The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Sepsis is a lethal condition resulting from the host's dysregulated response, involving complex pathophysiological mechanisms, including the host's biphasic immune response and metabolic disturbances. Diagnosing and treating sepsis remain formidable challenges, with the absence of definitive biomarkers and effective therapeutic interventions to date. Animal models of sepsis are pivotal in unraveling the disease's pathogenesis and identifying potential treatments, playing a crucial role in enhancing our comprehension of its intrinsic nature. However, there is no animal model that can comprehensively and accurately simulate the complex pathophysiological process of human sepsis. This review discusses the widely used sepsis animal models, exploring their advantages and limitations in terms of pathogenesis, inflammatory response, pathophysiological changes, and organ dysfunction. It summarizes the application scenarios and latest research advancements of these models and provides an outlook on potential future improvements.
Sepsis/physiopathology* ; Animals ; Disease Models, Animal ; Humans

Objective To explore the network structure of anxiety,depression and sleep among individuals under long-term high-altitude exposure.Methods A total of 303 subjects who had resided at high altitudes for more than 6 months on end were selected.The insomnia severity index(ISI),patient health questionnaire(PHQ-9),and generalized anxiety disorder scale(GAD-7)were employed to assess insomnia,depression and anxiety before network analysis was conducted to identify the central and bridge nodes in the symptom network.Results The incidence of moderate or severe depression,anxiety and insomnia were 38.9％[95％confidence interval(CI):33.4％-44.5％],23.1％(95％CI:18.3％-27.9％),and 18.5％(95％CI:14.1％-22.9％),respectively."Noticeability of sleep problems by others"had the highest expected influence centrality,followed by"sleep maintenance""uncontrollable worry""restlessness"and"sleep problems".Five bridge symptoms were identified:"sad mood""sleep problems""restlessness""feeling afraid"and"trouble relaxing".Conclusion Sleep-related symptoms play a crucial role in the overall network structure,serving as both central and bridge nodes.Additionally,the"feeling down or depressed"acts as a bridge node and holds importance in the comorbidity network of anxiety and depression.Targeting these key symptoms through intervention and prevention strategies may improve the psychological well-being of individuals with long-term residence in high-altitude regions.

Objective:To investigate the correlation between the expression level of serum exosome miR-29C and postoperative cognitive dysfunction (POCD) in elderly patients undergoing surgery.Methods:A total of 119 elderly patients who underwent elective spinal surgery in the Second Hospital of Shanxi Medical University from January 2021 to January 2022 were selected and scored on the Montreal Cognitive Assessment (MoCA) Scale 1 day before surgery and 1, 7 and 21 days after surgery. The selected patients were divided into POCD group (51 cases) and non-POCD group (68 cases) according to whether the MoCA Scale score decreased ≥2 points 1 day before surgery and 1 day after surgery. S100-β, neuron-specific enolase (NSE) levels and serum exosome miR-29C expression levels were detected and analyzed in all patients 1 day before and 1 day after surgery. Pearson correlation analysis showed the correlation between MoCA Scale score and S100-β, NSE and miR-29C. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of S100-β, NSE and miR-29C for POCD occurrence in elderly patients undergoing surgery.Results:The score of MoCA Scale in POCD group were significantly decreased 1, 7 and 21 days after surgery compared with 1 day before surgery (all P<0.05), while the score of MoCA Scale in non-POCD group were significantly decreased only 1 day after surgery compared with 1 day before surgery ( P<0.05). The levels of S100-β and NSE and the expression level of serum exosome miR-29C in 2 groups were significantly increased 1 day after surgery compared with 1 day before surgery (all P<0.05). Moreover, the levels of S100-β and NSE and the expression level of serum exosome miR-29C in POCD group were significantly higher than those in non-POCD group 1 day after surgery (all P<0.05). There was a negative correlation between the MoCA Scale score and the expression level of serum exosome miR-29C 1 day after surgery in the POCD group ( P<0.05). ROC curve analysis showed that the expression levels of NSE, S100-β and exosome miR-29C 1 day after surgery predicted the risk of POCD in elderly surgical patients with area under the curve (AUC) of 0.891, 0.908 and 0.918, respectively. Conclusions:The occurrence of POCD in elderly patients with surgery is related to the increase of the expression level of serum exosome miR-29C, and the expression level of serum exosome miR-29C is negatively correlated with MoCA Scale score. Early monitoring of the miR-29C expression level can provide a basis for the occurrence and development of postoperative POCD in elderly patients, disease diagnosis and clinical intervention.

Objective:To investigate the effects of Porphyromonas gingivalis ( P. gingivalis) fimbrillin (FimA) on the progression of esophageal squamous cell carcinoma (ESCC). Methods:Wild-type P. gingivalis and fimA gene-deleted P. gingivalis ( fimA-/-P. gingivalis) were used to infect ESCC cells after morphology and PCR identification. Immunofluorescence, CCK-8 and Transwell chamber were used to detect the effects of FimA on the infectivity of P. gingivalis and it influences on cell invasion, proliferation and migration. Western blot was used to detect pSmad2/3 changes. The growth of tumor was detected in a nude mouse model bearing subcutaneous tumor. Results:Deletion of FimA might reduce the interbacterial adhesion of P. gingivalis. Compared with wild-type P. gingivalis, less fimA-/-P. gingivalis could infect NE6-T cells. Moreover, the proliferation, migration and invasion of NE6-T and KYSE30 cells as well as the activation of pSmad2/3 induced by P. gingivalis were inhibited after deletion of FimA. The growth of KYSE30 infected by fimA-/-P. gingivalis in nude mice was significantly slower than that of the wild-type P. gingivalis group. Conclusions:FimA mediated the effects of P. gingivalis on promoting the evolution of ESCC and was a potential target molecule to block the tumor-promoting effect of P. gingivalis.

Objective:To explore the feasibility of emergency video call system in remote guidance of non-medical volunteers to implement single person cardiopulmonary resuscitation (CPR).Methods:A scenario of sudden cardiac arrest with a bystander in a public place was created at Clinical Skill Training Center. 60 non-medical volunteers were randomly (ramdom number) divided into video group ( n = 40) and audio group ( n = 20). Volunteers in video group were remote instructed with the smart phone application software (APP) of Emergency Video Call System to implement CPR; the audio group receives remote voice guidance for CPR with a smart phone. The pressing depth, pressing frequency, volume of ventilation and the time of the first compression were compared between the two groups. The video group was divided into 5 subgroups to compare the cardiopulmonary resuscitation effect of 5 different models of smart phones. Ten CPR cycles were observed in each group. Results:the accuracy rate of pressing position in the video group was significantly higher than that in the audio group (91.5% vs 71.35%, P < 0.05); the proportion of pressing depth in the range of 5-6 cm was significantly higher than that in the audio group (62.79% vs. 44.73%, P < 0.05); the average pressing frequency was 100-120 times / min (70% vs. 52%, P < 0.05); the ventilation volume was 500-600 mL / time (18.25% vs. 10.75%, P < 0.05); The proportion of ventilation volume greater than 500ml / min was higher than that of audio group (64.88% vs. 43%, P < 0.05). The first pressing time was longer in the video group than in the audio group (131 s vs. 106 s, P < 0.05). There was no significant difference in the first ventilation time between the two groups (148 s vs. 144 s, P > 0.05). The total pressing pause time in video group was less than that in audio group (122.4 s vs. 164.2 s, P < 0.05). There was no significant difference in the above indicators among the five different models of smart phones in the video group ( P > 0.05). Conclusions:compared with audio remote guidance, video emergency system has obvious advantages in the accuracy of pressing position, pressing depth, pressing frequency, ventilation volume and pressing pause time, but the first pressing time is slightly longer than that of audio group. The popularization and application of the video system is supposed to improve the CPR quality and recovery success rate of non-medical personnel, and facilitated to encourage the first witness to implement CPR.

Objective: To explore the related factors of subependymal hemorrhage (SEH) and cerebral hemodynamic changes. Methods: From October 2012 to October 2017, 200 cases of children with subependymal hemorrhage diagnosed by ultrasound in our department of pediatrics were selected as the observation group , and a total of 150 children who were admitted to the Department of Pediatrics in the same period due to craniocerebral diseases and other serious diseases were selected as control group. The independent risk factors of the children in the observation group were analyzed, and the difference of the maximum systolic blood flow velocity (SV), the diastolic maximum flow velocity (DV), the systolic and diastolic velocity ratio (S/D), the resistance index (RI), and the pulsatile index (PI) were compared between the two groups. Results: Neonatal asphyxia, preterm birth, acidosis, neonatal respiratory distress syndrome (NRDS), patent ductus arteriosus and coagulation dysfunction were independent risk factors for subependymal hemorrhage. The bleeding side SV and DV of the observation group were higher than those of the control group, with statistically significant difference (P<0.001). In the observation group, the bleeding side SV and DV were higher than those of the healthy side, with statistically significant difference (P<0.001). There was no significant difference in bleeding side SV, DV, S/D, RI and PI in 110 cases of single side ependymal hemorrhage (P>0.05). Conclusions Children with ependymal hemorrhage can observe the hemodynamic indexes of anterior cerebral artery (ACA) dynamically by craniocerebral ultrasound, and judge the therapeutic effect by evaluating the systolic and diastolic blood flow velocity, so as to prevent the further aggravation of subependymal hemorrhage

Objective: Buyinqianzheng Formula (BYQZF) is clinically employed in traditional Chinese medicine to treat Parkinson's disease (PD) by improving mitochondrial dysfunction. However, the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown. Therefore, we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway. Methods: Cell survival rates were assessed by Cell Counting Kit-8 assay. Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR. Protein expression levels of PINK1, PINK1-Ser228, Parkin, Parkin-Ser65, Drp1, and Drp1-Ser637 were examined by western blotting. PINK1, Parkin, and Mito-Tracker? Red CMXRos (MTR) were stained by triple-labeled immunofluorescence, and observed under laser confocal microscopy. Results: Cell survival rate, mitochondrial form factor, mean length and number of mitochondrial network branches, mitochondrial activity, mRNA expression levels of PINK1 and Parkin, and protein expression levels of PINK1, Parkin, and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium (MPP+) intervention. In contrast, Pearson's correlation coefficients between PINK1 and Parkin, and between Parkin and MTR, as well as protein expression levels of PINK1-Ser228, Parkin-Ser65, and Drp1 increased significantly after MPP+intervention. Treatment with BYQZF increased cell survival rate, mitochondrial form factor, mean length and number of mitochondrial network branches, mitochondrial activity, mRNA expression levels of PINK1 and Parkin, and expression of PINK1, Parkin, and Drp1-Ser637 proteins. Pearson's correlation coefficients between PINK1 and Parkin, and between Parkin and MTR, as well as protein expression levels of PINK1-Ser228, Parkin-Ser65, and Drp1 decreased after BYQZF treatment. Conclusion: These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model, and the mechanism is related to the PINK1/Parkin pathway.

Objective To investigate the expression of FoxO1 gene in idiopathic congenital talipes equinovarus(ICTEV) in Xinjiang Uigur and its correlastion with deformity degree of ICTEV.Methods The FoxO1 protein expression level of foot muscle tissues in 51 Uigur children cases of ICTEV and 25 Uigur normal children were detected by Western blot,the relative expression level of FoxO1 mRNA in different deformity degrees of ICTEV was detected by using real time fluorescence quantitative PCR.Results The Western Blot detection results showed that the expression level of FoxO1 protein in ICTEV children patients was (0.52 ± 0.03),which was lower than(1.61 ± 0.15) in normal children,the difference was statistically significant (P =0.017).The real time fluorescence quantitative PCR detection showed that the relative expression level of FoxO1 mRNA in the Dimeglio type Ⅱ,Ⅲ and Ⅳ were 1.02±0.24,0.67±0.15 and 0.24±0.19 respectively.There was negative correlation between the deformity degree of ICTEV and FoxO1 mRNA relative expression level.Conclusion The transcription level of FoxO1 gene is gradually decreased with the deformity degree aggravation of ICTEV,suggesting that the FoxO1 gene may involve in the whole onset process of Uigur ICTEV.