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Guang-Yun Wang,1 Tie-Zheng Wang,1 Yuan-Yuan Zhang,1 Fang Li,1 Bo-Yang Yu,2 Jun-Ping Kou1 1State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of China; 2State Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Resource and Development of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaCorrespondence: Jun-Ping KouState Key Laboratory of Natural Products, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaEmail junpingkou@cpu.edu.cnPurpose: Our previous studies have indicated that non-muscle myosin heavy chain IIA (NMMHC IIA) is involved in H2O2-induced neuronal apoptosis, which is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. However, the neuroprotective effect of NMMHC IIA inhibition with an adeno-associated virus (AAV) vector after transient middle cerebral artery occlusion (MCAO) and its role in caspases-3/ROCK1/MLC pathway remain blurred.Methods: Green fluorescent protein (GFP) and a small hairpin RNA targeting Myh9 (encoding NMMHC IIA) were cloned and packaged into the AAV9 vector. AAV-shMyh9 or control vector were injected into C57BL/6J mice four weeks prior to 60 min MCAO. Twenty-four hours after reperfusion, functional and histological analyses of the mice were performed.Results: In this study, AAV-shMyh9 was used to down-regulate NMMHC IIA expression in mice. We found that down-regulation of NMMHC IIA could improve neurological scores and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis, and this effect was partially attenuated when NMMHC IIA was inhibited by AAV-shMyh9. In addition, AAV-shMyh9 significantly reduced cerebral ischemic/reperfusion (I/R)-induced NMMHC IIA-actin interaction, caspase-3 cleavage, Rho-associated kinase1 (ROCK1) activation and myosin light-chains (MLC) phosphorylation.Conclusion: Consequently, we showed that AAV-shMyh9 inhibits I/R-induced neuronal apoptosis linked with caspase-3/ROCK1/MLC/NMMHC IIA-actin cascade, which has also been confirmed to be a positive feedback loop. These findings put some insights into the neuroprotective effect of AAV-shMyh9 associated with the regulation of NMMHC IIA-related pathway under ischemic attack and provide a therapeutic strategy for ischemic stroke.Keywords: NMMHC IIA, adeno-associated virus, ischemic stroke, apoptosis

Background To evaluate one-stage repair with ascending to abdominal aorta extra-anatomical bypass combined with cardiac surgery for adult aortic coarctation (COA) concomitant with cardiac diseases. Methods Between February 2009 and September 2016, 24 consecutive patients (79.17% male, mean age 36.04 ± 13.67 years) with COA and concomitant cardiac diseases underwent one-stage repair (ascending to abdominal aorta extra-anatomical bypass combined with cardiac surgery). Two (2) patients who underwent off-pump coronary artery surgery combined with ascending to abdominal aorta bypass did not require cardiopulmonary bypass. Twenty-two (22) patients underwent one-stage repair under cardiopulmonary bypass. Results No in-hospital mortality was observed. There was a significant reduction in baseline systolic blood pressure from 159.80 ± 23.58 to 127.0 ± 6.86 mmHg. Mean upper-lower limb blood gradient pressure decreased significantly from 37.80 ± 8.73 to 11.47 ± 2.12 mmHg after surgery. Two (2) patients required prolonged mechanical ventilation for respiratory dysfunction. One patient needed temporary continuous renal replacement therapy. No re-exploration for bleeding and gastrointestinal complications was needed. There was no postoperative paraplegia or permanent neurological abnormalities. Grafts were patent for all patients and no graft-related complications were observed in the hospital. Median follow-up was 41.50 months (interquartile range [IQR] 16.75–64.50 months) and 6-year survival was 76.39%. Median number of antihypertensive drugs was 0 (IQR 0–1), which was a significant reduction compared with preoperative drugs (2, IQR 1–3). Conclusions Ascending to abdominal extra-anatomical aorta bypass combined with cardiac surgery is a safe and effective one-stage repair technique for patients with COA concomitant with cardiac diseases.

Background Cirrhosis-associated immune dysfunction (CAID) contributes to high sepsis risk in patients with chronic liver disease. Various innate and; to a lesser extent; adaptive immune dysfunctions have been described as contributors to CAID leading to immune-paresis and impaired anti-microbial response in cirrhosis. In this study, we examined the phenotype of CD8+ T cells in chronic liver disease with the aim to evaluate changes that might contribute to impaired immune responses. Methods Sixty patients with cirrhosis were prospectively recruited for this study. CD8+ T cells from peripheral blood, ascites and liver explants were characterized using flow cytometry and immunohistochemistry, respectively. The transcriptional signature of flow-sorted HLA-DR+CD8+ T cells was performed using Nanostring™ technology. HLA-DR+CD8+ T cells interactions with PBMCs and myeloid cells were tested in vitro. Findings Peripheral CD8+ T cells from cirrhotic patients displayed an altered phenotype characterized by high HLA-DR and TIM-3 surface expression associated with concomitant infections and disease severity, respectively. Paired peritoneal CD8+ T cells expressed more pronounced levels of HLA-DR and PD-1 compared to peripheral CD8+ T cells. HLA-DR+CD8+ T cells were enriched in cirrhotic livers compared to controls. TIM-3, CTLA-4 and PD-1 levels were highly expressed on HLA-DR+CD8+ T cells and co-expression of HLA-DR and PD1 was higher in patients with poor disease outcomes. Genes involved in cytokines production and intracellular signalling pathways were strongly down-regulated in HLA-DR+CD8+ T cells. In comparison to their HLA-DR− counterparts, HLA-DR+CD8+ T cells promoted less proliferation of PBMCs and induced phenotypic and functional dysfunctions in monocytes and neutrophils in vitro. Interpretation In patients with cirrhosis, CD8+ T cells display a phenotypic, functional and transcriptional profile which may contribute to CAID. Fund This work was supported by Medical Research Council, the Rosetrees Charitable Trust, Robert Tournut 2016 grant (Societe Nationale Francaise de GastroEnterologie), Gilead® sciences, and NIHR Imperial Biomedical Research Centre.

To verify the efficacy of transcutaneous electrical acupoint stimulation (TEAS) on catheter related bladder discomfort after ureteroscopic lithotripsy.Sixty male patients with selective ureteroscopic lithotripsy under general anesthesia were randomly divided into a TEAS group (30 cases, one case dropped off) and a sham TEAS group (30 cases, 2 cases dropped off). Before anesthesia induction, the patients in the TEAS group were treated with TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) for 30 min, with disperse-dense wave, frequency of 2 Hz/ 15 Hz and current intensity of 6 to 10 mA. The patients in the sham TEAS group were treated with the same TEAS device at the same acupoints, but no electrical stimulation was given. After 30 min, anesthesia induction started. The total dosages of propofol and remifentanil in the two groups were recorded, and the time of operation and anesthesia, the time of wake-up and the time of stay in postanesthesia care unit (PACU) were recorded. The postoperative recovery was evaluated 5 min (TThe dosage of remifentanil in the TEAS group was significantly lower than that in the sham TEAS group (The 30-min TEAS at Guanyuan (CV 4), Zhongji (CV 3), Zusanli (ST 36) and Sanyinjiao (SP 6) before anesthesia induction could significantly control the severity of postoperative urinary tract irritation in patients with ureteroscopic lithotripsy, reduce the dosage of anesthetic drugs and relieve postoperative pain.

Background: Acute aorta dissection (AD) is a fatal emergency, however, studies addressing the clinical characteristics, management, and outcome of acute AD in young adult patients aged under 45 yea...

The molecular mechanism and signal transduction pathways involved in urothelial cancer (UC) after renal transplantation (RTx) remain unknown. In this study, we investigated the profiling of messenger RNA (mRNA) and long non-coding RNA (lncRNA) in RTx recipients with UC. The mRNA and lncRNA of six pairs of UC and corresponding normal urothelial tissues in RTx recipients were profiled using Arraystar Human lncRNA Microarray V3.0, which is designed for the global profiling of 26,109 coding transcripts and 30,586 lncRNAs. Quantitative real-time PCR (qRT-PCR) was used to validate the differentially expressed mRNAs and lncRNAs. Molecular function classification and biological process classification for the differentially expressed mRNAs were analyzed with Gene Ontology. The key pathways that were associated with UC after RTx were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Compared to normal urothelial tissues, 1597 mRNAs were upregulated and 1032 mRNAs were downregulated in UC; 2107 lncRNAs were upregulated and 1794 lncRNAs were downregulated (greater than twofold). Further qRT-PCR analysis of mRNA and lncRNA expression showed well consistency with the data of microarray analysis. The expression of matrix metalloprotease (MMP)-3, MMP-10, MMP-12, and MMP-13 was significantly increased, while the expression of CD36 was decreased in UC after RTx. Co-expression analysis of lncRNAs and their nearby coding genes showed that lncRNAs may play critical roles in regulating nearby genes in the carcinogenesis of UC. Our results also suggest that peroxisome proliferator-activated receptor (PPAR) signaling may be involved in UC after RTx. Moreover, several cytokines and their receptors were also significantly upregulated in UC after RTx, suggesting that cytokines might be modulated and participated in the carcinogenesis of UC after RTx. We analyzed the potential molecular mechanism and pathways involved in the UC of RTx recipients. Our results revealed that several key regulatory pathways and lncRNAs play critical roles in the carcinogenesis of UC, and suggest that UC in RTx recipients may be more likely to invade and metastasis. However, the detailed functional analysis of these mechanisms should be further performed in the future.

To analyze the clinical outcome of corticosteroid and/or immunosuppressive treatment preoperatively in patients with Takayasu's arteritis.Forty-six patients with Takayasu's arteritis who received cardiovascular surgery between January 2010 and December 2015 in Beijing Anzhen Hospital were enrolled in this study. Their clinical characteristics, preoperative drug therapy, surgical treatment, and pathological examination results were retrospectively analyzed for the effect of drugs on outcome of the surgery.All 8 patients with active disease prior to surgery had postoperative complications including one death due to stubborn perivalvular regurgitation induced heart failure during the perioperative period. Among 38 patients without active disease prior to surgery, only 4 patients (10.5%) had postoperative complications. Thirty-four patients showed symptomatic relief in the perioperative period, of whom 23 patients treated with corticosteroid and/or immunosuppressive agents preoperatively.The surgery can effectively improve the symptoms of patients with Takayasu's arteritis. Active disease of Takayasu's arteritis markedly increased risk for postoperative complication and resulted in poor outcome of the surgery. Treatment with corticosteroid and/or immunosuppressive agents before surgery can effectively control the patient's condition, improve the rate of remission, and effectively reduce the incidence of postoperative complications.

The aim of the present study was to explore the roles and possible molecular mechanism of the alleviating effect of sevoflurane pre‑treatment on the extracorporeal circulation and to investigate the possible involvement of the Toll‑like receptor (TLR3) signaling pathway. A total of 64 male Sprague Dawley rats were randomly divided into three groups: The sham operation group (H group; n=8), cardiopulmonary bypass (CPB) group (C group; n=24) and sevoflurane pre‑conditioning group (S group; n=32). The C group was subjected to tracheal intubation and mechanical ventilation, vessel puncture and catheter placement in the right femoral artery and right internal jugular vein, while no CPB was performed in the H group. The S group was pre‑treated with 2.4% sevoflurane for 1 h prior to establishing the CPB model. The CPB in the C and S groups was performed for 1 h. Blood of the rats was analyzed and clinical parameters were detected prior to, during and at various time‑points after CPB. In addition, eight rats from the C and S groups each were sacrificed at these time‑points and brain tissue samples were analyzed. The levels of the brain damage‑specific protein S100‑β as well as IL‑6 and IFN‑β in the serum were detected by ELISA; furthermore, the expression levels of TLR3 and TIR‑domain‑containing adapter‑inducing interferon‑β (TRIF) in the left hippocampus were assessed by ELISA and/or western blot analysis. The right hippocampus was assessed for neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mean arterial pressure, heart rate and hematocrit were significantly decreased following CPB (P

Aim To evaluate the acting mechanism of bone morphogenetic protein-7 in anti-ischemic protective effect, we investigate the effects of BMP-7 transfection on cell apoptosis, NF-kappaB activity, and downstream genes in neonatal rat cardiomyocytes during simulated ischemia-reperfusion. Method In vitro cultured neonatal rat cardiomyocytes were divided into four groups: normal control group (Group C), simulated ischemia-reperfusion group (Group IR: cultured cardiomyocytes were subjected to 2 hours hypoxia followed by 4 hours reoxygenation), transfected group (Group BT: after transfection with pcDNA3.1-BMP-7 plasmid, cardiomyocytes were subjected to 2 hours hypoxia/4 hours reoxygenation), and empty vector control group (Group ET: same as group BT except that cells were transfected with empty pcDNA3.1 vector). Malondialdehyde content, superoxide dismutase activity, and Ca(2+) concentration were measured. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining and fluorescence activated cell sorting assay were applied to determine the apoptotic rate of cardiomyocytes and immunocytochemistry and Western blot were used to detect nuclear expression of NF-kappaB in cardiomyocytes. Reverse transcription-polymerase chain reaction was used to detect mRNA expression of monocyte chemoattractant protein-1 and intercellular cell adhesion molecule-1. Results Compared with Group IR, malondialdehyde content of Group BT significantly decreased, whereas superoxide dismutase activity significantly elevated. In addition, intracellular Ca(2+) concentration of Group BT significantly reduced and apoptotic cells were significantly less. Decreased optical density ratio of NF-kappaB in the nucleus and reduced monocyte chemoattractant protein-1 and intercellular cell adhesion molecule-1 mRNA expression were also detected. Conclusion These results suggest that rat recombinant BMP-7 transfection provides sustained support for the repair of myocardium from ischemia injury through reducing cell apoptosis, inhibiting lipid peroxidation, antagonizing intracellular Ca(2+) overload, and preventing the activation of downstream signaling factors in signal transduction pathway mediated by NF-kappaB.

Naringin is a flavonoid that exists in many plants and traditional Chinese medicines. In this study, a highly sensitive and specific electrospray ionization (ESI) liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for quantification of naringin and its two metabolites, naringenin and naringenin glucuronide. Naringin and naringenin were extracted from rat plasma with ethyl acetate, using hesperidin as an internal standard. Components in the extract were separated on a 100 mm x 2.0 mm Betabasic 5 microm C18 ODS column by isocratic elution with 70% methanol. The components were analyzed in the multiple-reaction-monitoring (MRM) mode in the precursor/product ion pair of m/z 581.3/273.4 for naringin, m/z 273.4/153.1 for naringenin and m/z 611.5/303.4 for hesperidin, respectively. Linear calibration curves were obtained in the range of 5-1000 ng/ml, using 0.1 ml rat plasma. The within-day coefficients of variation (CVs) were 3.1, 1.8 and 2.2% for naringin, 3.0, 3.3, 3.1% for naringenin at 5, 50 and 500 ng/ml (n=5). The between-day CVs were 3.4, 1.7 and 4.9% for naringin and 4.0, 3.0, 4.6% for naringenin (n=5) at 5, 50 and 500 ng/ml respectively. A formulation based on PEG400 was used and orally administered to Sprague-Dawley male rats. Plasma drug concentrations were measured by this method and the pharmacokinetics was analyzed by WinNonlin computer software. Plasma concentration-time profiles of naringin were found to increase quickly and decline rapidly within 2 h and could not be detected after 24 h. Naringenin and naringenin glucuronide occurred slower and the T(max) were about 9 and 7.5 h later, respectively.

A highly sensitive and specific electrospray ionization (ESI) liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for quantitation of naringenin (NAR) and an explanation for the double peaks phenomenon was developed and validated. NAR was extracted from rat plasma and tissues along with the internal standard (IS), hesperidin, with ethyl acetate. The analytes were analyzed in the multiple-reaction-monitoring (MRM) mode as the precursor/product ion pair of m/z 273.4/151.3 for NAR and m/z 611.5/303.3 for the IS. The assay was linear over the concentration range of 5-2500 ng/mL. The lower limit quantification was 5 ng/mL, available for plasma pharmacokinetics of NAR in rats. Accuracy in within- and between-run precisions showed good reproducibility. When NAR was administered orally, only little and predominantly its glucuronidation were into circulation in the plasma. There existed double peaks phenomenon in plasma concentration-time curve leading to the relatively slow elimination of NAR in plasma. The results showed that there was a linear relationship between the AUC of total NAR and dosages. And the double peaks are mainly due to enterohepatic circulation.

1. In the present study, we investigated the impact of 1.0% ropivacaine on the ultrastructure and proteome of the rat spinal cord. 2. Rats received three injections (90-min intervals, 0.2 mL/kg) of 0.9% NaCl, 0.5% ropivacaine or 1.0% ropivacaine via an implanted intrathecal catheter. Transmission electron microscopy was performed to exam the ultrastructure of the spinal cord. Two-dimensional electrophoresis followed by mass spectrometry identification were carried out to investigate the proteome. 3. In the rats administered 1.0% ropivacaine, deformed organelles, detached myelinated nerve fiber layer, and incomplete inner and outer shaft membranes were observed in the spinal cord and posterior root shrunken nuclei. Furthermore, in the rat spinal cord 1.0% ropivacaine induced the down-regulation of voltage-dependent anion channel 2 (VDAC2) and mitochondrial pyruvate dehydrogenase subunit alpha (ODPA), the upregulation of myelin basic protein (MBP), the disappearance of myelin transcription factor 1 (MYT1) and the appearance of heat shock protein 25 (HSP25). Little change was observed in the 0.5% ropivacaine or control groups. 4. Our results suggest that 1.0% ropivacaine treatment led to neurotoxicity, as shown by ultrastructural and proteomic changes in the rat spinal cord. Specific proteins were identified that are implicated in 1.0% ropivacaine-induced neurotoxicity.

Postoperative cognitive dysfunction (POCD) is associated with cardiopulmonary bypass (CPB). We investigated the effect of different doses of inhaled sevoflurane administered prior to CPB on cerebral oxygen supply and demand, and the incidence of associated early POCD. One hundred and twenty patients were randomly allocated into four treatment groups (n = 30, each) and administered a high- [1.5 minimum alveolar concentration (MAC)], moderate- (1.0 MAC), low- (0.5 MAC), or no- sevoflurane dose prior to CPB. Standard blood gas parameters, serum S-100 protein, and neuron-specific enolase (NSE) were measured at different time points. The mini-mental state examination (MMSE) was administered 1 day before and 24 and 72 h after surgery. The jugular bulb venous oxygen saturation (SjvO2) in the moderate- and high-dose groups at a nasopharyngeal temperature of 25–28 °C was significantly higher compared with the control group, while the arteriovenous oxygen content difference (AVDO2) and cerebral extraction of oxygen (CEO2) were significantly reduced. The serum S-100 protein and NSE concentrations of the moderate- and high-dose groups at 1 and 6 h after the cessation of CPB were significantly lower than that of the control group. The 24 h postoperative MMSE scores of the moderate- and high-dose groups were significantly higher than those of the low-dose and control groups. An inhaled optimal concentration of sevoflurane may be beneficial for cerebral oxygen balance during CPB, and may ameliorate cognitive damage. However, the effect is dose-dependent.

To evaluate the therapeutic effects of mitral valve repair for the treatment of the anterior leaflet prolapse of mitral valve.From November 1998 to October 2007, 210 patients with severe anterior leaflet prolapse of mitral valve underwent valve repair. The condition of valve was preoperative, intraoperative, and postoperative assessed with echocardiography.Edge-to-edge repair technique was used in 134 cases (63.8%). The cardiac function was NYHA class I in 168 cases and class II in 40 cases after operation. Patients were followup for 1 - 150 (25.7 +/- 29.0) months, two patients (0.95%) died of postoperative low cardiac output syndrome. Echocardiography examination indicated that the mean JP2 postoperative left atrial diameter was (37.7 +/- 9.2) mm against the preoperative value of (47.5 +/- 12.7) mm (P0.05), the mean postoperative left ventricular end-diastolic diameter was (51.7 +/- 7.9) mm against the preoperative value of (67.7 +/- 10.3) mm (P0.05), the mean postoperative left ventricular ejection fraction was (62.2 +/- 3.2)% against the preoperative value of (52.2 +/- 6.4)% (P0.05), and the mean preoperative regurgitation area was (10.4 +/- 4.1) cm(2) against the postoperative value of (4.1 +/- 1.7) cm(2) (P0.01).Optimal outcome was achieved by appropriate edge-to-edge technique or other mitral valve repair techniques for anterior leaflet prolapse of mitral valve. Edge-to-edge technique is a reliable and efficient surgical technique.

The initial 85 patients who successfully underwent percutaneous mitral valvuloplasty (PMV) with the Inoue balloon catheter at the Guangdong Cardiovascular Institute between November 1985 and November 1988 had a mean follow-up period of 5 +/- 1 year (range 43 to 79 months). Before and after PMV and at follow-up, mean diastolic mitral gradients by the catheter method were 17.5 +/- 6.2, 3.1 +/- 3.3 and 3.3 +/- 3.4 mm Hg, respectively (p0.001 before vs after PMV and before vs follow-up; and p0.05 after PMV vs follow-up). Mean diastolic mitral gradients by the Doppler method were 18 +/- 6, 8 +/- 5 and 9 +/- 5 mm Hg, respectively (p0.001 before vs after PMV and before vs follow-up; and p0.05 after PMV vs follow-up). Mean diastolic mitral gradients by the Doppler method were 18 +/- 6, 8 +/- 5 and 9 +/- 5 mm Hg, respectively (p0.001 before vs after PMV and before vs follow-up; and p0.05 after PMV vs follow-up). Mitral valve areas by the echo-Doppler method were 1.1 +/- 0.3, 2.0 +/- 0.4 and 1.8 +/- 0.5 cm2, respectively (p0.001 before vs after PMV and before vs follow-up; and p0.05 after PMV vs follow-up). Phonocardiographic and vectorcardiographic studies, and cardiopulmonary exercise testing showed significant improvement after PMV and at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphoid tissue inducer cells (LTi) play an important role in the development of lymphoid tissue in embryos. Adult CD4(+)CD3(-) LTi-like cells present a similar phenotype and gene expression to their embryonic counterpart and have important roles in CD4(+) T-cell memory and lymphoid tissue recovery following viral infection. However, adult LTi-like cells are heterogeneous populations and the factors that regulate their survival and accumulation within secondary lymphoid organs remain unclear, in particular whether the T-zone stroma is involved. Here we report the identification and characterization of a distinct subset of podoplanin(+) murine splenic stromal cells that support adult LTi-like cell survival. We have identified and isolated CD45(-)podoplanin(+) stromal cell populations which have a similar but distinct phenotype to T-zone reticular cells in LN. CD45(-)podoplanin(+) fibroblast-like cells mediate LTi-like cell survival in vitro; surprisingly this was not dependent upon IL-7 as revealed through blocking Ab experiments and studies using LTi-like cells unable to respond to gamma chain cytokines. Our findings show that adult LTi-like cells require extrinsic signals from podoplanin(+) splenic stromal cells to survive and suggest that IL-7 is not necessary to mediate their survival in the adult spleen.

To introduce the methods of dacron flap application and its indications in treating fracture of multiple ribs, in order to reduce the incidence of the complications of fracture displacement.From September 2006 to March 2008, 12 patients with fracture of multiple ribs were treated with absorbable rib fixed nail and dacron flap. Included 8 males and 4 females,the age was from 22 to 51 years with an average of 38.2 years,the operative time was 2 hours to 3 days after injured. All the patients were closed injury and simultaneously accompanied with significant chest pain and chest tightness. 4 cases with dyspnea, blood in sputum and blood oxygen saturation decreased. The X-ray showed 3 cases of unilateral fracture and 9 cases of bilateral rib fractures and all cases accompanied with hemopneumothorax.All patients were followed up from 2 to 26 months with an average of 8 months. All the fractures healed. According to clinical criteria, pain, breathing, ribs alignment etc. to observe the effect, 10 cases got excellent result, 1 case good, 1 case poor.It is safe and effective to use absorbable rib fixed nails and dacron flap for treating fracture of multiple ribs and especially for the patients of osteoporosis, comminuted fracture or oblique fracture.

To investigate the preventive effect of endothelial nitric oxide synthase (eNOS) gene transfer on chronic hypoxic pulmonary hypertension (CHPH) in rats.Twenty-four male Wistar rats were randomly divided into four groups with 6 rats in each group: normoxia group (group N), hypoxia group (group H), hypoxia with LacZ group (group H-LacZ) and hypoxia with eNOS group (group H-eNOS). AdCMVceNOS, AdCMVLacZ or normal saline (NS) was injected intratracheally 3 days before the beginning of exposure to normoxia or hypoxia. Rats in group H-eNOS received 50 microl of AdCMVceNOS (5 x 10(12)pfu/L), rats in group H-LacZ received equal dose of AdCMVLacZ, rats in group N and group H received equal dose of NS. Hemodynamic parameters [including mean systemic arterial pressure (MSAP), heart rate (HR) and mean pulmonary arterial pressure (MPAP)], pulmonary vascular remodeling (percentage of muscularized arteries in small pulmonary vessels) and right ventricular hypertrophy (ratio of right ventricle to left ventricle + septum weight) were measured after 2 weeks of exposure to normoxia or hypoxia. The expression of eNOS, cyclic guanosine monophosphate (cGMP) and nitric oxide (NO) level were also measured in lungs.The MPAP, right ventricular hypertrophy index and pulmonary vascular remodeling in rats in group H-eNOS were obviously lower than those in group H and H-LacZ, but higher than that in group N (all P0.01). There was no significant difference with regard to HR and MSAP in rats in all groups (all P0.05). The eNOS protein in group H and H-LacZ was obviously higher than that in group N, but obviously lower than that in group H-eNOS (all P0.01). The NO level in rat lungs in group H and H-LacZ was obviously lower than that in group N, and value in group H-eNOS was higher than that in the other groups (P0.05 or P0.01). With regard to cGMP in rat lungs, there was no significant difference among group N, H and H-LacZ (all P0.05), but they were all obviously lower than that in group H-eNOS (all P0.01).Intratracheal eNOS gene transfer upregulates the activity of eNOS protein, elevates the level of NO/cGMP in lungs, and alleviates CHPH in rats.

To explore the effect of subchronic exposure to acrylamide on the reproduction and testis endocrine function of rats.Forty healthy adult male SD rats were randomly divided into 4 groups of equal number, exposed to acrylamide at the dose of 0, 4, 10 and 18 mg/(kg x d) respectively for 9 weeks, and then subjected to the determination of the hindlimb landing foot splay, sperm vitality and morphology, the activities of acid phosphatase (ACP) and alkaline phosphatase (ALP) in the testis homogenate, and the levels of testosterone (T) and estradiol (E2) in the serum and testis homogenate. Based on the primary Leydig cell culture models exposed to acrylamide of 0, 0.1, 0.75, 4 and 8 mmol/L, the activity of Leydig cells was measured by the CCK-8 method.Following acrylamide exposure, the hindlimb landing foot splay increased markedly with dose increase (P0.01). The rates of sperm vitality were (6.86 +/- 5.46)%, (65.43 +/- 5.16)%, (60.86 +/- 4.26)% and (46.86 +/- 2.73)% in the exposed groups, significantly lower than in the control (P0.01); the rates of abnormal sperm were (39.00 +/- 10.95)%, (35.43 +/- 7.54)%, (45.71 +/- 13.28)% and (56.71 +/- 17.01)%, significantly increased in the 10 and 18 mg/(kg x d) groups (P0.05); ACP activities were (82.93 +/- 11.05), (73.52 +/- 8.77), (77.67 +/- 3.04) and (68.56 +/- 3.09) U/g prot, showing a decreasing tendency, while ALP activities were (0.96 +/- 0.15), (1.07 +/- 0.22), (1.12 +/- 0.22) and (0.74 +/- 0.10) U/g prot, displaying a tendency of first increasing and then decreasing. Both ACP and ALP activities were inhibited significantly in the 18 mg/(kg x d) group as compared with the control (P0.05). A marked reduction was noted in T levels in the serum, (13.44 +/- 4.76), (7.69 +/- 3.84), (5.23 +/- 1.42) and (1.36 +/- 0.86) ng/ml, as well as in the testis homogenate, (4.95 +/- 1.64), (3.01 +/- 0.76), (2.44 +/- 0.91) and (0.85 +/- 0.49) ng/mg prot, (P0.01), but no significant changes were observed in 17beta-E2 levels. After 24 hours exposure to acrylamide, the optical densities were 0.82 +/- 0.06, 0.56 +/- 0.07, 0.44 +/- 0.06, 0.26 +/- 0.03 and 0.45 +/- 0.21, showing an evident inhibition of the activity of Leydig cells at the dose of 0.1, 0.75, 4 and 8 mmol/L (P0.01).Subchronic exposure to acrylamide could affect the normal development of sperm, cause changes of the activity of some enzymes in the testis and significantly influence hindlimb motor coordination. Acrylamide directly damages Leydig cells and affects the endocrine function of the testis.

Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor numbers in the peripheral blood but not the bone marrow compartment. PECAM-1(-/-) mice have higher levels of HSC progenitors in the blood compared to their littermate controls. We show that PECAM-1 is required on both progenitors and bone marrow vascular cells in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1(-/-) bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. These findings suggest a novel role for PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the blood.

Acrylamide is a common chemical material, extensively used in industry and scientific experiments. Recently, it has been reported that starchy food cooked at high temperature can produce acrylamide. Acrylamide monomer has several toxic effects and the extensive concern for its toxicity has arisen with the finding of acrylamide formation in some processed foods. Researches have shown that acrylamide monomer can cause reproductive toxicity, including toxic effects on male reproductive behavior, male reproductive endocrine function and spermatogenesis. The mechanisms may include the effects of acrylamide on Leydig cells, the formation of motor protein/ chromosomal/DNA alkylation and damage by oxidative stress.

To evaluate the clinical results and perioperative management of primary total knee arthroplasty (TKA) in hemophilic patients.From February 1997 to February 2006, the data of 6 total knee arthroplasty performed in 4 hemophilic patients was reviewed retrospectively. The values of coagulation factor were maintained at suitable level by monitoring the activity of the factors and their inhibitors during perioperative period. The mean follow-up time was 4.4 years, knee society score and the last postoperative radiographs were recorded.After TKA, the hemophilic patients felt pain of knee relieved, the knee function was improved, but the range of motion increased limitedly. At the early post-operative stage, 3 knees in 2 patients with hemarthrosis or muscle bleeding, 1 of the 2 patients complicated with formation of inhibitor of factor VIII and healing problem in 1 knee after TKA, 1 patient with transient paralysis of the common peroneal nerve, 1 patient with venous circulation insufficiency crisis, but no compartment syndrome. In the late stage after TKA, 1 patient with hemarthrosis of both elbows, but no late infection, loosening, displacement and fracture of the prosthesis in the 6 knees.Total knee arthroplasty could alleviate knee pain and improve joint function in advanced severe hemophilic arthritic patients. It is important to monitor the activity and inhibitors of coagulation factor VIII or IX, which could decrease the early and late postoperative complications.

To discuss the outcomes and complications of total knee arthroplasty (TKA) for extension ankylosing deformity of the knee.From January 1996 to June 2006, total knee arthroplasty was performed on 8 patients (9 knees) with extension ankylosing deformity. The preoperative ROM of all patients was 0 degrees . Preoperative knee and function score of KSS were 44 points (from 10 to 68) and 17 points (from -10 to 55) respectively.The complications of all TKAs included patellar tendon avulsion in 1 knee, partial fracture of inferior patella in 1 knee, hematoma in 1, superficial infection in 1. All patients were followed up for an average of 40.4 months (from 7.0 to 120.0). The average postoperative ROM was 89 degrees (from 50 degrees to 120 degrees ). Postoperative knee and function score of KSS were 81 points (from 55 to 93) and 79 points (from 50 to 90) respectively. Extension lag occurred in 2 knees, one was 10 degrees and the other was 25 degrees . One knee had undergone re-revision of changing the thicker tibial spacer for the reason of instability of joint 1 year after revision.TKA performed in extension ankylosing deformity can get less satisfactory clinical results comparing with fixed flexion deformity. Exposure of the knee joint and separation of the fused bones, providing a mobile joint space plays crucial procedure for the next step of surgery. Preservation of sufficient bone stock of patella, protection of patellar tendon and blood supply of the knee and proper soft tissue balance are the key to TKA for extension ankylosing deformity.

To examine the two to eight-year results associated with the use of this hip system.Between November 1996 and January 2001, 56 revision total hip arthroplasties with insertion of a Zweymüller BICON-PLUS cup and a cementless SLR-PLUS stem were performed in 55 consecutive patients (average age, fifty-nine years old, range, thirty to eighty years old).At the time of the latest follow-up, 23 patients (24 hips) had lost to follow-up, leaving 32 patients for a minimum of 2 years of clinical and radiographical follow-up. The mean follow-up time was 4 years. Only 3 peri-operative complications occurred, including 1 great trochanter fracture during implant removal, 1 dislocation 2 d after operation with successful closed reduction, and 1 deep wound infection which necessitated reentry and debridement. No femoral stems or cups needed re-revision surgery. The average Harris hip score increased from 40.6 points preoperatively to 80.4 points at final follow-up. Radiographic analysis demonstrated that the position of stems and cups was unchanged and all showed radiographic evidence of bone ingrowth.The favourable medium-term clinical results with the cementless Zweymüller hip system show that it is suitable as a revision system for total hip failures of both cemented and cementless primary fixation.

To determine the effects of Varglaucocalyx on c-fos gene expression during global myocardial ischemia-reperfusion.Forty Wistar rats were divided into 5 groups: group N as control; group CN as ischemia-reperfusion control and group XH, XM and XL treated with Varglaucocalyx 5%, 1%, 0.5% respectively prior to ischemia-reperfusion. The isolated rat hearts were perfused in condition of constant temperature and pressure, and then the left ventricular myocardiums were extracted for use. The expression of c-fos protein was detected by immunochemical method. The expression of c-fos protein were quantified by using computer image analysis system.Compared with the values of group N, protein expressions relative area of c-fos gene (PERA) were increased significantly in group CN, XH, XM, XL(P0.01), but decreased significantly in group XH, XM, XL, compared with those of group CN (P0.05). The PERA of c-fos gene in group XM, XL were significantly lower than in group XH (P0.01), and the PERA of c-fos gene in group XM were lower than in group XL(P0.05).Varglaucocalyx can effectively depress the expression of c-fos gene in myocardium which may account for its protection against myocardial ischemia-reperfusion injury, and the middle and the low concentrations of Varglaucocalyx are more effective than the high concentrations.

To identify the mutation of spondyloepiphyseal dysplasia tarda (SEDL) gene in a large Chinese family with X-linked spondyloepiphyseal dysplasia tarda and to make a discussion on the pathogenesis of SEDL at the molecular level.In two patients, four exons comprising the SEDL open reading frame as well as their exon/intron boundaries were analyzed by bi-directional direct sequencing of PCR products. The sequencing results were compared against the normal sequences in GenBank to find the mutation. Then the mutation was identified in other members of the family.A nucleotide substitution of the splice acceptor in SEDL intron 2, IVS2 -2A--C,was detected in two affected individuals (IV(15) V(3)) in the Chinese family with SEDL, but no sequence change occurring on exons 3-6 was detected. The transversion was also identified in four heterozygous carriers. The mutation was not found in two unaffected male individuals and fifteen normal controls. Furthermore, four potential carriers were identified in the family.The mutation IVS2 -2A--C of SEDL gene was firstly determined in the world. The change of the splice acceptor in SEDL intron 2 may cause skipping of exon 3 which is responsible for the disease. Molecular diagnosis can be made by detecting the mutation.

Between November 1985 and December 1991, percutaneous balloon mitral valvuloplasty (PBMV) with the Inoue balloon catheter (Toray Marketing & Sales [America], Inc., New York, N.Y.) was performed in 53 patients with rheumatic mitral stenosis and associated mild to moderate aortic regurgitation. Mean left atrial pressure was 22.5 +/- 8.6 mm Hg and 9.7 +/- 5.5 mm Hg before and after PBMV, respectively (p < 0.001). The mean diastolic mitral gradient as determined by the catheter method decreased from 18.7 +/- 11.4 mm Hg to 2.1 +/- 3.1 mm Hg (p < 0.001). The echocardiographic mitral valve area was 1.0 +/- 0.2 cm2, 2.0 +/- 0.6 cm2, and 1.9 +/- 0.5 cm2, before and after PBMV and at follow-up (p < 0.001 before PBMV vs after PBMV and at follow-up). The mean diastolic mitral gradient as determined by two-dimensional and Doppler echocardiography was 19.3 +/- 8.4 mm Hg, 5.2 +/- 4.1 mm Hg, and 6.6 +/- 3.3 mm Hg, before and after PBMV and at follow-up, respectively (p < 0.001). The phonocardiographic interval between the Q wave and the mitral component of the first heart sound was 85.2 +/- 15.2 msec, 74.2 +/- 13.4 msec, and 72.3 +/- 15.7 msec before and after PBMV and at follow-up (p < 0.001 before PBMV vs after PBMV and at follow-up). The phonocardiographic interval between the aortic second sound and opening snap was 73.4 +/- 18.1 msec, 88.7 +/- 9.6 msec, and 92.1 +/- 11.7 msec before and after PBMV and at follow-up (p < 0.001 before PBMV vs after PBMV and at follow-up). The voltage of P loop in the frontal plane of the vectorcardiogram was 0.25 +/- 0.04 mV, 0.21 +/- 0.04 mV, and 0.20 +/- 0.03 mV before and after PBMV and at follow-up (p < 0.001 before PBMV vs after PBMV and at follow-up). The New York Heart Association classification improved from class II in 26 patients and class III in 27 patients before PBMV to class I in 48 patients and class II in five patients after PBMV. These hemodynamic, noninvasive, and clinical results were not significantly different from those that were obtained in 112 patients with mitral stenosis without associated aortic regurgitation, who were studied during the same period in our cardiac catheterization laboratory. It was concluded that patients with rheumatic mitral stenosis are suitable candidates for PBMV whether or not they have associated aortic regurgitation of mild to moderate degree.