Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BackgroundPatients with chronic schizophrenia often suffer from cognitive impairment. Traditional cognitive rehabilitation training has problems such as a single form and poor compliance， making it urgent to develop new cognitive intervention methods. ObjectiveTo explore the intervention effect of smartphone games on the cognitive function of patients with chronic schizophrenia， and to analyze the differences in cognitive function improvement between patients of different genders， in order to provide references for the cognitive function intervention of these patients. MethodsThis study was a prospective cohort study. A total of 30 patients who were hospitalized in the Psychiatry Department of Chaohu Hospital Affiliated to Anhui Medical University from March to October 2021， met the diagnostic criteria for schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）， and had a disease duration of above 5 years， were selected as the research subjects. All patients received smartphone game intervention for 12 weeks， 5 times a week， each session lasting 1 hour， in addition to conventional antipsychotic drug treatment. At the baseline and at 3， 6， 9， and 12 weeks of the intervention， the cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）， the Positive and Negative Syndrome Scale （PANSS） was used to assess mental symptoms， and the Problematic Mobile Gaming Questionnaire （PMGQ） was used to assess addiction symptoms. ResultsA total of 26 patients （86.67%） completed the study， including 13 females and 13 males. The time effects， group effects， and interaction effect between time and group for the immediate memory factor score of RBANS in the female group and the male group were all statistically significant （F=36.682， 5.712， 3.090， P<0.05 or 0.01）， and the time effects and group effects for the verbal and delayed memory factors as well as the total score in both groups were also statistically significant （F=3.841， 6.149， 15.372， P<0.05 or 0.01）. The time effects and group effects of the total score of PANSS in both groups had no statistical significance （F=2.041， 0.623， P>0.05 for both）， and the interaction effect between time and group was statistically significant （F=5.728， P<0.01）. The time effects， group effects， and interaction effect of the total score of PMGQ in both groups were all without statistical significance （F=2.672， 0.166， 0.642， P>0.05 for both）. ConclusionSmartphone game intervention may help improve the cognitive function of patients with chronic schizophrenia （especially immediate memory， verbal function， and delayed memory）， and the benefits are greater for female patients. The smartphone game intervention did not induce game addiction， but no significant improvement in psychotic symptoms was observed. ［Funded by Excellent Young Talents Support Program of Anhui Provincial Department of Education （number， gxyqZD2022022）； www.chictr.org.cn number， ChiCTR2100044113］

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.

Objective: To evaluate the diagnostic performance of magnetic resonance spectroscopy (MRS) in discriminating fumarate hydratase-deficient (FH-d) uterine leiomyomas (ULs) from FH-preserved ULs. Materials and Methods: This study consisted of three stages, with independent cohorts recruited for each stage: 1) sample-size estimation was retrospectively performed on UL specimens (diameter ≥3 cm; age, 20–40 years) from our database with immunohistochemistry (IHC) for 2-succinocysteine (2-SC) as the reference, without genetic testing, 2) MRS sequence optimization in confirmed FH germline mutation participants with ultrasound-detected ULs (diameter ≥3 cm), without IHC analysis, and 3) prospective diagnostic test accuracy was evaluated in consecutive participants with ultrasound-detected ULs (diameter ≥3 cm;age, 20–40 years), using IHC for 2-SC for determining the FH status and subsequent genetic testing in those with positive 2-SC results to identify whether FH mutations were germline or somatic in origin. The choline and fumarate peaks in MRS were classified as positive, negative, or technical failure (TF). TFs were analyzed separately and excluded from the primary diagnostic accuracy calculations. T1-, T2-, and diffusion-weighted images were interpreted as hyperintense or hypointense. The enhancement rate and apparent diffusion coefficient were also acquired. Diagnostic performance was compared between MRS and various magnetic resonance imaging (MRI) features. Results: The optimal MRS parameters for the fumarate peak were echo time (TE) = 140 ms and an average of 256. Among the 360 prospective participants, 37 were confirmed to have FH-dULs. MRS showed positive fumarate peaks in 35 of 37 FH-dULs.After excluding six TFs, the positive fumarate peak on MRS showed 94.6% (35/37) sensitivity, 99.7% (316/317) specificity, and 99.2% (351/354) accuracy, all of which were significantly superior to those of other MRI features (P ≤ 0.002). Conclusion A positive fumarate peak on MRS may be a useful imaging biomarker for diagnosing FH-dULs.

OBJECTIVE To investigate the mechanism of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in knee osteoarthritis （KOA） rats based on Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Seventy-five male SD rats were randomly divided into sham operation group （Sham group）， KOA group， Xibining Ⅱ low-dose group （XBNⅡ-L group， 4 g/kg）， Xibining Ⅱ high-dose group （XBNⅡ-H group， 8 g/kg）， and Xibining Ⅱ high-dose combined with STAT3 activator Colivelin trifluoroacetate （C-TFA） group [C-TFA group， 8 g/kg Xibining Ⅱ+ 1.0 mg/（kg·d） C-TFA]， with 15 rats in each group. Except for the Sham group， the KOA model was established by anterior cruciate ligament transection in the other groups. After successful modeling， each group was given corresponding drugs by intragastric administration and （or） intraperitoneal injection once daily for 28 consecutive days. After the last medication， the pathological changes of synovial tissue of knee joint in each group were evaluated and the indicators were calculated. The levels of serum inflammatory factors were detected. The positive expressions of phosphorylated JAK2 （p-JAK2） and phosphorylated STAT3 （p-STAT3） in synovial tissue of the knee joint were detected. The expressions of JAK2/STAT3 pathway-related proteins and mRNAs in synovial tissue were detected. RESULTS Compared with the Sham group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement； the Krenn score， fibrosis ratio， positive area percentage of p-JAK2 and p-STAT3， p-JAK2/JAK2 and p-STAT3/STAT3， protein expression of Collagen-Ⅰ and α -smooth muscle actin， the mRNA expression of JAK2， STAT3， Collagen-Ⅰ and α -smooth muscle actin， as well as serum levels of interleukin-1β and interleukin-18 were significantly increased （ P ＜0.05）. Compared with the KOA group， the above pathological changes were significantly improved in each dose group of Xibining Ⅱ formula， and all indicators were significantly decreased （ P ＜0.05）， with the XBNⅡ-H group showing better effects than the XBNⅡ-L group （ P ＜0.05）. Compared with the XBNⅡ-H group， the above pathological damages were aggravated in the C-TFA group， and all indicators were significantly worsened （ P ＜0.05）. CONCLUSIONS Xibining Ⅱ formula can alleviate synovial inflammation and fibrosis in KOA rats， and its mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway.

ObjectiveTo investigate the effect of Sanet Vision Integrator (SVI)-based visuomotor integration training on the severity of neglect symptoms, upper limb motor function and activities of daily living (ADL) in patients with post-stroke unilateral spatial neglect (USN). MethodsFrom July, 2023 to September, 2025, 41 patients with post-stroke USN in Beijing Bo'ai Hospital were enrolled and randomly assigned to control group (n = 20) and experimental group (n = 21). Both groups received conventional rehabilitation and visual scanning training, while the experimental group received supplementary SVI-based visuomotor integration training, including saccadic, rotation and hand-eye coordination training, for eight weeks. They were assessed with Chinese Behavioral Inattention Test-Hong Kong version (CBIT-HK), Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI) before and after treatment. ResultsAfter treatment, all the scores significantly improved in both groups (|t| > 4.004, P < 0.001), and the total scores of CBIT-HK and the core visual search sub-items (star cancellation, line crossing and letter cancellation), FMA-UE and MBI were better in the experimental group than in the control group (t > 2.096, P < 0.05). ConclusionSVI-based visuomotor training can effectively alleviate the USN symptoms, broaden the span of visual attention, facilitate the functional recovery of the affected upper extremity, and improve ADL in patients after stroke.

ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis （KOA） with cold-dampness obstruction syndrome， and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group， a treadmill plus climate chamber group， an anterior cruciate ligament transection （ACLT） plus climate chamber group， an ACLT group， a destabilization of the medial meniscus （DMM） plus climate chamber group， a DMM group， an intra-articular injection plus climate chamber group， and an intra-articular injection group， with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model， while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee， and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate （MIA） into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber （relative humidity 60%， temperature 4 ℃， wind speed 6 m/s） simultaneously with aforementioned interventions， once daily for 2 h each time， for 14 consecutive days. Mice in the control group underwent sham surgery， involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity， followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation， undergoing high-intensity treadmill exercise at a speed of 20 m/min， an inclination of 5°， for 30min per session， 5 times per week for 28 consecutive days， while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling， knee joint pathological changes were observed using HE and Safranin O-Fast Green staining， and quantified using Mankin and Osteoarthritis Research Society International （OARSI） scores. Serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by ELISA. Protein and mRNA expression levels of pain-related markers， including calcitonin gene-related peptide （CGRP）， protein gene product 9.5 （PGP9.5）， and cellular proto-oncogene Fos （c-Fos）， and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 （TRPA1） and transient receptor potential melastatin 8 （TRPM8） in the dorsal root ganglion （DRG） tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group， the remaining groups showed decreased cold pain thresholds in the cold plate tese， increased cold pain thresholds in the acetone low-temperature test， elevated Mankin and OARSI scores， and increased serum TNF-α and IL-1β levels， upregulated protein and mRNA expression levels of CGRP， PGP9.5， c-Fos， TRPA1， and TRPM8 in the DRG， and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue （P＜0.05 or P＜0.01）， along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT， DMM， and intra-articular injection groups， the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators （P＜0.01）. Furthermore， changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group， DMM plus climate chamber and intra-articular injection plus climate chamber group （P＜0.01）， exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome， with the ACLT combined with the artificial climate chamber being the optimal modeling approach.

ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis （KOA） with cold-dampness obstruction syndrome， and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group， a treadmill plus climate chamber group， an anterior cruciate ligament transection （ACLT） plus climate chamber group， an ACLT group， a destabilization of the medial meniscus （DMM） plus climate chamber group， a DMM group， an intra-articular injection plus climate chamber group， and an intra-articular injection group， with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model， while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee， and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate （MIA） into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber （relative humidity 60%， temperature 4 ℃， wind speed 6 m/s） simultaneously with aforementioned interventions， once daily for 2 h each time， for 14 consecutive days. Mice in the control group underwent sham surgery， involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity， followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation， undergoing high-intensity treadmill exercise at a speed of 20 m/min， an inclination of 5°， for 30min per session， 5 times per week for 28 consecutive days， while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling， knee joint pathological changes were observed using HE and Safranin O-Fast Green staining， and quantified using Mankin and Osteoarthritis Research Society International （OARSI） scores. Serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by ELISA. Protein and mRNA expression levels of pain-related markers， including calcitonin gene-related peptide （CGRP）， protein gene product 9.5 （PGP9.5）， and cellular proto-oncogene Fos （c-Fos）， and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 （TRPA1） and transient receptor potential melastatin 8 （TRPM8） in the dorsal root ganglion （DRG） tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group， the remaining groups showed decreased cold pain thresholds in the cold plate tese， increased cold pain thresholds in the acetone low-temperature test， elevated Mankin and OARSI scores， and increased serum TNF-α and IL-1β levels， upregulated protein and mRNA expression levels of CGRP， PGP9.5， c-Fos， TRPA1， and TRPM8 in the DRG， and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue （P＜0.05 or P＜0.01）， along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT， DMM， and intra-articular injection groups， the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators （P＜0.01）. Furthermore， changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group， DMM plus climate chamber and intra-articular injection plus climate chamber group （P＜0.01）， exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome， with the ACLT combined with the artificial climate chamber being the optimal modeling approach.

ObjectiveTo summarize the incidence and clinical features of drug hypersensitivity reactions in children treated with sustained-releasing gonadotropin-releasing hormone agonists （GnRHa）， aiming to provide guidance for the safe clinical application of GnRHa in children. MethodsThe medical data of children diagnosed with central precocious puberty （CPP） or early and fast puberty （EFP） were retrospectively analyzed， who received GnRHa treatment at the Children's Growth Center of the First Affiliated Hospital of Sun Yat-sen University between January 1990 and July 2023. The occurrence of GnRHa-related drug hypersensitivity reactions were summarized， including the incidence and clinical features of systemic reactions and sterile abscesses. ResultsAmong the 1 684 children treated with GnRHa for CPP/EFP， the female-to-male ratio was 3.8∶1. A total of nine children （0.53%） developed 44 occurrences of drug hypersensitivity reactions. Four children （0.24%） presented with sterile abscesses （21 occurrences）， and five children （0.30%） experienced systemic hypersensitivity reactions （14 occurrences）. Four children were hypersensitive to triptorelin acetate， three were hypersensitive to leuprorelin acetate， and two were hypersensitive to both triptorelin acetate and leuprorelin acetate. The predominant hypersensitivity reactions to leuprorelin acetate were sterile abscesses， observed in four cases （4/277， 1.44%）， whereas the main reactions to triptorelin acetate were systemic hypersensitivity reactions， affecting five cases （5/1 501， 0.33%）. Case one presented with a severe and complex condition， exhibiting hypersensitivity to multiple GnRHa preparations （sustained-releasing triptorelin， sustained-releasing leuprorelin， and short-acting triptorelin）， and presenting with diverse manifestations， including induration， sterile abscesses， systemic hypersensitivity reactions， and even loss of suppression of the hypothalamic-pituitary-gonadal axis， leading to treatment failure. ConclusionsThe proportion of children experiencing drug hypersensitivity reactions to sustained-releasing GnRHa is relatively low at 0.53%， with diverse manifestations. The reactions primarily manifest as sterile abscesses and systemic hypersensitivity reactions， and in severe cases， may lead to treatment failure due to loss of suppression of the hypothalamic-pituitary-gonadal axis.