Based on the theory of collateral disease， the treatment of late-stage sequela of cerebrovascular disease is considered to be primarily associated with deficiency and obstruction of cerebral collaterals and dysfunction of the spirit mechanism. Therefore， the fundamental therapeutic principle is to unblock and supplement the brain collaterals. Clinically， the late-stage sequelae of cerebrovascular disease are classified into four patterns， which are malnourishment， deficiency-heat， stasis obstruction， and phlegm clouding of brain collaterals. These are treated respectively with Tiansui Tongqiao Decoction （填髓通窍汤） to supplement essence and nourish the brain through moistening， unblocking and supplementing， Qingnao Touluo Decoction （清脑透络汤） to enrich yin， regulate spirit， and unblock collaterals through clearing and penetrating， Yiqi Tongluo Decoction （益气通络汤） to tonify qi and resolve stasis while softening tendons and unblocking collaterals， and Xinrun Touqiao Beverage （辛润透窍饮） to unblock and tonify yin and yang while unblocking the collaterals through acrid-moistening medicinals. Flexible modification of prescriptions according to individual symptoms was applied， resulting in favorable therapeutic outcomes.

Objective To investigate the correlation between levels of intercellular adhesion molecule-1 (ICAM-1), platelet surface P-selectin (CD62P), and inflammatory factors and cerebral artery stenosis in patients with acute cerebral infarction (ACI). Methods A total of 305 patients with ACI complicated with cerebral artery stenosis admitted to Zhongwu Hospital of Suqian City and Xinyi People's Hospital from January 2021 to December 2023 were selected as the research subjects. According to the degree of cerebral artery stenosis, they were divided into grade I group (stenosis degree<50%, n=85), grade II group (stenosis degree of 50%-75%, n=128), and grade III group (stenosis degree>75%, n=92). Sixty-eight ACI patients without cerebral artery stenosis during the same period were included in the reference group. The levels of serum inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8)], ICAM-1 and CD62P were compared among the four groups. Spearman analysis was used to analyze the correlation between each factor and degree of cerebral artery stenosis. Results The levels of CRP, TNF-α, IL-6, IL-8, ICAM-1 and CD62P in the grade I, II and III groups were higher than those in the reference group. The levels of these factors were higher in the grade II and III groups than those in the grade I group, while the levels of various factors were higher in the grade III group than those in the grade II group (P<0.05). Spearman analysis showed that CRP, TNF-α, IL-6, IL-8, ICAM-1, and CD62P were positively correlated with the degree of cerebral artery stenosis in patients with ACI complicated with cerebral artery stenosis (P<0.05). Conclusion The levels of serum inflammatory factors, ICAM-1 and CD62P are significantly correlated with cerebral artery stenosis degree in patients with ACI.

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Objective:To investigate the expression of protein kinase D2(PRKD2)in bladder cancer(BLCA)tissue using bioinformatics analysis method and its effect on the prognosis of BLCA patients,and to clarify the role of PRKD2 in the occurrence and development of BLCA.Methods:The data from 9 normal bladder samples,19 BLCA paracancerous samples,and 407 BLCA tumor samples were downloaded from the UCSC Cancer Genome Database.The Mann-Whitney U test was applied to analyze the difference in expression of PRKD2 mRNA in BLCA tumor and normal bladder tissues,and the Human Protein Atlas(HPA)database was used for proteomic validation.DESeq2 package in R software was applied to screen the differentially expressed genes(DEGs)in BLCA tissue in PRKD2 low-and high-expression groups.The co-expression heatmaps of PRKD2 were plotted using the ggplot2 package,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation analysis and pathway enrichment analysis of DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the gene sets that were significantly enriched for DEGs.The BLCA samples were divided into low-and high-expression groups according to the expression level of PRKD2,and the correlations between PRKD2 expression and immune cell infiltration in the BLCA patients were analyzed with GSVA package.The relationship between PRKD2 and prognosis of BLCA patients was further analyzed using the survival package and the survminer package.The PRKD2 gene mutations in BLCA tissue were analyzed using the cBioPortal database.The cystitis,bladder polyp and BLCA tissues were collected,and the expression levels of interleukin-17F(IL-17F)protein in BLCA and control tissues were detected using immunohistochemical staining technique.Results:PRKD2 was highly expressed in a variety of malignant tumors,and the expression levels of PRKD2 mRNA and protein in BLCA tissue were significantly increased compared with those in normal bladder tissue(P＜0.05).Single gene differential analysis of PRKD2 yielded a total of 1 058 DEGs,of which a total of 29 genes were up-regulated and 1 029 were down-regulated.The results of GO functional enrichment analysis showed that DEGs were mainly enriched in the biological process(BP),such as chemical stimuli involved in sensory perception,Cajal body,and endopeptidase inhibitor activity.The results of KEGG pathway analysis showed that DEGs were mainly enriched in the pathway of Staphylococcus aureus infection and the pathway of maturity onset diabetes of the young.GSEA analysis showed that DEGs were mainly enriched in the Notch signaling pathway,the retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ)-like receptor signaling pathway,the cytoplasmic DNA screening pathway,the base excision repair signaling pathway,natural killer(NK)cell-mediated cytotoxicity signaling pathway and T cell receptor signaling pathway.The results of immune infiltration analysis indicated that the expression of PRKD2 was positively correlated with five types of cells,such as activated dendritic cells(aDC),NK CD56dim cells and central memory T cells(Tcm)(P＜0.05),and negatively correlated with three types of immune cells,including macrophages,effector memory T cells(Tem)and plasmacytoid dendritic cells(pDC)(P＜0.05).The clinical characteristic subgroup analysis results showed that the expression levels of PRKD2 mRNA in BLCA patients who were over 70 years old and developed lymphovascular invasion were decreased(P＜0.05);the overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in the BLCA patients with PRKD2 high expression were significantly longer than those with PRKD2 low expression(P＜0.05).The univariate and multivariate Cox analyses indicated that distant metastasis,primary therapy outcome and clinicopathologic stage were the important factors affecting BLCA prognosis.About 9％patients had PRKD2 gene mutations,including missense mutation,gene amplification,mRNA low or high expression,and multi-motif mutation.The immunohistochemistry results showed that the expression level of IL-17F protein in BLCA tissue was significantly higher than that in cystitis tissue(P＜0.05).Conclusion:The expression level of PRKD2 in BLCA tissue is obviously increased,which could up-regulate the expression of IL-17F protein,and the decrease of PRKD2 protein expression may be a potential factor for the poor prognosis of BLCA patients.

Objective:To predict the monthly incidence of hemorrhagic fever with renal syndrome (HFRS) in Hebei Province by using the generalized additive model (GAM).Methods:The incidence data of HFRS in Hebei from 2006 to 2020 were collected, and the correlation coefficients between meteorological factors and the monthly incidence of HFRS in Hebei were analyzed by Spearman's correlation, and the meteorological factors were lagged by 0-6 orders, and those with the largest absolute values of the correlation coefficients were screened to be included in the multifactorial GAM to evaluate the effects of meteorological factors.Results:The monthly incidence of HFRS had the strongest correlation with monthly mean air temperature at lag order 2, monthly mean wind speed at lag order 0, monthly mean sunshine at lag order 4, monthly mean precipitation at lag order 2 and monthly mean humidity at lag order 1, which were diagnosed by the variance inflation factor and included in the multifactorial GAM, and the results showed significant differences among the factors (all P<0.001), and they showed non-linear relationships with the monthly incidence of HFRS. Mean monthly temperature was an important factor influencing HFRS incidence. Mean monthly air temperature, mean monthly sunshine and mean monthly wind speed were negatively associated with HFRS incidence, whereas mean monthly precipitation and mean monthly humidity were positively associated with HFRS incidence. Conclusions:There was a complex non-linear relationship between meteorological factors and the incidence of HFRS. GAM incorporated with lagged meteorological factors can be used to predict the incidence of HFRS in Hebei.

Objective:To predict the monthly incidence of hemorrhagic fever with renal syndrome (HFRS) in Hebei Province by using the generalized additive model (GAM).Methods:The incidence data of HFRS in Hebei from 2006 to 2020 were collected, and the correlation coefficients between meteorological factors and the monthly incidence of HFRS in Hebei were analyzed by Spearman's correlation, and the meteorological factors were lagged by 0-6 orders, and those with the largest absolute values of the correlation coefficients were screened to be included in the multifactorial GAM to evaluate the effects of meteorological factors.Results:The monthly incidence of HFRS had the strongest correlation with monthly mean air temperature at lag order 2, monthly mean wind speed at lag order 0, monthly mean sunshine at lag order 4, monthly mean precipitation at lag order 2 and monthly mean humidity at lag order 1, which were diagnosed by the variance inflation factor and included in the multifactorial GAM, and the results showed significant differences among the factors (all P<0.001), and they showed non-linear relationships with the monthly incidence of HFRS. Mean monthly temperature was an important factor influencing HFRS incidence. Mean monthly air temperature, mean monthly sunshine and mean monthly wind speed were negatively associated with HFRS incidence, whereas mean monthly precipitation and mean monthly humidity were positively associated with HFRS incidence. Conclusions:There was a complex non-linear relationship between meteorological factors and the incidence of HFRS. GAM incorporated with lagged meteorological factors can be used to predict the incidence of HFRS in Hebei.

Objectives:To investigate the relationship between QRS duration and its changes during hospitalization and long-term all-cause mortality in patients with chronic heart failure.Methods:A total of 3 580 patients who attended three tertiary hospitals in Shanxi Province(First Hospital of Shanxi Medical University,Shanxi Cardiovascular Hospital,Shanxi Bethune Hospital)and were diagnosed with chronic heart failure from March 2014 to November 2021,were enrolled in this study.QRS duration at admission and discharge were collected,and the changes in QRS duration during hospitalization(ΔQRS)and the ΔQRS ratio(ΔQRS/admission QRS duration×100% )were calculated.Patients were divided into three group according to tertiles of ΔQRS:the group with decreasing QRS duration(n=1 364),the group with stable QRS duration(n=1 248),and the group with progressing QRS duration(n=968).Telephone follow-up was conducted at months 1,3,6,12,and every 6 months thereafter after discharge till May 1,2023,long-term all-cause mortality was the primary endpoint.Survival curves were plotted using the Kaplan-Meier method,and comparisons between groups were made using the log-rank method.Cox proportional risk regression model was used for prognostic analysis,and restricted cubic spline curves were calculated to evaluate QRS duration-related variables during hospitalization and the risk of long-term all-cause mortality in patients with chronic heart failure.Results:The median follow-up was 71(56,92)months,and all-cause mortality occurred in 502(14.0% )patients.Long-term all-cause mortality was lower in the group with decreasing QRS duration and the group with stable QRS duration compared with the progressing QRS duration group(13.9% vs.10.7% vs.18.6%,χ2=28.607,P<0.001).Multifactorial Cox regression analysis showed that admission QRS duration(HR=1.005,95% CI:1.002-1.009,P=0.003)and higher ΔQRS ratio during hospitalization(HR=2.071,95% CI:1.247-3.440,P=0.005)were independent influencing factors of long-term all-cause mortality in chronic heart failure patients.Restricted cubic spline curves showed that when the admission QRS duration was>96.36 ms,the longer the QRS duration,the higher the risk of all-cause mortality;when the admission QRS duration fluctuated from 89.32-96.36 ms,the QRS duration was a protective factor for long-term all-cause mortality in patients with chronic heart failure;and when the ΔQRS ratio during hospitalization was≥3.40%,higher ΔQRS ratio was linked with increased risk of all-cause mortality.Conclusions:QRS duration and ΔQRS ratio during hospitalization are independent predictors of long-term all-cause mortality in patients with chronic heart failure.Admission QRS duration>96.36 ms and ΔQRS ratio during hospitalization≥3.40% are associated with increased risk of long-term all-cause mortality in patients with chronic heart failure.

Objectives:To investigate the relationship between QRS duration and its changes during hospitalization and long-term all-cause mortality in patients with chronic heart failure.Methods:A total of 3 580 patients who attended three tertiary hospitals in Shanxi Province(First Hospital of Shanxi Medical University,Shanxi Cardiovascular Hospital,Shanxi Bethune Hospital)and were diagnosed with chronic heart failure from March 2014 to November 2021,were enrolled in this study.QRS duration at admission and discharge were collected,and the changes in QRS duration during hospitalization(ΔQRS)and the ΔQRS ratio(ΔQRS/admission QRS duration×100% )were calculated.Patients were divided into three group according to tertiles of ΔQRS:the group with decreasing QRS duration(n=1 364),the group with stable QRS duration(n=1 248),and the group with progressing QRS duration(n=968).Telephone follow-up was conducted at months 1,3,6,12,and every 6 months thereafter after discharge till May 1,2023,long-term all-cause mortality was the primary endpoint.Survival curves were plotted using the Kaplan-Meier method,and comparisons between groups were made using the log-rank method.Cox proportional risk regression model was used for prognostic analysis,and restricted cubic spline curves were calculated to evaluate QRS duration-related variables during hospitalization and the risk of long-term all-cause mortality in patients with chronic heart failure.Results:The median follow-up was 71(56,92)months,and all-cause mortality occurred in 502(14.0% )patients.Long-term all-cause mortality was lower in the group with decreasing QRS duration and the group with stable QRS duration compared with the progressing QRS duration group(13.9% vs.10.7% vs.18.6%,χ2=28.607,P<0.001).Multifactorial Cox regression analysis showed that admission QRS duration(HR=1.005,95% CI:1.002-1.009,P=0.003)and higher ΔQRS ratio during hospitalization(HR=2.071,95% CI:1.247-3.440,P=0.005)were independent influencing factors of long-term all-cause mortality in chronic heart failure patients.Restricted cubic spline curves showed that when the admission QRS duration was>96.36 ms,the longer the QRS duration,the higher the risk of all-cause mortality;when the admission QRS duration fluctuated from 89.32-96.36 ms,the QRS duration was a protective factor for long-term all-cause mortality in patients with chronic heart failure;and when the ΔQRS ratio during hospitalization was≥3.40%,higher ΔQRS ratio was linked with increased risk of all-cause mortality.Conclusions:QRS duration and ΔQRS ratio during hospitalization are independent predictors of long-term all-cause mortality in patients with chronic heart failure.Admission QRS duration>96.36 ms and ΔQRS ratio during hospitalization≥3.40% are associated with increased risk of long-term all-cause mortality in patients with chronic heart failure.

BACKGROUND:The clinical application of Mongolian Medicine Erdun-uril in the treatment of osteoarthritis is effective,but its therapeutic effect and related mechanism are still unclear. OBJECTIVE:To observe the repairing process of osteoarthritis in rats by Mongolian Medicine Erdun-uril and analyze its mechanism. METHODS:Thirty male Sprague-Dawley rats(8 weeks of age)were selected to establsih an osteoarthritis model using intraarticular injection of sodium iodoacetate solution into the unilateral knee joint.Two weeks after modeling,the model rats were randomly divided into three groups:control group(n=6)was given normal saline by gavage,and low and high dose groups(n=12 per group)were given Erdun-uril 1.4 and 2 g,respectively,3 times per day.After 2 and 4 weeks of continuous administration,blood samples,articular cartilage and periarticular bone tissue were taken from rats to detect changes in cartilage metabolic markers(cartilage oligomeric matrix protein,proteoglycan),bone metabolic markers(bone alkaline phosphatase,keratan sulfate),inflammatory markers(interleukin 6,tumor necrosis factor α),lipid metabolic markers(total cholesterol,triacylglycerol).Histopathological changes were also observed. RESULTS AND CONCLUSION:qRT-PCR results showed that after 2 and 4 weeks of administration,the mRNA expression of cartilage oligomeric matrix protein,proteoglycan and bone alkaline phosphatase and keratan sulfate in knee cartilage of rats were significantly reduced in the low and high dose groups compared with the control group(P<0.05,P<0.01,P<0.001),with the reduction being more significant in the high dose group.After 2 and 4 weeks of administration,compared with the control group,serum tumor necrosis factor α and interleukin 6 levels were decreased(P<0.01,P<0.001)and total cholesterol and triacylglycerol levels were increased(P<0.05,P<0.01,P<0.001)in the low and high dose groups,with the improvement being more significant in the high dose group.Hematoxylin-eosin staining results showed that in the control group,there were large defective areas on the surface of the knee cartilage with unknown structure and severe inflammatory cell infiltration;in the low dose group,the surface of the knee cartilage was rough with disordered cell arrangement and the cartilage structure did not improve significantly after 2 weeks of administration,while the number of inflammatory cells in the knee cartilage was reduced and the cartilage structure was restored to some extent after 4 weeks of administration;in the high dose group,the structure of the knee cartilage become clear after 2 weeks of administration and even clearer after 4 weeks of administration,and the inflammation was significantly reduced after 2 weeks of administration.To conclude,Mongolian Medicine Erdun-uril with better anti-inflammatory properties can improve cartilage metabolism and obviously alleviate osteoarthritis in rats.

Objective:To investigate the effects of early percutaneous coronary intervention (PCI) on myocardial perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction (STEMI) after thrombolysis.Methods:A total of 108 patients with STEMI treated in the Second Hospital of Hebei Medical University from January 2020 to December 2022 were divided into early PCI following thrombolysis group ( n=65) and primary PCI (pPCI) group ( n=43). The general clinical data, and the parameters of routine echocardiography at 1 day after PCI and before discharge were compared between the two groups. Myocardial contrast echocardiography (MCE) was used to evaluate myocardial perfusion at 1 day after PCI and before discharge. Results:There were no significant differences in general clinical data between the early PCI following thrombolysis group and the pPCI group (all P>0.05). The left ventricular ejection fraction (LVEF) in the early PCI following thrombolysis group and pPCI group before discharge was significantly higher than that on the 1st day after PCI(both P<0.05). The difference of LVEF was significant between the early PCI following thrombolysis group and the pPCI group before discharge and 1 day after PCI ( P<0.05). Compared with 1 day after PCI, the global longitudinal strain (LVGLS) of left ventricle increased in early PCI following thrombolysis group and pPCI group before discharge(both P<0.05). The difference of LVGLS between early PCI following thrombolysis group and pPCI group before discharge and 1 day after discharge was statistically significant( P<0.05). There were no significant differences in left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial volume (LAV), ratio of mitral early diastolic velocity to late diastolic velocity (E/A), mean early diastolic velocity of mitral annulus (Em) and E/Em 1 day after PCI and before discharge between early PCI following thrombolysis group and pPCI group (all P>0.05). MCE showed that the MCE score index of early PCI following thrombolysis group and pPCI group before discharge was significantly lower than that of 1 day after PCI(both P<0.001). Compared to the 1 day after PCI, the early PCI following thrombolysis group showed a significant increase in the proportion of normal microvascular perfusion (nMVP) and a decrease in the proportion of delayed microvascular perfusion (dMVP) and microvascular obstruction (MVO) before discharge (all P<0.05). In contrast, the pPCI group demonstrated a significant decrease in the proportion of both nMVP and dMVP before discharge compared to the first day after PCI (all P<0.05). However, the decrease in the proportion of MVO was not statistically significant ( P>0.05). Conclusions:Early PCI following thrombolysis and pPCI can enhance left ventricular systolic function and myocardial perfusion in patients with acute ST-elevation myocardial infarction. Early PCI following thrombolysis may offer additional advantages in improving left ventricular systolic function and myocardial perfusion.