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 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 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.

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.

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.

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.

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.

Objective:To explore the predictive value of preoperative pelvic floor electromyography(EMG)parameters for the risk of urinary incontinence after prostate cancer surgery.Methods:This study retrospectively analyzed the medical records of 271 patients who underwent radical prostatectomy in the urology department of Peking University First Hospital from January 2020 to October 2022.The data included patient age,body mass index(BMI),international prostate symptom score(IPSS),prostate-specific antigen(PSA)levels,Gleason score,type of surgery,urethral reconstruction,lymph node dis-section,nerve preservation,catheterization duration,D'Amico risk classification,American Society of Anesthesiologists(ASA)score,Charlson comorbidity index,postoperative duration,prostate volume,and pelvic floor EMG parameters(pre-resting mean,fast muscle mean,and slow muscle mean scores).Independent risk factors affecting early postoperative urinary incontinence were identified through multiva-riate Logistic regression analysis.The predictive efficacy of pelvic floor EMG results was evaluated by cal-culating the area under the receiver operating characteristic(ROC)curve,and the optimal threshold for early postoperative urinary incontinence was determined based on the Youden index and clinical signifi-cance.Results:The study included 271 prostate cancer patients,with an 81.9％rate of voluntary urinary control post-surgery.The median score for fast pelvic floor muscles was 23.5(18.2,31.6),and for slow muscles,it was 12.5(9.6,17.3).Among the patients,179(66.1％)did not preserve nerves,and 110(40.6％)underwent urethral reconstruction.Advanced age and low fast muscle scores were identified as independent risk factors for urinary incontinence.Patients aged ≤60 had 5.482 times the voluntary urinary control rate compared with those aged ≥70(95％CI:1.532-19.617,P＜0.05).There was a significant correlation between fast muscle scores and urinary incontinence recovery(OR=1.209,95％CI:1.132-1.291,P＜0.05).When the optimal threshold for preoperative fast muscle score was set at 18.5,the ROC sensitivity and specificity were 80.6％and 61.2％,respectively.Con-clusion:Preoperative pelvic floor EMG parameters show good predictive accuracy and clinical applicabili-ty for the risk of urinary incontinence after prostate cancer surgery.These parameters can be used for ear-ly identification of urinary incontinence risk,with age and fast muscle scores being important predictors.

Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.