Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

OBJECTIVE To explore the mechanism by which Cuscuta chinensis flavonoids （CCF） promote decidualization and improve recurrent spontaneous abortion （RSA）. METHODS HTR-8/SVneo cells in logarithmic growth phase were randomly divided into blank group， lipopolysaccharide （LPS） group， CCF group， SGK2 inhibitor （GSK650394， abbreviated as “GSK”） group and CCF+GSK group. Each group was treated with the corresponding agents accordingly. HTR-8/SVneo cells with SGK2 knockdown were randomly divided into small interfering RNA of SGK2 （siSGK2） group and siSGK2+CCF group； additionally， blank group and LPS group were established； each group was treated with the corresponding agents accordingly. The cell survival rate， expression levels of WNK signaling pathway- and decidualization-related proteins and mRNAs， as well as mitochondrial membrane potential levels， were assessed in each group before and after SGK2 knockdown. RSA mice model was constructed and randomly divided into model group， CCF low-dose group， CCF high-dose group， GSK group， and combined dosing group， with 4 mice in each group. Other 4 normal pregnant female mice were selected as the control group. The number of implanted embryos， viable fetuses， and lost embryos in mice was recorded. The morphological changes of endometrium and decidualization were observed， and WNK signaling pathway- and decidualization-related proteins and mRNAs expressing levels as well as mitochondrial membrane potential levels were all detected. RESULTS Compared with the blank group， the cell survival rate， as well as the protein and mRNA expression levels of SGK2， WNK1， WNK4， prolactin， insulin-like growth factor- binding protein-1， oxidative stress responsive kinase 1， and Ste20-like proline-/alanine-rich kinase were significantly reduced in the LPS group （P＜0.05）； compared with the LPS group， the cell survival rate and the expression levels of the above- mentioned proteins and mRNAs were significantly increased in the CCF group， while the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly decreased in the GSK group （P＜0.05）； compared with the CCF group， the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the CCF+GSK group （P＜0.05）. After knocking down SGK2， compared with the LPS group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the siSGK2 group （P＜0.05）； compared with the siSGK2 group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly increased in the siSGK2+CCF group （P＜0.05）. The in vivo experimental results showed that CCF treatment can significantly improve the number of implanted embryos and viable fetuses in RSA model mice and reduce lost embryos， the expression levels of the above-mentioned proteins and mRNAs in endometrial tissue were significantly increased， and the red/green fluorescence intensity ratio was significantly increased （P＜ 0.05）； the combined dosing group could reverse the effect of CCF （P＜0.05）. CONCLUSIONS CCF can activate SGK2， up- regulate the WNK signaling pathway， promote endometrial decidualization， and improve RSA.

Objective To investigate the immediate effect of early acupuncture and drug treatment on cerebral arterial blood flow and the degree of nerve damage in patients with acute ischemic stroke.Methods A total of 100 cases acute ischemic stroke patients treated in Quanzhou First Hospital Affiliated to Fujian Medical University were selected from June 2021 to June 2023,using clinical random number table method,the patients were divided into acupuncture treatment group(35 cases),non acupoint acupuncture group(32 cases),and conventional drug treatment group(33 cases).After admission to the hospital,all stroke patients were treated with conventional western medicine treatment,Both acupuncture treatment group and non acupoint acupuncture group received initial acupuncture treatment on the first day of enrollment without using drugs to improve circulation.Three groups of patients were treated continuously for 14 days,and their cerebral hemodynamic indicators before and after treatment were observed,including systolic peak velocity(Vs),diastolic peak velocity(Vd),pulsatile index(PI),resistance index(RI),and mean blood flow velocity(MFV).The levels of brain nerve injury markers in patients before and after treatment were measured,and the degree of neurological impairment were evaluated using National Institute of Health stroke scale(NIHSS).Results Compared with before treatment,the Vs and MFV levels of patients in conventional drug treatment group and non acupoint acupuncture group increased after treatment(P＜0.05),and PI decreased significantly compared with before treatment(P＜0.05);The levels of Vs,Vd,and MFV in acupuncture treatment group were all increased(P＜0.05);PI and RI decreased compared to before treatment(P＜0.05);After comparing the three treatment groups,the improvement of Vs,Vd,PI,RI,and MFV in acupuncture treatment group were better than those in non acupoint acupuncture group and conventional drug treatment group(P＜0.05).The Vs,Vd,PI,RI,and MFV of patients in the acupuncture treatment group improved after the first acupuncture,and the degree of improvement was better than that of the non acupoint acupuncture group(P＜0.05).After treatment in the three groups,the levels of serum S-100 β protein,heart-type fatty acid binding protein(H-FABP),and neuron specific enolase(NSE)were significantly reduced(P＜0.05),among which the index levels in acupuncture group were lower than those in the other two groups(P＜0.05),and the NIHSS score was lower in acupuncture group after 2 weeks of treatment and 30 days of follow-up compared with non acupoint acupuncture group and conventional drug treatment group(P＜0.05).Conclusion Early acupuncture treatment can improve the blood flow of the middle cerebral artery in patients with acute ischemic stroke and reduce the degree of nerve damage.

Background Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with various cancers, and recent studies suggest it may also increase the risk of retinoblastoma (RB) in newborns. However, the pathogenic mechanisms remain unclear. Objective By constructing an adverse outcome pathway (AOP) framework based on public databases to elucidate the potential mechanisms linking PFAS and RB. Methods Chemical-gene interactions and disease-gene interactions from the Comparative Toxicogenomics Database were retracted to identify key toxicological disruption pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) and a priori knowledge. The Pathview package in R was employed to predict molecular initiating events, key events, and their associated phenotypes, for further understanding the relevant gene-molecule interaction toxicity pathway network. Molecular docking techniques were utilized to validate the affinity of PFAS for these molecular initiating events. An AOP framework focused on toxicological pathways was developed using classical AOP methodologies. Results The PI3K-AKT/MAPK signaling pathway was identified as a potential toxicological pathway involved in PFAS-related RB development, based on KEGG and a priori knowledge. The activation of receptor tyrosine kinases (RTKs) served as the molecular initiating event, leading to the activation of key oncogenes such as RAS and AKT, as well as nuclear factor kappa-light chainenhancer of activated B cells (NF-κB), along with the inhibition of the tumor suppressor gene P53. In this study, 14 types of PFAS demonstrated good binding affinity with most RTKs, with chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) showing particularly favorable predicted binding. Oncogenes, including the c-kit-encoded tyrosine kinase receptor for stem cell factor, epidermal growth factor receptor, and neurotrophic tyrosine kinase receptor 1, were identified as the receptors with the best predicted binding affinity. Conclusion The PI3K-AKT/MAPK signaling pathway may serve as a potential toxicological mechanism linking PFAS to an increased risk of RB.

Objective:To discuss the effects of walking function-guided interactive Tuina(Chinese therapeutic massage)on spatiotemporal gait parameters in children with spastic cerebral palsy(CP). Methods:Fifty children with spastic diplegic CP were divided into an observation group and a control group following a paired design and random number principle,with 25 cases in each group.The observation group was treated with the walking function-guided interactive Tuina,and the control group was offered the"six methods of spine and back"Tuina,20 min for each session and 5 sessions weekly for 3 consecutive months.The children's changes were assessed using the percentage of dimension E(walking,running,and jumping)of the gross motor function measure-88(GMFM-88)and three-dimensional gait analysis. Results:After treatment,the percentage of GMFM-88 dimension of dimension E(walking,running,and jumping)changed significantly in both groups(P<0.05),and the between-group difference was also statistically significant(P<0.05).After treatment,the step length,walking speed,and step frequency changed markedly in the observation group(P<0.05)and were significantly different from those in the control group(P<0.05).After the intervention,the stance phase and double support extended,and the swing phase became shorter in the observation group(P<0.05);the between-group differences were statistically significant(P<0.05).The maximal knee flexion angle and maximal posterior pelvic tilt angle decreased After treatment in the observation group,and the maximal anterior pelvic tilt angle increased,all showing statistical significance(P<0.05);the between-group differences were statistically significant(P<0.05). Conclusion:Compared with the passive Tuina manipulations,the"six methods of the spine and back",walking function-guided interactive Tuina has its advantage in improving walking function in children with spastic CP,manifesting as better lower-limb force line and walking efficiency.

This study utilized the CCK-8 assay to examine the effects of various concentrations of CoCl2(0,50,100,200,300,400 μmol/L)and different treatment durations(0,6,12,24,48 h)on the viability of adipocytes,in order to determine the most suitable treatment conditions.Western blot analysis was employed to investigate the impact of different concentrations of CoCl2(0,50,100,200,400 μmol/L)on the expression of hypoxia and its downstream key proteins in adipocytes.The results indicated that higher concentrations of CoCl2 led to lower adipocyte viability,with sig-nificant decreases in cell viability observed in the 300,400 μmol/L treatment groups(P＜0.01),while the 200 μmol/L group exhibited the highest cell viability.Compared to the control group,the 200 μmol/L CoCl2 treatment group showed a significant upregulation in the expression of hypoxia and its downstream signaling pathway key molecules:hypoxia-inducible factor 1-alpha(HIF-1α),glucose transporter type 4(GLUT4),vascular endothelial growth factor receptor 1(FLT-1),prolyl hydroxylase 2(PHD2),and vascular endothelial growth factor(VEGF)(P＜0.01).Addi-tionally,the 200 μmol/L CoCl2 treatment group exhibited higher levels of key lipolytic enzymes,including adipose triglyceride lipase(ATGL),perilipin 1(PLIN1),protein kinase A(PKA),and increased phosphorylation levels of hormone-sensitive lipase(HSL)in the 300 and 400 μmol/L groui ps(P＜0.01).CoCl2-mediated hypoxia in the 200 μmol/L treatment group also in-creased the protein expression of phosphatidylinositol 3-kinase(PI3K)and the phosphorylation level of protein kinase B(Akt).These findings suggest that adding 200 μmol/L CoCl2 can enhance the expression of hypoxia-related proteins,lipolytic enzymes,and insulin-related signaling proteins in primary bovine adipocytes.

Humans ; Asthma/drug therapy* ; Biological Therapy