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.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Objective:To investigate the effect of robot-assisted total knee arthroplasty (TKA) on the incidence of postoperative deep vein thrombosis (DVT) in the lower limbs.Methods:A total of 405 patients who underwent primary unilateral TKA in the Department of Orthopaedics, Peking University Third Hospital from June 2022 to June 2024 were retrospectively analyzed, consisting of 89 males and 316 females, with a mean age of 67.84±5.60 years. Patients were divided into the conventional group ( n=215) and the robot-assisted group ( n=190) according to the surgical approach. Postoperative DVT incidence, operative time, postoperative hemoglobin and hematocrit levels, perioperative blood loss, and transfusion rate were compared between the two groups to evaluate the impact of robot-assisted TKA on thrombotic events and related clinical indicators. Results:There were no significant differences in age, sex, height, weight, body mass index, or preoperative laboratory results including hemoglobin and hematocrit levels between the two groups ( P>0.05). The postoperative DVT incidence was 26.8% (51/190) in the robot-assisted group and 34.9% (75/215) in the conventional group, with no significant difference ( P>0.05). Univariate logistic regression analysis showed that sex ( P=0.013) and age ( P=0.024) were significantly associated with DVT occurrence. Multivariate logistic regression further revealed that female patients had a significantly higher incidence of DVT than males ( OR=0.438, P=0.005), and older patients had a significantly increased risk of DVT ( OR=1.046, P=0.025); body mass index remained not significantly associated with DVT ( P=0.092). The operative time in the robot-assisted group was 88.62±18.58 min, which was significantly longer than that in the conventional group 79.23±17.68 min ( t=-5.207, P<0.001). Perioperative total blood loss was 1 079.85±344.18 ml in the robot-assisted group and 1 141.47±363.70 ml in the conventional group, with no significant difference ( t=1.745, P=0.082). The transfusion rate was 5.3% in the robot-assisted group and 5.1% in the conventional group, respectively, with no significant differences (χ 2=0.004, P=0.947). Conclusion:Compared with conventional TKA, robot-assisted TKA results in longer operative time but does not increase perioperative blood loss or the risk of postoperative DVT.

Bone tissue engineering(BTE)is expected to be used as an autologous bone graft substitute for bone defects,and in the se-lection of BTE scaffold materials,collagen(Col)and hydroxyapatite(HA)have attracted attention due to their unique biomimetic ad-vantages.Collagen/hydroxyapatite(CHA)composite scaffolds made by combining the two have been shown to have excellent biocompat-ibility and bone-enhancing potential in various in vitro,in vivo,and clinical studies.With the development of three-dimensional(3D)printing technology in the field of tissue engineering,bone scaffolds constructed using 3D printing methods have been shown to possess superior clinical potential.This review describes new advances in 3D printed CHA composite scaffolds and introduces the application of 3D printed CHA scaffolds in oral and maxillofacial bone regenerative repair.

Objective:To investigate the effect of robot-assisted total knee arthroplasty (TKA) on the incidence of postoperative deep vein thrombosis (DVT) in the lower limbs.Methods:A total of 405 patients who underwent primary unilateral TKA in the Department of Orthopaedics, Peking University Third Hospital from June 2022 to June 2024 were retrospectively analyzed, consisting of 89 males and 316 females, with a mean age of 67.84±5.60 years. Patients were divided into the conventional group ( n=215) and the robot-assisted group ( n=190) according to the surgical approach. Postoperative DVT incidence, operative time, postoperative hemoglobin and hematocrit levels, perioperative blood loss, and transfusion rate were compared between the two groups to evaluate the impact of robot-assisted TKA on thrombotic events and related clinical indicators. Results:There were no significant differences in age, sex, height, weight, body mass index, or preoperative laboratory results including hemoglobin and hematocrit levels between the two groups ( P>0.05). The postoperative DVT incidence was 26.8% (51/190) in the robot-assisted group and 34.9% (75/215) in the conventional group, with no significant difference ( P>0.05). Univariate logistic regression analysis showed that sex ( P=0.013) and age ( P=0.024) were significantly associated with DVT occurrence. Multivariate logistic regression further revealed that female patients had a significantly higher incidence of DVT than males ( OR=0.438, P=0.005), and older patients had a significantly increased risk of DVT ( OR=1.046, P=0.025); body mass index remained not significantly associated with DVT ( P=0.092). The operative time in the robot-assisted group was 88.62±18.58 min, which was significantly longer than that in the conventional group 79.23±17.68 min ( t=-5.207, P<0.001). Perioperative total blood loss was 1 079.85±344.18 ml in the robot-assisted group and 1 141.47±363.70 ml in the conventional group, with no significant difference ( t=1.745, P=0.082). The transfusion rate was 5.3% in the robot-assisted group and 5.1% in the conventional group, respectively, with no significant differences (χ 2=0.004, P=0.947). Conclusion:Compared with conventional TKA, robot-assisted TKA results in longer operative time but does not increase perioperative blood loss or the risk of postoperative DVT.

Bone tissue engineering(BTE)is expected to be used as an autologous bone graft substitute for bone defects,and in the se-lection of BTE scaffold materials,collagen(Col)and hydroxyapatite(HA)have attracted attention due to their unique biomimetic ad-vantages.Collagen/hydroxyapatite(CHA)composite scaffolds made by combining the two have been shown to have excellent biocompat-ibility and bone-enhancing potential in various in vitro,in vivo,and clinical studies.With the development of three-dimensional(3D)printing technology in the field of tissue engineering,bone scaffolds constructed using 3D printing methods have been shown to possess superior clinical potential.This review describes new advances in 3D printed CHA composite scaffolds and introduces the application of 3D printed CHA scaffolds in oral and maxillofacial bone regenerative repair.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of thyroid diffuse large B-cell lymphoma(DLBCL).Methods·From November 2003 to December 2021,a total of 66 patients with thyroid DLBCL[23 cases(34.8%)with primary thyroid DLBCL,and 43 cases(65.2%)with secondary thyroid DLBCL]admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival and prognostic factors.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes)in 40 patients.Results·Compared to primary thyroid DLBCL,secondary thyroid DLBCL had advanced ratio of Ann Arbor stage Ⅲ?Ⅳ(P=0.000),elevated serum lactate dehydrogenase(LDH)(P=0.043),number of affected extranodal involvement≥2(P=0.000),non-germinal center B cell(non-GCB)(P=0.030),BCL-2/MYC double expression(DE)(P=0.026),and international prognostic index(IPI)3?5-scores(P=0.000).The proportion of patients who underwent thyroid surgery(P=0.012)was lower than that of patients with primary thyroid DLBCL.The complete remission(CR)rate in primary thyroid DLBCL patients was higher than that in secondary thyroid DLBCL patients(P=0.039).Fifty-five patients(83%)received rituximab combined with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)-based first-line regimen.The estimated 5-year progression free survival(PFS)rate of primary thyroid DLBCL patients was 95.0%,higher than the 49.7%of the secondary patients(P=0.010).Univariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.411,95%CI 1.373?14.170),elevated LDH(HR=5.500,95%CI 1.519?19.911),non-GCB(HR= 5.291,95%CI 1.667?16.788),and DE(HR=6.178,95%CI 1.813?21.058)were adverse prognostic factors of PFS in patients with thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ(HR=7.088,95%CI 0.827?60.717),elevated LDH(HR=6.982,95%CI 0.809?60.266),and DE(HR=18.079,95%CI 1.837?177.923)were adverse prognostic factors of overall survival(OS).Multivariate analysis showed that Ann Arbor Ⅲ?Ⅳ(HR=4.693,95%CI 1.218?18.081)and elevated LDH(HR=5.058,95%CI 1.166?21.941)were independent adverse prognostic factors of PFS in patients with thyroid DLBCL.Targeted sequencing data showed mutation frequency>20%in TET2(n=14,35%),KMT2D(n=13,32%),TP53(n=11,28%),GNA13(n=10,25%),KMT2C(n=9,22%),and TP53 were adverse prognostic factors of PFS in patients with thyroid DLBCL(P=0.000).Conclusion·Patients with primary thyroid DLBCL have better PFS and OS than those with secondary thyroid DLBCL.Ann Arbor Ⅲ?Ⅳ,elevated LDH,non-GCB,and DE(MYC and BCL2)are adverse prognostic factors in thyroid DLBCL.TET2,KMT2D,TP53,GNA13,and KMT2C are commonly highly mutated genes in thyroid DLBCL,and the prognosis of patients with TP53 mutations is poor.

[Objective] To investigate the value of total cholesterol to high-density lipoprotein cholesterol ratio (THR), monocyte to high-density lipoprotein cholesterol ratio (MHR), and neutrophil to high-density lipoprotein cholesterol ratio (NHR) in predicting patients’ coronary artery stenosis severity and percutaneous coronary intervention (PCI). [Methods] A total of 6 281 patients who underwent coronary angiography at our hospital between June 2021 and June 2023 were retrospectively included in this study. These patients were divided into two groups: PCI group and non-PCI group. The clinical data, laboratory findings, and interventional treatment data of all patients were collected and analyzed. Pearson correlation analysis was employed to evaluate the correlation of THR, MHR and NHR with the degree of coronary artery stenosis. Binary Logistic stepwise regression and receiver operating characteristic (ROC) curve were utilized to assess the influencing factors and predictive value of THR, MHR and NHR single and combined indexes for coronary artery disease patients undergoing PCI. [Results] The PCI group was observed to be older, with a higher proportion of males, individuals with diabetes mellitus, and those who had undergone THR, MHR, NHR, and a Gensini score than the non-PCI group. Conversely, the proportion of previous stent implantation was less than that of the non-PCI group (P<0.05). The results of Pearson correlation analysis showed a significant and positive correlation of the Gensini score with THR (r=0.351, P<0.001), MHR (r=0.192, P<0.001), and NHR (r=0.236, P<0.001) levels, indicating that these variables had a significantly positive correlation with the degree of coronary artery stenosis. The results of multifactorial Logistic regression demonstrated that age >50 years, male sex, diabetes mellitus, THR, MHR, and NHR were independent risk factors for PCI in patients with coronary artery disease. Conversely, a history of previous stent implantation was identified as a protective factor for PCI in patients with coronary artery disease. Furthermore, the results of ROC curves indicated that the combined area under the curve (AUC) was the largest for THR, MHR, and NHR (AUC=0.809, 95%CI: 0.798-0.820). [Conclusion] THR, MHR and NHR correlate with the degree of coronary stenosis and have strong clinical applications in the assessment of coronary artery disease for PCI.

Objective:To compare short-term clinical outcomes and patient satisfaction between robotic-assisted total hip arthroplasty (THA) and conventional THA.Methods:Patient data of unilateral primary THA with the same prosthesis by the same operator due to osteoarthritis, osteonecrosis of the femoral head, and other diseases in Peking University Third Hospital from September 2019 to February 2022 was retrospectively analyzed. Patients were divided into robot-assisted THA group and conventional THA group according to surgical methods. The preoperative general data, operation time, intraoperative complications and other intraoperative data were collected. Anteroposterior X-ray of pelvis and cross-table X-ray of hip were taken. Main outcome measures consisted of total blood loss, blood transfusion rate, hospitalization stay, postoperative complications, and the inclination and anteversion angle of the acetabular cup, while the dislocation rate outside the Lewinnek and Callanan safe zone was also analyzed. Other outcomes measures included visual analogue scale, Harris score, quality of life score (QOL) and satisfaction score.Results:There was no significant difference in gender, age, height, weight, body mass index (BMI), operation side, preoperative blood volume and Harris score between the two groups ( P>0.05); Loosening of positioning screws occurred in 2 patients due to osteoporosis in robot-assisted THA group, so conventional THA was performed. Therefore, 84 cases in robot-assisted THA group and 87 cases in conventional THA group were enrolled in this study at last. There was no significant difference in follow-up time between conventional THA group and robot-assisted THA group (19.7±6.8 months vs. 18.6±5.4 months, t=1.16, P=0.249); The operation time of robot-assisted THA group was longer than that of conventional THA group (106.99±31.91 min vs. 73.79±29.48 min, t=7.07, P<0.001), but there was no significant difference in hospitalization stay between conventional THA group and robot-assisted THA group (6.40±2.40 d vs. 6.49±1.95 d, t=0.26, P=0.796). There was also no significant difference in total blood loss and blood transfusion rate between the two groups ( P>0.05). There was no significant difference in inclination angle (38.79°±6.93° vs. 39.41°±3.01°, t=0.58, P=0.449) and anteversion angle (14.81°±6.49° vs. 13.33°±4.32°, t=3.06, P=0.082) between conventional THA group and robot-assisted THA group, while the percentage in Lewinnek safe zone (96.4% vs. 73.6%, χ 2=15.60, P<0.001) and Callanan safe zone (92.9% vs. 65.5%, χ 2=17.61, P<0.001) was significantly higher in conventional THA than that of robot-assisted THA. There were no significant differences in postoperative VAS, Harris score and QOL score between the two groups ( P>0.05), but the excellent and good rate of Harris score of conventional THA group was lower than that of robot-assisted THA group (83.91% vs. 95.24%, χ 2=5.83, P=0.016); The overall satisfaction of patients in robot-assisted THA group was better than that in conventional THA group ( Z=-3.47, P=0.001), and 95.2% (80/84) of patients in robot-assisted THA group were very satisfied, which was higher than that in conventional THA group (75.86%, 66/87). The satisfaction of patients in robot-assisted THA group on pain relief ( Z=-2.44, P=0.015) and improvement of leisure activity ( Z=-2.12, P=0.034) was better than that in conventional THA group, but there was no significant difference in the satisfaction of ability of doing house work between the two groups ( Z=-0.49, P=0.626). Conclusion:Compared with conventional THA, robot-assisted THA has longer operation time but better short-term clinical outcomes and higher patient satisfaction after surgery.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method