[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 summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

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.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， with a complex pathogenesis. Mitochondria play a pivotal role in this disease process， and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance， while mitochondrial DNA （mtDNA） is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA， it can be recognized by intracellular pattern recognition receptors， which in turn triggers innate immune responses and causes tissue damage， forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently， there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway， its pathological role in the development and progression of MAFLD， and the current intervention strategies targeting this mechanism， in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.

To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE).

Objective:To investigate the effects of SS31 peptide on cognitive function and cortical oxidative stress in Alzheimer's disease (AD) model mice.Methods:Eighteen SPF grade male 8-month-old APP/PS1 mice were randomly divided into model group and SS31 group according to the random number table method, with nine mice in each group. Additionally, nine C57BL/6J mice with matched weight were selected as the control group. The mice in SS31 group were intraperitoneally injected with SS31 peptide (3 mg/kg, 0.3 mg/mL), while the mice in model group and control group were intraperitoneally injected with an equal volume of 0.9% NaCl solution.The response ability and daily living ability of mice were evaluated by nest building test (NBT).The learning, memory and exploration abilities of mice were assessed by new object recognition (NOR) and Morris water maze test (MWM). ELISA was used to detect the levels of β -amyloid protein (Aβ) and reactive oxygen species (ROS) in cerebral cortex of mice, and immunofluorescence (IF) was used to detect the number of Aβ plaques.Flow cytometry was used to detect neuronal apoptosis rate, Nissl staining was used to detect neuronal damage, and transmission electron microscopy was used to observe neuronal and mitochondrial morphology. Statistical analysis was conducted by SPSS 25.0 software. One-way ANOVA or repeated measures ANOVA or Kruskal-Wallis H test were used for multi-group comparison. Results:(1) The cognitive evaluation results showed that there were statistically significant differences in NBT latency, 15 hour nest building score, and NOR recognition index among the 3 groups of mice ( F=5.488, 6.750, 10.379, all P<0.05), as well as the platform crossing frequency( H=6.742, P<0.05).The time and group interaction of MWM escape latency in the 3 groups of mice were not significant( F=0.975, P=0.460), but the main effect of time and group were significant( F=14.011, 4.173, both P<0.05).The percentage of platform quadrant dwell time in the model group ((22.91 ± 5.16)%) was lower than that in the control group ((39.96±4.69)%) ( P<0.05), but there was no statistically significant difference compared to the SS31 group ((25.18±3.04)%) ( P>0.05). (2) The ELISA results showed that there were statistically significant differences in the levels of Aβ40, Aβ42 and ROS in cerebral cortex of the 3 groups of mice ( F=12.634, 43.670, 7.143, all P<0.01).All the above indicators of cerebral cortex in the model group were higher than those in control group and SS31 group (all P<0.05). The IF results also confirmed that the numbers of Aβ40 and Aβ42 plaques in cerebral cortex of the model group were higher than those of the control group and SS31 group (all P<0.05). (3) The results of flow cytometry and Nissl staining showed that there were statistically significant differences in the apoptosis rate and injury rate of cortical neurons among the 3 groups of mice ( F=234.086, 43.800, both P<0.05), and the two indicators of cortical neurons in the model group were higher than those in control group and SS31 group (all P<0.05). The transmission electron microscopy results showed that compared with the control group, the structure and morphology of cortical neurons and mitochondria in the model group were abnormal, while the structure and morphology of the SS31 group were close to normal. Conclusion:SS31 peptide can improve cognitive function in AD model mice by inhibiting oxidative stress and neuronal apoptosis in cerebral cortex.

Objective This study aimed to investigate the relationship between malnutrition and coronary inflammation,and explore the interaction and mediating effects of coronary inflammation in the association between malnutrition and major adverse cardiovascular events(MACE).Methods A retrospective analysis was conducted on 428 patients diagnosed with coronary heart disease at the Central China Fuwai Hospital from May 2018 to July 2022.All patients underwent coronary angiography(CAG)and coronary computed tomography angiography(CCTA).The TCB index(triglycerides×total cholesterol×body weight)and the coronary fat attenuation index around the proximal right coronary artery(RCA-FAI)were used to assess patients' nutritional state and the degree of coronary inflammation,respectively.The study endpoint was MACE.We used linear regression models to analyze the correlation between TCBI and RCA-FAI,cox regression models to assess the correlation of TCBI and RCA-FAI with MACE,and mediation analysis to investigate whether RCA-FAI mediated the relationship between TCBI and MACE.Results A total of 428 patients were included in the study.There was a negative correlation between RCA-FAI and TCBI(r=-0.224,P<0.001).After adjusting for potential confounders,each standard deviation decrease in the TCBI index was associated with a 2.20 HU increase in RCA-FAI(95%CI:-3.40～-1.19,P<0.001).During a mean follow-up period of 2.15 years,51 MACE occurred.MACE risk in the low TCBI/high RCA-FAI group was 6.58 times higher than that in the high TCBI/low RCA-FAI group(adjusted HR=6.580,95%CI:2.237～19.360,P=0.001),and the interaction between TCBI and RCA-FAI was identified.Mediation analysis revealed that RCA-FAI mediated 37.5%of the associations between TCBI and MACE.Conclusions In patients with coronary artery disease,malnutrition is associated with increased coronary inflammation.There is a significant interaction between malnutrition and coronary inflammation in the risk of MACE,and coronary inflammation partially mediates the relationship between malnutrition and MACE.The combination of the TCBI index and RCA-FAI can help identify patients at high cardiovascular risk.Improving malnutrition and controlling coronary inflammation may provide addi-tional benefits for patients with coronary artery disease.

Objective:To investigate the effects of SS31 peptide on cognitive function and cortical oxidative stress in Alzheimer's disease (AD) model mice.Methods:Eighteen SPF grade male 8-month-old APP/PS1 mice were randomly divided into model group and SS31 group according to the random number table method, with nine mice in each group. Additionally, nine C57BL/6J mice with matched weight were selected as the control group. The mice in SS31 group were intraperitoneally injected with SS31 peptide (3 mg/kg, 0.3 mg/mL), while the mice in model group and control group were intraperitoneally injected with an equal volume of 0.9% NaCl solution.The response ability and daily living ability of mice were evaluated by nest building test (NBT).The learning, memory and exploration abilities of mice were assessed by new object recognition (NOR) and Morris water maze test (MWM). ELISA was used to detect the levels of β -amyloid protein (Aβ) and reactive oxygen species (ROS) in cerebral cortex of mice, and immunofluorescence (IF) was used to detect the number of Aβ plaques.Flow cytometry was used to detect neuronal apoptosis rate, Nissl staining was used to detect neuronal damage, and transmission electron microscopy was used to observe neuronal and mitochondrial morphology. Statistical analysis was conducted by SPSS 25.0 software. One-way ANOVA or repeated measures ANOVA or Kruskal-Wallis H test were used for multi-group comparison. Results:(1) The cognitive evaluation results showed that there were statistically significant differences in NBT latency, 15 hour nest building score, and NOR recognition index among the 3 groups of mice ( F=5.488, 6.750, 10.379, all P<0.05), as well as the platform crossing frequency( H=6.742, P<0.05).The time and group interaction of MWM escape latency in the 3 groups of mice were not significant( F=0.975, P=0.460), but the main effect of time and group were significant( F=14.011, 4.173, both P<0.05).The percentage of platform quadrant dwell time in the model group ((22.91 ± 5.16)%) was lower than that in the control group ((39.96±4.69)%) ( P<0.05), but there was no statistically significant difference compared to the SS31 group ((25.18±3.04)%) ( P>0.05). (2) The ELISA results showed that there were statistically significant differences in the levels of Aβ40, Aβ42 and ROS in cerebral cortex of the 3 groups of mice ( F=12.634, 43.670, 7.143, all P<0.01).All the above indicators of cerebral cortex in the model group were higher than those in control group and SS31 group (all P<0.05). The IF results also confirmed that the numbers of Aβ40 and Aβ42 plaques in cerebral cortex of the model group were higher than those of the control group and SS31 group (all P<0.05). (3) The results of flow cytometry and Nissl staining showed that there were statistically significant differences in the apoptosis rate and injury rate of cortical neurons among the 3 groups of mice ( F=234.086, 43.800, both P<0.05), and the two indicators of cortical neurons in the model group were higher than those in control group and SS31 group (all P<0.05). The transmission electron microscopy results showed that compared with the control group, the structure and morphology of cortical neurons and mitochondria in the model group were abnormal, while the structure and morphology of the SS31 group were close to normal. Conclusion:SS31 peptide can improve cognitive function in AD model mice by inhibiting oxidative stress and neuronal apoptosis in cerebral cortex.

Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7％)had strictures in the upper ureter,9(12.7％)in the middle ureter,15(21.1％)in the lower ureter,and 11(15.5％)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1％)and appendiceal flap ureteroplasty(8/36,22.2％).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1％)and ureteroureterostomy(1/9,11.1％)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3％)and ileal ureter replacement(4/9,44.4％)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7％),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2％)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.