[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 explore the role of cysteine aspartic protease-8(Caspase-8)/gasdermin E(GSDME)pathway in the regulation of macrophage pyroptosis in myocardial infarction(MI)rat model and its possible mechanism.Methods Thirty rats were randomly divided into sham operation group,MI group and Caspase-8 inhibition(Z-IETD-FMK)group,with 10 rats in each group.The cultured rat macrophages RMa-bm were divided into control group,hypoxia group and Z-IETD-FMK group.The pathological changes of myocardial tissue were detected by H&E staining.Masson staining was used to detect myocardial fibrosis.The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8,GSDME,NLR family Pyrin domain protein 3(NLRP3),apoptosis-related speck-like protein(ASC)and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA.TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages.Results Compared with the sham operation group,myocardial tissue of rats in MI group was broken and disturbed,inflammatory cell infiltration,a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8,GSDME protein and mRNA in myocardial tissue increased,the differences were statistically significant(t=16.19,27.60;21.18,23.73,all P<0.05).Compared with MI group,Z-IETD-FMK group improved myocardial structural damage,reduced inflammatory cells and collagen deposition,cell apoptosis decreased and decreased Caspase-8,GSDME protein and mRNA expressions in myocardial tissue,with statistical significance(t=20.34,14.56;11.97,24.46,all P<0.05).Compared with the control group,the apoptosis of macrophages in hypoxia group was increased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were increased(tprotein=17.53～120.90,tmRNA=18.42～60.30),the contents of IL-1β and IL-18 in macrophages were increased(t=25.88,45.74),and the differences were staistically significant(all P<0.05).Compared with the hypoxia group,the apoptosis of macrophages in Z-IETD-FMK group was decreased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were decreased(tprotein=17.08～35.08,tmRNA=11.21～47.96),IL-1β and IL-18 content decreased(t=27.38,25.82),and the differences were staistically significant(all P<0.05),respectively.Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

Objective To analyze the research hotspots and frontier trends of transcranial magnetic stimulation(TMS)in the field of rehabilitation in the last decade.Methods The literatures of TMS in the field of rehabilitation from January,2014 to September,2024 were searched in the database of Web of Science core collection,and the visual analysis was carried out by using CiteSpace 6.4.R1 software.Results A total of 1 065 articles were included,showing an increasing trend in annual publication volume.China was the leading country in publication volume,Harvard University was the institution with the largest number of pub-lished articles,and Simone Rossi was the most frequently cited author.Keywords with high co-occurrence fre-quency included stroke,noninvasive brain stimulation,plasticity,cortical excitability,θ burst stimulation and up-per limb.Brain-computer interface was the bursting keyword in the past two years.Conclusion In the past decade,the research interest in TMS in the field of rehabilitation has been on the rise.It focused on the application of multimodal combined therapies,including TMS,to improve the upper limb function and aphasia of stroke patients and to explore the plasticity of brain nerves.Future research should focus on the deep integration of TMS and brain-computer interface technology to realize the individualization and accuracy of TMS treatment.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.

Objective To explore the role of cysteine aspartic protease-8(Caspase-8)/gasdermin E(GSDME)pathway in the regulation of macrophage pyroptosis in myocardial infarction(MI)rat model and its possible mechanism.Methods Thirty rats were randomly divided into sham operation group,MI group and Caspase-8 inhibition(Z-IETD-FMK)group,with 10 rats in each group.The cultured rat macrophages RMa-bm were divided into control group,hypoxia group and Z-IETD-FMK group.The pathological changes of myocardial tissue were detected by H&E staining.Masson staining was used to detect myocardial fibrosis.The protein and mRNA levels of Caspase-8 and GSDME in myocardial tissue and Caspase-8,GSDME,NLR family Pyrin domain protein 3(NLRP3),apoptosis-related speck-like protein(ASC)and Caspase-1 in macrophages were detected by RT-qPCR and Western blotting.The levels of IL-1β and IL-18 in macrophages were detected by ELISA.TUNEL staining was used to detect apoptosis of cardiomyocytes and macrophages.Results Compared with the sham operation group,myocardial tissue of rats in MI group was broken and disturbed,inflammatory cell infiltration,a large amount of collagen fiber deposition in the gap,cell apoptosis increased and the expression of Caspase-8,GSDME protein and mRNA in myocardial tissue increased,the differences were statistically significant(t=16.19,27.60;21.18,23.73,all P<0.05).Compared with MI group,Z-IETD-FMK group improved myocardial structural damage,reduced inflammatory cells and collagen deposition,cell apoptosis decreased and decreased Caspase-8,GSDME protein and mRNA expressions in myocardial tissue,with statistical significance(t=20.34,14.56;11.97,24.46,all P<0.05).Compared with the control group,the apoptosis of macrophages in hypoxia group was increased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were increased(tprotein=17.53～120.90,tmRNA=18.42～60.30),the contents of IL-1β and IL-18 in macrophages were increased(t=25.88,45.74),and the differences were staistically significant(all P<0.05).Compared with the hypoxia group,the apoptosis of macrophages in Z-IETD-FMK group was decreased,and the protein and mRNA expressions of Caspase-8,GSDME,NLRP3,ASC,Caspase-1 in macrophages were decreased(tprotein=17.08～35.08,tmRNA=11.21～47.96),IL-1β and IL-18 content decreased(t=27.38,25.82),and the differences were staistically significant(all P<0.05),respectively.Conclusion Down-regulating Caspase-8/GSDME pathway can improve myocardial injury and hypoxic macrophage scorch death in MI rats.

Objective To analyze the factors influencing iodine nutritional status in pregnant women dur-ing pregnancy,based on thyroid function and thyroid autoantibody levels,and to explore the association between iodine nutritional abnormalities and pregnancy outcomes.Methods A total of 838 pregnant women who underwent routine prenatal checkups at Qinghai Provincial People's Hospital between January 2021 and June 2023 were pro-spectively enrolled in this study.All participants were followed until delivery.Seven cases were lost to follow-up,resulting in a final sample size of 831 participants.Among them,276 were in the first trimester,384 in the second trimester,and 171 in the third trimester.Data on urinary iodine concentration(UIC),urinary creatinine(UCr),thyroid function indicators,and thyroid autoantibodies were collected.Based on their iodine nutritional status,the participants were categorized into either the iodine-sufficient group or the iodine-abnormal group(including iodine-deficient,iodine-hyper-sufficient,and iodine-excessive subgroups).This study analyzed the iodine nutritional sta-tus of pregnant women during different gestational periods,compared thyroid function indices,prevalence of thy-roid diseases,and the positivity rates of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),and thyroid-stimulating hormone receptor antibody(TRAb)among different iodine status groups.Additionally,ad-verse pregnancy outcomes were compared across groups.Multivariate logistic regression analysis was conducted to identify risk factors associated with iodine abnormalities during pregnancy,and a predictive model was developed to assess its potential predictive value.Results Among the 831 pregnant women included in the study,373 cases(44.89％)exhibited iodine sufficiency,while 458 cases(55.11％)presented with iodine abnormalities,including 282 cases of iodine deficiency,144 cases of iodine hypersufficiency,and 32 cases of iodine excess.No statistically significant differences were observed in the iodine nutritional status across different trimesters(P>0.05).The se-rum level of thyroid-stimulating hormone(TSH)was significantly higher in the iodine abnormal group compared to the iodine sufficient group(P<0.05).Additionally,the iodine abnormal group demonstrated higher positivity rates of TPOAb alone,TGAb,and TRAb,as well as increased incidence of thyroid dysfunction and total adverse pregnancy outcomes compared to the iodine sufficient group(all P<0.05).These adverse indicators were also sig-nificantly elevated in the iodine-deficient,iodine super-sufficient,and iodine overdose subgroups compared to the iodine sufficient group(P<0.05).Elevated serum TSH levels and the presence of TPOAb,TGAb,and TRAb were identified as risk factors for iodine abnormalities during pregnancy(P<0.05).The predictive model con-structed for identifying iodine abnormalities in pregnant women demonstrated an area under the curve(AUC)of 0.876,with a sensitivity of 72.27％and a specificity of 89.01％.Conclusions The prevalence of iodine nutritional abnormalities among pregnant women during pregnancy was high,with most cases presenting iodine deficiency.These abnormalities were associated with thyroid function,thyroid autoimmunity,and pregnancy outcomes,but showed no significant correlation with gestational age.Furthermore,the prediction model developed based on iden-tified risk factors demonstrated effective performance in predicting iodine nutritional abnormalities during preg-nancy.

Objective To analyze the research hotspots and frontier trends of transcranial magnetic stimulation(TMS)in the field of rehabilitation in the last decade.Methods The literatures of TMS in the field of rehabilitation from January,2014 to September,2024 were searched in the database of Web of Science core collection,and the visual analysis was carried out by using CiteSpace 6.4.R1 software.Results A total of 1 065 articles were included,showing an increasing trend in annual publication volume.China was the leading country in publication volume,Harvard University was the institution with the largest number of pub-lished articles,and Simone Rossi was the most frequently cited author.Keywords with high co-occurrence fre-quency included stroke,noninvasive brain stimulation,plasticity,cortical excitability,θ burst stimulation and up-per limb.Brain-computer interface was the bursting keyword in the past two years.Conclusion In the past decade,the research interest in TMS in the field of rehabilitation has been on the rise.It focused on the application of multimodal combined therapies,including TMS,to improve the upper limb function and aphasia of stroke patients and to explore the plasticity of brain nerves.Future research should focus on the deep integration of TMS and brain-computer interface technology to realize the individualization and accuracy of TMS treatment.

Objective To investigate the effects of miR-126 on myocardial remodeling and macrophage polarization after acute myocardial infarction(AMI).Methods(1)Twenty-one rats were divided into a sham operation group and an AMI group.The AMI group was further divided into postoperative days 1,3,5,7,9,and 11 days(AMI-1,AMI-3,AMI-5,AMI-7,AMI-9,AMI-11),with 3 rats in each group,and postoperative day 3 was selected for subsequent study.(2)Thirty rats were randomly divided into three groups:sham operation group,AMI group and miR-126 overexpression group,with 10 rats in each group.RT-qPCR was used to detect the expression levels of miR-126 mRNA.2,3,5-Triphenyltetrazole chloride(TTC)staining was used to detect the infarct size.Myocardial fibrosis was detected by Masson staining.The cross-sectional area of the myocardium was determined by H&E staining.Immunofluorescence staining was used to detect the protein levels of CD86 and CD206 in myocardial tissue.Western blotting was used to detect the protein levels of CD86 and CD206 in myocardial tissue.The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in serum were detected by ELISA kit.Results Compared with the sham operation group,the expression level of miR-126 mRNA in myocardial tissue of rats in the AMI group was significantly decreased on postoperative day 1(P<0.05),reached the lowest level on postoperative day 3.And then although it rose to a certain extent,it remained lower than that of the sham operation group on postoperative day 11(P<0.05),and postoperative day 3 was selected for further study.Compared with the sham operation group,the expression of miR-126 mRNA in myocardial tissue of the AMI group was decreased(P<0.05),and the myocardial fibrosis,infarct size and myocardial cross-sectional area were increased(P<0.05).The expression of CD86 protein in myocardial tissue was increased and the expression of CD206 protein was decreased(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were increased(P<0.05).Compared with the AMI group,the rats in the miR-126 overexpression group had a significant increase in the mRNA expression of miR-126 in myocardial tissue(P<0.05),a significant reduction in myocardial fibrosis,infarct size,and myocardial cross-sectional area(P<0.05),a significant reduction in the expression of CD86 protein in myocardial tissue,and a significant increase in the expression of CD206 protein(P<0.05).The serum levels of TNF-α,IL-6 and IL-1β were significantly decreased(P<0.05).Conclusion Over-expression of miR-126 can improve myocardial remodeling and promote M2 macrophage polarization in AMI rats.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.