[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Metabolic associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， and its progression is closely associated with the development of liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. However， there is still a lack of effective therapies for MAFLD in clinical practice. Telomere is the protective structure at the end of chromosomes， and telomere shortening and functional impairment have been identified as one of the key factors regulating the pathological progression of MAFLD. This article systematically reviews the core mechanism of action of telomere regulation in MAFLD， including its molecular functions in nucleotide metabolism， oxidative stress， and epigenetic regulation， as well as its pathological effect in hepatocytes and hepatic stellate cells. In addition， this article explores the clinical prospects of telomeres as biomarkers and therapeutic targets for MAFLD， in order to provide a theoretical reference for improving the precise diagnosis and treatment system of MAFLD.

Objective To explore the correlation between the test panel of serum CC chemokine ligand 3(CCL3),soluble podoplanin(sPDPN),fatty acid-binding protein 5(FABP5)and the severity of lung injury and clinical outcomes in children with severe pneumonia.Methods A total of 168 children with severe pneumonia who visited our hospital from January 2022 to January 2023 were included in this study as severe group.The patients were assigned to good outcome group(137 cases)or poor outcome group(31 cases)based on their prognosis.Additional 80 children with mild or moderate pneumonia were treated as non-severe group.In addition,80 children who underwent health checkup were included as control group.Baseline data such as body mass index and duration of disease were observed and recorded for all children.Enzyme linked immunosorbent assay(ELISA)was applied to detect the expression levels of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),CCL3,sPDPN,and FABP5 in the serum of all children.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)score and Lung Injury Prediction(LIPS)score were rated to evaluate the degree of lung injury.Multivariate logistic regression was used to analyze the impact of various factors on the poor outcome of children with severe pneumonia.Spearman correlation was applied to analyze the correlation between the expression levels of CCL3,sPDPN,FABP5 and poor outcome,the severity of lung injury,APACHE Ⅱ score,and LIPS score in children with severe pneumoniae.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCL3,sPDPN,and FABP5 expression levels for poor outcome in children with severe pneumonia.Z-test was used to compare the differences in area under the curve(AUC).Results The baseline data such as duration of disease,body mass index,age,and sex did not show significant differences among the control group,non-severe group,and severe group(P＞0.05).The levels of serum CRP,PCT,IL-6,TNF-α,CCL3,sPDPN increased,while the level of FABP5 decreased gradually from the control group to non-severe group,and severe group(P＜0.05).The patients with poor outcomes showed higher serum levels of CRP,PCT,IL-6,TNF-α,CCL3,sPDPN,APACHE Ⅱ score,and LIPS score but lower FABP5 level compared to the patients with good outcomes(P＜0.05).TNF-α,CCL3,sPDPN,APACHE Ⅱ,and LIPS scores were independent risk factors for poor outcomes in children with severe pneumonia,while FABP5 level was independent protective factor for poor outcomes in children with severe pneumonia(P＜0.05).The levels of CCL3 and sPDPN were positively correlated with APACHE Ⅱ score and LIPS score,while FABP5 was negatively correlated with APACHE Ⅱ score and LIPS score(P＜0.05).The AUC of CCL3,sPDPN,and FABP5 alone was 0.802,0.864,and 0.859 respectively for predicting poor prognosis in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 was superior to CCL3,sPDPN,or FABP5 alone(Zcombination-CCL3=3.842,Zcombination-sPDPN=2.585,Zcombination-FABP5=2.957,P＜0.05).Conclusions The serum levels of CCL3 and sPDPN are positively correlated with the severity of lung injury,while FABP5 is negatively correlated with the severity of lung injury in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 is valuable for predicting poor outcomes in children with severe pneumonia.

Objective To explore the correlation between the test panel of serum CC chemokine ligand 3(CCL3),soluble podoplanin(sPDPN),fatty acid-binding protein 5(FABP5)and the severity of lung injury and clinical outcomes in children with severe pneumonia.Methods A total of 168 children with severe pneumonia who visited our hospital from January 2022 to January 2023 were included in this study as severe group.The patients were assigned to good outcome group(137 cases)or poor outcome group(31 cases)based on their prognosis.Additional 80 children with mild or moderate pneumonia were treated as non-severe group.In addition,80 children who underwent health checkup were included as control group.Baseline data such as body mass index and duration of disease were observed and recorded for all children.Enzyme linked immunosorbent assay(ELISA)was applied to detect the expression levels of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),CCL3,sPDPN,and FABP5 in the serum of all children.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)score and Lung Injury Prediction(LIPS)score were rated to evaluate the degree of lung injury.Multivariate logistic regression was used to analyze the impact of various factors on the poor outcome of children with severe pneumonia.Spearman correlation was applied to analyze the correlation between the expression levels of CCL3,sPDPN,FABP5 and poor outcome,the severity of lung injury,APACHE Ⅱ score,and LIPS score in children with severe pneumoniae.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCL3,sPDPN,and FABP5 expression levels for poor outcome in children with severe pneumonia.Z-test was used to compare the differences in area under the curve(AUC).Results The baseline data such as duration of disease,body mass index,age,and sex did not show significant differences among the control group,non-severe group,and severe group(P＞0.05).The levels of serum CRP,PCT,IL-6,TNF-α,CCL3,sPDPN increased,while the level of FABP5 decreased gradually from the control group to non-severe group,and severe group(P＜0.05).The patients with poor outcomes showed higher serum levels of CRP,PCT,IL-6,TNF-α,CCL3,sPDPN,APACHE Ⅱ score,and LIPS score but lower FABP5 level compared to the patients with good outcomes(P＜0.05).TNF-α,CCL3,sPDPN,APACHE Ⅱ,and LIPS scores were independent risk factors for poor outcomes in children with severe pneumonia,while FABP5 level was independent protective factor for poor outcomes in children with severe pneumonia(P＜0.05).The levels of CCL3 and sPDPN were positively correlated with APACHE Ⅱ score and LIPS score,while FABP5 was negatively correlated with APACHE Ⅱ score and LIPS score(P＜0.05).The AUC of CCL3,sPDPN,and FABP5 alone was 0.802,0.864,and 0.859 respectively for predicting poor prognosis in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 was superior to CCL3,sPDPN,or FABP5 alone(Zcombination-CCL3=3.842,Zcombination-sPDPN=2.585,Zcombination-FABP5=2.957,P＜0.05).Conclusions The serum levels of CCL3 and sPDPN are positively correlated with the severity of lung injury,while FABP5 is negatively correlated with the severity of lung injury in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 is valuable for predicting poor outcomes in children with severe pneumonia.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.

Objective:To analyze the therapeutic effect of a virtual reality (VR)-based accommodation training device on accommodative excess visual fatigue.Methods:A case-control study was conducted.A total of 20 normal subjects (20 eyes) and 20 patients with accommodative excess visual fatigue (20 eyes) were recruited at Zhongshan Ophthalmic Center, Sun Yat-sen University between January and December 2022.The study consisted of two phases.In the first phase, the effect of watching videos with VR glass on the subjects' subjective and objective visual function was evaluated.Normal subjects wore VR device to watch a 2D video for 30 minutes, and assessments were performed before and after viewing.These assessments included binocular accommodation/convergence function (accommodation response, accommodative convergence to accommodation ratio [AC/A]), tear film function (first tear film break-up time), subjective symptoms (visual fatigue score), and basic visual health parameters including best corrected visual acuity (BCVA) and intraocular pressure (IOP).In the second phase, the improvement in subjective and objective visual fatigue metrics with the VR-based accommodation training device was investigated.Patients with visual fatigue were divided into a traditional training group using traditional flipper lenses and a VR training group using the VR accommodation training device, with 10 eyes in each group.The effects of the VR accommodation training device on indicators such as accommodative sensitivity, accommodation response, convergence function, visual fatigue score, acceptability score, system usability score, BCVA, and IOP were evaluated and compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.IIT2021007).Written informed consent was obtained from each subject.Results:In normal subjects, there was no statistically significant difference in first tear film break-up time, distance phoria, near phoria, AC/A, accommodative response, BCVA, or IOP before and after 30 minutes of continuous viewing of 2D video using VR glass ( t=1.155, 1.360, 4.479, 1.979, -1.249, -3.017, 2.211; all P>0.05).The visual fatigue score remained unchanged at (1.00±0.00) points before and after viewing.Among the subjects with visual fatigue, there were statistically significant differences in binocular accommodative sensitivity, dominant eye accommodative sensitivity, and BCVA before and after using the VR accommodation training device ( F=8.693, 4.078, 4.942; all P<0.05).Ocular accommodation sensitivity at 8 weeks after training was improved compared with 1 week after training, and BCVA at 4 weeks after training was improved compared with before training, and the differences were statistically significant (both P<0.05).In the VR training group, the average tear film break-up time, first tear film break-up time, and BCVA increased and the visual fatigue score decreased compared with before training, the differences were statistically significant (all P<0.05).In the traditional training group, the accommodation sensitivity of the dominant eye increased after training compared with before training, with a statistically significant difference ( P<0.05). Conclusions:Watching 2D videos with VR glass for 30 minutes does not induce subjective or objective symptoms of visual fatigue.The VR-based accommodation training paradigm effectively improves accommodative sensitivity and alleviates subjective symptoms of visual fatigue in individuals with accommodative excess visual fatigue.

Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.