Objective:To assess health-related quality of life and disease burden of Chinese Phenylketonuria(PKU)patients and inform optimized management and support strategies.Methods:A cross-sectional survey is conducted to explore questionnaires.The Delphi method was applied to form a standardized questionnaire.Results:A total of 263 valid questionnaires were collected.The average patient age was 7.6 years.Younger patients reported better quality of life.Mean total medical cost per patient was 238 461.9 yuan,exceeding the 2024 national per capita disposable income.Conclusion:PKU patients are facing significant challenges in both quality of life and economic burden.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To assess health-related quality of life and disease burden of Chinese Phenylketonuria(PKU)patients and inform optimized management and support strategies.Methods:A cross-sectional survey is conducted to explore questionnaires.The Delphi method was applied to form a standardized questionnaire.Results:A total of 263 valid questionnaires were collected.The average patient age was 7.6 years.Younger patients reported better quality of life.Mean total medical cost per patient was 238 461.9 yuan,exceeding the 2024 national per capita disposable income.Conclusion:PKU patients are facing significant challenges in both quality of life and economic burden.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To investigate the risk factors and their warning effectiveness for meniscus tear secondary to delayed anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective cohort study was conducted to analyze the clinical data of 114 patients (114 knees) with ACL injury, who were admitted to Affiliated Hospital of Nanjing University of Chinese Medicine from December 2018 to December 2023, including 78 males and 36 females, aged 11-50 years [29(21, 35)years]. The patients were divided into tear group ( n=46) and non-tear group ( n=68) according to whether combined with meniscus tear or not during the surgery. Gender, age, duration of disease, smoking history, Body Mass Index (BMI), cause of injury, mechanism of injury, side of the injury, Beighton score, difference of KT-2000 examination, Tegner activity scale of the knee joint, anterior tibial translation sign, medial posterior tibial slope angle, lateral posterior tibial slope angle, and pivot shift grading of the patients in the two groups were recorded. Correlations between the above-mentioned indicators and occurrence of meniscus tear secondary to delayed ACL reconstruction were assessed. In the meantime, the independent risk factors were determined by univariate and multivariate binary logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the warning effectiveness of each risk factor for meniscal tear secondary to delayed ACL reconstruction. Results:Univariate analysis showed correlation of duration of disease, BMI, Tegner activity scale of the knee joint, medial posterior tibial slope angle, lateral posterior tibial slope angle and high-grade pivot shift with occurrence of meniscus tear secondary to delayed ACL reconstruction ( P<0.01). The results of multivariate binary logistic regression analysis showed that the duration of disease ≥14.5 weeks ( OR=1.20, 95% CI 1.05, 1.38, P<0.01), BMI≥26.9 kg/m 2 ( OR=1.36, 95% CI 1.03, 1.81, P<0.05), Tegner activity scale of the knee joint ≥4 points ( OR=2.29, 95% CI 1.18, 4.46, P<0.05), medial posterior tibial slope angle ≥11.2° ( OR=2.27, 95% CI 1.06, 4.89, P<0.05) and high-grade pivot shift ( OR=0.03, 95% CI 0.01, 0.03, P<0.05) were significantly correlated with occurrence of meniscus tear secondary to delayed ACL reconstruction. Results of ROC curve analysis showed that the medial posterior tibial slope angle (AUC=0.86, 95% CI 0.80, 0.93) and duration of disease (AUC=0.85, 95% CI 0.77, 0.92) had good warning value, BMI (AUC=0.78, 95% CI 0.69, 0.87) and Tegner activity scale of the knee joint (AUC=0.73, 95% CI 0.64, 0.83) had ordinary warning value, and the warning value of high-grade pivot shift (AUC=0.60, 95% CI 0.49, 0.71) was the lowest. The combination of the risk factors revealed superior warning effectiveness for meniscus tear second to delayed ACL reconstruction (AUC=0.97, 95% CI 0.96, 1.00). Conclusions:The duration of disease ≥14.5 weeks, BMI ≥26.9 kg/m 2, Tegner score ≥4 points, medial posterior tibial slope angle ≥11.2°and high-grade pivot shift are independent risk factors for meniscus tear secondary to delayed ACL reconstruction. The medial posterior tibial slope angle and duration of disease have good warning value, BMI and Tegner scores have ordinary warning value and high-grade pivot shift has the lowest warning value. The combination of the above risk factors has better warning effectiveness for meniscus tear secondary to delayed ACL reconstruction.

Tyrosine kinase inhibitors （TKIs） represent a class of small-molecule targeted drugs that improve the survival time of patients with gastrointestinal stromal tumor （GIST）. Imatinib， sunitinib， regorafenib， ripretinib， and avapritinib are commonly used TKIs in the clinical treatment of various types of GIST. This article provides a comprehensive review of the pharmacokinetics and therapeutic drug monitoring （TDM） of these five drugs， finding that there is significant individual variability in the pharmacokinetics of these drugs. Among them， the absorption of imatinib， regorafenib， and avapritinib are influenced by food intake. Imatinib should be taken with meals and 200 mL of water， regorafenib is taken with a low-fat meal， while avapritinib is taken on an empty stomach. TKIs are mainly metabolized by cytochrome P450 3A4 （CYP3A4）， and when used in combination with CYP3A4 inducers or inhibitors， drug exposure levels will significantly change； apart from metabolic enzymes， the exposure levels of TKIs are also influenced by interactions with the transporter proteins P-glycoprotein and breast cancer resistance protein. Currently， research on TDM for TKIs is still in the exploratory stage， with a substantial amount of literature reporting the effective concentrations of imatinib， sunitinib and regorafenib. However， the precise relationship between exposure levels and efficacy/ toxicity needs further exploration. Currently， there is a lack of research on the correlation between exposure levels and efficacy/ toxicity of ripretinib and avapritinib. It is recommended to implement TDM in patients taking these drugs and explore their therapeutic window in combination with pharmacokinetic models. The commonly used methods for clinical TDM of TKIs include immunoassay， chromatography， and surface-enhanced Raman spectroscopy， providing a technical basis for clarifying the therapeutic window of TKIs.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

OBJECTIVE To study the effects and mechanisms of serum containing Wenjing Tongluo Decoction on interleukin-1β(IL-1β)-induced mouse primary chondrocyte injury.METHODS The IL-1β-induced primary chondrocyte injury model was estab-lished,and the mRNA expression of inflammatory factors IL-1β,IL-6,TNF-α,cartilage degradation-related proteases matrix metal-loproteinase 3(MMP3),MMP9,MMP13,ADAM metallopeptidase containing thrombospondin 1 motif 4(ADAMTS4),and glycoly-sis-related enzymes lactate dehydrogenase A(LDHA),M2 pyruvate kinase(PKM2),reduced coenzyme Ⅱ oxidase 2(NOX2)and re-duced coenzyme Ⅱ oxidase 4(NOX4)in the cells was detected;the intracellular MMP3,MMP13,P65,IκB-ζ,hypoxia-inducible factor 1α(HIF-1α)and LDHA protein expression levels were determined;the concentrations of nitric oxide(NO),malondialdehyde(MDA)and lactic acid in the cell supernatant were further detected,and the ratio of the reduced state(NADH)and oxidized state(NAD+)of intracellular coenzyme Ⅰ(NAD),as well as intracellular reactive oxygen species(ROS)levels were assayed.RESULTS Serum containing Wenjing Tongluo Decoction significantly inhibited the mRNA expression of IL-1β,IL-6,and TNF-α in IL-1β chondrocytes(P＜0.01),reduced the NO concentration in the cell supernatant(P＜0.05,P＜0.01),and downregulated the protein ex-pression of IκB-ζ(P＜0.05)and P65(P＜0.05,P＜0.01).Serum containing Wenjing Tongluo Decoction significantly downregulated the mRNA expression of MMP3,MMP9,MMP13 and ADAMTS4(P＜0.01),and inhibited the protein expression of MMP13(P＜0.05,P＜0.01)and MMP3(P＜0.05).In terms of oxidative stress,it significantly suppressed the production of ROS in chondrocytes,increased the NADH/NAD+ratio,reduced the MDA concentration in the supernatant,and downregulated the expression of HIF-1α protein(P＜0.01).The serum containing Wenjing Tongluo Decoction significantly reduced the lactic acid concentration,downregulated the expression of LDHA,PKM2,NOX2 and NOX4,and reduced the level of intracellular glycolysis(P＜0.05,P＜0.01).CONCLU-SION The serum containing Wenjing Tongluo Decoction can alleviate IL-1β-induced mouse primary chondrocyte injury by inhibiting inflammation,cartilage degradation,oxidative stress and glycolysis,which may be related to the regulation of IκB-ζ/HIF-1α/LDHA axis.

BACKGROUND:Transposition of the long head of biceps tendon is a commonly surgical method for massive rotator cuff tears.Currently,there are a few reports on the clinical efficacy of the transposition of the long head of biceps tendon and there is no consensus on the influencing factors for retearing. OBJECTIVE:To observe the outcome of arthroscopic long head of the biceps tendon in the treatment of massive rotator cuff tear. METHODS:The clinical data of 28 patients with massive rotator cuff tears,aged(61.79±10.50)years,admitted at Jiangsu Province Hospital of Chinese Medicine from March 2019 to May 2022 were retrospectively analyzed.All patients underwent arthroscopic long head of the biceps tendon.Patients were assessed for visual analog scale scores,University of California at Los Angeles scores,American Shoulder and Elbow Surgeons scores,Constant-Murley scores,and shoulder range of motion before and 1 year after operation.MRI of the shoulder joint was performed for observing the integrity of the repaired structure at 1 year after operation.Twenty-three patients(5 of 28 lost to follow-up)were categorized into the intact tendon group(n=18)and the tendon retear group(n=5)according to the Sugaya typing at 1 year after operation;the patients were divided into the normal group(n=8),the degeneration group(n=9),and the partial tear group(n=6)according to the intraoperative quality of the long head of the biceps tendon.Differences in the above indexes were compared between groups. RESULTS AND CONCLUSION:When followed up at 1 year after surgery,the range of motion,visual analog scale scores,University of California at Los Angeles scores,American Shoulder and Elbow Surgeons scores,Constant-Murley scores of the shoulder were significantly improved compared with preoperative data(P＜0.05).There was a significant difference in Goutellier grading between intact tendon and tendon retear groups(P＜0.05),while no significant difference was observed in the other influencing factors(P＞0.05).There were no significant differences in visual analog scale scores,University of California at Los Angeles scores,American Shoulder and Elbow Surgeons scores,Constant-Murley scores,and shoulder range of motion at 1 year after operation among the normal,degeneration,and partial tear groups(P＞0.05).MRI findings indicated that the sutured tendon healed well in 18 patients,with a healing rate of 78%.Arthroscopic long head of the biceps tendon for augmented repair can provide a reliable repair for massive rotator cuff tear that is refractory,significantly alleviate the pain of the shoulder joint,and restore the function of the shoulder joint.