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.

Digestive system malignant tumors （DT） are one of the leading causes of death globally and carry a heavy economic burden. Gut microbiota plays a critical role in maintaining host health， including providing nutrition， defending against pathogens， and promoting immune development. In recent years， more and more studies have shown that dysbiosis of gut microbiota is closely associated with DT such as gastric cancer， liver cancer， and colon cancer. Therefore， targeted regulation of gut microbiota plays a potential role in inhibiting the growth and metastasis of DT， while its specific regulatory mechanism remains unclear. As the studies about the anti-tumor effects of traditional Chinese medicine （TCM）， especially the basic and clinical studies on the regulation of gut microbiota by TCM in tumor treatment， have been growing， the therapeutic effects of TCM on DT have attracted much attention. This paper provides a systematic review of the relationship between gut microbiota and DT， as well as the related studies on the modulation of gut microbiota by TCM against DT， with the aim of providing a foundation and direction for future basic and clinical studies on DT. The literature review shows that gut microbiota influence the occurrence and development of DT through multiple pathways. These pathways include triggering chronic inflammation， producing oncogenic metabolites， inducing genomic instability， regulating the immune system， and altering the tumor microenvironment. TCM can exert anti-DT effects by regulating the composition of gut microbiota， modulating gut microbiota metabolites， repairing intestinal barrier function， and influencing immune functions. Therefore， understanding the relationship between gut microbiota and DT and the regulatory mechanisms of TCM may provide new strategies for future prevention and treatment of DT.

Objective: To assess parental expectations for the development of children with autism spectrum disorder (ASD) and identify factors associated with these expectations, so as to provide references for improving rehabilitation outcomes and long term development in children with ASD. Methods: From June 2024 to January 2026, a total of 877 children with ASD and their parents were recruited from 27 rehabilitation institutions in Hefei. The children had been diagnosed by chief physicians at tertiary level hospitals. Demographic characteristics and data on parental expectations were collected by the Parental Expectations Questionnaire. Differences in parental expectations between groups were assessed using the Mann-Whitney U- test and Kruskal-Wallis H-test, and associated factors were examined using quantile regression. Results: The mean item score for overall parental expectations among parents of children with ASD was (4.55±0.47), and scores for all dimensions were higher than those among parents of typically developing children ( t =11.11-31.14, all P <0.01). Child age, school enrollment, and maternal personality were associated with daily living expectation scores, learning and special talents and strengths expectation scores, and special talents and strengths expectation scores, respectively ( H =6.16-8.18, all P <0.05). Parents of preterm children had higher expectations for social interaction, physical and mental well being, and daily living than parents of non-preterm children ( Z =-2.56, -2.48, -2.39, all P <0.05). Multivariate quantile regression analysis showed that children’s age was associated with the expected level of self care ability; school enrollment status was associated with the expected level of learning and specialty strengths; maternal personality was associated with the expected levels of social competence, physical and mental health, self care ability, and specialty strengths; parental age was associated with the expected levels of physical and mental health and specialty strengths; and parental educational attainment was associated with the expected level of self care ability ( β =-0.36-0.41, all P <0.05). Conclusion Parents of children with ASD in Hefei generally have high expectations for their children s development across the domains of learning, daily living, social interaction, and physical and mental well being.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT), intensity modulated radiation therapy (IMRT) and tomotherapy (TOMO) techniques applied in the irradiation of pediatric whole central nervous system tumors.Methods:Taking the target area of a 14-year-old pediatric patient clinically diagnosed with atypical teratoid/rhabdomyoid tumor, meningeal metastasis by Shandong Cancer Hospital and Institute, and undergoing craniospinal irradiation (CSI) as an example, IMPT, IMRT and TOMO plans were designed respectively based on the clinical prescription of the target area and the limit requirements of organs at risk (OARs). The conformal index (CI), homogeneity index (HI) and gradient index (GI) of each planning target volume, as well as the dose volume index of normal tissues, were evaluated to compare the dosimetric characteristics of the three types of plans.Results:The CI (0.71), HI (0.05) and GI (3.13) of the IMPT plan were comparable to those of IMRT plan (0.80, 0.08, 3.14). The HI (0.03) and GI (2.54) of the TOMO plan were excellent, which were all within the clinically acceptable range. The irradiation dose to parallel organs in the IMPT plan was lower than that in the IMRT and TOMO plan. In the IMPT plan, V 5 of lungs was 2.9%, IMRT plan was 37.6%, and TOMO plan was 43.5%. The D mean of liver in the IMPT plan was 0.01 Gy (RBE), IMRT plan was 6.12 Gy, and TOMO plan was 6.39 Gy. In the IMPT plan, none of the bladder, rectum, and femoral head received the dose, while there was low-dose radiation in both IMRT and TOMO plan. For serial organs adjacent to and within the target area, the D max of spinal cord and brainstem in IMPT plan was 39.89 and 39.88 Gy (RBE), respectively; in IMRT plan, they were 39.43 and 38.59 Gy, respectively; and in TOMO plan, they were 38.41 and 37.69 Gy, respectively. The low-dose area in the IMPT plan was significantly better than the photon radiotherapy plans. Among them, the absolute volume IMPT plan occupied by 10% of the prescribed dose area in the patient's body was reduced by 70.10% compared with IMRT plan and 76.96% compared with TOMO plan; the 30% prescribed dose volume IMPT plan was reduced by 53.49% compared with IMRT plan and 62.51% compared with TOMO plan; the 50% prescribed dose volume IMPT plan was reduced by 39.06% compared with IMRT plan and 42.23% compared with TOMO plan. Conclusions:The IMPT plan demonstrated significantly reduced low-dose exposure and lower doses to parallel OARs compared to both IMRT and TOMO plans in pediatric CSI. The CI, HI and GI of the three plans can all meet the clinical requirements. However, for serial organs adjacent to and within the target area, the D max of the IMPT plan may be higher than that of IMRT and TOMO plans.

Objective:To explore the dosimetric characteristics of proton and photon radiotherapy in the treatment of breast cancer.Methods:Four female breast cancer patients who needed radiotherapy at Shandong Cancer Hospital and Institute from January 2024 to May 2024 were selected as the research subjects. The target area ranges of 4 patients were left-sided breast cancer with lymph node involvement, left-sided breast cancer with lymph node involvement and internal mammary node, right-sided breast cancer with lymph node involvement and internal mammary node and synchronous bilateral breast cancer. Intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) plans were designed respectively based on the prescribed dose in the target area and the limits of organs at risk (tomotherapy plan for bilateral breasts). The conformity index (CI), homogeneity index (HI), gradient index (GI) and organs at risk doses were evaluated. The dosimetric characteristics of IMPT and photon radiotherapy were compared.Results:Both IMPT and photon radiotherapy plans of the 4 breast cancer cases met the clinical dose requirements. The HI value of IMPT plans (0.10-0.14) was comparable to that of photon radiotherapy plans (0.10-0.12), and the average CI of the photon radiotherapy plans was 0.10 higher than that of the IMPT plans, and the average GI was 0.55 lower than that of the IMPT plans. The D mean of ipsilateral lung and heart of IMPT was lower, especially in the low-dose area (V 0-3), which was significantly lower than the photon radiotherapy plans, D mean of ipsilateral lung was reduced by 12.2%, 6.1%, 16.1% and 34.8%, respectively, D mean of heart was reduced by 47.2%, 57.0%, 72.4% and 83.0%, respectively. The ipsilateral lung V 20 of IMPT was not lower than photon radiotherapy plans (unilateral breast: IMPT was 30.0%-34.0%, IMRT was 29.0%-35.9%) . Conclusions:IMPT significantly reduces the D mean to the ipsilateral lung and heart while ensuring dose coverage of the target in breast cancer, preventing more volume of surrounding normal tissues from being irradiated. However, IMPT does not show much more advantage than photon radiotherapy plans in the ipsilateral lung V 20.

Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) for typical abdominal and pelvic tumors.Methods:Three patients with abdominal and pelvic tumors (one case each of liver cancer, cervical cancer, and prostate cancer) admitted to Shandong Cancer Hospital and Institute from January to June 2024 were selected as the research subjects. IMPT and IMRT plans were designed for each case based on clinical target volume (CTV) and organs at risk (OARs) constraints. Dosimetric parameters, including conformity index (CI), homogeneity index (HI), and gradient index (GI) for target coverage, as well as OARs dose metrics, were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all three cases, IMRT plan demonstrated higher CI values (0.82, 0.81, and 0.86) compared to IMPT plan (0.61, 0.62, and 0.43). IMPT plan yielded lower HI values (0.053, 0.075, and 0.020) than IMRT plan (0.060, 0.120, and 0.080) and lower GI values (3.45, 2.63, and 3.80 vs. 7.28, 4.76, and 4.66 for IMRT plan). In liver cancer, IMPT plan reduced the D mean of normal liver tissues and right kidney by 37.8% and 78.5%, respectively, and decreased the D max of spinal cord by 13.2%. For cervical cancer, IMPT plan reduced the V 30 of the small bowel by 22.0%, D mean of the bladder, rectum and bone marrow by 15.7%, 14.3% and 12.6%, and spinal cord D max by 4.8%. In prostate cancer, IMPT plan lowered bladder and rectal D mean by 14.9% and 36.5%, respectively, but resulted in an increase of 35.3% and 6.1% in the D mean and V 40 of the left femoral head, respectively, and an increase of 23.6% and 10.8% in the D mean and V 40 of the right femoral head, respectively. IMPT plan reduced the volumes receiving 10%, 30%, and 50% of the prescription dose by 48.9%-64.8%, 22.0%-47.0%, and 22.0%-57.7%, respectively, compared to IMRT plan. Conclusions:Comparison between IMPT and IMRT plans for abdominopelvic tumors: IMPT plan offers advantages in reducing doses to normal organs such as the liver, kidneys, spinal cord, small intestine, rectum, and bladder. However, its advantage is less pronounced regarding the dose to the femoral heads. IMPT plan notably minimizes additional dose deposition within the body.

Objective:To investigate the dosimetric characteristics of intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT) in typical head and neck malignant tumors.Methods:Three types of typical head and neck tumors (nasopharyngeal carcinoma, parotid gland carcinoma, laryngeal carcinoma) treated at Shandong Cancer Hospital and Institute from December 2023 to December 2024 were taken as research subjects. IMPT and VMAT radiotherapy plans were created according to clinical prescription requirements of target and organs at risk limits respectively. The conformity index (CI), homogeneity index (HI) and gradient index (GI) for target coverage of two radiotherapy plans were evaluated for 3 patients, as well as the dosimetric indicators of organs at risk.Results:The CI of IMPT for nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma were 0.70, 0.72 and 0.67, respectively. The HI were 0.11, 0.08 and 0.08, respectively. The GI were 3.08, 2.49 and 3.75, respectively. The CI of VMAT plans were 0.77, 0.82 and 0.91, respectively. The HI were 0.12, 0.10 and 0.04, respectively. The GI were 3.67, 2.63 and 3.45, respectively. The results showed that CI of IMPT plan was slightly lower than that of VMAT plan, and HI of IMPT plan was comparable to that of VMAT plan, the GI of the IMPT plan for patients with nasopharyngeal carcinoma and parotid gland carcinoma was lower than that of the VMAT plan, and the GI of the IMPT plan for patient with laryngeal carcinoma was higher than that of the VMAT plan, and all were within the clinically acceptable range. The IMPT plan has demonstrated significant dose advantages in the treatment of nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma. For patient with nasopharyngeal carcinoma, the IMPT plan reduced the D max of the left and right crystals by 54.1% and 50.4%, respectively, compared to VMAT plan, and reduced the D mean of the oral and laryngeal tissues by 40.5% and 49.6%, respectively. For patient with parotid gland carcinoma, IMPT plan reduced the D max of the brainstem and spinal cord by 66.2% and 40.5%, respectively, compared to VMAT plan. For patient with laryngeal carcinoma, IMPT reduced spinal cord D max by 77.0%, while thyroid cartilage D mean increased by 8.0% compared to VMAT plan. For the additional dose in the patients' body, taking the absolute volumes occupied by the prescribed dose areas of 10%, 30%, and 50% in the patients' body as examples, IMPT plan of nasopharyngeal carcinoma patient decreased by 29.7%, 29.6%, and 34.9% compared to VMAT plan, respectively. IMPT plan of parotid gland carcinoma patient decreased by 61.0%, 39.7%, and 17.4% compared to VMAT plan, respectively. IMPT plan of laryngeal carcinoma patient decreased by 63.9%, 31.7%, and 4.1% compared to VMAT plan, respectively. Conclusions:Compared with VMAT plan, IMPT plan can effectively reduce the irradiation dose of most organs at risk near the target of head and neck tumors, but the dose of string organs close to the target area may be higher, which needs attention.

Objective:To investigate the dosimetric characteristics of intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) for lung cancers.Methods:Three lung cancer patients (central-lower, central, and peripheral types) admitted to Shandong Cancer Hospital and Institute from January 2024 to May 2024 were selected as the research subjects. IMPT and IMRT plans were designed for each case based on the anatomical location of the clinical target volume and the dose constraints for organs at risk (OARs). Dosimetric parameters, including conformity index (CI), homogeneity index (HI), and gradient index (GI) for target coverage, as well as OARs dosimetric parameters were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all three cases, IMRT plans demonstrated higher CI values (0.80, 0.60, and 0.79) compared to IMPT plans (0.61, 0.57, and 0.34). IMPT plans yielded lower HI values (0.07, 0.06, and 0.06) than IMRT plans (0.09, 0.15, and 0.09) and lower GI values (2.84, 2.47, and 4.56 vs. 4.91, 3.09, and 4.99 for IMRT plans). Compared with the IMRT plans, the low-dose region in the ipsilateral lung was significantly reduced in IMPT plans (V 5 of the IMPT plans were 20.59%, 46.29%, 10.94%, respectively; V 5 of the IMRT plans were 48.91%, 60.63%, 19.92%, respectively), but there was no significant advantage in the high-dose region compared to IMRT plans (V 20 of the IMPT plans were 12.88%, 34.75%, 5.21%, respectively; V 20 of the IMRT plans were 21.70%, 36.50%, 5.31%, respectively). The dose to the contralateral lung and heart was significantly reduced in IMPT plans [the D mean of the contralateral lung in the IMPT plans were 0.08, 0.04, and 0.00 Gy (RBE), respectively, and those in the IMRT plans were 3.25, 1.18, and 0.55 Gy, respectively; the heart D mean in the IMPT plans were 6.23, 7.04, and 0.00 Gy (RBE), respectively, while those of the IMRT plans were 18.33, 10.27, and 0.08 Gy, respectively). IMPT plans significantly reduced the volumes receiving 10% of the prescription dose by 65.94%, 25.57% and 72.47%, respectively, compared to IMRT plans. The volumes IMPT plans occupied by 30% of the prescription dose area in the body were reduced by 54.97%, 26.47% and 39.04%, respectively, compared to the IMRT plans. The volumes IMPT plans occupied by 50% of the prescription dose area in the body were reduced by 54.49%, 30.43% and 28.89%, respectively, compared to the IMRT plans. Conclusions:IMPT plan significantly reduces the V 5 of the ipsilateral lung, the D mean of the contralateral lung and the heart, while maintaining target coverage compared with IMRT plan for lung cancers. However, IMPT plan does not show much more advantage than IMRT plan in the ipsilateral lung V 20. IMPT can reduce the additional exposure volume within the body.