapy （SBRT）. MethodsA total of 27 patients with unresectable solitary cholangiocarcinoma without metastasis who underwent SBRT in The Fifth Medical Center of Chinese PLA General Hospital from February 2012 to July 2020 were enrolled. The prescribed dose to planning target volume was 42-60 Gy in 5-8 fractions， with 5-11 Gy/fraction. Among these patients， five patients were also treated with chemotherapy and transcatheter arterial chemoembolization. The 6-， 12-， 18-， and 24-month overall survival （OS） rates， progression-free survival （PFS） rates， and local control （LC） rates were used as the assessment indices for treatment outcome； Common Terminology Criteria for Adverse Events v.4.03 was used to evaluate adverse reactions； the Kaplan-Meier method was used to calculate OS， PFS， and LC rates. ResultsThe median follow-up time was 17 months. For all 27 patients， the 6-， 12-， 18-， and 24-month OS rates were 100%， 88%， 57.5%， and 47.9%， respectively； the 6-， 12-， 18-， and 24-month PFS rates were 74.1%， 58.6%， 47.9%， and 35.9%， respectively； the 6-， 12-， 18-， and 24-month LC rates were 96.3%， 91.9%， 84.8%， and 76.4%， respectively. No grade 3 or above toxic reactions were observed. Five patients were diagnosed with radiation-induced liver injury， but there was no death due to radiation-induced liver injury. ConclusionSBRT is safe and effective in the treatment of unresectable cholangiocarcinoma， with relatively high survival rate， PFS rate， and LC rate and low toxicity， and therefore， SBRT can be used as an alternative treatment method for patients with cholangiocarcinoma who are not candidates for surgery.

The finite element method is a new method to study the mechanism of brain injury caused by blunt instruments. But it is not easy to be applied because of its technology barrier of time-consuming and strong professionalism. In this study, a rapid and quantitative evaluation method was investigated to analyze the craniocerebral injury induced by blunt sticks based on convolutional neural network and finite element method. The velocity curve of stick struck and the maximum principal strain of brain tissue (cerebrum, corpus callosum, cerebellum and brainstem) from the finite element simulation were used as the input and output parameters of the convolutional neural network The convolutional neural network was trained and optimized by using the 10-fold cross-validation method. The Mean Absolute Error (MAE), Mean Square Error (MSE), and Goodness of Fit ( R ²) of the finally selected convolutional neural network model for the prediction of the maximum principal strain of the cerebrum were 0.084, 0.014, and 0.92, respectively. The predicted results of the maximum principal strain of the corpus callosum were 0.062, 0.007, 0.90, respectively. The predicted results of the maximum principal strain of the cerebellum and brainstem were 0.075, 0.011, and 0.94, respectively. These results show that the research and development of the deep convolutional neural network can quickly and accurately assess the local brain injury caused by the sticks blow, and have important application value for understanding the quantitative evaluation and the brain injury caused by the sticks struck. At the same time, this technology improves the computational efficiency and can provide a basis reference for transforming the current acceleration-based brain injury research into a focus on local brain injury research.
Brain ; Brain Injuries ; Computer Simulation ; Finite Element Analysis ; Humans ; Neural Networks, Computer

ObjectiveTo investigate the efficacy and safety of sequential lenvatinib therapy after stereotactic body radiotherapy (SBRT) in the treatment of advanced primary liver cancer. MethodsA total of 18 patients with advanced primary liver cancer who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from October 2018 to May 2019 were enrolled, among whom there were 4 patients with BCLC stage B liver cancer and 14 patients with BCLC stage C liver cancer. The prescribed dose of planning target volume was 48-55 Gy (median 50 Gy) in 6-9 fractions, and the median of single dose was 6 (5-9) Gy per fraction. Oral administration of lenvatinib was given since 1 week after SBRT was finished, with a median medication time of 9.5 (3.6-25.8) months. Follow-up was performed once a month for the first 3 months after treatment and once every 3 months after 3 months of treatment. The Kaplan-Meier method was used to calculate overall survival (OS) rate, progression-free survival (PFS) rate, and local control (LC) rate, and the incidence rates of adverse reactions and complications were also observed. ResultsUp to the follow-up on November 30, 2020, a total of 8 patients died, among whom 3 died of liver failure, 3 died due to tumor progression, 1 died of perforation of gallbladder, and 1 died of gastrointestinal bleeding. At 3, 6, 9, 12, and 18 months of treatment, the OS rates were 100%, 94%, 83%, 72%, and 67%, respectively, the PFS rates were 100%, 67%, 50%, 22%, and 17%, respectively, and the LC rates were 100%, 94%, 94%, 94%, and 94%, respectively; the median OS time was ＞18 months, and the median PFS time was 9 months. Of all patients, 1 (6%) had a grade 3 adverse reaction during SBRT and 2 (11%) experienced a grade 3 adverse reaction during lenvatinib treatment, and no fatal adverse reaction was observed. ConclusionIt is preliminarily proved that sequential lenvatinib therapy after SBRT is an effective and safe treatment method for advanced primary liver cancer.

Objective:To investigate the role of Sestrin2 overexpression in regulating mitochondrial fission and its mechanism in human neuroblastoma SH-SY5Y cell model of glucose and oxygen deprivation/recovery (OGD/R). Methods:(1) SH-SY5Y cells were divided into normal control group, OGD/R group, Vector group, and Sestrin2 overexpression group; Sestrin2 overexpression or empty vector stable cell lines in the Sestrin2 overexpression group and Vector group were constructed by lentivirus infection; cells in the later 3 groups were subjected to oxygen-glucose deprivation (OGD) for 4 h followed by restoration of O 2 supply for 18 h. The cell survival rate was detected by cell counting kit (CCK)-8 assay. The protein levels of Sestrin2, dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Kelch-like ECH-related protein 1 (Keap1) in the cytoplasm and nuclear factor E2-related factor (Nrf2) in the nucleus were detected by Western blotting. The mitochondria ultrastructure was observed by transmission electron microscope. The Nrf2 nuclear translocation was detected by immunofluorescence staining. (2) Cell lines with Sestrin2 overexpression were divided into Sestrin2 overexpression group, Brusatol+ Sestrin2 overexpression group, and DMSO+ Sestrin2 overexpression group. Cells in the Brusatol+ Sestrin2 overexpression group were pretreated with normal medium containing Brusatol (Keap1/Nrf2 pathway inhibitor, final concentration: 100 nmol/L) for 4 h before OGD/R; cells in the DMSO+ Sestrin2 group were pretreated with normal medium containing DMSO (final volume fraction: 0.1%) for 4 h before OGD/R. Cells in these groups were then subjected to OGD for 4 h followed by restoration of O 2 supply for 18 h. The protein levels of Drp1, Fis1, Keap1 in the cytoplasm, and Nrf2 in the nucleus were measured by Western blotting. Results:(1) As compared with those in the OGD/R group, cells in the Sestrin2 overexpression group had significantly increased survival rate (61.33%±1.15% vs. 81.00%±3.00%), significantly up-regulated Bcl-2/Bax ratio (0.467±0.006 vs. 0.880±0.010), significantly decreased Drp1, Fis1 and cytoplasmic Keap1 protein levels (1.089±0.033 vs. 0.865±0.014; 0.829±0.009 vs. 0.350±0.007; 0.967±0.017 vs. 0.881±0.024), and significantly up-regulated nuclear Nrf2 protein level (0.627±0.025 vs. 0.957±0.015, P<0.05). The mitochondrial structure in the Sestrin2 overexpression group under electron microscope was more complete than that in the OGD/R group, and obvious nuclear translocation of Nrf2 was noted. (2) As compared with the Sestrin2 overexpression group, Brusatol+ Sestrin2 overexpression group had significantly decreased nuclear Nrf2 protein level (0.920±0.013 vs. 0.627±0.035), and statistically increased Drp1 and Fis1 protein levels (0.994±0.020 vs. 1.084±0.005; 0.728±0.010 vs. 0.906±0.022, P<0.05). Conclusion:Sestrin2 overexpression could suppress mitochondrial fission, reduce cell apoptosis, and attenuate OGD/R injury of SH-SY5Y cells by activating Keap1/Nrf2 pathway via down-regulating cytoplasmic Keap1 protein level and promoting Nrf2 nuclear translocation.

Objective To analyze the survival and toxicity after concurrent chemoradiotherapy in patients of different ages with stage Ⅳ non-small cell lung cancer (NSCLC).Methods Clinical data of 282 NSCLC patients in two prospective studies were retrospectively analyzed,who completed the protocol (at least 2 cycles of chemotherapy and thoracic radiation doses of ≥36 Gy).Among them,44 patients were assigned into in the young group (≤ 45 years old),161 patients in the middle-age group (46-64 years old) and 77 patients in the elderly group (≥ 65 years old).The clinical characteristics of patients among different groups were analyzed by x2 test.The overall survival (OS) was calculated by Kaplan-Meier method.Stratified analysis was performed by Log-rank test.Multi-factor prognosis analysis was conducted by Cox's proportional hazards regression model.Results The incidence of NSCLC in the male patients in the elderly group was higher than that in the middle-age and young groups.The 1-,2-,3-and 5-year OS did not significantly differ among different groups (P=0.810).The OS did not significantly differ among patients of the same gender,pathological type,T stage,N stage,metastasis status,same chemotherapy cycle,primary tumor dose and comprehensive treatment and short-term response (all P＞0.05).The incidence of adverse events did not considerably differ among different groups.Multivariate analysis demonstrated that age was not an independent factor for survival (P＞ O.05).Conclusion Patients of different ages with stage Ⅳ NSCLC obtain similar survival benefits and adverse events after concurrent chemoradiotherapy.

Objective To investigate the impact of the changes of posttreatment karnofsky performance status (KPSpost) on the overall survival (OS) for patients with stage Ⅳ non-small cell lung cancer (NSCLC) underwent concurrent chemoradiation.Methods A total of 279 patients (male 198 and female 81) with histological confirmed stage Ⅳ NSCLC were enrolled in this study with a median age of 58 years old (range 22 to 80 years old).There were 166 cases of squamous carcinoma,87 cases of adenocarcinoma,and 22 cases of unclassified carcinoma,respectively.All enrolled patients received more than 2 cycles of chemotherapy and more than 36 Gy of concurrent radiotherapy.Kaplan-Meier method and Log-rank test were applied to evaluate OS.Multivariate analyses were carried out by the Cox proportionalhazard model.Chi-square test and logistic regression analysis were used to explore the related factors of KPSpost.Results There were 198 patients with improved KPSpost and 81 patients with decreased KPSpost,respectively.Univariate and multivariate analyses indicated that the improvement of KPSpost was associated with longer OS.Logistic regression analysis showed that the improvement of KPSpost was positively related with treatment of more than 4-6 cycles chemotherapy concurrent with over 63 Gy radiation to primary tumor.The improvement of KPSpost also correlated positively with disease control rate (DCR),but negatively with PLT toxicity and radiation esophagitis.Conclusions KPSpost was an independent prognostic factor of OS for patients with stage Ⅳ NSCLC underwent concurrent chemoradiation.Chemotherapy of 4-6 cycles and concurrent over 63 Gy radiotherapy dose to primary tumor,as well as DCR were positive factors for KPSpost improvement.However,stage 3-4 PLT toxicities and radiation esophagitis decreased the KPSpost.

BACKGROUND:Vertebroplasty and kyphoplasty can effectively repair osteoporotic vertebral compression fractures, but bone cement injection can cause the change of stress in the fractured vertebrae and adjacent vertebrae after surgery, leading to new fractures.
OBJECTIVE: To analyze the stress changes of the fractured vertebrae and adjacent vertebrae after vertebroplasty with different elastic modulus bone cement by a three-dimensional finite element method.
METHODS: One healthy adult male volunteer was selected for lumbar spine CT scan. The acquired images were imported for three-dimensional reconstruction using Mimics. The three-dimensional model was smoothed, polished and denoised by Geomagic software, and then the solid mode was built under Workbench Ansys. An osteoporotic vertebral compression fracture model in L2-4 segments was established after assignment. Bone cement (4 mL) with different elastic moduli (8 000, 4 000, 2 000 and 1 000 MPa) injected into the L3 segment distributed in the middle of the vertebrae as spherical shape. 500 N pre-load was applied on the L2 surface with an additional bending moment of 50 N?m. The lower surface free degree of L4 was restrained. The L2-4 forward flexion, posterior extension, right flexion and axial rotation on the right side were stimulated. The stress changes of the fractured vertebrae and the upper and lower adjacent vertebrae before and after bone cement injection with different elastic moduli were compared.
RESULTS AND CONCLUSION:The stress of the fractured vertebrae and adjacent vertebrae were significantly increased compared with that before operation. With the increase of elastic modulus, the stress of the fractured vertebrae increased, but there were no changes in the stress of adjacent vertebrae. These findings indicate that the elastic modulus of bone cement may be a method to reduce new fractures of the fractured and adjacent vertebrae after bone cement injection.

Human papillomavirus (HPV) is the main cause for cervical cancer,anogenital cancers and genital warts.Three HPV vaccines have been licensed abroad.Data from clinical trials showed high efficacy of the HPV vaccines in young women with 90％-100％ vaccine-related HPV diseases prevented.Though efficacy of the vaccine appears lower in older women,this population can still benefit from vaccination.Immunobriging trials show that the two-dose schedule in 9-14 years old girls elicits non-inferior immune response than the three-dose one in young adults.In addition,HPV vaccines can reduce the recurrent rates in CIN2 + patients after therapeutic surgery and the vaccines have cross-protection aganist diseases caused by non-vaccine type HPV.Safety data on HPV vaccines are assuring.Thus HPV vaccine should be widely used in adolescent girls and women of appropriate age groups.

BACKGROUND:Vertebroplasty and kyphoplasty can effectively repair osteoporotic vertebral compression fractures, but postoperative change of stress in the fractured vertebrae and adjacent vertebrae can lead to new fractures. OBJECTIVE:To analyze the stress changes of the fractured and adjacent vertebrae with different bone cement injection volume by three-dimensional finite element method. METHODS:One healthy adult male volunteer was selected for lumbar spine CT scan. The acquired images were imported for three-dimensional reconstruction using Mimics. The three-dimensional model was smoothed, polished and denoised by Geomagic software, and then the solid mode was built under Workbench Ansys. The osteoporotic vertebral compression fracture model in L2-L4 segments was established after assignment. Bone cement of 1, 2, 4, 6 mL was injected into the L3 vertebrae respectively and distributed in the middle of the vertebrae as spherical shape. 500 N pre-load was applied on L2 surface with an additional moment of 50 N·m. The lower surface free degree of L4 was restrainted. The L2-L4 forward flexion, extension, right flexion and axial rotation on the right side were stimulated to compare the stress changes of fractured vertebrae and adjacent vertebrae before and after the bone cement injection with different volume. RESULTS AND CONCLUSION:The stresses of fractured and adjacent vertebrae after the bone cement injection were significantly increased; meanwhile, the stresses of fractured and adjacent vertebrae increased with the increase of bone cement injection volume, which may be one of the factors leading to the compression fractures of adjacent vertebrae.