AIM:To evaluate specific metabolomics profiles in the serum of patients with chronic mountain sickness (CMS) and to explore the potential metabolic biomarkers in the native Tibetans living on the Qinghai-Tibet Plateau.METHODS:A gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) approach as a metabolomics technique was used to evaluate metabolic differences.The native Tibetan CMS patients (n =10) and healthy Tibetan controls (n =10) were enrolled from YuShu in Qinghai province in this study.The serum samples were collected and analyzed by GC-TOF-MS coupled with a series of multivariate statistical analyses such as principal component analysis (PCA),partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA).RESULTS:The intergroup differences between CMS patients and control subjects have been observed.A list of differential metabolites and several top altered rnetabolic pathways have been identified.The levels of fumaric acid,an intermediate in the tricarboxylic acid (TCA) cycle,and inosine were highly upregulated in the CMS patients,suggesting a greater effort to hypoxic adaptation in high elevation area.Other differential metabolites,such as methyl phosphate,2-ketoadipate,lyxose and phytanic acid were also identified.Importantly,the differential metabolites possessed higher area under the ROC curve (AUC) values,indicating an excellent clinical ability for the prediction of CMS.Increased levels of amino acids (isoleucine,glycine,serine,L-cysteine,citrulline and trimethyllysine) were detected in CMS group,yet significantly decreased levels of sulfuric acid,oxamic acid,lyxose and glutamine were also detected in CMS group than those in control group.At the same time,the levels of ribose and glucose-1-phosphate were markedly elevated in CMS group (P ＜ 0.05).CONCLUSION:The metabolic activities are significantly altered in the serum of CMS patients.High altitude hypoxia may act on the disturbed glucose metabolism and amino acid metabolism in part of the Tibetan triggered by CMS.

OBJECTIVETo investigate the anti-tumor activity of combined gemcitabine with dihydroartemisinin, and the mechanism of the anti-tumor effect of gemcitabine enhanced by dihydroartemisinin on pancreatic cancer.

METHODSFor cultured cells, cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis and confocal laser scanning microscope stained with Annexin V-FITC/PI. The nuclear extract for determining NF-kappaB DNA-binding activity was analyzed by EMSA, while nuclear P65 and its downstream gene expression was determined by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to agents. TUNEL assay was used to assess tumor cell apoptosis in tumor tissue.

RESULTSAfter combination of gemcitabine and dihydroartemisinin treatment, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and Panc-1 reached up to (81.1 +/- 3.9)% and (76.5 +/- 3.3)%, and the apoptosis rates were up to (53.6 +/- 3.8)% and (48.3 +/- 4.3)%, the differences were significantly (P < 0.01) compared with gemcitabine [(24.8 +/- 2.9)% and (21.8 +/- 3.5)%]. All the treatment groups inhibited the growth of pancreatic xenograft tumors in nude mice. The tumor volume and apoptosis index were (262 +/- 37) mm(3) and (50 +/- 4)% respectively in the combined treatment, compared to those of [(384 +/- 56) mm(3) and (25 +/- 3)%] in gemcitabine, the differences were significantly (P < 0.05). EMSA showed that gemcitabine alone obviously enhanced its DNA-binding activity compared to control. However, dihydroartemisinin significantly reduced its DNA-binding activity, so that abrogated the inducing effect of gemcitabine on NF-kappaB activation. Western blot assay indicated that dihydroartemisinin downregulated expression of nuclear P65, and combined treatment not only downregulated the expression of Cyclin D1, Bcl-xL and Bcl-2 while upregulated Bax, thus reduced the Bcl-2/Bax ratio, but also increased the caspase-3 activation, all of which increased apoptosis in both BxPC-3 and Panc-1 cells.

CONCLUSIONDihydroartemisinin significantly abrogated the inducing effect of gemcitabine on NF-kappaB activation and downregulated the expression of NF-kappaB targeted gene products, which may be one possible mechanism by which dihydroartemisinin augments the anti-tumor effect of gemcitabine on pancreatic cancer.

Animals ; Antimetabolites, Antineoplastic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Apoptosis ; drug effects ; Artemisinins ; therapeutic use ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Humans ; Male ; Mice ; Mice, Nude ; NF-kappa B ; metabolism ; Pancreatic Neoplasms ; drug therapy ; metabolism ; pathology ; Xenograft Model Antitumor Assays

OBJECTIVETo observe the therapeutic effect of hyperbaric oxygen (HBO) on acute pancreatitis (AP) by downregulating hypoxia-inducible factor (HIF).

METHODSForty Wistar rats were randomly divided into 4 groups (n = 10): sham group, AP group, normo-oxygen group (NP) and HBO group. At 4 hours after taurocholate-induced AP, the rats of NP group and HBO group were respectively treated with oxygen or HBO for 90 min. Several parameters were measured to evaluate oxygen stress after treatment including oxygen saturation (SaO2), partial pressure of oxygen (PO2), pH, and serum LDH. Pancreatic tissues were subjected to histopathological analysis, immunostained, and homogenized for Western blotted analysis of HIF-1alpha and VEGF, and measuring myeloperoxidase activity. The serum TNF-alpha and pancreatic histopathological scores were evaluated the severity of AP.

RESULTSIt was proved by immunohistochemisty that HIF in acinar cell and polymorphonuclear leukocytes (PMNs) was activated and transferred from cytoplasm into nucleus in AP group, NP group, and HBO group, following upregulation of VEGF. HBO therapy elevated blood SaO2 (99.6% +/- 0.7% vs. 87.7% +/- 1.8% or 91.2% +/- 2.5%, P < 0.05) and PaO2 [(369.1 +/- 67.6) mm Hg (1 mm Hg = 0.133 kPa) vs. (86.6 +/- 5.6) mm Hg or (99.9 +/- 4.0) mm Hg, P < 0.05]. HBO therapy attenuated the severity of AP through inhibiting AP-induced upregulation of HIF-1alpha and VEGF, as evidenced by reducing histopathological scores (12.40 +/- 1.21 vs. 16.45 +/- 1.10 or 16.38 +/- 1.10, P < 0.05), dry/wet weight ratio of pancreatic tissues, and myeloperoxidase activity.

CONCLUSIONSHIF-1alpha plays a key role in the pathogenesis of AP. HBO therapy attenuates the severity of AP through downregulating the expression of HIF-1alpha.

Animals ; Hyperbaric Oxygenation ; Oxygen ; Pancreatitis ; therapy ; Rats, Sprague-Dawley ; Rats, Wistar

OBJECTIVETo evaluate the association between vasectomy and prostate cancer.

METHODSWe searched comprehensively the databases, CBMDisc, CMCC, CMAC, CNKI (from 1978 to January 6, 2009), and PubMed (from 1965 to January 6, 2009) using the key words "vasectomy" and "prostate cancer", screened the retrieved literature according to the inclusion and exclusion criteria, performed a Meta-analysis with the software RevMan 4.2 after identification of the relevant data, and calculated the overall pooled OR (95% CI) as well as that of the association of prostate cancer with <20 and > or =20 yr vasectomy.

RESULTSA total of 20 088 cases and 232 506 controls in 27 reports (7 cohort and 20 case-control studies) were included in this investigation. The overall pooled OR (95% CI) was 1.10 (0.97-1.24), and those of <20 and > or =20 yr vasectomy were 0.94 (0.83-1.06) and 1.05 (0.90-1.23), respectively.

CONCLUSIONNo existing literature show any positive association between vasectomy and prostate cancer.

Humans ; Male ; Prostatic Neoplasms ; epidemiology ; etiology ; Risk Factors ; Vasectomy ; adverse effects

OBJECTIVETo investigate the relationship of seminal plasma levocarnitine with sperm concentration, vitality and motility.

METHODSEnrolled in this study were 64 infertile men, who were divided according to the results of routine sperm tests into a normozoospermia (n = 12), an oligozoospermia (n = 16), an asthenozoospermia (n = 20) and an oligoasthenozoospermia group (n = 16). The level of seminal plasma levocarnitine was detected by LC-MS-MS, the concentration of seminal plasma testosterone measured by chemiluminescence immunoassay, the correlation of seminal plasma levocarnitine with sperm concentration, motility and vitality determined by bivariate correlation analysis with SPSS15.0, and so was the correlation between the carnitine and sperm concentration by partial correlation analysis with seminal plasma testosterone as a control variable to exclude the influence of testosterone.

RESULTSThe concentrations of total seminal plasma levocarnitine, free seminal plasma levocarnitine and seminal plasma acetolevocarnitine were (91.33 +/- 40.49) mg/L, (40.89 +/- 24.13) mg/L and (50.44 +/- 21.90) mg/L; the Pearson coefficients of correlation of the levocarnitine level with sperm motility, vitality and concentration were 0.161 (P = 0.235), 0.114 (P = 0.370) and 0.637 (P < 0.001), those of free seminal carnitine with sperm motility and vitality were 0.325 (P = 0.024) and 0.316 (P = 0.029), respectively, with the oligozoospermia group excluded, and that of partial correlation between the concentrations of seminal levocarnitine and sperm was 0.641 (P < 0.001).

CONCLUSIONThe level of seminal plasma levocarnitine is positively correlated with sperm motility and vitality, and more significantly with sperm concentration.

Adult ; Carnitine ; analysis ; Humans ; Infertility, Male ; physiopathology ; Male ; Semen ; chemistry ; cytology ; Sperm Count ; Sperm Motility ; physiology ; Spermatozoa ; cytology ; physiology ; Young Adult

OBJECTIVETo investigate the application of the Chinese Urological Association (CUA) Guidelines on Prostatitis and its effects on the clinical practice patterns of diagnosing and treating chronic pelvic pain syndrome (CPPS) among Chinese urologists and andrologists.

METHODSWe conducted a questionnaire investigation on the application of the CUA Guidelines on Prostatitis among the urologists and andrologists of 173 hospitals in 21 cities of China, and performed statistical analyses on all the eligible questionnaires collected.

RESULTSOf the 1 056 questionnaires distributed, 851 (80.6%) were eligible, of which 71.6% were from the urologists or andrologists in grade 3 hospitals, 80.7% of them with senior or intermediate professional titles and 97.5% had studied the CUA Guidelines. Most of the subjects agreed that Type III prostatitis is a clinical syndrome, whose diagnosis should exclude other conditions with similar symptoms, and whose treatment should aim at relieving pain, alleviating urination symptoms and improving the quality of life. Those who had and those who had not studied the CUA Guidelines differed in their viewpoints on CPPS as illustrated in the book. In clinical practice, the most common treatment options for CPPS were psychological therapy (80.7%), medication (80.4%) and life style adjustment (79.6%), and the most frequently used drugs were phytotherapy (80.0%), alpha-blockers (68.9%) and antibiotics (61.0%).

CONCLUSIONCUA Guidelines on Prostatitis has gained a nationwide application and promoted the standardization of the management of CPPS in China.

Humans ; Male ; Pelvic Pain ; diagnosis ; therapy ; Physicians ; Practice Guidelines as Topic ; Prostatitis ; diagnosis ; therapy ; Surveys and Questionnaires

BACKGROUNDNoninvasive functional magnetic resonance imaging (fMRI) techniques have opened a "window" into the brain, allowing us to investigate the anatomical and physiological function involving acupuncture needling. Imaging its sustained effect rather than acute effect on the brain networks may further help elucidate the mechanisms by which acupuncture achieves its therapeutic effects. In this study, we aimed to investigate the functional brain networks during the post-resting state following acupuncture at KI3 in comparison with acupuncture at GB40.

METHODSNeedling at acupoints GB40 and KI3 was performed in twelve subjects. Six minutes of scanning at rest were adopted before and after acupuncture at different acupoints. Then we divided the whole brain into 39 regions and constructed functional brain networks during the post-acupuncture resting states (PARS).

RESULTSFor direct comparisons, increased correlations during post-resting state following acupuncture at KI3 compared to resting state (RS) were primarily located between the dorsolateral prefrontal cortex (DLPFC) and post temporal cortex, ventromedial prefrontal cortex (vmPFC) and post temporal cortex. These brain regions were all cognitive-related functions. In contrast, the increased connections between the anterior insula and temporal cortex mainly emerged following acupuncture at GB40 compared with the RS.

CONCLUSIONSThe present study demonstrates that acupuncture at different acupoints belonging to the same anatomic segment can exert different modulatory effects on the reorganizations of post-acupuncture RS networks. The heterogeneous modulation patterns between two conditions may relate to the functional specific modulatory effects of acupuncture.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Brain ; metabolism ; physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Young Adult

OBJECTIVE: To determine the effect of activation of specific anti-tumor cytotoxic T lymphocytes (CTL) and the ability of cross-presentation in vitro by fusion of HLA-A2+ human dendritic cells (DCs) with HLA-A2- melanoma cells. METHODS: The HLA-A2+ human dendritic cells and HLA-A2- melanoma cells were fused by PEG and were cultivated in complete RPMI1640 media containing FCS (10%) and GM-CSF for 24-48 h, and then co-cultured fusion cells with Melan-A specific T cells. HLA-A2- melanoma cells were negative control,While T2 cells and DC+Pts were positive control. The activation of anti-tumor CTL elicited by the fusion cells was detected by intracellular cytokine staining. RESULTS: The immature DC could express CD80, CD83, CD86, HLA-DR, and HLA-ABC,but the mature DC induced by TNF-alpha, PGE-2, and CD40L further highly expressed above molecules. The rate of specific CTL cells primed by the fusion cells was 16.72%+/-4.26%, negative control was 0.21%+/-1.84%,and positive control was 28.60%+/-5.67%. The CTL from vaccine by fusing DC and LAR6 induced lysis of HLA-A2+ LAR1 cells. CONCLUSION The HLA-A2 restricted specific anti-tumor CTL can be induced in vitro by fusion of HLA-A2+ human dendritic cells with HLA-A2- melanoma cells.
Antigen Presentation ; immunology ; Antigens, Neoplasm ; immunology ; Cancer Vaccines ; immunology ; Cell Fusion ; Cell Line, Tumor ; Dendritic Cells ; cytology ; immunology ; HLA-A2 Antigen ; immunology ; Humans ; MART-1 Antigen ; immunology ; Melanoma ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; immunology

Objective To develop a batch process method for kinematics data of mass population based on MATLAB. Methods Based on MATLAB, the original coordinate data of markers from motion capture system were first batch-read with interpolation processing for eliminating the error points. The body-fixed base of contiguous rigid body attached on human body was then constructed as the reference base and body-fixed base of relative joint kinematics computing. The flexion/extension, abduction/adduction, internal and external rotation angular displacement, angular velocity and angular acceleration of joints were obtained based on the rigid body kinematics, the basic description of rigid body posture and the direction cosine matrix. Results Taking climbing upstairs and squatting as samples, the joint kinematics of lower extremity were analyzed and calculated by the batch process method for kinematics data of mass population based on MATLAB to prove the effectiveness and accuracy of the method. Conclusions The batch process method for kinematics data of mass population based on MATLAB was proved to be effective and accurate, and can be provided as a statistical analysis tool for anthropometry, human engineering, etc.

Rotator cuff injury often leads to shoulder pain and dysfunction. For the injured rotator cuff tendon without continuous interruption, conservative treatment is often used. However, the shoulder is used frequent in daily life, which makes that the rotator cuff injury generally shows gradual aggravation and eventually progresses to complete tear due to poor blood supply of the rotator cuff tendon tissue and weak repair ability. In order to reverse the pathophysiological changes after rotator cuff injury and promote the repair of injured rotator cuff tendon, a series of conservative treatments for rotator cuff injury have been explored. Extracorporeal shock wave therapy (ESWT) is one of the representative treatments, but its molecular biological mechanism in promoting rotator cuff repair is still unclear. Therefore, the authors review the progress of ESWT for rotator cuff injury from aspects of the molecular biological mechanism and clinical application status, so as to provide a reference for future researches and clinical application of ESWT.