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

The bony window technique refers to cutting the intact bone plate to form a bone window and a free bone block to get access to lesions under the bone. At the end of the surgery, the dislocated bony lid needs to be repositioned to its original position. In endodontic microsurgery, compared with conventional osteotomy, the bony window technique has the advantages of improving the view of surgery and operability, reducing postoperative bone defects, promoting bone healing, and maintaining the integrity of the jaw outline. Accurate positioning and preparation of the bony window are important prerequisites for subsequent operations during the surgery, but it′s difficult in some situations, such as when the operative area is located posteriorly or the bone cortex on the lesion surface is thick and intact. What′s more, whether the free bone block can be stabilized in situ after repositioning is closely related to the prognosis of the surgery. The complementary application of digital navigation technology and bone cavity filling materials may help to improve the bony window technique and provide more possibilities for the retention of affected teeth in difficult cases.

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.

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.

Objective:To evaluate the clinical efficacy and safety of endoscopic ultrasound (EUS)-guided coil implantation combined with glue injection for preventing rebleeding of tumorous gastric fundal varices.Methods:A retrospective analysis was performed on the clinical data of patients who underwent EUS-guided coil implantation combined with glue injection due to tumorous gastric fundal variceal bleeding from September 2017 to December 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The basic characteristics and endoscopic manifestations of patients treated with this technique were analyzed, and the success rate of this technique, the usage of tissue glue and coil, the variceal obliteration rate and the incidence of complications such as pulmonary embolism were analyzed. Patients were followed up over a long period of time to obtain data on rebleeding. At the same time, patients were divided into complete obliteration group and incomplete obliteration group according to the endoscopic performance after the treatment, and the rebleeding rate in the two groups was compared.Results:Among the 41 patients included in this study, 18 cases (43.90%) had single isolated gastric varices type 1, and 23 cases (56.10%) had gastroesophageal varices combined. Fourteen cases had signs of recent bleeding such as thrombi and ulcers under endoscopy, and 13 cases had combined portal hypertensive gastropathy. All patients successfully completed the operation of EUS-guided coil implantation combined with glue injection. The technical success rate for the first attempt was 92.68% (38/41). The one-time pre-installation success rate of coils was 95.12% (39/41). The success rate of target vessel aspiration under EUS guidance was 100.00% (41/41). The release success rate of coil was 97.56% (40/41). The number of coils used was 1.12±0.33, and the amount of tissue glue used after inserting the coils was 1.54±0.46 mL. The target vessel obliteration rate after operation was 97.56% (40/41), and the complete gastric fundal variceal obliteration rate was 51.22% (21/41). There were 2 cases (4.88%) of intraoperative bleeding, 1 case stopped spontaneously, and 1 case successfully stopped bleeding after additional injection of tissue glue under direct endoscopic vision. No patient had symptoms of pulmonary embolism such as decreased oxygen saturation during the operation. Postoperative computed tomography angiography of pulmonary artery or lung computed tomography was performed in 24 cases, of which 1 case (4.17%) showed distal pulmonary artery embolism, but there were no relevant clinical manifestations. The patients were followed up for 21.64±16.86 months (1-50 months) after the surgery. There were 13 cases (31.71%) of recurrent gastrointestinal bleeding after the surgery, no rebleeding within 5 days, 2 cases of rebleeding within 3 months, 5 cases from 3 to 12 months, and 6 cases more than 1 year. Among the 13 cases of recurrent bleeding after the surgery, the recurrence rate of bleeding after operation in the complete obliteration group was 23.81% (5/21), which was lower than that in the incomplete obliteration group with 40.00% (8/20), but there was no statistically significant difference ( χ2=1.240, P=0.265). Conclusion:EUS-guided coil implantation combined with glue injection has good secondary prevention value and safety for tumorous gastric fundal variceal bleeding, and is worthy of clinical promotion and application.

The mutual recognition of medical examination results is significant for improving the utilization efficiency of limited resources in large public hospitals,promoting the sharing of quality medical resources,alleviating the high costs and diffi-culties of healthcare for the public,reducing pressure on medical insurance funds,and enhancing the efficiency of fund utiliza-tion.This study reviews the research on mutual recognition of medical examination results in China,analyzing it from four as-pects:regulatory norms,platform construction,policy awareness,and performance distribution.It identifies research hotspots and directions related to mutual recognition,clarifies the challenges and key points in the implementation of relevant policies,and suggests future research directions,including strengthening theoretical research,improving empirical studies,and innovating re-search methods.

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.