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.

ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology （ART） in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer （IVF/ICSI-ET）. These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics， outcomes of the first ART cycle， and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data， the total amount of gonadotropin （Gn） and the days of use between the case group and the control group （P>0.05）. However， the case group had significantly fewer retrieved oocytes， mature oocytes （MII）， lower fertilization and cleavage rates， and fewer transferable and high-quality embryos， as well as fewer embryos transferred during the first cycle （P < 0.05）. However， there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups （P>0.05）. In the analysis of cumulative outcomes， the two groups did not show statistically significant differences in the cumulative pregnancy rate， clinical pregnancy rate per transfer cycle， the number of oocyte retrieval cycles required per live birth， the number of embryo transfer cycles required per live birth， and the number of embryos used for each live birth （P>0.05）. However， the cumulative live birth rate was significantly lower in the case group compared to the control group （P=0.005）. ConclusionAfter treatment for thyroid cancer， when ART is used to help pregnant women， the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.

Objective: To provide evidence for improving emergency blood supply protocols by analyzing the clinical characteristics and disease distribution of emergency transfusion patients, especially those receiving≥10 units of red blood cells (RBCs). Methods: The data of 4 157 patients who urgently applied for large-volume blood transfusion in various hospitals in Shanghai from May 2024 to April 2025 were selected and analyzed statistically. Results: Tertiary gradeA hospitals accounted for the largest proportion of total transfusion volume (U) (48.79%, 8 420/17 256.5), with no statistically significant differences in RBC transfusion volumes among hospitals of different grades (P>0.05). All blood products are most widely used in tertiary hospitals. Obstetric blood transfusion (U)(19.07%, 3 277.5/17 190.5) was the most frequent. A-mong the hospitals of patients who received emergency blood transfusion with red blood cell suspension≥10 U, tertiary gradeA hospitals also had the largest transfusion volume (U)(47.19%, 1 107/2 346). In terms of disease types, the top three diseases in terms of blood transfusion volume (U) were obstetric transfusion (24.59%, 572/2 326), digestive diseases (14.53%, 338/2 326) and tumors (14.19%, 330/2 326). Conclusion: Tertiary grade A hospitals are the main demand units for emergency blood transfusion, with pregnant women and cancer patients being the core blood-using groups. It is suggested that the safety, timeliness and sufficiency of emergency blood transfusion be guaranteed by establishing a hierarchical blood supply mechanism, formulating single-disease blood transfusion plans and promoting precise blood transfusion guided by thromboelastography.

Objective To explore the feasibility of using high-definition thoracoscopy to identify sympathetic ganglia during thoracic sympathicotomy for primary palmar hyperhidrosis. Methods The clinical data of patients with primary palmar hyperhidrosis who underwent high-definition thoracoscopic sympathicotomy in Taikang Xianlin Drum Tower Hospital from June to July 2023 were retrospectively analyzed. Intraoperative visualization rates and anatomical variations of sympathetic ganglia were recorded, and the consistency between white-light thoracoscopy and near-infrared fluorescence imaging was compared. Additionally, surgical videos from previous fluorescence-guided procedures were reviewed. Results Finally 100 patients were collected, including 54 females and 46 males, with an average age of (21.92±6.56) years. All patients underwent endoscopic thoracic sympathicotomy at R3 level. The overall intraoperative ganglion visualization rate was 92.5% (740/800), with G2-G5 rates of 95.5% (191/200), 94.0% (188/200), 94.0% (188/200), and 86.5% (173/200), respectively. Ganglion variations occurred in 32.0% (237/740), predominantly at G3 (29.8%) and G4 (42.6%). In 5 indocyanine green-enhanced patients, the concordance rate between white-light and near-infrared fluorescence imaging was 100.0% (38/38). Video analysis of 14 near-infrared fluorescence-guided surgeries demonstrated a 99.1% (107/108) consistency rate. Postoperative palmar hyperhidrosis improvement reached 100.0% (100/100) with no Horner’s syndrome. Conclusion With the wide clinical application of high-definition thoracoscopy, accurate thoracic sympathicotomy has the feasibility of clinical application.

OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

Background and purpose:Single-week ultra-hypofractionated whole breast irradiation(WBI)after breast-conserving surgery could shorten the treatment duration while ensuring efficacy and safety,making it a viable option for WBI.However,ultra-hypofractionated WBI requires daily image-guided radiotherapy(IGRT),and its impact on setup errors remains unclear.This study aimed to identify factors associated with set-up errors in ultra-hypofractionated WBI guided with daily cone-beam computed tomography(CBCT)and calculate margin expanded from clinical target volume(CTV)to planning target volume(PTV).Methods:This study included patients enrolled in a prospective trial that explored the safety of single-week ultra-hypofractionated WBI(NCT04926766)in Shanghai Ruijin Hospital,which was approved by Shanghai Ruijin Hospital Ethics Committee(No.2020-352).All patients received CBCT1 after positioning.After correcting errors,patients received CBCT2.CBCT3 was conducted after radiotherapy was completed.The translational errors between CBCT1,CBCT2,and plan CT were initial and residual inter-fractional errors.The translational error between CBCT2 and CBCT3 was an intra-fractional error.The PTV margin was calculated according to the van Herk formula.Results:A total of 34 patients were enrolled in this study,and 510 CBCT images were collected.Daily CBCT significantly reduced set-up error in anterior-posterior(AP),superior-inferior(SI)and right-left(RL)directions(initial inter-fractional error vs residual inter-fractional error:AP,2.8 mm vs 0.4 mm;SI,1.6 mm vs 0.5 mm;RL,1.8 mm vs 0.3 mm,all P＜0.001).Higher CTV volume(＞402.5 cm3 vs≤402.5 cm3)was associated with larger residual inter-fractional error(0.5 mm vs 0.3 mm,P=0.023)and intra-fractional error(0.5 mm vs 0.2 mm,P=0.001)in AP direction.Higher CTV volume was also associated with larger residual inter-fractional error in the SI direction(0.6 mm vs 0.5 mm,P=0.037).Higher BMI(＞23.2 kg/m2 vs≤23.2 kg/m2)and larger weight(＞60.0 kg vs≤60.0 kg)were associated with larger intra-fractional error in AP direction:0.7 mm vs 0.2 mm(P＜0.001)and 0.5 mm vs 0.2 mm(P=0.033),respectively.Under guidance with daily CBCT,the recommended margins were 2.3 mm in AP direction,2.8 mm in SI direction,and 2.0 mm in RL direction.However,in patients with CTV volume＞402.5 cm3 and BMI＞23.2 kg/m2,a larger margin was recommended in SI direction:3.1 mm and 3.4 mm,respectively.Conclusion:The 3 mm margin was feasible under guidance with daily CBCT.The CTV to PTV margin should be larger in patients with higher BMI or CTV volume.

Background and purpose:In breast cancer surgery,margin status assessment significantly impacts patient prognosis,with positive margins indicating higher recurrence and metastasis risks.Ensuring complete tumor resection is thus critical for surgical success.Indocyanine green(ICG)has garnered attention for its potential real-time imaging of breast cancer lesions under near-infrared light.This study employed ICG for intraoperative assessment of breast cancer lesion margin status and further explored the possibility of optimizing the safe margin distance surround the lesion in normal breast tissue.Methods:Clinical data of patients admitted to the Department of Thyroid and Breast Surgery,the Fourth Affiliated Hospital of Anhui Medical University(Affiliated Chaohu Hospital),from December 2021 to September 2022 were collected.A retrospective clinical study was conducted on breast cancer patients who were randomly assigned to either the ICG group or the conventional surgery group.Two to three hours before surgery,patients in the ICG group received a peripheral intravenous injection of 0.5 mg/kg ICG.Intraoperative fluorescence imaging was performed on the specimen before and after resection,as well as on the residual cavity.Near-infrared fluorescence imaging equipment was used to quantitatively measure fluorescence intensity of resected lesions at 4 directions(12,3,6,and 9 o'clock)and detect fluorescence in the residual cavity after lesion removal.Specimens were promptly sent to the pathology department for pathological examination,and safety margins of normal breast tissue in the 4 directions were recorded.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this study.This study was approved by the Ethics Committee of the Fourth Affiliated Hospital of Anhui Medical University(Affiliated Chaohu Hospital)(No.KYXM-202310-46).Results:This study included 50 breast cancer patients,with 24 in the ICG group and 26 in the traditional surgery group.In the ICG group,fluorescence signals were detected at all lesion sites.Specifically,fluorescence density values at the lesion center,margin,and surrounding normal breast tissue were measured as 251.08±10.73,208.08±19.74,and 156.76±16.47,respectively,showing a gradual decrease from center outward with statistically significant differences(P＜0.05).Additionally,fluorescence ratios between the lesion center and margin,and center and surrounding normal tissue,were 1.22±0.13 and 1.62±0.19,respectively.After resection,abnormal fluorescence was observed in 2 of 24 cases in the residual cavity,with 1 case being invasive carcinoma with ductal carcinoma in situ and the other normal breast tissue.Ultimately,this study demonstrated that ICG achieved a sensitivity of 95.9%and a specificity of 97.9%in margin assessment.After specimen resection,the safety margins of normal glandular tissue surrounding the lesion were measured.The safety widths for the ICG group and the concurrent breast cancer surgery group were(8.36±6.42)mm and(15.08±4.75)mm,respectively.This difference was statistically significant(P＜0.05).Conclusion:ICG is a real-time,efficient,and cost-effective tracer that can be used to determine breast cancer margins,with excellent sensitivity and specificity.For early-stage breast cancer patients who are eligible for breast-conserving surgery,this tracer helps to reduce the amount of healthy breast tissue that is removed around the lesion.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.