BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

BACKGROUND:Fracture healing is a very complex physiological process,which is influenced by many factors.In recent years,the use of biomechanical factors in fracture healing has been a major focus in the field of orthopedics,and the mechanical stress environment around the fracture end has an important role in regulating fracture healing.Among them,the study of the mechanism of compressive mechanics on the cytokines of fracture ends is a hot spot for bone-related researchers.OBJECTIVE:To summarize the current status and recent advances in the study of the mechanism of action of compressive stress on cytokines in fracture healing in recent years.METHODS:A search with the keywords of"compressive stress,fracture healing,cytokine,bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,tumor necrosis factor-α"in Chinese and English was conducted in the CNKI,WanFang,PubMed,and Web of Science.Initially 506 articles were retrieved,and 94 eligible articles that met the criteria were screened and finally summarized.RESULTS AND CONCLUSION:Current studies have found that compressive stress has different effects on different cytokines during fracture healing,which can be achieved mainly by influencing cell signaling,gene expression regulation,and modulation of cell behavior.Among them,compressive stress can be linked to cytokines such as bone morphogenetic protein,fibroblast growth factor,platelet-derived growth factor,vascular endothelial growth factor,interleukin,and tumor necrosis factor-α.This process involves cell proliferation,differentiation and migration,inflammatory response,and changes in the environmental and nutritional conditions of the fracture end,which are key factors affecting fracture healing.The whole paper summarizes the complexity of cytokine action mechanism,the mechanism of compressive stress on its regulation needs to be further carried out in-depth research,and the problems and limitations in the research are considered and future prospects.

ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

Pre-admission is a critical initiative to optimize medical service processes and alleviate the challenge of "difficult access to healthcare. "However, there is currently a lack of standardized protocols for pre-admission procedures. This study aims to systematically analyze key nodes and risk factors in pre-admission process design and propose optimization strategies, providing a foundation for policy formulation and hospital practices. By constructing a "forward-reverse" dual-process model of pre-admission and identifying risk points based on stakeholder theory (patients, hospitals, healthcare administration, and insurance), the study reveals that while pre-admission can reduce the average length of stay, improve bed turnover rates, and enhance patient satisfaction, it also presents risks such as cross-period financial settlement, challenges in insurance policy adaptability, demands for information system integration, and the need for defining medical safety boundaries. To optimize the pre-admission process and mitigate these risks, this study explores framework improvements in areas including eligibility criteria, mode selection, cost settlement, transition between pre-admission and inpatient status, and cancellation of pre-admission, offering practical guidance for public hospitals. The authors argue that pre-admission requires tripartite collaboration among hospitals, insurers, and healthcare administrations: hospitals should establish top-level design, continuously refine processes, and implement dynamic risk assessment mechanisms; insurance providers should support cross-period settlement policies; and healthcare administrations should issue guiding policies or standardized protocols. Through multi-department coordination and collaborative efforts, the optimization and innovation of pre-admission processes can be advanced, ultimately delivering more efficient and convenient healthcare experiences for patients.

Objectives:This study aims to investigate the incidence,characteristics and clinical outcomes of vagal response(VR)during pulmonary vein isolation(PVI).Methods:A total of 702 patients with nonvalvular atrial fibrillation(AF)who received the first PVI radiofrequency ablation in Central China Fuwai Hospital from January 2022 to December 2023 were consecutively enrolled.PVI was initiated from right superior pulmonary vein(RSPV),followed by other pulmonary veins(PVs).The VR was defined as atrioventricular block(AVB),asystole or a 50%increase in the RR interval.Results:Among 702 patients with AF,380 patients(54.1%)were paroxysmal AF and 322 patients(45.9%)were persistent AF.77 patients(11.0%)developed 81 VR episodes,which were more common in paroxysmal group than in persistent AF group(19.5%vs.0.9%,P<0.001).VR manifestations included 51 sinus arrest(63.0%),26 sinus bradycardia(32.1%),and 4 atrioventricular block(AVB,4.9%).Most VR episodes were observed in the left superior ganglionated plexi(67[82.7%]).Paroxysmal AF(OR=18.667,95%CI:6.638-52.491,P<0.001),body mass index(BMI)≥28.0 kg/m2(OR=2.361,95%CI:1.376-4.051,P=0.002)and left ventricular ejection fraction(LVEF)≥62.0%(OR=1.964,95%CI:1.119-3.447,P=0.019)were independent risk factors of VR.During a mean of(13.0±7.1)months follow up,among paroxysmal AF patients,6 patients(8.1%)with VR and 33 patients(10.8%)without VR experienced AF recurrence(P=0.496).Kaplan-Meier curves estimated that the AF-free survival rate was similar between VR group and non-VR group among paroxysmal AF patients(log-rank P=0.735).Conclusions:The most common sites of VR when initiating PVI from right RSPV occur in left superior ganglionated plexi.Paroxysmal AF,BMI≥28.0 kg/m2 and LVEF≥62.0%are independent risk factors of VR.VR does not affect AF-free survival.

Anxiety is a major emotional disorder manifested in the individual's expectation of future threats.The incidence rate of anxiety is about 7.3％,with the highest lifetime prevalence rate among mental health conditions.The mechanism of anxiety overlaps with depression,and anxiety is a typical symptom of various mental diseases or emotional disorders in traditional Chinese medicine.The high rates of comorbidity and disability pose serious threats to people's health.Animal models are important tools for studying anxiety and are of great use for deciphering the pathogenesis of anxiety and for developing drugs.The traditional paradigm of stress-induced anxiety,however,is relatively limited.Based on traditional theory combined with clinical and animal experimental data,we propose a new hypothesis of"insufficiency of ZhiYi'causing anxiety,defined as"an anxiety state induced by the inability of an individual to meet their own needs,limited or lacking after multiple attempts,rendered hindered and powerless by an inability to meet their desires".This hypothesis is more in line with the typical manifestations of despair,lack of pleasure,and social withdrawal in clinical patients,and is supported by traditional theory and experimental data showing"hunger but unable to eat,food but unable to obtain,and gain but not full".Based on this,the established modeling paradigm is easy to apply,with good repeatability and low cost,and can be used to establish anxiety models in rats and mice,to provide a theoretical and model basis for the development and pharmacological evaluation of anti-anxiety drugs.

Objective:To determine whether the Rb1 of ginsenoside has protective effects on PA induced oxidative stress in endothelial cells.Methods:Established a model of palmitic acid-induced oxidative stress injury in human umbilical vein endothelial cells(HUVECs).Using MTT assay,flow cytometry,fluorescent probe staining,and Western blot analysis to detect whether Rb1 of ginsenoside has effects on the cell viability,apoptosis rate,ROS and NO production,mitochondrial membrane potential,and the expression levels of related proteins.Results:MTT assay and flow cytometry revealed that ginsenoside Rb1 can reduce PA-induced apoptosis in HUVECs(P＜0.05).The mechanism may be related to the following two points:(1)reducing ROS production and increasing NO levels,thereby enhancing the antioxidant capacity of HUVECs;(2)regulating the expression of Bcl-2 family proteins,increasing the BCL-2/Bax ratio(P＜0.05),modulating mitochondrial membrane permeability,reducing cytochrome C release(P＜0.001),and decreasing Caspase protein activation(P＜0.01),thereby attenuating PA-induced apoptosis.Conclusion:After the stimulation with PA,ROS production in human umbilical vein endothelial cells increased while NO content and cell activity decreased,oxidative stress induced apoptosis in cells.By regulating the production of ROS and NOx stabilizing the mitochondrial transmembrane potential,reducing the leakage of cytochrome C,Ginsenoside Rb1 can reduce HUVECs apoptosis induced by PA.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.