Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.

Objective To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone(ROT)-induced Parkinson's disease(PD)model mouse.Methods SPF C57BL/6 mice were randomly divided into 6 groups,including control group,solvent control group,ROT model group,ACT001 5 mg/kg group(ROT+ACT001-5),ACT001 20 mg/kg group(ROT+ACT001-20),and levodopa(L-dopa)positive control group(ROT+L-dopa),with 9 mice in each group.The control group received an equivalent amount of intraperitoneal injection of saline,the solvent control group received an equivalent amount of rotenone solvent without rotenone,the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone.Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001,while the positive control group received levodopa intraperitoneally for 15 consecutive days.Behavioral changes in mice were assessed using open field,rotarod,pole-climbing,and balance beam tests.Immunofluorescence(IF)assay to detect the expression of tyrosine hydroxylase(TH)neurons,content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain;Real-time PCR was employed to measure the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)in the substantia nigra of the mouse brain.Western blotting was used to measure the protein levels of TH,nuclear factor-κB(NF-κB)p65,NF-κB inhibitor α(IκBα),and phosphorylated IκBα(p-IκBα)in the substantia nigra of the mouse brain.Results Compared to the control group and the solvent control group,the rotenone-induced PD model group exhibited motor impairments in behavioral tests,a decrease in the number of TH positive neurons in the substantia nigra(P＜0.0001),decreased levels of TH-positive fibers in the striatum,activation of midbrain substantia microglia,and elevated levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 expression.ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice,increased the number of TH-positive neurons in the substantia nigra,increased levels of TH-positive fibers in the striatum,inhibition of microglial cell activation in the midbrain substantia nigra,and elevated the protein expression levels of IκBα while reducing the levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 in the substantia nigra(P＜0.05).At a dose of 5 mg/kg,ACT001 significantly improved behavioral impairments in rotenone-induced PD mice,reduced the loss of dopaminergic neurons,and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the suppression of inflammation.In summary,the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain,increased the number of TH-positive neurons,and augmented the population of dopaminergic neurons in the substantia nigra,exerting a protective effect on neurons.Conclusion ACT001 significantly improves behavioral deficits in ROT-induced PD mice,ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum,inhibits the activation of nigrostriatal microglia in the midbrain,and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway.

Objective To investigate the effects of remimazolam(REM)on cerebral ischemia-reperfusion injury(CIRI)rats and the AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods One hundred rats were selected to construct the CIRI rat model(Mod)and stochastically separated into a Mod group,low,medium,and high dose remifentanil groups(REM-L,REM-M,REM-H),and high dose remifentanil+pathway inhibitor Compound C group(REM-H+Compound C),with 20 rats in each group.Another 20 healthy rats were included as the control(Ctrl)group.All rats were subjected to neurobehavioral scoring.The water content,infarct area,and oxidative stress indicators of brain tissue were detected.The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining.Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway.Results Compared with the Mod group,with the increase of REM dose,the movement disorders in rats were alleviated,the overall structure of brain tissue gradually recovered,pathological damage was reduced,the area of cerebral infarction,brain water content,and apoptosis rate of brain tissue cells decreased,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,and NLRP3 and Caspase-1 protein expression levels decreased,superoxide dismutase the(SOD)content and AMPK protein expression level increased(P＜0.05).Compared with the REM-H group,the REM-H+Compound C group showed aggravated motor disorders,and more severe pathological damage to brain tissue,the area of cerebral infarction,cerebral water content and apoptosis rate of brain tissue cells increased,the ROS level,MDA content and the protein expression of NLRP3 and Caspase-1 increased,while the content of SOD and the protein expression decreased(P＜0.05).Conclusion Remimazolam can enhance the antioxidant function of the body,reduce brain cell apoptosis,alleviate brain tissue injury,and thus have a certain protective effect on ischemia-reperfusion brain injury in rats,the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Objective To analyze the research status and hotspots in the field of astragalus polysaccharides;To provide references for further research.Methods Research literature about astragalus polysaccharides was retrieved from CNKI,Wanfang Data,VIP,PubMed,and Web of Science databases from 1st,Jan.2013 to 1st,July 2023.NoteExpress 3.7 software was used to manage the literature and ultimately establish a database.Excel 2019,CiteSpace 6.2.2R and VOSviewer 1.6.18 were used to visually analyze the publication volume,authors,institutions,and keywords of the included literature.Results A total of 2 462 articles were included,with 1 284 Chinese articles and 1 178 English articles.The main research institutions were Gansu University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,and Beijing University of Chinese Medicine.The core authors of Chinese literature were Liu Yongqi,Wang Hongxin,Lu Meili,etc.The core authors of English literature included Zhang Wei,Li Ke,Yang Xiaojun,etc.High-frequency keywords of Chinese literature included Astragali Radix,rats,polysaccharides,cell apoptosis,and oxidative stress,etc.High frequency keywords in English literature included expression,in vitro,oxidative stress,apoptosis,etc.Conclusion The research on astragalus polysaccharides focuses on their pharmacological effects and mechanisms.Intestinal flora,immune regulation,autophagy and apoptosis are the hot action mechanisms in this field.The focus of disease research involves tumor and diabetes,and antiviral,anti infection and other pharmacological effects are the research trend.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To analyze the characteristics of healthcare-associated infection(HAI)in patients in liver transplantation intensive care unit(ICU),and provide basis for the effective prevention and control of liver post-transplantation infection.Methods Targeted surveillance data of HAI in liver transplantation ICU from 2018 to 2022 were analyzed retrospectively.Incidence,incidence trend,infection site,pathogens and drug resistance were analyzed.Results A total of 3 762 liver transplantation patients were surveilled,106 patients developed 133 cases of HAI,with an incidence of 2.82％and a case incidence of 3.54％.There was no significant difference among the years(P=0.473).Infection mainly occurred within 2 weeks after admission to ICU,accounting for 85.85％.The main infection sites included blood system(26.32％),respiratory system(22.56％),and surgical site(19.55％).The average utilization rates of central veinous catheterization,urethral catheterization,and ventilator were 85.77％,70.58％,and 40.83％,respectively.The incidences of central line-associated bloodstream infection(CLABSI),catheter-associated urinary tract infection(CAUTI),and ventilator-associated pneumonia(VAP)were 0.54‰,0.33‰,and 1.84‰,respectively.A total of 131 strains of pathogens were detected,of which Gram-negative bac-teria accounted for 38.17％and Gram-positive bacteria accounted for 29.77％.The top three pathogens were Kleb-siella pneumoniae(15.27％),Enterococcus faecium(11.45％),and Acinetobacter baumannii(9.16％).Conclusion Effective prevention and control measures should be taken based on the characteristics of HAI in the liver transplan-tation ICU,so as to curb bacterial resistance and reduce liver post-transplantation HAI.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.