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 investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Objective:To investigate immune status changes and prognostic factors of patients with persistent cervix intraepi-thelial neoplasia Ⅰ(CINⅠ)after Ella-Photodynamic(ALA-PDT)treatment.Methods:A total of 160 patients with persistent CINⅠwho were admitted to Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from June 2020 to October 2022 were selected as study objects,and divided into good prognosis group(n=100)and poor prognosis group(n=60)according to recurrence 12 months after operation.General data,clinical indicators affecting poor prognosis and therapeutic effect of ALA-PDT were compared between two groups.Risk factors affecting poor prognosis was analyzed by multivariate Logistic regression and nomogram model was established.Logistic regression and clinical decision analysis(DCA)curve were used to analyze predictive value of prognostic factors,and danger stratification was performed by X-tile software.Results:Total effective rate was 96.88%,and inflammatory condition were improved after treatment(P<0.05).After ALA-PDT treatment,expressions of IL-2,IFN-γ,CD3+T,CD4+T and CD8+T were signifi-cantly higher than before treatment,and expression of IL-4 was significantly lower than before treatment(P<0.05).There were signifi-cant differences in expressions of IL-2,IL-4,IFN-γ,CD3+T,CD4+T and CD8+T when severe cervical erosion occurred and lesions involved glands.Patients with persistent CINⅠ had lesions involving glands and severe cervical erosion,increased IL-4 level and decreased IL-2,IFN-γ,CD3+T,CD4+T and CD8+T levels at 6～12 months after treatment with ALA-PDT were independent risk factors for poor prognosis(P<0.05).Prediction nomogram model based on independent influencing factors had high differentiation,accuracy and clinical applicability.Conclusion:ALA-PDT has an ideal therapeutic effect for persistent CINⅠ.If patients have lesions involving glands and severe cervical erosion,abnormal IL-2,IL-4,IFN-γ,CD3+T,CD4+T and CD8+T after treatment,attention should be paid to occurrence of poor prognosis.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To investigate the association between serum thyroid-stimulating hormone(TSH) level and the 10-year risk of atherosclerotic cardiovascular disease(ASCVD) in men over 50 years old with type 2 diabetes mellitus(T2DM).Methods:This study included male T2DM patients aged≥50 years, diagnosed at the First Hospital of Lanzhou University between July 2021 and March 2022. Patients were categorized into three groups based on serum TSH level: elevated TSH group(T3, TSH>5.91 mIU/L) and normal TSH group, which was further divided into T1(0.56 mIU/L≤TSH<3.24 mIU/L) and T2(3.24 mIU/L≤TSH≤5.91 mIU/L) group. The 10-year ASCVD risk index was compared across groups. Spearman correlation and multiple linear regression analyses were used to assess the independent association between TSH level and 10-year ASCVD risk index. Results:A total of 490 male T2DM patients aged≥50 years were included(T1: 310, T2: 131, T3: 49). The 10-year ASCVD risk index was significantly higher in T3 group than that in T1 group(18.40% vs 13.90%, χ2=9.47, P<0.05). Serum TSH level showed a positive correlation with the 10-year ASCVD risk( r=0.144, P<0.05). After adjusting for confounders such as age, hypertension, lipid profile, diabetes duration, aspartate aminotransferase, albumin, lactate dehydrogenase, estimated glomerular filtration rate, creatinine, and phosphorus, multiple linear regression confirmed that TSH level was independently associated with the 10-year ASCVD risk index( β=0.23, 95% CI 0.02-0.45). Conclusions:Higher serum TSH level is independently associated with an increased 10-year ASCVD risk in men over 50 years old with T2DM. Regular TSH monitoring may aid in cardiovascular risk stratification in this population.

Objective:To investigate immune status changes and prognostic factors of patients with persistent cervix intraepi-thelial neoplasia Ⅰ(CINⅠ)after Ella-Photodynamic(ALA-PDT)treatment.Methods:A total of 160 patients with persistent CINⅠwho were admitted to Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from June 2020 to October 2022 were selected as study objects,and divided into good prognosis group(n=100)and poor prognosis group(n=60)according to recurrence 12 months after operation.General data,clinical indicators affecting poor prognosis and therapeutic effect of ALA-PDT were compared between two groups.Risk factors affecting poor prognosis was analyzed by multivariate Logistic regression and nomogram model was established.Logistic regression and clinical decision analysis(DCA)curve were used to analyze predictive value of prognostic factors,and danger stratification was performed by X-tile software.Results:Total effective rate was 96.88%,and inflammatory condition were improved after treatment(P<0.05).After ALA-PDT treatment,expressions of IL-2,IFN-γ,CD3+T,CD4+T and CD8+T were signifi-cantly higher than before treatment,and expression of IL-4 was significantly lower than before treatment(P<0.05).There were signifi-cant differences in expressions of IL-2,IL-4,IFN-γ,CD3+T,CD4+T and CD8+T when severe cervical erosion occurred and lesions involved glands.Patients with persistent CINⅠ had lesions involving glands and severe cervical erosion,increased IL-4 level and decreased IL-2,IFN-γ,CD3+T,CD4+T and CD8+T levels at 6～12 months after treatment with ALA-PDT were independent risk factors for poor prognosis(P<0.05).Prediction nomogram model based on independent influencing factors had high differentiation,accuracy and clinical applicability.Conclusion:ALA-PDT has an ideal therapeutic effect for persistent CINⅠ.If patients have lesions involving glands and severe cervical erosion,abnormal IL-2,IL-4,IFN-γ,CD3+T,CD4+T and CD8+T after treatment,attention should be paid to occurrence of poor prognosis.

BACKGROUND:Preliminary research by our group suggests that targeting fibroblast growth factor receptor 1(FGFR1)may be an effective strategy for treating RA. OBJECTIVE:To investigate the effects of an FGFR1 inhibitor(PD173074)on bone destruction in rats with collagen-induced arthritis. METHODS:Twenty-five female Sprague-Dawley rats were randomly divided into five groups:normal control group,model group,methotrexate group,low-dose PD173074 group,and high-dose PD173074 group.Except for the normal control group,rat models of type Ⅱ collagen-induced arthritis were made in each group.After successful modeling,rats were injected intraperitoneally with sterile PBS in the normal and model groups,1.04 mg/kg methotrexate in the methotrexate group,and 5 and 20 mg/kg in the low-dose group and high-dose PD173074 groups,once a week.After 4 weeks of drug administration,clinical symptoms and joint swelling in rats were observed.Micro-CT was used for three-dimensional reconstruction and analysis of the ankle joints.Pathological changes in the ankle joints were observed.Periarticular angiogenesis and the expression of receptor activator of nuclear factor-Κb ligand were detected.The expression levels of p-FGFR1,vascular endothelial growth factor A,and tartrate-resistant acid phosphatase in the synovial membrane were measured.Pathological changes in the liver,spleen,and kidney were observed and liver,spleen,and kidney indices were calculated. RESULTS AND CONCLUSION:PD173074 could alleviate clinical symptoms and joint swelling,delay bone loss,improve bone structure,reduce synovial invasion and cartilage bone erosion,reduce the number of periarticular osteoclasts,inhibit angiogenesis in synovial tissues,reduce the expression of receptor activator of nuclear factor-Κb ligand,and inhibit the expression of FGFR1 phosphorylated protein,tartrate-resistant acid phosphatase and vascular endothelial growth factor A.Pathologic observation of the liver,spleen and kidney in rats showed no obvious toxic side effects after PD173074 treatment.To conclude,the FGFR1 inhibitor can delay the progression of joint inflammation and bone destruction and inhibit angiogenesis in the rat model of type Ⅱ collagen-induced arthritis.The therapeutic effect of PD173074 has been preliminarily validated in the type Ⅱ collagen-induced arthritis model and may act by inhibiting FGFR1 phosphorylation,which provides a direction for the search of new therapeutic targets for rheumatoid arthritis.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.