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.

[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 investigate the clinical significance of elevated cytokeratin 19 fragment (CYFRA21-1) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:142 consecutive cases with newly onset anti-MDA5(+) (MADEDM)-DM admitted to the first affiliated hospital of Zhengzhou University from June 2018 to October 2021 were enrolled. They were divided into two groups, the low serum CYFRA21-1 group (CYFRA21-1≤4 ng/ml) and the high serum CYFRA21-1 group (CYFRA21-1>4 ng/ml). The clinical manifestations, laboratory tests results, imaging examinations treatment and outcome were collected for statistical analysis. Enumeration data were expressed as the number of cases and percentage (%). Normally distributed parameters were tested by t-test. Parameters with skewed distribution were tested by Mann-Whitney Wilcoxon analysis. Categorical variables were compared by the Chi-square test or Fisher′s exact test. Risk factor analysis was performed using Logistic regression. Cumulative survivals were described by Kaplan-Meier curves. Results:The age of onset in the high CYFRA21-1 group [(56±9)years vs. (50±10) years, t=-3.50, P=0.001] was higher than that in the low CYFRA21-1 group. Fever [63.3% (38/60) vs. 40.2% (33/82), χ2=7.39, P=0.007] was more common in the high CYFRA21-1 group, and arthritis [41.7% (25/60) vs. 69.5%(57/82), χ2=11.01, P=0.001] was less common. Myalgia, myasthenia, rashes, Raynaud′s phenomenon and skin ulcers had no significant difference between the two groups. The WBC count [5.2(4.1, 6.9)×10 9/L vs. 4.3(3.2, 6.2)×10 9/L, Z=-2.57, P=0.010], neutrophil count [4.0(2.9, 5.5)×10 9/L vs. 2.9(2.1, 4.5)×10 9/L, Z=-3.25, P=0.001] and neutrophil/lymphocyte ratio [5.75(3.50, 9.20) vs. 3.55(2.64, 5.41), Z=-3.77, P<0.001] in high CYFRA21-1 group were significantly higher than those in low CYFRA21-1 group. At the same time, LDH [384(302, 519)U/L vs. 318(260, 405)U/L, Z=-2.98, P=0.003], ferritin [1 204(677, 2 039)ng/ml vs. 570(229, 846)ng/ml, Z=-4.78, P<0.001], KL-6 [995(658, 1 491)U/ml vs. 750(563, 1 197)U/ml, Z=-2.49, P=0.013], ESR [36(22, 61)mm/1 h vs. 28(15, 46)mm/1 h, Z=-2.18, P=0.029] and CRP [9.2(4.7, 31.5)mg/L vs. 3.1(1.1, 11.6)mg/L, Z=-3.53, P<0.001] were significantly increased in the high level of CYFRA21-1 group, while serum albumin[(32±5)g/L vs. (35±5)g/L, t=3.92, P<0.001] was significantly decreased. There was no significant difference in the titers of serum anti-MDA5 antibodies between the two groups. The positive rate of anti-RO52 antibody [44(74.6%) vs. 44(53.7%), χ2=6.40, P=0.011] in high CYFRA21-1 group was higher than that in low CYFRA21-1 group. The ground glass opacity (GGO) score [1.75(1.33, 2.42) vs. 1.09(0.67, 1.67), Z=-4.60, P<0.001] based on high resolution CT (HRCT) was also significantly increased in the CYFRA21-1 high level group. Compared with the low CYFRA21-1 group, the high CYFRA21-1 group had a higher probability of RP-ILD [48.3%(29/60) vs. 23.2%(19/82), χ2=9.80, P=0.002] and a higher 6-month mortality rate[48.3%(29/60) vs.13.4%(11/82), χ2=19.70, P<0.001]. Logistic regression analysis showed that age ≥53 years old [ OR(95% CI)=5.197(1.781, 15.165), P=0.003], duration < 2 months [ OR(95% CI)=3.314 (1.058, 10.378), P=0.040], NE/LYMP >5 [ OR(95% CI)=3.443(1.120, 10.586), P=0.031], CRP>5 mg/L[ OR(95% CI)=6.271(1.749, 22.480), P=0.005], CA125>14 U/ml[ OR(95% CI)=7.500 (2.409, 23.345), P=0.001] and CYFRA21-1>4 ng/ml[ OR(95% CI)=3.665(1.258, 10.676), P=0.017] were independent risk factors for death within 6 months in MDA5-DM patients. Kaplan-Meier survival curve showed that the survival rate of the high CYFRA21-1 group was significantly lower than that of the low CYFRA21-1 group( P<0.001). Conclusion:Elevated CYFRA21-1 is an independent risk factor for early mortality in MDA5-DM patients and can serve as a novel serological marker for risk stratification in these patients.

Objective To investigate the effects of miR-126 on myocardial remodeling and macrophage polarization after acute myocardial infarction(AMI).Methods(1)Twenty-one rats were divided into a sham operation group and an AMI group.The AMI group was further divided into postoperative days 1,3,5,7,9,and 11 days(AMI-1,AMI-3,AMI-5,AMI-7,AMI-9,AMI-11),with 3 rats in each group,and postoperative day 3 was selected for subsequent study.(2)Thirty rats were randomly divided into three groups:sham operation group,AMI group and miR-126 overexpression group,with 10 rats in each group.RT-qPCR was used to detect the expression levels of miR-126 mRNA.2,3,5-Triphenyltetrazole chloride(TTC)staining was used to detect the infarct size.Myocardial fibrosis was detected by Masson staining.The cross-sectional area of the myocardium was determined by H&E staining.Immunofluorescence staining was used to detect the protein levels of CD86 and CD206 in myocardial tissue.Western blotting was used to detect the protein levels of CD86 and CD206 in myocardial tissue.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in serum were detected by ELISA kit.Results Compared with the sham operation group,the expression level of miR-126 mRNA in myocardial tissue of rats in the AMI group was significantly decreased on postoperative day 1(P<0.05),reached the lowest level on postoperative day 3.And then although it rose to a certain extent,it remained lower than that of the sham operation group on postoperative day 11(P<0.05),and postoperative day 3 was selected for further study.Compared with the sham operation group,the expression of miR-126 mRNA in myocardial tissue of the AMI group was decreased(P<0.05),and the myocardial fibrosis,infarct size and myocardial cross-sectional area were increased(P<0.05).The expression of CD86 protein in myocardial tissue was increased and the expression of CD206 protein was decreased(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were increased(P<0.05).Compared with the AMI group,the rats in the miR-126 overexpression group had a significant increase in the mRNA expression of miR-126 in myocardial tissue(P<0.05),a significant reduction in myocardial fibrosis,infarct size,and myocardial cross-sectional area(P<0.05),a significant reduction in the expression of CD86 protein in myocardial tissue,and a significant increase in the expression of CD206 protein(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05).Conclusion Over-expression of miR-126 can improve myocardial remodeling and promote M2 macrophage polarization in AMI rats.

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

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 role of cysteine aspartic protease-8(Caspase-8)/gasdermin E(GSDME)pathway in the regulation of macrophage pyroptosis in myocardial infarction(MI)rat model and its possible mechanism.Methods Thirty rats were randomly divided into sham operation group,MI group and Caspase-8 inhibition(Z-IETD-FMK)group,with 10 rats in each group.The cultured rat macrophages RMa-bm were divided into control group,hypoxia group and Z-IETD-FMK group.The pathological changes of myocardial tissue were detected by H&E staining.Masson staining was used to detect myocardial fibrosis.The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8,GSDME,NLR family Pyrin domain protein 3(NLRP3),apoptosis-related speck-like protein(ASC)and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA.TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages.Results Compared with the sham operation group,myocardial tissue of rats in MI group was broken and disturbed,inflammatory cell infiltration,a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8,GSDME protein and mRNA in myocardial tissue increased,the differences were statistically significant(t=16.19,27.60;21.18,23.73,all P<0.05).Compared with MI group,Z-IETD-FMK group improved myocardial structural damage,reduced inflammatory cells and collagen deposition,cell apoptosis decreased and decreased Caspase-8,GSDME protein and mRNA expressions in myocardial tissue,with statistical significance(t=20.34,14.56;11.97,24.46,all P<0.05).Compared with the control group,the apoptosis of macrophages in hypoxia group was increased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were increased(tprotein=17.53～120.90,tmRNA=18.42～60.30),the contents of IL-1β and IL-18 in macrophages were increased(t=25.88,45.74),and the differences were staistically significant(all P<0.05).Compared with the hypoxia group,the apoptosis of macrophages in Z-IETD-FMK group was decreased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were decreased(tprotein=17.08～35.08,tmRNA=11.21～47.96),IL-1β and IL-18 content decreased(t=27.38,25.82),and the differences were staistically significant(all P<0.05),respectively.Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.

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*