[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。

BackgroundMonitoring the blood concentrations of antipsychotic drugs and their metabolites can guide the adjustment of clinical treatment plans， improving therapeutic efficacy while reducing adverse effects. However， there is currently a lack of a method that can accurately and efficiently quantitatively detect multiple antipsychotic drugs and their metabolites. ObjectiveTo establish a ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous identification and quantitation of 12 antipsychotic drugs and their main metabolites in human serum. MethodsUsing UPLC-MS/MS technology， protein precipitation method was employed for sample pretreatment. An Agela Technologies Durashell C₈ chromatographic column （50 mm×3.0 mm， 5 μm） was selected for chromatographic separation with gradient elution. The flow rate was 0.4 mL/min， and the total analysis time was 5 minutes. The column temperature was 40℃. The mass spectrometry detection was carried out in the multiple reaction monitoring （MRM） mode， and the isotope internal standard method was used for quantification. ResultsThe relative standard deviation （RSD） of the internal standard normalization matrix effect factor for 12 antipsychotic drugs and their main metabolites at low and high quality concentrations was all less than 15%. The extraction recovery rate was 85% to 115%. They showed good linear relationships within their respective standard curve ranges （r>0.995）. At low， medium， and high quality concentrations， the accuracy was 85.24% to 114.71%， and the RSD of intra-batch and inter-batch precision was all ≤14.15%， with good stability. ConclusionAll the analytical performance indicators of this method meet the verification requirements， providing an analytical means for the quantitative detection of antipsychotic drugs and their main metabolites in human serum. ［Funded by The Third Batch of Science and Technology Projects in Chaozhou City in 2023 （number， 202303GY02）］

Sixteen compounds were isolated from the solid rice culture of the endophytic fungus Alternaria alstroemeriae WZ-419 derived from Pseudostellariae Radix, using silica gel, ODS, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated based on physicochemical properties and comprehensive spectroscopic analyses, and identified as alterpenoid A (1), tricycloalternarene A (2), altenusin (3), 4'-epialtenuene (4), altenuene (5), alternariol (6), altenuisol (7), 3-hydroxyalternariol-5-O-methylether (8), alternariol-9-methyl ether (9), alternariol 1′-hydroxy-9-methyl ether (10), stemphyperylenol (11), dihydroalterperylenol (12), alterinone A (13), 4-hydroxy-3-methoxy-5-(2E,6E-3,7,11-trimethyldodeca-2,6,10-trien-1-yl) benzoic acid (14), hexylitaconic acid (15), and altechromone A (16). Among them, compound 1 and 13 were new, and compounds 14 and 15 were isolated from the genus Alternaria for the first time. The antibacterial activities of compounds 1–16 were evaluated in vitro. Compounds 3, 6–8, 10, 11, 13, and 14 exhibited notable inhibitory effects against Gram-positive bacteria, with minimal inhibitory concentrations ranging from 8 to 64 µg/mL.This study isolated a series of antimicrobial metabolites from the endophytic fungi of Pseudostellariae Radix, providing new insights into their bioactive constituents and laying a foundation for further pharmacological investigations.

Objective To explore the feasibility of magnetic compression technique (MCR) in the treatment of severe single mid-ureteral stricture in a rabbit model. Methods After 10 female New Zealand rabbits were selected, the distal end of the right ureter was ligated with silk thread. Two weeks after the operation, when the right ureter was dilated, the mid-ureter was ligated again with silk thread to create a severe single mid-ureteral stricture animal model. Longitudinal incisions were made at the upper and lower ends of the ligation site, and cylindrical NdFeB magnets with central holes (sub-magnets and main magnets) were placed to anastomose and recanalize the mid-ureteral stricture. The magnets were adjusted to the appropriate position to automatically align and attract each other. The longitudinal incision sites of the ureter were sutured with 6-0 Prolene thread, and the abdominal cavity was closed layer by layer. The operation time was recorded. X-ray films were taken every two days to confirm the position of the magnets and record the time of magnet detachment. Three weeks after the operation, the anastomotic specimens were obtained, and the formation of the anastomosis was evaluated with gross observation and histological staining. Results Two weeks after ligation, all experimental rabbits showed obvious dilation of the right ureter. The mid-ureteral ligation and placement of the male and female magnets were successfully completed in all 10 experimental rabbits, with an operation time of (24.00±5.15)minutes. The male and female magnets attracted each other well. X-ray examination showed that the magnets detached and entered the distal ureter (14.0±1.9) days after magnetic compression. The recanalization of the severe single mid-ureteral stricture was successfully achieved. The gross specimens and histological examination of the anastomosis showed that the anastomosis remained patent and the mucosal healing was good. All experimental rabbits survived well after the operation without serious complications. Conclusion MCT provides a new idea and novel method for the treatment of mid-ureteral stricture. This study confirmed the feasibility of this technique in treating severe single mid-ureteral stricture in a rabbit model. The operation is relatively simple and has potential for clinical application.

Objective To investigate the current status of work readiness and its influencing factors among patients returning to work after lung cancer surgery. Methods A retrospective study was conducted on young and middle-aged postoperative lung cancer patients who were treated at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to September 2023 and returned to their jobs. Data were collected through a general information questionnaire, readiness for return-to-work scale (RRTW), general self-efficacy scale (GSES), and simplified coping style questionnaire (SCSQ). Univariate and multivariate logistic regression analyses were used to explore the factors affecting the work readiness of patients returning to work. Results A total of 219 patients were included, with 59 males and 160 females aged 18-60 years. Among the postoperative lung cancer patients returning to work, 73.1% were in the active maintenance stage of return-to-work readiness with a RRTW score of (17.59±1.48) points, and 26.9% were in the uncertain maintenance stage with a RRTW score of (16.22±1.50) points. Multivariate logistic regression analysis showed that patients aged≤30 years (OR=52.381), employees of enterprises and institutions (OR=7.682), agricultural, pastoral, fishery, forestry laborers (OR=15.665), positive coping (OR=5.043), those with higher self-efficacy (OR=1.157) and engaged in physically demanding work (OR=2.449) had higher return-to-work readiness, while patients with≥2 children (OR=0.055), self-payment (OR=0.044), and those working more than 40 hours per week (OR=0.122) had lower return-to-work readiness. Conclusion The return-to-work readiness of young and middle-aged postoperative lung cancer patients needs to be improved, and occupation, job nature, main coping styles, general self-efficacy and other factors are associated with return-to-work readiness.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

Objective To investigate the effects of HIF1A-AS1 on the proliferation and apoptosis of gastric cancer cells lines BGC-823 and MKN28 and its possible mechanism.Methods The expression of HIF1A-AS1 in gastric cancer tissues was analyzed by bioinformatics.H1F1A-AS1 over expression and silenced BGC-823 and MKN28 cell strains were constructed.HIF1A-AS1 expression was detected by real-time PCR,cell proliferation was detected by CCK-8 assay,and apoptosis was detected by flow cytometry.Western blot was used to detect the expression of HIF1A protein in cytoplasm and nucleus and cellular immunofluorescence was used to detect HIF1A protein into nucleus.Results Models of BGC-823 and MKN28 gastric cancer cells with HIF1A-AS1 over-expression and silence were successfully constructed.HIF1A-AS1 over-expression decreased cell proliferation(P＜0.05),while HIF1A-AS1 over-expression significantly increased cell proliferation(P＜0.05).HIF1A-AS1 silencing significantly increased the apoptosis(P＜0.05),and HIF1A-AS1-over expression significantly decreased the apoptosis(P＜0.05).HIF1A-AS1 silencing inhibited the nucleation of HIF1A protein and over-expression promoted the nucleation of HIF1A pro-tein.HIF1A-AS1 silencing significantly decreased the expression of HIF1A cytoplasmic protein(P＜0.05)and over-expression of HIF1A-AS1 significantly increased the expression of HIF1A cytoplasm protein(P＜0.05).HIF1A-AS1 silencing significantly decreased the expression of HIF1A nuclear protein(P＜0.05)while HIF1A-AS1 over-expression significantly increased the expression of HIF1A nuclear protein(P＜0.05).Conclusions HIF1A-AS1 may promote the proliferation and inhibit apoptosis of BGC-823 and MKN28 gastric cancer cells by regulating the expression of parental gene HIF1A.