The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

The Solomon four-group design， a critical method for improving internal validity in clinical research， can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results， which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design， summarized its applications in clinical research at home and abroad， explored its advantages and limitations， and discussed the potential value in traditional Chinese medicine （TCM） clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies， and reduce the bias in the evaluation of subjective indicators. Meanwhile， given the complexity of the Solomon four-group design and the particularity of TCM clinical research， it is proposed that future TCM clinical studies should focus on using psychological scales， know-ledge， attitude， and behavior measurements， and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.

Based on the clinical thinking of combining diseases and patterns， we combined disease identification， pattern differentiation， and constitution identification， and put forward the theory of identifying and treating critical hypertension， which is "examining the symptoms first， identifying the constitutions as reference， and combining the diseases and patterns". Firstly， the starting point of identifying the disease is to examine the symptoms， and those with precise diagnosis and strong specificity will be diagnosed with the disease， while those with relatively broad diagnosis and fuzzy characteristics will be emphasised on identifying constitutions and differentiating patterns. Focusing on the impact of constitution identification on disease identification and pattern differentiation， constitution identification could be the basis when no symptoms to identify， and based on the theory of "constitution-disease correlation" and "constitution-pattern correlation" to improve the understanding of borderline hypertension from the group and individual level， which helps to identify and predict the development of the diseases and patterns； if the symptoms are complicated and difficult to identify， it is necessary to take syndrome as the outline， use the syndrome to unify the disease， and then refer to the constitution to legislate and prescribe medications. This paper summarizes the traditional Chinese medicine clinical differentiation and treatment strategy of borderline hypertension clear and easy to grasp， with a view to provide a feasible and efficient reference for prevention and treatment of borderline hypertension with traditional Chinese medicine.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective:To investigate short-term safety, efficacy and the learning curve of this self-developed novel transcatheter valve repair system (Neonova?) in patients with mitral regurgitation, and explore the role of perioperative echocardiography.Methods:Ten patients who visited the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from June 2021 to March 2022 and met the inclusive criteria were prospectively enrolled. All the patients were at high risk of surgery with moderate to severe or severe mitral regurgitation (MR). Clamps of Neonova? were implanted under guidance of transesophageal echocardiography and digital subtraction angiography. Clinical outcomes, echocardiography indexes and learning curves of this technique were evaluated immediately after intervention, 7 d, 1 month and 3 months post-intervention.Results:The technical success rate was 100% with MR relieved in all patients immediately after intervention. The device and procedural success rates were both 90.0% with 1 patient received surgical replacement at 37 days post-intervention while the others′ reduced to mild (8/9) and moderate (1/9) MR. New York Heart Association class and the Kansas City Cardiomyopathy Questionnaire improved significantly (all P<0.001). Mean mitral valve pressure gradient didn′t increase significantly after intervention when compared with that before intervention( P=0.324), and no mitral stenosis was observed. Left ventricular end-diastolic diameter decreased significantly ( P=0.008) during follow up.Procedure duration ranged from 60 to 300 (175.8±75.2)minutes. The simple linear regression model between procedure volume and duration showed that procedure duration decreased significantly with the increase of procedure volume ( F=15.857, P=0.004). Conclusions:Neonova? implantation can improve MR severity and clinical symptoms safely and effectively. Transthoracic echocardiography and transesophageal echocardiography are essential for perioperative management of transcatheter mitral valve repair.

Objective:To investigate the current status of family caregivers learned helplessness in patients with advanced digestive tract tumor and analyze its influencing factors, so as to provide reference for the physical and mental management of cancer families.Methods:Totally 181 family caregivers of advanced digestive tract tumor patients from July 2018 to November 2019 in 4 gradeⅢclass A hospitals in Fuzhou were selected by convenient sampling method for investigation with the general information questionnaire and Learned Helplessness Scale. Multiple linear regression analysis was used to analyze the influencing factors of learned helplessness of family caregivers of patients with advanced digestive tract tumor.Results:The total score and the average items score of learned helplessness was (38.61 ± 15.40), (2.15 ± 0.88) points, which was at a lower level. Multiple linear regression analysis showed that the gender of caregiver, physical condition of caregivers, average monthly household income were significant influencing factors of family caregivers learned helplessness in patients with advanced digestive tract tumor ( P<0.05). Conclusions:The learned helplessness of family caregivers of patients with advanced digestive tract tumor is at a mild level. Nurses should focus on the physical and mental conditions of low-income groups and female caregivers with advanced digestive tract tumor, and regularly assess their nursing needs and health status to improve their quality of life.

Objective:To evaluate the efficacy of the domestic D-Shant device for the treatment of patients with chronic heart failure (CHF) using echocardiography.Methods:Twenty-four CHF patients who were treated with domestic D-Shant device in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2020 to December 2021 were enrolled in the study. Pulmonary capillary wedge pressure (PCWP)/ left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure, interatrial septal gradient pressure, cardiac index and pulmonary/systemic blood flow ratio (Qp/Qs) were measured before and after implantation using right heart catheterization.Left atrial end-diastolic area index (LAEDAI), left atrial end-diastolic volume index (LAEDVI), left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), right atrial end-diastolic diameter, right ventricular end-diastolic diameter, tricuspid annular plane systolic excursion (TAPSE), right ventricular tractional area change (RVFAC), device shunt aperture, velocity and pressure, together with mitral and tricuspid regurgitation severity were measured using echocardiography before, and 1 month as well as 3 months after D-Shant device implantation. Clinical data were collected and analyzed including 6-minute walking test (6MWT), New York Heart Association (NYHA) classification and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation analysis was used to determine the relation between the changes in PCWP/LAP as well as echocardiographic parameters before and 3 months after implantation and NYHA classification. Binary Logistic regression analysis was performed to determine the predictive factors of NYHA classification improvement at 3-month follow-up after D-Shant device implantation.Results:①D-Shant devices were successfully implanted in all patients. ②Compared with preoperative values, invasive PCWP/LAP systolic, diastolic and mean pressures, transatrial septal gradient, and pulmonary systolic, diastolic and mean pressures decreased significantly after implantation(all P<0.001); Qp/Qs increased significantly after implantation( P<0.001). ③Compared with preoperative values, TAPSE, RVFAC and pulmonary artery flow velocity increased at 1 month after implantation(all P<0.05), whereas a significant reduction in mitral regurgitation grade, and an increase in LVEF and pulmonary artery flow velocity at 3 months after implantation(all P<0.05). Right atrial end-diastolic diameter, right ventricular end-diastolic diameter, LAEDAI, LAEDVI, LVEDVI, LVESVI, ratio of early to late diastolic peak velocities of mitral inflow(E/A), systolic peak velocity of mitral annulus at septal site(S′), ratio of early diastolic peak velocity of mitral inflow to diastolic peak velocity of mitral annulus(E/e′), pulmonary artery diameter, inferior vena cava diameter and degree of tricuspid regurgitation did not change among before, and 1 month as well as 3 months after implantation. There were no significant changes in the device shunt aperture, velocity and pressure between 1 month and 3 months after implantation(all P>0.05). ④The significant improvements in NYHA classification, KCCQ scores and 6MWT were observed at 1 and 3 months after implantation compared with preoperative values (all P<0.01). ⑤NYHA classification at 3 months after implantation was correlated with LVEF pre-post, PCWP/LAP pre-post, TAPSE pre-post and RVFAC pre-post ( rs=0.738, -0.730, 0.738, 0.723; all P<0.001). Logistic regression analysis showed that LVEF pre-post was an independent predictor for NYHA classification improvement at 3 months after implantation ( OR=0.687, 95% CI=0.475-0.992, P=0.045) . Conclusions:Domestic D-Shant device can effectively improve the cardiac function and clinical symptoms in patients with CHF. Echocardiography is a feasible and effective method to evaluate the benefits of domestic D-Shant device for the treatment of CHF.

【Objective】 To explore the effects of massive intraoperative RBC transfusion on multiple clinical test indicators and prognosis of patients, underwent tumor surgery in order to provide evidence for rational blood transfusion and effective intervention of complications caused by massive blood transfusion in tumor patients. 【Methods】 A total of 208 patients who underwent tumor resection in our hospital from January 2019 to December 2020 and received intraoperative RBC transfusion(>10 U) were selected as the study subjects. According to the amount of blood transfusion, they were divided into group A: 10~15 U, 144 patients; Group B: >15~25 U, 48 people; Group C: >25 U, 16 people. Data of liver function, coagulation, electrolyte, platelet count and short-term prognosis were collected and compared among 3 groups before and after surgery. 【Results】 No significant difference was noticed in patient pre-operation variables including ALT (U/L), AST (U/L) and TBIL (μmol/L) among three groups recieved massive blood transfusion (P>0.05), while AST was significantly lower than that after operation (P<0.05) : 105.33±238.18 vs 113.50±185.04 vs 291.25±457.33 (P<0.05). After operation, PT (s) (14.12±2.10, 14.79±2.67 and 16.10±4.06), INR(1.25±0.20, 1.31±0.26 and 1.44±0.38) and APTT (s) (30.52±5.63, 34.57±12.80 and 34.80±10.49) extended significantly than those before operation (P<0.05), while Plt (×10⁹/L) decreased significantly (142.32±70.07, 100.04±57.50 and 85.40±41.10)(P<0.05). After operation, serum K⁺ and Ca²⁺ decreased significantly, Na⁺ and Cl^- increased significantly, and pH value decreased (P < 0.05). Hospital stay of group C (d) was 33.73±34.62 vs 17.74±14.83 vs 20.92±17.69 (P<0.05). The mortality rate was 2.8%(4/44) vs 6.3%(3/48) vs 18.8%(3/16)(P<0.05), and mortality rate of group C was higher than the other two groups. 【Conclusion】 Postoperative dysfunction of liver and coagulation in tumor patients may be related to intraoperative RBC transfusions and consequent acid-base imbalance and electrolyte disturbance. The more the units of RBC transfused, the more abnormal the patients' clinical indicators, also the longer the hospital stay and the worse the short-term prognosis.

Dysfunction of the Hippo pathway enables cells to evade contact inhibition and provides advantages for cancerous overgrowth. However, for a significant portion of human cancer, how Hippo signaling is perturbed remains unknown. To answer this question, we performed a genome-wide screening for genes that affect the Hippo pathway in Drosophila and cross-referenced the hit genes with human cancer genome. In our screen, Prosap was identified as a novel regulator of the Hippo pathway that potently affects tissue growth. Interestingly, a mammalian homolog of Prosap, SHANK2, is the most frequently amplified gene on 11q13, a major tumor amplicon in human cancer. Gene amplification profile in this 11q13 amplicon clearly indicates selective pressure for SHANK2 amplification. More importantly, across the human cancer genome, SHANK2 is the most frequently amplified gene that is not located within the Myc amplicon. Further studies in multiple human cell lines confirmed that SHANK2 overexpression causes deregulation of Hippo signaling through competitive binding for a LATS1 activator, and as a potential oncogene, SHANK2 promotes cellular transformation and tumor formation in vivo. In cancer cell lines with deregulated Hippo pathway, depletion of SHANK2 restores Hippo signaling and ceases cellular proliferation. Taken together, these results suggest that SHANK2 is an evolutionarily conserved Hippo pathway regulator, commonly amplified in human cancer and potently promotes cancer. Our study for the first time illustrated oncogenic function of SHANK2, one of the most frequently amplified gene in human cancer. Furthermore, given that in normal adult tissues, SHANK2's expression is largely restricted to the nervous system, SHANK2 may represent an interesting target for anticancer therapy.