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 correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Objective:To analyze the selection of outcome indicators for randomized controlled trials (RCT) on exercise rehabilitation in patients with atrial fibrillation (AF), promote the construction of the core outcome set and provide reference for the research design of subsequent RCT.Methods:The RCT literature related to exercise rehabilitation of patients with atrial fibrillation was systematically searched from CNKI, Wanfang, VIP, PubMed, Web of Science, Embase and Cochrane Library databases, and the search period was from establishment of the databases until July 31, 2023. After literature screening, Cochrane Risk of Bias Assessment Tool was used for quality evaluation, information extraction, classification of outcome indicators, frequency of use statistics, analysis and extraction of current shortcomings in the selection of outcome indicators, and corresponding suggestions were proposed.Results:A total of 32 articles were included, and 19 RCT were evaluated twice for outcome measures. The number of outcome measures ranged from 2 to 17, with 10 RCT setting outcome measures according to primary and secondary criteria and 6 RCT setting safety outcome measures. A total of 96 outcome indicators were extracted in this study, total 266 frequency, which could be divided into 4 categories, such as safety evaluation (18 times), clinical response (75 times), patient-reported outcomes (68 times) and laboratory and other examination (105 times) .Conclusions:Existing RCT outcome indicators of exercise rehabilitation in patients with atrial fibrillation emphasize the changes in subjective feelings and objective indicators of individuals, covering four aspects such as the physical condition, exercise ability, quality of life and psychological status of individuals. However, there is a lack of uniform standards and the safety evaluation indicators are fewer. The categories of exercise rehabilitation indicators for atrial fibrillation patients extracted in this paper can provide a reference for the design of future RCT studies and promote the generation of higher quality evidence-based medical evidence.

Diabetes and its complications pose a serious threat to human life and health. It has become a public health problem of wide concern worldwide. Currently, diabetes is mainly treated with insulin injection in clinic. However, manual insulin injection still has many shortcomings. In recent years, with the deepening of research, it has been found that an automated insulin delivery system (AID), which combines a continuous glucose monitoring device with an insulin pump, can significantly improve the effectiveness of diabetes treatment and reduce the incidence of complications in patients. This paper firstly introduces the composition of the AID system and its working principle, and then details the development history and current status of the related technologies from the aspects of continuous glucose monitoring technology, insulin pumps and the development of closed-loop control algorithms, etc. Finally, this paper looks forward to the application prospect and future development of AID system in the field of diabetes treatment, providing theoretical reference for further research.
Humans ; Insulin Infusion Systems ; Insulin/administration & dosage* ; Blood Glucose Self-Monitoring/instrumentation* ; Diabetes Mellitus/drug therapy* ; Algorithms ; Hypoglycemic Agents/administration & dosage* ; Blood Glucose/analysis* ; Pancreas, Artificial ; Automation

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

【Objective】 To investigate the effects of different anticoagulants on platelet-rich plasma(PRP) release content of growth factor and injection pain. 【Methods】 A total of 15 voluntary blood donors were selected, with each blood donor using four kinds of anticoagulant tubes with EDTA-K2 anticoagulation, EDTA-NA2 anticoagulation, citrate anticoagulation, ACD-A anticoagulation respectively as group A, B, C and D. PRP was isolated and prepared by the rich plasma method, and the contents of PDGF-AA, TGF-β, IGF-1, VEGF, and PF-4 were detected by enzyme-linked immunosorbent assay. Meanwhile, SD rats (20, 4 / group) were injected subcutaneously or intradermally with the supernatant of PRP and PG gel prepared in the 4 groups and normal saline in the control group. The pain status of SD rats during the injection was observed and recorded. The pain status of the 5 groups of experimental animals was evaluated according to the American Laboratory Animal Pain Guide. 【Results】 The platelet counts in PRP in group D was the highest [(1 294.53±277.37) × 10⁹/L], which was significantly higher than that in group A [ (789.13±377.13) ×10⁹/L] and group C [ (990.94±493.12) ×10⁹/L] (P<0.05). The OD value of PDGF-AA in group A, B, C, and D were 1.51± 0.18, 1.69±0.21, 0.66±0.19and 1.72±0.13, respectively, with statistically significant difference between groups (P<0.05 ) and group D better than the other three groups. The OD value of PF-4 was 1.18±0.24, 1.61±0.14, 0.65±0.26 and 1.72±0.10 respectively, with statistically significant difference between groups (P<0.05) and group D better than other three groups. The OD value of IGF-1 was 1.02±0.08, 0.98±0.11, 1.06±0.11 and 1.32±0.65 respectively, with no significant difference between groups (P>0.05). The OD value of VEGF was 0.13±0.04, 0.21±0.14, 0.08±0.02 and 0.13±0.04 respectively, with statistically significant difference between group B and C (P<0.05). The OD value of TGF-β was 0.14±0.01, 0.15±0.01, 0.28±0.17 and 1.10±0.37 respectively, with statistically significant difference between groups (P<0.05) and group D better than other three groups. Comparison of injection pain: when the supernatant of PRP and PG gel was injected, there were significant differences between group A, B, C and D, and the control group (P<0.05) . The median pain scores of PRP injection of group A, B, C, and D were 6 (1.5), 5 (0.75), 4.5 (2.5), and 3(3) respectively, with group D lower than other three groups, and no statistically significant difference was noticed (P>0.05) . The median pain scores of the PG supernatant injection of group A, B, C, and D were 4 (2.25), 3 (2.75), 4 (3), 1 (1.5), and the difference was not statistically significant (P>0.05). There was no significant difference between the PRP injection group and the PG supernatant group (P> 0.05). 【Conclusion】 PRP prepared by two-step centrifugation with ACD-A anticoagulant can obtain the higher platelet counts and the maximum release of PDGF-AA, PF-4, IGF-1, and TGF-β. In terms of pain, ACD-A anticoagulant injection has the lowest pain with the animals.

【Objective】 To develop a spray-on membrane dressing for wound repair containing platelet rich plasma (PRP) sodium alginate (SA)/agarose(AG)/carboxymethyl chitosan (CMCS). 【Methods】 SA/AG/ CMCS were mixed in different proportions to prepare biodegradable quick setting spray (BQSS) by blending film method, and the film-forming time, moisture retention and compression resistance of the prepared BQSS were tested. Then PRP and BQSS were mixed in the proportion of 3∶7, 4∶6, 5∶5, 6∶4 and 7∶3 to prepare PRP-BQSS spray film dressings. The film-forming time, moisture retention, compressive strength, porosity and slow-release effect of growth factors of PRP-BQSS spray film dressings were studied. 【Results】 In the preparation of BQSS compound spray film solution, when SA, AG, CMCS and sterile distilled water were 0.6∶0.6∶0.6∶98.2g, the film-forming time (7.73±0.31) s, moisture retention (75. 54±3.03) % and compression resistance (791.00±68.02) g of the spray-film dressing were the best. The basic properties of PRP-BQSS spray-on film dressings and the release of growth factors show that PRP-BQSS spray-on film dressings can exist in different forms, and with the decrease of PRP concentration percentage, its film-forming time, moisturizing performance and compressive strength showed an upward trend. When the PRP content is 30%, the porosity of the dressing is the highest, about(84.34±0.90)%. The release of platelet-derived growth factor-AA(PDGF-AA), platelet factor-4(PF-4) and transforming growth factor beta (TGF-β) was in a slow upward trend, and the release of the three growth factors was higher than that of PRP group in 48 hours. 【Conclusion】 The preparation method of PRP-BQSS spray film dressing designed in this study is simple and mild, and can form a film quickly, with good biological properties and better growth factor inhibition and sustained-release effect.

Objective:To explore the relationship between the imaging features of enhanced MRI in patients with central chronic pulmonary artery thromboembolism (CPTE) and pulmonary vascular resistance (PVR).Methods:Thirty-nine patients with CPTE who had contrast-enhanced MRI examination were retrospectively enrolled this study from January 2018 to December 2020. And 33 patients who received right heart catheterization were divided into two groups based on PVR=1 000 dyn·s·cm -5. The differences of imaging features of CPTE in enhanced MRI between the two groups were compared. The relationship between gender, duration of disease, age, pleural thickening, bilateral bronchial artery dilation, number of the involved vascular segments, number of thrombosis, number of the thrombus-related delayed enhancement of artery wall and PVR was analyzed by binary logistic regression. Results:In 39 patients with central CPTE, the dilated lumen (168, 43.30%) and delayed enhancement of wall (122, 31.52%) were found in most of pulmonary arteries. The rate of the lumen dilatation associated with thrombus was the highest among that of the lumen abnormality (66, 52.80%). There were more thrombi in PVR<1 000 dyn·s·cm -5 group than those in PVR≥1 000 dyn·s·cm -5 group (χ 2=9.55, P=0.002). There was no significant difference in the incidence of wall delayed enhancement associated the thrombus between the two groups (χ 2=0.90, P=0.344). The incidence of bilateral bronchial arterial dilatation in PVR<1 000 dyn·s·cm -5 group was higher than that in PVR≥1 000 dyn·s·cm -5 group ( P=0.019). Logistic regression analysis showed that female, the less number of involved vascular segments and bilateral bronchial artery dilation were correlated with the lower PVR. Conclusions:Enhanced MRI is helpful to accurately evaluate the lumen abnormality of pulmonary artery and wall remodeling in central CPTE, which is of great value for the assessment of patients′ conditions and treatment effect.

Objective:To analyze the late gadolinium enhancement (LGE) manifestations, cardiac function, and myocardial strain by feature tracking (FT) in Takayasu arteritis (TA) with pulmonary artery involvement (PTA) using cardiac MR (CMR), and then to investigate manifestations of the impaired myocardial structure and function.Methods:A retrospective study was performed on 32 patients with PTA and 21 healthy subjects without cardiopulmonary diseases from January 2017 to December 2020. All of them underwent CMR examinations. According to the presence of pulmonary arterial hypertension (PAH),PTA patients were divided into two groups including PAH group (11 cases) and non-PAH group (21 cases). LGE manifestations were observed and Fisher exact test was used for statistical analysis between the two groups. Cardiac function parameters and FT values including global peak strain of the left and right ventricle were calculated separately in PAH, non-PAH group of patients and healthy controls, using One-way ANOVA or non-parametric Kruskal-Wallis test for statistical analysis including a pairwise comparison between groups. The correlations between FT values of the PAH group and parameters measured by right heart catheterization test (RHC) and transthoracic echocardiography were analyzed using Pearson or Spearman correlation analysis.Results:There were 23 PTA patients (71.9%) with LGE. LGE in the interventricular insertion points (IPs)(11/11), and in the mid-wall (11/11) or epicardial (10/11) myocardium was more common ( P values were 0.006,<0.001 and 0.011, respectively) in PAH group, compared with LGE in the IPs (11/21), and in the mid-wall (7/21) or epicardial (9/21) myocardium in non-PAH group. The absolute values of left ventricular global peak circumferential strain (LVGPCS), left ventricular global peak longitudinal strain (LVGPLS) and right ventricular global peak longitudinal strain in PAH group were smaller than those in healthy subjects ( P<0.05). The absolute values of LVGPCS and LVGPLS in non-PAH group were smaller than those in healthy subjects ( P<0.05). In PAH group, mean pulmonary artery pressure of RHC was correlated with several FT parameters ( P<0.05), especially left ventricular global peak radial strain ( r=-0.807, P=0.009) and LVGPCS ( r s=0.817, P=0.007). Conclusions:Myocardial injury can be seen in PTA patients. And LGE in the IPs and LGE in the mid-wall or epicardial myocardium is more common in PTA patients with PAH. LVGPCS and LVGPLS can early indicate left heart dysfunction in PTA patients without PAH.