Objective To evaluate the impact of an integrated management mode of prenatal diagnosis-postnatal treatment for congenital heart disease (CHD) on perioperative and long-term outcomes of the arterial switch operation (ASO), and to analyze the efficacy of ASO in a single center. Methods This retrospective study analyzed the clinical data of 183 children who underwent ASO at Guangdong Provincial People’s Hospital from 2018 to 2024. The cohort included 106 (57.9%) patients of transposition of the great arteries with intact ventricular septum (TGA/IVS), 61 (33.3%) patients of transposition of the great arteries with ventricular septal defect (TGA/VSD), and 16 (8.7%) patients of Taussig-bing anomaly (TBA). Perioperative indicators were compared between 91 patients in the prenatal-postnatal integrated management group (an integrated group) and 92 patients in the traditional management group (a non-integrated group). Long-term survival and reoperation rates were analyzed using Kaplan-Meier curves. Results The overall perioperative mortality rate was 4.9% (9/183), showing a downward trend year by year. The primary cause of perioperative mortality was low cardiac output syndrome (LCOS), which occurred in 12 patients (6.6% incidence) with a mortality rate of 75.0%. The integrated group had a higher proportion of males (89.0% vs. 72.8%, P<0.05) and lower body weight [3.1 (2.7, 3.3) kg vs. 3.3 (3.0, 3.7) kg, P<0.05] compared to the non-integrated group. The age at surgery was significantly earlier in the integrated group [7 (3, 10) d vs. 14 (9, 48) d, P<0.05], and all children in the integrated group underwent ASO within the optimal surgical window (100.0% vs. 82.6%, P<0.05). Intraoperatively, cardiopulmonary bypass time [173 (150, 207) min vs. 186 (159, 237) min, P<0.05] and aortic cross-clamp time [100 (90, 117) min vs. 116 (97, 142) min, P<0.05] were significantly shorter in the integrated group. Although the integrated group had longer postoperative mechanical ventilation time [145 (98, 214) h vs. 116 (77, 147) h, P<0.05] and higher 48-hour maximum vasoactive inotropic score [15 (10, 21) points vs. 12 (8, 16) points, P<0.05], there was no statistically significant difference in the incidence of severe complications (LCOS, necrotizing enterocolitis, extracorporeal membrane oxygenation) or mortality rate (3.3% vs. 6.5%, P=0.51) between the two groups, despite earlier surgical intervention and a higher proportion of critically ill cases in the integrated group. The length of hospital stay in the emergency surgery group was significantly shorter than that in the elective surgery group [20 (15, 28) d vs. 25 (21, 30) d, P<0.05], suggesting that early surgery may be of potential benefit. A total of 163 patients were successfully followed up for a median of 4.7 years, with a 5-year survival rate of 95.1% and a freedom from reintervention survival rate of 95.1%. There were no late deaths, and the most common postoperative complication was pulmonary artery stenosis. Conclusion The integrated management model allowed critically ill children with lower body weights to safely undergo surgery, significantly optimizing the timing of surgery and shortening intraoperative times. The long-term risk of reoperation after ASO is primarily concentrated on pulmonary artery stenosis, necessitating long-term follow-up and monitoring.

As an innovative form of combining traditional aromatherapy with modern nasal medicine delivery technology， "olfactory administration of Chinese medicine" carries the theoretical essence of traditional Chinese medicine （TCM）， which is "moving and channeling Qi and fragrance， dredging and awakening the mind". Based on the systematic records of olfactory therapies in ancient books in emergency care， disorders of consciousness， lung system， and gynecological diseases， this paper examines the historical evolution of its clinical application， and elucidates the profound historical basis and theoretical feasibility of "olfactory administration of Chinese medicine" as a new form. Combined with the innovation and precise application of modern Chinese medicine olfactory agents in multi-system diseases such as nervous， respiratory， and cardiovascular diseases， this paper further analyzes the multi-dimensional mechanism of olfactory receptor pathway， olfactory brain pathway， nasal mucosal blood vessels， and lymphatic channels， and demonstrates its advantages of rapid onset， targeted brain entry， and systemic regulation. Under the background of continuous growth in the demand for external TCM treatment， continuous breakthroughs in the technology of nasal dosage forms， and increasingly accurate drug delivery paths， Chinese medicine olfactory agents have shown significant practical applicability and development potential. This study aims to provide theoretical support and practical direction for the system construction of this form.

Objective To compare the differences in the average transaction costs per-referral patients under different models of Integrated Delivery Systems(IDS).Methods Using a typical case sampling method,it selected referred patients from three IDS models:the county medical alliance in D City(Qinghai Province),the urban medical consortium in J District(Zhengzhou City,Henan Province),and the health management coalition in N County(Shandong Province).Structured questionnaires collected demographics,average transaction costs per-referral and cost perceptions.t-tests and ANOVA assessed cost differences;generalized linear regression identified influencing factors.Results Among 915 patients,the average transaction costs per-referral were 1 035.05 yuan(county alliance),195.31 yuan(urban consortium),and 700.97 yuan(health management coalition),with statistically significant differences(P＜0.05).The urban consortium exhibited lower time costs and specialized input costs.Key influencing factors included older age(county alliance),education level,employment status,and referral travel time(urban consortium),as well as urban-rural disparities(health management coalition).Patients'cost perceptions significantly differed across models(P＜0.05).Conclusion The urban medical consortium demonstrated the lowest patient the average transaction costs,highlighting its institutional advantage in minimizing financial burdens.

Objective To investigate the relationship between serum IL-8,homocysteine(Hey),C-reactive protein(CRP)levels and severity of coronary lesions in patients with coronary heart disease(CHD)complicated by chronic heart failure(CHF),as well as their prognostic value.Methods A total of 118 elderly eligible patients admitted to our hospital from January 2023 to September 2024 were prospectively recruited,and according to their Gensini score,they were divided into mild,moderate and severe stenosis groups(45,50 and 23 cases,respectively).Accord-ing to the clinical outcomes after follow-up,they were divided into a good prognosis group(82 cases)and a poor prognosis group(36 cases).The serum levels of IL-8,Hcy and CRP were com-pared among the three groups of different stenosis,and Pearson correlation analysis was used to examine the relationship between the three indicators and the severity of coronary lesions.Cox regression analysis was performed to identify factors influencing poor prognosis in patients with CHD and CHF,and receiver ROC curve analysis was conducted to assess the diagnostic value of serum IL-8,Hey,and CRP levels in predicting prognosis.Results The serum levels of IL-8,Hey and CRP were gradually decreased in the severe,moderate and mild stenosis groups in turn,with statistical significances(P＜0.05).Pearson correlation analysis indicated that serum IL-8,Hcy,and CRP levels were positively correlated with the severity of coronary lesions in the patients with CHD and CHF(r=0.364,0.355,0.372,P＜0.01).Significant differences were found in age,NT-proBNP,D-D,IL-8,Hcy,and CRP levels between the good and poor prognosis groups(P＜0.05).Cox regression analysis revealed that age,NT-proBNP,D-D,IL-8,Hcy,and CRP were influencing factors for poor prognosis in patients with CHD and CHF(P＜0.05).ROC curve ana-lysis showed that the AUC value of IL-8,Hey,CRP,and their combination in predicting prognosis was 0.698,0.714,0.723 and 0.899,respectively.Conclusion In the patients with CHD and CHF,serum IL-8,Hcy,and CRP levels are associated with the severity of coronary lesion and prognosis.Moreover,combining these three indicators has significant diagnostic value for predicting patient outcomes.

Cerebral ischemia-reperfusion injury （CIRI）， a common cerebrovascular disease damage， has garnered increasing attention in the treatment of acute ischemic stroke. Restoration of blood flow and reperfusion to ischemic brain tissue is the key to treatment， while this process often triggers a variety of complex pathophysiological responses， such as oxidative stress， apoptosis， inflammation， mitochondrial dysfunction， angiogenic abnormalities， and disruption of the blood-brain barrier. These responses not only impede the recovery of neurological functions but also may lead to damage or even death of nerve cells， seriously affecting the neurological function and quality of survival of patients. As an important transcription factor， nuclear factor E₂-related factor 2 （Nrf2） has the pharmacological effect of alleviating CIRI by regulating antioxidant， anti-apoptosis， anti-inflammation， mitochondrial function， angiogenesis， and blood-brain barrier pathways. This reveals the potential mechanism of traditional Chinese medicine （TCM） in intervening in CIRI and shows the potential of Nrf2 as a new pathway for dealing with ischemia stroke. This paper comprehensively analyzes the effects and mechanisms of active components and compound prescription of TCM in treating CIRI by modulating the Nrf2 signaling pathway， while pointing out the shortcomings of available studies and proposing a multidimensional exploration. This review aims to provide patients with more comprehensive， safe， and effective therapeutic regimens and improve the quality of survival and prognosis of patients. In addition， in-depth research on TCM should be promoted to reveal the potential mechanism for treating CIRI， providing new ideas and directions for the development of novel therapeutic drugs and methods.

Cerebral ischemia-reperfusion injury （CIRI）， a common cerebrovascular disease damage， has garnered increasing attention in the treatment of acute ischemic stroke. Restoration of blood flow and reperfusion to ischemic brain tissue is the key to treatment， while this process often triggers a variety of complex pathophysiological responses， such as oxidative stress， apoptosis， inflammation， mitochondrial dysfunction， angiogenic abnormalities， and disruption of the blood-brain barrier. These responses not only impede the recovery of neurological functions but also may lead to damage or even death of nerve cells， seriously affecting the neurological function and quality of survival of patients. As an important transcription factor， nuclear factor E₂-related factor 2 （Nrf2） has the pharmacological effect of alleviating CIRI by regulating antioxidant， anti-apoptosis， anti-inflammation， mitochondrial function， angiogenesis， and blood-brain barrier pathways. This reveals the potential mechanism of traditional Chinese medicine （TCM） in intervening in CIRI and shows the potential of Nrf2 as a new pathway for dealing with ischemia stroke. This paper comprehensively analyzes the effects and mechanisms of active components and compound prescription of TCM in treating CIRI by modulating the Nrf2 signaling pathway， while pointing out the shortcomings of available studies and proposing a multidimensional exploration. This review aims to provide patients with more comprehensive， safe， and effective therapeutic regimens and improve the quality of survival and prognosis of patients. In addition， in-depth research on TCM should be promoted to reveal the potential mechanism for treating CIRI， providing new ideas and directions for the development of novel therapeutic drugs and methods.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective To explore the efficacy of Yishen Yangyin Gujing Prescription[derived from Zuogui Wan(Bolus for Replenishing Kidney-Yin)]for the treatment of diabetic nephropathy in type 2 diabetes mellitus(T2DM)with qi and yin deficiency syndrome,and to observe its effects on inflammatory responses,pancreatic β-cell function and renal function.Methods A total of 162 T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome who admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from May 2020 to July 2023 were randomly divided into an observation group and a control group according to the random number table method,with 81 cases in each group.The control group was given conventional western medicine treatment for lowering blood pressure and renal protection,while the observation group was treated with Yishen Yangyin Gujing Prescription on the basis of treatment for the control group.The course of treatment for the two groups covered 12 weeks.Before and after the treatment,the changes in the outcomes of the two groups were observed,and the outcomes included the total scores of traditional Chinese medicine(TCM)syndrome,insulin sensitivity index,insulin secretion index,24-h urine total protein quantification(24hUTP),and serum levels of glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fasting blood glucose(FBG),serum creatinine(SCr),blood urea nitrogen(BUN),transforming growth factor β1(TGF-β1),NLRP3 inflammasome,interleukin 6(IL-6),superoxide dismutase(SOD)and sphingosine-1-phosphate(S1P).After treatment,the clinical efficacy of the two groups of patients was compared.Results(1)After 12-week treatment,the total effective rate of the observation group was 93.83%(76/81),and that of the control group was 83.95%(68/81).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group(χ2=9.163,P<0.05).(2)After treatment,the insulin sensitivity index and insulin secretion index in the two groups of patients were increased(P<0.05)and the total scores of TCM syndromes were decreased(P<0.05)when compared with those before treatment,and the increase of insulin sensitivity index and insulin secretion index as well as the decrease of the total scores of TCM syndrome in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,the serum levels of HbA1c,FINS,FBG,SCr,BUN and 24hUTP in the two groups of patients were decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the serum TGF-β1,IL-6,and NLRP3 inflammasome levels in the two groups of patients were decreased(P<0.05)and the serum S1P and SOD levels were increased(P<0.05)when compared with those before treatment,and the decrease of serum TGF-β1,IL-6,and NLRP3 inflammasome levels as well as the increase of serum S1P and SOD levels in the observation group was significantly superior to that in the control group(P<0.05).Conclusion For T2DM patients with diabetic nephropathy of qi and yin deficiency syndrome,the combined use of western medicine and Yishen Yangyin Gujing Prescription treatment is helpful to alleviate inflammatory response,improve the function of pancreatic β-cells,regulate the blood glucose level,improve renal function,and enhance the clinical efficacy.

OBJECTIVES: To investigate the association between methylation levels of tumor suppressing subtransferable candidate 1 (TSSC1) and melanophilin (MLPH) genes in peripheral blood and coronary heart disease (CHD) in Chinese population. METHODS: This case-control study was conducted in 86 CHD patients and 95 healthy individuals, whose methylation levels of TSSC1 and MLPH genes in peripheral blood were determined using mass spectrometry. Mann-Whitney U test was used to compare the methylation levels in different subgroups. The correlation of TSSC1 and MLPH gene methylation levels with age and gender were evaluated using Spearman correlation coefficient and contingency coefficient, respectively. RESULTS: Compared with the healthy individuals, the CHD patients showed a significant correlation between MLPH hypermethylation and myocardial infarction (MI) (MLPH_CpG_2.7: P=0.045; MLPH_CpG_3/cg06639874: P=0.049; MLPH_CpG_5: P=0.019), and this correlation was even stronger in individuals below 65 years of age (MLPH_CpG_2.7: P=0.014; MLPH_CpG_4: P=0.001) and in male subjects (MLPH_CpG_2.7: P=0.004; MLPH_CpG_3/cg06639874: P=0.044). The methylation level of TSSC1 gene in peripheral blood was not found to correlate with CHD or its subtypes. CONCLUSIONS Our findings suggest a correlation of MLPH hypermethylation in peripheral blood with CHD and MI in Chinese population, especially in individuals below 65 years and in male individuals.
Humans ; DNA Methylation ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Coronary Disease/blood* ; Adult ; CpG Islands

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.