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.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

This research aims to construct a stable epithelial cell senescence model for screening and e-valuation of senolytics.We explored the optimal conditions for doxorubicin-induced senescence of non-transformed epithelial cells MCF 10A,including the optimal induction concentration,the optimal inter-vention time,and the optimal senescence duration,and confirmed the feasibility of MCF 10A as an epi-thelial senescence model by multiple ways.The optimal condition for Doxorubicin-induced senescence of MCF 10A cells was treatment with 0.6 μmol/L Doxorubicin for 16 h to achieve the best senescence state on the 8th day.Under the optimal induction conditions,the positive rate of senescence-associated β-gal-actosidase(SA-β-gal)staining in the treated group reached 97％.At the same time,biochemical results of detecting the expression of mRNA,proteins,and immunofluorescence demonstrated that the expression levels of senescence-associated secretory phenotype(SASP),p16,p21 and p53 in the treated group were significantly higher than those in the control cells,and Lamin B1 was significantly decreased(P＜0.001),which were consistent with the specific characteristics of senescence.In summary,an epithelial senescence model was successfully induced in MCF 10A cells by Doxorubicin in this study,which will promote the screening of senolytics for senescent epithelial cells.

Objective To explore the influencing factors of neonatal pneumonia complicated with myocardial damage and Th1/Th2 cytokines,and construct a line chart model.Methods A total of 390 neonates with pneumonia who were treated in Mianyang People's Hospital were selected as the study subjects and randomly divided into a modeling cohort(n=273)and a validation cohort(n=117)according to a 7∶3 ratio.They were further divided into myocardial damage group and non-myocardial damage group according to whether they had concurrent myocardial damage.Enzyme linked immunosorbent assay(ELISA)was used to measure Th1/Th2 cytokines(IFN-γ,IL-6,TNF-α,IL-4,IL-2 and IL-10),and the Mindray BS-280 automatic biochemical analyzer was used to measure hs-cTn I,CK-MB,LDH and CK.Logistic regression equation was used to screen the influencing factors of neonatal pneumonia complicated with myocardial damage.R software was used to construct a line chart model,and the receiver operating characteristic curve(ROC)and area under the ROC curve(AUC)were used to analyze the predictive ability of the model.The Hosmer-Lemeshow goodness-of-fit test was used,and a calibration curve was drawn to evaluate the calibration of the model.The decision curve analysis(DCA)was used to evaluate the clinical effectiveness.Results The incidence of myocardial damage in 390 neonates with pneumonia was 28.21%.Modeling cohort and validetion cohort,the 1min Apgar score in the myocardial damage group was lower than that in the non-myocardial damage group(t=3.314,2.619),and CK-MB,LDH,CK,hs-cTnI,IL-2,IFN-γ,TNF-α,IL-6,IL-10 and IL-4 were higher than those in the non-myocardial damage group(t=5.805～18.914),and the proportions of severe pneumonia,low birthweight infant,premature infants were higher than those in the non-myocardial damage group(χ2=4.464～41.497),and the differences were statistically significant(all P<0.05),respectively.The Logistic regression equation showed that low birth weight,1-minute Apgar score,premature birth,hs-cTnI,IL-2,IFN-γ,IL-6 and IL-4 were factors affecting neonatal pneumonia complicated with myocardial damage(Wald χ2=10.330～14.328,all P<0.05).The AUC(95%CI)of the nomogram model constructed based on the factors affecting neonatal pneumonia complicated with myocardial damage was 0.880(0.839～0.921)in the modeling cohort and 0.910(0.856～0.964)in the validation cohort,with slopes of the calibration curves close to 1,and the clinical net benefit rate was the highest in the ranges of 0.1～0.8 and 0.0～0.7.Conclusion The nomogram model,which includes Th1/Th2 cytokines,hs-cTnI,1-minute Apgar score,premature infants and low-birth-weight infants has high predictive value for neonatal pneumonia complicated with myocardial damage.It can help clinicians identify high-risk populations,take reasonable diagnostic and treatment measures,and reduce the risk of myocardial damage.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

Objective:To investigate the predictive value of elevated calprotectin S100A9 (S100A9) concentration during living-donor liver transplantation (LDLT) for early acute lung injury (ALI) in children with biliary atresia.Method:A retrospective analysis was conducted on 280 pediatric patients with biliary atresia who underwent LDLT using hyperreduced left lateral segment grafts at Tianjin First Central Hospital between January 2019 and January 2021. Based on intraoperative serum S100A9 levels at 30 minutes after graft reperfusion, patients were divided into the high S100A9 group (≥9.05 μg/L, 141 cases) and the low S100A9 group (<9.05 μg/L, 139 cases). General clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed to examine the correlation between S100A9 levels and early postoperative ALI. The predictive value of risk factors was assessed using receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) .Result:A total of 280 eligible children were included in the study, with 141 in the high S100A9 group and 139 in the low S100A9 group. The incidence of ALI was significantly higher in the high S100A9 group (31.2%) compared to the low S100A9 group (10.8%). Multivariate regression analysis identified elevated preoperative creatinine levels ( OR=1.191, 95% CI: 1.069~1.321, P=0.002), increased intraoperative S100A9 concentrations ( OR=1.426, 95% CI: 1.272~1.599, P=0.021), and higher intraoperative blood transfusion volume ( OR=0.985, 95% CI: 0.973~0.997, P=0.017) as independent risk factors for postoperative ALI in pediatric LDLT. The predictive value of intraoperative S100A9 levels for ALI was significant, with an AUC of 0.816 (95% CI: 0.758~0.874), a sensitivity of 80.5%, a specificity of 73.7%, and an optimal cutoff value of 9.49 μg/L. Furthermore, preoperative albumin and creatinine levels were found to be correlated with increased intraoperative S100A9 levels. Conclusion:Elevated intraoperative S100A9 levels, increased preoperative creatinine levels, and higher intraoperative blood transfusion volumes are independent risk factors for early ALI following pediatric LDLT. S100A9 levels have strong predictive value for ALI occurrence, highlighting the need for perioperative monitoring and intervention strategies to improve postoperative outcomes.

Objective:To investigate the impact of different CT reconstruction kernels on the quantitative analysis of small pulmonary vessels in patients with chronic obstructive pulmonary disease (COPD) and high-risk patients.Methods:This study was a cross-sectional study. Clinical and imaging data of 73 COPD and high-risk patients visiting the China-Japan Friendship Hospital between March and April 2024 were retrospectively analyzed. All patients underwent high-resolution CT of the chest and pulmonary function tests, with the ratio of forced expiratory volume in one second to forced vital capacity (FEV 1/FVC) obtained. The raw CT data were reconstructed using different kernels: the FC86 group used the adaptive iterative dose reduction(AIDR) 3D standard lung sharp reconstruction algorithm, the FC18 group used the AIDR 3D standard Body standard reconstruction algorithm, the advanced intelligent clear-IQ engine(AiCE) Lung group used the AiCE deep learning reconstruction algorithm for lung, and the AiCE Body group used the AiCE deep learning reconstruction algorithm for body. Image signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image noise were calculated. The pulmonary vessel segmentation & Measurement software was used to segment and extract pulmonary arteries and veins of four groups in thin-slice whole-lung CT imaging, obtaining the ratio of small pulmonary arteries (%V artery<5) and the ratio of small pulmonary veins (%V vein<5). The One-way repeated measures ANOVA or Friedman test was used to compare the differences in SNR, CNR, image noise, %V artery<5, and %V vein<5 among the four groups, followed by Bonferroni post hoc or Bonferroni-Dunn test with P-value correction to analysis differences between subgroups. The correlations between %V artery<5 and FEV 1/FVC, as well as between %V vein<5 and FEV 1/FVC were analyzed using Spearman rank correlation analysis in all four groups. Results:The overall differences in image noise, SNR, and CNR in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). Except for the difference in CNR values between the AiCE Lung group and the FC18 group, which was not statistically significant ( P=0.192), all differences were statistically significant ( P<0.016 7). The overall differences in %V artery<5 values and %V vein<5 values in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). The %V artery<5 and %V vein<5 values in the FC18 group were lower than those in the AiCE Lung, AiCE Body, and FC86 groups ( P<0.016 7), and the rest of the differences were not statistically significant ( P>0.016 7). %V artery<5 and %V vein<5 were positively correlated with FEV 1/FVC in all 4 groups ( P<0.05), with the highest correlation coefficient between %V vein<5 and FEV 1/FVC in the AiCE Body group ( r=0.501, P=0.001). Conclusions:DLR-AiCE-based kernel reconstruction optimizes image quality and significantly affects the results of quantitative parameters of small pulmonary vessels. The reconstruction kernel prioritized for quantitative analysis of small vessels within the lungs in COPD based on the CT scanner in this study is AiCE Body.