This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Objective To explore the relationship between plantar fascia stiffness and windlass mechanism and their impact on the arch,and provide a biomechanical mechanism explanation for plantar fascia and arch-related diseases.Methods A foot-plate model with 30° flexion angle at the metatarsophalangeal joint was constructed.The musculoskeletal model combined with the three-dimensional finite element analysis method was used,and the dynamic data of the foot during walking at the speed of 5 km/h was obtained using dual fluoroscopic imaging system(DFIS).The finite element model was verified,and the influence of plantar fascia stiffness on the capstan mechanism and arch-related mechanical parameters was explored.Results The finite element simulation analysis results were highly consistent with the foot data obtained by DFIS,confirming the validity of the model.With the increase of plantar fascia stiffness,the windlass effect and the stiffness of the longitudinal arch of the foot both showed an increasing trend,but the flexion angle of the metatarsophalangeal joint decreased,the distal stress of the plantar fascia gradually decreased,and the proximal stress increased;when the plantar fascia stiffness was 25％-150％,the width of the transverse arch of the foot increased with the increase of plantar fascia stiffness,while the height of the transverse arch decreased with the increase of plantar fascia stiffness;when the plantar fascia stiffness was 150％-200％,the width of the transverse arch of the foot decreased,the height increased,and the stiffness also increased.Conclusions An increase in plantar fascia stiffness can enhance the windlass mechanism to some extent,but it also leads to a reduction in metatarsophalangeal joint flexion.The stiffness of the plantar fascia affects the metatarsophalangeal joint flexion,thereby impacting the windlass mechanism and the distal tensile force of the plantar fascia.Together with the ground reaction force at the distal end of the metatarsals,these factors collectively influence the stiffness of the transverse arch of the foot.

Objective To explore the distribution patterns of traditional Chinese medicine(TCM)syndromes in patients with metabolic syndrome caused by antipsychotic drugs.Methods A standardized TCM syndrome survey was performed to collect diagnostic information from 160 patients diagnosed with metabolic syndrome due to antipsychotic drug use.Subsequent frequency analysis,cluster analysis,and Bayesian network analysis were carried out.The syndrome pattern distribution was ultimately determined through relevant literatures and expert opinions.Results Five TCM syndromes were identified through frequency,cluster,and Bayesian network analyses.The most common syndrome was qi deficiency with phlegm-dampness(30％),followed by spleen deficiency with phlegm-Heat(23.75％),qi and yin deficiency Pattern(21.88％),yin deficiency with damp-heat(17.50％),and stomach fire hyperactivity pattern(6.88％).Conclusion The pathogenesis of antipsychotics-induced metabolic syndrome involves a complex interplay of deficiency and excess factors.The primary disease is mainly located at the spleen and stomach,with involvement of the liver,kidney,and heart.Pathogenic factors include qi deficiency,yin deficiency,dampness,heat,pathogenic fire,and phlegm.

Objective To explore the relationship between plantar fascia stiffness and windlass mechanism and their impact on the arch,and provide a biomechanical mechanism explanation for plantar fascia and arch-related diseases.Methods A foot-plate model with 30° flexion angle at the metatarsophalangeal joint was constructed.The musculoskeletal model combined with the three-dimensional finite element analysis method was used,and the dynamic data of the foot during walking at the speed of 5 km/h was obtained using dual fluoroscopic imaging system(DFIS).The finite element model was verified,and the influence of plantar fascia stiffness on the capstan mechanism and arch-related mechanical parameters was explored.Results The finite element simulation analysis results were highly consistent with the foot data obtained by DFIS,confirming the validity of the model.With the increase of plantar fascia stiffness,the windlass effect and the stiffness of the longitudinal arch of the foot both showed an increasing trend,but the flexion angle of the metatarsophalangeal joint decreased,the distal stress of the plantar fascia gradually decreased,and the proximal stress increased;when the plantar fascia stiffness was 25％-150％,the width of the transverse arch of the foot increased with the increase of plantar fascia stiffness,while the height of the transverse arch decreased with the increase of plantar fascia stiffness;when the plantar fascia stiffness was 150％-200％,the width of the transverse arch of the foot decreased,the height increased,and the stiffness also increased.Conclusions An increase in plantar fascia stiffness can enhance the windlass mechanism to some extent,but it also leads to a reduction in metatarsophalangeal joint flexion.The stiffness of the plantar fascia affects the metatarsophalangeal joint flexion,thereby impacting the windlass mechanism and the distal tensile force of the plantar fascia.Together with the ground reaction force at the distal end of the metatarsals,these factors collectively influence the stiffness of the transverse arch of the foot.

Objective To explore the distribution patterns of traditional Chinese medicine(TCM)syndromes in patients with metabolic syndrome caused by antipsychotic drugs.Methods A standardized TCM syndrome survey was performed to collect diagnostic information from 160 patients diagnosed with metabolic syndrome due to antipsychotic drug use.Subsequent frequency analysis,cluster analysis,and Bayesian network analysis were carried out.The syndrome pattern distribution was ultimately determined through relevant literatures and expert opinions.Results Five TCM syndromes were identified through frequency,cluster,and Bayesian network analyses.The most common syndrome was qi deficiency with phlegm-dampness(30％),followed by spleen deficiency with phlegm-Heat(23.75％),qi and yin deficiency Pattern(21.88％),yin deficiency with damp-heat(17.50％),and stomach fire hyperactivity pattern(6.88％).Conclusion The pathogenesis of antipsychotics-induced metabolic syndrome involves a complex interplay of deficiency and excess factors.The primary disease is mainly located at the spleen and stomach,with involvement of the liver,kidney,and heart.Pathogenic factors include qi deficiency,yin deficiency,dampness,heat,pathogenic fire,and phlegm.

Abstract Child abuse is a global public health problem, which has emerged as a neglected yet pressing issue in global development. Early and accurate identification of abuse at a lower-age group is of great significance for treatment, which might reduce the risk of re-maltreatment and promote children s physical and mental health development. Therefore, by reviewing the clinical characteristics, risk factors and existing abuse identification and screening tools of child abuse, the study aims at providing basic evidence for the development of child abuse risk identification tools and the establishment of child maltreatment system in China, so as to take timely intervention measures to prevent adverse outcomes or reduce their severity.