Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.
Animals ; Mice ; Rodentia ; Virtual Reality ; Cognition ; Recognition, Psychology

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

OBJECTIVE: To investigate the clinical application and efficacy of ¹²⁵Ⅰ radioactive seeds implantation in the treatment of recurrent salivary gland carcinoma after external radiotherapy. METHODS: From July 2004 to July 2016, 43 cases of recurrent salivary gland carcinoma of the neck after external radiotherapy or surgery combined with external radiotherapy were treated. According to the conventional segmentation radiotherapy for head and neck cancer (once a day, 1.8-2.0 Gy each time, 5 days per week), the cumulative radiation dose of the patients in this group was calculated. In the study, 26 patients received 50-60 Gy, 7 patients received less than 50 Gy, 4 patients received 60-70 Gy, and 6 patients received more than 80 Gy (range: 80-120 Gy). The interval between the last external irradiation and local recurrence was 4-204 months, and the median interval was 48 months. Among them, 25 cases were treated with ¹²⁵Ⅰ radioactive seeds implantation only and 18 cases were treated with ¹²⁵Ⅰ radioactive seeds implantation after operation. The prescription dose was 100-140 Gy. The control rate, survival rate and disease-free survival rate were recorded to evaluate the side effects. RESULTS: The median follow-up time was 27 months (ranging from 2.5 to 149.0 months). Among them, the median follow-up time of adenoid cystic carcinoma patients was 31 months (range: 2.5-112.0 months), and the median follow-up time of mucoepidermoid carcinoma patients was 18 months (range: 5-149 months). The local control rates for 1, 3 and 5 years were 66.5%, 48.8% and 42.7%, respectively. The 1-, 3- and 5- year survival rates were 88.0%, 56.7% and 45.8%, respectively. The disease-free survival rates of 1, 3 and 5 years were 58.3%, 45.4% and 38.1%, respectively. There was no statistically significant difference in local control rate, survival rate, and disease-free survival between the radioactive seeds implantation group and the radioactive seeds implantation group after surgical resection. There were 2 cases of acute radiation reaction Ⅰ/Ⅱ and 3 cases of reaction Ⅲ or above. In the late stage of radiotherapy, there were 8 cases with Ⅰ/Ⅱ grade reaction and 3 cases with Ⅲ grade or above reaction. The incidence of radiation reactions of Grade Ⅲ and above was 7%. CONCLUSION ¹²⁵Ⅰ radioactive seeds implantation provides an alternative method for the treatment of recurrent salivary gland carcinoma after external radiotherapy. The local control rate and survival rate are improved on the premise of low incidence of side effects.
Brachytherapy/adverse effects* ; Humans ; Iodine Radioisotopes/therapeutic use* ; Neoplasm Recurrence, Local/radiotherapy* ; Salivary Gland Neoplasms/radiotherapy* ; Salivary Glands

OBJECTIVE: To retrospectively analyze the results of treatment outcome by surgery combined with ₁₂₅I brachytherapy and correlative factors of adenoid cystic carcinoma (ACC). METHODS: In the study, 75 patients with primary ACC of oral and maxillofacial region were treated by surgery combined with ₁₂₅I seeds brachytherapy. Radical resection or subtotal resection was applied for the tumor. The brachytherapy treatment planning system was used to create implant plans with the prescribed dose of 60 Gy to 120 Gy. The ₁₂₅I seeds were implanted intraoperatively or postoperatively. The regular follow-up was required. The Kaplan-Meier method was used to assess the tumor control rate and the patients' survival rates. Meanwhile, the Cox regression analysis was used to find out the prognostic factors. RESULTS: Local control rates at the end of 3 and 5 years were as follows: T1-T2, 92.2% and 82.0%; T3-T4, 82.6% and 82.6%; and overall, 90.0% and 78.8%. The disease-free survival rates were 74.9% and 54.3%, respectively. The overall survival rates for all the patients were 86.0% and 79.6%, respectively at the end of 3 and 5 years and were 91.3% and 91.3% for T1-T2 patients vs. 73.9% and 59.7% for T3-T4 patients. Distant metastasis-free survival rates at the end of 3 and 5 years were 84.4% and 76.7%, respectively. The distant metastasis-free survival rates at the end of 3 and 5 years were 83.4% and 79.6% with T1-T2 lesion compared with 86.0% and 67.8% with T3-T4 lesion. According to the COX univariate analysis and multivariate analysis, the risk of local recurrence would be raised by the age. Tumor stage and tumor site were the prognostic factors of the overall survival rates. CONCLUSION ₁₂₅I brachytherapy conducted as an adjuvant therapy postoperatively of ACC of oral and maxillofacial region can acquire satisfactory localregional control, distant metastasis-free survival, disease-free survival and overall survival. Tumors are prone to recur on the older patients. Patients having advanced tumor stage or tumor located in the nasal cavity or sinuses will suffer lower survival rates.
Brachytherapy ; Carcinoma, Adenoid Cystic ; Combined Modality Therapy ; Humans ; Iodine Radioisotopes ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Survival Rate

Objective To investigate the effect of measuring value transfer for human serum samples assigned by the reference laboratory network on improving the trueness of seven enzyme activities in clinical laboratories,such as ALT,AST,GGT,LDH,CK,AMY and ALP.Methods Depending on the medical imtitutions at all levels contacted by 5 reference laboratories in North China,South China,East China and Southwest China,the corresponding clinical laboratory measuring value transfer/traceability network was established.The frozen human serum samples with good interehangeability and standard material characteristics,including calibrator,sample 1 and sample 2,were provided by Beijing Aerospace General Hospital,and were assigned by 5 reference labotatories in four regiom.These samples were sent to 48 clinical laboratories.These clinical laboratories measured sample 1 and sample 2 according to their standard operating procedures,and then measured.the two samples again after adjusting their measurement system by using the supplied calibrator.The changes of trueness of detection results in these laboratories were evaluated according to the WS/T 403-2012 standard,and the changes of consistency for ALT and AST before and after measuring value tramfer were investigated.Results The results of AMY,ALP,GGT,CK and LDH calibrator,sample 1 and sample 2 assigned by the established network were 138.7 U/L,278.5 U/L and 68.3 U/L,265.3 U/L,94.5 U/L and 134.4 U/L,195.8 U/L,89.0 U/L and 158.9 U/L,393.7 U/L,260.0 U/L and 645.3 U/L,and 302.0 U/L,250.0 U/L and 452.7 U/L,respectively.The percentages of sample 1 and sample 2 which met the bias requirements of the WS/T 403-2012 standard before measuring value transfer for AMY,ALP and GGT were 65.9％ and 61.0％,76.6％ and 78.7％,and 66.7％ and 70.8％,respectively,while after measuring value transfer,they were 89.2％ and 83.8％,86.7％ and 80.0％,and 85.4％ and 91.7％,respectively.The percentages of sample 2 which met the bias requirements of the WS/T 403-2012 standard before measuring value transfer for CK and LDH were 64.6％ and 58.3％,respectively,while after measuring value trander,they were 93.5％ and 84.8％,respectively.The coefficients of variation (consistency) of sample 1 and sample 2 for ALT and AST before measuring value tramfer were 12.9％ and 11.3％,and 10.2％ and 8.9％,respectively,while after measuring value transfer,they were 9.3％ and 8.2％,and 5.6％ and 5.9％,respectively.Conclusion The calibration of routine measurement systems based on the measuring value transfer for human serum samples assigned by the reference laboratory network may improve the comparability of 7 enzyme actvities measurement results in chnical laboratories at all levels obviously,which deserves to be further spread.

Objective:To study the effects of brachytherapy with 125I in the treatment of malignant adenogenous tumors invaded into cranial base area,and to evaluate the correlative factors of prognosis.Methods:24 patients with malignant adenogenous tumors invaded into cranial base area were treated by 125I seeds implanted into the tumors with the spacing of 1-1.5 cm and guided by CT,individual guide plate and navigation system respectively or in combination with the dose of 60-160 Gy.Survival rate,local recurrence rate,distant metastasis and safty of the treatment were evaluated.The correlative factors of prognosis included age,pathology diagnosis,diameter of the tumor,area of tumor invasion and history of radiotherapy were analyzed.Results:The follow-up time of the patients was 3-76 months and the median was 27 months.2 patients came up with radiotherapy reaction of level 4.The total survival rate was 41.7％,the local recurrence rate was 25.0％ and the distant metastasis rate was 37.5％.The cumulative survival rate of 1,3 and 5 years was 79％,67％ and 24％ respectively.Significant correlation was found between prognosis and local recurrence as well as the diameter of the tumor.Conclusion:125I brachytherapy provides a safe and feasible technique with minimal damage for treating malignant adenogenous tumors invaded into cranial base area.The prognosis is related to local recurrence and the diameter of the tumor.

Objective: To investigate clinical features of distant metastases from malignant salivary gland carcinomas after treated by 125I internal brachy therapy alone.Methods: Between 2002 and 2010, 43 patients with locally advanced unresectable or recurrent malignant salivary gland carcinomas were treated by 125I internal brachy therapy alone at Peking University School and Hospital of Stomatology.All of them had been follow-up at least 2 years.The primary sites of malignant salivary gland carcinomas were the parotid for 12 patients, infratemporal fossa for 9 patients, tongue for 7 patients, maxilla for 6 patients, parapharyngeal for 4 patients, floor of months for 3 patients, submandibular gland for 1 patient, and lip for 1 patient.The overall survival rate, local control rate, and distant metastases were retrospectively reviewed.Results: Distant metastases occurred in 23 of the 43 patients (53.5%).Distant metastases developed from 5 to 96 months, with an average interval of (27.0±23.7) months from the time of initial diagnosis, the mean interval was 21 months.The commonest site of distant metastases overall was the lung 69.6%(16/23).The most common pathological types of distant metastases were adenoid cystic carcinoma (14/23, 60.9%) and nonspecific adenocarcinoma (7/23, 30.4%).At the time of the last follow-up, 26 patients died, and 18 of them due to distant metastases (69.2%, 18/26).In the study, 27 patients got complete remission(CR), 12 got partial remission(PR) more than 50%, 2 less than 50%, and 2 patients were invalid.The effective rate (CR+ PR) was 90.7%.The 3 year loco-regional control rate and survival rate were 60.1%, 82.6%, respectively, and the 5 year's 53.4% and 56.0%.Conclusion: The 125I brachy therapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent malignant salivary gland carcinomas.However, further studies are needed with larger numbers of patients and for a longer follow-up assessment.Distant metastasis was the main cause of treatment failure, and the lung was the most common site of distant metastases.

OBJECTIVETo explore the values of autologous cytokine-induced killer cells combined with rhIL-2 for therapy of elderly patients with B-cell malignant lymphoma.

METHODSEighty-five elderly patients with B-cell malignant lymphoma were treated by cytokine induced killer cells combine with rhIL-2 (CIK+IL-2 group), 85 elderly patients with B-cell malignant lymphoma treated without cytokine induced killer cells combined with rhIL-2 were used as the control group. The patients in CIK+IL-2 group and control group were divided into 4 subgroups accerding to lymphoma types: group A: diffuse large B cell lymphoma (DLBCL), group B: mucosa-associated lymphoid tissue type (MALT), group C: lymphoplas macytic lymphoma (LPL) and group D: hodgkin's lymphma (HL). The clinical effects, T-lymphocyte, β2 microglobulin level, quality of life and long-term survival were observed.

RESULTSThe levels of CD3+, CD3+/CD8+, CD3+/CD56+ after treatment in the 4 subgroups of CIK+IL-2 group were higher than levels before treatment and the control group (P<0.05); the levels of β2 microglobulin after treatment for the 4 groups were lower than before treatment and the control group (P<0.05); with 1 case death, 16 cases were turned from CRu and PR to CR; the CR rate was not significantly different among the 4 subgroups (P>0.05); the scores of physical performance, role function, cognitive function, emotional functioning, and social function after treatment in the 4 subgroups were higher than the those before treatment (P<0.05); the survival time of patients in the CIK+IL-2 group lasted for 8-76 months, their median survival time was (22.36±5.38) months; the survival of the control group lasted for 7-55 months, their median survival time was (16.15±3.62) months. The survival time of the CIK+IL-2 group was longer than that of the control group (P<0.05).

CONCLUSIONThe treatment of aged patients with B-cell malignant lymphoma by autologous cytokine-induced killer cells combined with rhIL-2 can effectively improve the T-lymphocyte subsets, β2 microglobulin level and quality of life, and can prolong survival time of patients.

Aged ; Cytokine-Induced Killer Cells ; cytology ; Humans ; Interleukin-2 ; therapeutic use ; Lymphoma, Large B-Cell, Diffuse ; therapy ; Quality of Life ; Recombinant Proteins ; therapeutic use ; T-Lymphocyte Subsets