Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Septic shock, a prevalent critical condition in intensive care units (ICU) and a major cause of patient mortality, is fundamentally attributed to microcirculatory dysfunction. Traditional macrocirculatory parameters are often insufficiently sensitive to reflect microcirculatory status. Consequently monitoring peripheral microcirculatory function holds crucial significance for assessing disease progression and evaluating therapeutic efficacy in septic shock. The peripheral perfusion index (PPI), obtained from a standard pulse oximeter, is based on photoplethysmography (PPG). It calculates the differential absorption of red and infrared light emitted by the sensor between pulsatile arterial blood and non-pulsatile tissue, enabling real-time reflection of peripheral perfusion and thus providing non-invasive, continuous monitoring of microcirculatory function. Although often overlooked compared to other ICU monitoring parameters, PPI has demonstrated notable clinical advances in septic shock management. Specifically, in early identification, PPI combined with sequential organ failure assessment (SOFA) predicts disease progression, with its dynamic changes further aiding prognosis assessment. During fluid resuscitation, it guides fluid responsiveness evaluation and serves as a therapeutic target to optimize strategies. In circulatory support, it assists in determining vasoactive drug initiation timing and dosage titration. Additionally, PPI aids mechanical ventilation weaning and organ dysfunction evaluation. This article reviews the principles, influencing factors, and clinical application advances of PPI in septic shock, aiming to provide clinicians with a basis for individualized intervention, improved patient outcomes, and the advancement of precision medicine in septic shock management.
Humans ; Shock, Septic/therapy* ; Microcirculation ; Perfusion Index ; Prognosis ; Photoplethysmography

AIM:To analyze the characteristics and correlation of phacoemulsification parameters and anterior segment parameters in cataract patients with different blood glucose levels.METHODS:A total of 45 type 2 diabetic cataract patients(45 eyes)treated in our hospital from March 2023 to April 2024 were stratified into two groups based on glycosylated hemoglobin(HbA1c)levels: group A: HbA1c <7%(n=18)and group B: 7%≤HbA1c<8.5%(n=27); a total of 94 age-matched age-related cataract patients(94 eyes)were enrolled as the control group(group C). All underwent phacoemulsification with intraocular lens implantation. Anterior segment parameters, including corneal, lens and anterior chamber measurements, were recorded. Correlations between phacoemulsification parameters and anterior segment parameters were analyzed, and differences among groups were compared.RESULTS: In groups A and B, effective phacoemulsification time(EPT)negatively correlated with corneal endothelial cell density(CECD)(r=-0.315, P=0.035). Average phacoemulsification time(APT)positively correlated with the anterior corneal surface radius of curvature(Rm; r=0.402, P=0.006)and negatively correlated with the flat axis meridian curvature(K1), steep axis meridian curvature(K2), mean curvature(Km)of the anterior corneal surface, and lens density at 6 mm zones(PDZ3; all P<0.05). Average phacoemulsification energy(AVE)positively correlated with mean lens density(LD-mean), lens density at 2 mm zones(PDZ1), lens density at 4 mm zones(PDZ2), and PDZ3(all P<0.05), and negatively with pupil diameter(r=-0.385, P=0.009). In the group C, EPT showed a positive correlation with Pentacam nucleus staging(PNS)density grade, PDZ1, PDZ2, and PDZ3(all P<0.05). A positive correlation was observed between AVE and PNS classification(r=0.246, P=0.018). Conversely, AVE exhibited a negative correlation with CECD(r=-0.245, P=0.018). EPT in groups A and B was higher than that in the group C(P<0.05). Both EPT and APT in the group B were higher than those in the group A(P<0.05). In diabetic cataract patients, CECD, corneal density(CD), and posterior corneal surface height positively correlated with diabetes duration(P<0.05). Posterior corneal surface K1 and Rm positively correlated with 7%≤HbA1c<8.5%(P<0.05). Total corneal astigmatism negatively correlated with HbA1c, 2-hour post-breakfast blood glucose(2hPBG), and fasting insulin(FINS; P<0.05). CD and lens thickness(LT)positively correlated with FINS(P<0.05).CONCLUSION: Phacoemulsification parameters and blood glucose-related indices exhibited varying degrees of correlation with anterior segment parameters in cataract patients with different blood glucose levels. EPT in diabetic cataract patients was higher than that in age-related cataract patients, while EPT and APT in diabetic cataract patients with poor glycemic control were higher than those with good glycemic control.

Objective:To develop an admission assessment index system for hospice care tailored to emergency patients.Methods:Using a mixed-methods approach, a preliminary framework was established through literature review and qualitative interviews. From May to September 2024, a two-round Delphi consultation was conducted with 26 experts to screen and refine indicators. The final system was determined using a priority chart method for weight assignment.Results:Twenty-five experts in fields of emergency medicine, emergency nursing, palliative care nursing, palliative care medicine and general practice completed both consultation rounds. The experts ranged in age from 36 to 56 years and had 12 to 36 years of work experience. All held intermediate or higher professional titles. The effective recovery rates for the two rounds of consultation questionnaires were 96.15%(25/26) and 100.00%(25/25), respectively. Expert authority coefficients were 0.891 and 0.911, with Kendall′s coordination coefficients of 0.348 and 0.399 ( P<0.001), and variation coefficients ranging from 0.040 to 0.204 and 0.000 to 0.179. The finalized system comprises 5 primary indicators (weighted coefficients: life-limiting disease status 0.268, symptom control 0.236, patient/familywishes 0.201, social support needs 0.162, medical resource utilization 0.133) and 27 secondary indicators. Conclusion:The index system developed in this study provides a comprehensive and practical tool for identification of emergency patients requiring hospice care, facilitating timely clinical decision-making.

Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Abastract:Objective To validate the performance of six different lipoprotein(a)[Lp(a)]immunoassay detection systems,compare the correlation and consistency of the measurement results of different detection systems,and explore their clinical application in the e-valuation of atherosclerotic cardiovascular disease(AsCVD).Methods A total of 150 AsCVD patients attending Peking Union Medi-cal College Hospital were retrospectively selected as the subjects of study group,and 50 individuals of physical examination during the same period were selected as healthy control group.Lp(a)levels were measured in 200 serum samples using six immunoassay detection systems,including two Lp(a)particle concentration assays in nmol/L(Roche and Mindray Ⅱ),and four Lp(a)mass concentration assays in mg/L(Mindray,MedicalSystem,BSBE,and Sekisui).All assays'precisions were evaluated.The results of each assay sys-tem were compared with the mean value of all the Lp(a)assays.Passing-Bablok regression analysis and Bland-Altman bias plots were used to assess the accuracy of assays,and the consistency between different systems was analyzed using the concordance correlation co-efficient(CCC).In addition,the consistencies of different assays in assessing AsCVD in clinical setting were compared using weighted Kappa statistical method,and the positive rates of Lp(a)particle concentration and mass concentration,as well as the overestimation and underestimation of mass concentration were also assessed for both the study group and the healthy control group.Results The pre-cision of the six Lp(a)assays ranged from 0.6％to 2.1％.Passing-Bablok regression analysis showed that the Spearman correlation co-efficients of the regression equations were all greater than 0.970,and the intercepts and slopes of the regression lines were-43.311 to 39.456 and 0.547 to 5.500,respectively.The Bland-Altman bias plots showed that the percent bias of the six assays compared to the mean value of Lp(a)determination was in the range of-25.939％to 40.205％.The results of the Lp(a)mass concentration detection system showed a positive deviation in Mindray and MedicalSystem,and a negative deviation in BSBE and Sekisui.Compared with the mean value of Lp(a),the results of consistency analysis showed that Roche and Mindray Ⅱ had excellent consistency(CCC:0.992 to 0.993).Mindray,MedicalSystem and BSBE had good consistency(CCC:0.950 to 0.986),and Sekisui showed moderate consistency(CCC:0.935).In descending order,the positivity rates of Lp(a)in the study groups were:MedicalSystem＞BSBE＞Mindray＞Roche=Mindray Ⅱ＞Sekisui.The overall concordances of Mindray,MedicalSystem,BSBE and Sekisui compared to Lp(a)particle concentration assay in different groups were 97.33％,93.33％,97.33％and 98.00％with Kappa values of 0.910,0.798,0.912 and 0.927,respec-tively.Conclusion The two assays for Lp(a)particle concentration have fine correlation and consistency,but there were significant differences between the four assays for Lp(a)mass concentration.Compared to the Lp(a)particle concentration assays,the four assay for Lp(a)mass concentration resulted in overestimation or underestimation of Lp(a)levels in the assessment of AsCVD.Accurate de-termination of Lp(a)concentration should be of great importance in accurately assessing the overall risk of AsCVD in patients.

Objective To explore the influencing factors of urinary dysfunction in patients with rectal cancer after laparoscopic surgery,and to construct and validate a column chart prediction model.Methods A retrospective analysis was conducted on the clinical data of 415 rectal cancer patients in our hospital from January 2021 to April 2024.According to the computer-generated allocation order,they were stochastically grouped into a modeling group of 311 cases and a validation group of 104 cases in a 3∶1 ratio.The modeling group was further separated into a urinary dysfunction group of 55 cases and a non urinary dysfunction group of 256 cases.The patient's sex,diabetes history,tumor diameter and other relevant data were collected;MultivariateLogisticregression analysis was used to screen for risk factors;R software was used to construct a column chart prediction model for predicting urinary dysfunction in patients with colorectal cancer after laparoscopic surgery;The Hosmer-Lemeshow test,ROC curve,calibration curve,and DCA curve were used to validate the predictive performance of the column chart model.Results Male[OR(95％CI)=3.512(1.637～7.533),P=0.001],diabetes[OR(95％CI)=3.684(1.639～8.280),P=0.002],tumor diameter ≥ 5 cm[OR(95％CI)=4.459(1.993～9.979),P=0.000],large intraoperative bleeding[OR(95％CI)=1.018(1.011～1.026),P=0.000],anterior resection of rectum combined with abdominal perineum resection[OR(95％CI)=3.885(1.901～7.940),P=0.000]were Independent risk factors for postoperative urination dysfunction in rectal cancer patients after laparoscopic surgery.In internal and external validations,the Hosmer-Lemeshau test for the column chart model showed x2=0.159,P=0.254＞0.05,and x2=5.991,P=0.648＞0.05.The areas under the receiver operating characteristic curve were 0.846 and 0.828,respectively.The calibration curve indicated that the simulated curve had a similar trend to the actual curve,indicating good discrimination and calibration of the column chart prediction model.Clinical decision curve analysis results showed that when the high-risk threshold probability was between 0.05 and 0.98,the column chart prediction model could produce better clinical benefits.Conclusion The column chart model constructed by integrating independent risk factors for urinary dysfunction in rectal cancer patients after laparoscopic surgery has high predictive value.

Objective A joint Poisson-logistic model in a Bayesian framework is proposed to constructed using tuberculosis(TB)reporting data from 14 prefectures in Xinjiang from 2014 to 2020 in combination with relevant social,economic,and environmental factors affecting the reported incidence rate of TB to explore potential underreporting areas of the TB reporting data,and to provide a strong evidence－based support for the subsequent decision－making on the precision prevention and control of TB.Methods Relevant factors affecting the reporting process and disease process of TB were collected,and important covariates were screened for inclusion in the model using the factor detector in the Geo-detector method,and the reported incidence model of TB and the expected incidence model of TB in Xinjiang were constructed separately,which together constituted a hybrid model of underreporting of TB(Poisson-logistic joint model).The mixed model was used to estimate the risk of TB underreporting in each prefecture of Xinjiang,and to explore the regional distribution of the potential risk of TB underreporting.Results Factor detector result pairs showed that GDP per capita was associated with the largest contribution to the risk of TB underreporting(0.5481);goodness－of－fit test showed that the data were well fitted(Bayesian P－value<0.001),and the Bayesian Poisson-logistic joint model could be applied to the study of the risk of underreporting of TB reporting data in Xinjiang from 2014 to 2020.The results showed that the risk of underreporting of TB The risk of underreporting of reported data was concentrated in the four southern Xinjiang prefectures,with the greatest risk of underreporting of TB reported data in Kashgar 0.1426(0.1403,0.1445).The lower risk of underreporting was concentrated in the eastern and central parts of Xinjiang,with the lowest risk of underreporting in the city of Karamay[0.1017(0.9983,0.1034)].In a joint Bayesian Poisson-logistic model,it was found that population density(IRR＝1.0060,95%CI:1.0059~1.0061)and average annual temperature(IRR＝1.0087,95%CI:1.0086~1.0088)were risk factors for underreporting of TB,and GDP per capita(IRR＝0.9385,95%CI:0.9365~0.9394)and an increase in the number of registered nurses(IRR＝0.9916,95%CI:0.9913 to 0.9920)reduced the risk of TB underreporting.Conclusion The Bayesian Poisson-logistic joint model estimated the potential incidence of TB in Xinjiang Uygur Autonomous Region and revealed significant discrepancies between reported and true TB incidence rates.It identified underreporting trends and localized potential underreporting risk areas,providing a theoretical basis for tailored and precise TB prevention and control strategies in Xinjiang.

Objective A joint Poisson-logistic model in a Bayesian framework is proposed to constructed using tuberculosis(TB)reporting data from 14 prefectures in Xinjiang from 2014 to 2020 in combination with relevant social,economic,and environmental factors affecting the reported incidence rate of TB to explore potential underreporting areas of the TB reporting data,and to provide a strong evidence－based support for the subsequent decision－making on the precision prevention and control of TB.Methods Relevant factors affecting the reporting process and disease process of TB were collected,and important covariates were screened for inclusion in the model using the factor detector in the Geo-detector method,and the reported incidence model of TB and the expected incidence model of TB in Xinjiang were constructed separately,which together constituted a hybrid model of underreporting of TB(Poisson-logistic joint model).The mixed model was used to estimate the risk of TB underreporting in each prefecture of Xinjiang,and to explore the regional distribution of the potential risk of TB underreporting.Results Factor detector result pairs showed that GDP per capita was associated with the largest contribution to the risk of TB underreporting(0.5481);goodness－of－fit test showed that the data were well fitted(Bayesian P－value<0.001),and the Bayesian Poisson-logistic joint model could be applied to the study of the risk of underreporting of TB reporting data in Xinjiang from 2014 to 2020.The results showed that the risk of underreporting of TB The risk of underreporting of reported data was concentrated in the four southern Xinjiang prefectures,with the greatest risk of underreporting of TB reported data in Kashgar 0.1426(0.1403,0.1445).The lower risk of underreporting was concentrated in the eastern and central parts of Xinjiang,with the lowest risk of underreporting in the city of Karamay[0.1017(0.9983,0.1034)].In a joint Bayesian Poisson-logistic model,it was found that population density(IRR＝1.0060,95%CI:1.0059~1.0061)and average annual temperature(IRR＝1.0087,95%CI:1.0086~1.0088)were risk factors for underreporting of TB,and GDP per capita(IRR＝0.9385,95%CI:0.9365~0.9394)and an increase in the number of registered nurses(IRR＝0.9916,95%CI:0.9913 to 0.9920)reduced the risk of TB underreporting.Conclusion The Bayesian Poisson-logistic joint model estimated the potential incidence of TB in Xinjiang Uygur Autonomous Region and revealed significant discrepancies between reported and true TB incidence rates.It identified underreporting trends and localized potential underreporting risk areas,providing a theoretical basis for tailored and precise TB prevention and control strategies in Xinjiang.

Objective To explore the influencing factors of urinary dysfunction in patients with rectal cancer after laparoscopic surgery,and to construct and validate a column chart prediction model.Methods A retrospective analysis was conducted on the clinical data of 415 rectal cancer patients in our hospital from January 2021 to April 2024.According to the computer-generated allocation order,they were stochastically grouped into a modeling group of 311 cases and a validation group of 104 cases in a 3∶1 ratio.The modeling group was further separated into a urinary dysfunction group of 55 cases and a non urinary dysfunction group of 256 cases.The patient's sex,diabetes history,tumor diameter and other relevant data were collected;MultivariateLogisticregression analysis was used to screen for risk factors;R software was used to construct a column chart prediction model for predicting urinary dysfunction in patients with colorectal cancer after laparoscopic surgery;The Hosmer-Lemeshow test,ROC curve,calibration curve,and DCA curve were used to validate the predictive performance of the column chart model.Results Male[OR(95％CI)=3.512(1.637～7.533),P=0.001],diabetes[OR(95％CI)=3.684(1.639～8.280),P=0.002],tumor diameter ≥ 5 cm[OR(95％CI)=4.459(1.993～9.979),P=0.000],large intraoperative bleeding[OR(95％CI)=1.018(1.011～1.026),P=0.000],anterior resection of rectum combined with abdominal perineum resection[OR(95％CI)=3.885(1.901～7.940),P=0.000]were Independent risk factors for postoperative urination dysfunction in rectal cancer patients after laparoscopic surgery.In internal and external validations,the Hosmer-Lemeshau test for the column chart model showed x2=0.159,P=0.254＞0.05,and x2=5.991,P=0.648＞0.05.The areas under the receiver operating characteristic curve were 0.846 and 0.828,respectively.The calibration curve indicated that the simulated curve had a similar trend to the actual curve,indicating good discrimination and calibration of the column chart prediction model.Clinical decision curve analysis results showed that when the high-risk threshold probability was between 0.05 and 0.98,the column chart prediction model could produce better clinical benefits.Conclusion The column chart model constructed by integrating independent risk factors for urinary dysfunction in rectal cancer patients after laparoscopic surgery has high predictive value.