Objective To analyze the trends in the disease burden of tracheal, bronchus, and lung cancer (TBL) in China and in low-, middle-, and high-socio-demographic index (SDI) countries and regions from 1990 to 2021, with the aim of providing evidence for the formulation of targeted prevention and control strategies. Methods Utilizing data from the Global Burden of Disease (GBD) Study 2021, we extracted TBL-related data from 1990 to 2021, stratified by sex, age group, and year. We assessed the disease burden and trends of TBL across different groups, conducted a decomposition analysis to identify the leading contributors to the change in disease burden, and examined the relationship between disability-adjusted life years (DALYs) and SDI. Results In 2021, the overall burden of TBL in China was substantially higher than that in other groups. The fold-increase in the number of prevalent cases, deaths, and DALYs was significantly greater in China. Moreover, the growth rates of the age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) in China were higher than the overall levels in other SDI countries. In all groups, the ASPR of TBL generally followed a pattern of increasing and then decreasing with age; however, for males in China and middle-SDI countries, the ASPR exhibited a decline in the 80-84 age group. Decomposition analysis revealed that the primary drivers of the increasing TBL burden varied among groups: the rise in DALYs in China and middle-SDI countries was mainly driven by population aging, in low-SDI countries by population growth, and in high-SDI countries by epidemiological transition. While global health inequality in TBL showed some improvement, low-SDI countries continued to bear a disproportionately heavy health burden. Conclusion The disease burden of TBL in China has progressively increased from 1990 to 2021, now ranking among the highest globally. Multiple factors, predominantly driven by population aging, are exacerbating this burden. The burden of TBL is influenced by advancing age, sex differences, and SDI levels. China, along with low- and middle-SDI countries, should implement targeted intervention strategies based on epidemiological findings, including expanding investment in public health services and strengthening healthcare systems, to mitigate the growing burden of TBL.

ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

AIM:To evaluate the accuracy of a portable non-contact tonometer(PNCT)compared with a traditional non-contact tonometer(NCT)in measuring intraocular pressure(IOP)at different levels.METHODS:Patients who presented to Ningbo Eye Hospital between January 2025 and January 2026 were retrospectively included. All patients underwent measurements using PNCT, NCT, and Goldmann applanation tonometry(GAT). Based on the GAT measurements, the patients were categorized into a low IOP group(IOP≤16 mmHg), a moderate IOP group(16 mmHg0.05). Spearman correlation analysis revealed that the IOP values measured by both PNCT and NCT were positively correlated with those measured by GAT(rs=0.86 and 0.84, respectively, P<0.05). Intraclass correlation coefficient(ICC)analysis demonstrated an ICC of 0.89 between PNCT and GAT(P<0.05), and 0.88 between NCT and GAT(P<0.05), with an overall ICC of 0.88 among the three instruments(P<0.05). Bland-Altman analysis indicated a mean bias of 0.1 mmHg [95% limits of agreement(LoA): -7.3 to 7.6 mmHg] between PNCT and GAT, and a mean bias of 0.1 mmHg(95%LoA: -8.4 to 8.6 mmHg)between NCT and GAT. Based on the GAT measurements, the eyes were categorized into a low IOP group(60 eyes, 32.6%, IOP≤16 mmHg), a moderate IOP group(63 eyes, 34.2%, 16 mmHg0.05), whereas the difference between NCT and GAT showed a positive correlation with CCT(rs=0.23, P<0.05).CONCLUSION:The IOP measurements obtained by PNCT, NCT, and GAT demonstrated strong correlation and good agreement, with PNCT being less influenced by CCT. However, as IOP levels increased, the measurement errors of both PNCT and NCT also increased. Therefore, PNCT and NCT readings should only serve as references and cannot replace GAT.

ObjectiveTo investigate the effects and mechanisms of pulchinenoside A （PSA） on tumor necrosis factor-α （TNF-α） -induced abnormal proliferation， migration， and invasion of synovial fibroblasts. MethodsA synovitis model was established by stimulating SW982 synovial cells with TNF-α. The low-density lipoprotein receptor-related protein 1 （LRP1） was knocked down using LRP1-specific siRNA or inhibited by the receptor-associated protein （RAP）. Cells were treated with various concentrations of PSA， and cell viability was assessed by CCK-8 assay. Protein levels of LRP1， matrix metalloproteinase-3 （MMP3）， and N-cadherin were measured by Western blotting. Proliferation was evaluated using an EdU incorporation assay. Migration and invasion capacities were examined by Transwell and wound-healing assays. mRNA expression of LRP1， MMP3， N-cadherin， IL-1β， IL-6， and TNF-α was detected by reverse transcription quantitative real-time PCR （RT-qPCR）. Immunofluorescence staining was used to visualize the expression of MMP3 and N-cadherin. The involvement of LRP1 was further verified with the inhibitor RAP. ResultsCompared with the TNF-α-treated model group， PSA treatment significantly reduced SW982 cell viability （P<0.05）， downregulated MMP3 and N-cadherin expression （both P<0.01）， and decreased the proportion of EdU-positive cells （P<0.05）. Moreover， TNF-α stimulation upregulated LRP1 expression compared with normal controls （P<0.01）， whereas PSA treatment reversed this increase （P<0.05）. LRP1 knockdown or inhibition markedly decreased MMP3 and N-cadherin levels compared with the model group （both P<0.01）. Similarly， the combination of PSA and RAP led to significant reductions in MMP3 and N-cadherin expression compared with the model group （both P<0.01）. ConclusionPSA inhibits TNF-α-induced abnormal proliferation， migration， and invasion of synovial， at least in part， by downregulating LRP1 expression.

Abstract The cooccurrence of multi disease among children and adolescents has become increasingly prominent, necessitating a shift from "single disease separate treatment" to "multi disease co prevention". Focusing on four common health problems in children and adolescents, namely, myopia, depression, overweight/obesity, and spinal abnormalities, the paper systematically reviews the association between four categories of factors, society, environment, family, and individual behavior, and the co occurrence of the aforementioned health problems. The findings indicate that particulate matter 2.5 exposure, light at night, physical inactivity, excessive screen time, and unhealthy diet constitute the primary cross dimensional risk network. Based on these findings, the paper proposes a collaborative action framework involving family, school, and society, emphasizing systematic strategies ranging from upstream environmental governance to downstream behavioral intervention, so as to provide evidence for the practice and policy making of multi disease co-prevention in children and adolescents.

Objective To explore the feasibility and clinical value of endoscopic resection of duodenal papilla tumors with a maximum diameter greater than 3 cm. Methods A retrospective analysis was conducted on the clinical data of all 12 patients who underwent endoscopic resection of duodenal papilla tumors at the Endoscopy Center of Zhongshan Hospital (Xuhui Hospital), Fudan University and Rongcheng Hospital of Traditional Chinese Medicine from September 2017 to May 2023. The size of the tumors all exceeded 3 cm. Results All 12 patients successfully completed the operation, with a complete resection rate of 91.7% (11/12) and an en-bloc resection rate of 91.7% (11/12). One patient experienced delayed bleeding due to unclosed wound during operation and received endoscopic hemostasis; 11 cases underwent partial wound closure operation with pancreatic and biliary stent placement, without perforation or postoperative stenosis. Among them, 2 cases (18.2%) experienced delayed bleeding and received endoscopic hemostasis treatment. After operation, 1 case (8.3%) experienced nausea, vomiting, upper abdominal discomfort, and elevated blood amylase levels, who was later treated conservatively. During the mean follow-up period of 30.5 (1.0-69.0) months, 1 patient experienced recurrence and underwent surgical resection. Conclusions Endoscopic resection of duodenal papilla tumors can treat large diameter duodenal papilla tumors exceeding 3 cm, but postoperative complications may occur and require special attention. Postoperative placement of pancreatic and biliary stents and wound closure may reduce the incidence of complications.

Objective To explore the clinical application of needle-embedding therapy for preventing and treating postoperative constipation in the patients with thoracolumbar vertebral fractures based on the theory of"preventing illness".Methods Eighty patients meeting the criteria for postoperative constipation af-ter thoracolumbar vertebral surgery in a tertiary hospital of Hangzhou City from January 2023 to February 2024 were selected as the study subjects.The patients were divided into the control group and experimental group by using the random number table method,40 cases in each group.The control group adopted the treat-ment of orally taking lactulose oral solution and the nursing such as routine postoperative food and drink and bed defecation training.The experimental group was given the needle-embedding therapy on the basis of rou-tine care.The gastrointestinal syndrome rating scale(GSRS)score,intra-abdominal pressure(IAP),abdomi-nal circumference,defecation and exhausting situation before and after intervention were performed the statis-tics and compared between the two groups.Results At 36,72 h after oeperation,the GSRS score,IAP and ab-dominal circumference in the both groups were significantly declined or decreased compared with those imme-diately after the operation,the above indicators in the experimental group were superior to those in the control group,and the differences were statistically significant(P＜0.01).The first exhausting and defecation time of the experimental group was earlier than that of the control group,and the difference was statistically signifi-cant(P＜0.01).Conclusion Under the basis of"preventing illness",the needing-embedding therapy has signif-icant therapeutic effects in preventing and treating postoperative constipation in thoracolumbar fractures,could effec-tively reduce IAP,alleviate the symptoms of constipation in the patients and improve their quality of life.

Objective To explore the effects of chronic stress and stress cessation on hypothalamic appetite regulators in mice,and to explore the stress-dependent mechanism of appetite change.Methods A total of 32 male C57BL/6 mice were randomly divided into control(Ctrl)group(n=16)and chronic unpredictable mild stress(CUMS)group(n=16).The mice in the CUMS group were given CUMS to establish the stress model,and those in the Ctrl group were fed normally.The food intake and weight of mice were recorded.The CUMS model was verified through tail suspension experiments and forced swimming experiments.Eight mice in the Ctrl group and 8 mice in the CUMS group were randomly sacrificed at the 12th week.The Ctrl group was re-grouped into the cessation-control(C-Ctrl)group(n=8),the CUMS group was re-grouped into the cessation-stress(C-CUMS)group(n=8),and the mice were sacrificed at the 15th week.The mRNA and protein levels of appetite-regulating factors,including orexin 1 receptor(OX1R),leptin receptor(LEPR)and agouti-related protein(AgRP)in the hypothalamus,were detected by quantitative polymerase chain reaction and immunochemistry.Results From week 2 to week 11 of stress,the food intake of the mice in the CUMS group was significantly higher than that in the Ctrl group(all P＜0.05),while there was no significant difference in body weight between the 2 groups within 11 weeks(all P＞0.05).Compared with the Ctrl group,the immobility durations of forced swimming and tail suspension of the CUMS group were markedly longer after 11 weeks(both P＜0.01),indicating successful modeling.AgRP and OX1R mRNA expression in the hypothalamus of the CUMS group was significantly increased(both P＜0.01),while LEPR mRNA expression was significantly decreased(P＜0.01);AgRP protein in the hypothalamic arcuate nucleus of the CUMS group was significantly higher than that of the Ctrl group(P＜0.05),and LEPR protein was markedly lower than that of the Ctrl group(P＜0.01).However,after 3 weeks of stress cessation,the C-CUMS group had less food intake and lower body weight than the C-Ctrl group(both P＜0.05).The LEPR mRNA of the C-CUMS group was significantly increased(P＜0.01),while AgRP and OX1R mRNA were not significantly different(both P＞0.05).There was no significant difference in AgRP protein levels between the C-CUMS group and the C-Ctrl group(P＞0.05),while LEPR protein level of the C-CUMS group was significantly higher than that of the C-Ctrl group(P＜0.01).Conclusion CUMS can lead to increased appetite in mice,which may involve the functional regulation of LEPR and AgRP.After the stress cessation,the appetite decreases,which may involve the functional regulation of LEPR.

Infant acute myeloid leukemia（IAML）is a clinically rare hematological malignancy.Compared to older children，IAML patients usually have significantly higher-risk biological characteristics，namely a low induction remission rate and a high recurrence risk.Although continuous research has been conducted on its molecular mechanisms and treatment methods，the 5-year survival rate by traditional treatment regimens is only 50%~60%.Therefore，targeted therapies，such as CD33 monoclonal antibodies，and cellular immunotherapy，have become key strategies to overcome treatment barriers.This article reviews the progress on the molecular characteristics of IAML，the efficacy and challenges of traditional chemotherapy optimization schemes and targeted therapy，as well as CAR-T cell immunotherapy.

Objective:To evaluate the relationship between the mechanism of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) in preventing brain neurotoxicity caused by multiple sevoflurane anesthesia and peroxisome proliferator-activated receptor gamma (PPARγ)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) signaling pathway in neonatal mice.Methods:This study was performed in 2 parts. Part Ⅰ Using a random number table method, 6 C57BL/6 pregnant mice were assigned to receive a standard diet, 3 pregnant mice were assigned to receive a diet supplemented with fish oil from day 2 of gestation to day 14 after parturition (ω-3 PUFAs 300 mg were added to every 20 g of conventional diet). Healthy C57BL/6 mice of both sexes, aged 6 days, weighing 3-5 g, were selected after parturition. Seventeen neonatal pups from 3 pregnant mice that were fed a conventional diet were assigned to control group (C group), 17 neonatal pups from 3 pregnant mice that were fed a conventional diet were assigned to sevoflurane group (S group), and 17 neonatal pups from pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS1 group) using the random number table method. Part Ⅱ Four C57BL/6 pregnant mice were assigned to receive a diet supplemented with fish oil from day 2 of gestation to day 14 after parturition. After parturition, 12 neonatal pups from 2 pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus sevoflurane group (PS2 group), and 12 neonatal pups from 2 pregnant mice that were fed a diet supplemented with fish oil were assigned to ω-3 PUFAs plus PPARγ inhibitor GW9662 plus sevoflurane group (PGS group) using a random number table method. GW9662 (2 mg/kg) was intraperitoneally injected at 30 min before exposure to sevoflurane in PGS group. All offspring mice were breastfed until 21 days of age, after which they were housed separately from the mother and allowed ad libitum access to a conventional diet. S, PS1, PS2 and PGS groups inhaled 3% sevoflurane in 40% oxygen for 2 h daily on postnatal days 6, 7 and 8. C group inhaled only 40% oxygen instead. Y maze test was performed on days 33 after birth. The rotarod test was performed on day 35 after birth. After the behavioral testing, the expression of PPARγ, PGC1α, mitofusin-1 (MFN1), MFN2, dynamin-related protein 1 (DRP1), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), and tumor necrosis factor-α (TNF-α) was detected by Western blot, the ultrastructure of mitochondria in hippocampal neurons was observed with a transmission electron microscope, and the mitochondrial membrane potential (MMP), level of reactive oxygen species (ROS) and content of ATP were determined.Results:Part Ⅰ Compared with C group, the time of stay at the new-arm and time spent on the rotarod were significantly shortened, the percentage of movement distance in the new-arm was decreased, the expression of PPARγ, PGC1α, MFN1 and MFN2 in the hippocampus was down-regulated, the expression of DRP1, IL-6, IL-1β and TNF-α in the hippocampus was up-regulated, the MMP and content of ATP were decreased, and the level of ROS was increased in S group ( P<0.05). Compared with S group, the time of stay at the new-arm and time spent on the rotarod were significantly prolonged, the percentage of movement distance in the new-arm was increased, the expression of PPARγ, PGC1α, MFN1 and MFN2 in the hippocampus was up-regulated, the expression of DRP1, IL-6, IL-1β and TNF-α in the hippocampus was down-regulated, the MMP and content of ATP were increased, and the level of ROS was decreased in PS1 group ( P<0.05). Part Ⅱ Compared with PS2 group, the time of stay at the new-arm and time spent on the rotarod were significantly shortened, the percentage of movement distance in the new-arm was decreased, the MMP and content of ATP were decreased, the level of ROS was increased, and the expression of IL-6, IL-1β and TNF-α was up-regulated ( P<0.05). Conclusions:The mechanism by which ω-3 PUFAs prevent brain neurotoxicity caused by multiple sevoflurane anesthesia is related to the activation of the PPARγ/PGC1α signaling pathway and alleviation of mitochondrial dysfunction and neuroinflammation in neonatal mice.