Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

PURPOSE: To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis. METHODS: We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included. EXCLUSION CRITERIA: pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA. RESULTS: Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24 h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score. CONCLUSIONS In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.
Humans ; Retrospective Studies ; Female ; Male ; Middle Aged ; Sepsis/mortality* ; Aged ; Adult ; Continuous Renal Replacement Therapy/methods* ; Intraabdominal Infections/mortality* ; APACHE ; Organ Dysfunction Scores ; Intensive Care Units ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
Humans ; Lung Neoplasms/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Chromatin Assembly Factor-1/metabolism* ; Animals ; Mice ; Male ; Female

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective To analyze the correlation between venous thromboembolism(VTE)and traditional Chinese medicine(TCM)constitution types in elderly frail patients.Methods A retrospective study was conducted on 1 428 elderly frail patients admitted to the Second Comprehensive Department of Guangdong Provincial Hospital of Chinese Medicine from January 2019 to June 2023.Patients were divided into a venous thrombsis(VT)group(n=187)and a non-VT group(n=1 241)based on VTE occurrence.Baseline data,including age distribution,Padua scores,Wells scores,and TCM constitution types,were compared between the two groups.Multivariate logistic regression analysis was performed to identify factors for influencing VTE in elderly frail patients.Results(1)Compared with the non-VT group,the VT group had significantly higher total hospitalization costs,length of stay,age,Fried scores,Padua scores,and Wells scores,with statistically significance(P＜0.001).(2)Compared with the non-VT group,the VT group had a higher proportion of high VTE-risk individuals and those with Wells scores of 2 points,with statistically significance(P＜0.001).(3)The age distribution of VTE patients showed an increasing trend in the age groups of 60-69,70-79,80-89,and ≥90-year-old,with a significant difference compared to the non-VT group(P＜0.001).(4)The VT group had a higher proportion of qi-deficiency,blood-stasis,and qi-depression constitutions than the non-VT group(P＜0.05 or P＜0.001).(5)Multivariate logistic regression analysis(after adjusting age,gender,frailty,and other scores)showed that qi-deficiency and yang-deficiency constitutions were non-susceptible,while damp-heat,blood-stasis,and qi-depression constitutions were susceptible to VTE in elderly frail patients(P＜0.05 or P＜0.01).Conclusion VTE in elderly frail patients is significantly correlated with TCM constitution types.Deviated constitutions are characteristic of TCM constitution types in elderly frail patients,and damp-heat,blood-stasis,and qi-depression constitutions are risk factors for VTE in this population.

The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurode-generative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for in-flammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effec-tively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC50)of 0.478 μM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

OBJECTIVE:At present,there are many reports on the related factors associated with the incidence of cervical spine instability in patients with rheumatoid arthritis,but there are problems such as small sample size and many confounding factors,and the research results of various studies on the same related factors are also different.This article analyzed the factors related to cervical spine instability in patients with rheumatoid arthritis by means of a systematic review. METHODS:Articles related to cervical spine instability in patients with rheumatoid arthritis were collected by searching both Chinese and English databases until March 2023.The outcome of cervical spine instability in patients with rheumatoid arthritis was used as the grouping criterion to abstract basic information,baseline patient characteristics,laboratory-related tests,medication use,and other relevant risk factors.Meta-analysis was done using Stata 14.0 software. RESULTS:(1)Sixteen relevant studies,all of moderate or above quality,were included,including seven studies with case-control studies and nine with cross-sectional studies.The overall incidence of cervical spine instability in patients with rheumatoid arthritis was 43.08%.(2)Meta-analysis showed:Related risk factors included female(OR=0.60,95%CI:0.44-0.82,P=0.002);age at disease onset(SMD=-0.52,95%CI:-0.86 to-0.18,P=0.003);duration of disease(SMD=0.58,95%CI:0.14-1.02,P=0.01);body mass index(OR=0.74,95%CI:0.63-0.88,P=0.001);rheumatoid factors positive univariate analysis subgroup(OR=1.33,95%CI:1.02 to 1.72,P=0.04),C-reactive protein(SMD=0.26,95%CI:0.16-0.35,P=0.00),erythrocyte sedimentation rate(SMD=0.15,95%CI:0.002-0.29,P=0.047),anti-cyclic-citrullinated peptide antibodies(OR=1.73,95%CI:1.19-2.51,P=0.004),28-joint Disease Activity Score(SMD=0.20,95%CI:0.04-0.37,P=0.02),destruction of peripheral joints(OR=2.48,95%CI:1.60-3.85,P=0.00),and corticosteroids(OR=1.91,95%CI:1.54-2.37,P=0.00)were strongly associated with the development of rheumatoid arthritis-cervical spine instability.Female and corticosteroid use were independently associated with the occurrence of rheumatoid arthritis-cervical spine instability. CONCLUSION:Based on clinical evidence from 16 observational studies,the overall incidence of rheumatoid arthritis-cervical spine instability was 43.08%.However,the incidence of cervical spine instability in rheumatoid arthritis patients varied greatly among different studies.Gender(female)and the use of corticosteroids were confirmed as independent correlation factors for the onset of cervical spine instability in patients with rheumatoid arthritis.The results of this study still provide some guidance for early clinical recognition,diagnosis,and prevention of rheumatoid arthritis-cervical spine instability.