Background and aims As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied. Methods Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis. Results PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased in vivo by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown. Conclusions Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.

Objective:To explore the potential categories and influencing factors of medication compliance in patients with cardiometabolic multimorbidity, and provide a reference for formulating targeted intervention measures.Methods:A cross-sectional study design was adopted. From March to October 2024, the patients with cardiometabolic multimorbidity in the First Hospital Affiliated with Hunan Normal University (Hunan Provincial People′s Hospital) were selected by convenience sampling method as research objects. Data were collected using a general information questionnaire, Medication Adherence Rating Scale (MARS), Perceived Social Support Scale (PSSS), and Medication Literacy Questionnaire. The latent class analysis was used to explore the characteristics and classifications of medication compliance in cardiometabolic multimorbidity, and unordered multivariate Logistic regression was used to analyze the influencing factors of different latent classes.Results:A total of 421 subjects were included, consisting of 291 males and 130 females, aged (64.28±9.74) years old. The overall medication adherence score was 6.00 (5.00, 8.00) points, which could be divided into four categories: overall good adherence group (24.47%, 103/421), subjective perception-poor adherence group (15.91%, 67/421), forgetfulness-poor adherence group (37.53%, 158/421), and overall poor adherence group (22.09%, 93/421). The results showed that when taking the overall good adherence group as a reference, the inability to obtain pharmaceutical information from social media, medication literacy scores, social support scores were the influencing factors for the subjective perception-poor adherence group ( OR=4.210, 0.516, 0.733, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), age, social support scores were the influencing factors for the forgetfulness-poor adherence group( OR=0.173, 1.155, 0.781, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), failure to receive medication guidance from medical staff, medication literacy scores and social support scores were the influencing factors for the overall poor adherence group( OR values were 0.136-5.275, all P<0.05). When taking the overall poor adherence group as a reference, failure to receive medication guidance from medical staff and medication literacy scores were the influencing factors for the subjective perception-poor adherence group ( OR=0.310, 1.752, both P<0.05). Failure to receive medication guidance from medical staff, age, medication literacy scores and social support scores were the influencing factors for the forgetfulness-poor adherence group ( OR values were 0.315-2.554, all P<0.05). Conclusions:There is significant heterogeneity in medication adherence among patients with cardiometabolic multimorbidity. Healthcare professionals should consider individual characteristics in clinical practice and provide targeted, precise interventions to improve adherence in different patient categories.

Objective:To summarize the current status and research hotspots in volume management among patients with heart failure, and to predict future research trends.Methods:Literature related to volume management in heart failure patients published between January 1, 2004 and August 1, 2024 was retrieved from the China National Knowledge Infrastructure and Web of Science Core Collection databases. CiteSpace software was used to perform visual analysis of publication volume, authors, institutions, countries, and keywords.Results:A total of 5 008 articles were retrieved, of which 145 were Chinese and 202 were English publications. The overall publication trend showed a steady increase over the past two decades. The most prolific author was Fudim (7 publications), the leading institution was Mayo Clinic (14 publications), and the country with the highest output was the United States (91 publications). Keyword co-occurrence, clustering, and burst detection analyses revealed that current research hotspots in both Chinese and English literature mainly focus on the management and control of volume overload, exploration of nursing strategies, and patient self-management and home-based rehabilitation. Emerging trends include out-of-hospital volume overload control and intelligent volume management technologies.Conclusions:Research on volume management in heart failure patients is evolving toward diversification and integration. Clinical interventions and standardized guidelines have gained increasing attention. Home-based volume management and overload control continue to be key areas of interest. In the future, the integration of artificial intelligence and the development of individualized home self-management programs will likely become important directions to improve the quality of life in patients with heart failure.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective:To improve the understanding of patients with diffuse large B-cell lymphoma (DLBCL) with pulmonary cryptococcosis.Methods:The clinical data of 1 DLBCL patient with pulmonary cryptococcosis in the Central Hospital of Fengxian District of Shanghai in May 2023 were retrospectively analyzed, and the relevant literatures were reviewed.Results:This 75-year-old female patient was asymptomatic after 2 cycles of R-CHOP chemotherapy. The high-resolution CT of lung showed that lung nodules were progressively enlarged. Antibacterial treatment was ineffective. Pulmonary cryptococcosis was confirmed by bronchoalveolar lavage fluid (BALF) targeted high-throughput sequencing (tNGS) and cryptococcus capsular antigen (CrAg) detection. The central nervous system was not involved. And the long-term adequate-dose fluconazole was prescribed for 6 months, and the treatment against lymphoma was given synchronously. The lung nodule lesions reduced after antifungal therapy for 1 month. The lung nodules disappeared after the follow-up of 6 months after completion of final chemotherapy. The evaluation of lymphoma indicated complete remission.Conclusions:Pulmonary cryptococcosis occurs insidiously and shows no specific symptoms; its imaging manifestations are variable and routine anti-infection is ineffective. Immunochemotherapy for lymphoma patients is a high-risk factor for cryptococcal infection. tNGS and CrAg testing for BALF are effective methods of the confirmed diagnosis. The early and long-term adequate-dose antifungal treatment is the key to preventing the recurrence or progression.

Objective:To explore the potential categories and influencing factors of medication compliance in patients with cardiometabolic multimorbidity, and provide a reference for formulating targeted intervention measures.Methods:A cross-sectional study design was adopted. From March to October 2024, the patients with cardiometabolic multimorbidity in the First Hospital Affiliated with Hunan Normal University (Hunan Provincial People′s Hospital) were selected by convenience sampling method as research objects. Data were collected using a general information questionnaire, Medication Adherence Rating Scale (MARS), Perceived Social Support Scale (PSSS), and Medication Literacy Questionnaire. The latent class analysis was used to explore the characteristics and classifications of medication compliance in cardiometabolic multimorbidity, and unordered multivariate Logistic regression was used to analyze the influencing factors of different latent classes.Results:A total of 421 subjects were included, consisting of 291 males and 130 females, aged (64.28±9.74) years old. The overall medication adherence score was 6.00 (5.00, 8.00) points, which could be divided into four categories: overall good adherence group (24.47%, 103/421), subjective perception-poor adherence group (15.91%, 67/421), forgetfulness-poor adherence group (37.53%, 158/421), and overall poor adherence group (22.09%, 93/421). The results showed that when taking the overall good adherence group as a reference, the inability to obtain pharmaceutical information from social media, medication literacy scores, social support scores were the influencing factors for the subjective perception-poor adherence group ( OR=4.210, 0.516, 0.733, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), age, social support scores were the influencing factors for the forgetfulness-poor adherence group( OR=0.173, 1.155, 0.781, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), failure to receive medication guidance from medical staff, medication literacy scores and social support scores were the influencing factors for the overall poor adherence group( OR values were 0.136-5.275, all P<0.05). When taking the overall poor adherence group as a reference, failure to receive medication guidance from medical staff and medication literacy scores were the influencing factors for the subjective perception-poor adherence group ( OR=0.310, 1.752, both P<0.05). Failure to receive medication guidance from medical staff, age, medication literacy scores and social support scores were the influencing factors for the forgetfulness-poor adherence group ( OR values were 0.315-2.554, all P<0.05). Conclusions:There is significant heterogeneity in medication adherence among patients with cardiometabolic multimorbidity. Healthcare professionals should consider individual characteristics in clinical practice and provide targeted, precise interventions to improve adherence in different patient categories.

Objective:To summarize the current status and research hotspots in volume management among patients with heart failure, and to predict future research trends.Methods:Literature related to volume management in heart failure patients published between January 1, 2004 and August 1, 2024 was retrieved from the China National Knowledge Infrastructure and Web of Science Core Collection databases. CiteSpace software was used to perform visual analysis of publication volume, authors, institutions, countries, and keywords.Results:A total of 5 008 articles were retrieved, of which 145 were Chinese and 202 were English publications. The overall publication trend showed a steady increase over the past two decades. The most prolific author was Fudim (7 publications), the leading institution was Mayo Clinic (14 publications), and the country with the highest output was the United States (91 publications). Keyword co-occurrence, clustering, and burst detection analyses revealed that current research hotspots in both Chinese and English literature mainly focus on the management and control of volume overload, exploration of nursing strategies, and patient self-management and home-based rehabilitation. Emerging trends include out-of-hospital volume overload control and intelligent volume management technologies.Conclusions:Research on volume management in heart failure patients is evolving toward diversification and integration. Clinical interventions and standardized guidelines have gained increasing attention. Home-based volume management and overload control continue to be key areas of interest. In the future, the integration of artificial intelligence and the development of individualized home self-management programs will likely become important directions to improve the quality of life in patients with heart failure.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.