Optimizing the management of electrophysiology labs in Chinese hospitals using a discrete event simulation tool.

BACKGROUND: The growing demand for electrophysiology (EP) treatment in China presents a challenge for current EP care delivery systems. This study constructed a discrete event simulation (DES) model of an inpatient EP care delivery process, simulating a generalized inpatient journey of EP patients from admission to discharge in the cardiology department of a tertiary hospital in China. The model shows how many more patients the system can serve under different resource constraints by optimizing various phases of the care delivery process. METHODS: Model inputs were based on and validated using real-world data, simulating the scheduling of limited resources among competing demands from different patient types. The patient stay consists of three stages, namely: the pre-operative stay, the EP procedure, and the post-operative stay. The model outcome was the total number of discharges during the simulation period. The scenario analysis presented in this paper covers two capacity-limiting scenarios (CLS): (1) fully occupied ward beds and (2) fully occupied electrophysiology laboratories (EP labs). Within each CLS, we investigated potential throughput when the length of stay or operative time was reduced by 10%, 20%, and 30%. The reductions were applied to patients with atrial fibrillation, the most common indication accounting for almost 30% of patients. RESULTS: Model validation showed simulation results approximated actual data (137.2 discharges calculated vs. 137 observed). With fully occupied wards, reducing pre- and/or post-operative stay time resulted in a 1-7% increased throughput. With fully occupied EP labs, reduced operative time increased throughput by 3-12%. CONCLUSIONS: Model validation and scenario analyses demonstrated that the DES model reliably reflects the EP care delivery process. Simulations identified which phases of the process should be optimized under different resource constraints, and the expected increases in patients served.

Hydrogen-assisted post-growth substitution of tellurium into molybdenum disulfide monolayers with tunable compositions.

Herein we report the successful doping of tellurium (Te) into molybdenum disulfide (MoS2) monolayers to form MoS2x Te2(1-x) alloy with variable compositions via a hydrogen-assisted post-growth chemical vapor deposition process. It is confirmed that H2 plays an indispensable role in the Te substitution into as-grown MoS2 monolayers. Atomic-resolution transmission electron microscopy allows us to determine the lattice sites and the concentration of introduced Te atoms. At a relatively low concentration, tellurium is only substituted in the sulfur sublattice to form monolayer MoS2(1-x)Te2x alloy, while with increasing Te concentration (up to ∼27.6% achieved in this study), local regions with enriched tellurium, large structural distortions, and obvious sulfur deficiency are observed. Statistical analysis of the Te distribution indicates the random substitution. Density functional theory calculations are used to investigate the stability of the alloy structures and their electronic properties. Comparison with experimental results indicate that the samples are unstrained and the Te atoms are predominantly substituted in the top S sublattice. Importantly, such ultimately thin Janus structure of MoS2(1-x)Te2x exhibits properties that are distinct from their constituents. We believe our results will inspire further exploration of the versatile properties of asymmetric 2D TMD alloys.

Anisotropic Spectroscopy and Electrical Properties of 2D ReS2(1-x) Se2x Alloys with Distorted 1T Structure.

2D black phosphorus (BP) and rhenium dichalcogenides (ReX2 , X = S, Se) possess intrinsic in-plane anisotropic physical properties arising from their low crystal lattice symmetry, which has inspired their novel applications in electronics, photonics, and optoelectronics. Different from BP with poor environmental stability, ReX2 has low-symmetry distorted 1T structures with excellent stability. In ReX2 , the electronic structure is weakly dependent on layer numbers, which restricts their property tunability and device applications. Here, the properties are tuned, such as optical bandgap, Raman anisotropy, and electrical transport, by alloying 2D ReS2 and ReSe2 . Photoluminescence emission energy of ReS2(1-x) Se2x monolayers (x from 0 to 1 with a step of 0.1) can be continuously tuned ranging from 1.62 to 1.31 eV. Polarization behavior of Raman modes, such as ReS2 -like peak at 212 cm-1 , shifts as the composition changes. Anisotropic electrical property is maintained in ReS2(1-x) Se2x with high electron mobility along b-axis for all compositions of ReS2(1-x) Se2x .

[Clinical efficacy and mechanism of total glucosides from white paeony for radioactive liver damage].

To discuss the effects of total glucosides from white paeony on preventing and treating radioactive liver damage, and explore its possible mechanisms. Thirty-six patients with primary hepatic carcinoma from 105th Hospital of Chinese PLA were treated with 3-dimensional conformal radiotherapy and randomly divided into simple irradiation group, total glucosides from white paeony group, and control group. The levels of AST, ALT, HA, LN, PCⅢ, CIV and TGF-ß1 in serum of various groups were determined by using ELISA method. As compared with the simple irradiation group and control group, total glucosides from white paeony could obviously decrease the levels of AST, ALT, HA, LN, PCⅢ, CIV and TGF-ß1(P<0.05, P<0.01). The results showed that the total glucosides from white paeony could effectively prevent and treat radioactive liver damage, and its mechanism might be associated with decreasing the levels of TGF-ß1, and inhibiting the synthesis of collagen synthesis.

Preparation of Single-Layer MoS(2x)Se2(1-x) and Mo(x)W(1-x)S2 Nanosheets with High-Concentration Metallic 1T Phase.

The high-yield and scalable production of single-layer ternary transition metal dichalcogenide nanosheets with ≈66% of metallic 1T phase, including MoS(2x)Se2(1-x) and Mo(x)W(1-x)S2 is achieved via electrochemical Li-intercalation and the exfoliation method. Thin film MoS(2x)Se2(1- x) nanosheets drop-cast on a fluorine-doped tin oxide substrate are used as an efficient electrocatalyst on the counter electrode for the tri-iodide reduction in a dye-sensitized solar cell.

Activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration and are associated with tumor recurrence in patients.

BACKGROUND & AIMS: The pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second most common hepatic cancer, is poorly understood, and the incidence of ICC is increasing worldwide. We searched for mutations in human ICC tumor samples and investigated how they affect ICC cell function. METHODS: We performed whole exome sequencing of 7 pairs of ICC tumors and their surrounding nontumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and nontumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). RESULTS: Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4 of 7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1 of 9 PTP genes; 41.1% had mutations in PTPN3. Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3(L232R) and PTPN3(L384H), which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than nontumor tissues had higher rates of disease recurrence than patients whose tumors did not have these characteristics. CONCLUSIONS: Using whole exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3. Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence.

Incidence, impact and predictors of residual device patency after left atrial appendage closure with the LACbes device.

BACKGROUND: The residual device patency (RDP) after left atrial appendage closure (LAAC) with the LACbes device has not been specifically explored in atrial fibrillation (AF) patients. This study aims to explore the incidence, impact and predictors of RDP detected by cardiac computed tomography angiography (CCTA) post LAAC. METHODS: AF patients implanted with the LACbes device were prospectively enrolled. CCTA device surveillance was performed at 3 months post-procedure. Major adverse events (MAEs), including stroke/transient ischemic attack, major bleeding and all-cause death, were evaluated. RESULTS: Among 141 patients with CCTA surveillance, 56 (39.7%) showed no visible leak and 85 (60.3%) showed RDP. During the median follow-up of 443 [232, 706] days, the presence of RDP was not associated with an increased risk of MAEs (adjusted hazard ratio [HR]: 4.07, 95% confidence interval [CI]: 0.49-34.24, p = 0.196), while peri-device leak (PDL) at the lobe was associated with heightened risks of MAEs (adjusted HR: 6.85, 95% CI: 1.62-28.89, p = 0.009). In patients with PDL at the lobe, antiplatelet after 6 months (HR: 0.20, 95% CI: 0.05-0.91, p = 0.038) was independent protective predictor of MAEs. Besides, current smoking (odds ratio [OR]: 7.52, 95% CI: 2.68-21.08, p < 0.001) and maximum diameter of LAA orifice (OR: 1.16, 95% CI: 1.00-1.34, p = 0.048) were independent predictors of PDL at the lobe. CONCLUSIONS: Presence of PDL at the device lobe detected by CCTA at 3-month post LAAC with LACbes is associated with unfavorable prognosis in AF patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03788941.

Real world risk of discontinuing oral anticoagulation after successful catheter ablation for atrial fibrillation.

Background: Many patients with atrial fibrillation (AF) discontinued oral anticoagulation (OAC) therapy after successful catheter ablation. We aimed to determine the real-world risks and consequences of discontinuing OAC use after catheter ablation for AF. Methods: Patients who underwent successful catheter ablation for AF from January 2004 to December 2020 were divided into continued long-term OAC (On-OAC, n = 1062) and discontinued (Off-OAC, n = 1055) groups. The long-term outcomes including thromboembolic events, major bleeding, all-cause mortality and major adverse cardiovascular events (MACE), were compared between the two groups. Results: The CHA2DS2-VASc score was 3.44 ± 1.12. After a mean follow-up of 37.09 months, thromboembolism risk was higher and major bleeding risk was lower in the Off-OAC than in the On-OAC group (Both log-rank P < 0.001). CHA2DS2-VASc score-stratified subgroup analysis showed similar cumulative event rates between the two groups in men and women with scores of 2 and 3 (intermediate risk for stroke), respectively, (P > 0.05), except for a higher major bleeding rate in the On-OAC group (P = 0.002). Patients at high risk for stroke (men and women with scores ≥3 and ≥ 4) had better non-thromboembolic and non-MACE results (Both log-rank P < 0.05). Conclusion: Men with a CHA2DS2-VASc score of 2 and women with a score of 3 had a relatively low incidence of stroke events after successful catheter ablation for AF and may be safe for anticoagulation cessation. Greater benefits from long-term OAC were observed in men with CHA2DS2-VASc score ≥3 and women with score ≥4.

Prognostic Impact of Left Atrial Appendage Patency After Device Closure.

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.

Kounis syndrome caused by bee sting: a case report and literature review.

Kounis syndrome is defined as an acute coronary syndrome (ACS) secondary to allergic or hypersensitivity reactions. It can be further categorised into subtypes such as coronary vasospasms, acute myocardial infarction or stent thrombosis based on the pathogenesis. Kounis syndrome is most likely an underdiagnosed condition in China, given the many triggers reported in the literature. Herein, we report a case of Kounis syndrome, possibly triggered by a bee sting. The patient had late onset of angina symptoms with delayed diagnosis due to unfamiliarity with this condition. In patients with clinical signs of ACS that are superimposed on a hypersensitivity reaction, especially those with pre-existing cardiovascular risk factors, Kounis syndrome should be considered, so that appropriate assessment and treatment can be initiated. Prompt management of both the allergic reaction and the ACS is vital for Kounis syndrome.

Efficacy of Left Atrial Appendage Closure and Oral Anticoagulation After Atrial Fibrillation Catheter Ablation.

Left atrial appendage closure (LAAC) proved to be noninferior to oral anticoagulation (OAC) in nonablated patients with atrial fibrillation (AF). This study aimed to compare the efficacy and safety of LAAC with those of OAC therapy in patients after AF ablation. This study included patients who underwent catheter ablation (CA) of AF between January 2016 and December 2020. The cohort was divided into CA + LAAC and CA + OAC, where propensity score matching was used to select controls, and each group contained 682 subjects. The enrolled patients' mean age was 70.34 ± 8.32 years, and 47.3% were female; their CHA2DS2-VASc score was 3.48 ± 1.17. Baseline characteristics were similar between groups. After a 3-year mean follow-up, the incidence of thromboembolic events was 1.25 and 1.10 and that of major bleeding events was 0.65 and 1.72 per 100 patient-years in the CA + LAAC, and CA + OAC groups, respectively. The rate of thromboembolisms and major adverse cardiovascular events was similar between the 2 groups (hazard ratio [HR] 1.162, 95% confidence interval [CI] 0.665 to 2.030, p = 0.598, HR 0.711, 95% CI 0.502 to 1.005, p = 0.053); however, that of major bleeding and all-cause death was significantly reduced with LAAC (HR 0.401, 95% CI 0.216 to 0.746, p = 0.004, HR 0.528, 95% CI 0.281 to 0.989, p = 0.046). There was no significant difference in periprocedural complications (p >0.05) and the rate of AF recurrence (OAC vs LAAC: 39.44% vs 40.62%, p = 0.658). LAAC is a reasonable and safer alternative to OAC therapy in high-risk patients after AF ablation.

Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency.

The ARID1A gene, which encodes a subunit of the SWI/SNF chromatin remodeling complex, has been found to be frequently mutated in many human cancer types. However, the function and mechanism of ARID1A in cancer metastasis are still unclear. Here, we show that knockdown of ARID1A increases the ability of breast cancer cells to proliferate, migrate, invade, and metastasize in vivo. The ARID1A-related SWI/SNF complex binds to the second exon of CDH1 and negatively modulates the expression of E-cadherin/CDH1 by recruiting the transcriptional repressor ZEB2 to the CDH1 promoter and excluding the presence of RNA polymerase II. The silencing of CDH1 attenuated the migration, invasion, and metastasis of breast cancer cells in which ARID1A was silenced. ARID1A depletion increased the intracellular enzymatic processing of E-cadherin and the production of C-terminal fragment 2 (CTF2) of E-cadherin, which stabilized ß-catenin by competing for binding to the phosphorylation and degradation complex of ß-catenin. The matrix metalloproteinase inhibitor GM6001 inhibited the production of CTF2. In zebrafish and nude mice, ARID1A silencing or CTF2 overexpression activated ß-catenin signaling and promoted migration/invasion and metastasis of cancer cells in vivo. The inhibitors GM6001, BB94, and ICG-001 suppressed the migration and invasion of cancer cells with ARID1A-deficiency. Our findings provide novel insights into the mechanism of ARID1A metastasis and offer a scientific basis for targeted therapy of ARID1A-deficient cancer cells.

Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma.

UNLABELLED: It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c-Met in hepatocellular carcinoma (HCC) remains unclear. We found that expression of CD151 was positively related to metastatic potential of HCC cell lines, and modified cells with CD151(high) showed higher secretion of matrix metalloproteinase 9 and aggressiveness in vitro and higher metastatic ability in vivo. Furthermore, HCC patients with vascular invasion, large tumors, multiple tumors, high tumor-node-metastasis stage, and undifferentiated tumor were prone to have higher CD151 expression. The postoperative 3-, 5-, and 7-year overall survival (OS) of patients in HCCs with CD151(high) were significantly lower than those in the CD151(low) group, and correspondingly cumulative recurrence rates in HCCs with CD151(high) were significantly higher than those in the CD151(low) group. Both CD151 and c-Met were remarkably overexpressed in HCCs, compared with adjacent nontumorous and normal liver tissues. Pearson correlation analysis showed a slight correlation between CD151 and c-Met in HCCs. Importantly, the 5- and 7-year OS rates in CD151(high)/c-Met(high) patients were 50.5% and 37.8%, respectively, significantly lower than those of CD151(low)/c-Met(low) patients (63.9% and 54.6%, respectively). Five- and 7-year cumulative recurrence rates in CD151(high)/c-Met(high) patients were 53.3% and 71.9%, respectively, markedly higher than those of CD151(low)/c-Met(low) patients (39.0% and 52.5%, respectively). Multivariate analysis revealed that CD151 and combination of CD151/c-Met were independent prognostic indicators for OS and cumulative recurrence. CONCLUSION: CD151 is positively associated with invasiveness of HCC, and CD151 or combination of CD151/c-Met is a novel marker in predicting the prognosis of HCC and a potential therapeutic target.

[Effects of recipe for invigorating kidney on expression of estrogen receptors in ovariectomized rats].

OBJECTIVE: To observe the effects of recipe for invigorating kidney on expression of estrogen receptors in ovariectomized rats. METHODS: The rats, which were given high-cholesterol diet after ovariectomy, were chosen as experimental subjects. After fed kidney-invigorating recipe for 16 weeks, the rats were killed and the levels of serum lipid and estradiol of these rats were examined. The expressions of estrogen receptor alpha and beta mRNAs in aorta, pituitary gland and hypothalamus, and the affinity of estrogen receptor-ligand were also detected. RESULTS: The kidney-invigorating recipe could increase the expression levels of estrogen receptor alpha and beta mRNAs in different parts such as aorta, pituitary gland and hypothalamus, and enhance the affinity of estrogen receptor-ligands. CONCLUSION: The recipe for invigorating kidney may meliorate atherosclerosis in ovariectomized rats by regulating the estrogen receptors.

Angiopoietin-1 and Angiopoietin-2 Expression Imbalance Influence in Early Period After Subarachnoid Hemorrhage.

PURPOSE: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional-an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other's expression. METHODS: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6-72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. RESULTS: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. CONCLUSIONS: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

[Assessment and explorations on the mechanism of neuroprotection of patients in ischemic stroke by traditional Chinese medicine].

Ischemic stroke is a common clinical emergency, with thrombolysis and neuroprotection as its cardinal treatment, and nowadays the latter is more and more stressed by stroke researchers. On the basis of pathophysiology and ischemic cascade of ischemic stroke, we now try to analyze the conceivable mechanism of intervention by tradition Chinese medicine (TCM) and hopefully provide experience for experimental and clinical research in the future.

A comparison between three-dimensional conformal radiotherapy combined with interventional treatment and interventional treatment alone for hepatocellular carcinoma with portal vein tumour thrombosis.

INTRODUCTION: We investigated the therapeutic effects of three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolisation (TACE) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). METHODS: Sixty-three HCC patients with PVTT were divided into two groups. Group A (30 patients) was treated with three-dimensional conformal radiotherapy followed by 2-3 series of TACE, while group B (33 patients) was only treated with TACE. RESULTS: The 1- and 2-year survival rates of group A were 62.40% and 20.81%, respectively, with a mean survival time of 13.0 months. The 1- and 2-year survival rates of group B were 56.49% and 18.83%, respectively, with a mean survival time of 9.0 months. There were significant differences between the two groups (log-rank chi-square value = 3.950, P = 0.047). CONCLUSION: Three-dimensional conformal radiotherapy combined with TACE can significantly improve clinical outcomes in patients with HCC and PVTT compared with TACE alone.

Endoscopic banding ligation can effectively remove the submucosal tumor.

Endoscopic band ligation for variceal bleeding in cirrhosis has been proved its safety and efficacy. We tried to treat submucosal tumors the gastrointestinal (GI) tract by endoscopic band ligation. The aim of this study was to evaluate the efficacy and safety of endoscopic band ligation in the treatment of submucosal tumors of the GI tract. There are 29 patients (15 men, 14 women, age range: 25-67 years old) with 30 submucosal lesions of the GI tract, including 15 lesions in the esophagus, 14 lesions in the of stomach and 1 lesion in the duodenal bulb. The average maximum diameter of the lesions was 7.78 mm (range: 2.4-23.6 mm). All submucosal lesions were successfully removed by band ligation. There is no bleeding and perforation in all patients. No recurrence was observed for the one month following-up. Endoscopic band ligation promises could be considered as a safe and effective for the treatment submucosal tumors of the GI tract, especially for the diameter of tumor < 25 mm.

D-2-hydroxyglutarate is essential for maintaining oncogenic property of mutant IDH-containing cancer cells but dispensable for cell growth.

Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing α-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting α-KG dependent dioxygenases. We investigated the function of D-2-HG in tumorigenesis using IDH1 and IDH2 mutant cancer cell lines. Inhibition of D-2-HG production either by specific deletion of the mutant IDH1-R132C allele or overexpression of D-2-hydroxyglutarate dehydrogenase (D2HGDH) increases α-KG and related metabolites, restores the activity of some α-KG-dependent dioxygenases, and selectively alters gene expression. Ablation of D-2-HG production has no significant effect on cell proliferation and migration, but strongly inhibits anchorage independent growth in vitro and tumor growth in xenografted mouse models. Our study identifies a new activity of oncometabolite D-2-HG in promoting tumorigenesis.

[Study of an animal model of post-menopausal atherosclerosis in rabbit and observation of the effect of herbal formula of tonifying-kidney on it].

OBJECTIVE: To establish an animal model imitating post-menopausal atherosclerosis in rabbit and observe the effect of the herbal formula of tonifying-kidney on this animal model. METHODS: The New Zealand rabbits were treated with ovariectomy, high cholesterol diet plus immune injury, and both of ovariectomy and high cholesterol diet plus immune injury respectively. The blood lipid level and the intima and media of the aorta were observed. RESULTS: The rabbits treated with ovariectomy and high cholesterol diet plus immune injury changed markedly and had low level of estrogen, high levels of CHOL, TG and dysfunction of the arterial endothelium cells. however, the chinese herbal formula of tonifying-kidney could relieve these changes. CONCLUSION: The New Zealand rabbits treated with both of ovariectomy and high cholesterol diet plus immune injury could result in the changes imitating post-menopausal atherosclerosis, and it could be improved by the treatment of herbal formula of tonifying-kidney, so we think that the changes of the animal model are related to the deficiency of the kidney in traditional Chinese medicine.