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*

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

OBJECTIVE: To investigate the clinical features, treatment and prognosis of extranodal NK/T-cell lymphoma, nasal type (ENKTL) with skin lesions as initial symptom. METHODS: The clinical data of 11 ENKTL patients with skin lesions as initial symptom were retrospectively analyzed from August 2016 to January 2023 in Wuhan First Hospital and Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. RESULTS: Among the 11 patients, there were 6 males and 5 females, with a median age of 50(32-80) years. All patients had different forms of skin lesions as initial clinical symptom, including rash, ulcerative mass, painful skin nodules, infiltrating macula, etc. Most of the skin lesions were involved in the limbs and trunk but also appeared in the lower limbs alone. Five patients had hemophagocytic lymphohistiocytosis (HLH) at initial diagnosis, and 8 patients had B symptoms. All patients were diagnosed with advanced clinical staging (Lugano staging IV), and classified as high risk (PINK-E score ≥3). Immunohistochemical examination revealed that the positive rates of CD56 and EBER were both 100%, and the median Ki-67 index was 75%(50%-80%). Plasma EBV-DNA tests were all positive (≥5×10² copies/ml). Most of the induction chemotherapy regimens were combination chemotherapy (MESA, p-Gemox, SMILE) containing pegaspargase or L-asparaginase, or combined with PD-1 monoclonal immunotherapy, or HLH regimens (HLH-04 regimen, L-DEP). The median follow-up time and overall survival (OS) time were both 4.5(0.5-27) months. During the follow-up period, all 8 patients who did not receive autologous hematopoietic stem cell transplantation (ASCT) died, most of whom died of rapid disease progression. Three patients received ASCT, one died of central nervous system recurrence after transplantation, and two survived. The OS of three patients who underwent ASCT was 21, 27, and 19 months, and PFS was 11, 20, and 13 months, respectively. The plasma EBV-DNA copy number was monitored irregularly after transplantation, and the load of EBV was consistent with the changes of the disease. CONCLUSIONS Early clinical symptoms of ENKTL patients with skin lesions as initial symptom are more atypical, and early diagnosis is particularly difficult. The disease progresses rapidly and the prognosis is poor. There is still no uniform standard for the best treatment strategy. The survival of patients can be significantly prolonged by applying ASCT as soon as possible after complete remission obtained by high-dose induction chemotherapy.
Humans ; Male ; Female ; Lymphoma, Extranodal NK-T-Cell/diagnosis* ; Middle Aged ; Adult ; Retrospective Studies ; Aged ; Prognosis ; Aged, 80 and over

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Objective:To investigate the vaccination status, characteristics and prognosis of patients suffering from a combination of COVID-19 and chronic lymphocytic anemia (CLL) in China.Methods:Clinical data of 328 patients with chronic lymphocytic leukemia (CLL) who were first diagnosed with COVID-19 and treated in the Department of Hematology of Jiangsu Provincial People’s Hospital between November 2022 and February 2023 were retrospectively analyzed. Univariate and multivariate analysis of data of patients with severe/critical COVID-19 were conducted by applying the binary logistic regression model.Results:The median age of the CLL patients was 60 (24-87) years. 23.5% (77/328) of these patients suffered from severe/critical COVID-19 infection. Univariate analysis of the data demonstrated that a combination of factors including age >67 years ( OR=2.15, 95% CI 1.24- 3.73, P=0.006), diabetes ( OR=2.09, 95% CI 1.05-4.20, P=0.037), chronic hepatitis B ( OR=2.91, 95% CI 1.30-6.51, P=0.010), CLL progressive ( OR=3.79, 95% CI 1.57-9.15, P=0.003) and CD20 antibody-based treatments within three months prior to the COVID-19 infection ( OR=2.79, 95% CI 1.35-5.77, P=0.006) were the risk factors for severe/critical COVID-19. According to the multivariate analysis, CLL progressive ( OR=2.98, 95% CI 1.10-8.10, P=0.033) was an independent risk factor for severe/critical COVID-19 and administration of the BTK (Bruton tyrosine kinase) inhibitor monotherapy might exert a protective effect and influence a positive outcome of the COVID-19 infection ( OR=0.38, 95% CI 0.16-0.90, P=0.028). Among the 242 patients who were followed up until October 2023, 9.1% (22/242) had multiple subsequent COVID-19 infections (≥3), and 2.1% (5/242) had persistent COVID-19 infections (patients with persistent positive test for the SARS-CoV-2 antigen testing until missing follow-up for any reason). The peak value of the anti-SARS-CoV-2-IgG titres was observed between three and four months post symptom onset (median: 3.511 S/CO vs 1.047 S/CO, P<0.05). The levels of immunoglobulin A gradually decreased following infection with COVID-19, and its trough levels were attained between two to four weeks post infection (median: 0.30 g/L vs 0.74 g/L, P<0.05). According to this study the mortality of patients suffering from a combination of COVID-19 infection and CLL was 2.7% (9/328), and the main reason for their death was respiratory failure and heart failure. Conclusions:A low rate of COVID-19 vaccination and a high rate of severe/critical COVID-19 infection was observed in the CLL patients. CLL progressive was associated with severe/critical COVID-19. Anti-CD20-based treatments received within the past three months might be a risk factor for exacerbation of COVID-19 infection, whereas a monotherapy with BTK inhibitors exert a protective effect and improve outcome of COVID-19 infection.

Objective : To explore the effect of esketamine on anxiety-depressive-like behavior in mice and its rela- tionship with inflammation． Methods : SPF grade healthy adult male C57BL/6J mice，weighing 20 －24 g，were used in the exprement．The random number table method was used to divide into 5 groups (n = 8) : control group ( Con group) ，esketamine group (ESK group) ，model group ( LPS group) ，model + esketamine prevention group (LPS + ESK1 group) and model + esketamine treatment group ( LPS + ESK2 group) ．An inflammation-induced anxiety-depression model was prepared by intraperitoneal injection of LPS 0. 83 mg / kg．The ESK group was injec- ted with esketamine 10 mg / kg ; LPS group was injected with LPS 0. 83 mg / kg ; LPS + ESK1 group was injected with LPS 0. 83 mg / kg before 24 hours intraperitoneal injection of esketamine 10 mg / kg ; and the LPS + ESK2 group was injected with LPS 0. 83 mg / kg and 30 minutes later with esketamine 10 mg / kg．24 h after intraperitoneal injec- tion of LPS，the anxiety-depression-like behaviors of mice were measured using behavioral experiments．At the end of behavioral experiments，the spleen was taken immediately ; hippocampal tissues were taken and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-1 β (IL-1 β) ，tumor necrosis factor al- pha (TNF-α) and interleukin 6 (IL-6) and neuronal pathological changes in hippocampal tissues were observed by HE staining. Results : Compared with the Con group，mice in the LPS group showed increased anxiety and depres- sion-like behavior (P＜0. 05) ，increased spleen weight / body weight (P ＜0. 05 ) ，increased hippocampal tissue concentrations of IL-1 β , TNF-α and IL-6 (P＜0. 05) ，and increased neuronal degeneration necrosis，there was no statistically significant difference in these indicators in the ESK group compared with the Con group．Compared with the LPS group，mice in the LPS + ESK1 and LPS + ESK2 groups showed reduced anxiety-depression-like behavior (P＜0. 05) ，decreased splenic weight / body weight (P ＜0. 05) ，hippocampal tissue IL-1 β , TNF-α , IL- 6 con- centrations were reduced (P＜0. 05) ，and neuronal degeneration necrosis was reduced．Compared with the LPS + ESK1 group，the LPS + ESK2 group showed an increase in the distance travelled in the central area of the open field experiment and the distance into the open arm of the elevated cross maze experiment (P＜0. 05) ，a decrease in IL-6 and TNF-α concentrations (P＜0. 05) ，and a reduction in the degree of neuronal damage． Conclusion Esketamine ameliorates LPS-induced anxiety-depression-like behavior and neuronal damage in mice by a mechanism that may be related to reduced inflammation.

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.
Humans ; Dentistry, Operative ; Consensus ; Endodontics ; Root Canal Therapy ; Dental Care

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.
Humans ; Middle Aged ; Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Biopsy ; Disease Progression

【Objective】 To study the changes of platelet components(PC), apheresis platelets (AP) and pooled platelet concentrates (PPC) production of 19 provincial blood centers before and during the COVID-19 epidemic. 【Methods】 The data related to the collection of AP and the preparation of PPC from 2016 to 2021 of 19 provincial blood centers was collected. The production of PC, AP and PPC during the four years before the epidemic (i.e. 2016-2019) and during the COVID-19 epidemic (i.e. 2020 and 2021) were calculated respectively, and the change of production was analyzed. 【Results】 The total production of PC in 19 blood centers steadily increased from 2016 to 2019, with a decrease of 4.16% in 2020 and an increase of 15.60% in 2021, exceeding the output before the COVID-19 epidemic. In 2020, the production of PC of 42.11% (8/19) blood centers decreased compared with 2019, while 94.74% (18/19) in 2021 increased compared with 2020. The changes of AP output was basically consistent with the trend of PC. The total production of PPC in 2017 and 2018 both doubled compared to the previous year, while decreased by 67.98% in 2019, increased by 30.38% in 2020 and decreased by 27.08% in 2021. 【Conclusion】 The total production of PC kept increasing steadily between 2016 and 2019, but decreased in 2020 under the COVID-19 epidemic, with some blood centers being significantly affected. In 2021, with the strong support from government and various measures by blood centers, the total production of PC increased.