[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 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.

Objective:To assess the association between possible sarcopenia and the risk for frailty in middle-aged and elderly adults in China.Methods:A prospective cohort study design was used in this study. Data were from the China Health and Retirement Longitudinal Study during 2011-2018 and the baseline data in 2011, the follow up was conducted in 2013, 2015 and 2018, respectively. Frailty index was used to evaluate frailty status, and grip strength and repetitive sitting-up time were measured to detect possible sarcopenia. Cox proportional hazards regression model was used to estimate the association between possible sarcopenia and the risk for frailty in middle-aged and older adults.Results:In a 44 884 person-years follow-up, a total of 586 cases with frailty were recorded, and the incidence density of frailty was 13.06 per 1 000 person-year. The risk for frailty was also higher in those who were aged 60 years and above ( HR=2.05, 95% CI: 1.71-2.45), had a primary school education level or below ( HR=1.55, 95% CI: 1.29-1.85), had waist-to-height ratio ≥0.5 ( HR=1.39, 95% CI: 1.11-1.75) and had depression ( HR=1.52, 95% CI: 1.28-1.81). Drinking was associated with reduced risk for frailty ( HR=0.76, 95% CI: 0.62-0.94). The risk for frailty increased ( HR=1.73, 95% CI: 1.47-2.05) in those who might has possible sarcopenia. Conclusions:In middle-aged and elderly adults, those with possible sarcopenia, lower education level, central obesity and depression might be at high risk for frailty, and early interventions for high-risk population can be taken to slow the progression of frailty.

Objective:To explore the association of central obesity, pain, their joint effect, and interaction with frailty in middle-aged and old people in China.Methods:A total of 14 359 participants aged ≥45 years in 2011, 2013 and 2015 were selected from the China Health and Retirement Longitudinal Study to construct a cohort database. Cox proportional hazards regression models were used to estimate the association of waist-to-height ratio (WHtR) and pain with the risk for frailty. Joint effect and interaction analyses were performed.Results:In the follow-up of 77 783 person-years, frailty developed in 3 198 participants, with an incidence density of 41.11 per 1 000 person-years. Compared with the Q1 level of WHtR, its Q2, Q3 and Q4 level increased risk for frailty by 17% ( HR=1.17, 95% CI: 1.05-1.31), 24% ( HR=1.24, 95% CI: 1.11-1.40), and 43% ( HR=1.43, 95% CI: 1.25-1.63), respectively. Compared with painlessness, suffering from pain increased the risk for frailty by 97% ( HR=1.97, 95% CI: 1.83-2.11), and having 1, 2, and ≥3 pain sites increased the risk by 42% ( HR=1.42, 95% CI: 1.25-1.61), 86% ( HR=1.86, 95% CI: 1.64-2.11), and 138% ( HR=2.38, 95% CI: 2.18-2.60), respectively. The results of restricted cubic spline showed that WHtR level was associated with the risk for frailty in a J-type dose-response relationship (total P<0.001, nonlinear P<0.001), and pain quantity was positively associated with the risk in a nonlinear dose-response relationship (total P<0.001, nonlinear P<0.001). Threshold effect analysis revealed that the inflection points of WHtR and pain site number were 0.46 and 2.00, respectively ( P<0.001). Joint effect analysis showed that the Q2, Q3 and Q4 levels of WHtR combined with pain increased the risk for frailty by 146% ( HR=2.46, 95% CI: 2.11-2.87), 169% ( HR=2.69, 95% CI: 2.30-3.16), and 157% ( HR=2.57, 95% CI: 2.18-3.03). Conclusions:The risk for frailty increased with the level of WHtR and the number of pain sites in middle-aged and old people, and there was joint effect between WHtR and pain. Comprehensive management and intervention of obesity and pain are significant for the early prevention of frailty.

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.

Objective:To explore the relationship and underlying mechanisms between servant leadership and satisfaction of medical staff in tertiary hospitals, and to provide references for improving satisfaction of medical personnel.Methods:From January to June 2023, a questionnaire survey was conducted among on-duty medical staff at a tertiary hospital in Guangzhou using a simple random sampling method. Data corresponding to four key variables: servant leadership, hospital management level, affective commitment, and satisfaction of medical staff were collected. SPSS 25.0 software was used to perform independent samples t-tests and one-way analysis of variance (ANOVA) to examine group differences, and Pearson correlation analysis was conducted to explore the relationships among multiple variables. Amos 24.0 software was employed to construct a structural equation model to conduct confirmatory factor analysis of the four key variables, analyze potential mediating effects, and use multi-group analysis to examine differences in path parameters and structure among groups. Results:A total of 632 valid questionnaires were obtained. The satisfaction score of medical staff was (4.50±0.66)(maximum score was 5 points). Age, years of work experience, and job category had statistically significant effects on satisfaction of medical staff ( F = 5.799, 6.483, 7.671; P = 0.001). All four key variables were significantly positively correlated ( P<0.001). Servant leadership, hospital management level, and affective commitment all had direct positive effects on satisfaction of medical staff, with path coefficients of 0.207, 0.386, and 0.345, respectively ( P <0.05, critical ratio>1.96). Hospital management level and affective commitment each had independent partial mediating effects between servant leadership and satisfaction of medical staff (path coefficients of 0.353 and 0.067, respectively; P = 0.007, 0.018). They also jointly exerted a chain mediating effect (path coefficient of 0.243, P = 0.013). Differences in path effects among different job categories (clinical doctors, nurses, and administrative support staff) were statistically significant ( χ2 = 43.344, df = 24, P = 0.009). Conclusions:The servant leadership in tertiary hospitals can directly influence the satisfaction of medical staff, as well as indirectly influence it through emotional commitment and hospital management level. Moreover, the mechanisms of influence vary among medical staff of different professional categories. Tertiary hospitals should introduce and promote servant leadership styles, enhance the servant leadership behaviors of management personnel, and strengthen the synergistic effects of servant leadership, hospital management level, and affective commitment. Differential adjustment mechanisms should be implemented for different job categories.

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 assess the association between possible sarcopenia and the risk for frailty in middle-aged and elderly adults in China.Methods:A prospective cohort study design was used in this study. Data were from the China Health and Retirement Longitudinal Study during 2011-2018 and the baseline data in 2011, the follow up was conducted in 2013, 2015 and 2018, respectively. Frailty index was used to evaluate frailty status, and grip strength and repetitive sitting-up time were measured to detect possible sarcopenia. Cox proportional hazards regression model was used to estimate the association between possible sarcopenia and the risk for frailty in middle-aged and older adults.Results:In a 44 884 person-years follow-up, a total of 586 cases with frailty were recorded, and the incidence density of frailty was 13.06 per 1 000 person-year. The risk for frailty was also higher in those who were aged 60 years and above ( HR=2.05, 95% CI: 1.71-2.45), had a primary school education level or below ( HR=1.55, 95% CI: 1.29-1.85), had waist-to-height ratio ≥0.5 ( HR=1.39, 95% CI: 1.11-1.75) and had depression ( HR=1.52, 95% CI: 1.28-1.81). Drinking was associated with reduced risk for frailty ( HR=0.76, 95% CI: 0.62-0.94). The risk for frailty increased ( HR=1.73, 95% CI: 1.47-2.05) in those who might has possible sarcopenia. Conclusions:In middle-aged and elderly adults, those with possible sarcopenia, lower education level, central obesity and depression might be at high risk for frailty, and early interventions for high-risk population can be taken to slow the progression of frailty.

Objective:To explore the association of central obesity, pain, their joint effect, and interaction with frailty in middle-aged and old people in China.Methods:A total of 14 359 participants aged ≥45 years in 2011, 2013 and 2015 were selected from the China Health and Retirement Longitudinal Study to construct a cohort database. Cox proportional hazards regression models were used to estimate the association of waist-to-height ratio (WHtR) and pain with the risk for frailty. Joint effect and interaction analyses were performed.Results:In the follow-up of 77 783 person-years, frailty developed in 3 198 participants, with an incidence density of 41.11 per 1 000 person-years. Compared with the Q1 level of WHtR, its Q2, Q3 and Q4 level increased risk for frailty by 17% ( HR=1.17, 95% CI: 1.05-1.31), 24% ( HR=1.24, 95% CI: 1.11-1.40), and 43% ( HR=1.43, 95% CI: 1.25-1.63), respectively. Compared with painlessness, suffering from pain increased the risk for frailty by 97% ( HR=1.97, 95% CI: 1.83-2.11), and having 1, 2, and ≥3 pain sites increased the risk by 42% ( HR=1.42, 95% CI: 1.25-1.61), 86% ( HR=1.86, 95% CI: 1.64-2.11), and 138% ( HR=2.38, 95% CI: 2.18-2.60), respectively. The results of restricted cubic spline showed that WHtR level was associated with the risk for frailty in a J-type dose-response relationship (total P<0.001, nonlinear P<0.001), and pain quantity was positively associated with the risk in a nonlinear dose-response relationship (total P<0.001, nonlinear P<0.001). Threshold effect analysis revealed that the inflection points of WHtR and pain site number were 0.46 and 2.00, respectively ( P<0.001). Joint effect analysis showed that the Q2, Q3 and Q4 levels of WHtR combined with pain increased the risk for frailty by 146% ( HR=2.46, 95% CI: 2.11-2.87), 169% ( HR=2.69, 95% CI: 2.30-3.16), and 157% ( HR=2.57, 95% CI: 2.18-3.03). Conclusions:The risk for frailty increased with the level of WHtR and the number of pain sites in middle-aged and old people, and there was joint effect between WHtR and pain. Comprehensive management and intervention of obesity and pain are significant for the early prevention of frailty.

Objective:To explore the relationship and underlying mechanisms between servant leadership and satisfaction of medical staff in tertiary hospitals, and to provide references for improving satisfaction of medical personnel.Methods:From January to June 2023, a questionnaire survey was conducted among on-duty medical staff at a tertiary hospital in Guangzhou using a simple random sampling method. Data corresponding to four key variables: servant leadership, hospital management level, affective commitment, and satisfaction of medical staff were collected. SPSS 25.0 software was used to perform independent samples t-tests and one-way analysis of variance (ANOVA) to examine group differences, and Pearson correlation analysis was conducted to explore the relationships among multiple variables. Amos 24.0 software was employed to construct a structural equation model to conduct confirmatory factor analysis of the four key variables, analyze potential mediating effects, and use multi-group analysis to examine differences in path parameters and structure among groups. Results:A total of 632 valid questionnaires were obtained. The satisfaction score of medical staff was (4.50±0.66)(maximum score was 5 points). Age, years of work experience, and job category had statistically significant effects on satisfaction of medical staff ( F = 5.799, 6.483, 7.671; P = 0.001). All four key variables were significantly positively correlated ( P<0.001). Servant leadership, hospital management level, and affective commitment all had direct positive effects on satisfaction of medical staff, with path coefficients of 0.207, 0.386, and 0.345, respectively ( P <0.05, critical ratio>1.96). Hospital management level and affective commitment each had independent partial mediating effects between servant leadership and satisfaction of medical staff (path coefficients of 0.353 and 0.067, respectively; P = 0.007, 0.018). They also jointly exerted a chain mediating effect (path coefficient of 0.243, P = 0.013). Differences in path effects among different job categories (clinical doctors, nurses, and administrative support staff) were statistically significant ( χ2 = 43.344, df = 24, P = 0.009). Conclusions:The servant leadership in tertiary hospitals can directly influence the satisfaction of medical staff, as well as indirectly influence it through emotional commitment and hospital management level. Moreover, the mechanisms of influence vary among medical staff of different professional categories. Tertiary hospitals should introduce and promote servant leadership styles, enhance the servant leadership behaviors of management personnel, and strengthen the synergistic effects of servant leadership, hospital management level, and affective commitment. Differential adjustment mechanisms should be implemented for different job categories.