Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Colon cancer is a common malignant tumor in the human digestive system.5-fluorouracil(5-FU)is a first-line treatment for colon cancer,which can be used alone or in combination with other chemo-therapy drugs.However,with the increase of 5-FU use time,colon cancer cells are prone to develop primary and secondary resistance to 5-FU.In recent years,a lot of significant research progress has been made on 5-FU resistance related genes at different levels,such as molecular mechanisms,animal models,and clinical trials.This article reviews the latest research progress on 5-FU resistance in terms of DNA damage repair mecha-nisms,increased expression of adenosine triphosphate(ATP)binding box transporter,abnormal signaling pathways,abnormal nucleoside metabolizing enzymes,forkhead box protein M1(FOXM1),etc.,in order to provide reference and basis for the treatment of colon cancer.

Objective To investigate the value of serum tumor markers in the diagnosis of lung cancer.Methods A total of 138 patients with newly diagnosed lung cancer patient(lung cancer group)and 52 patients with benign lung diseases(control group)in Anhui NO.2 Provincial People's Hospital from June 2020 to March 2024 were selected as the research objects.The clinical data and serum tumor markers[neuron-specific enolase(NSE),cytokeratin 19 fragment(CYFRA21-1),carcinoembryonic antigen(CEA),Pro-gastrin-relea-sing peptide(ProGRP)and squamous cell carcinoma antigen(SCC)]of all groups were compared.Results There were significant differences in age and smoking history between the two groups(P＜0.05).The serum levels of NSE,CYFRA21-1,CEA,ProGRP and SCC in lung cancer group were significantly higher than those in control group,and the differences were statistically significant(P＜0.05).The results of binary Logistic regression analysis showed that smoking history,age,CYFRA21-1 and CEA levels were all influen-cing factors for the occurrence of lung cancer(P＜0.05).Receiver operating characteristic(ROC)curve analy-sis results showed that the area under the curve(AUC)of smoking history,age,CEA and CYFRA21-1 in the combined diagnosis of lung cancer was 0.906(95％CI:0.865-0.947),which was higher than the AUC for the individual diagnosis of each index.The levels of serum CYFR21-1 and CEA in the stage Ⅰ—Ⅱ group were significantly lower than those in the stage Ⅲ-Ⅳ group,and the difference was statistically significant(P＜0.05).The results of binary Logistic regression analysis showed that CYFRA21-1 and CEA levels were influ-ential factors in the occurrence of lung cancer stage Ⅲ-Ⅳ(P＜0.05).ROC curve analysis showed that the AUC of CEA and CYFRA21-1 for the diagnosis of lung cancer stage Ⅲ-Ⅳ were 0.750(95％CI:0.667-0.832)and 0.771(95％CI:0.691-0.852),respectively.The AUC of combined diagnosis was 0.834(95％CI:0.765-0.902),the sensitivity was 58.9％,and the specificity was 95.3％.Conclusion Smoking history,age,CEA,and CYFRA21-1 may be potential biomarkers for the diagnosis and prognosis of lung cancer,espe-cially CEA and CYFRA21-1,which are also of great significance for the staging of lung cancer from stage Ⅲ to stage Ⅳ.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To analyze the association between daily physical activity patterns and dyslipidemia among people receiving physical examination aged 40-65 years.Methods:This cross-sectional study consecutively enrolled 864 participants aged 40-65 years and met the inclusion and exclusion criteria who underwent health check-ups at the Physical Examination Center of Fuquan First People′s Hospital from March to November in 2022. The data of general characteristics, physical activity, physical examination findings, and lipid profiles were collected. The daily physical activity patterns were identified using K-means clustering analysis. The unconditional binary logistic regression was employed to explore the associations between these activity patterns and dyslipidemia, followed by subgroup analyses.Results:The physical activity of the 864 study participants (517 males and 347 females) included in the analysis was divided into 4 patterns (G1: low physical activity; G2: active commuting; G3: housework; G4: leisure exercise). Using G1 as a reference, after adjusting for confounders, G4 was negatively associated with low high density lipoprotein cholesterol (HDL-C) ( OR=0.37, 95% CI: 0.14-1.00) ( P=0.05). In the male, G3 was negatively associated with dyslipidemia ( OR=0.44, 95% CI: 0.21-0.93) and low HDL-C ( OR=0.25, 95% CI: 0.10-0.68) (both P<0.05). In the subjects aged 50 years and above, G2 was negatively associated with dyslipidemia ( OR=0.52, 95% CI: 0.30-0.90), hypertriglyceridemia ( OR=0.50, 95% CI: 0.28-0.90) and low HDL-C ( OR=0.47, 95% CI: 0.24-0.91) (all P<0.05). In those who never or occasionally stayed up late, G2 was negatively associated with hypertriglyceridemia ( OR=0.31, 95% CI: 0.13-0.75) ( P<0.05); in those who stayed up late often, G4 was negatively associated with dyslipidemia ( OR=0.33, 95% CI: 0.13-0.85) and low HDL-C ( OR=0.19, 95% CI: 0.04-0.84) (both P<0.05). In the centrally obese population, G2 was negatively associated with dyslipidemia ( OR=0.55, 95% CI: 0.35-0.88) and hypertriglyceridemia ( OR=0.54, 95% CI: 0.33-0.86) (both P<0.05). Conclusions:Association between different physical activity patterns and dyslipidemia varied among adults aged 40-65 years undergoing health check-ups. Leisure-time exercise is associated with a reduced risk of dyslipidemia, while household activities also emerges as a beneficial factor linked to lower dyslipidemia risk particularly in the male population.

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.

Objective:To analyze the association between daily physical activity patterns and dyslipidemia among people receiving physical examination aged 40-65 years.Methods:This cross-sectional study consecutively enrolled 864 participants aged 40-65 years and met the inclusion and exclusion criteria who underwent health check-ups at the Physical Examination Center of Fuquan First People′s Hospital from March to November in 2022. The data of general characteristics, physical activity, physical examination findings, and lipid profiles were collected. The daily physical activity patterns were identified using K-means clustering analysis. The unconditional binary logistic regression was employed to explore the associations between these activity patterns and dyslipidemia, followed by subgroup analyses.Results:The physical activity of the 864 study participants (517 males and 347 females) included in the analysis was divided into 4 patterns (G1: low physical activity; G2: active commuting; G3: housework; G4: leisure exercise). Using G1 as a reference, after adjusting for confounders, G4 was negatively associated with low high density lipoprotein cholesterol (HDL-C) ( OR=0.37, 95% CI: 0.14-1.00) ( P=0.05). In the male, G3 was negatively associated with dyslipidemia ( OR=0.44, 95% CI: 0.21-0.93) and low HDL-C ( OR=0.25, 95% CI: 0.10-0.68) (both P<0.05). In the subjects aged 50 years and above, G2 was negatively associated with dyslipidemia ( OR=0.52, 95% CI: 0.30-0.90), hypertriglyceridemia ( OR=0.50, 95% CI: 0.28-0.90) and low HDL-C ( OR=0.47, 95% CI: 0.24-0.91) (all P<0.05). In those who never or occasionally stayed up late, G2 was negatively associated with hypertriglyceridemia ( OR=0.31, 95% CI: 0.13-0.75) ( P<0.05); in those who stayed up late often, G4 was negatively associated with dyslipidemia ( OR=0.33, 95% CI: 0.13-0.85) and low HDL-C ( OR=0.19, 95% CI: 0.04-0.84) (both P<0.05). In the centrally obese population, G2 was negatively associated with dyslipidemia ( OR=0.55, 95% CI: 0.35-0.88) and hypertriglyceridemia ( OR=0.54, 95% CI: 0.33-0.86) (both P<0.05). Conclusions:Association between different physical activity patterns and dyslipidemia varied among adults aged 40-65 years undergoing health check-ups. Leisure-time exercise is associated with a reduced risk of dyslipidemia, while household activities also emerges as a beneficial factor linked to lower dyslipidemia risk particularly in the male population.

Objective:To analyze the association between body health score and the risk of hypertension among health examination population aged 40-65 years.Methods:This study was a cross-sectional study, and 1 104 people aged 40-65 years who underwent physical examination at the Physical Examination Centre of the First People′s Hospital of Fuquan City from March to November 2022 were selected. Clinical data, such as general information, physical examination, body composition and history of hypertension diseases, were collected. The body health score was reported by the Xiaomi Body Fat Scale′s accompanying exercise health software, and was calculated by combining body fat, water and other body composition data. The association between body health score and the risk of hypertension was analyzed using restricted cubic spline regression models, while a sensitivity analysis and sex-stratified analyses were performed. Multivariate logistic regression combined with stratified analysis was used to explore the association between dimensions of body composition and the risk of hypertension.Results:The body health score was significantly lower in hypertensive patients than in non-hypertensive patients among the 1 104 health examination population [52.0(30.0) vs 69.0(35.8) points] ( Z=-8.547, P<0.001). The lower the body health score, the higher the risk of hypertension ( χ2=18.48, PNonlinear<0.001). In the total population, high body mass index was associated with an increased risk of hypertension ( OR=1.744, 95% CI: 1.104-2.765), high protein content was associated with a reduced risk of hypertension ( OR=0.587, 95% CI: 0.344-0.982) (both P<0.05). Gender-stratified analyses showed that high protein content was associated with a reduced risk of hypertension only in men ( OR=0.233, 95% CI: 0.080-0.592) ( P=0.004). High body mass index was positively associated with the risk of hypertension when the body health score was ≥60 points ( OR=2.378, 95% CI: 1.255-4.542) ( P=0.008). High visceral adiposity index (VAI) was positively associated with the risk of hypertension when the body health score was <60 points ( OR=4.395, 95% CI: 1.466-13.620), and high protein content was negatively associated with the risk of hypertension ( OR=0.255, 95% CI: 0.091-0.638) (all P<0.05). Conclusions:Health examination population aged 40-65 years with lower scores of physical health are more likely to have a risk of hypertension. Men should pay attention to the impact of body protein in hypertension risk prevention and control. The effect of body mass index should be noted when body health scores are ≥60 points, and the effect of VAI and body protein should be considered when body health scores are <60 points.

Ischemic stroke(IS)is a severe cerebrovascular disease that seriously endangers human health.Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine.In recent years,trimethylamine N-oxide(TMAO)as a gut microbiota metabolite has received widespread attention in cardiovascular diseases.Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis,atrial fibrillation,hypertension,and type 2 diabetes.TMAO exacerbates neurological damage in IS patients,increases the risk of IS recurrence,and is an independent predictor of post-stroke cognitive impairment(PSCI)in patients.Current research suggests that the mechanisms of TMAO action include endothelial dysfunction,promoting of foam cell formation,influence on cholesterol metabolism,and enhancement of platelet reactivity.Lowering plasma TMAO levels through the rational use of traditional Chinese medicine,dietary management,vitamins,and probiotics can prevent and treat IS.