ObjectiveTo elucidate the efficacy connotation of Shudi Qiangjin pills （SQP） against liver and kidney deficiency in steroid-induced osteonecrosis of femoral head （SONFH） from the perspective of the "disease-syndrome-formula" association and to clarify the underlying mechanisms based on in vivo and in vitro experiment validation. MethodsThe chemical components and the corresponding putative targets of SQP were collected from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， the Encyclopedia of Traditional Chinese Medicine （ETCM） v2.0， and HERB databases. The SONFH-related genes were identified based on the differential expression profiles of peripheral blood of patients with SONFH compared to the healthy volunteers， and the disease phenotype-related targets were collected from the TCMIP v2.0 database. Then， the interaction network of "SONFH-related genes and candidate targets of SQP" was constructed based on "gene-gene interaction information"， and the major network targets were screened by calculating the topological characteristic values of the network followed by the functional mining according to the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and the SoFDA database. After that， the SONFH rat model was prepared by lipopolysaccharide combined with methylprednisolone injection， and 2.5， 5， 7.5 g·kg^-1 SQP （once per day， equivalent to 1， 2， and 3 times the clinical equivalent dose， respectively） or 7.3×10^-3 g·kg^-1 of alendronate sodium （ALS， once per week， equivalent to the clinical equivalent dose） was given for 8 weeks. The effect characteristics of SQP and ALS in the treatment of SONFH were evaluated by micro-computed tomography scanning， hematoxylin and eosin staining， alkaline phosphatase （ALP） staining， immunohistochemical staining， enzyme-linked immunosorbent assay， and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL）staining， and a comparative efficacy analysis was conducted with ALS. In addition， SONFH cell models were prepared by dexamethasone stimulation of osteoblasts， and the intervention was carried out with the medicated serum of SQP at the aforementioned three doses. Cell counting kit-8， ALP staining， ALP activity assay， alizarin red staining， and flow cytometry were employed to investigate the regulatory effect of SQP on osteoblasts. The expression levels of osteogenesis-related proteins and key factors of the target signaling axis were detected by quantitative real-time polymerase chain reaction and Western blot. ResultsThe network analysis results demonstrated that the candidate targets of SQP primarily exerted their therapeutic effects through key signaling pathways， including phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt）， lipid metabolism and atherosclerosis， prolactin， chemokines， and neurotrophic factors pathways. These pathways were significantly involved in critical biological processes such as muscle and bone metabolism and the regulation of the "neuro-endocrine-immune" network， thereby addressing both modern medical symptoms （e.g.， delayed skeletal maturation and recurrent fractures） and traditional Chinese medicine （TCM） symptoms （e.g.， fatigue， aversion to cold， cold limbs， and pain in the limbs and joints in patients with SONFH characterized by liver and kidney deficiency syndrome. Among these pathways， the PI3K/Akt signaling pathway exhibited the highest degree of enrichment. The in vivo experimental results demonstrated that starting from the 4^th week after modeling， the modeling group exhibited a significant reduction in body weight compared to the control group （P<0.05）. After six weeks of treatment， all dosage groups of SQP showed significantly higher body weights compared to the model group （P<0.01）. Compared with the normal group， the model group exhibited significant decreases in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular number （Tb.N）， osteocalcin （OCN）， alkaline phosphatase （ALP） levels in femoral head tissue， and serum bone-specific alkaline phosphatase （BALP） （P<0.01）， along with significant increases in trabecular separation （Tb.Sp）， empty lacunae rate in tissue， and apoptosis rate （P<0.01）. In comparison to the model group， the SQP intervention groups showed significant improvements in BMD， BV/TV and Tb.N （P<0.01）， significant reductions in Tb.Sp， empty lacunae rate and apoptosis rate （P<0.05）， and significant increases in protein levels of OCN and ALP as well as BALP content （P<0.05）. The in vitro experimental results revealed that all dosage groups of SQP medicated serum showed no toxic effects on osteoblast. Compared with the normal group， the model group displayed significant suppression of osteoblast proliferation activity， ALP activity， and calcified nodule formation rate （P<0.01）， significant decreases in mRNA transcription levels of OCN and Runt-related transcription factor 2 （RUNX2） （P<0.01）， significant reductions in protein content of osteopontin （OPN）， typeⅠ collagen （ColⅠ）A1， B-cell lymphoma-2 （Bcl-2）， PI3K， and phosphorylated （p）-Akt （P<0.01）， and a significant increase in apoptosis rate （P<0.01）. Compared with the model group， the SQP medicated serum intervention groups exhibited significant increases in proliferation activity， ALP activity， calcified nodule formation rate， mRNA transcription levels of OCN and RUNX2， and protein content of OPN， ColⅠA1， Bcl-2， PI3K， and p-Akt （P<0.05）， along with a significant decrease in apoptosis rate （P<0.01）. ConclusionSQP can effectively reduce the disease severity of SONFH with liver and kidney deficiency syndrome and improve bone microstructure， with the therapeutic effects exhibiting a dose-dependent manner. The mechanism may be related to its regulation of key processes such as muscle and bone metabolism and the correction of imbalances in the "neuro-endocrine-immune" network， thereby promoting osteoblast differentiation and inhibiting osteoblast apoptosis. The PI3K/Akt signaling axis is likely one of the key pathways through which this formula exerts its effects.

AIM:To explore the effect of miR-1246 on high glucose-induced retinal microvascular endothelial cells(RMECs)injury by regulating methyltransferase like 3(METTL3)mediated sirtuin 1(SIRT1)N6-methyladenosine(m6A)modification.METHODS:Dual luciferase assay was used to detect miR-1246 regulation of METTL3 expression; RMECs cells were divided into control group, high glucose(HG)group, high glucose+knocking down control(HG+anti-miR-NC)group, high glucose+knocking down miR-1246 expression(HG+anti-miR-1246)group, high glucose+overexpression control(HG+NC)group, high glucose+overexpression METTL3(HG+METTL3)group, high glucose+overexpression miR-1246+control(HG+miR-1246+NC)group, and high glucose+overexpression miR-1246+METTL3(HG+miR-1246+METTL3)group. After induction of high glucose for 48 h, CCK-8 method was used to detect cell survival; Annexin V-FITC/PI method was used to detect cell apoptosis; Transwell experiment was used to detect cell migration and invasion; ELISA method was used to detect cell oxidative stress and inflammation levels; Colorimetric method was used to detect m6A methylation level in total RNA; MeRIP-qPCR method was used to detect SIRT1 m6A methylation level; Real-time quantitative PCR was used to detect miR-1246, METTL3, SIRT1 mRNA expression in cells; Western blot was used to detect METTL3, SIRT1 and endothelial mesenchymal transition(EndMT)markers protein expression in cells.RESULTS: The MiR-1246 regulated METTL3 expression. Compared with the control group, cell survival rate was decreased in the HG group, apoptosis rate was increased, and the number of migrating and invading cells were increased, lactate dehydrogenase(LDH)activity, tumor necrosis factor-α(TNF-α), and interleukin(IL)-6 levels in cell culture supernatant were increased, IL-10 level was decreased, malondialdehyde(MDA)level was increased, superoxide dismutase(SOD)activity was decreased, miR-1246 expression was increased, total RNA m6A level and SIRT1 m6A level were decreased, METTL3, SIRT1, cluster of differentiation 31(CD31)and vascular endothelial cadherin(VE-cadherin)expression were decreased, while Vimentin and Snail1 expression were increased(all P<0.05); compared with the HG+anti-miR-NC group, cell survival rate was increased in the HG+anti-miR-1246 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05); compared with the HG+NC group, cell survival rate was increased in the HG+METTL3 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05); compared with the HG+miR-1246+NC group, cell survival rate was increased in the HG+miR-1246+METTL3 group, apoptosis rate was decreased, and the number of migrating and invading cells were decreased, LDH activity, TNF-α, and IL-6 levels in cell culture supernatant were decreased, IL-10 level was increased, MDA level was decreased, SOD activity was increased, miR-1246 expression was decreased, total RNA m6A level and SIRT1 m6A level were increased, METTL3, SIRT1, CD31 and VE-cadherin expression were increased, while Vimentin and Snail1 expression were decreased(all P<0.05).CONCLUSION:The miR-1246 promotes high glucose-induced apoptosis, invasion and metastasis, oxidative stress, inflammatory response, and EndMT process in RMECs cells by regulating METTL3 mediated SIRT1 m6A modification.

BACKGROUND:Plate fixation is the mainstream method for the surgical treatment of distal femoral fractures.The intramedullary nailing has the advantages of minimally invasive,such as less soft tissue injury and bone blood supply destruction.At the same time,it is a central fixation and has better biomechanical effect.Therefore,retrograde intramedullary nailing has become another option for the internal fixation of distal femoral fractures.OBJECTIVE:The biomechanical characteristics of new retrograde intramedullary nail on lateral femur condyle,common femoral retrograde intramedullary nail,and lateral femur condyle anatomical locking plate for the treatment of A2-type distal femoral fractures were compared using finite element analysis,and the advantages of new retrograde intramedullary nail on lateral femur condyle was studied.METHODS:A new retrograde intramedullary nail on lateral femur condyle was designed,which was inserted into the bone cortex in front of the insertion point of the lateral collateral ligament of the lateral femoral condyle.A CT scan was performed on the lower limb bone of a male volunteer,and a three-dimensional model of the femur was established.The model was then segmented to create a three-dimensional model of a femoral distal A2-type fracture,The three-dimensional models of small(small group),standard type retrograde intramedullary nail on the lateral femoral condyle(standard group),common retrograde intramedullary needle(common group),and lateral femur condyle anatomical locking plate(plate group)were established respectively.The axial stresses of 600,1 800 N and the torsional load of 4 000,8 000 N·mm were applied to the models,and the displacement and stress of femur and the displacement,stress and shear force of internal fixators were observed in each group.RESULTS AND CONCLUSION:(1)When subjected to axial load of 600 and 1 800 N,the femoral peak displacement,the femoral peak stress,and the peak stress of interal fixation in the standard group were the lowest among the four groups.(2)When subjected to torsional load of 4 000 and 8 000 N·mm,the femoral peak displacement and peak displacement of the internal fixation in the standard group were the lowest among the four groups.(3)Compared with femoral lateral condylar locking plate and common retrograde intramedullary needle,the new retrograde intramedullary needle on lateral femur condyle has mechanical advantages of reducing stress concentration and decreasing the risk of internal fixation failure.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

ObjectiveTo investigate the molecular mechanism by which Yifei Xuanfei Jiangzhuo prescription regulates the nuclear factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway to improve neuronal function in vascular dementia （VaD） rats. MethodsA VaD model was established by intermittently clamping the bilateral common carotid arteries （CCA） combined with bilateral vascular occlusion （2-VO）. Eighty-four SD rats were randomly divided into a blank group， sham group， model group， piracetam group （0.2 g·kg^-1）， and low-， medium-， and high-dose Yifei Xuanfei Jiangzhuo prescription groups （6.09， 12.18， and 24.36 g·kg^-1）. Drug administration began on day 7 after surgery， once daily for 28 consecutive days. Behavioral experiments were used to evaluate learning and spatial memory. Hematoxylin-eosin （HE） staining was applied to observe pathological morphological changes in the CA1 region of the hippocampus. Transmission electron microscopy was used to examine the ultrastructure of hippocampal neurons. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect neuronal apoptosis in the CA1 region. Immunohistochemistry was performed to determine the positive expression rate of neuronal nuclear antigen （NeuN）. Immunofluorescence single staining was used to assess nuclear expression of NF-κB p65 in brain tissue. Western blot was used to detect the protein expression levels of inhibitor of κB kinase （IKK）， NF-κB p65， NLRP3， Caspase-1， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β）. ResultsCompared with the blank group， the model group showed a significant reduction in platform-crossing frequency （P0.01）， aggravated hippocampal injury， a significant increase in neuronal apoptosis （P0.05）， decreased NeuN positivity in the CA1 region （P0.05）， increased nuclear expression of NF-κB p65 （P0.05）， and significantly elevated expression of p-IKK， p-NF-κB p65， NLRP3， cleaved Caspase-1， ASC， and cleaved IL-1β （P0.05）. Compared with the model group， all drug-treated groups improved learning and spatial memory in VaD rats， alleviated hippocampal pathological injury and neuronal apoptosis， and protected neuronal ultrastructure. Yifei Xuanfei Jiangzhuo prescription at doses of 12.18 and 24.36 g·kg^-1 reduced hippocampal expression levels of p-IKK， p-NF-κB p65， NLRP3， Caspase-1， ASC， and cleaved IL-1β in VaD rats （P0.05）， showing dose-dependent inhibition of the NF-κB/NLRP3 signaling pathway. ConclusionYifei Xuanfei Jiangzhuo prescription may exert neuroprotective effects by regulating the NF-κB/NLRP3 signaling pathway， thereby reducing neuroinflammation and inhibiting hippocampal neuronal apoptosis.

Objective To systematically analyze the literature characteristics of Journal of Organ Transplantation since its inception. Methods Using the China National Knowledge Infrastructure (CNKI) academic journal full-text database as the data source, all articles published in the Journal of Organ Transplantation from January 2010 to August 2025 were retrieved. After excluding non-academic papers, a total of 1 568 research papers were included. R language 4.3.0, Bibliometrix package 3.2.1, and Citespace software were used to analyze the number of publications, publishing institutions, authors, keywords and other aspects. Results The number of publications in Journal of Organ Transplantation increased from an average of 82 articles per year in the early years after its inception to 113 articles per year in recent years, a growth of 37.8%. The geographical distribution of publishing institutions covers 32 provinces, cities and autonomous regions nationwide, mainly concentrated in the South China, East China and North China regions, and has now basically covered the central and western regions in recent years. The author collaboration network includes 45 authors distributed across 7 major collaboration clusters, forming a stable multi-level national research system centered on key university-affiliated hospitals. The high-frequency keywords are dominated by "liver transplantation" (425 times) and "kidney transplantation" (396 times). The theme evolution shows a clear three-stage characteristic: initially focusing on clinical technology application, deepening to immune mechanism exploration in the middle stage, and recently (since 2022) focusing on cutting-edge research areas such as xenotransplantation. Conclusions Journal of Organ Transplantation has witnessed the rapid development of China's organ transplantation cause, fully reflecting the research status and trends in China's organ transplantation field, and has provided an important platform for the future development and international cooperation in China's organ transplantation field.

OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

OBJECTIVE To explore the influencing factors for successful detoxification in patients undergoing methadone maintenance therapy. METHODS A retrospective selection of 161 methadone maintenance therapy patients from the South Branch of Zhongshan Second People’s Hospital （including methadone maintenance treatment sites in Shiqi District， Xiqu District， Development Zone of Zhongshan City） from January 1， 2012， to January 1， 2025， was conducted as the study object. Data collected included patients’ sociodemographic information， drug abuse history， laboratory test results， medication records， etc. Patients were divided into the unsuccessful detoxification group and the successful detoxification group based on whether methadone detoxification was achieved. Univariate， univariate Cox regression， and multivariate Cox proportional hazards regression were used for influencing factor analysis， and the Kaplan-Meier method was employed for survival analysis. RESULTS Among the 161 methadone maintenance therapy patients， 96 were in the successful detoxification group and 65 in the unsuccessful detoxification group， yielding a successful detoxification rate of 59.63%. Multivariate Cox proportional hazards regression analysis revealed that age， registered residence status， age at first drug use， and duration of drug abuse were key influencing factors for successful detoxification in methadone maintenance therapy patients （P＜0.05）. Specifically， the successful detoxification rate for patients with Zhongshan local registered residence was 8.364 times higher than that for patients with non-local registered residence； for every 1-year increase in patient age， the successful detoxification rate decreased by 22.7%； for every 1-year increase in age at first drug use， the successful detoxification rate rose by 33.4%； and for every 1-year increase in duration of drug abuse， the successful detoxification rate increased by 33.5%. Survival analysis showed that the successful detoxification rate in the methadone low-dose group （≤30.8 mg） was significantly higher than that in the methadone high-dose group （＞30.8 mg） （P＝0.015）， and the successful detoxification rate in the population with Zhongshan local registered residence was significantly higher than that in those with non-local registered residence （P＜0.001）. CONCLUSIONS Age， registered residence status， age at first drug use， and duration of drug abuse are key influencing factors for successful detoxification in patients undergoing methadone maintenance therapy， and the last methadone dose may be associated with successful detoxification.

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.