Objective To explore the predictive model and its value of irAEs based on peripheral blood markers.Methods The baseline clinical data,laboratory tests,and irAEs follow-up results of 825 malignant tumor patients treated with PD-1/PD-L1 antibodies in the First Affiliated Hospital of Kunming Medical University were retrospectively collected from December 2020 to December 2023.The patients were divided into irAEs group and non-irAEs group according to the presence or absence of irAEs.The differences between and within groups were analyzed by t-test,rank-sum test,chi-square test and Fisher exact probability method.LASSO,Ridge and Elastic-net logistic regressions were used to screen the predictors and establish the risk prediction models for irAEs.Results 136 patients experienced 178 irAEs,of which endocrine toxicity accounted for 42.64％,hepatitis 35.29％,pneumonia 20.58％,grade≥G3 accounted for 19.07％,involving more than two organs accounted for 24.26％of the total number of irAEs.Univariate analysis showed that baseline CD4+T cell count,IL-6,IL-17,TSH,GLB and ALB were associated with irAEs.GLB,ALB,IL-17 and TSH were selected as the important risk factors by Ridge,LASSO and Elastic-Net logistic regression.The results showed that the AUC of the three algorithms were over 0.800.The AUC of internal validation set by LASSO-Logistic was 0.800(95％CI 0.739～0.862).The AUC of external validation set was 0.800(95％CI 0.739～0.861)and the DCA curve results indicated the highest net return for this predictive model.Conclusion GLB,ALB,IL-17 and TSH are independent predictors of irAEs,and the predictive model of irAEs based on them is effective.

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: Renal cell carcinoma (RCC) is a malignant renal tumor that poses a significant threat to patient health. Accurate preoperative pathological grading plays a crucial role in determining the appropriate treatment for this disease. Currently, deep learning technology has become an important method for pathological grading of RCC. However, existing methods primarily rely on single-phase computed tomography (CT) imaging for analysis and prediction, which has limitations such as missing small lesions, one-sided evaluation, and local focusing issues. Therefore, this study proposes a multi-modal deep learning algorithm that integrates multi-phase enhanced CT images with clinical variable data, aiming to provide a basis for predicting the pathological grading of RCC. METHODS: First, the algorithm took four-phase enhanced CT images from the plain scan, arterial phase, venous phase, and delayed phase, along with clinical variables, as inputs. Then, an embedding encoding module was used to extract heterogeneous information from the clinical variables, and a 3-dimensional (3D) ResNet50 model was employed to capture spatial information from the multi-phase enhanced CT image data. Finally, a Fusion module deeply integrated the feature information from clinical variables and each phase's CT image features, further utilizing a cross-self-attention mechanism to achieve multi-phase feature fusion. This approach comprehensively captures the deep semantic information from the patient data, fully leveraging the complementary advantages of multi-modal and multi-phase data. To validate the effectiveness of the proposed method, a total of 1 229 RCC patients were approved by ethics review were included to train the model. RESULTS: Experimental results demonstrated superior performance compared to traditional radiomics and state-of-the-art deep learning methods, achieving an accuracy of 83.87%, a recall rate of 95.04%, and an F1-score of 82.23%. CONCLUSIONS The proposed algorithm exhibits strong stability and sensitivity, significantly enhancing the predictive performance of RCC pathological grading. It offers a novel approach for accurate RCC diagnosis and personalized treatment planning.
Humans ; Carcinoma, Renal Cell/pathology* ; Deep Learning ; Kidney Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Algorithms ; Neoplasm Grading ; Male ; Female ; Middle Aged

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*

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Objective:To compare the efficacy of anrikefon and tegileridine for analgesia in patients with moderate-to-severe pain after abdominal surgery with general anesthesia.Methods:In this multicenter, randomized, double-blind, active-controlled clinical trial, 101 patients with moderate to severe pain (numeric pain rating scale [NRS] score ≥4 within 4 h after operation) after abdominal surgery with general anesthesia between February 24 and April 1, 2025, aged 18-70 yr, with a body mass index of 18-40 kg/m 2, were assigned to anrikefon group ( n=50) and tegileridine group ( n=51) in a 1∶1 ratio using stratified blocked randomization. Double-dummy design was employed to maintain blinding. Each group received an initial intravenous injection of anrikefon 1 μg/kg or tegileridine 1 mg, followed by connection to a patient-controlled intravenous analgesia (PCIA) pump (the PCIA solution contained normal saline in anrikefon group; the PCIA solution contained tegileridine 5 mg in tegileridine pump) within 10 min. If the patient′s NRS score ≥4 at 8 and 16 h after the initial injection, anrikefon 1 μg/kg was intravenously injected in anrikefon group, and tegileridine group received the equal volume of normal saline. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 24 h after the initial dose (SPID 0-24h). The secondary efficacy endpoints included the incidence and severity of vomiting and nausea, incidence of postoperative nausea and vomiting(PONV), the proportion of patients who received antiemetic treatment, and total consumption of antiemetics within 0-24 h after the initial dose, NRS score at rest ≤ 1 at 24 h after the initial dose, and NRS score at rest ≤ 3 over the first 24 h after the initial dose. Safety indicators included adverse events, vital signs, physical examination findings, 12-lead ECG and laboratory test indicators, and adverse events of special interest. Results:Compared with tegileridine group, no significant change was found in the SPID 0-24h ( P>0.05), and the incidence of vomiting, PONV, proportion of patients requiring antiemetic medication, and total consumption of antiemetics were significantly decreased within the first 24 h after the initial dose in tegileridine group ( P<0.05). One treatment-emergent adverse event of Common Terminology Criteria for Adverse Events grade 3 or higher occurred in tegileridine group, while no treatment-emergent adverse events of Common Terminology Criteria for Adverse Events grade 3 or higher were found in anrikefon group. Among the adverse events of special interest, one case of respiratory depression and one case of cough occurred in tegileridine group, while one case of cough occurred in anrikefon group, with no respiratory depression. Conclusions:Anrikefon and tegileridine provide comparable analgesic efficacy for moderate-to-severe pain after abdominal surgery with general anesthesia. However, anrikefon exhibits an advantage in reducing the risk of PONV, with a superior safety profile.