Objective To investigate the impact of kinesin family member 2A(KIF2A)on the resistance of hepatocellular carcinoma cells to 5-FU and its underlying mechanism.Methods The drug resistance of hepatocellular carcinoma cell line BEL7402 to 5-FU was induced through an increasing concentration gradient combined with high-dose intermittent shock to construct a drug-resistant strain,BEL7402/5-FU.KIF2A-silenced BEL7402/5-FU cells were then built using the lentivirus technique.Valproic acid(VPA),an agonist of the Notch1/Hes1signaling pathway,was employed to treat the KIF2A-silenced BEL7402/5-FU cells.The cell viability,apoptosis rate,and protein expressions of KIF2A,cleaved-caspase-3,Notch1,and Hes1 were detected by CCK-8 assay,western blot,immunofluorescence,and flow cytometry,respectively.Results The BEL7402/5-FU cells exhibited strong resistance to 5-FU,with an IC50 value of 344.2μmol/L,which was 92 times that of the BEL7402 cells(IC50=3.730μmol/L).Compared to the BEL7402 cells,the expression of the KIF2A protein in the BEL7402/5-FU cells was significantly increased(P＜0.001).Compared with the si-NC group,the viability of the BEL7402/5-FU cells in the si-KIF2A group was significantly decreased(P＜0.001).At the same time,the apoptosis rate and the expression of the cleaved-caspase-3 protein were significantly increased(P＜0.001),and the expressions of Notch1 and Hes1 protein were significantly decreased(P＜0.001).Compared with the si-NC+5-FU group,the activity of BEL7402/5-FU cells in the si-KIF2A+5-FU group was significantly decreased(P＜0.001)and the apoptosis rate was significantly increased(P＜0.001).Compared with the si-KIF2A+5-FU group,the activity of BEL7402/5-FU cells in the si-KIF2A+5-FU+VPA group was significantly increased(P＜0.001),the apoptosis rate was significantly decreased(P＜0.001),and the expressions of Notch1 and Hes1 proteins were significantly increased(P＜0.001).Conclusion Silencing KIF2A reduces the drug resistance of BEL7402/5-FU cells to 5-FU by inhibiting the activity of the Notch1/Hes1signaling pathway.

Objective:To compare the efficacy of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunnotherapy and transarterial chemoembolization (TACE) combined with targeted therapy and immunnotherapy in the treatment of unresectable hepatocellular carcinoma HCC.Methods:We retrospectively analyzed the clinical data of 40 patients with unresectable HCC treated with HAIC combined with targeted therapy and immunnotherapy and TACE combined with targeted therapy and immunnotherapy in Tongde Hospital of Zhejiang Province and Zhejiang Provincial People's Hospital.The patients were divided into HAIC group ( n=14) and TACE group ( n=26) according to the different treatment methods. Baseline data, surgical conversion and intraoperative situation, tumor response, portal vein cancer thrombus control rate, leukocyte reduction rate, platelet reduction rate, incidence of liver function abnormalities, objective remission rate, and disease control rate were compared between the two groups. Results:The HAIC group had a later baseline tumor staging than the TACE group (higher percentage of portal vein cancer thrombus, CNLC stage Ⅲa).The surgical conversion rate of the HAIC and TACE groups were 28.6%(4/14) and 26.9%(7/26), respectively, with the difference of no statistical significance ( P>0.05);The operation time and intraoperative bleeding were (329.5±19.9) min vs.(413.4±26.4) min, (272.2±49.9) ml vs.(536.0±123.6) ml, and the differences were statistically significant ( P<0. 05); The maximum tumor diameter reduction rate [(30.7%±15.1%) vs.(7.2%±12.6%)] and portal vein cancer thrombus control rate [100% (12/12) vs. 64.3% (9/14)], the differences were statistically significant ( P<0.05);The incidences of leukocyte and platelet decrease in the two groups during the course of treatment were 71.4%(10/14) vs. 34.6%(9/26)、78.5%(11/14) vs. 38.5%(10/26), and the incidences of liver function abnormalities were 35.7%(5/14) vs. 69.2%(18/26), the differences were statistically significant ( P<0.05);The objective response rate and disease control rate were 57.1%(8/14) vs. 30.8% (8/26)、71.4% (10/14) vs. 53.8%(14/26), all statistically significant. Conclusion:HAIC combined with targeted therapy and immunnotherapy is a safe and effective treatment for middle and advanced HCC, especially suitable for patients with portal vein tumor thrombus(PVTT), large tumor, or poor liver function.

Objective To analyze the mechanism of action of Sini Jia Renshen decoction in the treatment of myocardial infarction complicated with heart failure based on network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search the active ingredients of Sini Jia Renshen decoction.The target of Sini Jia Renshen decoction was obtained by using String and UniProt database.Targets related to myocardial infarction complicated with heart failure were searched through GeneCards database,OMIM database,etc.Obtain the intersection of the target of the active ingredient and the disease-related target.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of intersection targets were carried out.Results There were 112 active ingredients of Sini Jia Renshen decoction,233 active ingredients and 4980 associated targets of myocardial infarction complicated with heart failure.The intersection targets of drugs and diseases were 188.Quercetin,β-sitosterol,isorhamnetin and naringenin were the core active ingredients of Sini Jia Renshen decoction treatment of myocardial infarction complicated with heart failure.The pathway enrichment analysis showed that it was mainly involved in lipid and atherosclerosis,advanced glycation end product(AGE)/AGE receptor,vascular endothelium activated by shear stress,interleukin-17 and other signaling pathways.Conclusion The treatment of myocardial infarction complicated with heart failure by Sini Jia Renshen decoction has the characteristics of multi-components,multi-targets and multi-pathways.It may play a role in myocardial infarction complicated with heart failure through lipid and atherosclerosis pathways and so on.

Objective:To explore the potential categories of emotional behavior and its influencing factors in obese junior high school students.Methods:A total of 1 841 obese junior high school students were selected by convenient sampling method and surveyed by basic information scale, co-residence (CRS), online time (OT), outdoor exercise intensity (OEI) and subjective socioeconomic status scale for adolescent(SSS-A) score, Chinese version of perceived stress scale(CPSS), short grit scale(Grit-S), adolescent mental health literacy assessment questionnaire(AMHLAQ) and strengths and difficulties questionnaire (SDQ).Statistical analysis were conducted by SPSS 26.0 software and Mplus 8.3 software.The latent class analysis was used to group the students according to the SDQ scores, and the disordered multivariate Logistic regression was used to explore the influencing factors of each category.Results:There were 4 latent categories of emotional behavior in obese junior high school students, which were anxiety-independence group (22.49%), depression-passive group (28.25%), contradiction-affinity group(24.72%) and stability-sociability group (24.55%).Students with low CPSS, Grit-S, AMHLAQ and SSS-A scores were more likely to enter the anxiety-independence group with stability-sociability group as a reference( B=0.893, OR=2.442, 95% CI=1.083-5.509; B=-1.645, OR=0.193, 95% CI=0.067-0.553; B=0.030, OR=1.031, 95% CI=1.007-1.055; B=-0.177, OR=0.883, 95% CI=0.812-0.953; B=-0.066, OR=0.934, 95% CI=0.899-1.081; B=-0.302, OR=0.739, 95% CI=0.695-0.786), living with one parent, and having low CPSS, Grit-S, and AMHLAQ scores; students with OT<1 h OEI≥4 d and low Grit-S total score were more likely to enter the depression-passive group( B=0.930, OR=2.715, 95% CI=1.206-5.945; B=-0.447, OR=0.572, 95% CI=0.363-0.953; B=-0.201, OR=0.818, 95% CI=0.793-0.844); students with high CPSS total score and low Grit-S and AMHLAQ total scores were easy to enter the contradiction-affinity group( B=-1.752, OR=0.174, 95% CI=0.054-0.562; B=0.087, OR=1.091, 95% CI=1.065-1.118; B=-0.273, OR=0.783, 95% CI=0.752-0.871; B=-0.036, OR=0.965, 95% CI=0.938-0.991); OEI≥4 d and OT <1 h were the protective factors of the stability-sociability group ( P<0.05). Conclusion:There is heterogeneity in the emotional and behavioral characteristics of obese junior high school students, which can be divided into four categories.Living with parents, controlling the length of time on the internet, maintaining a certain intensity of outdoor sports, strengthening stress management and perseverance quality training, and improving mental health literacy can help prevent emotional and behavioral problems.

Objective:To investigate lung function differences in patients with varying severities of chronic obstructive pulmonary disease and construct a risk decision tree prediction model.Methods:A prospective cross-sectional study was conducted among 102 patients with chronic obstructive pulmonary disease (COPD) who received treatment at Tongde Hospital of Zhejiang Province between September 2022 and September 2023. The severity of each patient's condition was evaluated according to the "Guidelines for the Diagnosis and Management of Chronic Obstructive Pulmonary Disease (Revised Version 2021)." All patients were grouped based on the evaluation results. Upon admission, all patients underwent assessments of pulmonary function, ventilation function, blood gas analysis, and laboratory indicators. The baseline data of the patients were statistically analyzed and compared. Risk factors associated with the progression of COPD were analyzed using ordinal regression, and a decision tree model was constructed using the Classification and Regression Trees algorithm. The receiver operating characteristic curve was used to evaluate the predictive value of the decision model for the progression of COPD in patients.Results:The results of the ordinal regression analysis indicated that being female and having a high diffusing capacity of the lungs for carbon monoxide (DLCO) level were protective factors for the development of COPD ( OR < 1, both P < 0.05), while a high concentration of alveolar nitric oxide (CaNO) was a risk factor ( OR > 1, P < 0.05). According to the decision tree, CaNO, DLCO, and female sex were identified as independent risk factors, with CaNO having the most considerable effect. The receiver operating characteristic curve was generated based on the decision tree model. The results showed that the area under the curve of the decision tree model in the moderate group was 0.782, with an optimal cut-off value of 0.314, a specificity of 0.721, a sensitivity of 0.780, and a Youden index of 0.501. The area under the curve of the severe group was 0.845. Conclusions:Sex, DLCO levels, and CaNO levels are factors affecting the development of COPD in patients. The decision tree model based on these factors can effectively predict the risk of COPD progression.

Objective:To explore the potential categories of emotional behavior and its influencing factors in obese junior high school students.Methods:A total of 1 841 obese junior high school students were selected by convenient sampling method and surveyed by basic information scale, co-residence (CRS), online time (OT), outdoor exercise intensity (OEI) and subjective socioeconomic status scale for adolescent(SSS-A) score, Chinese version of perceived stress scale(CPSS), short grit scale(Grit-S), adolescent mental health literacy assessment questionnaire(AMHLAQ) and strengths and difficulties questionnaire (SDQ).Statistical analysis were conducted by SPSS 26.0 software and Mplus 8.3 software.The latent class analysis was used to group the students according to the SDQ scores, and the disordered multivariate Logistic regression was used to explore the influencing factors of each category.Results:There were 4 latent categories of emotional behavior in obese junior high school students, which were anxiety-independence group (22.49%), depression-passive group (28.25%), contradiction-affinity group(24.72%) and stability-sociability group (24.55%).Students with low CPSS, Grit-S, AMHLAQ and SSS-A scores were more likely to enter the anxiety-independence group with stability-sociability group as a reference( B=0.893, OR=2.442, 95% CI=1.083-5.509; B=-1.645, OR=0.193, 95% CI=0.067-0.553; B=0.030, OR=1.031, 95% CI=1.007-1.055; B=-0.177, OR=0.883, 95% CI=0.812-0.953; B=-0.066, OR=0.934, 95% CI=0.899-1.081; B=-0.302, OR=0.739, 95% CI=0.695-0.786), living with one parent, and having low CPSS, Grit-S, and AMHLAQ scores; students with OT<1 h OEI≥4 d and low Grit-S total score were more likely to enter the depression-passive group( B=0.930, OR=2.715, 95% CI=1.206-5.945; B=-0.447, OR=0.572, 95% CI=0.363-0.953; B=-0.201, OR=0.818, 95% CI=0.793-0.844); students with high CPSS total score and low Grit-S and AMHLAQ total scores were easy to enter the contradiction-affinity group( B=-1.752, OR=0.174, 95% CI=0.054-0.562; B=0.087, OR=1.091, 95% CI=1.065-1.118; B=-0.273, OR=0.783, 95% CI=0.752-0.871; B=-0.036, OR=0.965, 95% CI=0.938-0.991); OEI≥4 d and OT <1 h were the protective factors of the stability-sociability group ( P<0.05). Conclusion:There is heterogeneity in the emotional and behavioral characteristics of obese junior high school students, which can be divided into four categories.Living with parents, controlling the length of time on the internet, maintaining a certain intensity of outdoor sports, strengthening stress management and perseverance quality training, and improving mental health literacy can help prevent emotional and behavioral problems.

Objective:To explore the latent classes of fatigue trajectories and influencing factors in elderly patients with chronic pneumonia.Methods:A convenience sampling method was used to select 188 elderly patients with chronic pneumonia admitted to the Department of Geriatrics at Zhejiang Provincial Tongde Hospital from January 2023 to January 2024. General Data Questionnaires, Nutrition Risk Screening 2002, Athens Insomnia Scale, Hamilton Anxiety Scale, Community Commitment Scale, and Fatigue Scale were used to assess the patients. Patients were followed up for fatigue Scale at the time of consultation (T0) , and at the third (T1) and sixth (T2) months after consultation. Latent class growth analysis was used to model the trajectory of fatigue changes in elderly patients with chronic pneumonia.Results:A total of 188 questionnaires were distributed, with 165 valid responses, yielding an effective response rate of 87.8% (165/188) . The Fatigue Scale scores at T0, T1, and T2 were (4.63±1.74) , (5.54±1.90) , and (7.82±2.84) , respectively. The fatigue trajectories could be classified into three latent classes: low fatigue-slow increase group (74.5%, 123/165) , low fatigue-worsening group (10.3%, 17/165) , and high fatigue-slow increase group (15.2%, 25/165) . Multivariate logistic regression analysis showed that age, smoking index, number of chronic diseases, sleep, anxiety, and duration of cough and sputum were significant influencing factors for the fatigue trajectory in elderly patients with chronic pneumonia ( P<0.05) . Conclusions:Fatigue trajectories in elderly patients with chronic pneumonia exhibit group heterogeneity. Healthcare providers should develop targeted nursing measures based on different trajectory classes to alleviate fatigue and improve quality of life.

Objective To analyze the mechanism of action of Sini Jia Renshen decoction in the treatment of myocardial infarction complicated with heart failure based on network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search the active ingredients of Sini Jia Renshen decoction.The target of Sini Jia Renshen decoction was obtained by using String and UniProt database.Targets related to myocardial infarction complicated with heart failure were searched through GeneCards database,OMIM database,etc.Obtain the intersection of the target of the active ingredient and the disease-related target.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of intersection targets were carried out.Results There were 112 active ingredients of Sini Jia Renshen decoction,233 active ingredients and 4980 associated targets of myocardial infarction complicated with heart failure.The intersection targets of drugs and diseases were 188.Quercetin,β-sitosterol,isorhamnetin and naringenin were the core active ingredients of Sini Jia Renshen decoction treatment of myocardial infarction complicated with heart failure.The pathway enrichment analysis showed that it was mainly involved in lipid and atherosclerosis,advanced glycation end product(AGE)/AGE receptor,vascular endothelium activated by shear stress,interleukin-17 and other signaling pathways.Conclusion The treatment of myocardial infarction complicated with heart failure by Sini Jia Renshen decoction has the characteristics of multi-components,multi-targets and multi-pathways.It may play a role in myocardial infarction complicated with heart failure through lipid and atherosclerosis pathways and so on.

Objective To investigate the impact of kinesin family member 2A(KIF2A)on the resistance of hepatocellular carcinoma cells to 5-FU and its underlying mechanism.Methods The drug resistance of hepatocellular carcinoma cell line BEL7402 to 5-FU was induced through an increasing concentration gradient combined with high-dose intermittent shock to construct a drug-resistant strain,BEL7402/5-FU.KIF2A-silenced BEL7402/5-FU cells were then built using the lentivirus technique.Valproic acid(VPA),an agonist of the Notch1/Hes1signaling pathway,was employed to treat the KIF2A-silenced BEL7402/5-FU cells.The cell viability,apoptosis rate,and protein expressions of KIF2A,cleaved-caspase-3,Notch1,and Hes1 were detected by CCK-8 assay,western blot,immunofluorescence,and flow cytometry,respectively.Results The BEL7402/5-FU cells exhibited strong resistance to 5-FU,with an IC50 value of 344.2μmol/L,which was 92 times that of the BEL7402 cells(IC50=3.730μmol/L).Compared to the BEL7402 cells,the expression of the KIF2A protein in the BEL7402/5-FU cells was significantly increased(P＜0.001).Compared with the si-NC group,the viability of the BEL7402/5-FU cells in the si-KIF2A group was significantly decreased(P＜0.001).At the same time,the apoptosis rate and the expression of the cleaved-caspase-3 protein were significantly increased(P＜0.001),and the expressions of Notch1 and Hes1 protein were significantly decreased(P＜0.001).Compared with the si-NC+5-FU group,the activity of BEL7402/5-FU cells in the si-KIF2A+5-FU group was significantly decreased(P＜0.001)and the apoptosis rate was significantly increased(P＜0.001).Compared with the si-KIF2A+5-FU group,the activity of BEL7402/5-FU cells in the si-KIF2A+5-FU+VPA group was significantly increased(P＜0.001),the apoptosis rate was significantly decreased(P＜0.001),and the expressions of Notch1 and Hes1 proteins were significantly increased(P＜0.001).Conclusion Silencing KIF2A reduces the drug resistance of BEL7402/5-FU cells to 5-FU by inhibiting the activity of the Notch1/Hes1signaling pathway.

Objective:To investigate lung function differences in patients with varying severities of chronic obstructive pulmonary disease and construct a risk decision tree prediction model.Methods:A prospective cross-sectional study was conducted among 102 patients with chronic obstructive pulmonary disease (COPD) who received treatment at Tongde Hospital of Zhejiang Province between September 2022 and September 2023. The severity of each patient's condition was evaluated according to the "Guidelines for the Diagnosis and Management of Chronic Obstructive Pulmonary Disease (Revised Version 2021)." All patients were grouped based on the evaluation results. Upon admission, all patients underwent assessments of pulmonary function, ventilation function, blood gas analysis, and laboratory indicators. The baseline data of the patients were statistically analyzed and compared. Risk factors associated with the progression of COPD were analyzed using ordinal regression, and a decision tree model was constructed using the Classification and Regression Trees algorithm. The receiver operating characteristic curve was used to evaluate the predictive value of the decision model for the progression of COPD in patients.Results:The results of the ordinal regression analysis indicated that being female and having a high diffusing capacity of the lungs for carbon monoxide (DLCO) level were protective factors for the development of COPD ( OR < 1, both P < 0.05), while a high concentration of alveolar nitric oxide (CaNO) was a risk factor ( OR > 1, P < 0.05). According to the decision tree, CaNO, DLCO, and female sex were identified as independent risk factors, with CaNO having the most considerable effect. The receiver operating characteristic curve was generated based on the decision tree model. The results showed that the area under the curve of the decision tree model in the moderate group was 0.782, with an optimal cut-off value of 0.314, a specificity of 0.721, a sensitivity of 0.780, and a Youden index of 0.501. The area under the curve of the severe group was 0.845. Conclusions:Sex, DLCO levels, and CaNO levels are factors affecting the development of COPD in patients. The decision tree model based on these factors can effectively predict the risk of COPD progression.