Myocardial ischemia-reperfusion injury （MIRI） is a major complication following coronary revascularization. Studies indicate that its pathophysiological mechanisms of MIRI are closely associated with oxidative stress， iron overload， inflammatory responses， and lipid peroxidation. Oxidative stress refers to an imbalance in redox homeostasis under pathological conditions， characterized by the abnormal accumulation of reactive oxygen species （ROS）， which disrupts the dynamic balance between pro-oxidant systems and antioxidant defense networks. In recent years， traditional Chinese medicine （TCM） has demonstrated unique advantages in the prevention and treatment of MIRI due to its multi-target and multi-pathway antioxidant properties. Research reveals that TCM primarily exerts protective effects against oxidative stress-induced MIRI by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2 （Nrf2）， adenosine monophosphate-activated protein kinase （AMPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， nuclear factor kappa-B （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and protein kinase C beta Ⅱ/nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species （PKCβⅡ/NOX2/ROS）. This article reviews recent literature on TCM monomers， compound formulas， and their active components， which alleviate oxidative stress to prevent and treat MIRI by modulating the aforementioned signaling pathways. It summarizes a concise overview of the molecular mechanisms by which oxidative stress-related signaling pathways lead to MIRI， discusses how TCM regulates these pathways to reduce oxidative stress-induced MIRI， and explores clinical application prospects and research challenges， aiming to provide a theoretical reference for the research and clinical management of MIRI.

Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.
Humans ; Colorectal Neoplasms/etiology* ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease/genetics*

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans

Objective:To construct the clinical management model of a new type of smoke-purifying temperature-controlled moxibustion device based on the whole life cycle theory,and to explore its management effect on the new type of smoke-purifying temperature-controlled moxibustion device.Methods:The clinical management model of a new type of smoke purification and temperature-controlled moxibustion device was constructed based on the whole life cycle theory with the architecture of the basic layer,access layer,service layer,data layer and application layer.Eighteen new type of smoke purification and temperature-controlled moxibustion devices in clinical use in the Shijiazhuang Pingan Hospital from 2021 to 2022 were selected,and the conventional new smoke-purifying temperature-controlled moxibustion device management scheme(referred to as the conventional management mode)and the new smoke purification and temperature-controlled whole life cycle management model(referred to as the whole life cycle management mode)were adopted respectively according to different management modes.The management effect of the new smoke-purifying temperature-controlled moxibustion therapy device and the satisfaction of the relevant management personnel were compared between the two management modes.Results:The average scores of the management quality,temperature control effect,smoke control effect and moxa smoke purification effect of the new smoke purification moxibustion device using the whole life cycle management mode were(89.37±3.48)points,(93.53±4.26)points,(0.13±0.04)points and(0.11±0.03)points,respectively,the average scores of management quality and temperature control effect were higher those of the conventional management mode,and the average scores of smoke control effect and moxa smoke purification effect were lower than those of the conventional management mode,the difference was statistically significant(t=11.744,14.850,11.266,24.593,P<0.05).The satisfaction scores of engineers,medical staff and patients in the use of the new smoke purification and temperature control moxibustion therapy device adopting the whole life cycle management model were(95.69±6.62)points,(96.82±5.87)points and(95.34±5.14)points,respectively,which were higher than those of conventional management mode,the difference was statistically significant(t=9.334,19.549,33.694,P<0.05).Conclusion:The application of the clinical management model of a new type of smoke-purifying temperature-controlled moxibustion device based on the whole life cycle theory to new type of smoke purification and temperature control moxibustion therapy device can effectively improve the quality of equipment management,improve the temperature control effect of the new smoke and temperature control moxibustion device,and improve the satisfaction of relevant users.

Objective: This study aimed to explore the feasibility of functional evaluation of the lateral pterygoid muscle (LPM) using diffusion tensor imaging (DTI) in patients with temporomandibular joint disorders (TMDs). Materials and Methods: A total of 119 patients with TMD (23 male and 96 female; mean age ± standard deviation, 41 ± 15 years; 58 bilateral and 61 unilateral involvements for a total of 177 joints) and 20 healthy volunteers (9 male and 11 female;40 ± 13 years; 40 joints) were included in this prospective study. Based on DTI of the jaw in the resting state, the diffusion parameters, apparent diffusion coefficient (ADC), fractional anisotropy (FA), λ1, λ2, and λ3 of the superior and inferior heads of the LPM (SHLPM and IHLPM) were measured. Patients with TMD with normal disc position (ND), anterior disc displacement with reduction (ADWR), and anterior disc displacement without reduction (ADWOR) were compared. Results: Patients with TMD overall, and ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 in both the SHLPM and IHLPM than those in volunteers (p < 0.05 for all), whereas the ND subgroup only had significantly higher ADC and λ1 (p < 0.001). Meanwhile, significant differences in FA in the SHLPM and IHLPM were found between volunteers and ADWOR (p = 0.014 and p = 0.037, respectively). Among the three TMD subgroups, except for λ3 and FA in the ADWR subgroup, ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 and lower FA than those in the ND group (p < 0.050). There was no significant difference in diffusion variables between ADWR and ADWOR. In ADWOR, the osteoarthritis group had significantly higher λ3 and lower FA values in the IHLPM than those in the non-osteoarthritis group. Conclusion DTI successfully detected functional changes in the LPM in patients with TMD. The unsynchronized diffusivity changes in the LPM in different subgroups of TMD signified the possibility of using diffusion parameters as indicators to identify the severity of LPM hyperfunction at various stages of TMD.

Objective:To investigate the value of serum CD64, heparin binding protein (HBP) and procalcitonin (PCT) in early diagnosis of septic shock and its prognostic value.Methods:The clinical data of 40 children with sepsis (sepsis group) and 40 children with septic shock (septic shock group) in Children′s Hospital of Xuzhou Medical University from January 2018 to November 2021 were retrospectively analyzed. PCT was detected by chemiluminescence, HBP was detected by enzyme-linked immunosorbent assay, and CD 64 was detected by flow cytometry. All children were followed up within 1 month after discharge, and the occurrence of poor prognosis (including multiple organ failure and death) was recorded. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum CD 64, HBP and PCT for septic shock. Multivariate Logistic regression was used to analyze the independent risk factors for poor prognosis in children with septic shock. Results:The serum CD 64, HBP and PCT in septic shock group were significantly higher than those in sepsis group: 0.667 ± 0.120 vs. 0.501 ± 0.115, (116.46 ± 11.41) μg/L vs. (87.34 ± 23.49) μg/L and (11.41 ± 1.25) μg/L vs. (9.29 ± 1.31) μg/L respectively, and there were statistical differences ( P<0.05). ROC curve analysis result showed that the area under curve (AUC) of serum CD 64, HBP and PCT for predicting septic shock were 0.837, 0.894 and 0.880 respectively, and the optimal cut-off values were 0.586, 106.2 μg/L and 11.28 μg/L respectively; the AUC of serum CD 64, HBP and PCT combined detection for predicting septic shock was 0.914, with a sensitivity of 75.7%, specificity of 96.0%, and accuracy of 71.7%. According to the optimal cut-off values of serum CD 64, HBP and PCT, 40 children with septic shock were divided into high expression group and low expression group. The prognosis was good in 25 cases and bad in 15 cases. The incidence of poor prognosis in CD 64 high expression group, HBP high expression group and PCT high expression group was significantly higher than that in corresponding CD 64 low expression group, HBP low expression group and PCT low expression group: 56.52% (13/23) vs. 2/17, 10/17 vs. 21.74% (5/23) and 11/18 vs. 18.18% (4/22), and there was statistical difference ( P<0.01 or <0.05). Multivariate Logistics regression analysis result showed that serum CD64, HBP and PCT were independent risk factors for poor prognosis in children with septic shock ( OR = 0.818, 1.204 and 3.633; 95% CI 0.674 to 0.994, 1.022 to 1.419 and 1.090 to 12.108; P = 0.043, 0.026 and 0.036). Conclusions:The serum levels of CD 64, HBP and PCT in children with septic shock are significantly increased, which play an important role in the occurrence and development of septic shock, and which have predictive value for septic shock. The combined detection of the 3 indexes could be used to evaluate the prognosis, with a higher predictive value.

Objective To investigate the effect and its molecular mechanism of phosphoglycerate mutase 5 (PGAM5) mediated pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57 mouse models of liver IRI were established and randomly divided into the 6 h reperfusion (6 h group) and 12 h reperfusion (12 h group), and sham operation group (sham group) was established too, 10 rats in each group. The effect of IRI on the parameters in the liver tissues and serum samples was evaluated. The expression levels of PGAM5 and cysteinyl aspartate specific proteinase (Caspase)-1 in the liver tissues during IRI were quantitatively detected. The IRI models of liver cells were established (IRI group). The IRI models of liver cells were established after pretreatment with Caspase-1 inhibitor Z-YVAD-FMK (inhibitor group). The untreated AML12 cells were allocated into the control group. The effect of inhibiting Caspase-1 activity on pyroptosis was analyzed. AML12 cells were transfected with PGAM5 small interfering ribonucleic acid (siRNA) (siRNA group) and siRNA-negative control (siRNA-NC) (siRNA-NC group) by liposome 3000, and then IRI models of liver cells were established. The untreated AML12 cells were assigned into the control group. The effect of PGAM5 mediated pyroptosis on IRI of liver cells was assessed. Results In the 6 h and 12 h groups, partial liver cell edema, hepatic sinusoid narrowing, central vein congestion and occasional spot necrosis were observed in the mouse liver tissues, and these changes in the 12 h group were more aggravated than those in the 6 h group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 h and 12 h groups were higher than those in the sham group, and the values in the 12 h group were higher than those in the 6 h group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased in the 6 h and 12 h groups, and the values in the 12 h group were lower than those in the 6 h group. The relative expression levels of IL-1β messenger ribonucleic acid (mRNA) in the mouse liver tissues in the 6 h and 12 h groups were up-regulated, and the value in the 12 h group was lower than that in the 6 h group. The cell apoptosis rates in the liver tissues were significantly increased in the 6 h and 12 h groups, and the value in the 12 h group was remarkably lower than that in the 6 h group (P < 0.01-0.05). Compared with the sham group, the relative expression levels of PGAM5 mRNA and protein in the mouse liver tissues in the 6 h and 12 h groups were significantly up-regulated, and the values in the 12 h group were significantly higher than those in the 6 h group (P < 0.01-0.05). The protein expression levels of PGAM5 and Caspase-1 in the liver tissues were up-regulated in the 6 h and 12 h groups. Compared with the control group, the relative expression levels of NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1 and Gasdermin D (GSDMD) proteins were up-regulated and the fluorescence intensity of GSDMD was increased in the IRI group. Compared with the IRI group, the relative expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated and the fluorescence intensity of GSDMD was considerably decreased in the inhibitor group (P < 0.01-0.05). Compared with the control group, the cell survival rate was significantly decreased, and the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly up-regulated in the siRNA-NC group (P < 0.01-0.05). Compared with the siRNA-NC group, the cell survival rate was remarkably increased, whereas the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated in the siRNA group (P < 0.01-0.05). Conclusions PGAM5 may aggravate the liver IRI in mouse models probably by mediating pyroptosis via PGAM5/Caspase-1/GSDMD signaling pathway and aggravating liver cell injury.

Objective:To explore the application and value of metagenomic next-generation sequencing (mNGS) in refractory infection after organ transplantation.Methods:A case report discussed about a patient with lumbar spine infection after kidney transplantation and the relevant literature was reviewed. The recipient was a 63-year-old man with low back pain after kidney transplantation. Lumbar spine magnetic resonance imaging showed lumbar spine infection. Multiple operations plus antibacterial and antituberculosis treatments were ineffective. Before and after treatment, numerous tests of traditional pathogenic microorganisms failed to detect any positive bacteria.Results:The detection of lumbar secretion by mNGS suggested aspergillus infection. The symptoms improved after dosing of voriconazole.Conclusions:The incidence of fungal infection of lumbar spine is low. The imaging manifestations are non-typical so that it is easy to misdiagnose. mNGS helps to timely diagnose and guide treatment. With a review of the literature, mNGS has some application value for some difficult and rare infectious diseases.