OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants （DOACs） and triazole antifungals， and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System （FAERS） from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms （PTs） were selected. The Ω shrinkage measure， additive model， multiplicative model， and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included， among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations： apixaban-fluconazole， apixaban-posaconazole， rivaroxaban-itraconazole， dabigatran etexilate-fluconazole， apixaban-voriconazole， and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding （ Ω ＝2.73， Ω 025 ＝2.05） and hemoptysis （ Ω ＝2.17， Ω 025 ＝0.83）； the apixaban-fluconazole combination exhibited stronger signals for hematoma （ Ω ＝2.30， Ω 025 ＝1.47） and hematuria （ Ω ＝1.71， Ω 025 ＝0.74）； the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis （ Ω ＝2.01， Ω 025 ＝0.90） and hematoma （ Ω ＝1.93， Ω 025 ＝0.42）； no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events， with differences in signal strength and signal distribution across various drug combinations. In clinical practice， particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations， close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.

Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.

OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.

Objective To evaluate the differential diagnostic value of synthetic magnetic resonance imaging(syMRI)and field of view optimized and constrained undistorted single shot diffusion weighted imaging(FOCUS DWI)in patient with breast imaging reporting and data system(BI-RADS)4 breast lesions.Methods A total of 68 patients who underwent breast MRI and were classified as BI-RADS category 4 were prospectively enrolled.Among them,there were 31 cases of benign lesions(benign group)and 37 cases of malignant lesions(malignant group).All patients underwent T1WI,T2WI,FOCUS DWI,dynamic contrast-enhanced magnetic resonance ima-ging(DCE-MRI)and syMRI.Two radiologists delineated the region of interest(ROI)on quantitative parameters images of syMRI and the apparent diffusion coefficient(ADC)images generated from FOCUS DWI and calculated T1,T2,proton density(PD)and ADC values,respectively.The thresholds and diagnostic efficacy of syMRI and FOCUS DWI parameters were evaluated by the receiver op-erating characteristic(ROC)curve.Logistic regression analysis was used to combine the parameters of the two sequences and evalu-ate the diagnostic efficacy.Results The T2,PD,and ADC values in the malignant group were significantly lower than those in the benign group(P＜0.05),but there were no statistically significant difference in T1 values between the groups(P＞0.05).T2 and ADC values could be used as important diagnostic indexes in patient with malignant lesions of BI-RADS 4 breast lesions,and the area under the curve(AUC)of T2 and ADC was 0.833 and 0.867,respec-tively.There was no significant difference in AUC of T2 and ADC between benign and malignant groups(Z=0.485,P=0.627).The AUC of T2 value combined with ADC value was 0.910,and the sensitivity and specificity was 90.3％and 89.2％,respectively.Conclusion T2 value of syMRI and ADC value of FOCUS DWI can be used as quantitative diagnostic indicators in patients with BI-RADS 4 breast lesions.The combination of T2 and ADC values can further improve the differential diagnosis efficiency.

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

Objective:To investigate the application value of biological muscle flap in laparo-scopic radical proximal gastrectomy with esophagogastric anastomosis.Methods:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 10 patients with adeno-carcinoma of esophagogastric junction who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from May 2023 to August 2023 were collected. All patients were males, aged (65±5)years. All patients underwent laparoscopic radical proximal gastrectomy and esophagogastric anastomosis with digestive tract reconstruction using the esophagogastric biological muscle flap. Observation indicators: (1) surgical situations and early complications; (2) follow-up and late com-plications. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations and early complications. All 10 patients success-fully completed the surgery without conversion to open surgery, and the operation time was (166±18)minutes. Cases with digestive tract reconstruction as end-to-side anastomosis and Overlap anas-tomosis were 1 and 9, respectively. The time of digestive tract reconstruction, the number of lymph node dissected, volume of intraoperative blood loss, time to postoperative first anal exhaust, time to postoperative first intake of liquid food, duration of postoperative hospital stay were (40±12)minutes, 24±6, (41±9)mL, (3.4±0.5)days, (4.1±1.0)days, (8.3±0.7)days in the 10 patients. Of 4 cases with postoperative early complications, 1 case developed pulmonary infection (Clavien-Dindo grade Ⅱ) on the second day after surgery, with pulmonary infection absorbed after 5 days of antibiotic treat-ment. Two cases experienced chest distress and shortness of breath on the third day after surgery, with the diagnosis of a small to moderate amount of pleural effusion after chest B-ultrasound examination. After pleural puncture and active treatment, the symptoms of them were improved and the pleural effusion disappeared. There was 1 case with choking sensation when eating solid food, which was started from the third week after surgery. Upper gastrointestinal imaging revealed mild anastomotic stenosis of Clavien-Dindo grade Ⅰ in the patient, who was improved after conservative treatment. On the 7th day after surgery, all 10 patients underwent upper gastrointestinal angiography, and no anastomotic leakage or stenosis occurred. There was no sign of contrast agent reflux in the supine position and 30° head down position. (2) Follow-up and late complications. All 10 patients were followed up for 59.5(range, 31.0-127.0)days. The esophageal reflux scale score of 10 patients was 1.4±0.3. During the follow-up, 1 case underwent gastroscopy on 40 days after surgery, which showed reflux esophagitis with Los Angeles grade as B and the Clavien-Dindo grade as Ⅰ. There was no clinical symptom such as heartburn or acid reflux. Results of 24-hour pH monitoring showed that the patient experienced 24 instances of reflux in an upright position and 15 instances of reflux in a supine position, with no prolonged reflux. The total reflux time within 24 hours was 75 minutes. The DeMeester score was 38.3. Results of esophageal pressure measurement showed that the esophageal contraction morphology was normal, but the anastomotic opening was not well relaxed. The rest of 9 cases had no complication such as reflux esophagitis.Conclusion:Biological muscle flap applied in the laparoscopic radical proximal gastrectomy with esophagogastric anastomosis is safe and feasible, with satisfied short-term efficacy.