[Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children].

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Investigating the prognostic value of m6A methylation-related genes in renal cell carcinoma patients.

OBJECTIVE: The objective of this research was to explore the importance of N6-methyladenosine (m6A) methylation-associated genes concerning the clinical outcome of patients with renal cell carcinoma (RCC) by employing the Cancer Genome Atlas (TCGA) database along with various bioinformatics methodologies. MATERIALS AND METHODS: The transcriptome and clinical data of RCC patients were obtained from the TCGA database. We identified the differential expression of 13 genes and selected potential predictive genes for further analysis of their prognostic values. RESULTS: Ten genes (YTHDC2, FTO, YTHDF2, METTL3, KIAA1429, ZC3H13, METTL14, ALKBH5, WTAP, and RBM15) exhibited altered expression levels in RCC. Subgroup analysis based on m6A methylation-related gene expression levels revealed no significant differences in survival rates, but significant differences were observed in grade, T stage, and gender. Five potential predictors (FTO, RBM15, YTHDC2, ZC3H13b, and ALKBH5) demonstrated independent predictive value. Multivariate analysis selected two regulators (METTL14 and METTL3), and based on these, prognostic signals for RCC were constructed, independent of potential confounding factors. The model clearly distinguished between samples with good and poor prognoses. CONCLUSIONS: The expression levels of m6A methylation-related genes in RCC patients were found to differ and were associated with survival rates and prognosis. These findings suggest that m6A methylation-related genes could serve as prognostic indicators and promising therapeutic targets for RCC patients.

Cosmic Ray Background Removal With Deep Neural Networks in SBND.

In liquid argon time projection chambers exposed to neutrino beams and running on or near surface levels, cosmic muons, and other cosmic particles are incident on the detectors while a single neutrino-induced event is being recorded. In practice, this means that data from surface liquid argon time projection chambers will be dominated by cosmic particles, both as a source of event triggers and as the majority of the particle count in true neutrino-triggered events. In this work, we demonstrate a novel application of deep learning techniques to remove these background particles by applying deep learning on full detector images from the SBND detector, the near detector in the Fermilab Short-Baseline Neutrino Program. We use this technique to identify, on a pixel-by-pixel level, whether recorded activity originated from cosmic particles or neutrino interactions.

The role of alternative oxidase in plant hypersensitive response.

The innate immune system of plants is crucial in defining the fate of a plant cell during plant-pathogen interactions. This response is often accompanied by a hypersensitive reaction leading to the death of a plant cell and restricted pathogen growth. Plant mitochondria, in this case, play a key role by maintaining a balance between cell respiration and reactive oxygen species formation. One of the key features of the hypersensitive response is the shift of the normal plant respiratory pathway to a special 'alternative' pathway. Plants contain an enzyme, alternative oxidase, for maintaining metabolic homeostasis of the cell. This energy dissipating respiration provides a branch in normal respiration by using ubiquinone to form water and heat, thus maintaining the energy status of the cell. Alternative oxidase is thought to minimize production of reactive oxygen species and can also function in 'anti-apoptotic' machinery in plant cells. In this mini review, we briefly describe the alternative respiratory pathway and explain the role of alternative oxidase in important cellular processes, such as programmed cell death and the hypersensitive response.

The role of cyanide-resistant respiration in Solanum tuberosum L. against high light stress.

Cyanide-resistant respiration in potato mitochondria is an important pathway for energy dissipation. It can be activated by high light; however, it is unclear what roles cyanide-resistant respiration plays in the response to high light stress in potato. We designed a CRISPR vector for the functional gene StAOX of the potato cyanide-resistant respiratory pathway. Agrobacterium tumefaciens GV3101 was transformed into potato. Hydrogen peroxide level, MDA content, antioxidant activity and cyanide-resistant respiratory capacity of potato leaves under high light stress were determined. Photosynthetic efficiency and chlorophyll content were determined. In addition, the operation of the malate-oxaloacetate shuttle route and transcription level of photorespiration-related enzymes were also examined. The results showed that two base substitutions occurred at the sequencing target site on leaves of the transformed potato. Accumulation of ROS and increased membrane lipid peroxidation were detected in the transformed potato leaves and lower photosynthetic efficiency was observed. The transcription level of the malate-oxaloacetate shuttle route and photorespiration-related enzymes also significantly increased. These results indicate that the cyanide-resistant respiration is an important physiological pathway in potato in response to high light stress. It also suggests that plant cyanide-resistant respiration is closely related to photosynthesis. This implies the unexplored importance of plant cyanide-resistant respiration in plant photosynthesis, energy conversion and carbon skeleton formation.

Heart failure and fracture risk: a meta-analysis.

This meta-analysis was conducted to investigate whether heart failure is associated with an increased risk of fractures by summarizing all the available evidence. The PubMed, EMBASE, and Cochrane Library databases were searched for all relevant studies published from the date of database inception to April 2018. Studies that investigated the association between heart failure and fracture risk and conducted a comparison with controls were included. Seven cohort studies were finally identified as eligible for inclusion in the meta-analysis. All included studies were of high quality as evaluated by the Newcastle-Ottawa Scale. There was a significantly higher risk of any fracture in patients diagnosed with heart failure (N = 53,038) than in controls (N = 126,727) (RR 1.66, 95% CI 1.14-2.43, I2 = 94%, P = 0.008). The results were the same for hip (RR 3.45, 95% CI: 1.86-6.40, I2 = 95%, P < 0.0001) and humerus fractures (RR 1.91, 95% CI 1.07-3.40, I2 = 39%, P = 0.03) but not for vertebral and forearm fractures. To conclude, this meta-analysis demonstrated that patients with heart failure had an increased risk of fractures, especially hip and humerus fractures. Patients with heart failure may need to pay greater attention to their bone health. This meta-analysis found a significantly higher risk of fractures in patients with heart failure than in those without heart failure. Greater attention should be paid to bone health in patients with heart failure.

[MiR-222-3р Regulates the Proliferation and Differentiation of C2C12 Myoblasts by Targeting BTG2].

MiR-222-3р has been implicated in tumor cell proliferation and has an important role in the differentiation and maturation of myogenic cells. However, its role in skeletal myoblast proliferation is still unclear. In this study, we found that miR-222-3р expression increases initially and then decreases during C2C12 myoblast proliferation. Using synthetic miRNA mimics and inhibitors in gain- or loss-of-function experiments, we snowed that miR-222-3р overexpression in C2C12 cells promotes myoblast proliferation and represses myofiber formation, while miR-222-3р downregulation has the opposite effect. Using a prediction program, BTG2 was identified as a possible target gene of miR-222-3р. During myogenesis, miR-222-3р mimics repress BTG2 expression, while miR-222-3р inhibitors promote BTG2 expression. Using dual-luciferase reporter assay, we further demonstrated that miR-222-3р specifically targets BTG2. Additionally, we show that siRNA-mediated downregulation of BTG2 expression in C2C12 myoblasts promotes the proliferation and suppresses differentiation. In conclusion, we provide a novel insight into the mechanism by which miR-222-3р regulates the proliferation and differentiation of C2C12 myoblasts by targeting BTG2. This information contributes to our understanding of the role of miRNAs in skeletal muscle development.

Tunable surface plasmon-polaritons based on quantum coherence.

Tunable surface plasmons on the interface of a multilevel atomic medium with a cross coupling of the electric and magnetic components of a plasmonic field are investigated. The strong chirality resulting from the quantum coherence leads to some exciting properties of the surface plasmons. Compared to the traditional chiral-metal interface, surface plasmonic mode can still be found at the interface between such atomic media and a dielectric even when both the permittivity and the permeability of the medium are positive. This is in contrast to the conventional plasmonic systems where the signs of the permittivities or permeabilities on the two sides of the interface are opposite. We call this phenomenon an electromagnetically induced plasmon. Additionally, as the chirality and effective refractive index of the atomic medium are dependent on the intensity and phase of the controlling field, we can conveniently manipulate the properties of the surface plasmons.

[Robot-assisted partial nephrectomy for treating renal hilar tumors: a clinical study of 22 cases].

Objective: To analyze and summarize the surgical experience of robotic-assisted laparoscopic partial nephrectomy (RAPN) for treating renal hilar tumors, and assess the efficacy and safety of this surgery. Methods: The clinical data of 22 renal hilar tumor patients who underwent RAPN in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine between September 2015 and September 2017 was analyzed. The patients included 19 males and 3 females, with an average age of (55.6 ±13.0) years old and the age range was 28-75 years. In 13 cases, the tumors were in left kidney, and 9 in the right. There were 10 large tumors (>4 cm diameter), the average tumor size was (3.7±1.9) cm. Preoperative glomerular filtration rate was normal in all cases. Results: The surgery was successfully finished in all of the cases, with no conversion to open surgery. The mean duration of the surgery was 80-270 min, with an average of (134.7±44.5) min. The blood loss was 80-500 ml, with an average of (135.9±130.7) ml, and none of the cases needed intraoperative blood transfusion. The warm ischemia time was 8-25 min, with an average of (18.2±4.0) min. The postoperative length of hospitalization was 7-23 d, with an average of (11.5±4.1) d. Serious gross hematuria occurred in 1 patient, and paroxysmal atrial fibrillation occurred in 1 patient after surgery. The post-operative pathology showed renal clear cell carcinoma in 18 cases, papillary renal cell carcinoma in 2 cases, chromophobe cell carcinoma in 1 case and well differentiated neuroendocrine tumor in 1 case. The tumor resection margin was negative in all cases. Neither local recurrence nor metastasis was observed during a follow-up of 1 to 15 months. Renal function of all the patients was in normal range. Conclusion: RAPN is a safe, useful approach and a minimally invasive operation for treating renal hilar tumors and it owns crucial advantages in complete and accurate resection of the renal hilar tumors and the reconstruction of the kidney.

The Immune Protection Induced by a Serine Protease Inhibitor From the Foodborne Parasite Trichinella spiralis.

Serine protease inhibitors (SPI) are a superfamily of the proteins able to suppress serine protease activity, and may exert the major biological function in complement activation, inflammation, and fibrinolysis. A SPI was identified from Trichinella spiralis adult worms (AW) by immunoproteomics with early infection sera. The aim of this study was to investigate the protective immune elicited by TsSPI. The complete TsSPI cDNA sequence was cloned into pQE-80 L and then expressed in Escherichia coli BL21. The rTsSPI was purified and its antigenicity was determined by Western blotting analysis. By using anti-rTsSPI serum the native TsSPI was identified in somatic and ES proteins from muscle larvae (ML). The results of qPCR and immunofluorescence assay (IFA) revealed that the expression of the TsSPI gene was observed throughout all developmental stages of T. spiralis (ML, intestinal infective larvale, 3- and 6-days AW, and newborn larvae, NBL), located principally in cuticles, stichosome, and embryos of this parasitic nematode. Vaccination of mice with rTsSPI triggered high level of anti-TsSPI IgG response, and showed a 62.2 and 57.25% worm burden reduction in the recovery of intestinal AW at 6 days post-infection (dpi) and ML at 35 dpi, respectively. The TsSPI might be a novel potential target for anti-Trichinella vaccine.

[Response and prognosis of neoadjuvant dose-dense or standard schedule chemotherapy with anthracyclines and taxanes for Luminal B breast cancer].

Objective: To evaluate the efficacy and safety of neoadjuvant dose-dense or standard schedule chemotherapy with anthracyclines and taxanes for Luminal B (HER2-)Breast Cancer. Methods: From January 2010 to December 2014, 168 Luminal B (HER2-) breast cancer patients with stageⅡA-ⅢC confirmed by pathology were randomly assigned to receive one of the following regimens: (group A) concurrent TEC× 4 every 3 weeks, ( group B ) sequential EC× 4-T × 4 every 3 weeks, (group C ) dose-dense TEC× 4 every 2 weeks with G-CSF, (group D) sequential EC× 4(dose-dense)-T × 4 with dose-dense every 2 weeks . Results: A total of 168 patients completed the neoadjuvant chemotherapy as planned. The pathologic complete response (pCR) was 16.8% in the 4 groups.The pCR were 30.9% and 26.1% in the group C and group D respectively, significantly higher than patients with group A and group B(9.5%and 7.1%) ( P<0.05). Median follow-up was 43 months (IQR 3-63). The 3-year disease free survival (DFS) rate was 64.7%, 55.5%, 87.8% and 92.1% and the 3-year overall survival(OS)rate was 79.4%, 77.7%, 95.1%, 97.3% in the 4 groups respectively. Patients in the dose-dense group had better 3-year DFS and 3-year OS than those with the regular group.The side-effects could be evaluated in 154 patients.The incidence of neutropenia was 29.2% and 21.9% in the group C and group D versus 65.7%and 51.3% in the regular group(P<0.05), the incidence of nervous toxicity was 54.2%, 18.9%, 60.0%, 26.8% in the 4 groups respectively. The incidence of nervous toxicity in the dose-dense group was lower than that in the regular regimen group(P<0.05). Conclusion: Neoadjuvant dose-dense chemotherapy with anthracyclines and taxanes for Luminal B (HER2-)Breast Cancer was effective and can improve the pCR, DFS and OS.Comparing the two dose dense regimens, sequentially with anthracyclines and taxanes, the incidence of nervous toxicity were lower.

Proteomic Analysis of Trichinella spiralis Adult Worm Excretory-Secretory Proteins Recognized by Sera of Patients with Early Trichinellosis.

The most commonly used serodiagnostic antigens for trichinellosis are the excretory-secretory (ES) antigens from T. spiralis muscle larvae (ML), but the specific antibodies against the ML ES antigens are usually negative during early stage of Trichinella infection. The recent studies demonstrated that T. spiralis adult worm (AW) antigens were recognized by mouse or swine infection sera on Western blot as early as 7-15 days post-infection (dpi), the AW antigens might contain the early diagnostic markers for trichinellosis. The purpose of this study was to screen early diagnostic antigens in T. spiralis AW ES proteins recognized by sera of early patients with trichinellosis. T. spiralis AW were collected at 72 h post-infection (hpi), and their ES antigens were analyzed by SDS-PAGE and Western blot. Our results showed that 5 protein bands (55, 48-50, 45, 44, and 36 kDa) were recognized by sera of early patients with trichinellosis collected at 19 dpi, and were subjected to shotgun LC-MS/MS and bioinformatics analyses. A total of 185 proteins were identified from T. spiralis protein database, of which 116 (67.2%) proteins had molecular weights of 30∼60 kDa, and 125 (67.6%) proteins with pI 4-7. Bioinformatic analyses showed that the identified proteins have a wide diversity of biological functions (binding of nucleotides, proteins, ions, carbohydrates, and lipids; hydrolase, transferase, and oxidoreductase, etc.). Several enzymes (e.g., adult-specific DNase II, serine protease and serine protease inhibitor) could be the invasion-related proteins and early diagnostic markers for trichinellosis. Moreover, recombinant T. spiralis serine protease (rTsSP-ZH68) was expressed in E. coli and its antigenicity was analyzed by Western blot with the early infection sera. The rTsSP-ZH68 was recognized by sera of infected mice at 8-10 dpi and sera of early patients with trichinellosis at 19 dpi. T. spiralis AW proteins identified in this study, especially serine protease, are the promising early diagnostic antigens and vaccine candidates for trichinellosis.

[Clinical application of Acutegastrointestinal injury grading system assocaited with clinical severity outcome in critically ill patients: a multi-center prospective, observational study].

Objective: To investigate the feasibility of utilizing the current acute gastrointestinal injury(AGI) grading system, and explore the association of severity of AGI grade with clinical outcome in critically ill patients. Methods: The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24 h were recruited, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed based on GIsymptoms, feeding details and organ dysfunctionon the first week of admission to ICU.The intra-abdominal pressures(IAP) was measured using AbViser device. Results: Of 550 patients enrolled, mean values for age and APACHE Ⅱ score were (64.9±17.2) years and (19.5±7.4), respectively. 456 patients(82.9%) took mechanical ventilation, and 470 patients were identified for AGI. The distribution of AGI grade on the frist day of ICU admission were 50.6%(Ⅰ grade, n=238), 34.2%(Ⅱ grade, n=161), 12.4%(Ⅲ grade, n=58) and 2.8%(Ⅳ, n=13), respectively, while the distribution of the global AGI grade based on the 7-day AGI assessment of ICU admission were 24.5%(Ⅰ grade, n=115), 49.4%(Ⅱ grade, n=232), 20.6%(Ⅲ grade, n=97) and 5.5%(Ⅳ, n=26), respectively. 28- and 60-day mortality rate was 29.3%(n=161) and 32.5%(n=179), respectively. The patients with AGI had a higher 28-(31.1% vs 18.8%, P=0.025) and 60-day survival rate(34.7% vs 20.0%, P=0.01) than those with non-AGI, and also there were positive correlations between AGI grade and 28- and 60-day mortality(P<0.001). Univariate Cox regression analysis showed that age, the source of medicial admission, diabetes mellitus, coronary heart disease, the use of vasoactive drugs, serum creatinine and lactate, mechanical ventilation, APACHE Ⅱ score, the AGI grade in the first day of ICU admission and feeding intolerance within the first week of ICU stay were significantly(P≤0.02) associated with mortality. In multivariate analysis including all these variables, the source of medical admission(χ(2)=4.34, P=0.04), diabete mellitus(χ(2)=3.96, P=0.05), the use of vasoactive drugs(χ(2)=6.55, P=0.01), serum lactate(χ(2)=4.73, P=0.03), the global AGI grade in the 7-day of ICU admission(χ(2)=7.10, P=0.008), and APACHE Ⅱ score(χ(2)=12.1, P<0.001) remained independent predictors for 60-day mortality.In the further subgroup analysis including 402 patients with 7-day survival, the feeding intolerance within the first week of ICU stay could provide independent and incremental prognostic value of 60-day mortality wtih increased χ(2)value of Cox regression model(χ(2)=52.2 vs 41.9, P=0.007) . Conclusion: The AGI grading system is useful for identifying the severity of gastrointestinal dysfunction, and could be used as a strong predictor of impaired outcome. The results provide evidence to support that feeding intolerance within 7 days of admission to ICU was an independent determinant of mortality.

Efficacy of drug-eluting stent for chronic total coronary occlusions at different follow-up duration: a systematic review and meta-analysis.

OBJECTIVE: DESs have been proved to be beneficial for patients with chronic total coronary occlusions (CTO) in terms of cardiac function and other prognosis. We aim to compare the efficacy and safety of drug-eluting stent (DES) and bare-metal stent (BMS) in CTO recanalization at different follow-up duration. METHODS: Articles comparing outcomes between DES and BMS implantation in patients with CTO was searched. A fixed-effect (inverse-variance weighted) and random-effect (DerSimonian and Laird) model were used to analyze the pooling results. RESULTS: A total of 29 comparative studies including 24 cohort studies and 5 randomized controlled studies were identified with a total of 9140 patients (5008 received BMS and 4132 received DES). The risk of all cause death for DES was higher at 6 months and lower at 12 months than BMS, and no significant difference was shown at 24, 36 and 60 months. DES group had lower risk of MI after 12 months implantation, and no difference was shown at 6, 24, 36 and 60 months. Major adverse cardiovascular event (MACE)-free survival was clinically and significantly improved by 73%, 68%, 49%, 40% and 37% respectively in DES group at 6,12, 24, 36, and 60 months. CONCLUSIONS: DES is superior to BMS in binary restenosis, reocclusion and MACE-free survival during long-term follow up. The occurrences of all-cause death and MI show that the risk rate of BMS is higher than that of DES at 12 months. The frequency of all-cause death of DES is higher than BMS at 6 months. DES has higher risk of in-stent thrombosis than BMS at 36 months of implantation.

Targeting type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis.

Most deaths from breast cancer are caused by metastasis, a complex behavior of cancer cells involving migration, invasion, survival and microenvironment manipulation. Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) regulates focal adhesion assembly and its phosphorylation at Y639 is critical for cell migration induced by EGF. However, the role of this lipid kinase in tumor metastasis remains unclear. Here we report that PIPKIγ is vital for breast cancer metastasis. Y639 of PIPKIγ can be phosphorylated by stimulation of EGF and hepatocyte growth factor (HGF), two promoting factors for breast cancer progression. Histological analysis revealed elevated Y639 phosphorylation of PIPKIγ in invasive ductal carcinoma lesions and suggested a positive correlation with tumor grade. Orthotopically transplanted PIPKIγ-depleted breast cancer cells showed substantially reduced growth and metastasis, as well as suppressed expression of multiple genes related to cell migration and microenvironment manipulation. Re-expression of wild-type PIPKIγ in PIPKIγ-depleted cells restored tumor growth and metastasis, reinforcing the importance of PIPKIγ in breast cancer progression. Y639-to-F or a kinase-dead mutant of PIPKIγ could not recover the diminished metastasis in PIPKIγ-depleted cancer cells, suggesting that Y639 phosphorylation and lipid kinase activity are both required for development of metastasis. Further analysis with in vitro assays indicated that depleting PIPKIγ inhibited cell proliferation, MMP9 secretion and cell migration and invasion, lending molecular mechanisms for the eliminated cancer progression. These results suggest that PIPKIγ, downstream of EGF and/or HGF receptor, participates in breast cancer progression from multiple aspects and deserves further studies to explore its potential as a therapeutic target.

Meta-analysis of the long term effects of different interventions on chronic total coronary occlusions.

BACKGROUND: Coronary chronic total occlusion (CTO) is the end stage of coronary artery atherosclerosis. CTO revascularization can be performed by percutaneous transluminal coronary angioplasty (PTCA), bare metal stent (BMS) or drug-eluting stent (DES). It is important to scientifically evaluate the effectiveness of CTO interventional treatments. METHODS: Relevant studies of long term outcomes for several kinds of CTO treatments were examined. Data were extracted and assessed by two independent clinical experts, pooled and analyzed using meta-analysis. RESULTS: (1) Totally 8 articles comparing outcomes between PTCA and BMS treatment were analyzed. Follow-up variables such as mortality, subsequent coronary artery bypass graft surgery (CABG), re-occlusion, re-stenosis and target lesion revascularization (TLR) were analyzed by meta-analysis. Compared with BMS intervention, PTCA was associated with significant higher rate of re-occlusion, re-stenosis, subsequent PTCA and TLR. (2) Totally 12 articles compared long term outcomes between BMS groups and DES groups, encompassed 3605 CTO patients. During the long-term follow-up, six variables as major adverse cardiac events (MACE), myocardial infarction, all-cause death, subsequent CABG, accumulated MACE-free survival rate, re-stenosis/re-occlusion rate were analyzed by meta-analysis. Compared with patients in DES groups, patients in BMS groups had significant higher MACE, subsequent CABG, re-stenosis/re-occlusion rate, TLR, target vessel revascularization, while lower MACE-free survival rate. CONCLUSIONS: Incidence of re-occlusion, re-stenosis, subsequent PTCA and TLR were significantly lower for BMS implantation than for PTCA procedure. Variables, including MACE, subsequent CABG, re-stenosis/re-occlusion rate were higher while accumulated MACE-free survival rate was lower in BMS groups than in DES groups.

Effects of astragalosides on cultured islets after cryopreservation in rats.

OBJECTIVE: To explore the effects of AST (astragalosides) on cultured rat islet yield, purity, and function after cryopreservation in rats. METHODS: Pancreatic islets were isolated from 30 Sprague-Dawley rats using the standard technique of collagenase P digestion and discontinuous Ficoll gradient purification. After thaw, the islets were randomly divided into AST group and control group (n=15). Next, the islet cells were cultured in AST-containing medium or standard medium for 7, 14, and 21 days after cryopreservation and thaw. The quantity, purity, and survival rate were calculated in the two groups before and after culture. Then the in vitro and in vivo function was observed in diabetic rats after islet transplantation. RESULTS: The quantity and purity of islets had no difference between the two groups before culture (P>.05) while the difference after culture was significantly (P<.05). The survival rate of islets was 48% in AST group and 32% in the control group 21 days after thaw (P<.05). After 3 days, there was significantly a higher simulation index in the AST group than in the control group (P<.05). There was a significant difference in blood glucose and insulin concentrations between the groups after 3 days (P<.05). CONCLUSION: AST can be added to the culture medium to reduce the loss of islet cryopreservation and be intravenously injected to improve culture islet function in vitro and prolong islet graft survival in diabetic rats.

CYP3A catalyses schizandrin biotransformation in human, minipig and rat liver microsomes.

Schizandrin is recognized as the major absorbed effective constituent of Fructus schisandrae, which is extensively applied in Chinese medicinal formula. The present study aimed to profile the phase I metabolites of schizandrin and identify the cytochrome P450 (CYP) isoforms involved. After schizandrin was incubated with human liver microsomes, three metabolites were isolated by high-performance liquid chromatography (HPLC) and their structures were identified to be 8(R)-hydroxyl-schizandrin, 2-demethyl-8(R)-hydroxyl-schizandrin, 3-demethyl-8(R)-hydroxyl-schizandrin, by liquid chromatography-mass spectrometry (LC-MS), (1)H-nuclear magnetic resonance (NMR), and (13)C-NMR, respectively. A combination of correlation analysis, chemical inhibition studies, assays with recombinant CYPs, and enzyme kinetics indicated that CYP3A4 was the main hepatic isoform that cleared schizandrin. Rat and minipig liver microsomes were included when evaluating species differences, and the results showed little difference among the species. In conclusion, CYP3A4 plays a major role in the biotransformation of schizandrin in human liver microsomes. Minipig and rat could be surrogate models for man in schizandrin pharmacokinetic studies. Better knowledge of schizandrin's metabolic pathway could provide the vital information for understanding the pharmacokinetic behaviours of schizandrin contained in Chinese medicinal formula.