Parkinson’s disease （PD） is a common chronic neurodegenerative disease with movement disorders as the main clinical manifestation. The nuclear factor-erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway is closely associated with the occurrence and progression of PD. TCM flavonoid monomers （luteolin， rutin， etc.）， alkaloids （camptothecin， sinomenine， and alkaloids extracted from Uncaria rhynchophylla）， terpenes （tanshinone ⅡA， carvacrol， paeoniflorin）， phenols （ellagic acid， rosmarinic acid）， saponins （ginsenoside RK1）， and traditional Chinese medicine compounds （Wuzi yanzong pill and PD formula-2） can resist oxidative stress damage， inhibit inflammatory responses and abnormal aggregation of α-synuclein， and regulate neurotrophic factors by activating the Nrf2/HO-1 signaling pathway， thereby alleviating dopaminergic neuronal damage.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective To explore the patterns of functional gait asymmetry during the support phase and the differentiation of bilateral foot functions,to gain insights into the human movement compensa-tion mechanisms and stability control characteristics,so as to provide theoretical references for the pre-vention and rehabilitation treatment of unilateral foot and ankle injuries.Methods Twelve young females with normal feet were recruited,and the time percentage of each phase of the support period,the change of longitudinal arch angle,the vertical ground reaction force and the center of plantar pressure trajectory of the dominant and non-dominant feet were collected by using a three-dimensional motion capture and a high-frequency plantar pressure testing system when the subjects walked at the optimum speed with the incremental loading of weights[0%body weight(BW),10%BW and 20%BW].The ef-fects of laterality(dominant foot,non-dominant foot)and load(0%BW,10%BW,20%BW)on arch changes and gait parameters,and the interactions between them,were analyzed using a two-way re-peated-measures ANOVA.Results The factors of laterality and load interacted significantly on arch changes,but not on gait parameters.(2)Compared with 0%BW,the time percentage of the buffering phase of the nondominant feet with the load of 20%BW increased(P<0.05),while that of the domi-nant ones decreased(P<0.05),with an increase in the buffering load of both feet with the load of 20%BW(P<0.05)and the buffering force excursion of both feet with the load of 10%BW(P<0.05).More-over,changes in longitudinal arch angle increased(P<0.05)with the load of 10%and 20%BW,the pedal extension load rate increased(P<0.05)with the above BW load in the non-dominant feet,and the horizontal slope of pedal extension decreased(P<0.05)with 20%BW load in the dominant feet.Compared with 10%BW,when the feed was loaded 20%BW,the time percentage in the buffering phase and the buffering force offset of the dominant feet decreased(P<0.05),while the buffering load of both feet increased(P<0.05).(3)Compared with the non-dominant feet,for the dominant feet,the buffering load rate at the load of 10%and 20%BW and changes in the longitudinal arch angle at the load of 20%BW decreased(P<0.05),while the horizontal slope of the pedal extension without load in-creased(P<0.05).Conclusion Walking with load induces function differentiation in bilateral feet.The dominant foot has more efficient horizontal extension without load and better buffering function in the vertical direction with loads,while the non-dominant feet perform a more adequate weight-bearing and extension function vertically with larger load.It is suggested that unilateral injury feet should not be given too much load,and it is inappropriate to select a single foot to represent and evaluate the func-tion and injury risk of the double feet in loaded walking.

Objective:To observe the effect of ubiquilin 2 gene (UBQLN2) on the radiosensitivity of human esophageal squamous cell carcinoma cells (ESCC) of EC109 and KYSE30, and explore underlying molecular mechanism.Methods:siRNA and lentivirus transfection techniques were used to establish UBQLN2-knockdown and UBQLN2-overexpression cell lines. The cells were irradiated with a dose of 4 Gy X-rays. UPLC-Q-TOF-MS technique was used for metabolite difference analysis and KEGG pathway analysis. The results of metabonomics analyses were verified by qRT-PCR assay. The influence of UBQLN2 level on the radiosensitivity of ESCC was confirmed by CCK-8 cell proliferation assay and clone formation assay and further verified by treating the cells with metabolic enzyme inhibitors and exogenous metabolites.Results:Compared with irradiation alone, down-regulating UBQLN2 in EC109 and KYSE30 cell lines reduced the cell survival by 32.29% and 16.42% ( t=5.35, 4.88, P<0.05), and reduced the clone formation rate by 11.07% and 7.47% after 4 Gy irradiation, respectively ( t=4.18, 5.09, P<0.05). On the contrary, up-regulating UBQLN2 in EC109 and KYSE30 cell lines increased the survival rate by 14.07% and 10.64% ( t=5.88, 4.21, P<0.05), and increased the clone formation rate by 6.53% and 7.87% after 4 Gy irradiation, respectively ( t=8.60, 8.26, P<0.05). Metabonomics study showed that the purine metabolic pathway was significantly enriched after down-regulating UBQLN2 in EC109 cell. The qRT-PCR experiment showed a positive correlation between the expression level of UBQLN2 and the mRNA level of five purine metabolism enzymes. The viability of irradiated UBQLN2-overexpression cells decreased by 18.28% and 25.58%, respectively ( t=7.76, 10.95, P<0.05), and the clone formation rate decreased by 9.33% and 9.93%, respectively ( t=5.97, 8.02, P<0.05) after adding mycophenolic acid(MPA). However, the survival rate of cells increased by by 8.28% and 10.74% ( t=2.83, 6.20, P<0.05), and the clone formation rate increased by 7.33% and 5.80%, respectively ( t=7.16, 5.49, P<0.05), when exogenous supplementation of nucleotides (ATP + GTP) were added. Conclusion:The expression level of UBQLN2 was negatively related to the radiosensitivity of ESCC by up-regulating purine metabolism.

Active immunotherapy for cancer aims to treat disease by inducing effective cellular immunity and humoral immunity.Research on virus-like particles(VLPs)vaccines has made tremendous progress in recent years,dramatically reducing morbidity and mortality from some infectious diseases.VLPs are nanoparticles self-assembled from one or more structural proteins,with highly ordered repeat sequences and good immunogenicity,which can induce strong cellular immune and humoral immune responses.VLPs can overcome immunosuppressive state of tumor microenvironment,break self-tolerance,and trigger strong cytotoxic T lymphocyte activity,which is critical for both viral clearance and destruction of cancer cells.This article mainly reviews current research progress of VLPs-based cancer vaccines and potential defects of VLPs as vaccine carriers in development of cancer vaccines.

Virus-like particles(VLPs)are nanoparticles that are self-assembled from one or more structural proteins,which can be arranged in several layers or contain a lipid outer membrane.Due to the lack of genetic material,VLPs cannot infect host cells,but are highly immunogenic and can induce immune responses different from conventional inactivated vaccines.VLPs can be produced using a variety of systems including bacterial,yeast,plant,insect and mammalian cells.Compared with traditional vaccines,VLPs have incomparable advantages,so they are becoming more and more popular in the biomedical field.To date,a series of vaccine candi-dates based on VLPs have been developed for immunization and prevention of various infectious diseases.At the same time,the recent successful application of VLPs in targeted drug delivery and gene therapy has attracted attention.This paper mainly reviews the com-monly used expression systems of VLPs and the research progress of their applications.

Innate immunity is the first line of the host cell defensing against viral infection,in which the pattern recognition re-ceptors(PRRs)such as Toll-like receptors(TLRs)and retinoic acid induces gene Ⅰ-like receptors(RLRs)play an important role.After virus infection,mitochondrial antiviral signaling protein(MAVS)in PRRs-mediated signaling pathway,which are of the com-mon linker molecule for downstream signal transmission,can receive signals transmitted by upstream TLR and RIG-Ⅰ,activate down-stream NF-κB and IRF3/7 signaling pathways leading to the activation of interferon(IFN)expression.Therefore MAVS acts as a bridge in the innate immune signaling pathway.More and more studies have shown that viruses have evolved a series of mechanism to escape the innate immune response over the long course of their evolution,and evaded the host's antiviral immune response by interfer-ing with multiple sites in the MAVS-mediated signaling pathway so as to complete its own replication and proliferation.In this paper,the role of MAVS in IFN-Ⅰ pathway and its latest research progress in the mechanism of anti-DNA viruses and anti-RNA viruses reac-tion are reviewed,providing theoretical basis for further studying the detailed mechanism of anti-virus of MAVS.

The tumors of central nervous system refer to a group of benign and malignant diseases originating from tissues or structures within the central nervous system. Common tumors of central nervous system are sporadic, but a few have familial onset. Compared with sporadic brain tumors, the clinical symptoms, diagnostic ideas and follow-up review plans of familial brain tumors are more complicated. The multidisciplinary diagnosis and treatment (MDT) mode usually refers to a treatment mode in which a case involving multiple organs and systems is discussed, and the best treatment plan is formulated for the patient based on the comprehensive opinions of various disciplines. Because familial brain tumors often involve multiple organs, multiple disciplines and multiple systems, and their low incidence leads to less clinical experience for neurosurgeons, the MDT model is more conducive to efficient diagnosis, treatment and management of familial brain tumors. This review elaborates on the neurosurgeon-led MDT model, and introduces the latest research on the epidemiology, genetic characteristics, clinical manifestations, diagnostic ideas and multidisciplinary management of familial brain tumors.

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.