ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

AIM To optimize the cellulase-assisted ultrasound extraction process for total flavonoids from Plumbago zeylanica L.,and to evaluate their anti-oxidant activity.METHODS With extraction time,liquid-solid ratio,cellulase addition amount,extraction temperature and ultrasonic power as influencing factors,extraction rate of total flavonoids as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.Subsequently,The scavenging rates of extract on DPPH,ABTS and OH free radicals were determined.RESULTS The optimal conditions were determined to be 34∶1 for liquid-solid ratio,3％for cellulase addition amount,51 ℃ for extraction temperature,38 min for extraction time,and 400 W for ultrasonic power,the extraction rate of total flavonoids was(33.411±0.97)％.The IC50 values of three free radicals were 0.13,0.042,3.29 mg/mL,respectively.CONCLUSION This reasonable and reliable method can be used for the cellulase-assisted ultrasound extraction of total flavonoids from P.zeylanica with strong anti-oxidant activity.

Objective:To observe the effect of applying intermittent theta burst stimulation (iTBS) in the rehabilitation of preschool children with autism spectrum disorder (ASD).Methods:Seventy preschool children with ASD were randomly divided into a control group and an experimental group, each of 35. Both groups were given routine rehabilitation training, while the experimental group was additionally provided with iTBS for 4 weeks. Before and after the treatment, the children′s language comprehension and expression ability were evaluated using the language retardation test and the Autism Treatment Assessment Scale (ATEC).Results:The language comprehension and expression of the children in both groups had improved after the treatment, but the children in the experimental group then had better language comprehension and expression abilities. And they scored better on average in the language, social interaction, cognition and behavior sub-sections of the ATEC. Their average total score was also lower.Conclusions:iTBS can safely and effectively improve the language comprehension ability and expression of preschool children with ASD.

Objective:To assess the disease burden of lung cancer associated with occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in China from 1990 to 2021 using the 2021 Global Burden of Disease (GBD) data.Methods:In July 2024, data on occupational PAHs exposure-associated lung cancer from 1990 to 2021 were extracted from the GBD database, including mortality rates, age-standardized mortality rates, number of deaths, disability-adjusted life years (DALYs) rates, age-standardized DALYs rates, and number of DALYs for different genders and ages. Descriptive statistics were used to analyze trends in lung cancer mortality rates, age-standardized mortality rates, DALYs rates, and age-standardized DALYs rates over different years, genders, and ages. Joinpoint regression models were used to calculate the annual percent change (APC) and average annual percent change (AAPC), and to identify change points and trends in different periods within the data.Results:From 1990 to 2021, the mortality rate of lung cancer associated with occupational PAHs exposure increased from 0.085 per 100000 to 0.259 per 100000, and the age-standardized mortality rate increased from 0.107 per 100000 to 0.162 per 100000. The DALYs rate increased from 2.746 per 100000 to 7.389 per 100000, and the age-standardized DALYs rate increased from 3.330 per 100000 to 4.679 per 100000. The number of lung cancer deaths and DALYs both peaked in the 65-69 age group. Joinpoint regression analysis showed significant upward trends in mortality, age-standardized mortality, DALYs rate, and age-standardized DALYs rate from 1990 to 2021, with AAPCs of 3.655%, 1.382%, 3.256%, and 1.108%, respectively (all P<0.001). From 2016 to 2021, both the mortality rate and age-standardized mortality rate increased, with APCs of 4.163% and 1.735%, respectively. From 2015 to 2021, the DALYs rate increased (APC: 3.137%), and from 2016 to 2021, the age-standardized DALYs rate also rose (APC: 1.578%). For females, both mortality and DALYs rates increased from 2015 to 2021 (APCs: 6.269% and 5.426%, respectively). Among males, the mortality rate increased from 2018 to 2021 (APC: 3.477%) . Conclusion:From 1990 to 2021, the disease burden of lung cancer related to occupational PAHs exposure in China has significantly increased, particularly among the elderly population. Public health policies should enhance screening and prevention efforts targeting the high-risk populations.

Objective:To develop a health management model tailored for the elderly population in rural areas and to evaluate its effectiveness.Methods:This before-and-after controlled intervention study was conducted from January 2024 to June 2024 in rural areas of Jiaocheng County, Shanxi Province. A multi-stage stratified random sampling method was used to include 5 000 permanent residents aged ≥65 years. A baseline health survey was first conducted to collect multidimensional data, including demographic characteristics, chronic disease information, cognitive and psychological scales, sleep quality, and health service utilization. Using the comprehensive health index as the outcome variable, seven machine learning models, including LightGBM, were constructed to identify key factors influencing health status and explore intervention pathways. Subsequently, under the framework of a "five-level linkage+shared database, " comprehensive interventions such as health communication, integrated medical and elderly care, and dynamic follow-ups were implemented. Differences in major health indicators were compared before and after the 6-month intervention.Results:At baseline, the prevalence rates of hypertension, diabetes, and coronary heart disease were 58.2%, 24.8%, and 16.1%, respectively. The rate of cognitive impairment was 36.9%, and the positive rates for depression and anxiety were 27.3% and 17.4%, respectively. Machine learning analysis showed that the Naive Bayes model had the best predictive performance (area under the curve=0.966), with key influencing factors including number of follow-ups, number of health lectures, and medical check-up frequency. After six months of intervention, systolic blood pressure decreased from (142.95±15.84) to (138.37±17.20) mmHg (1 mmHg=0.133 kPa), fasting glucose from (6.43±1.26) to (6.09±1.40) mmol/L, and MMSE scores increased from (25.04±3.28) to (25.71±3.29) points. The positive rates of anxiety and depression declined from 17.4% to 12.8% and 27.3% to 20.6%, respectively. Follow-up compliance improved from 76.5% to 80.5%, and health record completeness from 69.8% to 75.8% (all P<0.001). Conclusions:The integrated health management model based on the"five-level linkage+shared database,"incorporating health education and the integration of medical and elderly care, effectively improves chronic disease control and enhances cognitive and psychological health among older adults in rural areas of Shanxi Province. This model also strengthens service adherence and management efficiency.

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective To construct a prediction model for the progression of knee osteoarthritis(KOA)based on ultrasound score,magnetic resonance imaging(MRI)score,and serum levels of transforming growth factor-β1(TGF-β1)and cathepsin D(Cat D).Methods Clinical data from 270 patients with KOA in Hengshui People's hospital from December 2022 to June 2024 were retrospec-tively analyzed.The patients were randomly divided into a modeling set(n=189)and validation set(n=81)at a ratio of 7∶3.The patients in the modeling set were categorized into mild-to-moderate and severe groups based on the degree of disease progression.Mul-tivariate logistic regression analysis was used to identify factors influencing KOA progression,and a prediction model was constructed using R software.Results Multivariate logistic regression analysis showed that body mass index,knee injury history,ultrasound score,WORMS score,TGF-β1,and Cat D were significant predictors of KOA progression(P＜0.05).A nomogram-based prediction model was developed using these variables.The areas under the curve(AUC)of the nomograms for predicting disease progression in the modeling and validation sets were 0.889 and 0.860,respectively.The calibration curves showed that the predicted probability was in good agreement with the actual probability.Conclusion The prediction model developed in this study is effective in identifying patients at high-risk of KOA progression and may servce as a valuable tool for clinical assessment and decision making.

Objective:To assess the disease burden of lung cancer associated with occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in China from 1990 to 2021 using the 2021 Global Burden of Disease (GBD) data.Methods:In July 2024, data on occupational PAHs exposure-associated lung cancer from 1990 to 2021 were extracted from the GBD database, including mortality rates, age-standardized mortality rates, number of deaths, disability-adjusted life years (DALYs) rates, age-standardized DALYs rates, and number of DALYs for different genders and ages. Descriptive statistics were used to analyze trends in lung cancer mortality rates, age-standardized mortality rates, DALYs rates, and age-standardized DALYs rates over different years, genders, and ages. Joinpoint regression models were used to calculate the annual percent change (APC) and average annual percent change (AAPC), and to identify change points and trends in different periods within the data.Results:From 1990 to 2021, the mortality rate of lung cancer associated with occupational PAHs exposure increased from 0.085 per 100000 to 0.259 per 100000, and the age-standardized mortality rate increased from 0.107 per 100000 to 0.162 per 100000. The DALYs rate increased from 2.746 per 100000 to 7.389 per 100000, and the age-standardized DALYs rate increased from 3.330 per 100000 to 4.679 per 100000. The number of lung cancer deaths and DALYs both peaked in the 65-69 age group. Joinpoint regression analysis showed significant upward trends in mortality, age-standardized mortality, DALYs rate, and age-standardized DALYs rate from 1990 to 2021, with AAPCs of 3.655%, 1.382%, 3.256%, and 1.108%, respectively (all P<0.001). From 2016 to 2021, both the mortality rate and age-standardized mortality rate increased, with APCs of 4.163% and 1.735%, respectively. From 2015 to 2021, the DALYs rate increased (APC: 3.137%), and from 2016 to 2021, the age-standardized DALYs rate also rose (APC: 1.578%). For females, both mortality and DALYs rates increased from 2015 to 2021 (APCs: 6.269% and 5.426%, respectively). Among males, the mortality rate increased from 2018 to 2021 (APC: 3.477%) . Conclusion:From 1990 to 2021, the disease burden of lung cancer related to occupational PAHs exposure in China has significantly increased, particularly among the elderly population. Public health policies should enhance screening and prevention efforts targeting the high-risk populations.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.

[Purpose]To investigate the choice of medical institutions for the first-treatment of can-cer patients after diagnosis and the factors influencing it,so as to provide a reference basis for the rational allocation of health resources and the promotion of hierarchical diagnosis and treatment of cancer.[Methods]A total of 1 140 common cancer patients from 1 provincial,3 municipal and 6 county-level medical institutions in Shandong Province were included in the study,and a ques-tionnaire survey was conducted on their basic personal information and the selection of medical institutions.Chi-square test and Fisher exact test were used to compare different groups,and mul-ti-classification unordered Logistic regression were used to explore the factors influencing the se-lection of cancer patients.[Results]1 077 valid questionnaires were collected.The selection rates of first-treatment institutions for cancer patients were county hospitals(29.90％),city hospitals(35.28％),and provincial hospitals(34.82％),and the high level of medical care was the main reason for the selection of first-treatment institutions for cancer patients.The results of multi-clas-sification unordered Logistic regression showed that when choosing municipal and county medical institutions as the first treatment institution compared to choosing a county medical institution for the first treatment as a reference,compared to patients with stage Ⅰ tumors,patients with tumor stages at stage Ⅲ(OR=1.789,95％CI:1.014～3.158)and stage Ⅳ(OR=2.005,95％CI:1.179～3.409)were more likely to choose municipal medical institutions;and patients with annual house-hold income of 10 000～＜50 000 CNY(OR=0.625,95％CI:0.414～0.943)were less likely to choose mu-nicipal medical institutions compared to those with an annual household income of＜10 000 CNY.When choosing provincial and county medical institutions as the first treatment institution com-pared to patients in stage Ⅲ(OR=2.885,95％C1:1.549～5.372)and stage Ⅳ(OR=3.104,95％CI:1.724～5.586)compared to patients with stage Ⅰ tumors when choosing a county medical institu-tion for the first treatment was used as a reference;married(OR=2.248,95％CI:1.127～4.484)patients were more likely to choose provincial healthcare organizations than unmarried/divorced/widowed patients;patients with a family history of cancer compared to patients without a family history of cancer(OR=1.650,95％CI:1.115～2.441)were more inclined to choose provincial healthcare institutions;compared with patients＜45 years old,patients over 60 years old(OR=0.483,95％CI:0.242～0.962)were less inclined to choose provincial hospitals;and compared with patients who were not aware of knowledge related to cancer,those who were aware of knowledge related to cancer(OR=0.613,95％CI:0.441～0.852)patients were less inclined to choose provin-cial hospitals.[Conclusion]Vigorously carrying out publicity on cancer prevention and treatment knowledge,improving the cancer prevention and treatment literacy of cancer patients.strengthen-ing vertical cooperation among medical institutions at all levels,improving the provincial-munici-pal-county cancer prevention and treatment network,and promoting the sinking of high-quality medical resources are important ways to improve the cancer prevention and treatment capacity of counties and promote the work of hierarchical medical system.