[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。

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.

Breast cancer remains a substantial threat to women's health and is one of the most prevalent malignant tumors in women.Because breast cancer onset is closely associated with female physiological characteristics,this article proposes that breast cancer be classified as a"women's miscellaneous diseases"and that its treatment be explored from this perspective.Drawing from Chapter 8 on Golden Chamber of Prescriptions for Miscellaneous Diseases in Women of Synopsis of Golden Chamber,the initial pathogenesis of breast cancer is associated with"emotional stress,improper lifestyle,deficiency,cold,and stagnation."The fundamental mechanism behind its formation is"blood cold accumulation and hardened masses."Specifically,emotional imbalance and improper lifestyle habits contribute to the combined invasion of the uterus by"deficiency,""accumulated cold,"and"stagnant qi."Over time,"cold-blood stasis accumulates at the uterine ostium,"and the cold and the stasis ascends from the uterus along the thoroughfare and conception vessels,obstructing the breast collaterals.This combination of yang qi stagnation and yin cold congealment,ultimately leads to the development of breast cancer.The treatment principle should focus on"activating yang and dispersing cold."A therapeutic approach centered on Wenjing Decoction combined with Xiaoyao Powder can be adapted based on the stage and type of breast cancer while also considering the dynamic interplay between pathogenic factors and healthy qi,along with shifts in deficiency and excess patterns of disease.By adhering to the principles of consistency and flexibility and integrating disease and syndrome differentiation,the goal is to develop precise and personalized treatment strategies to improve clinical outcomes.

Breast cancer remains a substantial threat to women's health and is one of the most prevalent malignant tumors in women.Because breast cancer onset is closely associated with female physiological characteristics,this article proposes that breast cancer be classified as a"women's miscellaneous diseases"and that its treatment be explored from this perspective.Drawing from Chapter 8 on Golden Chamber of Prescriptions for Miscellaneous Diseases in Women of Synopsis of Golden Chamber,the initial pathogenesis of breast cancer is associated with"emotional stress,improper lifestyle,deficiency,cold,and stagnation."The fundamental mechanism behind its formation is"blood cold accumulation and hardened masses."Specifically,emotional imbalance and improper lifestyle habits contribute to the combined invasion of the uterus by"deficiency,""accumulated cold,"and"stagnant qi."Over time,"cold-blood stasis accumulates at the uterine ostium,"and the cold and the stasis ascends from the uterus along the thoroughfare and conception vessels,obstructing the breast collaterals.This combination of yang qi stagnation and yin cold congealment,ultimately leads to the development of breast cancer.The treatment principle should focus on"activating yang and dispersing cold."A therapeutic approach centered on Wenjing Decoction combined with Xiaoyao Powder can be adapted based on the stage and type of breast cancer while also considering the dynamic interplay between pathogenic factors and healthy qi,along with shifts in deficiency and excess patterns of disease.By adhering to the principles of consistency and flexibility and integrating disease and syndrome differentiation,the goal is to develop precise and personalized treatment strategies to improve clinical outcomes.

In patients with heart failure with reduced ejection fraction(HFrEF),some individuals demonstrate significant improvement in left ventricular ejection fraction(LVEF)during subsequent evaluations after treatment.The 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America(AHA/ACC/HFSA)heart failure management guidelines introduced the term"heart failure with improved ejection fraction(HFimpEF)"to describe patients with prior LVEF≤40%that subsequently increased above 40%during follow-up.Studies indicate that HFimpEF patients exhibit lower all-cause mortalities and heart failure rehospitalization rates,with a significantly better prognosis compared to HFrEF patients,establishing HFimpEF as a staged therapeutic target for HFrEF.Current discussion on HFimpEF primarily focuses on two aspects:characteristics of the target population and effective methods for LVEF improvement,and maintenance strategies for cardiac function preservation in HFimpEF patients;particularly the latter lacks clear clinical-guideline recommendations.Therefore,reviewing existing research to systematically summarize therapeutic strategies that promote the HFrEF-to-HFimpEF transition and effective maintenance approaches for HFimpEF becomes crucial.This article comprehensively reviews the LVEF-improving effects of current pharmacological,device-based,and surgical interventions,along with monitoring and management strategies for HFimpEF patients.In HFrEF patients,clinical evidence suggests that β-blockers and cardiac resynchronization therapy can significantly improve LVEF beyond 40%.Regarding HFimpEF management,sodium-glucose cotransporter-2 inhibitors(SGLT2i)and renin-angiotensin system inhibitors(RASi)demonstrate efficacy in maintaining LVEF and cardiac function.Additionally,this review identifies current research limitations in HFimpEF and proposes potential future research directions.

Objective:To investigate the longitudinal patterns and influencing factors of platelet counts among healthy adults in Sichuan Province from 2010 to 2021, and to inform the establishment of region-specific reference intervals for platelet counts.Methods:This study is a retrospective study. A total of 7 808 healthy adults who underwent annual physical examinations at West China Hospital, Sichuan University, between January 2010 and December 2021 were included. All participants were permanent Chengdu residents and completed consecutive complete blood count tests. Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of platelet count over the ten-year period. One-way analyses were then conducted to compare baseline demographic characteristics (sex and age) among the different trajectory groups.Results:Among 7 808 participants, 4 589 (58.8%) were male and 3 219 (41.2%) were female. Four platelet count trajectories were identified by GBTM: steadily increasing group [27.4% (2 139/7 808)], early increase-plateau group [44.1% (3 445/7 808)], early decrease-subsequent increase group [5.4% (422/7 808)], and steadily decreasing group [23.1% (1 802/7 808)], with an average growth rate of 3.3%, 1.6%, 0.7%, and -0.6%, respectively. There were statistically significant differences in both sex and age distributions among the four trajectory groups. Sex-distribution differed significantly across the four trajectory groups ( χ2=73.3, P<0.001). The male proportions in the four trajectory groups were 59.6% (1 275/2 139), 62.8% (2 165/3 445), 48.1% (203/422), and 52.5% (946/1 802), respectively. The baseline ages were 45 (36, 55), 43 (35, 53), 50 (40, 60), and 47 (39, 58) years, respectively (H=121.0, P<0.001). Conclusions:Healthy adults in Sichuan Province exhibit four longitudinal trajectories of platelet counts: steadily increasing, early increase-plateau, early decrease-subsequent increase, and steadily decreasing. The two trajectories characterized by rising platelet counts (steadily increasing group and early increase-plateau group) exhibited higher male predominance and lower median ages, whereas the early decrease-subsequent increase group and the steadily decreasing group exhibited lower male proportions and higher median ages. Therefore, while establishing reference intervals and developing health management strategies for platelet counts, it is essential to account for the sex, age characteristics and the population′s dynamic changes.

Charcot-Marie-Tooth disease (CMT) is a progressive hereditary peripheral neuropathy characterized by symmetrical distal muscle atrophy, sensory impairment, disappearance of tendon reflexes in both lower limbs, arch foot, claw hand, and scoliosis. This article reports a family of CMT type 4C (CMT4C), whose proband carries a compound heterozygous mutation of c.2782C>T and c.1586G>A in the SH3TC2 gene, with ataxia as the main symptom. The literatures related to CMT4C patients in major databases at home and abroad are summarized to provide reference for early identification and diagnosis of this type of patient.

Objective:The purpose of this study was to develop a dynamic prediction model for patients with gastric signet ring cell cancer (GSRCC)following laparoscopic radical gastrectomy in order to improve the precision and usefulness of prognoses prediction for overall survival and disease-free survival.Methods:From 2011 to 2018, 914 National Cancer Center patients participated in the study. To find independent prognostic indicators and create a prognostic nomogram model, univariate and multivariate regression analyses were performed. Calibration curves, receiver operating characteristic curves, and consistency indices were used to assess the model's performance. To make clinical application more convenient, two web-based prediction tools were created.Results:A training set of 639 cases and a validation set of 275 instances were randomly selected from among the patients. Important predictive variables such as age, tumor size, location, pN and pT staging, and postoperative chemotherapy were all incorporated in the model (all P<0.05). The model's consistency index and area under the receiver operating characteristic curves were both higher than 0.7, and the calibration curves demonstrated a good fit between the expected and actual values, indicating high accuracy and consistency in postoperative survival prediction for patients with gastric signet ring cell carcinoma. Conclusion:We successfully developed two dynamic prediction models in this study, which improved its clinical practicability using web-based tools and is anticipated to be crucial to clinical practice going forward.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.