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*

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Objective To establish and optimize an animal model of atopic march(AM),skin and lung tissue sensitization under single or combined modeling of ovalbumins(OVA)and calcipotriol(MC903)was compared.Methods 40 SPF BALB/c mice aged 6～8 weeks were randomly divided into a control group,model group A,model group B and model group C.The 3 of AM models were established with MC903,MC903+OVA and OVA,respectively,through skin sensitization(twice)and respiratory sensitization(once).Skin sensitization severity scoring system,immunohistochemistry,and enzyme-linked adsorption assay were used to compare skin lesion morphology,skin or lung histopathology,and immunophenotype.Results Compared to OVA or MC903 modeling alone,MC903+OVA modeled mice showed more significant changes in skin morphology,a higher score for skin sensitization severity,more severe skin and airway inflammatory cell infiltration,and more significant changes in the expression of the related inflammatory factors thymic stromal lymphopoietin(TSLP),interleukin 4(IL-4),IL-13 and IL-10(P＜0.05).Conclusions An AM animal model optimized by MC903 combined with OVA was successfully constructed that provides a good method ological basis for AM mechanism research.

Objective To investigate the stability of the two kinds of rat models of chronic renal failure,aiming to provide a basis for establishing a feasible and stable animal model of chronic renal failure.Methods The rat model of chronic renal failure was established by unilateral nephrectomy+adenine gavage+high-phosphorus diet and high-phosphorus+adenine diet,respectively.Erythrocyte and hemoglobin levels,serum urea and creatinine levels were detected at the end of modeling and 6 weeks after modeling,and histopathological examinations of kidney and bone were performed.The tubulointerstitial fibrosis index(TBI)and the percentage of collagen fiber area in renal tissue were calculated.Results At the end of modeling,compared with the normal group,the erythrocyte and hemoglobin in the model group 1(unilateral nephrectomy+adenine gavage+high-phosphorus)were significantly decreased(P＜0.05),the serum urea and creatinine were significantly increased(P＜0.05),TBI and the percentage of collagen fiber area in kidney tissue were slightly increased(P＜0.05),and the femur lesions were significantly increased.6 weeks after modeling,compared with the normal group,the erythrocyte and hemoglobin in model group 1 showed a slight decrease(P＜0.05),while there was no significant difference in serum urea and creatinine levels.The TBI and collagen fiber area percentage in renal tissue showed a slight increase(P＜0.05),and there was no obvious change in femoral lesions.At the end of the modeling,the erythrocyte and hemoglobin in the model group 2(high-phosphorus+adenine diet)were significantly decreased compared with the normal group(P＜0.05),serum urea,creatinine,TBI and the percentage of collagen fiber area in kidney tissue were significantly increased(P＜0.05),and the lesions of femur were obvious.6 weeks after the end of modeling,compared with the normal group,the erythrocyte and hemoglobin in the model group 2 were significantly decreased(P＜0.05),serum urea,creatinine,TBI and the percentage of collagen fiber area in kidney tissue were significantly increased(P＜0.05),and the lesions of femur were obvious.6 weeks after the end of modeling,compared with the model group 1,the erythrocyte and hemoglobin in the model group 2 were significantly decreased(P＜0.05),while the serum urea,creatinine,TBI,the collagen fiber area percentage of kidney tissue and femur lesions were significantly increased(P＜0.05).Conclusions A stable rat model of chronic renal failure can be established by high phosphorus+adenine diet.

The development,progression,and curative efficacy of head and neck squamous cell carcinoma(HNSCC)are influenced by complex interactions between epithelial and immune cells.Nevertheless,the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood.Cuproptosis,a form of programmed cell death that is dependent on copper,has been implicated in cancer pathogenesis.However,the understanding of cuproptosis in the context of HNSCC remains limited.In this study,we have discovered that cuproptosis-related long non-coding RNAs(CRLs)known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator(PLAU)by competitively binding to miR-193b-3p in HNSCC.The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation,migration,and invasion in HNSCC.Moreover,the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR,predominantly expressed on macrophages,thereby influencing the abnormal epithelial-immune interactome in HNSCC.Notably,the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor(EGFR)and cyclin-dependent kinase(CDK4/6)for the treatment of HNSCC.

Objective To establish and optimize an animal model of atopic march(AM),skin and lung tissue sensitization under single or combined modeling of ovalbumins(OVA)and calcipotriol(MC903)was compared.Methods 40 SPF BALB/c mice aged 6～8 weeks were randomly divided into a control group,model group A,model group B and model group C.The 3 of AM models were established with MC903,MC903+OVA and OVA,respectively,through skin sensitization(twice)and respiratory sensitization(once).Skin sensitization severity scoring system,immunohistochemistry,and enzyme-linked adsorption assay were used to compare skin lesion morphology,skin or lung histopathology,and immunophenotype.Results Compared to OVA or MC903 modeling alone,MC903+OVA modeled mice showed more significant changes in skin morphology,a higher score for skin sensitization severity,more severe skin and airway inflammatory cell infiltration,and more significant changes in the expression of the related inflammatory factors thymic stromal lymphopoietin(TSLP),interleukin 4(IL-4),IL-13 and IL-10(P＜0.05).Conclusions An AM animal model optimized by MC903 combined with OVA was successfully constructed that provides a good method ological basis for AM mechanism research.

Therapeutic plasma exchange can quickly remove the pathogenic macromolecular sub-stance in vivo,and its application is gradually expanded. With the maturity and development of plasma ex-change technology,the effect of high volume plasma exchange in liver failure,thrombotic thrombocytopenic purpura,sepsis and other diseases is obvious. But there is still controversy about the wide use of high volume plasma exchange in ICU. This review aimed to discuss the use of high volume plasma exchange in patients with critical diseases.

Objective To compare clinical efficacy between the situ secondary spleen pedicle amputation in laparoscopic splenectomy and open splenectomy for traumatic spleen rupture.Methods From January 2013 to June 2015 a total of 70 patients with splenic rupture undergoing splenectomy were devided into laparoscopic surgery (35 cases) and open surgery (35 cases) group.Clinical data included total intraoperative blood loss,the time spent on splenic artery ligation,total operation time,postoperative drainage volume,postoperative hemoglobin,platelet and albumin levels,time of anal exsufflation,hospital stay and postoperative complications.Results The average operation time in the OS group was shorter than that in LS group (P ＜ 0.05).However,LS group was better than the OS group in splenic artery ligation time,postoperative drainage volume,anus aerofluxus time,postoperative platelet count,postoperative albumin recovery,hospital stay and postoperative complications (all P ＜ 0.05).Conclusions The laparoscopic splenectomy by the amputation of in situ secondary spleen pedicle for traumatic spleen rupture has the advantages of a rapid recovery and a low postoperative complication.

Objective To investigate the protective effects and mechanism of insulin(INS) on brain in septic rats,and explore the possible role of uncoupling protein 2 (UCP2) in these effects.Methods Fifty male specific pathogen free(SPF) Sprague-Dawley rats were randomly divided into normal control (CN) group(n=10),lipopolysaccharide(LPS) group(n=20) and INS group (n=20) according to random number table.The septic rat model was established through an intraperitoneal injection of 15 mg/kg LPS of gram-negative bacteria.The rats in the INS group received a 1 U/kg INS injection subcutaneously 30 minutes before the injection of LPS,and the rats in the CN group were given equivalent 9 g/L saline in the same way.Eight rats in each group were killed,and their cerebral cortex were collected after the injection of LPS for 24 h.Pathological change of cerebral cortex was detected by Hematoxylin-Eosin(HE) staining.The cerebral cortex mitochondia were extracted for detecting the levels of reactive oxygen species(ROS),malondialdehyde (MDA) and the activity of superoxide dismutase(SOD).Neuronal apoptosis was detected by terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining.UCP2 mRNA expression was detected by quantitative real-time(RT)-PCR.Apoptosis-associated protein B lymphocyte tumor-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved cysteinyl aspartate specific protease(cleaved Caspase-9) and UCP2 protein expression were determined by Western blot.Results (1)Compared with the CN group,obvious abnormal pathological change was revealed by HE staining in cerebral cortex of rats in the LPS group and the INS group,but the pathological change was attenuated in the INS group compared with the LPS group.(2)Compared with the CN group,the levels of mitochondrial ROS[(210.01±14.09) RFU vs.(49.06±7.28) RFU] and MDA[(2.19±0.18) nmol/mg pro vs.(1.25±0.11)nmol/mg pro]in the LPS group significantly increased,whereas SOD activity significantly decreased [(238.49±35.60) U/g pro vs.(446.66±24.90)U/g pro],and the differences were significant(all P<0.05).Compared with the LPS group,the levels of ROS [(152.69±15.83) RFU vs.(210.01±14.09) RFU] and MDA[(1.55±0.14) nmol/mg pro vs.(2.19±0.18) nmol/mg pro] in the INS group decreased,while SOD activity increased[(327.8±23.26) U/g pro vs.(238.49± 35.60) U/g pro],and the differences were significant(all P<0.05).(3)Compared with the CN group,the neuronal apoptosis index of cortex in the LPS group was elevated[(54.16±6.84)% vs.(5.45±1.43)%],while the expression of Bcl-2 decreased (627±0.018 vs.0.739±0.020),but the expressions of Bax(0.768±0.019 vs.0.520±0.010) and cleaved Caspase-9(0.739±0.016 vs.0.467±0.030) increased,and the differences were significant(all P<0.05).Compared with the LPS group,the neuronal apoptosis index of cortex in the INS group decreased [(33.30±3.07)% vs.(54.16±6.84)%],but the Bcl-2 expression increased (0.743±0.022 vs.0.627±0.018),and Bax (0.687±0.034 vs.0.768±0.019) and cleaved Caspase-9(0.551±0.013 vs.0.739±0.016) were reduced,and the differences were significant (all P<0.05).(4)Compared with the CN group,the mRNA (2.248±0.155 vs.1.000±0.100) and protein expression of UCP2 (0.659±0.016 vs.0.599±0.018) were elevated in the LPS group.Compared with the LPS group,the UCP2 mRNA (2.944±0.117 vs.2.248±0.155) and UCP2 protein (0.719±0.018 vs.0.659±0.016) increased,and the differences were significant(all P<0.05).Conclusions INS can protect the brain of septic rats through alleviating mitochondrial oxidative stress and inhibiting the mitochondrial-initiated apoptotic pathway to reduce neuronal apoptosis.INS upregulates UCP2 expression in the brain of septic rats,which may play a role in the protective effects mentioned above.