OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

Objective: To investigate the prevalence and associated factors of depressive symptoms among junior and senior high school students in Beijing from 2019 to 2023, in order to provide a scientific basis for interventions targeting high risk groups. Methods: From 2019 to 2023, a stratified cluster random sampling method was used to select 88 927 junior and senior high school students from 16 districts in Beijing. The Center for Epidemiologic Studies Depression Scale(CES-D) was conducted to assess depressive symptoms. The Chi square test was used to compare the detection rates of depressive symptoms among different student groups, and the trend Chi square test was employed for trend analysis of detection rates across the years. Multivariate Logistic regression analysis was applied to examine the association between the detection of depressive symptoms and related factors among junior and senior high school students. Results: From 2019 to 2023, the prevalence rates of depressive symptoms among junior and senior high school students in Beijing were 20.45%, 18.19%, 16.64%, 17.89% and 18.17%, respectively, with an overall downward trend ( χ 2 trend =27.51, P <0.01). Multivariate Logistic regression analysis revealed that after adjusting for gender, monitoring year, educational stage,family structure,boarding status and has taken a medical leave of absence in the past year unhealthy dietary behaviors ( OR=1.80, 95%CI =1.73-1.87), physical inactivity ( OR=1.24, 95%CI =1.19-1.29), try smoking ( OR=1.46, 95%CI =1.35-1.58), try alcohol( OR=1.96, 95%CI =1.88-2.05), Internet addiction ( OR=3.88, 95%CI =3.57-4.22), and adverse ear related behavior ( OR=1.82, 95%CI =1.71-1.93) were all associated with an increased risk of depressive symptoms among junior and senior high school students (all P <0.05). Conclusions The prevalence depression symptoms among middle school students in Beijing showed a fluctuating downward trend from 2019 to 2023. Targeted interventions should be adopted to reduce the occurrence of depression symptoms among junior and senior high school students.

Objective: To understand the trends of classroom lighting and illumination of primary and secondary schools in Beijing from 2016 to 2023, so as to provide a scientific basis for targeted improvement measures. Methods: A sampling survey was conducted on the lighting and illumination indicators of 8 390 classrooms in primary and secondary schools in Beijing from 2016 to 2023. The survey included classroom daylight factor, window to floor area ratio, average illuminance and illuminance uniformity on the desks, average illuminance and illuminance uniformity on blackboards, as well as classroom lighting and blackboard illumination sources. Intergroup comparisons were performed using the Kruskal-Wallis H test and the Chi square test, and Spearman correlation analysis was used to examine the trend of classroom lighting and illumination changes. Results: Except the window to floor area ratio, the measured values and compliance rates of all lighting and illumination indicators showed an overall upward trend from 2016 to 2023 (daylight factor r = 0.27, χ 2 trend =206.80, average illuminance on the desk surface r =0.30, χ 2 trend =87.97, illuminance uniformity on the desk surface r =0.14, χ 2 trend =73.59, average illuminance on the blackboard r =0.33, χ 2 trend =477.43, illuminance uniformity on the blackboard r = 0.09, χ 2 trend =50.76) (all P ＜0.01). The lighting and illumination indicators of classrooms (included classroom daylight factor, average illuminance and illuminance uniformity on the desks, average illuminance and illuminance uniformity on blackboards) in urban schools, primary schools, and secondary schools from 2016 to 2023 showed an upward trend (urban r =0.23-0.40, χ 2 trend =88.66-392.18; primary school r =0.12-0.36, χ 2 trend =39.50-281.44; secondary schools r =0.06-0.31, χ 2 trend =11.79-213.73) (all P ＜ 0.01 ). The illuminance uniformity on the blackboard in suburban schools showed a downward trend ( r = -0.09, χ 2 trend =31.53, both P ＜0.01). The illuminance uniformity on the desk surface in suburban schools showed no significant change ( r =0.03, χ 2 trend =1.23, both P ＞0.05). The other indicators showed an upward trend (daylight factor r =0.28, χ 2 trend =40.69, average illuminance on the desk surface r =0.24, χ 2 trend =16.35, average illuminance on the blackboard r =0.25, χ 2 trend =118.05, all P ＜0.01). The trends of classroom and blackboard illumination sources were that fluorescent lamps decreased year by year and LED lamps increased by year (classroom illumination sources χ 2 trend =1 059.82, blackboard illumination sources χ 2 trend =1 070.25, both P ＜0.01). Conclusions The classroom lighting and illumination in primary and secondary schools in Beijing has shown an overall improving trend from 2016 to 2023. However, problems remain, such as limited improvement of illuminance uniformity indicators, late start and poor effect of reconstruction in suburban schools. Further improvements are still needed.

ObjectiveTo assess the predictive value of the bladder deformation index (BDI) in determining upper urinary tract (UUT) damage among patients with neurogenic bladder (NB). MethodsClinical data of 132 NB patients admitted to Beijing Bo'ai Hospital from January, 2015 to December, 2018 were retrospectively analyzed. Patients were divided into UUT damage group and normal UUT group according to the presence or absence of hydronephrosis. The demographics, biochemical parameters and video-urodynamics (VUDS) findings were collected, and BDI was calculated. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive capability. ResultsThere were 54 patients in UUT damage group and 33 in normal UUT group. The course of disease, creatinine level and BDI were siginificantly different between two groups (P < 0.05), while the area under the curve were 0.686, 0.836 and 0.928, respectively. ConclusionCourse of disease, creatinine level and BDI are associated with UUT damage in NB patients, and BDI demonstrates the highest sensitivity and specificity, which may play a role in diagnosis of UUT damage.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

OBJECTIVE: To investigate the clinical effect of minimally invasive technique in the treatment of moderate and severe gluteal muscle contracture. METHODS: A retrospective study was conducted on 85 patients (170 sides) with bilateral gluteal muscle contracture admitted from January 2016 to December 2019. All patients were treated with minimally invasive release of tendon knife. There were 32 males and 53 females, ranging in age from 15 to 37 years old, with an average age of (22.3±6.3) years old. Operation time, intraoperative blood loss, incision length, first postoperative ambulation time, complication rate, recurrence rate, and Harris hip score (HHS) were analyzed and evaluated. RESULTS: The average follow-up time was (16.2±4.6) months, ranging from 12 to 30 months. The operation time ranged from 7 to 15 min, with an average of (10.2±3.1) min. Intraoperative blood loss ranged from 2 to 20 ml, with an average of (8.4±2.2) ml. The incision length ranged from 0.6 to 2.0 cm, with an average of (0.8±0.3) cm. The time to postoperative ambulation ranged from 12 to 28 h, with an average of (20.0±3.2) h. All patients achieved primary wound healing without sciatic nerve injury or recurrence. HHS hip function scores ranged from 90 to 98, with an average score of (96.2±1.4). Complications included intraoperative tendon blade tip fracture in two cases (removed under fluoroscopic guidance) and subcutaneous hematoma in three cases-two resolved with compression and one with open evacuation.. Twenty-nine patients exhibited transient swaying gait postoperatively, of which 24 patients returned to normal after 4 weeks and 5 patients returned to normal after 6 weeks. CONCLUSION Minimally invasive tendon blade release is a safe and effective technique for treating gluteal muscle contracture, offering minimal trauma, rapid recovery, and excellent cosmetic and functional outcomes. However, it exhibits a low risk of blade tip fracture and sciatic nerve injury, warranting experienced surgical handling.
Humans ; Male ; Female ; Adult ; Minimally Invasive Surgical Procedures/methods* ; Adolescent ; Retrospective Studies ; Buttocks/surgery* ; Young Adult ; Contracture/surgery* ; Tendons/surgery* ; Muscle, Skeletal/surgery*

Objective:To investigate the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues and analyze their expression levels in relation to clinical features and prognosis. Methods:From January 1, 2019, to December 31, 2019, 69 cases of nasopharyngeal carcinoma tissues and adjacent non-cancerous tissues were collected from patients treated at Yunnan Cancer Hospital. Immunohistochemistry was employed to detect the expression of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues. The Kaplan-Meier method was used to predict survival time, and the clinicopathological features were evaluated using the log-Rank test. Results:The positive expression rates of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were 87.0% and 84.5%, respectively. Compared to adjacent normal tissues, the expression levels of NFAT5 and IGF1R in nasopharyngeal carcinoma tissues were significantly increased （P<0.05）. Furthermore, the expression of NFAT5 and IGF1R was positively correlated with T stage, N stage, skull base invasion, and cranial nerve palsy （P<0.05）. The overexpression of NFAT5 and IGF1R significantly affected the survival rate of patients with nasopharyngeal carcinoma and was negatively correlated with prognosis （P<0.05）. Conclusion:In nasopharyngeal carcinoma tissues, overexpression of NFAT5 and IGF1R is observed, which is closely linked to clinical features and patient outcomes. These markers may serve as valuable indicators for predicting the prognosis of nasopharyngeal carcinoma.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Nasopharyngeal Neoplasms/metabolism* ; Prognosis ; Female ; Receptor, IGF Type 1/metabolism* ; Male ; Transcription Factors/metabolism* ; Middle Aged ; Survival Rate ; Adult ; Neoplasm Staging

Objective:Retrospective analysis of the correlation between clinicopathologic features and related indexes and prognosis in patients with recurrent nasopharyngeal carcinoma. Methods:One hundred and eight nasopharyngeal cancer（NPC） patients with post-treatment recurrence in Yunnan Cancer Hospital from January 2013 to January 2018 were collected, and the survival time was estimated by Kaplan-Meier method, and clinicopathological characteristics were analyzed by log-rank test; risk factors and prognosis were analyzed by Cox proportional risk model for single-factor and multifactorial analysis. A P-value <0.05 was considered statistically significant. Results:The median survival of all patients was 54 months, with a 3-year survival rate of 80.2% and a 5-year survival rate of 39.8%. The 5-year overall survival rate was 50.2% for patients >46 years old and 27.9% for patients ≤46 years old（P<0.05）, a statistically significant difference. Univariate analysis showed that overall survival was associated with age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, γ-interferon, α-tumor necrosis factor, IL-10, and IL-4（P<0.05）. Multifactorial analysis revealed that age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, and interleukin 10 were independent influences on the prognosis of recurrent nasopharyngeal carcinoma（P<0.05）. Conclusion:Differences in chemotherapy regimens affect the prognosis of recurrent nasopharyngeal carcinoma. Elevated plasma D-dimer, glycan antigen 125, and interleukin 10 levels affect the overall survival of recurrent nasopharyngeal carcinoma, which may be a valid independent prognostic factor, and are expected to provide new biomarkers for nasopharyngeal carcinoma in the clinic.
Humans ; Prognosis ; Nasopharyngeal Neoplasms/mortality* ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Neoplasm Recurrence, Local ; Male ; Middle Aged ; Female ; Survival Rate ; Adult ; Risk Factors ; Interleukin-10/blood* ; Aged ; Proportional Hazards Models

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.