Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Objective:To establish VSV-G qPCR assay for detection of replication competent lentivirus(RCL) and verify its application.Methods:A real-time fluorescent quantitative PCR for VSV-G envelope gene was developed. Several parameters including specificity, linear, amplification efficiency, precision, trueness, dynamic range, limit of detection, limit of quantification and robustness were verified. Preliminary application on CAR-T cells, end of production cells and the harvest of lentivirus vector was performed by using the method developed.Results:The real-time fluorescent quantitative PCR assay for VSV-G was specific for the detection VSV-G without specific amplification on 293T, PBMC and C8166 cells. The linear range of the assay was 1×10 2 copies/test-1×10 9 copies/test with a R2 value more than 0.998 and amplification efficiency between 93% and 98%. The precision (relative standard deviation) of the assay was less than 12% and the trueness (the rate of recovery) of the assay was between 85% and 106%. The limit of detection (LOD) and limit of quantification (LOQ) of the assay was 5 copies/test and 40 copies/test. In addition, the robustness of the assay was also well. All the results of validation illustrated that the assay could meet the detection requirements. All of the 54 samples including CAR-T cells, lentivirus vector and end of product cells after amplification and passage on C8166 cells were negative of RCL by using the established assay. Conclusions:The real-time fluorescent quantitative PCR for VSV-G were established successfully. All of the validation results illustrated that the assay could meet the detection requirements. The application of the assay was conducive to further enhance the safety of the lentivirus vector related products.

Objective: To understand the awareness and influencing factors of medical healthcare APP among female college students in Weifang, and to provide references for healthy lifestyle and health literacy improvement. Methods: A total of 891 female college students were selected by stratified random sampling method, and were investigated regrading awareness on medical and health care APP and associated factors. Data were statistically analyzed by composition ratio, CHI-square test and binary Logistic regression. Results: There were 54.6% of the female college students who reported not aware of medical healthcare APP. The overall awareness rates of medical and health care APP for freshmen,sophomores, juniors, seniurs and above were 39.75%,45.59%,55.78% and 52.56%, respectively, and the difference was statistically significant(χ2=16.43，P<0.05). Logistic regression analysis showed that medical costs, medical healthcare information attention, medical health care information recognition, consulting the treatment scheme were positively associated with awareness of health care APP(OR=1.40,1.51,1.27,1.33,P<0.05). Conclusion The awareness rate of medical health care APP of female college students in Weifang is relatively low,and the difference between different groups is obvious. It is necessary to improve the scientific knowledge rate of the female college students to the APP, so as to influence the life style of the female college students.

Family physicians contracted service is an important choice to deepen the reform of China′s healthcare reform and achieve the strategic goal of " health for all" . In order to effectively promote the contracted service, the central government has successively issued a number of policy documents, which are echoed by the localities in their proactive explorations, achieving remarkable results. But there are also multiple roadblocks hindering the contracted service to progress. This article referred to the three-circle theory and studied policy implementation from the three dimensions of policy value, policy resources, and policy impetus. A thorough analysis of the problems in the implementation process revealed such main problems as insufficient family physicians, inadequacy of supporting policies and low level of policy acceptance among the young healthy age groups. The follow-up work will promote the long-term implementation of the family physicians contracted service policy by enriching the family physicians team, enriching supporting policies, and focusing on promotions to key age groups.

The healthcare plus aging care is a new type of aging care model that integrates medical services and aging care services. China has successively issued a series of policies, encouraging the localities to proactively explore such a model. The authors refer to the four dimensions of exchange and communication, policy resources, policy executor preferences and organizational structure in the Edwards policy execution model, for analyzing the implementation of such a policy. The study found such constraints for the policy as follows: unclear policy implementation standards, inadequate policy resources of manpower, financial and material resources, differences in preferences among local governments, general hospitals, primary medical institutions, and pension institutions, as well as decentralized and restricted organizational structures. At present, the policy of healthcare plus aging care remains in the stage of exploration and trial. The government should continue to define and revise the policy to ensure the smooth progress and long-term implementation of the policy of healthcare plus aging care.

Objective:Based on the perspective of status-seeking, to clarify the status quo of rural doctors′ subjective social status, and put forward countermeasures and suggestions to improve the subjective social status of rural doctors.Methods:By investigating 1 395 rural doctors in both 2015 and 2017 to clarify the status quo of rural doctors′ subjective social status through descriptive analysis, we compared the subjective social status of rural doctors with different characteristics by using differential analysis.Results:The overall subjective social status scoring of rural doctors was 3.17±0.48, including decision participation scoring(3.30±0.82), income scoring(2.19±0.80), social relationship scoring(4.05±0.61), career reputation scoring(3.09±0.84), career promotion scoring(2.38±0.67), and career value scoring(4.04±0.63). Rural doctors with middle or above academic titles, high-performance levels, as well as those comparable to doctors in township hospitals and self-employed clinics were found with higher subjective social status.Conclusions:Rural doctors held their subjective social status to be at an intermediate level, with higher ratings for interpersonal relationships and professional values and lower ratings for salary and training mechanisms. Positive feedback on the status-seeking behavior of rural doctors is recommended to improve village clinic services and reshape the image of rural doctors.

OBJECTIVE： To synthesize and identify rotundic acid esters derivatives， and to evaluate in vitro antitumor activity. METHODS： Using rotundic acid as raw material， rotundic acid esters derivatives were synthesized by 28-esterification， 3β and 23-position hydroxyl group combined with acid anhydride. The structure of rotundic acid esters derivatives were identified by HRMS， 1H-NMR， 13C-NMR and physicochemical properties. The in vitro antitumor activities were evaluated by MTT assay against paclitaxel （positive control）， rotundic acid and rotundic acid esters derivatives with human cervical cancer cells HeLa， human malignant melanoma cells A375， human lung adenocarcinoma cells SPC-A1 and human liver cancer cells HepG2 （take IC50 as an indicator）. RESULTS： Totally 6 kinds of rotundic acid esters derivatives were synthesized， i.e. rotundic acid methyl ester（compound 1）， 3， 23-O-di（acetyl） rotundic acid methyl ester（compound 2）， 3， 23-O-di（propionyl） rotundic acid methyl ester（compound 3）， 3， 23-O-di（butyryl） rotundic acid methyl ester（compound 4）， 3， 23-O-di（phthaloyl） rotundic acid methyl ester（compound 5） and 3， 23-O-di（succinyl） rotundic acid methyl ester（compound 6）. Compared with paclitaxel， the antitumor activity of compound 5 and compound 6 to Hela， A375， HepG2 and SPC-A1 was similar to it， and there was no significant difference between them （P＞0.05）； the IC50 of rotuntic acid and other compounds decreased with statistical significance （P＜0.05）. CONCLUSIONS： In the study， 6 kinds of rotundic acid esters derivatives are synthesized and compound 5 and compound 6 have significant antitumor activity in vitro， which can provide reference for further study.

Objective To investigate the correlation between incidence rate of tinnitus and noise exposure time,age,hearing condition in noise exposure workers.Methods A total of 1 985 noise exposure workers (age between 20～60 years old;working length between 1 ～30 years) in a large dockyard were randomly selected as the subject of this study with 1 831 male workers and 154 female workers in average 36.3±8.25 years old.The average noise exposure time was 9.1±6.50 years and pure tone threshold of final candidates in sound-proofed environment was evaluated (at 0.25～8 kHz).The subjects were divided into four groups according to the subjective tinnitus level:mild tinnitus,moderate tinnitus,severe tinnitus and no tinnitus to analysis the correlation among incidence rate of tinnitus and noise exposure time,age,hearing condition,etc.Results Among all 1 985 subjects enrolled the occurrence rate of tinnitus was 20.55％ (408/1 985),with 367 acquired mild tinnitus(89.95％),39 acquired moderate tinnitus (9.56％) and 2 for severe tinnitus (0.49％).Mild tinnitus and moderate tinnitus showed a multi-step raising according to noise exposure time.Mild tinnitus increased continually with age while moderate tinnitus showed an accumulation in age group over 55 years old.Female was less likely to be annoyed by tinnitus than male.Conclusion Tinnitus can be early warning of auditory damage by noise exposure;older male group with longer noise exposure time is more vulnerable to tinnitus.Tinnitus acquired in noise environment is more likely to be mild.

Objectives:To design a self-control training program based on the recent findings of self-control and self-regulation after taking full consideration of the unique characteristics of depression disorder,with an emphasis on behavioral activation and reinforcement.Methods:Totally 46 students who were diagnosed with major depression were randomly assigned to one of the two groups:Group 1 (n =23),and Group 2 (n =23).Participants in the Group 1 received 24-week self-control training program,as compared to Group 2 who received only baseline and post-24-week-intervention measurements,the measurements included Self-control Scale (SCS) and Beck Depression Inventory (BDI-Ⅱ).The self-control training included eight-week training modules and 16-week consolidation module.Results:In Group 1,the SCS scores were higher in post-intervention than in baseline measurement [(38.0 ± 6.3) vs.(34.7 ± 8.2),P ＜ 0.01],and the BDI-Ⅱ scores were lower in post-intervention than in baseline measurement [(19.0 ± 6.1) vs.(21.8 ± 4.8),P＜0.01] in Group 1.Whereas in Group 2,there were no significant differences between baseline and post-24-week-intervention measurements of SCS and BDI-Ⅱ scores (Ps ＞0.05).Conclusion:The study provides new evidence for the self-regulation model of depression.Self-control training could be an effective intervention strategy for the treatment of depression.

Objective To investigate the influence of proinflammatory factor interleukin-18(IL-18) on vein endothelial cell function by activating NF-κB mediated cell signal pathway and its association with deep vein thrombosis(DVT).Methods Recombinant human IL-18 was used to act on in vitro cultured human umbilical vein endothelial cell(HUVECs).The NF-κB activation inhibitor was used to conduct interference.The detection measures of real time fluorescence quantitative PCR,Western blot,immunofluorescence and flow cytometry were used to verify whether IL-18 affect the expression of endothelial cellular function markers such as HUVECs normal statusand vWF,P-selectin and tissue plasminogen activator(t-PA) by activating NF-κB mediated cell signal pathway.Moreover the mechanism of IL-18 participating in the DVT was performed the comprehensive analysis by combining with previous study.Results IL-18 could activate NF-κB in endothelial cell,increased the p65 expression in nucleus,decreased the intracellular IκBα expression and significantly increased early apoptosis cells in HUVECs;adding QNZ(EVP4593) could significantly inhibit the activation effect of IL-18 on NF-κB,the occurrence of cellular injury and apoptosis was significantly reduced;IL-18 could promote the abnormal expression of DVT related endothelial cell markers vWF,P-selectin and t-PA (P<0.05).But various markers could recover conventional expression after inhibiting NF-κB activation.Conclusion The interaction between Il-18 and NF-κB causes the abnormality of HUVECs growth status and function,which may be the DVT onset related pathogenic mechanism.