Decrypting the skeletal toxicity of vertebrates caused by environmental pollutants from an evolutionary perspective: From fish to mammals.

The rapid development of modern society has led to an increasing severity in the generation of new pollutants and the significant emission of old pollutants, exerting considerable pressure on the ecological environment and posing a serious threat to both biological survival and human health. The skeletal system, as a vital supportive structure and functional unit in organisms, is pivotal in maintaining body shape, safeguarding internal organs, storing minerals, and facilitating blood cell production. Although previous studies have uncovered the toxic effects of pollutants on vertebrate skeletal systems, there is a lack of comprehensive literature reviews in this field. Hence, this paper systematically summarizes the toxic effects and mechanisms of environmental pollutants on the skeletons of vertebrates based on the evolutionary context from fish to mammals. Our findings reveal that current research mainly focuses on fish and mammals, and the identified impact mechanisms mainly involve the regulation of bone signaling pathways, oxidative stress response, endocrine system disorders, and immune system dysfunction. This study aims to provide a comprehensive and systematic understanding of research on skeletal toxicity, while also promoting further research and development in related fields.

Long-term tralopyril exposure results in endocrinological and transgenerational toxicity: A two-generation study of marine medaka (Oryzias melastigma).

This study aims to investigate the impact of tralopyril, a newly developed marine antifouling agent, on the reproductive endocrine system and developmental toxicity of offspring in marine medaka. The results revealed that exposure to tralopyril (0, 1, 20 µg/L) for 42 days resulted in decreased reproductive capacity in marine medaka. Moreover, it disrupted the levels of sex hormones E2 and T, as well as the transcription levels of genes related to the HPG axis, such as cyp19b and star. Sex-dependent differences were observed, with females experiencing more pronounced effects. Furthermore, intergenerational toxicity was observed in F1 offspring, including increased heart rate, changes in retinal morphology and cartilage structure, decreased swimming activity, and downregulation of transcription levels of relevant genes (HPT axis, GH/IGF axis, cox, bmp4, bmp2, runx2, etc.). Notably, the disruption of the F1 endocrine system by tralopyril persisted into adulthood, indicating a transgenerational effect. Molecular docking analysis suggested that tralopyril's RA receptor activity might be one of the key factors contributing to the developmental toxicity observed in offspring. Overall, our study highlights the potential threat posed by tralopyril to the sustainability of fish populations, as it can disrupt the endocrine system and negatively impact aquatic organisms for multiple generations.

Chinese perfusion practice survey results in 2021: current situation and challenge / 中华胸心血管外科杂志

Objective:To investigate the current situation of cardiopulmonary bypass(CPB) in China and analyze the causes, to guide the formulation and implementation of technology standard.Methods:The survey task force sent out a nationwide survey to obtain up-to-date information on perfusion practice by ChSECC(Chinese Society of Extracorporeal Circulation). The unit of analysis for the survey was the medical center performs CPB. The survey consisted 48 questions covering four topics of qualifications, including certification and education, policies and practices, device and equipment, techniques used.Results:There were 540 of the 714 centers for an overall response rate of 76%. According to the annual number of CPB, they were divided into 4 groups: group A(≤50 cases/year), group B(50-100 cases/year), group C(100-500 cases/year) and group D(≥500 cases/year). The response rate of center with more than group D last year was 100%. Most of the perfusionists had certification issued by ChSECC. Although there were more than 80% of group D performed regular training and assessment of perfusionist, the result was still not ideal enough. Low utilization of safety equipment was not depend on the annual operation volume in most of responding centers. Ultrafiltration and blood protection technology had high application rate in group D compared with group A and B.Conclusion:The certification rate of perfusionists are high. Lower the number of annual CPB cases, lower the proportion of regular evaluation and training, and lower rate of standards performance. No matter the amount of CPB, the application rate of safety equipment is not ideal. Higher the number of CPB cases, higher the utilization rate of CPB related technologies.

Spinal Ninjurin2 contributes to the neuropathic pain via NF-κB-mediated neuroinflammation in the spared sciatic nerve injury rats.

OBJECT: Ninjurin2 (nerve injury induced protein 2, NINJ2) is a molecule which mediates cell-to-cell and cell-to-extracellular matrix interactions in the nervous system. Clinical study shows NINJ2 is associated with the development of postherpetic neuralgia. However, it is lack of direct evidence that NINJ2 participated in neuropathic pain. In this study, we aim to investigate the role of NINJ2 in the development of neuropathic pain in spared sciatic nerve injury rats and the underlying mechanism. METHOD: Spared sciatic nerve injury (SNI) models were established. The level of NINJ2 and p-p65 (a NF-κB family member) were measured in SNI rats by western blots and immunofluorescent staining. Lentivirus encoding small interfering RNA targeting NINJ2 (RNAi) was intrathecally injected into rats. Then the change of pain behavior of rats induced by NINJ2 RNAi was tested by Von-Frey hairs. The change of p-p65 in the spinal cord in rats after NINJ2 RNAi treatment was also measured by western blots. inhibitor of p-p65-induced change of TNF-α, IL-1ß, and IL-6 levels were measured by ELISA. RESULTS: NINJ2 and p-p65 were increased in the spinal cord of SNI rats on the 3, 7, 14th days after modeling. NINJ2 were mainly expressed in neurons, and co-located with p-p65 in the spinal dorsal horn. When down regulating the level of NINJ2 by RNAi, the development of pain in SNI rats was partially blocked. Phosphorylation of p65 was also inhibited by NINJ2 RNAi. Blocking the phosphorylation of NF-κB pathway could inhibit the increase of TNF-α, IL-1ß, and IL-6 in the spinal cord of SNI rats. CONCLUSION: NINJ2 protein was increased in the spinal cord of SNI rats. It participated in the development of nerve injury-induced neuropathic pain by activating neuroinflammation in the spinal cord via NF-κB pathway. This study provides a new target to investigate the mechanism of neuropathic pain.

The Roles of Chemokine CXCL13 in the Development of Bone Cancer Pain and the Regulation of Morphine Analgesia in Rats.

Chemokines are important regulators of immune, inflammatory, and neuronal responses in peripheral and central pain pathway. The aim of this study was to investigate whether chemokine (C-X-C motif) ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) involve in the development of bone cancer pain (BCP) and the regulation of morphine analgesia in rats. The change of pain behaviors in BCP rats were measured by testing paw withdrawal threshold (PWT). The levels of CXCL13, CXCR5 and signal pathway proteins (p-p38, p-ERK and p-AKT etc.) in the spinal cord were measured via western blots. The expression of CXCL13 and CXCR5 in spinal cord was increased in BCP rats. The BCP rats showed decrease of PWTs, which was relieved by CXCR5i. Intrathecally injection of murine recombinant CXCL13 (mrCXCL13) decreased the PWTs of BCP rats and opposed morphine-induced analgesia in BCP rats. In BCP rats, the signal pathway proteins (p38, ERK and AKT) in the spinal cord were activated. CXCL13 and morphine had contrary effect on the phosphorylation of these proteins. MrCXCL13 directly increased the levels of p-p38, p-ERK and p-AKT in BCP rats. However, morphine decreased the levels of these proteins in BCP rats. While blocking the activation of p-p38, p-ERK and p-AKT, morphine analgesia was enhanced. These results suggest CXCL13 participated in bone cancer pain and opposed morphine analgesia via p38, ERK and AKT pathways. It may be a target to enhance pain management in cancer pain patients.

Observation of neuropsychological development status in children after surgical treatment of congenital heart diseases / 中华胸心血管外科杂志

Objective To observe neuropsychological development status in children after surgical treatment of congenital heart diseases(CHDs)and analyze the risk factors. Methods 89 children who received outpatient review in Fuwai Hospital from September 2015 to March 2016 after surgical treatment of CHDs were recruited in this study and 90 normal children were recruited as the control group. The children with CHDs were divided into simple CHDs group(RACHS- 1 score≤2)and com-plex CHDs group(RACHS- 1 score≥3)according to RACHS- 1 classification. Neuropsychological development status was meas-ured according to pediatric-psychological mental test scale developed by Capital institute of pediatrics,Beijing and statistical a-nalysis was compared. Results The measurements of neuropsychological development showed the normal children behaved better than the children with CHDs(P < 0. 05). The simple CHDs group achieved better distribution of development quotient than complex CHDs group(P = 0. 032)and there was no difference between the normal control group and simple CHDs group (P = 0. 420). Multivariate regression analysis indicated that younger age at cardiac surgery,lower preoperative blood urea ni-trogen(BUN),higher preoperative creatinine(Cr)and prolonged duration of cardiopulmonary bypass(CPB)accounted for low-er scores in the test scale(P < 0. 05). Conclusion Distinct neuropsychological difficulties could be present especially in chil-dren with complex CHDs. Younger age at cardiac surgery,preoperative BUN,Cr and CPB duration were perioperative factors that were associated with long-time neuropsychological development.

The complete mitochondrial genome of the Tamarisk gerbil, Meriones tamariscinus (Rodentia: Muridae).

The complete mitochondrial genome of the Tamarisk jird, Meriones tamariscinus, was sequenced. The 16,389bp genome contains 37 genes, typical for rodent mitogenomes, including 22 tRNA genes, 2 rRNA genes, and 13 protein-coding genes. The total GC content of the mitochondrial genome is 36.8%, with a base composition of 34.0% A, 24.5% C, 12.3% G, and 29.2% T. The phylogenetic analysis showed that M. tamariscinus was classified in the genus Meriones, Muridae.

Cardioplegia solution plus metformin protects isolated rat hearts / 中华胸心血管外科杂志

Objective To evaluate the protective value of cardioplegia solution plus metformin in different cardiac arrest time and concentration of metformin in isolated rat hearts .Methods There were 36 male Sprague–Dawley rats divided into six groups randomly, according to the duration of cardioplegic arrest(30 min or 60min) and the concentrations of metformin(50μmol/L or 100 μmol/L) .Langendorff-perfused Sprague-Dawley rat hearts were perfused for 20 minutes with Krebs-Henseleit buffer followed by 30 or 60 minutes of crystalloid cardioplegia or plus metformin (50 or 100 μmol/L) and 60 minutes of reperfu-sion.The left ventricular performance was recorded at 5 time points.The expressions of AMPKαand phosphorylation of AMPKαwere detected by western Blot.The changes of myocardial mitochondria were observed under transmission electron mi-croscope.Results There were no significant differences in Con(A), 50(A) and 100(A) groups in LVDP, ±dp/dtmax and HR.Compared with Con(B) group subjected to 60 minutes of ischemia followed by 60 minutes of reperfusion, the 100(B) group significantly improved myocardial performance , and the ratio of p-AMPKα/AMPKαwas the highest in all 6 groups.The structure of myocardial mitochondria in 100(B) group was better protected than that of Con(B) group.Conclusion These findings suggested that the left ventricular performance was protected in rat heart perfused by cardioplegia plus 100 μmol/L after 60 minutes cardioplegic arrest .The mechanism may be the activation of AMPK and the protection of structures of myocardial mitochondria.

Outcome analysis of ECMO applying in extracorporeal cardiopulmonary resuscitation in adult cardiac arrest patients / 中华胸心血管外科杂志

Objective Summarizing single clinical experience with extracorpomreal membrane oxygenation(ECMO) as a supplement to extracorporeal cardiopulmonary resuscitation(ECPR) in adult patients with cardiac arrest to explore new ideas.Methods We retrospectively analyzed the characteristics of 17 patients who underwent ECMO as part of ECPR from July 2005 to September 2014 at Fuwai Hospital,and analyzed the differences between the survival group(n =6) and the in-hospital death group.Results The mean CPR time was(44.53 ± 21.39) min.The support duration of ECMO was(106.38-± 70.43) h.12 patients of all were successfully weaned from ECMO,and 6 patients survived to hospital discharge.There were significant differences between the two groups in terms of the last serum creatinine and blood lactate acid level before ECMO,and the time to lactate normalization.11 patients died,7 patients developed bleeding,and 8 cases developed infection.Conclusion Single-center data showed that applying ECMO as a means of ECPR improved the survival rate in cardiac arrest patients.Additionally,creatinine and lactic acid were good indicators for assessing prognosis.Refractory circulatory dysfunction and neurologic complications have an adverse impact on the survival of cardiac arrest patients.

Risk factors and outcomes of severe hemolysis during extracorporeal membrane oxygenation：a 5-year ;single-center retrospective analysis / 中华危重病急救医学

Objective To investigate the risk factors of severe hemolysis during extracorporeal membrane oxygenation (ECMO). Methods The clinical data of adult patients undergoing ECMO after cardiac surgery admitted to Fuwai Hospital from December 2010 to October 2015 were retrospectively analyzed. Demographic characteristics, renal function, primary disease, operation data, ECMO related data and outcomes were recorded. Patients were divided into normal free hemoglobin (FHB) group (FHB ≤ 500 mg/L) and severe hemolysis group (FHB > 500 mg/L) according to the FHB level during ECMO support. The parameters before and after ECMO support were compared between the two groups. Logistic regression was used to identify the independent risk factors of severe hemolysis. Results A total of 81 patients including 19 patients with severe hemolysis was enrolled, and 62 in normal FHB group. There was no difference in cardiopulmonary bypass (CPB) time, clamping time, lactate level before ECMO, cardiopulmonary resuscitation, intra-aortic balloon pump use and central catheter insertion between two groups. The maximums of serum creatinine (SCr) and FHB levels were higher in severe hemolysis group as compared with those in normal FHB group [maximal SCr (μmol/L): 281.02±164.11 vs. 196.67±87.31, maximal FHB (mg/L): 600 (600, 700) vs. 200 (100, 300)], the incidence of clots in circuit or oxygenator, infection, and hemofiltration in severe hemolysis group was increased [26.3% (5/19) vs. 4.8% (3/62), 31.6% (6/19) vs. 12.9% (8/62), 36.8% (7/19) vs. 14.5% (9/62), all P < 0.1]. As well as outcomes including the rate of site of surgery or intubation bleeding and acute renal failure [ARF, 57.9 % (11/19) vs. 30.6% (19/62), 94.7% (18/19) vs. 41.9% (26/62)], and the survival rate was lowered [10.5% (2/19) vs. 51.6% (32/62), all P < 0.05]. As result of univariate analysis, clots in circuit or oxygenator, infection and hemofiltration were associated with severe hemolysis. It was showed by logistic regression analysis that the clots in circuit or oxygenator was a risk factor of severe hemolysis during ECMO [odds ratio (OR) = 6.262, 95% confidence interval (95%CI) = 1.244-31.515, P = 0.026]. Conclusions The clots in circuit or oxygenator were independent risk factors of severe hemolysis during ECMO. Severe hemolysis can induce the increase of the rate of bleeding in the operation site or intubation and the rate of ARF, and decrease of the survival rate.

[Outcome of extracorporeal membrane oxygenation support for adult patients in Fuwai Hospital during the last 10 years: treatment strategy and risk factors].

OBJECTIVE: To retrospectively review the clinical data of patients receiving extracorporeal membrane oxygenation (ECMO) during the last 10 years in Fuwai Hospital in order to assess the factors associated with the outcome of patients who had undergone ECMO, as well as to summarize the clinical experience, and to adopt a treatment strategy for future clinical decision. METHODS: The clinical data of adult patients undergoing ECMO admitted to Fuwai Hospital from December 2004 to December 2014 were retrospectively analyzed. Demographic characteristics, diagnosis, ECMO related data, including ECMO indication, operation, undergoing cardiopulmonary resuscitation (CPR) or not, and site of establishment, clinical parameters before and 24 hours after ECMO, duration of ECMO, and complications were collected to set up a database. The patients were divided into survival group and non-survival group according to the prognosis. The risk factors of mortality in hospital after ECMO were analyzed by logistic regression. RESULTS There were 142 adult patients who had received ECMO support, with 106 male and 36 female. All patients received veno-arterial ECMO (V-A ECMO). The indication of ECMO in 59 patients was unsuccessful weaning from extracorporeal circulation (41.5%), and that of 44 patients was low cardiac output cardiogenic shock (31.0%). CPR was necessary in 34 out of 142 patients undergoing ECMO. In 37 patients intra-aortic balloon pump (IABP) was necessary. ECMO was successfully weaned in 99 patients (69.7%), and 84 patients (59.2%) survived. The most frequent complication during ECMO support was bleeding from site of catheterization or operation (45.8%). Logistic regression revealed that high lactic acid levels [odds ratio (OR) = 1.469, 95% confidence interval (95%CI) = 1.170-1.843, P = 0.001] and high blood glucose (OR = 0.984, 95%CI = 0.969-0.999, P = 0.037) at 24 hours after ECMO, multiple organ dysfunction syndrome (MODS, OR = 17.243, 95%CI = 3.177-93.581, P = 0.001), gastrointestinal bleeding (OR = 8.774, 95%CI = 1.414-54.457, P = 0.020) were risk factors of in-hospital mortality in adult patients undergoing ECMO. CONCLUSIONS: ECMO can provide effective auxiliary support in patients with respiratory and circulatory failure, which 'shows good clinical effect. Strict indication, timely ECMO support and sophisticated management are the keys to the success of ECMO. The most frequent complications during ECMO support is bleeding from site of catheterization or operation. High lactic acid levels at 24 hours after ECMO, MODS and gastrointestinal bleeding are predictors of in-hospital mortality in adult patients, and appropriate control of blood sugar was beneficial for the recovery of patients.

Advances in the application of extracorporeal membrane oxygenation in the treatment of severe burn / 中华烧伤杂志

Extracorporeal membrane oxygenation (ECMO) is a kind of technique that uses extracorporeal circulation system to draw patients' blood into the circuit, and then oxygenate the blood when it passes along the membrane, followed by returning the blood into patients. At present, ECMO is mainly used in treating patients with respiratory failure and circulatory failure, for whom the conventional treatment such as mechanical ventilation and vasoactive drugs are invalid. ECMO can provide cardiopulmonary support for burn patients with respiratory failure or circulatory failure, and put the heart and lung at rest. The purpose of this paper is to review the application of ECMO in the treatment of severe burn.

Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1ß and inhibiting syndecan-1 shedding in the intestinal mucosa.

Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1ß, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1ß and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.

The dynamic observation of plasma concentration of antimicrobial agents during balanced ultrafiltration in vitro / 中华胸心血管外科杂志

Objective Routine perioperative intravenous antimicrobial agents,was administered as surgical prophylaxis.However,whether balanced ultrafiltration during extracorporeal circulation can remove antimicrobial agent remains unclear.The concentrations of antimicrobial agent in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model.Methods Extracorporeal circulation consisted of cardiotomy reservoir (Ningbo Fly Medical Healthcare CO.,LTD.Ningbo,China),D902 Lilliput 2 membrane oxygenator (Sorin Group Asia Pte Ltd,Beijing,China) and Capiox (R) AF02 pediatric arterial line filter (Terumo Corporation,Beijing,China).HEMOCONCENTRATOR BC 20 plus (MAQUET Cardiopulmonary AG,Hirrlingen,Germany) was placed between arterial purge line and oxygenator venous reservoir.Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24％-28 ％.After 30 minutes of extracorporeal circulation,zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mm Hg(1 mm Hg =0.133 kPa) with Hoffman clamp.The rate of ultrafiltration (12 ml/min) was controlled by ultrafiltrate outlet pressure.Identical volume of plasmaslyte A was dripped into the circuit to maintain stable hematocrit during 45 minutes of experiment.Plasma and ultrafiltrate samples were drawn every 5 minutes and concentrations of antimicrobial agent (including Cefmetasole and cefotiam) were measured with high performance liquid chromatography.Results All these two antimicrobial agents were detected in ultrafiltrate,demonstrating hemoconcentration may remove antimicrobial agent.The concentration of plasma antimicrobial agent decreased lineally with the increase of ultrafiltrate volume.At end of balanced ultrafiltration,the concentration of plasma cefotiam was (104.96 ± 44.36) μg/ml,which is about (44.38 ± 7.42) ％ of the initial concentration (238.95 ± 101.12) μg/ml; the concentration of plasma cefmetazole decreased linearly to (25.76 ± 14.78) μg/ml,which is about (49.69 ± 10.49) ％ of the initial concentration (51.49 ± 28.03) μg/ml.The total amount of cefotiam in ultrafiltrate is (27.16 ± 12.17)％ of the total dose administered,whereas cefmetasole in ultrafiltrate is (7.74 ±4.17)％.Conclusion Balanced ultrafiltration may remove antimicrobial agent from serum and has significant influence on plasma concentration of antimicrobial agent.The strategy of surgical prophylaxis should consider this unique technique during extracorporeal circulation.

Study on the incidence and risk factors of HCV infection among heroin addicts who were on methadone maintenance treatment in Dehong prefecture,Yunnan province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the incidence and risk factors of HCV infection among heroin addicts who were receiving methadone maintenance treatment(MMT)in Dehong prefecture, Yunnan province.</p><p><b>METHODS</b>All heroin addicts who were HCV negative at the initiation of MMT in June 2005 through March 2012, in Dehong prefecture, were included in this cohort analysis. HCV incidence was calculated and related risk factors determined by using Cox proportional hazard regression model.</p><p><b>RESULTS</b>A total of 2390 MMT clinic attendants were qualified for this cohort study by March 2012. 731(30.6%) of them had never received any follow-up HCV testing so were recognized as loss to follow-up. The other 1659 (69.4%) participants had received at least one follow-up HCV testing and were observed for a total of 3509.12 person-years(py). During this period 99 new HCV infections or HCV sero-converters were identified. The overall HCV incidence was 2.82/100 py and was 3.62/100 py for 2006, 5.36/100 py for 2007, 6.71/100 py for 2008, 2.56/100 py for 2009, 1.90/100 py for 2010, and 0.44/100 py for 2011, respectively. Results from multiple regression analysis, using Cox proportional hazard model, indicated that after controlling for confounding variables, those who were unemployed, being injecting drug users(IDUs)or HIV positive at entry into the MMT program were more likely to be newly infected with HCV or HCV sero-converted during the follow-up period than those who were peasants, non-IDUs or HIV negative at entry into the MMT program(HR = 2.02, 95% CI:1.18-3.48; HR = 9.05, 95% CI:5.49-14.93; HR = 2.12, 95% CI: 1.37-3.56), respectively.</p><p><b>CONCLUSION</b>The incidence of HCV infection among MMT clinic attendants was decreasing since 2009 in Dehong prefecture. Those who were unemployed, injecting drug users and HIV positive were at higher risk of HCV infection.</p>

What does it take to synergistically combine sub-potent natural products into drug-level potent combinations?

There have been renewed interests in natural products as drug discovery sources. In particular, natural product combinations have been extensively studied, clinically tested, and widely used in traditional, folk and alternative medicines. But opinions about their therapeutic efficacies vary from placebo to synergistic effects. The important questions are whether synergistic effects can sufficiently elevate therapeutic potencies to drug levels, and by what mechanisms and at what odds such combinations can be assembled. We studied these questions by analyzing literature-reported cell-based potencies of 190 approved anticancer and antimicrobial drugs, 1378 anticancer and antimicrobial natural products, 99 natural product extracts, 124 synergistic natural product combinations, and 122 molecular interaction profiles of the 19 natural product combinations with collective potency enhanced to drug level or by >10-fold. Most of the evaluated natural products and combinations are sub-potent to drugs. Sub-potent natural products can be assembled into combinations of drug level potency at low probabilities by distinguished multi-target modes modulating primary targets, their regulators and effectors, and intracellular bioavailability of the active natural products.

[Control study on colonoscopy skills acquiring from endoscopic simulation system transfering to patients].

OBJECTIVE: To explore the feasibility of transferring the skills from the AccuTouch flexible endoscopy simulator colonoscopy training to clinical practices. METHODS: The novice colonoscopies were divided into 2 groups.Group A (control group) including 4 trainees for traditional training, Group B (experimental group) including 4 trainees for simulator training. After training, we compared the number of cases for achieving independent competence, assisted competence and incompetence in the first ten patients. RESULTS: No significant differences existed between two groups in terms of age and gender (both P > 0.05). Significant differences existed in educational background and the controlled group was better than the experimental group (Z = -2.005, P = 0.04). The cases of independent completion, assisted competence and incompetence of the control and experimental groups were 2, 4, 9 and 21, 29, 15 respectively. Rank tests show that the simulator training was better than the traditional counterpart (average rank: 56.14 vs 24.86, Z = -6.393, P = 0.00). CONCLUSIONS: The skills acquired from AccuTouch Endoscopy Simulator may be well transferred into the clinical colonoscopy environment. It clearly supports the scheme of integrating simulator training into colonoscopic education curricula.

Drug discovery prospect from untapped species: indications from approved natural product drugs.

Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery.

The pilot observation of cerebral blood flow during aortic arch reconstruction surgery in piglet's animal model / 中华胸心血管外科杂志

ObjectiveA single pump and double arterial lines piglet model was established in this piglet's experiment.The preliminary study of cerebral blood flow proportion and distribution was performed continuously during the procedure.MethodsEight female piglets were utilized in this study.The body weight ranged from 18 kg to 22 kg.The right atrium was carmulated for venous drainage.Double arterial lines were established through cannulating into right carotid artery and ascending aortic aorta.Selective antegrade cerebral perfusion (SACP) through right carotid artery started after bladder temperature was decreased to 20℃ and the perfusion from ascending aortic aorta was interrupted.The perfusion through ascending aortic aorta resumed following 60 minutes of circulatory arrest.Traditional rewarming strategy was adopted and the experiment ended when bladder temperature attained 36℃.The real-time blood flow in the double arterial lines was monitored using a TS410 transit-time tubing flowmeter (Transonic Systems Inc.,Ithaca,NY).Blood pressure in femoral artery,intra-circuit pressure was recorded every five minutes interval.Regional cerebral oxygen saturation ( rSO2 ) was assessed with NIRO-200 oximeter using Near-infrared spectroscopy (Hamamatsu Photonics,Hamamatsu City,Japan )and mixed venous oxygen saturation ( SvO2 ).Blood samples were drawn for blood chemistry measurement prior to extracorporeal circulation,before circulatory arrest and at the end of experiment.ResultsArterial blood pressure was maintained at (60 ± 20) mm Hg.Total blood flow perfusion was(85.30 ±6.81)ml · kg-1 · min-1 and(14.42 ±1.76) ml · kg-1 · min-1 in right carotid artery.The proportion of cerebral blood flow was (16.72 ± 2.77 )％ of total perfusion.Cerebral blood perfusion was controlled with( 15.11 ± 0.44)ml · kg - 1 · min - 1 during SACP.Compared to SvO2,rSO2 remained stable during the procedure.The plasma concentration of

Effects of peri-operative glucose levels on adverse outcomes in infants receiving open-heart surgery for congenital heart disease with cardiopulmonary bypass.

OBJECTIVE: Studies designed to evaluate the association of hyperglycemia and adverse events in pediatric patients receiving open cardiac surgery have yielded inconsistent results. The aim of this retrospective, observational study was to evaluate the effects of peri-operative glucose levels on adverse events in infants receiving open-heart surgery with CPB. METHODS: From Nov 2009 through Dec 2009, 100 infants undergoing open-heart surgery were enrolled. All glucose values during the operation and intensive care unit stay were documented. Metrics of glucose control, including mean, peak and minimum glucose levels were calculated. Hyperglycemia was defined as a mean glucose above 150 mg/dl. Hypoglycemia was defined as minimum glucose below 65 mg/dl. Multivariable regression analyses were used to determine relationships between these metrics of glucose control and a composite morbidity-mortality outcome after controlling for multiple variables known to influence early outcomes after congenital heart surgery. RESULTS: According to our definition, 43 patients (43%) developed hyperglycemia and 9 patients (9%) developed at least one episode of hypoglycemia. A total of 58 patients reached the overall composite morbidity-mortality end point at some point during the study period. After adjusting the effects of age, cross-clamp time and pre-operative percutaneous oxygen saturation by multivariable analysis, euglycemia, defined as mean glucose ≤150 mg/dl, was found to be a significant predictor for morbidity, with an odds ratio of 5.1(95% confidence interval 1.5-17.5). CONCLUSION: In contrast to adult critically ill patients, data from the present study did not prove that hyperglycemia was detrimental to infants receiving open-heart surgery with CPB. The existing literature and findings of our present study warranted future clinical studies of strict glycemic control in critically ill children, considering a more permissive glycemic range as a desirable target.