ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

Objective To explore the role of nucleolin 6(NOL6)in the occurrence and development of hypertension and its mechanism of regulating ribosome biogenesis.Methods Differentially expressed genes were screened based on the GEO database(chip GSE212338),and intersection analysis was conducted in combination with genes related to ribosome generation to obtain genes related to ribosome biogenesis in hypertension.The rats were divided into control group and model group(L-NAME group).The hypertensive rat model was induced by N-nitro-L-arginine methyl ester(L-NAME),and the thickness and pathological changes of the aortic wall in each group were observed by HE staining.The expression of ribosomal RNA(rRNA)in rat aortic tissues was detected by qPCR to reflect ribosome biogenesis,and the protein expression of NOL6 was detected by Western blotting.Human umbilical vein endothelial cells(HUVECs)were cultured and grouped for treatment(control group,L-NAME group,AngⅡ group,AngⅡ+si-NC group,AngⅡ+si-NOL6 group,and AngⅡ+CX-5461 group).The generation of neocRNA in HUVEC was detected by EU.The protein and mRNA expressions of NOL6 in HUVEC were detected by Western blotting and qPCR,respectively.Western blotting was used to detect the protein expressions of endothelial nitric oxide synthase(eNOS)and p-eNOS.Results By combining the differential expression analysis of the GEO hypertension dataset GSE212338 and the ribosome biogenesis gene set,six core genes with significantly altered expression in hypertension and related to ribosome biogenesis were identified.The difference in NOL6 was the most significant.Compared with the control group,the aortic wall thickness of rats in the L-NAME group increased significantly.Ribosomal RNA expression was significantly upregulated;the protein and mRNA expressions of NOL6 were significantly upregulated,too.Compared with the control group,the generation of neoRNA in the cells of the L-NAME group increased significantly;the levels of NOL6 protein and mRNA,ribosomal RNA and neoRNA in the Ang Ⅱ group were significantly increased compared with the control group but significantly decreased compared with the Ang Ⅱ+si-NC group.Compared with the Ang Ⅱ+si-NOL6 group,the protein and mRNA expressions of NOL6 in the AngⅡ+si-NC group and the AngⅡ+CX-5461 group cells were significantly increased.Compared with the AngⅡ+si-NC group,the levels of ribosomal RNA and neoRNA in the AngⅡ+si-NOL6 group and the AngⅡ+CX-5461 group were significantly decreased;the protein expressions of eNOS and p-eNOS were significantly increased.Conclusion NOL6 is associated with abnormal ribosome biogenesis in hypertension.NOL6 can affect the expression of eNOS by regulating ribosome biogenesis,thereby regulating the occurrence and development of hypertension.

Objective Exploring the application effect of fragmented resistance exercise in the exercise rehabili-tation of elderly patients with chronic obstructive pulmonary disease,providing references for improving their quality of life.Methods From October to December 2024,96 elderly patients with chronic obstructive pulmonary disease admitted to a tertiary hospital in Pingdingshan city were conveniently selected as the research subjects.They were randomly divided into an experimental group and a control group(all n=48)using a random number table method.The experimental group received a fragmented resistance exercise program on the basis of routine pulmonary reha-bilitation,while the control group received routine pulmonary rehabilitation nursing care for a duration of 3 months.The lung function,exercise endurance,quality of life,and exercise compliance were compared between the 2 groups before and after intervention.Results The experimental group ultimately included 46 cases,while the control group ultimately included 47 cases.The lung function of the experimental group was better than that of the control group after 3 months of intervention(P＜0.05),and the exercise compliance scores of the experimental group were high-er than those of the control group after 1 and 3 months of intervention(P＜0.001).Repeated measures ANOVA showed that there was an interaction effect(P＜0.05)in the comparison of exercise endurance and quality of life between the 2 groups.Simple effects analysis showed that the experimental group had better exercise endurance after 3 months of intervention than the control group(P＜0.05),and better quality of life after 1 and 3 months of intervention than the control group(P＜0.05).Conclusion Fragmented resistance exercise can effectively improve lung function,enhance exercise endurance and compliance,and improve quality of life in elderly patients with chronic obstructive pul-monary disease.

Objective To analyze the effects of tyrosinase on choroidal and retinal thickness and blood flow changes in guinea pigs,and to explore the role of tyrosinase in the development and progression of myopia.Methods A total of 30 three-week-old male tri-colored guinea pigs and 10 albino guinea pigs were selected and divided into four groups:control group(tri-colored hyperopic guinea pigs,with no intervention),albino group(albino myopic guinea pigs,with no inter-vention),myopia group(tri-colored myopic guinea pigs,with no intervention),and injection group[tri-colored hyperopic guinea pigs,injected with tyrosinase inhibitor(6 250 μg·L-1),100 μL per day].The experiment lasted for 4 weeks.The refractive status and axial length(AL)of the guinea pigs in each group were measured,along with ocular biometric param-eters related to axial length[anterior chamber depth,aqueous humor depth(AQD),central corneal thickness,lens diame-ter,vitreous chamber depth(VCD)].Optical coherence tomography was used to measure the retinal thickness,choroidal thickness(ChT),and choroidal blood perfusion(ChBP)in different regions of the guinea pigs.The tyrosinase activity in the vitreous and retina of guinea pigs in each group was measured.The expression levels of neurotransmitters in the vitre-ous and retina of guinea pigs in each group were detected.Results The differences in refractive status between the albi-no group and the control group at 0,2,and 4 weeks of the experiment were statistically significant(F=8.972,P＜0.05).At the 4th week of the experiment,the refractive status of the injection group was lower than that of the control group,and the AL was greater than that of the control group,with statistically significant differences(both P＜0.05).Further analysis of AL-related biometric parameters revealed that only AQD and VCD were associated with the changes in AL of guinea pigs in each group.At the 0th week of the experiment,the average retinal thickness of the control group was greater than that of the albino group,with a statistically significant difference(t=-9.007,P＜0.000 1).Moreover,the differences in reti-nal thickness in the outer retina across different directions and time points were statistically significant(all P＜0.05).The differences in retinal thickness between the control and albino groups were mainly concentrated in the outer retina.The ChT of the albino group was less than that of the control group,with a significant difference between groups(F=4.809,P=0.030).The ChBP of the control group was significantly higher than that of the albino group at 0,2,and 4 weeks of the experiment(all P＜0.05).At the 4th week of the experiment,the tyrosinase activity in the vitreous of the injection,albi-no,and myopia groups was lower than that of the control group,with statistically significant differences(all P＜0.05).The differences in neurotransmitters between the albino and control groups were mainly concentrated in the vitreous.In the retina,the ornithine level in the myopia group was higher than that in the albino and control groups,and the tryptophan levels in the myopia and control groups were higher than that in the albino group,with statistically significant differences(all P＜0.05).Conclusion Tyrosinase plays a crucial role in the development of myopia,regulating the development of refractive status by influencing the physiological properties of the retina and choroid.

Objective To evaluate the effectiveness of different tip positions applied to midline catheters(MC)and provide evidence-based evidence for venous catheter tip positioning in clinical practice.Methods Computerized searches of PubMed,Web of Science,Embase,Cochrane Library,CINAHL,CNKI,Wanfang Database,VIP,and CBM for studies on the effectiveness of applying MC with different tip positions were performed from the time of database construction to July 2024.Meta-analysis was performed using Rev Man 5.3 software after 2 investigators independently screened the studies,extracted the information and evaluated the quality of the included studies.Results A total of 9 studies with 2 302 hospitalized patients were included.The quality evaluation results of the included studies are all B-level.Meta-analysis showed that when the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the rate of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,and catheter-associated thrombosis were lower,with a statistically significant difference(P＜0.05).When the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the catheter retention time was longer,with a statistically significant difference(P=0.007).The descriptive analysis showed a lower rate of extubation due to complications when the tip of the MC was located in the subclavian vein compared with when the tip was located in the axillary vein(P＜0.05).Conclusion When the tip of the MC is located in the subclavian vein compared to when it is located in the axillary vein,the incidence of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,catheter-associated thrombosis,and the rate of catheter extractions due to complications were lower,and the catheter was left in place for a longer period of time.Due to the limitations of the quantity and quality of the included studies,more large-sample,high-quality studies are needed to further validate the effectiveness of different tip positions of MC.

AIM:To explore the mechanism of Salvia miltiorrhiza(Danshen)-derived exosome-like nanoparti-cles(DDN)in attenuating oxidative damage in endothelial cells through the activation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/endothelial nitric oxide synthase(eNOS)signaling pathway.METHODS:The DDN were characterized by transmission electron microscopy and dynamic light scattering.Fluorescence microscopy and flow cytometry were used to evaluate the uptake of DDN by human umbilical vein endothelial cells(HUVECs).The viability,migration and invasion of HUVECs were assessed using CCK8 assay,wound-healing assay and Transwell assay,respec-tively.The HUVECs were induced by angiotensin II(Ang II)for oxidative stress and intervened with DDN or LY294002(a PI3K inhibitor).The levels of reactive oxygen species were determined by flow cytometry,and intracellular nitric oxide(NO)content was measured using a biochemical assay kit.Additionally,the protein levels of NADPH oxidase 4(NOX4),NOX2,endothelial nitric oxide syntnase(eNOS),p-eNOS,Akt and p-Akt were examined by Western blot.RESULTS:(1)Transmission electron microscopy and dynamic light scattering analysis revealed that DDN had good bio-compatibility and stability.(2)According to fluorescence images and flow cytometry results,DDN were strongly taken up by HUVECs.(3)Compared with control group,DDN significantly promoted the viability,migration and invasion of HUVECs,showing a dose-dependent effect.(4)Compared with control group,DDN remarkably increased intracellular NO levels,thereby enhancing endothelial cell vasodilation via activating the PI3K/Akt/eNOS signaling pathway.(5)The PI3K/Akt/eNOS pathway played a critical role in mitigating oxidative stress and improving cellular function in response to DDN treat-ment.CONCLUSION:The DDN mediate PI3K/Akt/eNOS signaling pathway activation to significantly alleviate Ang II-induced oxidative damage in endothelial cells,suggesting a potential vascular protective effect of DDN.

Objective To investigate the effects of strength training and flexibility training on the strategy of crossing obstacles for the elderly women and the risk of tripping over obstacles.Methods Twenty five elderly women were randomly divided into strength training group(n=13)and flexibility training group(n=12),and received corresponding intervention training for 12 weeks.The kinematics data of obstacle crossing were collected using an infrared three-dimensional(3D)motion capture system before and after training.Results Both strength training and flexibility training could significantly improve the gait speed(P=0.033),stride length(P=0.020)and toe distance(P=0.014)during 25 cm obstacle crossing.The interactive effect of training and time was significant for the crossing height(15 cm:P=0.025;25 cm:P=0.019).The interactive effect of training and time was significant for the margin of stability(MOS)in the internal-external direction during 25 cm obstacle crossing(P<0.05).The minimum MOS in the first single support period(P=0.046)and the MOS at the time when the toe crossed directly above the obstacle(P=0.043)in strength training group were significantly increased.Conclusions Both strength training and flexibility training can improve the spatiotemporal characteristics of the elderly women during obstacle crossing.Compared with flexibility,muscle strength is the most important reason that restricts the crossing height of the elderly women.Strength training can effectively reduce the risk of tripping over obstacles by improving the crossing height and dynamic stability of elderly women.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

AIM:To explore the mechanism of Salvia miltiorrhiza(Danshen)-derived exosome-like nanoparti-cles(DDN)in attenuating oxidative damage in endothelial cells through the activation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/endothelial nitric oxide synthase(eNOS)signaling pathway.METHODS:The DDN were characterized by transmission electron microscopy and dynamic light scattering.Fluorescence microscopy and flow cytometry were used to evaluate the uptake of DDN by human umbilical vein endothelial cells(HUVECs).The viability,migration and invasion of HUVECs were assessed using CCK8 assay,wound-healing assay and Transwell assay,respec-tively.The HUVECs were induced by angiotensin II(Ang II)for oxidative stress and intervened with DDN or LY294002(a PI3K inhibitor).The levels of reactive oxygen species were determined by flow cytometry,and intracellular nitric oxide(NO)content was measured using a biochemical assay kit.Additionally,the protein levels of NADPH oxidase 4(NOX4),NOX2,endothelial nitric oxide syntnase(eNOS),p-eNOS,Akt and p-Akt were examined by Western blot.RESULTS:(1)Transmission electron microscopy and dynamic light scattering analysis revealed that DDN had good bio-compatibility and stability.(2)According to fluorescence images and flow cytometry results,DDN were strongly taken up by HUVECs.(3)Compared with control group,DDN significantly promoted the viability,migration and invasion of HUVECs,showing a dose-dependent effect.(4)Compared with control group,DDN remarkably increased intracellular NO levels,thereby enhancing endothelial cell vasodilation via activating the PI3K/Akt/eNOS signaling pathway.(5)The PI3K/Akt/eNOS pathway played a critical role in mitigating oxidative stress and improving cellular function in response to DDN treat-ment.CONCLUSION:The DDN mediate PI3K/Akt/eNOS signaling pathway activation to significantly alleviate Ang II-induced oxidative damage in endothelial cells,suggesting a potential vascular protective effect of DDN.

Objective To evaluate the effectiveness of different tip positions applied to midline catheters(MC)and provide evidence-based evidence for venous catheter tip positioning in clinical practice.Methods Computerized searches of PubMed,Web of Science,Embase,Cochrane Library,CINAHL,CNKI,Wanfang Database,VIP,and CBM for studies on the effectiveness of applying MC with different tip positions were performed from the time of database construction to July 2024.Meta-analysis was performed using Rev Man 5.3 software after 2 investigators independently screened the studies,extracted the information and evaluated the quality of the included studies.Results A total of 9 studies with 2 302 hospitalized patients were included.The quality evaluation results of the included studies are all B-level.Meta-analysis showed that when the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the rate of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,and catheter-associated thrombosis were lower,with a statistically significant difference(P＜0.05).When the tip of the MC was located in the subclavian vein compared with the tip of the MC in the axillary vein,the catheter retention time was longer,with a statistically significant difference(P=0.007).The descriptive analysis showed a lower rate of extubation due to complications when the tip of the MC was located in the subclavian vein compared with when the tip was located in the axillary vein(P＜0.05).Conclusion When the tip of the MC is located in the subclavian vein compared to when it is located in the axillary vein,the incidence of total catheter-related complications,phlebitis,blood leakage,infiltration,catheter occlusion,catheter dislocation,catheter-associated thrombosis,and the rate of catheter extractions due to complications were lower,and the catheter was left in place for a longer period of time.Due to the limitations of the quantity and quality of the included studies,more large-sample,high-quality studies are needed to further validate the effectiveness of different tip positions of MC.