An integrated strategy by absorbed component characterization, pharmacokinetics, and activity evaluation for identification of potential nephroprotective substances in Zhu-Ling decoction.

An efficient strategy for the identification of potential nephroprotective substances in Zhu-Ling decoction has been established with the integration of absorbed components characterization, pharmacokinetics, and activity evaluation. A qualitative method was developed to characterize the chemical constituents absorbed components in vivo of Zhu-Ling decoction by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. A quantitative method was established and validated for the simultaneous determination of eight compounds in rat plasma by using ultra-performance liquid chromatography-triple quadruple tandem mass spectrometry. Finally, the nephroprotective activities of absorbed components with high exposure were assessed by cell survival rate, superoxide dismutase, and malondialdehyde activities in hydrogen peroxide-induced Vero cells. As a result, 111 compounds in Zhu-Ling decoction and 36 absorbed components were identified in rat plasma and urine, and poricoic acid A, poricoic acid B, alisol A, 16-oxo-alisol A, and dehydro-tumulosic acid had high exposure levels in rat plasma. Finally, poricoic acid B, poricoic acid A, 16-oxo-alisol A, and dehydro-tumulosic acid showed remarkable nephroprotective activity against Vero cells damage induced by hydrogen peroxide. Besides, superoxide dismutase and malondialdehyde activities were obviously regulated in hydrogen peroxide-induced Vero cells by treatment with the four compounds mentioned above. Therefore, these four compounds were considered to be effective substances of Zhu-Ling decoction due to their relatively high exposure in vivo and biological activity. This study provided a chemical basis for the action mechanism of Zhu-Ling decoction in the treatment of chronic kidney diseases.

Electronic medical record-based model to predict the risk of 90-day readmission for patients with heart failure.

BACKGROUND: Several heart failure (HF) risk models exist, however, most of them perform poorly when applied to real-world situations. This study aimed to develop a convenient and efficient risk model to identify patients with high readmission risk within 90 days of HF. METHODS: A multivariate logistic regression model was used to predict the risk of 90-day readmission. Data were extracted from electronic medical records from January 1, 2017 to December 31, 2017 and follow-up records of patients with HF within 3 months after discharge. Model performance was evaluated using a receiver operating characteristic curve. All statistical analysis was done using R version 3.5.0. RESULTS: A total of 350 patients met the inclusion criterion of being readmitted within in 90 days. All data sets were randomly divided into derivation and validation cohorts at a 7/3 ratio. The baseline data were fairly consistent among the derivation and validation cohorts. The variables most clearly related to readmission were logarithm of serum N-terminal pro b-type natriuretic peptide (NT-proBNP) level, red cell volume distribution width (RDW-CV), and Charlson comorbidity index (CCI). The model had good discriminatory ability (C-statistic = 0.73). CONCLUSIONS: We developed and validated a multivariate logistic regression model to predict the 90-day readmission risk for Chinese patients with HF. The predictors included in the model are derived from electronic medical record (EMR) admission data, making it easier for physicians and pharmacists to identify high-risk patients and tailor more intensive precautionary strategies.

A Review on Daphnane-Type Diterpenoids and Their Bioactive Studies.

Natural daphnane diterpenoids, mainly distributed in plants of the Thymelaeaceae and Euphorbiaceae families, usually include a 5/7/6-tricyclic ring system with poly-hydroxyl groups located at C-3, C-4, C-5, C-9, C-13, C-14, or C-20, while some special types have a characteristic orthoester motif triaxially connectedat C-9, C-13, and C-14. The daphnane-type diterpenoids can be classified into five types: 6-epoxy daphnane diterpenoids, resiniferonoids, genkwanines, 1-alkyldaphnanes and rediocides, based on the oxygen-containing functions at rings B and C, as well as the substitution pattern of ring A. Up to now, nearly 200 daphnane-type diterpenoids have been isolated and elucidated from the Thymelaeaceae and Euphorbiaceae families. In-vitro and in-vivo experiments of these compounds have shown that they possess a wide range of biological activities, including anti-HIV, anti-cancer, anti-leukemic, neurotrophic, pesticidal and cytotoxic effects. A comprehensive account of the structural diversity is given in this review, along with the cytotoxic activities of daphnane-type diterpenoids, up to April 2019.

[Chemical constituents from green walnut husks and their antitumor activity in vitro].

Fourteen chemical constituents, including 5-hydroxy-4-methoxy-1-tetralone(1), 4,8-dihydroxy-1-tetralone(2), 4,5-dihydroxy-α-tetralone(3), blumenol B(4), dehydrovomifoliol(5), megastigm-5-ene-3,9-diol(6), juglanin B(7), blumenol C(8), loliolide(9), oleracone B(10), syringarsinol(11), pinoresinol(12), methyl 4-hydroxy-3-methoxybenzoate(13), and isovanillic acid(14), were isolated from the dichloromethane fraction of 95% methanol extract of green walnut husks by silica gel and MCI column chromatography, and Pre-HPLC. Their structures were determined by spectroscopic methods, such as NMR, MS and so on. Among them, compounds 1, 4-6, 8-13 were isolated from the green walnut husks for the first time, and compounds 4-6, 8, 10, 12, 13 were isolated from the Juglans genus for the first time. All of isolates were detected their inhibitory activities against HeLa, HGC-27 and Ht-29 cell lines by the MTT assay. The result showed that compounds 2, 3, 7, 9 and 11 exhibited inhibitory activity against the tested cell line. The IC_(50) of 7 were 26.5, 9.0, 25.4 µmol·L~(-1), respectively.

Four New Sesquiterpenoids from the Roots of Diarthron Tianschanica with Their Antineoplastic Activity.

Four new sesquiterpenoids, known as diarthronchas A⁻D (1⁻4), and one known daphnauranol B (5) were isolated from the methanol extract of the roots of Diarthron tianschanica. The compounds structures were determined on the basis of spectroscopic data. All of the isolated compounds were profiled for their antineoplastic activity.

Activation of autophagy improved the neurologic outcome after cardiopulmonary resuscitation in rats.

OBJECTIVE: Recent studies have shown the existence of autophagy in cerebral ischemia; however, there has been no research on the role of autophagy in cerebral injury after cardiopulmonary resuscitation (CPR). This study was conducted to determine the role of autophagy in an animal model of ventricular fibrillation (VF)/CPR. METHODS: Experiment 1: A total of 48 adult Wistar rats were untreated for 7 minutes after induction of VF using an external transthoracic alternating current, and subsequent CPR was performed to observe the existence of autophagy after the return of spontaneous circulation (ROSC). Experiment 2: A total of 72 rats were pretreated with intracerebroventricular injection of physiologic saline (control group), the autophagy inducer (rapamycin group), or the autophagy inhibitor 3-methyladenine (3-methyladenine group) before ROSC to evaluate the contribution of autophagy to neuronal injury after ROSC. RESULTS: The activation of autophagy was attenuated 2 to 4 hours after ROSC, which was related to the activity decrease of 5'-adenosine monophosphate-activated protein kinase after ROSC. Rapamycin treatment significantly increased the expressions of LC3-II and Beclin-1 after ROSC, attenuated the activation of caspase-3, promoted neuronal survival and decreased neuronal apoptosis, and improved the neurologic deficit score after CPR. CONCLUSIONS: The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.

[A study on the relationship between the composition and spectral feature parameters in chlorite].

In order to explore the intrinsic relationship of mineral spectral characteristics and its composition, and provide the basis for the detection of mineral micro information by using hyperspectral technology, based on the thinsection analysis, the authors identified the minerals characteristics and mineral assemblages in rock samples, delineated typical chlorite minerals and divided the occurrence characteristics of chlorite. The authors measured chemical composition of 146 typical chlorite mineral particles by using electron probe micro analysis technology, and calculated the relevant chemical parameters of n(Al(IV)), n(Al(VI)), n(Fe), n(Mg), and n(Fe)/n(Fe + Mg) ratio. In addition we analysed the rock and mineral spectra, and extracted chlorite characteristic spectral parameters. The relationship between the spectra feature parameters and the main crystal chemical parameters in chlorite was analyzed. The study indicated that the diagnostic spectral wavelength of chlorites moved to long wavelength. The results have important guiding significance for identifying the alteration and rock forming mineral species, composition and structure characteristics by usinghyperspectral remote sensing technology.

Early enhanced external counter pulsation improves neurological recovery after the return of spontaneous circulation in a mongrel dog cardiac arrest model*.

OBJECTIVES: The aim of this study was to investigate whether early enhanced external counter pulsation therapy after cardiopulmonary resuscitation improved neurological outcome in a mongrel dog cardiac arrest model. DESIGN: Randomized, animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Twenty-four healthy male adult dogs (12-14 kg). INTERVENTIONS: After minutes of untreated ventricular fibrillation followed by 2 minutes of cardiopulmonary resuscitation, the dogs were randomized to receive 4 hours of enhanced external counter pulsation therapy, to receive 4 hours of hypertension with over 140 mm Hg or to be a control. MEASUREMENTS: Blood pressure and left ventricular ejection fraction were recorded. Cerebral flow was assessed using magnetic resonance imaging. Arterial blood gases and endothelium-derived vasoactive substances were assessed before cardiac arrest and 4 hours after the return of spontaneous circulation. Neurological outcome was assessed by the neurologic deficit score and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: Enhanced external counter pulsation significantly improved the left ventricular ejection fraction and increased common carotid artery blood flow and shear stress. Enhanced external counter pulsation increased both relative cerebral blood volume (RCBV, p = 0.043) and relative cerebral blood flow (RCBF, p = 0.012) in animals 4 hours after return of spontaneous circulation. Enhanced external counter pulsation therapy promoted the production of nitric oxide and tissue plasminogen activator and decreased the release of endothelin-1 (p = 0.013) after return of spontaneous circulation. Treatment with norepinephrine in the high mean artery pressure also increased common carotid artery blood flow and shear stress. However, no effects on the left ventricular ejection fraction, the production of nitric oxide and tissue plasminogen activator, or the release of endothelin-1 were found. The neurologic deficit scores of the animals were significantly lower at 24, 48, 72, and 96 hours in the enhanced external counter pulsation group, as well as at 24, 72, and 96 hours compared with animals in the control group after return of spontaneous circulation. Fewer apoptotic neurons were observed in the animals in the enhanced external counter pulsation group compared with the animals in the control and hypertension groups. CONCLUSIONS: These data indicated that the treatment of early enhanced external counter pulsation improved neurological outcome by both increasing cerebral blood flow and improving the recovery of microcirculation after return of spontaneous circulation. The treatment of early enhanced external counter pulsation can be a good option for protecting the brain after return of spontaneous circulation.

Enhanced external counterpulsation improves cerebral blood flow following cardiopulmonary resuscitation.

BACKGROUND: To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of spontaneous circulation (ROSC) by cardiopulmonary resuscitation. METHODS: CA models were conducted using beagle dogs induced by alternating current. After successful ROSC by cardiopulmonary resuscitation, 16 dogs were randomly divided into the EECP and control group (n = 8 per group). Dogs underwent dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging at baseline prior to CA and during the 3 days following ROSC. Mean blood pressure, right common carotid artery blood flow, intracranial microcirculation and blood lactate levels were measured. Neurological outcome was assessed by the neurologic deficit score. Hematoxylin-eosin staining and transmission electron microscopy were performed for morphology and microconstruction of the cerebral cortex. RESULTS: The EECP group exhibited a significant elevation in right common carotid artery blood flow, intracranial microcirculation and a substantial decrease in blood lactate levels relative to the control group. Relative cerebral blood flow and volume were higher in the EECP group during the 3 days. Apparent diffusion coefficients were significantly higher in the EECP group on the first and third days. After ROSC, the neurologic deficit score was significantly higher in the control group compared to those in the EECP group during the three days of experiment. The cell swelling of neurons and increase of mitochondrial mass were more pronounced in the control group. CONCLUSION: EECP is beneficial for recovery of cerebral blood flow and attenuation of ischemic cerebral edema following CA and successful ROSC.

[Clinical analysis of drug-induced Pseudo-Bartter's syndrome: a report of five cases].

OBJECTIVE: To summarize the clinical characteristics and outcomes of Pseudo-Bartter's syndrome and explore its pathogenesis. METHODS: The clinical data of 5 cases of Pseudo-Bartter's syndrome at our ward from May 2008 to December 2010 was analyzed retrospectively. RESULTS: All patients were female. Long-term regimen of purgative or diuretics was prescribed. The clinical features included normotension, hypokalemic alkalosis and activation of renin-angiotensin-aldosterone. The pathological results of 3 cases of kidney biopsy showed the hyperplasia of juxtaglomerular apparatus, thickness of arteriole, infiltration of lymphocytes and monocytes and degeneration of renal tubule. Upon a definitive diagnosis, purgative or diuretics was discontinued and supplement therapy of potassium chloride initiated. The results of laboratory tests reverted to normal ranges within 4 weeks. CONCLUSION: Purgative or diuretics should be prescribed appropriately to avoid the occurrence of Pseudo-Bartter's syndrome.

[Clinical analysis of 6 cases of Bartter syndrome].

OBJECTIVE: To summarize the clinical characteristics of Bartter syndrome and investigate its pathogenesis. METHODS: The clinical data of 6 cases of Bartter syndrome at our hospital from November 2006 to May 2010 were analyzed retrospectively. RESULTS: The onset age of Bartter syndrome was 13-35 years old. The main symptoms included weakness (6/6), paralysis (1/6), numbness (5/6) and tetany (4/6). All patients had normal blood pressure. The biochemical tests showed persistent hypokalemia, metabolic alkalosis (6/6) and hyperreninemia. The pathological examination of deltoid muscle biopsy showed the swelling, degeneration and necrosis of myocytes and the deposition of immunocomplex in myolemma. And the pathological examination of renal biopsy showed the hyperplasia of juxtaglomerular apparatus (5/6) and the deposition of immunocomplex. All symptoms were relieved after a therapy of potassium supplementation or a combination of indomethacin, spironolactone and immunosuppressant. CONCLUSION: When such clinical features as weakness, paralysis, tetany, hypokalemic alkalosis and normotension are encountered, Bartter syndrome should be suspected. Serum electrolytes, blood gas analysis and activation of the renin-angiotensin-aldosterone system should be examined for a definite diagnosis. The treatment of choice includes potassium and magnesium supplementation or in combination with prostaglandin synthetase inhibitor, aldosterone antagonist and immunosuppressant. Immunologic mechanism may participate in the course of Bartter syndrome.

[Antibiotic resistance of gram-negative Bacillis isolated from children with bronchopneumonia].

OBJECTIVE: To study the distribution and antibiotic resistance of gram-negative pathogens isolated from children with bronchopneumonia. METHODS: The distribution and the results of susceptibility tests of 272 strains of gram-negative Bacillis isolated from children with bronchopneumonia during 2009 were analyzed. RESULTS: Among the isolates, the common pathogens were Klebsiella pneumoniae and Escherichia coli. The extended-spectrum ß-lactamase (ESBLs) production rate was 52.9%. Compared with the non-ESBLs producing strains, ESBLs-producing strains had a significantly higher drug resistance rate to many antibiotics except amikacin and meropenem (P<0.05). The lowest resistance to ESBLs producing gram negative strains was found for meropenem (0.7%), followed by imipenem, amikacin and cefoperazone/sulbactam. CONCLUSIONS: More attentions should be paid to the high rate of drug-resistance of ESBLs producing strains in children. Antimicrobial therapy should be based on the results of drug resistance surveillance.

Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study.

BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodeficiency virus (HIV)-negative patients with Talaromyces marneffei (T. marneffei) infection. METHODS: We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis. RESULTS: Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat (ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suffered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), myoglobin (Mb), procalcitonin (PCT), and galactomannan were related to poor prognosis (hazard ratio [HR]>1, P<0.05). CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

Investigation of the relationship between venticular fibrillation duration and cardiac/neurological damage in a rabbit model of electrically induced arrhythmia.

BACKGROUND: To establish a simple, economic, and reliable alternating current (AC)-induced cardiac arrest (ACCA) model in rabbits for cardiopulmonary cerebral resuscitation research. METHODS: Ventricular fibrillation was induced in 27 New Zealand rabbits by external transthoracic AC, which were randomly divided into three groups according to the duration of untreated ACCA (ACCA-3 minutes, ACCA-5 minutes, and ACCA-8 minutes). After ACCA, all animals received cardiopulmonary resuscitation for 2 minutes and subsequent defibrillation until return of spontaneous circulation (ROSC). The troponin I levels were measured at 4 hours after ROSC. Animals died spontaneously or were killed at 72 hours after ROSC. The hippocampus were removed and fixed in 3% formalin. TdT-mediated dUTP-biotin nick end labeling and Nissl stainings were performed in 10-µm thickness coronal sections. Furthermore, two rabbits (without induction of ventricular fibrillation, cardiopulmonary resuscitation, and defibrillation) served as normal control group. RESULTS: Mean survival times after ROSC were 48.57 hours ± 24.70 hours, 18.0 hours ± 15.13 hours, and 3.88 hours ± 2.39 hours for groups ACCA-3 minutes, ACCA-5 minutes, and ACCA-8 minutes, respectively. Survival was significantly different between ACCA-3 minutes and other two groups (p = 0.002 and p = 0.01). Neuronal necrosis and apoptosis were found in the hippocampus CA1, CA2, and CA3 areas of group ACCA-3 minutes. In contrast, neuronal necrosis and TdT-mediated dUTP-biotin nick end labeling positive cells were fewer in control animals. CONCLUSIONS: The rabbits in group ACCA-3 minutes had significant neuronal damage with apoptosis in hippocampus CA1, CA2, and CA3 areas at 72 hours after ROSC and survived longer than those in other groups. The model we describe may be a simple, economic, and reliable model for experimental investigation on cardiopulmonary cerebral resuscitation.

Long noncoding RNA HOTTIP promotes the metastatic potential of ovarian cancer through the regulation of the miR-615-3p/SMARCE1 pathway.

Upregulation of lncRNA HOXA transcript at the distal tip (HOTTIP) plays important roles in cancer progression. Nevertheless, its functions in the growth and metastasis of ovarian carcinoma are unknown. In this study, we demonstrated overexpression of HOTTIP in ovarian cancer cell lines and clinical tissues. Further, we showed that higher level of HOTTIP was associated with poor survival of ovarian cancer patients. Notably, HOTTIP silencing restrained proliferation, migration, and invasiveness of ovarian carcinoma cells. On the other hand, upregulation of HOTTIP remarkably exacerbated the aggressive traits of ovarian carcinoma cells. In addition, HOTTIP served as a sponge of miR-615-3p to upregulate SMARCE1 level. Further, upregulation of miR-615-3p or downregulation of SMARCE1 reversed the carcinogenic impacts of HOTTIP in ovarian cancer. HOTTIP and miR-615-3p expression levels in ovarian cancer cells were negatively correlated, whereas HOTTIP and SMARCE1 expression levels were positively correlated. In nude mice, downregulation of HOTTIP reduced cell growth in vivo. In summary, lncRNA HOTTIP promotes the growth and metastatic phenotypes of ovarian cancer via regulating miR-615-3p/SMARCE1 pathway.

Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha, China.

BACKGROUND: The outbreak of a new coronavirus, first reported in Wuhan, China, is spreading around the world. Information on the characteristics of children with Coronavirus Disease 2019 (COVID-19) is limited. METHODS: In this retrospective study, we recruited 10 children infected with SARS-COV-2 from January 27 to March 10, 2020, in Changsha, China. We report the epidemiological, clinical, laboratory, and high-resolution CT findings for these children. Qualitative descriptive analysis was used to describe the key results. RESULTS: Ten children were included. Three were male and seven were female. Three were from Wuhan, Hubei Province, and seven were from Changsha. All had a history of close contact with adults with COVID-19 before the onset of disease. Clinical manifestations included fever in four cases, respiratory symptoms in three cases, febrile convulsions in one case, vomiting in one case, abdominal pain in one case, and asymptomatic infection in two cases. All the children tested positive for nucleic acid in throat swabs at admission. Stool swabs of three cases were positive for nucleic acid after several days of fever. In nine children, blood routine results were normal, whereas in one case the white blood cell count was elevated. In four cases, CT findings of the lungs showed light ground-glass opacities, one case showed changes similar to bronchopneumonia, and the remaining cases were normal. All were treated with symptomatic support without complications. CONCLUSION: Our findings indicate that intrafamily transmission may be the main form of transmission of COVID-19 in children, and persistent intestinal excretion of virus is another characteristic among children. The results of stool swab tests should be considered for discharge and release from isolation.

Value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: Cervical lymph node metastasis in papillary thyroid carcinoma (PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; however, it is not accurate in determining lymph node metastasis. AIM: To evaluate the value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in PTC. METHODS: A total of 94 patients with PTC were recruited. According to pathological results, lymph nodes were divided into two groups: metastatic group (n = 50) and reactive group (n = 63). The routine ultrasound findings, contrast-enhanced ultrasound and elastography data were recorded and compared. Logistic regression was used to generate predictive probability distributions for the diagnosis of lymph node metastasis with different indicators. Receiver operating characteristic curve analysis was used to test the efficacy of contrast-enhanced ultrasound combined with elastography based on routine ultrasound in evaluating PTC cervical lymph node metastasis. RESULTS: The ratio of long diameter/short diameter (L/S) ≤ 2, irregular marginal morphology, missing lymphatic portal, peripheral or mixed blood flow distribution, peak intensity (PI), non-uniform contrast distribution and elasticity score in the metastatic group were significantly higher than those in the reactive group (P < 0.05). L/S ratio, missing lymphatic portal, PI and elasticity score had a significant influence on the occurrence of PTC cervical lymph node metastasis (P < 0.05). Furthermore, the area under the curve (AUC) for lymph node metastasis diagnosed using the combination of PI ratio, elasticity score, missing lymphatic portal and LS was 0.936, which was significantly higher than the AUC for PI ratio alone. The difference was statistically significant (P < 0.05). The fitting equation for the combined diagnosis was logit(P) = -12.341 + 1.482 × L/S ratio + 3.529 × missing lymphatic portal + 0.392 × PI + 3.288 × elasticity score. CONCLUSION: Based on the gray-scale ultrasound, the combination of contrast-enhanced ultrasound and elastography can accurately assess PTC cervical lymph node metastasis.

Nitroglycerin enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via nitric oxide pathway.

AIM: To investigate the effect of nitroglycerin (NTG) on cell proliferation and osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSC) and its mechanisms. METHODS: Primary HBMSC were cultured in osteogenic differentiation medium consisting of phenol red-free alpha-minimum essential media plus 10% fetal bovine serum (dextran-coated charcoal stripped) supplemented with 10 nmol/L dexamethasone, 50 mg/L ascorbic acid, and 10 mmol/L beta-glycerophosphate for inducing osteoblastic differentiation. The cells were treated with NTG (0.1-10 micromol/L) alone or concurrent incubation with different nitric oxide synthase (NOS) inhibitors. Nitric oxide (NO) production was measured by using a commercial NO kit. Cell proliferation was measured by 5-bromodeoxyuridine (BrdU) incorporation. The osteoblastic differentiation of HBMSC culture was evaluated by measuring cellular alkaline phosphatase (ALP) activity and calcium deposition, as well as osteoblastic markers by real-time RT-PCR. RESULTS: The treatment of HBMSC with NTG (0.1-10 micromol/L) led to a dose-dependent increase of NO production in the conditional medium. The release of NO by NTG resulted in increased cell proliferation and osteoblastic differentiation of HBMSC, as evidenced by the increment of the BrdU incorporation, the induction of ALP activity in the early stage, and the calcium deposition in the latter stage. The increment of NO production was also correlated with the upregulation of osteoblastic markers in HBMSC cultures. However, the stimulatory effect of NTG (10 micromol/L) could not be abolished by either N(G ) -nitro-L-arginine methyl ester, an antagonist of endothelial NOS, or 1400W, a selective blocker of inducible NOS activity. CONCLUSION: NTG stimulates cell proliferation and osteoblastic differentiation of HBMSC through a direct release of NO, which is independent on intracellular NOS activity.

Study on the development and usage of a cardiopulmonary resuscitation time point recorder.

BACKGROUND: To invent a novel cardiopulmonary resuscitation (CPR) time point recorder to synchronously and automatically record the time and to identify its effectiveness in humans. METHODS: A CPR time point recorder was invented after the doctors were familiar with the traditional Utstein recovery registration mode and mastered the registration time points required. The progress of CPR was simulated. The standard and correct times were recorded, and the doctors performing the recovery collected the data about the times using our CPR time point recorder or the memory registration mode. RESULTS: The deviation times were 21.4±24.7 seconds for the memory group and 3.57±4.58 seconds for CPR time point recorder group. The deviation of times increased significantly depending on the increase of the operation items in the memory group. A similar phenomenon was found in the timer group but with a smaller difference (P<0.01). CONCLUSION: A CPR time point recorder could reduce the deviation of operate-time, especially after a long-time operation, and for procedures with more operating items, compared with the memory mode. It was a more advantageous and accurate method for the Utstein registration.