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.

BACKGROUND:At present,the incidence of scoliosis is increasing year by year,especially in adolescent idiopathic scoliosis.Therefore,it is more and more important to strengthen the research on the treatment of adolescent scoliosis. OBJECTIVE:To summarize the current status,hotspots,emerging trends,and frontiers of global research on the treatment of adolescent idiopathic scoliosis to provide reference and guidance for future related research. METHODS:The literature related to the treatment of adolescent idiopathic scoliosis was retrieved on the Web of Science Core Collection(WOSCC)database from 2013 to 2023.CiteSpace 6.2.R1 software was used for visual analysis of countries,institutions,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 561 English articles were included in this study.Among countries,institutions,and authors,the United States has contributed the most.Nanjing University and Qiu,Yong(Affiliated Drum Tower Hospital,Nanjing University School of Medicine)are the most published institution and author.The academic journal with the largest number of articles is the European Spine Journal.(2)In the analysis of cited literature,the top 10 most cited articles mainly describe the effects of surgical treatment and conservative treatment on improving adolescent idiopathic scoliosis,especially improving the curvature of patients.(3)Through the summary of highly cited articles and the keyword clustering,keyword prominence in-depth mining,the research hotspots are currently the relationship between Cobb angle and treatment choice,the therapeutic effect of exercise therapy and the therapeutic effect of posterior vertebral fusion.(4)The prognosis of patients with different curvatures has not been studied in depth,and the etiology of adolescent idiopathic scoliosis has not been clarified,so the relationship between curvature and prognosis and the etiology of adolescent idiopathic scoliosis may be a new research trend in the future.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Feishu" (BL13) on immunoinflammatory response in rats with allergic rhinitis (AR) based on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, so as to explore its underlying mechanism. METHODS: Thirty-two male SD rats were randomly divided into a blank group (6 rats) and a modeling group (26 rats). In the modeling group, AR model was prepared using systemic and local attack sensitization method with ovalbumin. The successfully-modeled rats were randomized into a model group (6 rats), a medication group (6 rats) and a moxibustion group (14 rats). In the moxibustion group, the suspending moxibustion was operated at bilateral "Feishu" (BL13), 40 min each time, once daily, for 21 consecutive days; during which, the temperature of the body and tail was recorded. During intervention, if the temperature of the body and tail increased by >1 ℃, the heat-sensitive reaction at the point was determined in the rats of the moxibustion group, and these rats were collected in a heat-sensitive moxibustion group (8 rats involved and 6 rats of them were randomly collected to ensure the sample-size consistency); and those without heat-sensitive moxibustion reaction were assigned to a traditional moxibustion group (6 rats). In the medication group, fluticasone propionate nasal spray was applied, 8 μL on each side, once daily and for 21 days. The behavioral score for AR symptoms after modeling and intervention, and the content of serum immunoglobulin E (IgE) after modeling were observed. After intervention, the histological morphology of the nasal mucosa was observed using HE staining, the positive expression of thymic stromal lymphopoietin (TSLP) in the nasal mucosa was detected using immunohistochemistry, the levels of IgE, interleukin (IL)-4, IL-5, IL-13 and interferon-γ (IFN-γ) were detected by ELISA, and the protein expression of the member 4 of tumor necrosis factor receptor superfamily (OX40), phosphorylated protein kinase B (p-AKT), phosphorylated phosphatidylinositol 3-kinase (p-PI3K) in nasal mucosa was detected by Western blotting. RESULTS: After modeling, the behavioral score of AR symptoms and serum IgE level in the modeling group were higher than those of the blank group (P<0.01), suggesting the success of AR modeling. After intervention, compared with the blank group, the behavioral score of AR symptoms was increased (P<0.01)；the nasal mucosa structure was disordered, the inflammatory infiltration was severe; the positive expression of TSLP in the nasal mucosa increased (P<0.01), the levels of serum IgE, IL-4, IL-5, and IL-13 elevated (P<0.01), and the level of IFN-γ decreased (P<0.01); and the protein expression of OX40, p-AKT, and p-PI3K in the nasal mucosa increased (P<0.05) in the model group. Compared with the model group, the behavioral score of AR symptoms was reduced (P<0.01); the nasal mucosa structure, inflammatory infiltration, and vascular dilation were ameliorated to varying degrees; the positive expression of TSLP in the nasal mucosa decreased (P<0.01); the content of serum IgE, IL-4, IL-5, and IL-13 decreased (P<0.05), and that of IFN-γ increased (P<0.05) in the medication, traditional moxibustion, and heat-sensitive moxibustion groups. Compared with the model group, the protein expression of p-AKT was reduced in the medication and traditional moxibustion groups (P<0.05), the protein expression of OX40, p-AKT, and p-PI3K in the nasal mucosa decreased in the heat-sensitive moxibustion group (P<0.05). When compared with the medication group, the positive expression of TSLP in the nasal mucosa was reduced (P<0.05) in the heat-sensitive moxibustion group. In comparison with the traditional moxibustion group, the content of serum IL-13 was reduced and the content of IFN-γ elevated in the heat-sensitive moxibustion and the medication groups (P<0.05), the protein expression of p-PI3K reduced in the medication group (P<0.05), and the positive expression of TSLP and the protein expression of OX40 and p-PI3K in the nasal mucosa were reduced in the heat-sensitive moxibustion group (P<0.05). CONCLUSION Heat-sensitive moxibustion at "Feishu" (BL13) can alleviate the symptoms of AR rats, ameliorate the inflammatory infiltration and telangiectasia of nasal mucosa, and inhibit immunoinflammatory response, which may be obtained by regulating PI3K/AKT signal pathway.
Animals ; Moxibustion ; Male ; Rats ; Signal Transduction ; Rats, Sprague-Dawley ; Rhinitis, Allergic/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Acupuncture Points ; Humans ; Phosphatidylinositol 3-Kinases/immunology* ; Phosphatidylinositol 3-Kinase/immunology*

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Objective:To explore the potential categories and influencing factors of family resilience of breast cancer patients based on potential profile analysis to provide reference for targeted intervention.Methods:Cross-sectional investigation was used. From January 2022 to June 2023, 268 breast cancer patients revisited in the outpatient department or ward of the Second Affiliated Hospital of Guilin Medical College and Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the study objects. The subjects were investigated by general data questionnaire, Family Resilience Assessment Scale, Medical Coping Style Questionnaire and Perceptive Social Support Scale. Potential profile analysis was used to identify the potential categories of family resilience in breast cancer patients, and ordered multiple Logistic regression analysis was used to determine the influencing factors of family resilience.Results:Totally 268 cases of breast cancer, aged 30-65 (49.51 ± 3.23) years old; the total score of family resilience was (81.78 ± 13.71) points. The family toughness of breast cancer patients could be divided into three potential profiles: low toughness and low coping difficulty group (23.1%), medium toughness and medium coping difficulty group (33.2%), high toughness and high coping difficulty group (43.7%). The results of ordered multiple Logistic regression analysis showed that residence, per capita monthly household income, medical coping style and perceived social support had an impact on the potential categories of family resilience in breast cancer patients (all P<0.05). Conclusions:There is group heterogeneity in family resilience of breast cancer patients. Medical staff should pay attention to the classification of patients in different places of residence and family per capita monthly income, and formulate personalized and precise interventions from the aspects of coping styles and social support to improve family resilience.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To explore the predictive value of preoperative pelvic floor electromyography(EMG)parameters for the risk of urinary incontinence after prostate cancer surgery.Methods:This study retrospectively analyzed the medical records of 271 patients who underwent radical prostatectomy in the urology department of Peking University First Hospital from January 2020 to October 2022.The data included patient age,body mass index(BMI),international prostate symptom score(IPSS),prostate-specific antigen(PSA)levels,Gleason score,type of surgery,urethral reconstruction,lymph node dis-section,nerve preservation,catheterization duration,D'Amico risk classification,American Society of Anesthesiologists(ASA)score,Charlson comorbidity index,postoperative duration,prostate volume,and pelvic floor EMG parameters(pre-resting mean,fast muscle mean,and slow muscle mean scores).Independent risk factors affecting early postoperative urinary incontinence were identified through multiva-riate Logistic regression analysis.The predictive efficacy of pelvic floor EMG results was evaluated by cal-culating the area under the receiver operating characteristic(ROC)curve,and the optimal threshold for early postoperative urinary incontinence was determined based on the Youden index and clinical signifi-cance.Results:The study included 271 prostate cancer patients,with an 81.9％rate of voluntary urinary control post-surgery.The median score for fast pelvic floor muscles was 23.5(18.2,31.6),and for slow muscles,it was 12.5(9.6,17.3).Among the patients,179(66.1％)did not preserve nerves,and 110(40.6％)underwent urethral reconstruction.Advanced age and low fast muscle scores were identified as independent risk factors for urinary incontinence.Patients aged ≤60 had 5.482 times the voluntary urinary control rate compared with those aged ≥70(95％CI:1.532-19.617,P＜0.05).There was a significant correlation between fast muscle scores and urinary incontinence recovery(OR=1.209,95％CI:1.132-1.291,P＜0.05).When the optimal threshold for preoperative fast muscle score was set at 18.5,the ROC sensitivity and specificity were 80.6％and 61.2％,respectively.Con-clusion:Preoperative pelvic floor EMG parameters show good predictive accuracy and clinical applicabili-ty for the risk of urinary incontinence after prostate cancer surgery.These parameters can be used for ear-ly identification of urinary incontinence risk,with age and fast muscle scores being important predictors.