Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.

BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.

[Effects of different carbon sources on growth and active component contents in Salvia miltiorrhiza and S. castanea f. tomentosa hairy roots].

Salvia miltiorrhiza(Sm) and Salvia castanea f. tomentosa(Sc) hairy roots were used as experimental materials to study the effects of six different carbon sources, galactose, fructose, lactose, glucose, arabinose and sucrose(control), on fresh weight, dry weight, contents and yields of salvianolic acids and tanshinones. The results showed that galactose was most beneficial to the growth of two kinds of hairy roots, while lactose and arabinose were not conducive to their growth. As for Sm hairy roots, fructose significantly promoted the accumulation of salvianolic acid B, and the content increased by 5.801 times and 10.151 times compared with the control group, respectively. Glucose significantly promoted the accumulation of salvianolic acids. The content and yield of rosmarinic acid were 7.674 times and 9.260 times of that of the control group, and the content and yield of salvianolic acid B were 5.532 times and 6.675 times of the control group. For the hairy roots of Sc, galactose significantly increased the content and yield of rosmarinic acid, reaching 7.820 times and 9.944 times of the control group, respectively. Fructose promoted the increase of the content and yield of cryptotanshinone, reaching 9.242 times and 6.609 times of the control group, respectively. The study confirmed the optimal carbon source for the hairy root culture of Sm and Sc, and provided theoretical guidance for large-scale production of Sm drug-derived components and the utilization of Sc.

Low concentration of formononetin stimulates the proliferation of nasopharyngeal carcinoma cell line CNE2 by upregulating bcl-2 and p-ERK1/2 expression.

Context Formononetin is a typical phytoestrogen, which is a bioactive component found in red clover plants. Previous studies have shown that formononetin inhibits the proliferation of several types of cancer cells, including prostate cancer and osteosarcoma. However, how formononetin affects the proliferation of CNE2 is not clear. Objective The objective of this study is to investigate the effects of formononetin on nasopharyngeal carcinoma cells in vitro, along with the underlying mechanism. Materials and methods CNE2 cells were incubated with various concentrations of formononetin (0, 0.1, 0.2, 0.3 and 1 µM) for 48 h. Cell proliferation was measured by [3-(4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay, while the rate of apoptosis was measured by flow cytometry. Bcl-2 and bax mRNA expression levels were determined by real time polymerase chain reaction (RT-PCR), while p-ERK1/2 and bcl-2 protein expression levels were quantified by Western blotting. Results Formononetin promoted the proliferation of CNE2 cells at low concentrations (0, 0.05, 0.1, 0.2, 0.5, 1, 2 and 5 µM), OD values increased from 0.27 ± 0.01 to 0.30 ± 0.01, 0.30 ± 0.01,0.36 ± 0.01, 0.35 ± 0.01, 0.34 ± 0.01, 0.34 ± 0.01 and 0.32 ± 0.01, respectively. The percentage of late apoptosis declined from 6.77% ± 0.73% (0 µM group) to 6.2% ± 0.4% (0.1 µM group), 3.83% ± 0.71% (0.3 µM group) and 5.1% ± 0.52% (1M group). The mRNA levels of bax and bcl-2 were down- and upregulated, respectively, by formononetin. Bcl-2 and p-ERK1/2 protein levels were also upregulated. Conclusions Formononetin stimulates CNE2 cell proliferation and has an inhibitory effect on CNE2 cells apoptosis, which is mediated by the activation of the ERK1/2 signaling pathways.

The molecular characterization and RNAi silencing of SjZFP1 in Schistosoma japonicum.

During development, Schistosoma japonicum undergoes many morphological and physiological transformations as a result of profound changes in gene expression. Proteins containing zinc finger motifs usually play an important role in DNA recognition, RNA packaging, and transcriptional activation. In our current study, we cloned the open reading frame (ORF) of SjZFP1 of S. japonicum, which encodes a zinc finger protein. We analyzed the complementary DNA (cDNA) sequence of SjZFP1 and examined the expression of SjZFP1 messenger RNA (mRNA) at various developmental stages. We also tested the effects of RNA interference (RNAi) silencing on worm burden, spawning, and egg hatching. The ORF in the SjZFP1 cDNA was 1017 bp in length and was predicted to encode a 338-aa protein with a molecular mass of approximately 38.5 kDa and theoretical isoelectric point (pI) of 7.08. Several conserved regions, including a B-box-type zinc-binding domain, two bipartite nuclear localization signal domains, a paired amphipathic helix repeat, and overlapping RING and PHD finger domains, were identified in the predicted amino acid sequence of SjZFP1. Using real-time PCR, we showed that the SjZFP1 mRNA was expressed across all of the developmental stages of the parasite and that the level of transcription was highest in the cercariae, eggs, schistosomula, and mature adult worms. The level of SjZFP1 mRNA expression in cultured schistosomula treated with one of two SjZFP1-specific small interfering RNAs (siRNAs; AY770 and AY546) was reduced by over 80 %, compared with that in the controls. In RNAi experiments in BALB/c mice, the level of SjZFP1 mRNA increased significantly when the mice were treated with the same SjZFP1-specific siRNAs during the early stages of infection. By contrast, the level of SjZFP1 mRNA decreased significantly when the mice were treated with the SjZFP1-specific siRNAs during the middle to late stages of infection. In four independent experiments, fewer worms were recovered from mice treated with the SjZFP1-specific siRNAs, compared with the number of worms recovered from the control mice. Both the average number and hatching rates of liver eggs recovered from mice treated with the SjZFP1-specific siRNAs during the middle to late stages of infection were significantly lower than those of the liver eggs recovered from the control mice. Our results suggest that the SjZFP1 gene might be important for parasite development, spawning in the vertebrate host, and egg hatching.

[Optimal cut-off value of phalangeal radiographic absorptiometry to identify osteoporosis in postmenopausal women].

OBJECTIVE: To study the optimal cut-off value of phalangeal radiographic absorptiometry (RA) to identify osteoporosis in postmenopausal women. METHODS: A total of 650 postmenopausal women were recruited in this study. Bone mineral density (BMD) at lumbar spine and left proximal femur neck was measured by dual-energy X-ray absorptiometry (DXA) as the standard method to identify postmenopausal osteoprosis. Phalangeal bone density was estimated by the use of RA. Optimal cut-off value of phalangeal RA was determined using a ROC curve for screening the ostreoporosis cases. RESULTS: When the cut-off value of phalangeal RA was T score < or = -2.5, the sensitivity was 74.2%, the specificity was 72.9%. When the cut-off value was T score < or = -2.21, the sensitivity was 81.4%, the specificity was 62.0%. CONCLUSION: The cut-off value of phalangeal RA as T score -2.21. which has higher sensitivity could be optimal to identify postmenopausal osteoporosis.

[Risk factors of acute-phase response following the first-dose administration of zoledronic acid in the treatment of osteoporosis].

OBJECTIVE: To explore the risk factors of acute-phase response (APR) following the first-dose administration of zoledronic acid in the treatment of osteoporosis. METHODS: We reviewed the clinical data of the patients receiving the first use of zoledronic acid 5 mg treatment of osteoporosis from January 2009 to November 2012, and divided the patients into acute phase response group (APR+) and no response group (APR-). The age, body mass index (BMI), concomitant medications, comorbidities, laboratory parameters between the two groups were compared and analyzed. RESULTS: A total of 178 patients were eligible for inclusion in the study, of which 108 patients experienced APR. In APR group, there were 80 (44. 9%) patients developed fever, 14 (9. 6%) chills, 48 (27.0%) musculoskeletal pain, 19 (10.7%) gastrointestinal symptoms, 10 (5.6%) headache and dizziness, 7 (3.9%) palpitation,and 3 (1.7%) rash. APR was more common in the patients with higher baseline tartrate-resistant acid phosphatase 5b (TRACP-5b) and new-onset vertebral compression fractures (new-onset VCF). Stepwise logistic regression showed that the odds ratio (OR) of APR in higher baseline TRACP-5b and new VCF was 3. 3 and 2. 5 respectively. CONCLUSION: The first use of zoledronic acid in the treatment of osteoporosis appears high incidence of APR. High TRACP-5b levels and new vertebral fracture are risk factors for APR.

Uraemic serum induces dysfunction of vascular endothelial cells: role of ubiquitin-proteasome pathway.

The ubiquitin-proteasome pathway (UPP) has been indicated to contribute to dysfunction of endothelial cells (ECs). Nevertheless, the relationship between UPP and vascular complications of uraemia remains unknown. We aimed to determine whether the UPP is activated in vascular ECs when cultured with uraemic serum, and to examine the role of the UPP on dysfunction of ECs in uraemia. Rabbit aortic endothelial cells (RAECs) were cultured with normal serum or different concentrations of uraemic serum. The expression of the ubiquitin-activating enzyme (E1), an indicator of the UPP, was detected by real-time RT-PCR and Western blot; proteasome activity was determined by fluorescence spectrophotometry; and nuclear factor-κB (NF-κB) activity and expression, as well as tumour necrosis factor-α (TNF-α) expression, were also detected. We found that the expression of E1 and the activities of three kinds of proteasomes were increased significantly in RAECs after incubation with uraemic serum. Proliferation of RAECs was increased significantly by incubation with 3-15% uraemic serum but decreased markedly when incubated with uraemic serum above 15% (increased apoptosis). Incubation of RAECs with uraemic serum induced increased NF-B DNA-binding activity and nuclear translocation of NF-κB, decreased nitric oxide production and increased expression of TNF-α, which is the final effector of inflammatory activation of cells. All of these responses in RAECs were suppressed by the specific proteasome inhibitor, MG132. The inhibition of inflammatory responses by MG132 was further supported by a parallel experiment with pyrrolidine dithiocarbamate, a specific inhibitor of κNF-B. These findings suggest that the UPP was activated in RAECs by administration of uraemic serum, and played a pivotal role in the dysfunction of vascular ECs, such as inflammatory activation.

[Correlation between levels of serum growth differentiation factor-15 and acute coronary syndrome].

OBJECTIVE: To explore the association between the levels of serum growth differentiation factor-15(GDF-15) and acute coronary syndrome(ACS) in patients undergoing coronary angiography(CAG). METHODS: In this prospective study, 120 candidates (30 healthy controls and 90 patients with ACS) admitted to our hospital from March 2006 to April 2008 were included. The patients with ACS were divided into 3 groups: (1)Group AMI-emergency (AMI-E), including 30 patients with acute myocardial infarction (AMI) who underwent CAG within 12 hours of the onset of symptoms. (2) Group AMI 7-14 d, including 30 patients with AMI who underwent CAG within 7-14 days of the onset of symptoms. (3)Group UAP including 30 patients with unstable angina pectoris. The serum level of GDF-15 was determined by ELISA. RESULTS: The level of GDF-15 for group ACS was (649.0 ± 224.21) ng/L, which was significantly higher than that of control group [(537.2 ± 262.9)ng/L,P<0.01]. The level of serum GDF-15 significantly increased in group AMI-E [(801.6 ± 218.4)ng/L] compared with group AMI 7-14 d [(656.2 ± 252.4)ng/L,P=0.042, 95% CI 1.001-1.061], group UAP [(586.9 ± 225.6)ng/L, P=0.001, 95% CI 0.809-0.950] and control group(P<0.05, 95% CI 1.000-1.012) after being adjusted for relevant covariates. The elevated level of GDF-15 was related to biomarkers, such as white blood cells count (WBC, r(2)=0.276, P=0.002), lactate dehyerogenase(LDH, r(2)=0.288, P=0.004), creatine kinase 2(CK-MB, r(2)=0.350, P<0.001) and troponin T(TnT, r(2) =0.344, P=0.001). CONCLUSION: GDF-15 protein expression increases in ACS, and the level of GDF-15 rapidly increases and remains elevated in the early period of acute myocardial infarction. The elevated level of GDF-15 is related to biomarkers, such as WBC, LDH, CK-MB, and TnT. GDF-15 could be a new and independent biomarker in evaluating the patients with cardiovascular disease.

Metabolomics-based understanding of the olanzapine-induced weight gain in female first-episode drug-naïve patients with schizophrenia.

Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.

HIF-1α Alleviates High-Glucose-Induced Renal Tubular Cell Injury by Promoting Parkin/PINK1-Mediated Mitophagy.

It is well-established that mitophagy leads to Diabetic Nephropathy (DN) and renal failure. Mitophagy mediated by a Hypoxia-inducible factor-1α (HIF-1α) plays a beneficial role in many diseases. Nevertheless, the mechanisms underlying HIF-1α-mediated mitophagy in DN remain unclear. This study defines the role of HIF-1α mediated mitophagy in DN. The expression of HIF-1α was upregulated in HK-2 cells in an High-Glucose (HG) environment, and the YC-1 (a specific inhibitor of HIF-1α) further exacerbated the hypoxia-induced mitochondrial dysfunction. Conversely, the HIF-1α-mediated protective effect was strengthened by scavenger N-acetylcysteine (NAC), a type of reactive oxygen species. Moreover, HIF-1α-Parkin/PINK1-mediated mitophagy prevented apoptosis and ROS production in HK-2 cells subjected to HG exposure. In summary, HIF-1α mediated mitophagy on HK-2 cells under HG conditions could alleviate DN, suggesting that it has huge prospects for DN treatment.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Effects of 4-phenylbutyric acid on the process and development of diabetic nephropathy induced in rats by streptozotocin: regulation of endoplasmic reticulum stress-oxidative activation.

Oxidative stress may contribute to the pathogenesis of diabetic nephropathy (DN), although the precise regulatory mechanism is still unclear. Recent reports have shown that chemical molecular chaperone 4-phenylbutyric acid (4-PBA) can suppress oxidative stress by attenuating endoplasmic reticulum (ER) stress. We therefore hypothesized that 4-PBA could provide renoprotection through the suppression of oxidative stress in DN rats. Male Sprague-Dawley (SD) rats were randomly divided into three groups: a normal control (NC) group, a streptozotocin (STZ)-induced DN model group, and a DN plus 4-PBA (1g/kg) treatment group. At the end of 4, 8, and 12 weeks, hydroxyproline content, NADPH oxidase activity and the expression of phosphorylation of inositol-requiring enzyme-1alpha (p-IRE1alpha), p47phox, nitrotyrosine (NT) and NF-E2-related factor 2 (Nrf2) in the kidneys of all rats were determined; malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in serum and urine were also detected; renal nuclear factor kappaB (NF-kappaB) activity in all of the rats was examined at the end of 12 weeks. Compared with the NC group, the DN rats showed a significant increase in hydroxyproline content, NADPH oxidase activity, NF-kappaB activity, the expression of p-IRE1alpha, p47phox, NT and Nrf2 in renal tissue; markedly, MDA levels were higher and SOD activity was lower in serum and urine of DN rats than in NC rats for the indicated time. These alterations were inhibited by the administration of 4-PBA. These findings first demonstrated that treatment with 4-PBA significantly inhibits the process and development of diabetic nephropathy in rats through the regulation of ER stress-oxidative activation.

[Prognostic importance of abnormal glucose metabolism in chronic heart failure].

OBJECTIVE: To investigate the importance of abnormal glucose metabolism in a chronic heart failure (CHF) population. METHODS: A total of 444 patients were enrolled sequentially for decompensated CHF from January 1st, 2005 to December 31st, 2007 at our department. They were divided into diabetic (n = 153, 34.5%) and non-diabetic groups (n = 291, 65.5%). Among the non-diabetics, there were 113 (25.4%) with impaired fasting glucose (IFG) (FPG 5.6-6.9 mmol/L) and 178 (40.1%) with normal glucose levels. All subjects received a follow-up to record their clinical status, biochemical parameters and end-point events (all-cause death in one year). And the correlations of abnormal glucose metabolism and end-point events were analyzed. RESULTS: Among these patients, 83 (17.1%) died in 1 year, 31 (7.0%) were lost to follow-up; Among 83 dead patients, 15 (8.4%) were within normal glucose levels, 34 (21.2%) with IFG and 44 (28.8%) with diabetes mellitus. Compared with normal glucose level patients, the mortality rates of diabetes mellitus and IFG patients were higher (P < 0.01). There was no significant difference in mortality rate between diabetes mellitus and IFG patients. After adjustment for other prognostic attributes (age, sex and etc.), diabetes mellitus was a predictor of 1-year all-cause mortality (OR = 2.383, 95% CI: 1.317 to 4.312; P = 0.004). In diabetics, the mortality of the higher glucose level group (FPG > 7.0 mmol/L) was 30.4% and that of the lower glucose level group (FPG < or = 7.0 mmol/L) 27.4%. And there was no significant difference (P > 0.05). The FPG level could not predict the 1-year all-cause mortality. In non-diabetics, the mortality of IFG group (FPG 5.6 - 6.9 mmol/L) was significantly higher than that of normal glucose levels group (21.2% vs 8.4%, P < 0.01). IFG status predicted 1-year all-cause mortality (OR = 3.564, 95%CI: 1.494 - 8.497, P = 0.004). The FPG level was also associated with the 1-year all-cause mortality (OR = 1.791, 95%CI: 1.090 - 2.943, P = 0.021). CONCLUSION: Diabetes mellitus is an independent predictor of 1-year all-cause mortality for CHF. And IFG and a higher FPG level are associated with 1-year all-cause mortality for CHF without diabetes mellitus.

[Mitochondrial fusion protein Mfn2 and cardiovascular diseases].

Mitofusin 2 (Mfn2) is a mitochondrial dynamin-related protein involved in the mitochondrial fusion reaction and is also connected to an altered mitochondrial energy supply. Mfn2 is a signaling molecule, plays an important role in cell proliferation, differentiation and apoptosis, which participates in the pathophysiology of several cardiovascular diseases, such as hypertension, restenosis after angioplasty, atherosclerosis, cardiac hypertrophy, and cardiac oxidative stress injury. Regulating the mitochondria-related metabolism, Mfn2 affects diabetes and insulin resistance pathogenesis. In addition, Mfn2 could be an important biomarker and therapeutic target molecule for cardiovascular diseases.

Serum Ferritin Independently Predicts the Incidence of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

AIM: This study aimed to determine whether serum ferritin (SF) is an independent risk factor of the incidence of chronic kidney disease (CKD) and rapid renal function decline (RFD) in male Tibetan patients with type 2 diabetes mellitus (T2DM). METHODS: We performed a retrospective cohort study that included 191 male Tibetan patients with T2DM without CKD. Patients were divided into three groups according to the level of SF. The following outcomes were measured: cumulative incidence of chronic kidney disease [i.e. estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 and/or urinary albumin/creatine ratio (ACR) ≥30 mg/g] and RFD (i.e. decrease in eGFR of ≥25% from baseline or a decline rate of ≥3 mL/min per 1.73 m2 annually). RESULTS: In total, over a median follow-up period of 23 months, 30 (15.7%) and 89 patients (46.6%) developed CKD and RFD. In multivariable Cox models, a 100 ng/mL increment in SF was associated with a 1.12-fold (95% CI: 1.02-1.24) higher adjusted risk for incidence of CKD. The adjusted-HR of CKD was 1.31 (95% CI: 0.38-4.53) and 2.92 (95% CI: 0.87-9.77) for those in tertile 2 and tertile 3, respectively, compared with the patients in tertile 1. However, SF was not significantly associated with RFD (adjusted-HR: 1.06, 95% CI: 0.99-1.14). CONCLUSION: Serum ferritin independently predicts the incidence of CKD in male Tibetan patients with T2DM. High levels of serum ferritin may play a role in the pathogenesis leading to the development of CKD in T2DM.

[Analysis of HFE and Non-HFE Mutations in a Tibet Cohort with Iron Overload].

OBJECTIVE: The explore the molecular basis of iron-overload in Tibet nationality population of Tibet. METHODS: The inpatients with iron-overload in our department from Dec. 1st 2014 to Jul.31st 2016 were enrolled in this study. Abdominal MRI and the mutation sites C282Y and H63D in HFE exon were examined. For HFE mutation-negative patients, the non-HFE mutation was detected, including 5 HJV mutations of G320V, p.Q312X, p.D249H, p.I281T, p.C321X and 2 TFR2 mutations: (Y250X, I238M), and 2 SLC40A1 mutations: (V162del, N144H). RESULTS: Among 113 iron overload patients, only one showed homozygous p.H63D mutation, and one showed heterozygosis p.H63D mutation. In 73 patients accepted non-HFE gene detection, only one was heterozygosis p.D249N mutation in HJV, and one was heterozygosis p.I238M mutation in TFR2. CONCLUSION: Currently, the pathogenic gene for Tibetan iron-overload has not yet been found.

[Inhibition of cardiac hypertrophy by mitofusin 2 in neonatal rat cardiomyocytes].

OBJECTIVE: To study the expression and function of Mitofusin 2 (Mfn2) in cultured neonatal rat cardiomyocytes during PE-induced hypertrophy. METHODS: The hypertrophy neonatal rat cardiomyocytes model was induced by 0.01 mol/L PE. RT-PCR and Western blot were applied to assess Mfn2 mRNA expression and protein level respectively. Cultured neonatal rat cardiomyocytes were treated by PE after Ad GFP or Ad Mfn2 infection, the protein synthesis was determined by 3H-leucine incorporation assay. RESULTS: PE led to ANF mRNA level (by approximately 1 fold, P < 0.01) elevation and cell surface area (by approximately 1 fold, P < 0.01) increasing. Mfn2 mRNA (by approximatelt 50%, P < 0.01) and protein (by approximately 50%, P < 0.01) decreased remarkably in PE treated cardiomyocytes compared with those in control group. Compared with cells infected by Ad GFP (1.72+/-0.12 vs 2.47+/-0.06, P < 0.05, cell area (1.530+/-0.008 vs 0.830+/-0.009, P <0.01) and protein synthesis (0.98+/-0.10 vs 2.47+/-0.06, P < 0.01) were also largely abrogated in neonatal rat cardiomyocytes infected by Ad Mfn2. CONCLUSION: These results indicate that the expression of Mfn2 mRNA and Mfn2 protein decreased in PE-induced neonatal rat cardiomyocytes hypertrophy model. Overexpression of Mfn2 in cultured neonatal rat cardiomyocytes could attenuate the protein synthesis and cell surface area increase after PE treatment. Accordingly, Mfn2 is an important regulator in cardiomyocytes hypertrophy.

[The prognostic value of admission blood glucose level in acute myocardial infarction after primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the predictive value of the admission blood glucose level for in-hospital mortality and major adverse cardiac events (MACE) rate in patients with acute myocardial infarction (AMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: The cohort study comprised 312 consecutive patients with AMI who underwent primary PCI within 24 hours after the onset of chest pain, including diabetic patients and non-diabetic patients. According to the levels of the admission glucose (11 mmol/L), these patients were divided into two groups: a high admission glucose group and a normal admission glucose group. RESULTS: There were no significant differences in age, hypertension, hyperlipidemia, LVEF, CK-MB and hypersensitive C reactive protein. PCI success rate was similar in both groups (P > 0.05). The in-hospital mortality and 180-day MACE rate were significantly higher in patients with high concentration of admission glucose than in patients with normal concentration (18.2% vs 3.0% P < 0.001, 25% vs 12.7%, P = 0.047). However, there was no significant difference in mortality and 180-day MACE rate between diabetic and non-diabetic patients. Binary logistic regression analysis indicated that high concentration of the admission glucose remained an independent predicator of the in-hospital mortality (OR 5.15, 95% CI 1.74 - 15.28, P = 0.003) and higher occurrence rate of 180-day MACE (OR 2.84, 95% CI 1.18 - 6.83, P = 0.019). CONCLUSIONS: High concentration of admission glucose, but not the diagnosis of diabetes, was an important predictor for in-hospital mortality and 180-day MACE rate in patients with AMI who underwent primary PCI.

[Association between plasma adiponectin levels and coronary lesion complexity].

OBJECTIVE: To explore the association between the levels of plasma adiponectin and coronary artery lesion complexity in patients undergoing coronary angiography. METHODS: We measured the plasma concentrations of adiponectin in 105 candidates [28 healthy controls and 77 patients with coronary artery diseases (CAD)]. The complexity of coronary artery lesion was evaluated by the numbers of vessel disease and Gensini score. RESULTS: Plasma concentrations of adiponectin in healthy group were significantly higher than those in CAD patients. Among patients with CAD, those with multiple vessel lesions had significantly lower adiponectin levels than those with a single vessel lesion. Plasma concentrations of adiponectin in Gensini score > or = 30 group were significantly lower than those in <30 group and control group(P<0.05). Patients with acute coronary syndrome (ACS) had lower adiponectin levels than those without ACS [(0.731+/-0.361) mg/L vs. (1.097+/-0.617) mg/L,P=0.03]. Logistic analysis indicated that the lower level of adiponectin was independent risk factor of coronary stenosis (OR 0.214, 95% CI 0.071-0.646, P=0.006) and unstable plaque (OR 0.151, 95% CI 0.044-0.515, P= 0.003). Adiponectin concentrations were correlated positively with high density lipoprotein cholesterol(HDL-C) and negatively with C-reactive protein and triglyceride(TG). CONCLUSION: The decreased plasma adiponectin concentration might be associated with the coronary artery lesion and be used as an independent predictor of the occurrence and severity of coronary atherosclerosis and the stability of plaque.

[Intracoronary transfer autologous bone marrow stem cells can improve cardiac function in patients with left ventricular dysfunction after myocardial infarction].

OBJECTIVE: To evaluate the efficacy of intracoronary transfer of autologous bone marrow mononuclear stem cells in patients with heart dysfunction after myocardial infarction. METHODS: Forty-two patients with anterior myocardial infarction [BMSC(bone marrow mononuclear stem cells) group: 13 cases; control group: 29 cases] were treated by standard percutaneous coronary intervention (PCI) and medical therapy. Patients in BMSC group were also transplanted bone marrow mononuclear stem cells through coronary injection. Baseline and 12 months' follow-up evaluations included New York Heart Association Class ( NYHA class) and the level of plasma NT-proBNP, six minutes walk test, single photon emission computed tomography(SPECT). RESULTS: In BMSC group, the NYHA class improved significantly at the end of the 12 months' follow-up (1.54+/-0.27 vs. 2.62+/-0.33, P=0.002) and was better than that of control group (2.45+/-0.21, P=0.02). The level of plasma NTjproBNP reduced significantly [(701.05+/-154.60) ng/L vs. (1,921.70+/-373.70) ng/L, P=0.000 8]. The distances of six minutes walk test of the two groups increased significantly [BMSC group: (432.85+/-27.81) m vs. (363.77+/-20.14) m, P=0.000 6;control group: (381.48+/-17.72) m vs. (339.00+/-9.87) m, P=0.000 5], but the difference was not obvious between the two groups. The score of myocardial blood perfusion improved significantly in BMSC group at the end of the 12 months' follow-up (31.15+/-3.65 vs. 46.31+/-2.87, P=0.002) and was better than that of control group (42.59+/-2.08,P=0.015 7). The area of the perfusion defects in SPECT reduced significantly in BMSC group [(32.23+/-4.40)% vs. (39.54+/-3.76)%, P=0.000 1], but no obvious difference was found between the two groups. Global LVEF of BMSC group increased [(38.54+/-2.94)% vs. (35.38+/-2.16)%, P>0.05). CONCLUSION: Intracoronary transplantation of bone marrow mononuclear cells could improve myocardial blood perfusion and increase the systolic function in patients with heart failure after myocardial infarction.