[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.

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.

ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

Objective To investigate the role and mechanism of bergapten in treating osteoarthritis(OA)based on network pharmacology,molecular docking and in vitro experiments.Methods The functional targets of bergapten and the related targets of OA disease were obtained by searching Super-Pred,Swiss Target Prediction,Drug Bank.The obtained targets were intersected with Venny2.1.0,protein-protein interaction(PPI)analysis was performed using the STRING database,and molecular docking was conducted by AutoDock Vina.Subsequently,human chondrocyte C28/I2 cells were subjected in the following validation experiments.After the cells were treated with 0～50 μmol/L bergapten for 24,48 or 72 h,CCK-8 assay,RT-qPCR and immunofluorescence assay were used to detect the proliferation and apoptosis,and the expression of the molecules related to proliferation,inflammation and senescence(senescence associated secretory phenotype,SASP).Senescence β-galactosidase(SA-β-Gal)staining kit was employed to detect the change of SA-β-Gal level in the cells.Results There obtained 145 potential targets of bergapten for OA.PPI analysis revealed 4 potential core targets,HSP90AA1,EGFR,HIF1A,and PIK3CA,and they could form relatively stable complex with bergapten.CCK-8 assay showed that 10 μmol/L bergapten treatment for 48 h resulted in the highest proliferative activity of C28/12 cells(P＜0.05).Immunofluorescence assay,RT-qPCR and Western blotting indicated that bergapten treatment induced significant increases in the expression of cell proliferation markers such as PCNA,CCND1 and CCNE1(P＜0.05),while decreases in the expression of apoptosis markers Caspase3 and BAX(P＜0.05).Meanwhile,the expression levels of IL-1β-induced inflammatory factors IL-6 and TNF-α were reduced,while those of anti-inflammatory factors IL-4 and IL-10 were elevated after bergapten treatment(P＜0.05).The levels of SASP factors,such as P16,P21,MMP9 and MMP13 were also significantly declined(P＜0.05).SA-β-Gal staining displayed that the level of SA-β-Gal in C28/I2 cells was significantly enhanced after IL-1β induction(P＜0.05),while bergapten treatment could decrease the positive cell rate of the staining(P＜0.05).Conclusion Bergapten can reduce the expression of SASP factors such as IL-6,TNF-α,P16,P21,MMP9 and MMP13 in IL-1 β-stimulated chondrocytes,and thus exerts its anti-inflammatory and anti-aging effects in delaying the progression of OA.

Objective To investigate the expression of calumenin(CALU)in gastric cancer and its effect on metastasis and invasion of gastric cancer,and analyze its relationship with the prognosis of gastric cancer patients.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the expression level of CALU in gastric cancer and its impact on patient prognosis.A total of 102 pairs of gastric cancer and paracancerous tissue samples were collected from 189 gastric cancer patients who underwent partial gastrectomy in First Affiliated Hospital of Army Medical University from January 2018 to December 2022.The expression of CALU in gastric cancer and paracancerous tissues was detected by immunohistochemical assay,and the relationship of its expression with clinicopathological parameters was statistically analyzed.After gastric cancer cells with CALU knockdown and overexpression were constructed,and the efficiencies of knockdown and overexpression were evaluated by Western blotting as well as RT-qPCR.Transwell assay was applied to determine the effect of CALU on the migration and invasion abilities of gastric cancer cells.Results Bioinformation analysis found that CALU was significantly highly expressed in gastric cancer tissues(P<0.05),and its expression level was negatively correlated with the prognosis of patients(P<0.05).Immunohistochemical results showed that the expression level of CALU was obviously highly in gastric cancer tissues than the paracancerous tissues(P<0.01),and its level was positively correlated with the depth of infiltration(P<0.01),lymph node metastasis(P<0.01),and TNM stage(P<0.05).Statistical analysis revealed that the clinical data of 102 patients showed that CALU expression was positively correlated with the TNM stage(P=0.021)and T stage(P<0.001)and N stage(P=0.028).CALU knockdown significantly inhibited the migration and invasion abilities of gastric cancer cells(P<0.01),while over-expression obtained the opposite results.Conclusion CALU is highly expressed in gastric cancer tissues and promotes metastasis and invasion of gastric cancer and thus leads to poor prognosis in patients.

Objective To investigate the relationship between ferroptosis-related genes[heme oxygenase-1(HO-1),solute carrier family 7 member 11(SLC7A11),and long-chain acyl-coenzyme A synthetase 4(ACSL4)]expression and cardiovascular events in patients with chronic renal failure(CRF),aiming to pro-vide clinical insights for risk assessment of cardiovascular complications.Methods A total of 124 CRF pa-tients(CRF group)admitted to the hospital from January 2020 to January 2023 and 124 healthy people(con-trol group)who underwent physical examination in the hospital during the same period were selected as the research objects.The levels of ferroptosis-related gene HO-1,SLC7A11 and ACSL4 were detected and com-pared between the two groups.CRF patients were followed up for 12 months after discharge,and they were di-vided into concurrent group(n=56)and non-concurrent group(n=66)according to the occurrence of cardio-vascular events.Spearman correlation analysis was used to investigate the correlation between iron death relat-ed genes HO-1,SLC7A11,ACSL4 and cardiovascular events in CRF patients.Univariate and multivariate Lo-gistic regression analysis were used to investigate the influencing factors of cardiovascular events in CRF pa-tients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of iron death re-lated genes HO-1,SLC7A11,and ACSL4 for cardiovascular events in CRF patients.Results Serum HO-1 and SLC7A11 levels in CRF group were lower than those in control group(P＜0.05),and the ACSL4 level was higher than that in control group(P＜0.05).The serum HO-1 and SLC7A11 levels in concurrent group were lower than those in non-concurrent group(all P＜0.05),and the serum ACSL4 level was higher than that in non-concurrent group(P＜0.05).Ferroptosis-related genes HO-1 and SLC7A11 were negatively correlated with cardiovascular events(r=-0.708,—0.721,P＜0.05),while ACSL4 was positively correlated with car-diovascular events(r=0.699,P＜0.05).High serum ACSL4 expression and high cTnT level were risk fac-tors for cardiovascular events in CRF patients(P＜0.05),and high hemoglobin level and high serum HO-1 and SLC7A11 expression were protective factors for cardiovascular events in CRF patients(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum HO-1,SLC7A11,ACSL4,hemo-globin and cTnT alone for predicting cardiovascular events in CRF patients were 0.787,0.735,0.773,0.651 and 0.782,respectively.The AUC of the combined prediction of ferroptosis-related genes was 0.837,and the AUC of the combined application of five factors was 0.880.According to Delong's test,the AUC of both com-bined application models was significantly higher than those of individual application(P＜0.05).The nomo-gram model showed that all ferroptosis-related genes were positively expressed(HO-1＜1.5,SLC7A11＜1.15,ACSL4≥2.75),and the risk of developing concurrent cardiovascular events in CRF patients could reach over 75％.Conclusion The expression of serum HO-1 and SLC7A11 in CRF patients is decreased,and the ACSL4 expression is increased,which is closely related to cardiovascular events,and the combined detection of three indexes has high value in predicting cardiovascular events in CRF patients.

Objective To investigate the inhibitory effect of morin on the cell cycle progression and prolif-eration ability of lung adenocarcinoma cells by regulating the transforming growth factor β1(TGF-β1)/Smads signaling pathway.Methods Human lung adenocarcinoma cell line A549 was used for in vitro experiments.Different concentrations of morin(0,30,90,150 μg/mL)were used to treat human lung adenocarcinoma cell line A549.Cell survival rate was detected by CCK-8 method,cell cycle distribution was detected by Hoechst 33342 staining method,cell proliferation ability was detected by clone formation assay,cell invasion ability was detected by Transwell invasion assay,cell apoptosis was detected by TUNEL staining method,and the expres-sion levels of TGF-β1/Smads signaling pathway related proteins were analyzed by Western blot.Results CCK-8 experimental results showed that the survival rate of A549 cells in the morin-treated group significantly decreased with the increase in morin concentration(P＜0.05).The results of Hoechst 33342 staining showed that the proportion of G1 phase cells in the morin-treated group significantly increased,and the proportion of S phase and G2/M phase cells significantly decreased(P＜0.05).The results of the colony formation assay showed that the number of colonies formed in the morin-treated group was significantly less than that in the control group,and the colony formation rates in the 90 μg/mL and 150 μg/mL groups were reduced by approximately 50％and 70％respectively(P＜0.05).Transwell invasion assay results showed that the number of invasive cells in the morin-treated group was significantly reduced(P＜0.05).TUNEL staining results showed that the proportion of apoptotic cells in the morin-treated group significantly increased(P＜0.05).Western blot results showed that the expression levels of TGF-β1 and p-Smad2/3 in the morin-treated group were significantly reduced(P＜0.05),and the expression level of Smad7 was significantly in-creased(P＜0.05).Conclusion Morin blocks A549 cells in the G1 phase by regulating the TGF-β1/Smads signaling pathway,thereby inhibiting cell proliferation,reducing cell invasion ability,and inducing cell apopto-sis.This indicates that morin has potential application value in the treatment of lung adenocarcinoma.

ObjectiveTo investigate the chemical hazards in the production line of lithium batteries, so as to provide a scientific basis for the management of occupational-health risk and to promote the healthy and sustainable development of the lithium battery industry. MethodsAn on-site survey on the process flow of the production of lithium battery was conducted in an enterprise. Volatile organic compounds (VOCs) in the occupational environment were collected by Summa canisters, carbonates and N-methyl pyrrolidone (NMP) were collected using activated carbon tubes, and airborne metals were collected using filter membranes. VOCs, carbonates and NMP were detected by gas chromatography-mass spectrometry (GC-MS), and airborne metal elements in the dust samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). ResultsNon-targeted environmental monitoring results indicated that NMP was detected in the negative /positive electrode coating, assembly and drying filling workstations, dimethyl carbonate (DMC) was detected in the assembly, drying and electrolyte injection workstations, and ethyl methyl carbonate (EMC) was detected solely in the electrolyte injection workstation. Semi-quantitative analyses of VOCs identified 136 pollutants, including acrylonitrile and halohydrocarbons. Quantitative targeted environmental monitoring results revealed the highest geometric mean (GM) concentration of EMC (31.450 mg·m^-3) was found in the assembly and drying workstations, diethyl carbonate (DEC) was detected in all workstations. While vinylene carbonate (VC) and ethylene carbonate (EC) were detected only in electrolyte injection, assembly and drying workstations. NMP was detected in all positive electrode coating samples, with a GM concentration of 5.68 mg·m^-3 (concentration range: 4.0‒ 7.4 mg·m^-³). Lithium was exclusively detected in dust samples from the liquid injection workstation (GM: 0.014 μg·m^-³). ConclusionNMP, EMC, DEC, and other chemicals are identified at the key workstations such as the positive electrode coating, electrolyte injection, assembly and drying in the lithium production line. Furthermore, semi-quantitative VOCs analyses identified 136 pollutants, demonstrating a characteristic of multicomponent chemical exposure.

Objective To develop a core outcome set(COS)for treatment of progressive vitiligo in Uyghur medicine,and to standardize the selection and reporting of outcome measures in relevant studies.Methods Based on the existing core outcome domain set of randomized controlled trials for vitiligo,additional outcome indicators reflecting the advantages and characteristics of Uyghur medical treatment were developed.Specific indicators for Uyghur medical treatment of progressive vitiligo were collected through literature review and semi-structured questionnaire surveys,and then a list of indicators were formed.The Delphi survey and consensus meetings were used to select core indicators.Results A total of 54 studies were included,and 86 questionnaires were collected.Through literature review and questionnaire surveys,a list of 28 indicators were obtained.After two rounds of Delphi survey and one consensus meeting,12 outcome indicators in 7 domains were finally determined,including vitiligo lesion area,repigmentation,disease control time,maintenance of repigmentation,recurrence rate,immune indicators,psychological health,patients' quality of life,adverse events,adverse reaction incidence,liver and kidney function monitoring,and Uyghur medicine syndrome differentiation of mucus.Additionally,some measurement tools for certain indicators were recommended.Conclusion The development of the COS for vitiligo treatment in Uyghur medicine helps to comprehensively evaluate the efficacy of Uyghur medicine,and will provide a model for establishing efficacy evaluation methods that conform to the characteristics of ethnic minority medicine.