BACKGROUND:Long-term blood flow restriction combined with low-intensity resistance training has been shown to effectively treat obesity by alleviating chronic inflammation and endothelial dysfunction.However,the immediate effects of a single session on serum concentrations of vascular endothelial function and inflammatory biomarkers remain unclear.OBJECTIVE:To explore the short-term effects and recovery capacity of blood flow restriction during low-intensity resistance training on serum biomarkers of vascular endothelial function and inflammation in obese male college students.METHODS:Twenty obese male college students(body mass index＞30 kg/m2,body fat percentage＞25％)were randomly assigned to a control group(0％arterial occlusion pressure)or a blood flow restriction group(80％arterial occlusion pressure).Both groups performed a single session of low-intensity resistance training at an intensity corresponding to a perceived exertion of 11-13 on the Rate of Perceived Exertion Scale.The training was repeated three times,with each session lasting 30 minutes,totaling 1.5 hours.Serum biomarkers were measured before exercise,immediately post-exercise,1 hour post-exercise,and 24 hours post-exercise.The assessed biomarkers included vascular endothelial function markers,inflammatory markers,and insulin function indicators.RESULTS AND CONCLUSION:(1)Vascular endothelial function:Acute exercise increased vascular endothelial growth factor A concentrations in both groups.The blood flow restriction group significantly elevated serum platelet-derived growth factor and nitric oxide levels(P＜0.05),while the control group showed a significant increase in nitric oxide synthase levels(P＜0.05).Angiotensin Ⅱ concentrations decreased immediately after acute exercise in both groups but remained significantly higher than baseline in the blood flow restriction group after 24 hours of recovery,and there was a significant difference between the two groups(P＜0.05).(2)Regarding inflammatory markers,the blood flow restriction group induced higher levels of hypoxia and significantly upregulated tumor necrosis factor-α and hypoxia-inducible factor-1α concentrations(P＜0.05).Adiponectin and leptin levels upregulated in both groups,with a more pronounced rise in adiponectin level in the blood flow restriction group than the control group(P＜0.05).lnterleukin-6 concentrations decreased in both groups,with a greater reduction in the blood flow restriction group.(3)For insulin function,the blood flow restriction and control groups showed immediate increases and decreases in insulin levels after exercise,respectively,but these returned to below and above baseline levels after 24 hours of recovery.Both groups reduced insulin resistance index in adipose tissue,with a more significant improvement in the blood flow restriction group(P＜0.05).To conclude,compared with low-intensity resistance training,short-term blood flow restriction induces more favorable changes in inflammatory and vascular endothelial biomarkers,improving inflammation and endothelial dysfunction with longer-lasting effects.However,further studies are needed to validate these findings over long-term interventions.

BACKGROUND:Long-term blood flow restriction combined with low-intensity resistance training has been shown to effectively treat obesity by alleviating chronic inflammation and endothelial dysfunction.However,the immediate effects of a single session on serum concentrations of vascular endothelial function and inflammatory biomarkers remain unclear.OBJECTIVE:To explore the short-term effects and recovery capacity of blood flow restriction during low-intensity resistance training on serum biomarkers of vascular endothelial function and inflammation in obese male college students.METHODS:Twenty obese male college students(body mass index＞30 kg/m2,body fat percentage＞25％)were randomly assigned to a control group(0％arterial occlusion pressure)or a blood flow restriction group(80％arterial occlusion pressure).Both groups performed a single session of low-intensity resistance training at an intensity corresponding to a perceived exertion of 11-13 on the Rate of Perceived Exertion Scale.The training was repeated three times,with each session lasting 30 minutes,totaling 1.5 hours.Serum biomarkers were measured before exercise,immediately post-exercise,1 hour post-exercise,and 24 hours post-exercise.The assessed biomarkers included vascular endothelial function markers,inflammatory markers,and insulin function indicators.RESULTS AND CONCLUSION:(1)Vascular endothelial function:Acute exercise increased vascular endothelial growth factor A concentrations in both groups.The blood flow restriction group significantly elevated serum platelet-derived growth factor and nitric oxide levels(P＜0.05),while the control group showed a significant increase in nitric oxide synthase levels(P＜0.05).Angiotensin Ⅱ concentrations decreased immediately after acute exercise in both groups but remained significantly higher than baseline in the blood flow restriction group after 24 hours of recovery,and there was a significant difference between the two groups(P＜0.05).(2)Regarding inflammatory markers,the blood flow restriction group induced higher levels of hypoxia and significantly upregulated tumor necrosis factor-α and hypoxia-inducible factor-1α concentrations(P＜0.05).Adiponectin and leptin levels upregulated in both groups,with a more pronounced rise in adiponectin level in the blood flow restriction group than the control group(P＜0.05).lnterleukin-6 concentrations decreased in both groups,with a greater reduction in the blood flow restriction group.(3)For insulin function,the blood flow restriction and control groups showed immediate increases and decreases in insulin levels after exercise,respectively,but these returned to below and above baseline levels after 24 hours of recovery.Both groups reduced insulin resistance index in adipose tissue,with a more significant improvement in the blood flow restriction group(P＜0.05).To conclude,compared with low-intensity resistance training,short-term blood flow restriction induces more favorable changes in inflammatory and vascular endothelial biomarkers,improving inflammation and endothelial dysfunction with longer-lasting effects.However,further studies are needed to validate these findings over long-term interventions.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

BACKGROUND:The regulation of intestinal flora by exercise is closely related to human health,but intestinal flora involves many factors.Existing studies have lacked consistent evidence on the effect of exercise on the intestinal flora of college students. OBJECTIVE:To explore the effects of exercise on intestinal flora diversity and species composition of college students. METHODS:Through systematic search of PubMed,Web of Science,Embase,Medline,Cochrane Library,CNKI,WanFang Database and VIP database,eight empirical studies were selected and included,and semi-quantitative analysis was performed on them. RESULTS AND CONCLUSION:In terms of the species diversity of the intestinal flora,both high-intensity interval training and Tai Chi exercise significantly enhance the species diversity of intestinal flora in college students,while aerobic exercise does not have a significant effect on the enhancement of intestinal flora diversity in college students.In terms of the species composition of the intestinal flora,all three exercise modalities significantly alter the compositional structure of the intestinal flora in college students,which can increase the abundance of beneficial bacteria such as Ruminalococcus,Faecalis prevotelli,Blautia,and decrease the abundance of harmful bacteria such as Escherichia spp.Compared with high-intensity interval training,aerobic and Tai Chi exercise causes more elevated abundance of beneficial bacteria.In addition to changes in intestinal flora characteristics,exercise improves body composition,cardiorespiratory function,and executive function in college students,and these health benefits are closely linked to exercise-induced changes in intestinal flora that can produce health benefits for the body through metabolic regulation,barrier function,and neuromodulation.Although studies have confirmed the association between exercise and intestinal flora,the mechanism by which exercise affects intestinal flora has not yet been clarified,and at the same time,localizing the flora related to the host health is the key to targeting intestinal flora as a therapeutic target in the future,all of which are worthy of further attention and investigation.

The purpose of this study was to investigate the effect of medium-chain fatty acids(MC-FAs)caprylic acid(C8∶0)on lipid metabolism of calf hepatocytes.Primary calf hepatocytes were extracted and cultured,and 1.2 mmol/L nonesterified fatty acids(NEFAs)were added to the hep-atocytes to construct a model of hepatic lipid deposition in primary calf hepatocytes,Five process-ing groups have been set up:Control group(Ctrl),NEFA added group(NEFA),C8∶0 1.2 mmol/L treatment group(C8∶0 1.2),NEFA+C8∶0 0.2 mmol/L treatment group(NEFA+C8∶00.2),C8∶0 0.2 mmol/L treatment group(C8∶0 0.2).Stimulate calf liver cells for 12 hours,and the levels of triglyceride(TG),lipid oxidation(MDA),hydrogen peroxide(H2O2)and total SOD activity were detected by biochemical kit,and FAS,a protein related to lipid synthesis,was detec-ted by Western blot.The results showed that compared with the control group,the concentrations of TG,MDA and H2O2 in NEFA group increased significantly(P＜0.01),and the activity of SOD decreased significantly(P＜0.05).The protein expression levels of FAS,ACC1,DGAT2 and SREBP-1C were significantly up-regulated(P＜0.01),while the expression level of CPT1A was significantly down-regulated(P＜0.01).Compared with the NEFA group,the protein expression levels of SREBP-1C and DGAT2 in the NEFA+C8∶0(concentration 0.2 mmol/L)group de-creased significantly(P＜0.05),and the protein expression level of fatty acid β-oxidation related molecule CPT1A was slightly higher than that in the NEFA group,but there was no statistical sig-nificance(P＞0.05),and the MDA level in hepatocytes decreased significantly(P＜0.05).In a word,the results of this study show that C8∶0 has antioxidant effect,which can effectively reduce the liver injury caused by oxidative stress,regulate the expression of liver fat gene,and then pro-tect liver injury.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

OBJECTIVE To investigate the effects of ginsenosides as P-glycoprotein(P-gp)substrates in combination with paclitaxel on the proliferation and migration of colon cancer Caco-2 cells.METHODS Bio-layer interferometry(BLI)technology was used to detect the constants of ginsenosides and P-gp.Network molecular docking was adopted to predict the binding affinity energy of ginsenosides and P-gp.Caco-2 cells were divided into paclitaxel 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,ginsenoside Rg3 0,6.25,12.5,25,50,100 and 200 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 0,25,50,100 and 200 mg·L-1 groups.After 48 h of incubation,the growth inhibition rate of Caco-2 cells was detected by MTT assay,and the interaction between the two drugs was quantitatively evaluated using the"one-belt,one-line"modle.Caco-2 cells were divided into the cell control group,paclitaxel 5 mg·L-1 group,ginsenoside Rg3 50 and 100 mg·L-1 groups,and paclitaxel 5 mg·L-1+ginsenoside Rg3 50 and 100 mg·L-1 groups.After 24 h of incubation,the proliferation and migration ability of the cells were detected by colony assay and Transwell migration assay.Caco-2 cells were then divided into the cell control group,quinidine 12.5 mg·L-1 group,and ginsenoside Rg3 6.25 and 12.5 mg·L-1 groups.After 4 h of incubation,the expression levels of P-gp and total protein were detected by ELISA.RESULTS The affinity constants of ginsenoside Rb1,Rg3,Rg5 with P-gp were all less than 10-3 mol·L-1,while that of ginsenoside CK with P-gp was 10-2 mol·L-1.There was no typical binding dissociation curve between ginsenoside Re and P-gp.The absolute binding affinities of ginsenosides Rg3 and Rg5 to P-gp were determined to be 8.5 kcal·mol-1 and 7.6 kcal·mol-1,respectively.Ginsenosides mixed with PTX 5 mg·L-1 inhibited the growth of colon cancer cells through synergy and addition,and the dose range of the syner-gistic effect was[0+5,43.15+5]mg·L-1;[164.51+5,200+5]mg·L-1,the additive effect dose ranged from[43.15+5,164.51+5]mg·L-1.The combination of the two drugs could significantly reduce the proliferation and migration ability of Caco-2 cells(P<0.01).The ELISA results showed a decrease in total protein and P-gp content in both the ginsenoside and quinidine groups(P<0.05).CONCLUSION Ginsenoside bind to and inhibit the activity of P-gp,synergizing with paclitaxel to reduce the proliferative and migratory abili-ties of Caco-2 cells.The combination of ginsenosides and paclitaxel enhances the sensitivity of Caco-2 cells to paclitaxel induced inhibition.The combined use of these two substances is expected to achieve better anticancer effects compared to paclitaxel alone.

ObjectiveTo study the effect of Wulingsan on cerebral edema after intracerebral hemorrhage （ICH） in mice and explore the treatment mechanism. MethodsThe mouse model of ICH was established by injection of collagenase into the caudate nucleus. Mice were randomly assigned into the following groups： sham， ICH， intervention before modeling with low-dose and high-dose （3.69， 11.07 g·kg^-1， respectively） Wulingsan， and intervention after modeling with high-dose Wulingsan. The modified neurological severity score （mNSS） was recorded， and the small animal MRI T2 sequential scanning was performed to measure the volume of cerebral hemorrhage after the modeling of ICH in each group. The Y-maze test， open field test， and Morris water maze test were conducted to evaluate the neurological behaviors of mice in each group. Hematoxylin-eosin staining was employed to observe the pathological changes in the brain tissue. Immunohistochemistry was employed to observe the expression of aquaporin 4 （AQP4）， neuronal nuclei （NeuN）， and glial fibrillary acidic protein （GFAP） in the brain tissue. Western blot was employed to determine the protein levels of AQP4， Claudin-5， and zonula occludens-1 （ZO-1） in the hematoma area. ResultsCompared with the sham group， the ICH group showed increases in the mNSS， the cerebral hemorrhage volume， and the escape latency in the Morris water maze test （P<0.01）， decreases in the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， and reductions in the spontaneous alternation rate in the Y-maze test and the ratio of distance of center travel to total travel distance in the open field test （P<0.01）. Moreover， pathological changes such as cell disarrangement， cell space enlargement， and cell swelling were observed in the ICH group. Immunohistochemistry results showed that the ICH group had higher proportions of AQP4- and GFAP-positive cells and lower proportion of NeuN-positive cells than the sham group （P<0.01）. Compared with the sham group， the ICH group showed an up-regulated protein level of AQP4 and down-regulated protein levels of Claudin-5 and ZO-1 （P<0.01）. Compared with the ICH group， the intervention with Wulingsan decreased the mNSS， the volume of cerebral hemorrhage， and the escape latency in the Morris water maze test （P<0.05， P<0.01）， while increasing the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， the spontaneous alternation rate in the Y-maze test， and the ratio of distance of center travel to total travel distance in the open field test （P<0.05， P<0.01）. Furthermore， the intervention with Wulingsan alleviated the pathological changes in the brain tissue after ICH， decreased the proportion of AQP4- and GFAP-positive cells （P<0.01）， increased the proportion of NeuN-positive cells （P<0.01）， down-regulated the protein level of AQP4 （P<0.01）， and up-regulated the protein levels of Claudin-5 and ZO-1 （P<0.01）. ConclusionThe intervention with Wulingsan could reduce the neural function score and the cerebral hemorrhage volume， up-regulate the expression of Claudin-5 and ZO-1， and down-regulate the expression of AQP4 to ameliorate the neurological function defect and cerebral edema after ICH， thereby protecting the brain.

Objective Using meta-analysis to identify the risk factors for slow-flow or no-reflow during percutaneous coronary intervention(PCI)in patients with ST-segment elevation acute myocardial infarction(AMI).Methods A computerized retrieval of academic papers concerning the risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI from the databases of CNKI,Wanfang Database,VIP,SinoMed,PubMed,Web of Science,Embase,and Cochrane Library was conducted.The retrieval time period was from the establishment of the database to January 2024.In order to ensure the accuracy and reliability of the study,two independent reviewers screened the literature according to the preset inclusion and exclusion criteria,extracted key data,and strictly evaluated the quality of the literature.RevMan5.4 software was used to make meta-analysis.Results A total of 23 articles with a total of 9 780 cases were included in this analysis.The results of meta-analysis showed that reperfusion time ≥6 h(OR=1.52),preoperative TIMI blood flow≤level-Ⅰ(OR=1.12),heavy thrombus burden(OR=1.60),advanced age(OR=1.56),diabetes(OR=1.83),preoperative Killip grade≥Ⅲ(OR=2.52),long target vessel disease(OR=1.95),and collateral flow≤level-Ⅰ(OR=1.61)were the risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI.Preoperative systolic blood pressure＜90 mmHg(OR=1.17)and high white blood cell(WBC)count(OR=1.27)were not the risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI.Conclusion Reperfusion time ≥ 6 h,preoperative TIMI blood flow≤level-Ⅰ,heavy thrombus burden,advanced age,diabetes,preoperative Killip grade≥level-Ⅲ,long target vessel lesion,and collateral blood flow≤level-Ⅰ are the independent risk factors for slow-flow or no-reflow during PCI in patients with ST-segment elevation AMI.