ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is characterized by complex pathogenesis and poor prognosis. In recent years, epithelial-mesenchymal transition (EMT) in tumor initiation and progression has attracted increasing attention. Enhancer of zeste homolog 2 (EZH2), which is aberrantly expressed in various tumors, may be closely related to the EMT process. This study aims to examine the expression and correlation of EZH2 and EMT markers in ESCC cells and tissues, evaluate the effects of EZH2 knockdown on ESCC cell proliferation, invasion, and migration, and explore how EZH2 contributes to the malignant biological behavior of ESCC. METHODS: Bioinformatics analyses were used to assess EZH2 expression levels in ESCC. Small interfering RNA was used to knock down EZH2 in ESCC cell lines EC109 and EC9706. Cell proliferation, invasion, and migration were evaluated using cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Protein and mRNA expression levels of EZH2, E-cadherin (E-cad), and vimentin (Vim) were detected by Western blotting and real time fluorogenic quantitative PCR (RT-qPCR), respectively. Immunohistochemical (IHC) staining was performed on 70 ESCC tissue samples and 40 paired adjacent normal tissues collected from the First Affiliated Hospital of Shihezi University between 2010 and 2016 to assess the expression of EZH2, E-cad, and Vim, and to analyze their associations with clinicopathological feature and patient prognosis. RESULTS: Bioinformatics analysis showed that EZH2 was highly expressed in ESCC (P<0.001), and high EZH2 expression was associated with worse prognosis (P<0.001). CCK-8, wound healing, and Transwell assays demonstrated that EZH2 knockdown significantly suppressed the proliferation, invasion, and migration of ESCC cells (P<0.001). In addition, Vim expression was significantly reduced, while E-cad expression was significantly increased at both protein and mRNA levels in EZH2-silenced cells (all P<0.05). IHC staining analysis revealed higher expression of EZH2 and Vim and lower expression of E-cad in ESCC tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis showed that low expression of EZH2 and Vim and high expression of E-cad were associated with longer survival (all P<0.05). CONCLUSIONS EZH2 promotes malignant biological behavior in ESCC by mediating EMT. Elevated EZH2 expression is associated with poor prognosis in ESCC patients.
Humans ; Enhancer of Zeste Homolog 2 Protein/physiology* ; Esophageal Squamous Cell Carcinoma/pathology* ; Epithelial-Mesenchymal Transition/genetics* ; Esophageal Neoplasms/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement ; Cadherins/genetics* ; Vimentin/genetics* ; Male ; Female ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; RNA, Small Interfering/genetics* ; Gene Expression Regulation, Neoplastic

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

Background::Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.Methods::Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM 2.5) and/or ozone (O 3) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017. Results::In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O 3 in the total loss from the two pollutants was substantially lower than that of PM 2.5, but it was rapidly growing. The O 3-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM 2.5 and O 3 to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest. Conclusion::The disease burden from O 3 is lower than that of PM 2.5, the O 3-contribution has a significantly increasing trend with the growth of economy and O 3 concentration.

Toxoplasma gondii(T.gondii or Tg),is an obligatory intracellular parasite with humans as its intermediate hosts.In recent years,significant correlations between T.gondii infection and schizophrenia have been reported,including the possible mediating mechanisms.Currently,mechanisms and hypotheses focus on central neurotransmitters,immunity,neuroinflammation,and epigenetics;however,the exact underlying mechanisms remain unclear.In this article,we review the studies related to T.gondii infection and schizophrenia,particularly the latest research progress.Research on dopamine(DA)and other neurotransmitters,the blood-brain barrier,inflammatory factors,disease heterogeneity,and other confounders is also discussed.In addition,we also summarized the results of some new epidemiological investigations.

Consumptive thirst such as dry mouth and polydipsia,frequent urination polyuria,fear of heat and hyperhidrosis and loss of other body fluids,yin deficiency and internal heat expression,and irritability and other abnormal emotional symptoms are common.The Synopsis of Golden Chamber need to be further explored for the treatment of miscellaneous diseases.The dialectical thought has a high clinical application value.Lily disease treatment recommendations in the Synopsis of Golden Chamber are explored.The symptoms of lily disease are varied and uncertain,which are caused by the scattering and wandering aimlessly of heat pathogen.The pathogenesis of lily disease can be examined through external symptoms such as bitter taste in mouth,red urine,and faint and rapid pulse.Diabetes is also closely related to yin deficiency and internal heat,and the pathogenesis of the two is similar.Mental symptoms are common characteristics of lily disease and diabetes.The method taken from the Synopsis of Golden Chamber and Baihe-like prescriptions for the treatment of diabetes are effective.By identifying different patterns,symptoms,and indicators,we can select lily bulb,common anemarrhena,rhizome,figwort root,unprocessed rehmannia root,and other drugs to treat diabetes,in order to improve our understanding of lily disease and provide new ideas for diabetes treatment.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Innate immune response is the first line of immune defense in our body against invaded pathogens.After receive pathogen stimulation,immune cells synthesize abundant type Ⅰ interferons(IFNs)through activating three different signaling path-ways to establish strong antiviral immune response.Mounting evidences have revealed that selective autophagy participates in the regu-lation of innate type Ⅰ IFN response and prevents the excessive activation of immune responses.E3 ubiquitin ligases transfer different type of polyubiquitin chains to some key signaling proteins,and trigger the selective degradation of these proteins through autophago-some-lysosome pathway.Therefore,autophagy and E3 ubiquitin ligases integrate the spatiotemporal regulation of innate type Ⅰ IFN response.In this review,we summarized current data elucidating the critical role of autophagy and E3 ubiquitin ligases in the regula-tion of innate immune response.

Objective:To explore the competitive attitude of students of medical college and its influencing factors.Methods:A sample of 382 first to third year medical students was selected with the method of random sampling. The questionnaire consists of three parts: demographics, Competitive Attitude Scale of Chinese Version and Jefferson Scale of Physician Empathy. SPSS 25.0 was applied to perform the statistical analysis. Concrete methods that used involved statistical interpretation, Kruskal-Wallis test, Mann-Whitney U test and Spearman rank sum correlation analysis. Results:The benign competitive attitude of students was 51.00(45.00，56.00) and the excessive competitive attitude was 35.00(31.00，38.00). There was a statistically significant difference in the score of benign competitive attitude among medical students of different grades( H=22.31, P<0.001). There were statistically significant differences in the scores of benign competitive attitudes among the medical students who enjoy teamwork ( Z=-4.53, P<0.001), who had role models to follow in the medical field ( Z=-3.99, P<0.001), and who had careful career planning ( Z=-2.19, P=0.029). There were statistically significant differences in the scores of excessive competitive attitudes among the medical students who enjoy teamwork ( Z=-2.47, P=0.014), who had role models to follow in the medical field ( Z=-2.89, P=0.004), and who had careful career planning ( Z=-2.32, P=0.021). There was a weak positive correlation between empathy and benign competitive attitude ( r=0.20, P<0.001), but a negative correlation between empathy and excessive attitude ( r=-0.36, P<0.001). Conclusions:Medical students had a good competitive attitude. Medical college should pay more attention to improving medical students' sense of teamwork, career planning ability and willingness to learn from role models, guide students to develop a benign competitive attitude and focus on improving their professional quality.