Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Methods: Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Results: Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; ß-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and ß-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Conclusion: Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

A specific nanobody-based affinity chromatography resin as a platform for small ubiquitin-related modifier fusion protein purification.

As an excellent fusion tag for expressing heterologous proteins, yeast SUMO (small ubiquitin-related modifier) has unique advantages such as improving solubility, promoting stability, and reducing degradation, but it lacks a simple and rapid purification method. Camelid single-domain antibodies (VHHs or nanobodies) show great promise as an efficient tool in analytical application. In this study, VHHs against SUMO protein were isolated for the first time using biopanning of an immune camelid nanobody library. Among these nanobodies, VS2 demonstrated a high expression level (1.12 g L - 1), and a high affinity for SUMO (2.26 nM). Meanwhile, VHHs were coupled to agarose resins by cysteine at the C-terminal to form affinity chromatography resins. The VS2 resin showed excellent specificity and a dynamic binding capacity for SUMO, SUMO-DsbA (disulfide oxidoreductase) and SUMO-SAM (S-adenosylmethionine synthetase) were 2.41 mg/mL resin, 7.57 mg/mL resin and 16.23 mg/mL resin, respectively. Furthermore, the VS2 resin enabled one-step purification of SUMO-fusions [SUMO-Fc (human IgG1-Fc fragment), SUMO-IGF1 (human insulin-like growth factor 1), SUMO-FGF21 (human fibroblast growth factor 21), SUMO-G-CSF (human Granulocyte colony-stimulating factor), SUMO-PDGF (human platelet-derived growth factor) and SUMO-PAS200 (conformationally disordered polypeptide chains with expanded hydrodynamic volume comprising the small residues Pro, Ala-and Ser)], and maintained binding capacity and selectivity over 25 purification cycles, each including 15 min of cleaning-in-place with 0.1 M NaOH. This study demonstrated that the VS2 resin was a useful tool at the laboratory scale for one-step purification of various SUMO fusions from complex mixtures.

Open reduction through original fracture line and fixation with locking plate is a feasible approach for extra-articular distal radius fracture malunion.

OBJECTIVES: This study aims to investigate the effectiveness of open reduction through original fracture line and fixation with locking plate in treatment of extra-articular distal radius fracture (DRF) malunion. PATIENTS AND METHODS: Between January 2015 and December 2018, a total of 69 patients (27 males, 42 females; mean age: 62.0±8.9 years; range, 46 to 70 years) suffering from symptomatic extra-articular DRF malunion were included. All patients were followed for more than six months. Patient's demographics, hand dominance, data including Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, pain on a Visual Analog Scale (VAS) score, radius height, ulnar variance, wrist range of motion, volar tilt and radial inclination before and after surgery were analyzed. RESULTS: The median follow-up was 14.13 months, and the median time to fracture healing after the operation was 14.25 weeks. The mean QuickDASH score and VAS score were significantly reduced from 63.4±13.97 and 4.6±1.23 preoperatively to 7.8±4.67 and 1.3±0.76 at the final follow-up, respectively. Radius height, ulnar variance, volar tilt, radial inclination and wrist range of motion (flexion, extension, pronation, supination) were all significantly improved (p<0.001). Images showed good radius height, ulnar variance, volar tilt and radial inclination. The range of motion of wrist and forearm were improved substantially. Among 69 patients, two patients received allograft due to osteoporotic bone collapse. No serious complication was developed, except for minor pain in three patients during follow-up. CONCLUSION: Open reduction through original fracture line and fixation with locking plate is a feasible and effective treatment for selective DRF malunion.

MutiLoc Nail Versus Philos Plate in Treating Proximal Humeral Fractures: A Retrospective Study Among the Alderly.

BACKGROUND: Proximal humeral fractures (PHFs) account for 4-5% of all fractures in the elderly. There is still a controversy among the treatments in the displaced PHFs. Our aim was to explore the clinical outcome of PHFs with the treatment of MultiLoc nail or Philos plate in the elderly patients. METHODS: A total of 82 sustained elderly patients with PHFs were finally recruited between Dec 2016 and Dec 2017. 34 patients were treated with MultiLoc nail and 48 patients were treated with Philos plate. The demographics, fracture types, blood loss, operation time, union time, postoperative complications, visual analog scores (VASs), Constant scores, American Shoulder and Elbow Scores (ASESs), and neck-shaft-angle (NSA) between the two groups were compared. RESULTS: No differences were observed in the demographics, fracture types, VAS, Constant scores, and ASES scores between the two groups at final follow-up. Compared with the plate group, the blood loss, operation time, and union time were significantly lower in the nail group (all P < .05). The rate of general complications was 54.17% in the plate group, which was higher than that in the nail group (26.47%, P = .01). Three patients experienced reoperation in the plate group (3/48; 6.25%), but none in the nail group. Although there were no significant differences in intraoperative NSA between the two groups, the NSA at final follow-up in the nail group was much higher than the plate group (137.55 ± 5.53°vs 134.47 ± 5.92°, P = .02). CONCLUSIONS: Multiloc intramedullary nail showed the similar effectiveness of final VAS, final Constant scores, and ASES scores in PHFs treatment with Philos plate. However, MultiLoc nail is superior to Philos plate in blood loss, operation time, complications, reoperation rate, and the change of NSA.

Preclinical Pharmacokinetics, Tissue Distribution and Primary Safety Evaluation of a Novel Curcumin Analogue H10 Suspension, a Potential 17ß Hydroxysteroid Dehydrogenase Type 3 Inhibitor.

17ß Hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is the key enzyme in the biosynthesis of testosterone, which is an attractive therapeutic target for prostate cancer (PCa). H10, a novel curcumin analogue, was identified as a potential 17ß-HSD3 inhibitor. The pharmacokinetic study of H10 in rats were performed by intraperitoneal (i.p.), intravenous (i.v.) and oral (p.o.) administration. In addition, the inhibitory effects of H10 against liver CYP3A4 were investigated in vitro using human liver microsomes (HLMs). The acute and chronic toxicological characteristics were characterized using single-dose and 30 d administration. All the mice were alive after i.p. H10 with dose of no more than 100 mg/kg which are nearly the maximum solubility in acute toxicity test. The pharmacokinetic characteristics of H10 fitted with linear dynamics model after single dose. Furthermore, H10 could bioaccumulate in testis, which was the target organ of 17ß-HSD3 inhibitor. H10 distributed highest in spleen, and then in liver both after single and multiple i.p. administration. Moreover, H10 showed weak inhibition towards liver CYP3A4, and did not cause significant changes in aspartate transaminase (AST) and alanine transaminase (ALT) levels after treated with H10 for continuously 30 d. Taken together, these preclinical characteristics laid the foundation for further clinical studies of H10.

Quantum reinforcement learning during human decision-making.

Classical reinforcement learning (CRL) has been widely applied in neuroscience and psychology; however, quantum reinforcement learning (QRL), which shows superior performance in computer simulations, has never been empirically tested on human decision-making. Moreover, all current successful quantum models for human cognition lack connections to neuroscience. Here we studied whether QRL can properly explain value-based decision-making. We compared 2 QRL and 12 CRL models by using behavioural and functional magnetic resonance imaging data from healthy and cigarette-smoking subjects performing the Iowa Gambling Task. In all groups, the QRL models performed well when compared with the best CRL models and further revealed the representation of quantum-like internal-state-related variables in the medial frontal gyrus in both healthy subjects and smokers, suggesting that value-based decision-making can be illustrated by QRL at both the behavioural and neural levels.

An efficient procedure for preparing high-purity pingyangmycin and boanmycin from Streptomyces verticillus var. pingyangensis fermentation broth via macroporous cation-exchange resin and subsequent reversed-phase preparative chromatography.

Pingyangmycin (PYM) and boanmycin (BAM), two individual components of bleomycin (bleomycin A5 and bleomycin A6), are glycopeptide antitumor antibiotics. An efficient procedure for the preparation of PYM and BAM from Streptomyces verticillus var. pingyangensis fermentation broth using macroporous cation-exchange (MCE) resin followed by medium-pressure preparative liquid chromatography (MPLC) based on monodisperse poly(styrene-co-divinylbenzene) (p(st-dvb)) microspheres was investigated in this paper. Nine frequently used MCE resins were screened by static adsorption and desorption to enrich PYM and BAM fromthe fermentation broth, and D157 resin was found to be the most effective. After one run of column-based dynamic adsorption and desorption, the contents of PYM and BAM were increased by factors of 13.8 and 12.1 with recovery yields of 84.21% and 81.47%, respectively. The enriched samples were subjected to MPLC with columns prepacked with the PolyRP 10-300 microspheres. The operational parameters of the MPLC, including the stationary phase and mobile phase compositions, sample/stationary phase ratio, sample loading scale and flow rate, were screened and optimized. The results showed that the separation and purification for PYM and BAM by MPLC were dramatically improved with a mobile phase modifier of 0.15 mol/L ammonium chloride aqueoussolution, a flow rate of 10 mL/min and a sample/stationary phase ratio of 1.0:100 (m/v, g/mL), and PYM and BAM with purities of more than 98.65% and 99.12% were obtained, respectively. The total recoveries of PYM and BAM reached 75.38% and 70.31%. The separation and purification method is simple, efficient, energy-saving, environmentally friendly and suitable for the large-scale preparation of high-purity PYM and BAM from Streptomyces verticillus var. pingyangensis fermentation broth.

Snail modulates JNK-mediated cell death in Drosophila.

Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.

Spleen-kidney supplementing formula alleviates insulin resistance via regulating AKT/glycogen synthase kinase 3ß pathway in rats with type 2 diabetic induced by high-fat diet.

OBJECTIVE: To explore the molecular mechanism underpinning the action by investigating its effect on glycogen content and AKT (also known as protein kinase B)/glycogen synthase kinase 3ß (GSK- 3ß) pathway in the liver of rats with type 2 diabetic induced by high-fat diet. METHODS: The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injection. Diabetic rats were divided into five groups: the model control group, the Metformin group, spleen-kidney supplementing formula groups of low, medium and high doses. Fasting blood glucose (FBG) levels were measured before treatment and every two weeks during treatment. After the treatment, oral glucose tolerance test was performed, and hemoglobin A1c (HbA1c) and C-peptide were measured to assess the formula's effect on glucose metabolism and insulin resistance. The protein expression levels of AKT, GSK-3ß and their phosphorylated forms in the liver were also measured to study the formula's role in insulin signaling pathway. RESULTS: Spleen-kidney supplementing formula significantly relieved the symptoms of polydipsia, polyuria and weight loss in type 2 diabetic rats, reduced FBG and HbA1c levels, increased glycogen content, and improved insulin sensitivity. The anti-diabetic effects of spleen-kidney supplementing formula are dose dependent. It also increased the total AKT protein level and the GSK-3ß phosphorylation in the liver of type 2 diabetic rats. CONCLUSION: Spleen-kidney supplementing formula has hypoglycemic effect and relieves insulin resistance by enhancing AKT/GSK-3ß signaling pathway in the liver of type 2 diabetic rats.

A Mechanism Study Underlying the Protective Effects of Cyclosporine-A on Lung Ischemia-Reperfusion Injury.

AIM: This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. METHODS: Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP). The apoptotic cell was detected by the TUNEL staining. Western blot was performed to analyze the protein expression levels. RESULTS: CsA not only attenuated the histopathologic alterations in lung and mitochondria after I/R injury, but also attenuated I/R injury through increasing MPP and inhibiting MPTP opening. Besides, CsA attenuated I/R injury through suppressing the release of cytochrome-c (CytC), inhibiting cell apoptosis and decreasing the expression levels of cyclophilin-D (Cyp-D), adenine nucleotide translocase 1 (ANT1) and voltage-dependent anion channel 1 (VDAC1). Finally, we found that Cyp-D knockdown inhibits I/R injury-induced MPTP opening and cell apoptosis. CONCLUSION: Our study found that the protective role of CsA on lung I/R injury depends on the inhibition of MPTP and CytC release, suppression of the activation of mitochondrial apoptosis pathway and the expressions of apoptotic-related proteins, as well as the decreased expression levels of ANT1 and VDAC1.

Tonglian Decoction () arrests the cell cycle in S-phase by targeting the nuclear factor-kappa B signal pathway in esophageal carcinoma Eca109 cells.

OBJECTIVE: To investigate the anti-tumor activity and molecular mechanism of Tonglian Decoction (, TLD) on esophageal carcinoma Eca109 cells. METHODS: Eca109 cells were treated with TLD and its separated formulae, including the clearing-heat and detoxification formula (Q), activating-blood and promoting-qi formula (H) and nourishing-yin and blood formula (Z). Cell proliferation was measured using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell morphology was observed using a microscope, the cell cycle was measured using flow cytometry and the activity of the nuclear factor-kappa B (NF-κB) signal pathway was detected by Western blot. RESULTS: The half maximal inhibitory concentrations of TLD, Q and H were 386, 771 and 729 mg/L, respectively. TLD, Q and H significantly inhibited cell proliferation, with 69.43%, 60.84% and 61.90% of treated cells in the G phase of the cell cycle. The percentage of cells in S phase increased significantly after treatment with TLD, Q, and H compared with the control group (P<0.05), and TLD showed the strongest effect. Z had no influence on the cell cycle compared with the control group (P>0.05). Western blot detection indicated slight differences in the inhibition of the NF-κB pathway by the different formulae. TLD formula strongly inhibited IKKß, NF-κB, interleukin-6 and tumor necrosis factor-α expression compared with the control group. CONCLUSIONS: TLD inhibited Eca109 cell proliferation by arresting cells in S phase. The possible mechanism might be related to inhibiting the NF-κB transduction cascade. The combination of the herbs found in the three separate formulae, H, Q and Z, work synergistically in TLD to produce the inhibitory effects of TLD treatment on Eca109 proliferation.

Key genes expressed in different stages of spinal cord ischemia/reperfusion injury.

The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24-hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed four differentially expressed microRNAs (miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p) and their common target genes (Tmem69 and Cxcl10). Compared with the sham group, miR-22-3p was continuously upregulated in all three ischemia groups but was highest in the group with no reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.

[Clinical analysis of total aortic arch reconstruction with a novel individualized combined branched stent grafting technique for patients with Stanford A aortic dissection].

OBJECTIVE: To compare the clinical efficacy between total aortic arch reconstruction with a individualized combined branched stent grafting technique and total aortic arch replacement combined with stented elephant trunk implantation for patients with Stanford A aortic dissection. METHODS: Totally 44 patients with Stanford A aortic dissection treated with surgical treatment from January 2007 to July 2013 were included in this study. The patients were divided into two groups. Group A (n = 22) patients were treated by total arch replacement with stented elephant trunk procedure. Group B (n = 22) patients received individualized combined branched stent grafting technique. Age, gender and disease severity were similar between the two groups (all P > 0.05). Echocardiography and aortic CT angiography were performed pre-operation and at 1 month after operation. RESULTS: Operation was successful in all 44 patients. Cardiopulmonary bypass time, aortic cross clamp time, circulation arrest time and duration of ventilator assisted breathing were significantly longer, postoperative drainage volume and blood transfusion volume were significantly larger and hospitalization cost was significantly higher in group A patients compared those in group B patients (t = 2.791 to 43.465, all P < 0.05). One month after operation, the maximum internal diameter of aorta was smaller than pre-operation in both group A ((33 ± 1) mm vs. (45 ± 6) mm, t = 10.076, P = 0.000) and group B ((33 ± 2) mm vs. (45 ± 8) mm, t = 5.979, P = 0.000) . Left ventricular ejection fraction had no significant difference before and 1 month after operation in both groups (P > 0.05). CONCLUSION: The total aortic arch reconstruction with individualized combined branched stent grafting technique is technically easier, shortens the operation time, reduces the blood transfusion volume compared to the classical aortic arch operation.

Impact of endothelial nitric oxide synthase gene polymorphism on severity of enterovirus 71-infection in Chinese children.

OBJECTIVES: Genetic polymorphism G894T on the endothelial nitric oxide synthase (eNOS) gene has been reported as a susceptibility factor in a number of diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. This study investigated the possible association between this polymorphism (rs1799983) and disease severity in Chinese children with EV71 infection. DESIGN AND METHODS: 185 children with EV71 infection (83 with severe and 102 with mild disease) and 234 control healthy children underwent testing with polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) to detect G894T polymorphism. In addition, plasma levels of nitric oxide (NO), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and serum eNOS activity were measured according to genotype. RESULTS: The presence of GT+TT genotypes and T allele were associated with severe cases compared to genotype GG (OR 2.5, 95% CI 1.2-5.3, P=0.017) and G (OR 2.4, 95% CI 1.2-4.8, P=0.011). Furthermore, in EV71 encephalitis, GT+TT genotype and T allele were also more frequent than GG and G (P<0.05). The NO level and eNOS activity in T carriers (GT+TT) (84.3±2.5µmol/L and 14.4±1.8U/mL) were significantly less compared to in G carriers (GG) (92.0±1.5µmol/L and 19.1±1.7U/mL, P<0.001). But T carriers had higher plasma levels of IL-1ß, IL-6, and TNF-α than people without a T allele (P<0.001), and a significant negative correlation was observed between NO and cytokine levels. CONCLUSION: The results indicate that carrying the T allele of the eNOS G894T gene polymorphism was associated with EV71 infection, and could be a susceptibility factor in the development of EV71 infection in Chinese children.

[Study on effect of Hypericum perforatum on pharmacokinetics of zedoary turmeric oil in compound antiviral preparation].

OBJECTIVE: To study zedoary turmeric oil (ZTO) and the pharmacokinetics of its homemade compound antiviral preparation in New Zealand rabbits. METHOD: RP-HPLC was used to determinate the content of germacrone in rabbit plasma after oral administration. RESULT: After oral administration of ZTO and its homemade compound antiviral preparation, the plasma concentration-time curve of germacrone is in conformity to two-compartment open model. The pharmacokinetic parameters of ZTO: t1/2alpha, t1/2beta, Vd, CL, AUC and Ka were (1.52 +/- 0.59), (1.97 +/- 0.27) h, (47.59 +/- 2.29) L x kg(-1), (176.77 +/- 7.65) L x h(-1) x kg(-1), (5.70 +/- 0.70) mg x h x L(-1) and (0.97 +/- 0.11) h(-1), respectively, while those of compound preparation were (0.41 +/- 0.03), (1.47 +/- 0.35) h, (75.21 +/- 5.21) L x kg(-1), (287.79 +/- 6.39) L x h(-1) x kg(-1), (3.91 +/- 0.53) mg x h x L(-1) and (5.14 +/- 1.26) h(-1), respectively. There was no significant difference between the above two groups of pharmacokinetic parameters, expect that Ka of compound preparation was significantly higher than that of ZTO (P < 0.05). CONCLUSION: Hypericum perforatum in compound preparation doesn't impact the distribution and elimination of active ingredients of ZTO in New Zealand rabbits, but it improves the absorption speed, and shortens the time of drug absorption, which contributes to rapid efficacy of ZTO in rabbits.

Pulmonary artery perfusion with HTK solution prevents lung injury in infants after cardiopulmonary bypass.

BACKGROUND: Pulmonary artery perfusion during cardiopulmonary bypass (CPB) is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. METHODS: Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group (n = 12) and control group (n = 12). Oxygen index, alveolar-arterial O2 gradient, serum levels of malondialchehyche (MDA), interleukin (IL)-6, -8, -10, soluble intercellular adhesion molecule-1 (sICAM-1), and P-selectin were measured before commencement and serially for 48 hours after termination of bypass. RESULTS: Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB,but it was restored faster and earlier in the perfused group. The serum levels of IL-8, sICAM-1, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for sICAM-1. The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. CONCLUSION: In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.

Effect of partial liquid ventilation on oleic acid-induced inflammatory responses in piglets.

BACKGROUND: Pediatric patients are susceptible to lung injury. Acute lung injury (ALI) in children often results in a high mortality. Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models. This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA). METHODS: Twelve Chinese immature piglets were induced to develop ALI by oleic acid. The animals were randomly assigned to two groups (n = 6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group. RESULTS: Compared with MV group, PLV group got better cardiopulmonary variables (P < 0.05). These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2). Partial liquid ventilation reduced IL-1beta, IL-6, IL-10 and TNF-alpha both in plasma and tissue concentrations compared with MV group (P < 0.05). CONCLUSIONS: Partial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.

Overexpression of aveBIV leading to the improvement of 4'-epidaunorubicin production in Streptomyces coeruleorubidus strain SIPI-A0707.

The 4'-epidaunorubicin is the semisynthesis precursor of epirubicin which is a clinically useful antitumor drug thought to have slightly less cardiotoxicity than doxorubin. The 4'-epidaunorubicin was formed by overexpression of heterologous Streptomyces avermitilis aveBIV in Streptomyces coeruleorubidus SIPI-A0707 dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of daunorubicin. But there was a low-yield production of 4'-epidaunorubicin. In our study, product yields were enhanced considerably by increasing aveBIV gene copy number or changing means of aveBIV integration. The 4'-epidaunorubicin titer was improved by around threefold in the recombinant strain DYG1006 with the aveBIV increased threefold copy numbers. The transcript levels of aveBIV gene meet the expectation of fermentation levels of 4'-epidaunorubicin. The method described here provides the means to produce 4'-epidaunorubicin efficiently on an industrial scale.

[The application of three dimensional analysis system in measuring rotation angles of thumb carpometacarpal joints].

OBJECTIVE: To measure the axial rotation angles of the carpometacarpal joints during the digital opposition of thumb-index finger, thumb-medial finger, thumb-ring finger, thumb-little finger and the thumb's maximal opposition, then the application of these parameters were studied. METHODS: Twenty neutrality-occupation volunteers (female 10, male 10) with no history of hand injuries or related diseases were involved in the study. First, all the markers' 3-D coordinates were obstained using the 3D motion analysis system (EVaRT4.1) during the digital opposition movements of thumb. Then, the axial rotation angles were calculated. RESULTS: The average rotation angles of carpometacarpal joints during all kinds of digital oppositions were 29.1 degrees +/- 9.4 degrees (male), 24.8 degrees +/- 10.2 degrees (female), while the maximal rotation angles are: 35.3 degrees (male), 28.8 degrees (female). CONCLUSIONS: The combination of video-based 3-D analysis system and mathematics make it possible to measure the axial rotation angles of thumb in vivo, as a result, the rotation angles of thumb carpometacarpal joints are measured precisely for the first time. These results can provide a few parameters for treatment and rehabilitation of carpometacarpal arthrositis.