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 evaluate the clinical efficacy of Buyang Huanwu Decoction combined with medium-frequency pulsed electrical stimulation in the treatment of diabetic peripheral neuropathic pain (DPNP).Methods:A randomized controlled trial study was conducted. A total of 86 patients with DPNP in the endocrinology department of Xi'an Hospital of Traditional Chinese Medicine from September 2020 to September 2023 were selected as the observation objects and divided into 2 groups through the random number table method, with 43 cases in each group. The control group was combined with medium-frequency pulsed electrical stimulation on the basis of conventional Western medical treatment, while the observation group was supplemented with Buyang Huanwu Decoction on the basis of the control group. Both groups were treated for 12 weeks. TCM syndrome scores were conducted before and after the treatment respectively. The Toronto Clinical Scoring System (TCSS) was used to grade the severity of neuropathy. The motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) of the median nerve and common peroneal nerve were detected by electromyography evoked potential tester. Adverse reactions during the treatment were recorded to evaluate the clinical efficacy.Results:The total effective rate was 93.02% (40/43) in the observation group and 74.42% (32/43) in the control group, with statistical significance between the two groups ( χ2=5.46, P=0.019). After treatment, the scores of shortness of breath and fatigue, end-limb pain, listlessness, dull tongue and the total score in the observation group were lower than those in the control group ( t values were 3.06, 3.42, 3.09, 3.57 and 3.98 respectively, P<0.05); the scores of neurological symptoms, neural reflexes and sensory function examinations were lower than those in the control group ( t values were 4.54, 6.28 and 5.16 respectively, P<0.01). After treatment in the observation group, MCV of the median nerve [(47.96±5.98) m/s vs. (42.02±5.74) m/s, t=4.70] and SCV [(54.90±6.29) m/s vs. (48.04±6.16) m/s, t=5.11] were higher than those in the control group. The MCV of the common perbular nerve [(41.76±6.27) m/s vs. (37.04±6.18) m/s, t=3.52] and SCV [(50.35±6.41) m/s vs. (46.14±6.13) m/s, t=3.12] were higher than those in the control group ( P<0.01 or P<0.05). During the treatment period, the incidence of adverse reactions was 11.63% (5/43) in the observation group and 9.30% (4/43) in the control group, without statistical significance between the two groups ( χ2=0.12, P=0.725). Conclusion:Buyang Huanwu Decoction combined with medium-frequency pulsed electrical stimulation can effectively improve the degree of neuropathy in patients with DPNP, increase nerve conduction velocity, alleviate TCM syndromes, enhance clinical efficacy and has good safety.

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.

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.

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.

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 study the protective effects of butein on oxidative stress injury of PC12 cell and its effects on mitochondrial function. METHODS：Rats PC12 cells were divided into normal control group，model group，solvent control group（1 ‰ dimethyl sulfoxide），butein high，medium and low concentration groups（2，1，0.5 μmol/L）. The latter 4 groups were given relevant reagent/medicine for intervention；24 h later，other groups were given 100 mU/mL glucose oxidase to induce oxidant stress model except for normal control group. After 4 h culture，cell survival rate，apoptosis rate，the levels or activities of ROS，MDA，SOD，CAT，GSH-Px，ATP，IL-1β and TNF-α as well as the change of MMP were detected. RESULTS：Compared with normal control group，cell survival rate，the levels or activities of SOD，CAT，GSH-Px and ATP were all decreased significantly，and apoptotic rate，the content of ROS，the levels of MDA，IL-1β and TNF-α were all increased significantly（P＜0.05 or P＜0.01），while the MMP was decreased significantly. Compared with model group，above indexes of solvent control group had no significant change （P＞0.05），cell survival rates，the levels or activities of SOD （except for medium and low concentration groups），CAT，GSH-Px（except for medium and low concentration groups），ATP（except for low concentration group）were increased significantly in butein high，medium and low concentration groups，while apoptotic rates，the content of ROS，the levels of MDA，IL-1 β and TNF-α were decreased significantly（P＜0.05 or P＜0.01），while the MMP were increased significantly. CONCLUSIONS：Butein can increase the antioxidant enzyme activity， stabilize mitochondrial function， inhibit oxidative stress and inflammationthus， increase energy generation inhibiting neuronal cell apoptosis ultimately exerting a neuroprotective effect.