Objective To compare and analyze the changes in the use of lung cancer therapeutic drugs before and after the national initiation of health insurance negotiations, and to study the impact of a series of policies on the use of lung cancer drugs. Methods Descriptive statistical methods were used analyze the basic situation of lung cancer patients and the changes of corresponding therapeutic drugs in Peking University People's Hospital from 2014 to 2020, as well as to the hospital procurement data of lung cancer therapeutic drugs in the database of the Chinese Medicine Economic Information. Results From 2014 to 2020, the total cost per capita of lung cancer patients showed a trend of first increasing and then decreasing, increasing before the national drug negotiation and gradually decreasing after the negotiation. After 2017, the use of small ATC categories such as VEGF/VEGFR inhibitors and EGFR tyrosine kinase inhibitors increased significantly, along with a rise in the number of monoclonal antibody varieties. The DDDs of osimertinib, anlotinib, alectinib, crizotinib and other drugs in the medical insurance list increased significantly, and the average daily cost decreased significantly. Conclusion The number of hospitalization days for lung cancer patients had continued to shorten in recent years, and the structure of drug use had changed significantly. The adjustment of the medical insurance catalog had led to more innovative lung cancer drugs showing the trend of volume up and price down.

OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective:To evaluate the effectiveness and safety of belumosudil for the treatment of chronic graft-versus-host disease (cGVHD) .Methods:We retrospectively collected data on patients with cGVHD who received belumosudil at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2023 to March 2024. The study endpoints were overall response rate (ORR), organ-specific response rates, time to response (TTR), changes in Lee Symptom Scale (LSS) scores, tapering or discontinuation of corticosteroid treatment, failure-free survival (FFS), and adverse events.Results:The study included 20 patients with cGVHD who received belumosudil, of whom 15 were men and 5 women. The median age was 34.5 (12-67) years, and three patients were under 18 years old. The median follow-up duration was 5.0 (1.4 - 9.8) months. All patients had severe cGVHD, and 18 (90.0%) showed involvement of at least four organs. The median number of prior treatment lines was 4, and 15 patients (75%) had previously received ruxolitinib. All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8%), and all responses were partial responses. The median TTR was 1.6 (0.9 - 8.4) months. The LSS scores improved in a clinically meaningful way in 80.0% (16/20) of the patients within 3 months. The corticosteroid dose was reduced in 42.6% (6/14) of the patients. The 3-month FFS was 79.6% (95% CI: 61.4%-100.0%). Most adverse events were grade 1 or grade 2, and two patients (10.0%) experienced grade 3 or higher-grade adverse events. Conclusions:In the real-world setting, belumosudil demonstrated good effectiveness and safety in patients with cGVHD with a history of severe disease and multiorgan involvement.

The cultivation of top innovative nursing talents with Chinese characteristics in the new era lends critical support to the accomplishment of the strategic goal of the Healthy China Initiative.Herein,we reviewed the historical development of nursing science in China,clarified the conceptual framework of nursing science with Chinese characteristics in the new era,and identified the essential qualities and competencies required for top innovative nursing talents.Furthermore,we analyzed the mission and challenges in cultivating these nursing talents,and put forward new approaches,including formulating new ethics and political education theories specific to nursing science with Chinese characteristics,establishing a cross-disciplinary educational model of Nursing+X,and creating a new nursing talent cultivation ecosystem adapted to the era of human-machine symbiosis.This study provides theoretical insights into the cultivation of top innovative nursing talents who align their development well with national strategic needs,embody patriotism,and possess a strong sense of contemporary responsibility.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.

Objective:To explore the differences in clinicopathological features and prognosis between conventional adrenocortical carcinoma（ACC）and oncocytic ACC.Methods:The clinical and pathological data of patients with conventional ACC and oncocytic ACC who were admitted to Peking Union Medical College Hospital from March 2012 to Fabruary 2025 were retrospectively analyzed. Differences in clinical and pathological characteristics between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method，and differences in survival rates were compared using the log-rank test.Results:The conventional ACC group comprised 137 cases，with a mean age of（47.5 ± 12.6）years and 37.2%（51/137）being male. The oncocytic ACC group included 22 cases，with a mean age of（49.1 ± 15.3）years and 59.1%（13/22）being male. No statistically significant differences were observed in age or gender distribution between the two groups（ P > 0.05）. The conventional ACC group exhibited a significantly higher prevalence of classic Cushing’s syndrome symptoms compared to the oncocytic ACC group［35.2%（45/128）vs. 5.3%（1/19）； χ2 = 6.876， P < 0.01］. Additionally，the proportion of hypertension was higher in the conventional ACC group［49.2%（65/132）vs. 22.2%（4/18）； χ2 = 5.319， P < 0.05］，whereas the prevalence of adrenal sex characteristics was lower［22.0%（28/127）vs. 63.2%（12/19）； χ2 = 14.043， P < 0.01］. The Ki-67 proliferation index was significantly higher in conventional ACC patients［20%（10%，40%）vs. 12%（9%，20%）； Z = -2.113， P < 0.05］. Furthermore，the conventional ACC group demonstrated a lower 5-year overall survival rate than the oncocytic ACC group（44.5% vs. 67.3%， P < 0.05）. Conclusions:Conventional ACC patients have a higher proportion of Cushing’s symptoms and hypertension，and oncocytic ACC patients have a higher proportion of adrenal sexual characteristics abnormalities. The prognosis of oncocytic ACC is better than that of conventional ACC.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

Objective:To evaluate the effectiveness and safety of belumosudil for the treatment of chronic graft-versus-host disease (cGVHD) .Methods:We retrospectively collected data on patients with cGVHD who received belumosudil at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from May 2023 to March 2024. The study endpoints were overall response rate (ORR), organ-specific response rates, time to response (TTR), changes in Lee Symptom Scale (LSS) scores, tapering or discontinuation of corticosteroid treatment, failure-free survival (FFS), and adverse events.Results:The study included 20 patients with cGVHD who received belumosudil, of whom 15 were men and 5 women. The median age was 34.5 (12-67) years, and three patients were under 18 years old. The median follow-up duration was 5.0 (1.4 - 9.8) months. All patients had severe cGVHD, and 18 (90.0%) showed involvement of at least four organs. The median number of prior treatment lines was 4, and 15 patients (75%) had previously received ruxolitinib. All patients received 200 mg of belumosudil once daily in combination with other cGVHD systemic therapies. The ORR was 90.0% (95% CI: 68.3%-98.8%), and all responses were partial responses. The median TTR was 1.6 (0.9 - 8.4) months. The LSS scores improved in a clinically meaningful way in 80.0% (16/20) of the patients within 3 months. The corticosteroid dose was reduced in 42.6% (6/14) of the patients. The 3-month FFS was 79.6% (95% CI: 61.4%-100.0%). Most adverse events were grade 1 or grade 2, and two patients (10.0%) experienced grade 3 or higher-grade adverse events. Conclusions:In the real-world setting, belumosudil demonstrated good effectiveness and safety in patients with cGVHD with a history of severe disease and multiorgan involvement.