Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective To investigate stress distributions of the knee joint at 0 and 15th day after anterior cruciate ligament reconstruction(ACLR)under a compressive force through the axis of the femoral shaft onto the proximal femur.Methods A three-dimensional(3D)finite element model of the human knee joint incorporating viscoelastic material properties was developed.The one-dimensional(1D)Prony series viscoelastic constitutive model parameters for articular cartilage,menisci,ligaments,and anterior cruciate ligament(ACL)grafts were determined by fitting experimental creep curves.The viscoelastic parameters of ACL grafts at 15th day after ACLR surgery were extrapolated.Finite element simulations were then performed to analyze the von Mises stress distributions in knee ligaments,ACL grafts,articular cartilage,and menisci under 1.5 kN vertical downward compressive load applied to the femur,with loading durations of 1 second and 600 seconds.Results At 15th day after ACLR surgery,the initial relaxation modulus and equilibrium modulus of human ACL grafts remained elevated compared to native ACL tissues,resulting in a significantly higher stress concentration within the grafts relative to healthy ACL.Despite the compromised mechanical properties of the grafts after ACLR surgery,the vertical downward compressive force applied to the femur under both short-term(1s)and prolonged(600 s)loading durations,exhibited a minimal biomechanical impact on articular cartilage and meniscal structures.Conclusions Following ACLR,vertical compressive loads during weight-bearing rehabilitation exercises such as standing demonstrate minimal impact on articular cartilage and meniscus,while promoting fibrous regeneration of the graft.This renders such exercises a prudent early-stage rehabilitation strategy.Graft preparation requires balanced consideration of elastic and viscous properties,with grafts exhibiting higher relaxation modulus and viscosity coefficient than healthy ACL proving more effective in maintaining early postoperative knee stability.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

High altitude heart disease(HAHD)is a chronic mountain sickness in which the body is exposed to high altitude(＞2 500 m)hypobaric hypoxia environment for a long time.HAHD has high morbidity and poor prognosis,and pulmonary hypertension is the main causative mechanism for its develop-ment.The phosphodiesterase-5 inhibitor sildenafil has become a hot drug for the treatment of pulmonary hypertension.This paper reviews the progress of HAHD and discusses the mechanism of action and effectiveness of sildenafil in the treatment of HAHD,with a view to providing a basis for the treatment of HAHD with sildenafil.

Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome(PCOS).The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.Methods A customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used.The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice(8 mice per group)to establish the control group and letrozole-induced PCOS model group.Both groups were treated with a high-fat diet starting the day after administration.The modeling period lasted for 5 weeks,during which body weight and 24-hour food intake were monitored in each group every week.When samples were collected,liver weight was recorded.Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin(HE)staining,while hepatic lipid deposition was observed by Oil Red O staining.The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining,and hepatic fibrosis levels were observed by Masson's trichrome staining.Transcriptomic sequencing was performed to analyze differentially expressed genes(DEGs)in liver tissues between the control and model groups,followed by enrichment analysis of significant DEGs.Quantitative real-time fluorescent quantitative PCR(qPCR)was subsequently used to validate the expression of significant DEGs in liver tissues of both groups.Results Compared with the control group,the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight(P＜0.001),prominent polycystic ovarian morphology,and significantly decreased liver-to-body weight ratio(P＜0.05).However,no significant changes were observed in absolute liver weight(P＞0.05),hepatic histomorphology,or lipid deposition.Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice,which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis,steroid hormone metabolism,and inflammatory responses.qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver(P＜0.01),while mRNA expression of IL4,CCL2 and COL1A1 was downregulated(P＜0.05)in the model group compared with the control group.However,Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.Conclusion Subcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS.The model mice exhibited significant changes in hepatic gene expression.Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.

OBJECTIVE To analyze the blood components of Suanzaoren Decoction after oral administration using UHPLC-Q Exactive Orbitrap-MS technology.METHODS Female Sprague-Dawley(SD)rats were used as experimental subjects,and Suanza-oren Decoction was administered orally.Serum samples were collected,and the aqueous extract of Suanzaoren Decoction and the serum were analyzed using UHPLC-Q Exactive Orbitrap-MS technology to identify the prototype components and metabolites absorbed into the blood by comparing and analyzing with the LuMet-TCM database.RESULTS It showed that a total of 458 components were iden-tified in the aqueous extract of Suanzaoren Decoction,and 26 chemical components were identified in the blood,including 23 prototype components and 3 metabolites.CONCLUSION The prototype components absorbed into the blood discovered in this study may be the active ingredients of Suanzaoren Decoction,providing a reference for the research on the pharmacodynamic material basis of Suanza-oren Decoction.

Objective:To analyze the epidemiological characteristics and trends of preterm births in China using medical institution survey data, thereby providing epidemiological data support for perinatal care.Methods:Based on a nationwide sampling survey on healthcare quality data from 2017 to 2022, this study included 3 547, 4 436, 4 513, 4 535, 5 068, and 5 790 medical institutions, with 7 039 107, 8 926 441, 9 006 420, 7 051 984, 7 311 862, and 7 354 062 parturient women, respectively. The overall rates of preterm birth (live births at 28 to 36 +6 weeks of gestation/overall live births) and early preterm birth (live births at 28 to <34 weeks of gestation/overall live births) were calculated at the national level, across diverse provinces, autonomous regions, municipalities and Xinjiang Production and Construction Corps, and for various levels of medical institutions. Generalized estimating equations were used to analyze the influence of maternal characteristics and medical institution characteristics on the rates of preterm birth and early preterm birth. Results:From 2017 to 2022, both the preterm birth rate and the early preterm birth rate in China showed a continuous increase. The preterm birth rate rose from 5.13% (363 036/7 079 454) in 2017 to 6.56% (487 150/7 424 734) in 2022, and the early preterm birth rate increased from 1.32% (118 021/8 971 870) in 2018 to 1.43% (106 157/7 424 734) in 2022. These rates showed an overall increasing trend in private, secondary public specialty, and general hospitals. In tertiary public specialty hospitals, these rates fluctuated around 8.0% and 2.0% from the year 2018, respectively, while in tertiary public general hospitals, these rates peaked in 2020 at 8.63% (205 570/2 381 523) and 2.19% (52 197/2 381 523), respectively. Compared with 2017, by 2022, the preterm birth rate had increased to varying degrees in all provinces, autonomous regions, municipalities and Xinjiang Production and Construction Corps, except for Henan Province [preterm birth rate in 2017 was 6.22% (27 173/437 187); preterm birth rate in 2022 was 5.83% (37 604/645 104)]. As for the early preterm birth rate, it showed a decline in Fujian, Guangdong, Guangxi, Hainan, Henan, Jiangsu, Shanghai, Xinjiang, Yunnan, and Zhejiang, but had increased to varying degrees in all other provinces , autonomous regions, municipalities and Xinjiang Production and Construction Corps across the country. The grade and location of medical institutions both had a significant impact on the preterm birth rate and early preterm birth rate (both P<0.05). For every 1% increase in the proportions of multiparous women, women of advanced maternal age, or twin pregnancies, the preterm birth rate increased by 0.014%, 0.042%, and 0.763%, and the early preterm birth rate increased by 0.004%, 0.013%, and 0.239%, respectively (all P<0.05). Conclusion:From 2017 to 2022, the preterm birth rate and early preterm birth rate in China have continued to rise, reflecting the dual challenges of changing characteristics in the childbearing population and the uneven distribution of medical and health resources faced by maternal and child healthcare in China.

Objective To investigate stress distributions of the knee joint at 0 and 15th day after anterior cruciate ligament reconstruction(ACLR)under a compressive force through the axis of the femoral shaft onto the proximal femur.Methods A three-dimensional(3D)finite element model of the human knee joint incorporating viscoelastic material properties was developed.The one-dimensional(1D)Prony series viscoelastic constitutive model parameters for articular cartilage,menisci,ligaments,and anterior cruciate ligament(ACL)grafts were determined by fitting experimental creep curves.The viscoelastic parameters of ACL grafts at 15th day after ACLR surgery were extrapolated.Finite element simulations were then performed to analyze the von Mises stress distributions in knee ligaments,ACL grafts,articular cartilage,and menisci under 1.5 kN vertical downward compressive load applied to the femur,with loading durations of 1 second and 600 seconds.Results At 15th day after ACLR surgery,the initial relaxation modulus and equilibrium modulus of human ACL grafts remained elevated compared to native ACL tissues,resulting in a significantly higher stress concentration within the grafts relative to healthy ACL.Despite the compromised mechanical properties of the grafts after ACLR surgery,the vertical downward compressive force applied to the femur under both short-term(1s)and prolonged(600 s)loading durations,exhibited a minimal biomechanical impact on articular cartilage and meniscal structures.Conclusions Following ACLR,vertical compressive loads during weight-bearing rehabilitation exercises such as standing demonstrate minimal impact on articular cartilage and meniscus,while promoting fibrous regeneration of the graft.This renders such exercises a prudent early-stage rehabilitation strategy.Graft preparation requires balanced consideration of elastic and viscous properties,with grafts exhibiting higher relaxation modulus and viscosity coefficient than healthy ACL proving more effective in maintaining early postoperative knee stability.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.