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 observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

ObjectiveTo observe the activation patterns and functional connectivity in the prefrontal cortex of patients with post-stroke anxiety (PSA) using functional near-infrared spectroscopy, in order to explore the underlying neural mechanism. MethodsFrom December, 2024 to September, 2025, 120 stroke patients were selected in Changzhou De'an Hospital. They were divided into PSA group (n = 60) and non-PSA group (n = 60) according to the score of Hamilton Anxiety Scale (HAMA). All patients wore an 18-channel fNIRS acquisition cap for detection. The differences in resting-state functional connectivity between the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) were examined in both groups, as well as task-related activation in these brain regions. ResultsResting-state functional connectivity analysis revealed no statistically significant difference in network connectivity between two groups in the FPC and DLPFC regions (|t| < 1.301, P > 0.05). Task-related activation results revealed significantly reduced activation in the contralateral FPC of PSA group compared to the non-PSA group (Z = -2.063, P < 0.05). Activation levels in this region showed a negative correlation with the scores of HAMA (ρ = -0.201, P = 0.028). ConclusionActivation decreased in the contralateral frontal pole during the task state for patients with PSA, and the activation levels negatively correlates with anxiety severities.

AIM:To evaluate the optimal timing of preoperative intravitreal anti vascular endothelial growth factor(VEGF)therapy in proliferative diabetic retinopathy(PDR)using intraoperative fluorescein angiography(IOFA).METHODS:A retrospective case series study was conducted on patients who underwent vitrectomy for PDR with vitreous hemorrhage(VH)at Sichuan Provincial People's Hospital from January 2023 to February 2025. Patients were divided into three groups according to the interval between intravitreal conbercept injection and surgery: Group A(3 d before surgery), Group B(7 d before surgery), and Group C(14 d before surgery). IOFA was used to assess the number and size of retinal neovascularization(NV). Additional data were collected including preoperative best corrected visual acuity(BCVA), vitreous hemorrhage grading, operative time, frequency of intraoperative endodiathermy, duration of high perfusion pressure, vitreoretinal adhesion grade, postoperative BCVA, and central macular thickness(CMT). Multidimensional analyses were performed.RESULTS:This study enrolled a total of 91 patients(94 eyes)with PDR accompanied by vitreous hemorrhage. Among them, Group A consisted of 31 patients(31 eyes; 18 males, 13 females; mean age 53.26±12.38 y), Group B consisted of 34 patients(37 eyes; 21 males, 13 females; mean age 51.61±14.16 y), and Group C consisted of 26 patients(26 eyes; 18 males, 8 females; mean age 51.00±12.02 y), with baseline characteristics comparable among the three groups(all P>0.05). Comparative analysis of NV visualized via IOFA revealed that both the number and size of NVs were significantly lower in Groups B and C than in Group A(all P<0.0167), while no statistically significant differences were observed between Groups B and C(both P>0.05). No significant differences were found among the three groups regarding other intraoperative parameters, including operation time, frequency of electrocoagulation application, duration of high perfusion pressure, or grading of vitreoretinal adhesion(all P>0.05).CONCLUSION:IOFA confirms that preoperative anti-VEGF therapy administered 7 or 14 d before surgery is more effective than a 3 d interval in suppressing retinal NV activity in PDR patients.

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.