Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To seek any correlation between hypoesthesia and sensory disturbance to motor function among stroke survivors.Methods:One hundred and two stroke survivors with hyperalgesia were treated with sinusoidal alternating current at 2000Hz, 250Hz or 5Hz to stimulate the fingers and toes on their healthy and hemiplegic sides. Current perception thresholds (CPTs) and pain tolerance thresholds (PTTs) were recorded. The correlation between the degree of sensory disturbance in the hemiplegic limb and muscle strength was explored.Results:①The degree of sensory impairment in those who had suffered a cerebral hemorrhage was significantly greater than among those with cerebral infarction, without significant difference in pain tolerance between different genders and affected sides. ②All of the patients with sensory impairment showed significantly higher CPT and PTT values at the different frequencies, with a positive correlation between them. ③The CPT values of the affected hand and foot at the different frequencies were negatively correlated with muscle strength on the affected side.Conclusions:Both CPT and PTT can usefully represent the degree of sensory disturbance after a stroke. The CPT values of patients with different types of stroke are significantly different, and the degree of sensory disturbance is correlated with the muscle strength of the affected side. Therefore, it is helpful for prognostic judgment and individualized rehabilitation treatment planning by quantifying the degree of sensory disturbance.

Objective:To seek any correlation between hypoesthesia and sensory disturbance to motor function among stroke survivors.Methods:One hundred and two stroke survivors with hyperalgesia were treated with sinusoidal alternating current at 2000Hz, 250Hz or 5Hz to stimulate the fingers and toes on their healthy and hemiplegic sides. Current perception thresholds (CPTs) and pain tolerance thresholds (PTTs) were recorded. The correlation between the degree of sensory disturbance in the hemiplegic limb and muscle strength was explored.Results:①The degree of sensory impairment in those who had suffered a cerebral hemorrhage was significantly greater than among those with cerebral infarction, without significant difference in pain tolerance between different genders and affected sides. ②All of the patients with sensory impairment showed significantly higher CPT and PTT values at the different frequencies, with a positive correlation between them. ③The CPT values of the affected hand and foot at the different frequencies were negatively correlated with muscle strength on the affected side.Conclusions:Both CPT and PTT can usefully represent the degree of sensory disturbance after a stroke. The CPT values of patients with different types of stroke are significantly different, and the degree of sensory disturbance is correlated with the muscle strength of the affected side. Therefore, it is helpful for prognostic judgment and individualized rehabilitation treatment planning by quantifying the degree of sensory disturbance.

Fetal monitoring is an essential component of the prenatal examination. With electronic fetal heart monitoring, clinicians can effectively monitor the intrauterine situation of the fetus, promptly detect fetal distress, and intervene early to reduce the occurrence of adverse outcomes in newborns. In recent years, the leaps in internet technology have enabled the widespread utilization of remote electronic fetal heart monitoring based on ultrasound technology. This paper reviews the application, effectiveness, and safety of remote fetal heart monitoring, and the satisfaction level of healthcare professionals with this technology in recent years and compares it with traditional fetal heart monitoring, aiming to provide reference and insights for clinical applications of remote fetal heart monitoring.

Objective To observe the value of left atrial strain combined with electrocardiogram(ECG)P-wave parameters for predicting recurrence of paroxysmal atrial fibrillation(PAF)after pulmonary vein isolation(PVI)using radiofrequency catheter.Methods Totally 88 PAF patients who planned to receive the first PVI were prospectively enrolled and divided into recurrence group(n=30)and non-recurrence group(n=58)according to results of ECG within 6 months after PVI.The patients'basic data,the transthoracic echocardiography(TTE)parameters,including left atrial reservoir strain(LASr),left atrial conduct strain(LAScd)and left atrial contraction strain(LASct),as well as ECG parameters including P-wave duration,PR interval and P/PR(the ratio of P-wave duration to PR interval)were compared between groups.Multivariate logistic regression analysis was performed of parameters being statistically different between groups to screen independent predictors for recurrence of PAF after PVI.The receiver operating characteristic curve and the area under the curve(AUC)were used to evaluate the predicting efficacy of individual independent predictors alone and their combination,and DeLong test was used for comparison.Results No significant difference of patients'basic data was found between groups(all P＞0.05).Compared with those in non-recurrence group,LASr and LAScd decreased while P/PR increased in recurrent group(all P＜0.05).LASr(OR=0.805),LAScd(OR=0.850)and P/PR(OR=1.119)were all independent predictors for recurrence of PAF after PVI(all P＜0.05),with AUC of 0.755,0.643 and 0.771,respectively,all lower than their combination(AUC=0.869)(all P＜0.05).Conclusion TTE and ECG parameters could be used to predict recurrence of PAF after PVI.The predicting efficacy of the combination of LASr,LAScd and P/PR was better than that of each alone.

Objective To explore the research dynamics and hotspots of project management in the field of hospital man-agement,and analyze the contents that still need to be improved,so as to provide references for the subsequent research,and provide hospital managers with practical experience in hospital management.Methods Based on the PubMed database,we used the citexs data analysis platform to analyze the literature and big data from January 2012 to December 2022 on the application of project management in the field of hospital management.Results The effective literature was retrieved from 4236 articles,and the analysis found thatthe annualnumberofpublicationsinthisfield hasbeenincreasing,2021 sawthe highestannualnumberof 573 articles,and the fastest growth rate was 20.36% in 2017.The country with the most publications is the United States(1 546 articles,36.5% ),the research institution with the most publications is Monash University,Australia,the journal with the most publications is BMJ Open(124 articles),and the key words with the highest frequency of occurrence in the retrieved literature are quality improvement,primary care improvement,covid-19,telemedicine.Conclusion The research in this field has been rapidly developed and is in a fast rising phase.In almost every organization and industry,the share of project management or"projectization"is increasing,and project management has become an important part of hospital management research and prac-tice.In the context of building a modern hospital management system,the application of project management to hospital manage-ment is an effective means of improving the level of fine hospital management.

Purpose To assess the right atrial and right ventricular strain and right ventricular-pulmonary artery(RV-PA)coupling in rheumatoid arthritis(RA)via two-dimensional speckle tracking.Materials and Methods Sixty patients with RA in the General Hospital of Ningxia Medical University from June 2020 to June 2022 were prospectively selected,and all RA patients were divided into three groups according to pulmonary artery systolic pressure(PASP),including group A(n=20 cases)with PASP<33 mmHg,group B(n=20 cases)with PASP 33-39 mmHg as mild ePH,and group C(n=20 cases)PASP≥40 mmHg,twenty healthy individuals were selected as the control group.All subjects underwent transthoracic echocardiography,and right atrial and right ventricular systolic function was assessed by two-dimensional speckle tracking technique,and RV-PA coupling was assessed noninvasively by right ventricular free wall strain/pulmonary artery systolic pressure(RV FWS/PASP),pulmonary function was analyzed by pulmonary function instruments.Spearman's analysis was used to analyze the correlation between right heart function and RV-PA coupling to pulmonary diffusion function.Results There were statistical differences in right ventricular base diameter,right atrium diameter,tricuspid annular plane systolic excursion,inferior vena cava diameter,PASP,right ventricular global strain,RV FWS,right atrium strain-reservoi,right atrium strain-conduit(S-CD),RV FWS/PASP among the four groups(F/H=2.369-74.880,all P<0.05).Right atrium strain-reservoi[(36.0±7.9)%vs.(30.9±7.8)%],right atrium S-CD[(19.9±6.9)%vs.(15.3±4.7)%]and RV FWS/PASP(0.96±0.19 vs.0.56±0.13)in group B were significantly lower than those of group A(t=2.040,2.262,7.704,all P<0.05).There was a good correlation between diffusing capacity of the lung for carbon monoxide single-breathmethod and right ventricular global strain,RV FWS,right atrium S-CD and RV FWS/PASP in RA patients(r=0.392,0.472,0.431,0.572,all P<0.05).Conclusion The more increases of pulmonary artery pressures,the more decreases of right heart function in RA patients,and the more uncoupling in RV-PA.Right heart dysfunction and right ventricle-pulmonary artery uncoupling have developed in RA patients with PASP 33-39 mmHg,with association of pulmonary diffusion dysfunction.

Fetal monitoring is an essential component of the prenatal examination. With electronic fetal heart monitoring, clinicians can effectively monitor the intrauterine situation of the fetus, promptly detect fetal distress, and intervene early to reduce the occurrence of adverse outcomes in newborns. In recent years, the leaps in internet technology have enabled the widespread utilization of remote electronic fetal heart monitoring based on ultrasound technology. This paper reviews the application, effectiveness, and safety of remote fetal heart monitoring, and the satisfaction level of healthcare professionals with this technology in recent years and compares it with traditional fetal heart monitoring, aiming to provide reference and insights for clinical applications of remote fetal heart monitoring.

Pathological insulin resistance (IR) is closely related to gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in women with GDM. Increasing studies have investigated the efficacy of IR indices, such as quantitative insulin sensitivity index, homeostasis model assessment of insulin resistance, triglyceride-glucose index and sex hormone-binding globulin, in predicting GDM and related complications in recent years. This article reviews the research progress in the above topics.