ObjectiveTo explore the correlation between the blood stasis score of coronary heart disease（CAD） and mild cognitive impairment（MCI）， as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI（CADMCI） through a cross-sectional study， and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients. MethodsAccording to the diagnostic criteria of CAD and CAD blood stasis， patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included. According to the Montreal Cognitive Assessment（MoCA） scale score， the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group. The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model. The receiver operating characteristic（ROC） curve was drawn， and the area under the curve（AUC） was calculated to evaluate the sensitivity and specificity of the model. According to the blood stasis score， the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect plasma metabolites in each group of patients. The differential metabolites were screened according to variable importance in the projection（VIP） value≥1， fold change（FC）<0.67 or >1.5， and P<0.05. ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples. ResultsA total of 266 CAD patients were included in this study. Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI［odds ratio（OR）=1.619， 95% confidence interval（CI） 1.223-2.142， P<0.001， ROC curve AUC was 0.615（95% CI 0.547-0.683， P=0.001）］， indicating that the CAD blood stasis score has a certain predictive value for MCI. Plasma non-targeted metabolomics analysis showed that the main differential metabolites between CAD blood stasis and CADMCI blood stasis were lipid metabolites， among which phosphatidylcholine［20∶4（5Z， 8Z， 11Z， 14Z）/P-18∶1（11Z）］ had the best discriminatory efficiency（ROC curve AUC=0.867， 95% CI 0.754-0.942）. Further analysis of the differential metabolites between mild and severe blood stasis showed that lipid metabolites were also the main differential metabolites between mild and severe blood stasis. Among them， 1α，25-dihydroxy-2β-（2-hydroxyethoxy） vitamin D₃ had the best efficacy in distinguishing mild and severe CAD blood stasis（AUC=0.813， 95% CI 0.649-0.951）， and phosphatidylcholine 34∶2 had the best efficacy in distinguishing mild and severe CADMCI blood stasis（AUC=0.819， 95% CI 0.640-0.941）. ConclusionThere is a significant correlation between CAD blood stasis score and MCI. Phosphatidylcholine metabolites play an important role in the pathogenesis of CADMCI blood stasis and severe blood stasis. The CAD blood stasis score combined with the detection of phosphatidylcholine metabolites can provide a reference for the development of early and efficient identification strategies for CADMCI.

Liver being substantial Yin and functional Yang maintain normal function of Qi， blood and meridians. In clinical practice， it is often found that pan-vascular lesions with atherosclerosis as the predominant pathological change often co-occur with metabolic dysfunction-associated fatty liver disease（MAFLD）. MAFLD leads to increased risk and worse prognosis for many pan-vascular diseases， including cardiovascular disease. Dysregulation of energy homeostasis disrupts the hepatic homeostasis of body use， and representative drugs to improve metabolism， such as metformin， sodium-glucose co-transporter 2 inhibitors， and glucagon-like peptide-1 agonists， not only have a clear cardiovascular benefit， potential improvement of MAFLD has also been demonstrated. The liver stores blood and the heart pumps blood， and liver diseases affect the heart， that's why the unsmoothness of vessels appears. So the treatment should from the standpoint of liver， restoring liver function， soothing the liver and nourishing heart， activating blood and dredging meridian. It is of great significance to explore in depth the pathogenesis and treatment of pan-vascular lesions caused by MAFLD， and to restore the energy homeostasis by adjusting the balance of liver Yin and Yang.

Liver being substantial Yin and functional Yang maintain normal function of Qi， blood and meridians. In clinical practice， it is often found that pan-vascular lesions with atherosclerosis as the predominant pathological change often co-occur with metabolic dysfunction-associated fatty liver disease（MAFLD）. MAFLD leads to increased risk and worse prognosis for many pan-vascular diseases， including cardiovascular disease. Dysregulation of energy homeostasis disrupts the hepatic homeostasis of body use， and representative drugs to improve metabolism， such as metformin， sodium-glucose co-transporter 2 inhibitors， and glucagon-like peptide-1 agonists， not only have a clear cardiovascular benefit， potential improvement of MAFLD has also been demonstrated. The liver stores blood and the heart pumps blood， and liver diseases affect the heart， that's why the unsmoothness of vessels appears. So the treatment should from the standpoint of liver， restoring liver function， soothing the liver and nourishing heart， activating blood and dredging meridian. It is of great significance to explore in depth the pathogenesis and treatment of pan-vascular lesions caused by MAFLD， and to restore the energy homeostasis by adjusting the balance of liver Yin and Yang.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective To investigate the efficacy and safety of hybrid surgery for the recanalization of carotid artery occlusion after stenting.Methods Clinical data and results of 17 patients with occlusion after carotid artery stenting and treated with hybrid surgery from June 2016 to April 2023 at the Department of Neurosurgery Cerebral Blood Flow Reconstruction Center of Xuanwu Hospital,Capital Medical University were retrospectively analyzed.According to whether the recanalization was successful,17 patients were divided into the the successful recanalization group and the failed recanalization group.Successful recanalization was defined as achieving modified thrombolysis in cerebral infarction(mTICI)grade ≥2b and residual stenosis＜50％.Baseline data(age,sex,body mass index,smoking history,alcohol consumption history,hypertension history,diabetes history,hyperlipidemia history,coronary heart disease history),clinical data(National Institutes of Health Stroke Scale[NIHSS]score at admission,fasting blood glucose,low density lipoprotein,high density lipoprotein,total cholesterol,triglyceride,occlusion side and segment,combination with severe stenosis or occlusion of the contralateral carotid artery,opening of the anterior communicating artery,opening of the posterior communicating artery,compensation of the external and internal carotid artery,compensation of the pia artery,stump morphology,and time from imaging diagnosis of occlusion to recanalization)were documented and compared between groups.The recanalization of occlusive vessels and perioperative complications were recorded.Imaging and clinical follow-up were performed 3,6 months and≥1 year after surgery.Results Among the 17 patients,the ratio of successful recanalization was 13/17.One patient had re-occlusion after operation,which was re-opened after thrombolysis,but neck hematoma with dyspnea occurred,and recovered after emergency operation.There was no postoperative stroke or death.The incidence of perioperative complications was 1/17.Compared with the successful recanalization group,the levels of high density lipoprotein and total cholesterol in the failed recanalization group were higher,and the differences between the groups were statistically significant(high density lipoprotein[1.3±0.3]mmol/L vs.[0.9±0.3]mmol/L,t=-2.139;total cholesterol:[4.2±0.8]mmol/L vs.[3.1±0.7]mmol/L,t=-2.649;both P＜0.05);There were no significant differences in other baseline data and clinical data(all P＞0.05).Imaging follow-up was completed in 9 of the 13 patients in the successful recanalization group,and the follow-up time was 3.8-36.9 months,with a median follow-up time of 22.8(12.8,34.7)months.Among them,1 patient(1/9)developed restenosis of recanalization vessels at 33.0 months after surgery and underwent stent implantation again.Conclusions The preliminary analysis showed that the occlusion after carotid artery stenting had better recanalization success and lower perioperative complications.In patients with chronic occlusion after carotid stenting,the application of a hybrid surgery for opening may be attempted under multimodal imaging assessment.

Objective:To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model.Methods:A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect.Results:① Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×10 9/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio ( OR) = 3.063, 95% confidence interval (95% CI) was 1.200-7.819], blood purification catheter function ( OR = 4.429, 95% CI was 1.270-15.451), blood flow rate ( OR = 0.928, 95% CI was 0.900-0.957), and frequency of blood pump stops ( OR = 1.339, 95% CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95% CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. ② External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95% CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. Conclusion:The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.

Objective:To investigate the status of hepatitis E virus infection in unpaid blood donors in Wenzhou.Methods:A total of 5 241 blood samples were selected from donors who successfully donated blood between October 2022 and March 2023. These samples were tested for hepatitis E virus (HEV) through HEV-IgG antibodies, HEV-IgM antibodies, and nucleic acid tests (HEV RNA). Samples that tested positive for HEV RNA underwent quantitative detection and sequencing. Data regarding the blood donors were collected, the positive rates of each test result were recorded, and the HEV infection status among different populations was analyzed.Results:The positive rate of the HEV-IgG antibody test was 23.60% (1 237/5 241), while the positive rate of the HEV-IgM antibody test was 0.29% (15/5 241). The positive rate of the HEV RNA test was 0.08% (4/5 241). The positive rate of the HEV-IgG test increased with age ( χ2 = 379.493, P < 0.05), and males had a higher positive rate than females ( χ2 = 5.12, P < 0.05). Both the positive rates of HEV-IgG and HEV-IgM tests increased as the number of blood donations increased ( χ2 = 40.87, 8.30, both P < 0.05). Furthermore, the positive rates were significantly higher in 2023 than in 2022 ( χ2 = 51.03, 13.35, both P < 0.05), and they were also significantly higher in spring than in winter ( χ2 = 51.03, 13.35, both P < 0.05). Only one HEV RNA-positive blood donor tested positive for both HEV-IgG and HEV-IgM antibodies, while the remaining three donors tested negative. Only one case was genotyped, and it belonged to genotype Ⅳ. Conclusion:The incidence of HEV infection among unpaid blood donors in Wenzhou of Zhejiang Province is relatively high, with the prevalent HEV genotype being type Ⅳ. Characteristics such as sex, age, and the number of blood donations can be utilized as auxiliary screening reference indicators.