Zhuang-Gu-Fang intervenes vasculogenic and osteogenic coupling in GK rats through Notch1/Noggin/VEGF pathway.

Background: Zhuang-Gu-Fang (ZGF) has been proved to treat osteoporosis in ovariectomized rats by increasing osteogenic related factors Leptin, Ghrelin and Peptide YY(PYY). However, the mechanism of ZGF in the treatment of diabetic osteoporosis (DOP) remains unclear. The aim of this study was to explore the therapeutic effect of ZGF on DOP and its potential molecular mechanism. Methods: Using GK rats as models, the pharmacodynamic effects of ZGF on bone loss were evaluated by hematoxylin-eosin (H&E) staining and micro-computed.tomography (micro-CT). The expression levels of CD31 and endomucin (Emcn) were detected by immunofluorescence to assess the role of ZGF in angiogenic osteogenic coupling. Finally, real-time quantitative PCR (RT-PCR) and Western Blot (WB)were used to detect the expression levels of osteogenic and angiogenesis-related genes and proteins Notch1, Noggin and vascular endothelial growth factor (VEGF). Results: Administration of ZGF demonstrated a significant mitigation of bone loss attributable to elevated glucose levels. H&E staining and micro-CT showed that ZGF notably improved the integrity of the trabecular and cortical bone microarchitecture. Moreover, ZGF was found to augment the density of type H vessels within the bone tissue, alongside elevating the expression levels of Osterix, a transcription factor pivotal for bone formation. Furthermore, our findings suggest that ZGF facilitates the activation of the Notch1/Noggin/VEGF pathway, indicating a potential mechanism through which ZGF exerts its osteoprotective effects. Conclusion: Our results suggest that ZGF potentially facilitates the formation of type H vessels through the Notch1/Noggin/VEGF pathway. This action not only enhances angiogenic-osteogenic coupling but also contributes to the improvement of bone structure and density. Consequently, ZGF emerges as a promising therapeutic agent for the prevention and management of DOP, offering a novel approach by leveraging angiogenesis-dependent osteogenesis.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Ginsenoside Rg1 interferes with the progression of diabetic osteoporosis by promoting type H angiogenesis modulating vasculogenic and osteogenic coupling.

Ginsenoside Rg1 (Rg1) has been demonstrated to have antidiabetic and antiosteoporotic activities. The aim of this study was to investigate the protective effect of Rg1 against diabetic osteoporosis and the underlying mechanism. In vitro, we found that Rg1 increased the number of osteoprogenitors and alleviated high glucose (HG) induced apoptosis of osteoprogenitors by MTT assays and flow cytometry. qRT‒PCR and western blot analysis suggested that Rg1 can also promote the secretion of vascular endothelial growth factor (VEGF) by osteoprogenitors and promote the coupling of osteogenesis and angiogenesis. Rg1 can also promote the proliferation of human umbilical vein endothelial cells (HUVECs) cultured in high glucose, enhance the angiogenic ability of endothelial cells, and activate the Notch pathway to promote endothelial cells to secrete the osteogenesis-related factor Noggin to regulate osteogenesis, providing further feedback coupling of angiogenesis and osteogenesis. Therefore, we speculated that Rg1 may have similar effects on type H vessels. We used the Goto-Kakizaki (GK) rat model to perform immunofluorescence staining analysis on two markers of type H vessels, Endomucin (Emcn) and CD31, and the osteoblast-specific transcription factor Osterix, and found that Rg1 stimulates type H angiogenesis and bone formation. In vivo experiments also demonstrated that Rg1 promotes VEGF secretion, activates the Noggin/Notch pathway, increases the level of coupling between type H vessels and osteogenesis, and improves the bone structure of GK rats. All of these data reveal that Rg1 is a promising candidate drug for treating diabetic osteoporosis as a potentially bioactive molecule that promotes angiogenesis and osteointegration coupling.

Large-conductance Ca2 +-activated K+ channel ß1-subunit maintains the contractile phenotype of vascular smooth muscle cells.

Background: Vascular smooth muscle cells (VSMCs) phenotype switching is very important during the pathogenesis and progression of vascular diseases. However, it is not well understood how normal VSMCs maintain the differentiated state. The large-conductance Ca2+-activated K+ (BKCa) channels are widely expressed in VSMCs and regulate vascular tone. Nevertheless, there is limited understanding of the role of the BKCa channel in modulation of the VSMC phenotype. Methods and results: We assessed BKCa channel expression levels in normal and injured carotid arteries from rats of the balloon-injury model. A strong decrease of BKCa-ß1 was seen in the injured carotid arteries, accompanied by a parallel decrease of the VSMC contractile markers. BKCa-ß1 in primary rat aortic VSMCs was decreased with the increase of passage numbers and the stimulation of platelet-derived growth factor (PDGF)-BB. Conversely, transforming growth factor ß upregulated BKCa-ß1. Meanwhile, the BKCa-ß1 level was positively associated with the levels of VSMC contractile proteins. Intravenous injection of PDGF-BB induced downregulation of BKCa-ß1 expression in the carotid arteries. Knockdown of BKCa-ß1 favored VSMC dedifferentiation, characterized by altered morphology, abnormal actin fiber organization, decreased contractile proteins expression and reduced contractile ability. Furthermore, the resultant VSMC dedifferentiated phenotype rendered increased proliferation, migration, enhanced inflammatory factors levels, and matrix metalloproteinases activity. Studies using primary cultured aortic VSMCs from human recapitulated key findings. Finally, protein level of BKCa-ß1 was reduced in human atherosclerotic arteries. Conclusion: BKCa-ß1 is important in the maintenance of the contractile phenotype of VSMCs. As a novel endogenous defender that prevents pathological VSMC phenotype switching, BKCa-ß1 may serve as a potential therapeutic target for treating vascular diseases including post-injury restenosis and atherosclerosis.

The Establishment of Hypertrophic Cardiomyopathy Diagnosis Model via Artificial Neural Network and Random Decision Forest Method.

Hypertrophic cardiomyopathy is a hereditary disease characterized by asymmetric ventricular hypertrophy as the key anatomical feature. Currently, there exists no effective method for the early diagnosis of hypertrophic cardiomyopathy. In this analysis, we incorporated multiple GEO datasets containing RNA profiles of hypertrophic cardiomyopathic patient tissues, identified 642 differentially expressed genes, and performed GO and KEGG analyses. Furthermore, we narrowed down 46 characteristic genes from these differentially expressed genes using random decision forests and conducted transcription factor regulation analysis on them. Using 40 genes that showed overlap between the training set and the verification set, the artificial neural network was trained, and the final MPS scoring model was constructed, and a receiver-operating characteristic (ROC) curve was drawn. We used the MPS model to predict the verification dataset and drew the ROC curve, which demonstrated the good prediction performance of the model. In conclusion, this study combines a random decision forest and artificial neural network to build a diagnostic model for hypertrophic cardiomyopathy to predict the disease, aiming at early detection and treatment, prolonging the survival time, and improving the quality of life of patients.

Nosocomial Infections During Extracorporeal Membrane Oxygenation in Pediatric Patients: A Multicenter Retrospective Study.

Objective: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients with respiratory and/or cardiac failure. This study aimed to investigate the epidemiology and risk factors of nosocomial infection (NI) in pediatric patients who underwent ECMO for respiratory and/or circulatory failure. Methods: Medical records for patients that were administered underwent ECMO support at Xiangya Second Hospital of Central South University, The Sixth Medical Center of PLA General Hospital, and Children's Hospital Affiliation of Zhengzhou University, from September 2012 to December 2019 were retrospectively reviewed. Clinical data of the patients who developed NI were collected and analyzed. Univariate and multivariate logistic regressions were performed to identify the independent predictive factors of NI during ECMO. Results: A total of 54 first episodes of NI were identified in the 190 patients on ECMO, including 32 cases of respiratory tract infections, 20 cases of bloodstream infections, and 2 cases of surgical site wound infections. Gram-negative pathogens were the dominant pathogens isolated, accounting for 92.6% of the NI. The incidence of ECMO-related NI was 47.6 cases per 1,000 ECMO days. In the univariate logistic regression, ECMO mode, ECMO duration, ICU duration, and peritoneal dialysis were associated with the development of NI in patients with ECMO support. However, in the multivariate analysis, only ECMO duration (OR = 2.46, 95%CI: 1.10, 5.51; P = 0.029), ICU duration (OR = 1.35, 95%CI: 1.05, 1.59; P = 0.017) and peritoneal dialysis (OR = 2.69, 95%CI: 1.08, 5.73; P = 0.031) were the independent predictive factors for NI during ECMO support. Conclusion: This study identified the significant correlation between ECMO-related NI and ECMO duration, ICU duration, and peritoneal dialysis. Appropriate preventive measures are needed for hospitals to reduce the incidence of ECMO in pediatric patients.

Machine Learning-Based Personalized Risk Prediction Model for Mortality of Patients Undergoing Mitral Valve Surgery: The PRIME Score.

Background: Mitral valve surgery (MVS) is an effective treatment for mitral valve diseases. There is a lack of reliable personalized risk prediction models for mortality in patients undergoing mitral valve surgery. Our aim was to develop a risk stratification system to predict all-cause mortality in patients after mitral valve surgery. Methods: Different machine learning models for the prediction of all-cause mortality were trained on a derivation cohort of 1,883 patients undergoing mitral valve surgery [split into a training cohort (70%) and internal validation cohort (30%)] to predict all-cause mortality. Forty-five clinical variables routinely evaluated at discharge were used to train the models. The best performance model (PRIME score) was tested in an externally validated cohort of 220 patients undergoing mitral valve surgery. The model performance was evaluated according to the area under the curve (AUC). Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were compared with existing risk strategies. Results: After a median follow-up of 2 years, there were 133 (7.063%) deaths in the derivation cohort and 17 (7.727%) deaths in the validation cohort. The PRIME score showed an AUC of 0.902 (95% confidence interval [CI], 0.849-0.956) in the internal validation cohort and 0.873 (95% CI: 0.769-0.977) in the external validation cohort. In the external validation cohort, the performance of the PRIME score was significantly improved compared with that of the existing EuroSCORE II (NRI = 0.550, [95% CI 0.001-1.099], P = 0.049, IDI = 0.485, [95% CI 0.230-0.741], P < 0.001). Conclusion: Machine learning-based model (the PRIME score) that integrate clinical, demographic, imaging, and laboratory features demonstrated superior performance for the prediction of mortality patients after mitral valve surgery compared with the traditional risk model EuroSCORE II. Clinical Trial Registration: [http://www.clinicaltrials.gov], identifier [NCT05141292].

Large-Conductance Calcium-Activated Potassium Channel Opener, NS1619, Protects Against Mesenteric Artery Remodeling Induced by Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor.

Background Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AAs) extensively exist in patients with hypertensive diseases and have been demonstrated to play crucial roles in the pathophysiological process of vascular remodeling. However, the treatment options are limited. The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture. We have previously observed that AT1-AAs have an inhibitory effect on BK channels. However, whether BK channel dysfunction is involved in AT1-AAs-induced vascular remodeling and the therapeutic effect of BK channel opener is unclear. Methods and Results In our study, mesenteric arteries from AT1-AAs-positive rats exhibited increased wall thickness, narrowing of the arteriolar lumen, and increased collagen accumulation. Patch clamp test results showed that the voltage sensitivity of BK channel declined in mesenteric arteriolar smooth muscle cells from AT1-AAs-positive rats. Experiments with freshly isolated mesenteric arteriolar smooth muscle cells showed that AT1-AAs reduced the opening probability, open levels, open dwell time, and calcium sensitivity of BK channel. Experiments with HEK293T cells transfected with GFP-ZERO-BK α-subunit plasmids suggested a BK channel α-subunit-dependent mechanism. BK channel α-subunit deficient, namely KCNMA1-/- rats showed a phenotype of mesenteric artery remodeling. The administration of NS1619, a specific BK channel opener targeting the α-subunit, reversed the phenotypic transition and migration induced by AT1-AAs in cultured mesenteric arteriolar smooth muscle cells. Finally, perfusion of NS1619 significantly relieved the pathological effects induced by AT1-AAs in vivo. Conclusions In summary, we provide compelling evidence that BK channel α-subunit dysfunction mediates AT1-AAs-induced mesenteric artery remodeling. Preservation of BK channel activity may serve as a potential strategy for the treatment of AT1-AAs-induced maladaptive resistance artery remodeling.

Severe Patients With ARDS With COVID-19 Treated With Extracorporeal Membrane Oxygenation in China: A Retrospective Study.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis affecting over 200 countries worldwide. Extracorporeal membrane oxygenation (ECMO) has been increasingly used in the management of COVID-19-associated end-stage respiratory failure. However, the exact effect of ECMO in the management of these patients, especially with regards to complications and mortality, is unclear. Methods: This is the largest retrospective study of ECMO treated COVID-19 patients in China. A total of 50 ECMO-treated COVID-19 patients were recruited. We describe the main characteristics, the clinical features, ventilator parameters, ECMO-related variables and management details, and complications and outcomes of COVID-19 patients with severe acute respiratory distress syndrome (ARDS) that required ECMO support. Results: For those patients with ECMO support, 21 patients survived and 29 died (mortality rate: 58.0%). Among those who survived, PaO2 (66.3 mmHg [59.5-74.0 mmHg] and PaO2/FiO2 (68.0 mmHg [61.0-76.0 mmHg]) were higher in the survivors than those of non-survivors (PaO2: 56.8 mmHg (49.0-65.0 mmHg), PaO2/FiO2 (58.2 mmHg (49.0-68.0 mmHg), all P < 0.01) prior to ECMO. Patients who achieved negative fluid balance in the early resuscitation phase (within 3 days) had a higher survival rate than those who did not (P = 0.0003). Conclusions: In this study of 50 cases of ECMO-treated COVID-19 patients, a low PO2/FIO2 ratio before ECMO commencement may indicate a poor prognosis. Negative fluid balance in the early resuscitation phase during ECMO treatment was a predictor of increased survival post-ECMO treatment.

Extracorporeal membrane oxygenation (ECMO) for critically ill patients with coronavirus disease 2019 (COVID-19): A retrospective cohort study.

PURPOSE: The role of extracorporeal membrane oxygenatio (ECMO) for rescue therapy of respiratory failure in critically ill coronavirus disease 2019 (COVID-19) patients remains controversial. We aimed to evaluate the clinical outcomes of ECMO in the treatment of COVID-19 compared with conventional ventilation support. METHODS: In this retrospective cohort study, data were collected on extremely critical patients with COVID-19 from January 2020 to March 2020 in intensive care unit of a hospital in charge by national rescue team in Wuhan, China, the epicenter of pandemic. Patients were classified into the ECMO group and the conventional ventilation non-ECMO group. Clinical characteristics, technical characteristics, laboratory results, mortality, and complications of the two groups were analyzed. RESULTS: 88 patients with extremely critical COVID-19 were screened; 34 received ECMO support and 31 received conventional ventilation support. Both groups had comparable characteristics at baseline in terms of age, gender, and comorbidities. Before ECMO or conventional therapy, patients in the two groups had sever acute respiratory distress syndrome with a mean partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2 /FiO2 ) ratio of 69.6 and 75.4, respectively. At the time of reporting, patients in the ECMO had significantly lower in-hospital mortality compared with the control group (58.8 vs. 93.5%, p = .001). CONCLUSION: ECMO is shown to decrease the mortality of extremely critical ill COVID-19 patients compared with the conventional treatment. Although complications occurred frequently, ECMO could still be a rescue therapy for the treatment of COVID-19 during the pandemic.

MicroRNA-375-3p in endothelial progenitor cells-derived extracellular vesicles relieves myocardial injury in septic rats via BRD4-mediated PI3K/AKT signaling pathway.

OBJECTIVE: Sepsis can induce myocardial dysfunctions and endothelial progenitor cells (EPCs)-derived extracellular vesicles (EVs) can attenuate sepsis. Concerning to that, this article is intended to decode whether microRNA (miR)-375-3p in EPCs-EVs could affect myocardial injury in sepsis. METHODS: Rat bone marrow-derived EPCs and EPCs-EVs were harvested. A rat model of sepsis was established by cecal ligation and puncture. Septic rats were injected with EPCs-EVs that interfered with miR-375-3p, after which cardiac function, inflammatory response, pathological damage, oxidative stress and apoptosis were detected in myocardial tissues. miR-375-3p, bromodomain 4 (BRD4), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) expression in myocardial tissues, and their reciprocals were identified. RESULTS: Septic rats expressed reduced miR-375-3p and elevated BRD4 in myocardial tissues. EPCs-EVs improved cardiac function, suppressed inflammation, oxidative stress and apoptosis, as well as attenuated the pathological damage of myocardial tissues in septic rats. Up-regulated/down-regulated miR-375-3p in EPCs-EVs relieved/deteriorated myocardial injury in septic rats. miR-375-3p targeted BRD4 to activate PI3K/AKT pathway, thereafter to ameliorate myocardial injury in septic rats. CONCLUSION: It is illustrated that miR-375-3p in EPCs-EVs activates BRD4-mediated PI3K/AKT signaling pathway to ameliorate myocardial injury in septic rats, which provides a therapeutic target for myocardial injury in sepsis.

Circular RNA circFADS2 is overexpressed in sepsis and suppresses LPS-induced lung cell apoptosis by inhibiting the maturation of miR-15a-5p.

BACKGROUND: Circular RNA circFADS2 plays protective roles in LPS-induced inflammation, which promotes sepsis, suggesting its involvement in sepsis. METHODS: Expression of circFADS2, mature miR-15a-5p, and miR-15a-5p precursor in plasma samples from sepsis patients and healthy controls was determined by RT-qPCR. The circFADS2 expression vector was transfected in lung cells, followed by the measurement of the expression levels of mature miR-15a-5p and miR-15a-5p precursor to study the role of circFADS2 in miR-15a-5p maturation. Cell apoptosis was analyzed by cell apoptosis assay. RESULTS: CircFADS2 was upregulated in sepsis and inversely correlated with mature miR-15a-5p, but not miR-15a-5p precursor. In lung cells, circFADS2 overexpression decreased the level of mature miR-15a-5p, but not miR-15a-5p precursor. LPS treatment decreased miR-15a-5p expression and increased circFADS2 level. Cell apoptosis analysis showed that circFADS2 overexpression reduced miR-15a-5p overexpression-induced apoptosis of LPS-treated lung cells. CONCLUSIONS: CircFADS2 is upregulated in sepsis to suppress LPS-induced lung cell apoptosis by inhibiting miR-15a-5p maturation.

Robotically assisted coronary artery bypass graft surgery versus drug-eluting stents for patients with stable isolated proximal left anterior descending disease.

OBJECTIVE: To compare the midterm outcomes of patients with isolated left anterior descending disease (iLAD) who underwent robotically assisted coronary artery bypass graft (R-CABG) and percutaneous coronary intervention (PCI) with drug eluting stents (DES). METHOD: Clinic data was collected in 223 patients who underwent R-CABG in our hospital between July, 2007 to November, 2014. Cardiology Database System of our hospital was used to identify 4047 patients who underwent PCI with DES for LAD lesion between April, 2011 to November, 2014. Total 496 patients received DES and 108 patients underwent R-CABG after screening. Patients were propensity matched into 108 R-CABG and DES pairs according to vital statistic. Mortality, myocardial infarction (MI), stroke, repeat target lesion revascularization (r-TLR), main adverse cardiac and cerebral events (MACCE), and angina relief were compared across pairs. RESULT: Kaplan-Meier estimates for R-CABG and DES had no significant difference in mortality (p = 1.00), MI (p = .32), Stroke (p = .80), and MACCE (p = .47), but the rate of r-TLR (p = .03) were lower in R-CABG group. Patients who underwent R-CABG had better angina relief (p = .02), lower rate of arrhythmia (p < .001), and recurrent angina (p = .02) after operation compared patients received DES. CONCLUSION: R-CABG offers lower r-TLR rate and better angina relief compared with DES for revascularization in patients with isolated proximal LAD stenosis and there was no difference in mortality, MI, stroke, and MACCE between them.

Zhuang-Gu-Fang Treats Osteoporosis in Ovariectomized Rats by Increasing the Osteogenesis-Related Factors Leptin, Ghrelin, and PYY.

Zhuang-Gu-Fang is a Chinese medicinal compound mixture, which is mainly composed of traditional remedies like the Epimedium Herb, Astragalus, and Eucommia among many others. The study is aimed at investigating the therapeutic effect of Zhuang-Gu-Fang in ovariectomized rats. Fifty six-month-old Wistar rats were randomly selected and divided into 5 groups (n = 10), namely, model group, positive group, low-dose Chinese medicine group, medium-dose group, and high-dose group. Another 10 sham operation Wistar rats were taken as a negative control group. After 3 months of intervention, the bone mineral density (BMD), procollagen type I N-peptide (PINP), beta C-terminal cross-linked telopeptides of type I collagen carboxyl-terminal peptide (ß-CTX), Leptin, Ghrelin, and Peptide YY (PYY) of each group were measured. Besides, the ultrastructure of bone structure and osteoblasts was also observed by transmission electron microscopy. Western blot method was used to detect the expression levels of Leptin and Ghrelin in bone tissue, and RT-PCR detected the mRNA expression levels of Leptin and Ghrelin. BMD test indicated that Zhuang-Gu-Fang could effectively prevent the loss of tibia bone in ovariectomized rats. Histomorphology analysis showed that Zhuang-Gu-Fang could preserve trabecular bone structure integrity and improve osteoblast ultrastructure. Notably, the study found out that Zhuang-Gu-Fang worked through balancing the bone metabolism via increasing bone formation/resorption ratio. Additionally, Zhuang-Gu-Fang highlighted the recovery effects in multiple levels of osteogenesis- and osteanagenesis-related factors Leptin, Ghrelin, and PYY. Conclusively, the study proved the therapeutic potential of the Zhuang-Gu-Fang for postmenopausal osteoporosis (PMOP) and further revealed that its therapeutic effect was related to the balance of bone metabolism and the recovery effects of bone-related factors Leptin, Ghrelin, and PYY.

Robot-assisted Level III-IV Inferior Vena Cava Thrombectomy: Initial Series with Step-by-step Procedures and 1-yr Outcomes.

BACKGROUND: Level III-IV robot-assisted inferior vena cava (IVC) thrombectomy (RA-IVCT) has been reported in limited series. OBJECTIVE: To report our initial series of level III-IV RA-IVCT with step-by-step procedures and 1-yr outcomes. DESIGN, SETTING, AND PARTICIPANTS: From November 2014 to January 2018, 13 patients with level III-IV IVC tumor thrombi underwent RA-IVCT with a minimum of 1-yr follow-up. SURGICAL PROCEDURE: Level III RA-IVCT requires liver mobilization and clamping of first porta hepatis (FPH), and suprahepatic and infradiaphragmatic IVC. Level IV RA-IVCT requires establishment of cardiopulmonary bypass (CPB). Thoracoscopy-assisted thrombectomy was performed for the intra-atrium part of the thrombus under CPB. Infradiaphragmatic RA-IVCT was completed in a manner similar to that of level III RA-IVCT. MEASUREMENTS: Detailed techniques were described for various scenarios. Baseline and perioperative outcomes were reported, and descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Median operative time was 465 (interquartile range [IQR]: 338-567) min. Median estimated intraoperative blood loss was 2000 (IQR: 1000-3000) ml. The rates of intraoperative blood transfusion and postoperative transformation to the intensive care unit ward were 92.3% and 100%, respectively. Median FPH blocking time was 40 (IQR: 25-60) min and the CPB time was 72 (IQR: 51-87) min. Three cases had grade IV complications, including two vascular injuries that were treated with intraoperative endoscopic sutures and one perioperative death. The perioperative mortality rate was 7.7%. During an 18-mo follow-up, two patients died and one patient progressed. CONCLUSIONS: Although the risks involved are high, level III-IV RA-IVCT is feasible and serves as an alternative minimally invasive method for selected patients. It also requires more complex techniques and multidisciplinary cooperation. PATIENT SUMMARY: We studied the treatment of patients with level III-IV inferior vena cava (IVC) tumor thrombi using a robotic approach. This technique was feasible for well-selected patients. However, level III-IV robot-assisted IVC thrombectomy requires more complex techniques and multidisciplinary cooperation.

[Robotic surgery versus conventional open chest surgery for heart tumor: a propensity score matching analysis].

OBJECTIVE: To compare conventional open chest surgery and robotic surgery for their efficacy, short?term outcomes and patient selection in the treatment of heart tumors. Method The clinical data were collected from 225 patients (a total of 228 operations) who underwent cardiac neoplasm resection in our hospital between January, 1993 and April, 2016. A propensity score matching (PSM) was established according to the vital baseline data of the patients receiving conventional open chest surgery (n=125) and robotic surgery (n=60) after screening. The patients were matched for propensity into 60 pairs, and the efficacy, short?term outcomes and patient selection were compared between the two groups. RESULTS: Before PSM, the patients in conventional surgery group had significantly greater tumor size (P<0.001) and a higher proportion of patients with New York Heart Association functional class III and IV (P<0.001). The patients' baseline data were nearly balanced (P=0.982) between the two groups after matching. No significant differences were found between the two groups in cardiopulmonary bypass time (P=0.256), crossclamp time (P=0.862), in?hospital mortality (P=1.000), arrhythmia (P=1.000), delayed mechanical ventilation (>24 h; P=0.209), thoracic complications (P=0.611) or systemic embolism (P=1.000). The survival rates were 100% in both groups in the 6?month follow?up after the operation, and no significant difference was found between the two groups in the incidence of major adverse cardiac and cerebrovascular events within 6 months (P=0.438). CONCLUSION: Robotic heart tumor resection has a favorable efficacy with a good short?term prognosis, and can serve as an alternative for treatment of solitary lesions in low?risk patients receiving operations for the first time.

JinqiJiangtang tablets for pre-diabetes: A randomized, double-blind and placebo-controlled clinical trial.

This study observed the efficacy and safety of JinqiJiangtang tablets (JQJT tablets, a traditional Chinese patent medicine) for pre-diabetes. Four hundred patients with pre-diabetes at five centres were treated for 12months and followed for an additional 12months to investigate the preventative effects of JQJT tablets (Registration ID: ChiCTR-PRC-09000401). The incidence rate of diabetes mellitus was the primary endpoint. The risk of converting from pre-diabetes to diabetes was 0.58-fold less in the JQJT tablets group than in the placebo group [HR (95% CI): 0.58 (0.384, 0.876), P = 0.010]. Furthermore, the probability of achieving normalized blood glucose was 1.41-fold greater in the JQJT tablets group than in the placebo group [HR (95% CI): 1.41 (1.002, 1.996), P = 0.0049]. ITT analysis revealed that the incidence of diabetes upon treatment completion was 16.5% in the JQJT tablets group compared with 28.9% in the control group. The percentage of patients with normalized blood glucose upon 12-month intervention was 41.8% in the JQJT tablets group compared with 27.8% in the control group. JQJT tablets could be an effective intervention for preventative treatment of Type 2 diabetes mellitus.

Protective role of Pollen Typhae total flavone against the palmitic acid-induced impairment of glucose-stimulated insulin secretion involving GPR40 signaling in INS-1 cells.

Prolonged elevated levels of free fatty acids (FFAs) contribute to the impairment of insulin secretion function of pancreatic ß cells, a hallmark of type 2 diabetes, which is partly attributed to the dysfunction of G-protein-coupled receptor 40 (GPR40) signaling. Pollen Typhae total flavone (PTF), an extract from a Chinese herbal medicine named Pollen Typhae, has been reported to effectively treat type 2 diabetes, but the underlying mechanisms remain to be fully elucidated. In the present study, palmitic acid (PA), a saturated fatty acid, severely impaired glucose-stimulated insulin secretion (GSIS) in a time-dependent manner in INS-1 cells, and PTF treatment prevented the impairment in a dose-dependent manner. Moreover, PTF improved insulin secretion function in rats presenting with type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. Furthermore, PA exposure for 24 h decreased the protein expression of GPR40, phospholipase C (PLC)ß1, PLCß3, and protein kinase C (PKC), and inhibited the activity of PLC and PKC stimulated by GW9508, a GPR40 agonist. In addition, PTF enhanced the protein expression of GPR40 and to a certain extent strengthened the protein expression of PKC, increased cellular levels of triphosphoinositide (IP3) and diacylglycerol (DAG), and promoted GW9508-stimulated activity of PLC and PKC reduced by PA in INS-1 cells, which were blocked by PLC inhibitor U-73122 and PKC inhibitor staurosporine, respectively. Additionally, the improvement in PA-induced impairment of GSIS by PTF in INS-1 cells was restrained by U-73122, staurosporine, and calcium channel inhibitor nifedipine, respectively. The results indicate that PTF exerts a protective role against PA-induced impairment of GSIS involving GPR40 signaling in INS-1 cells.