Ankylosing spondylitis (AS) is a common chronic inflammatory arthritis, causing lasting back pain with progressive loss of spinal mobility. However, the exact pathogenesis of AS remains unclear. We aim to use the metabolomics analysis to characterize the metabolic profile of AS, in order to better understand the pathogenesis of AS and monitor disease activity and progression. The ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS) was used for investigating the serum amino acid metabolomic profiling of 30 AS patients, in comparison with 32 rheumatoid arthritis (RA) patients and 30 healthy controls, combined with multivariate statistical analysis. Metabolite association analysis with disease activity was performed using generalized linear regression. The metabolic pathway analysis for the important metabolites was performed using MetPA and the metabolic network was constructed. A total of 29 amino acids and biogenic amines were detected in all participants by UPLC-TQ-MS. It showed significant amino acid differences between the AS/RA patients and control subjects. Additionally, 4-hydroxy-L-proline, alanine, γ-aminobutyric acid, glutamine, and taurine were identified as candidate markers shared by AS/RA groups. Specifically, lysine, proline, serine, and alanine were found correlated with disease activity of AS. Furthermore, the most significant metabolic pathway identified were alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, aminoacyl tRNA biosynthesis and glycine, serine, and threonine metabolism. These preliminary results demonstrate that UPLC-TQ-MS analysis method is a powerful tool to identify metabolite profiles of AS. Research in identified disease activity–associated metabolites and biological pathways may provide assistance for clinical diagnosis and pathological mechanism of AS.
Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA.
Objective To evaluate the curative effect and security of thymopeptide and lamivudine as sequential antiviral therapy in patients with chronic hepatitis B. Methods Total of 554 cases with positive HBV DNA and positive HBeAg were enrolled. All 544 patients were randomly divided to 257 patients as the sequential therapy group and 287 patients as the lamivudine therapy group. After complete response, the patients continued to receive lamivudine therapy, patients of sequential therapy group continued to receive treatment for 14.80 months, and those of lamivudine alone group for 14.60 months. HBV DNA load, HBV surface markers, YMDD mutation and T lymphocyte subsets were detected, respectively. Results At the end of treatment, the rates of complete response, HBeAg negative conversion and HBeAg seroconversion in patients of sequential therapy group and lamivudine alone group were 57.59%, 47.08% and 46.30% vs. 43.21%, 32.06% and 31.71%, respectively, with significant differences (χ2 = 11.958, 12.850, 12.183; all P <0.001). The patient discontinued the treatment after obtained complete response following the guidelines. The average period of follow-up survey were 105.9 months and 104.02 months of patients in sequential therapy group and lamivudine group, respectively. The rates of cumulative sustained virological response, HBeAg negative conversion and HBeAg seroconversion were 37.74%, 34.24% and 33.46% in patients of sequential therapy group and 20.21%,16.38% and 16.38% of patients in lamivudine group, with significant differences (χ2 = 20.460, 23.193, 21.431, all P < 0.001). In the sequential treatment group, the T-lymphocyte subsets were measured before and after treatment in the patients who obtained complete response. The percentage of CD4 and NK cells were significantly increased after treatment (t = 2.984, 2.868, P = 0.045, 0.047) and the nomal rate of CD4/CD8 was increased (t = 3.012, P = 0.044). The incidences of adverse events were 12.45%and 18.82% in sequential therapy group and lamivudine groups, respectively, with significant differences (χ2 = 4.126, P = 0.042). The incidence of primary liver cancer (1.56%) in the sequential therapy group was significantly lower than that in the lamivudine group (5.92%), with significant differences (χ2 = 6.967, P =0.008). Conclusions The sequential treatment of chronic hepatitis B with thymosin and lamivudine could improve the efficacy of antiviral therapy and reduce the occurrence of primary liver cancer, which is a safe, economical and effective method for treatment of chronic hepatitis B.
Recently, microRNA (miR)-33b has been demonstrated to act as a tumor suppressor in osteosarcoma. However, the regulatory mechanism of miR-33b in osteosarcoma cell proliferation and migration remains largely unknown. In this study, real-time PCR showed that miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Its expression was also decreased in several common osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and migration. HIF-1α was further identified as a target of miR-33b, and its protein levels were reduced after overexpression of miR-33b in U2OS cells. Moreover, overexpression of HIF-1α significantly reversed the suppressive effect of miR-33b on U2OS cell proliferation and migration. In addition, HIF-1α was found to be significantly upregulated in osteosarcoma tissues compared to adjacent nontumor tissues, and their expression levels were inversely correlated to the miR-33b levels in osteosarcoma tissues. According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1α. Therefore, we suggest that the miR-33b/HIF-1α axis may become a promising therapeutic target for osteosarcoma.
Objective: To perform dual-bundle reconstruction of posterior cruciate ligament using full arthroscopic tibial inlay technology with self-designed tibia tunnel drilling system and to compare the effect of arthroscopic tibial inlay versus traditional technique for posterior cruciate ligament reconstruction. Material and methods: 32 patients were randomly divided into experiment group (improved tibial inlay, n = 17) and control group (traditional tibial inlay, n = 15). Self-designed tibia tunnel drill system was used to produce intraoperative deep-limited bone tunnel. During follow-up, the location of the bone block and the healing situation were checked by knee X-ray and spiral CT scan. Blood loss, operation time and nerve vascular injuries were evaluated. Results: Mean intraoperative blood loss was 123.53 ± 74.05 ml in the improved tibial inlay group compared with 332 ± 114.26 ml in the traditional tibial inlay group (t = 6.12, P < 0.05). Mean operation time was 235.27 ± 58.88 min in the improved tibial inlay group compared with 346.37 ± 59.67 min in the traditional tibial inlay group (t = 5.19, P < 0.05). Posterior drawer test were negative in 15 cases, slight positive in 2 with improved tibial inlay technique compared with 14 negative cases and 2 positive cases of traditional tibial Inlay technique. The X-ray and spiral CT scan showed the location of the bone block were perfect and healed well with the patent who received improved tibial inlay technology after 12 weeks postoperatively. Conclusion: Accurate depth-limited bone tunnel can be produced by the tibia tunnel drill system with minor trauma, less bleeding and reducing of nerves or vessels and the recent clinical effects of PCL reconstruction were pretty good.
The aim of the present study was to investigate the underlying molecular mechanisms of rheumatoid arthritis (RA) using microarray expression profiles from osteoarthritis and RA patients, to improve diagnosis and treatment strategies for the condition. The gene expression profile of GSE27390 was downloaded from Gene Expression Omnibus, including 19 samples from patients with RA (n=9) or osteoarthritis (n=10). Firstly, the differentially expressed genes (DEGs) were obtained with the thresholds of |logFC|>1.0 and P<0.05, using the t‑test method in LIMMA package. Then, differentially co-expressed genes (DCGs) and differentially co-expressed links (DCLs) were screened with q<0.25 by the differential coexpression analysis and differential regulation analysis of gene expression microarray data package. Secondly, pathway enrichment analysis for DCGs was performed by the Database for Annotation, Visualization and Integrated Discovery and the DCLs associated with RA were selected by comparing the obtained DCLs with known transcription factor (TF)-targets in the TRANSFAC database. Finally, the obtained TFs were mapped to the known TF-targets to construct the network using cytoscape software. A total of 1755 DEGs, 457 DCGs and 101988 DCLs were achieved and there were 20 TFs in the obtained six TF-target relations (STAT3-TNF, PBX1‑PLAU, SOCS3-STAT3, GATA1-ETS2, ETS1-ICAM4 and CEBPE‑GATA1) and 457 DCGs. A number of TF-target relations in the constructed network were not within DCLs when the TF and target gene were DCGs. The identified TFs may have an important role in the pathogenesis of RA and have the potential to be used as biomarkers for the development of novel diagnostic and therapeutic strategies for RA.
>HBeAg血清学转换对于HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者的治疗具有十分重要的意义,因此国内外有关指南均明确将HBeAg血清学转换作为重要治疗终点之一 [1-4] 。现有的抗病毒治疗药物中,替比夫定与干扰素治疗CHB均可获得较高的HBeAg血清学转换。最近国内外报道基线和治疗期间HBeAg水平可预测替比夫定的抗病毒疗效 [5] 。本研究收集101例替比夫定治疗1年以上的HBeAg阳性CHB患者资料,回顾性动态分析基线和治疗
Objective: To explore the short-term efficacy of artificial unicompartmental replacement of knee in the treatment of advanced unicompartmental knee artificial replacement. Methods: 37 cases of dvanced unicompartmental knee artificial replacement who were treated by artificial unicompartmental replacement and had been followed-up for more than 2 years from March 2007 to September 2011 were selected. X-ray of knee joint, wobbles, sinking and the other side compartment for any degenerative were observed. HSS score in the last follow-up, and the difference of pain and function were compared between bwfore and after operation. Results: All of 37 patients were followed-up, the time of follow-up was 22-38 months, on average 29.8 months, there was no aggravation of loosery, subsidence and the other side compartment degeneration or degeneration. HSS score was 95.5 ±1.7 in the last follow-up, which was significantly higher than that before surgery(68.5±2.1). The difference was statistically significant(P=0.016). Conclusion: Knee artificial unicompartmental replacement surgery possessed less invasive, fewer complications, quick recovery and good term efficacy, good function and good short-term outcome.
Objective: To compare the effect of improved tension band wire fixation and traditional tension band wire fixation on patellar fracture. Methods: From March 2007 to September 2011, 64 patients with patellar fracture followed up more than 1 year using Xu's tention band wire fixation and improved tension band wire fixation were selected. During the operation, Xu's tention band wire fixation and improved tension band wire fixation were adopt. According to the follow-up knee X-ray radiography examination, the situation of the joint's surface involution were observed, and then the joint's surface steps like dislocation was more than 2 centimeters were compared between two treatments. Results: There were 64 patients followed up, it was from eight months to twelve months, the average time was 13.2 months. And the fracture were healed, there was no significant difference in the Lysholm score(P=0.665) between two groups. It appeared 1(3.1%) and 7(21.9%) of articular step acquisition respectively between Xu's tention band wire fixation and improved tension band wire fixation, According to the frequency of appearing articular step acquisition, there was statistical significance(P=0.036). Conclusion: Xu's tension band wire fixation promoted the fixation of patella fracture after operation, the joint's surface joined better, which could effectively prevent the traumatic arthritis induced by step syndrome.
Objective To investigate the recent effect of full arthroscopic dual-beam reconstruction of the posterior cruciate ligament(PCL)using tibial Inlay technique.Methods From March 2007 to September 2009,17 PCL injured patients underwent full arthroscopic dual-beam PCL reconstruction using Inlay technique,including 16 males and 1 female,with an average age of 25 years(range,19-54).Of all cases,Lysholm score was(53.4±2.1)points,International Knee Documentation Committee(IKDC)rated C in 7,D in 10,and posterior drawer test(+)in 17.We used self-designed tibia tunnel drill system to produce the deep-limited bone tunnel.Follow-up began at 12 months after operation.Evaluate Lysholm knee score,IKDC rating,and posterior drawer test to compare the knee stability with that of preoperative.Observe the location of the bone block and healing by checking knee X-ray and spiral CT scan.Results Seventeen patients were followed up between 12 to 28 months,with an average of 17.8 months.In the last follow-up study,Lysholm score(93.5±1.7)points compared with that of preoperative was statistically significant different(P=0.016).IKDC rating of A grade in 15 cases,B in 2,compared with that of preoperative was statistically significant different(P=0.021).Posterior drawer test were negative in 15 cases,slight positive in 2.The X-ray and spiral CT scan showed the location of the bone block were perfect and healed well.Conclusion We can accurately produce the deep-limited bone tunnel by the tibia tunnel drill system with minor trauma,and the recent clinical effects of PCL reconstruction were pretty good.
胃癌是严重影响广大人民群众身体健康的恶性肿瘤.在准确进行术前分期综合的基础上,对胃癌患者的治疗多采用以手术治疗为中心的综合治疗(放疗、化疗、靶向治疗等).现就胃癌的治疗做一综述.
Objective To analyze the types of mutation in the RT region of HBV polymerase in patients after the treatment of nucleoside/nucleotide analogs.Methods The RT regions of HBV from 142 serum samples of hepatitis B patients received from February 2007 to November 2011 were sequenced,and the statistical significances were analyzed by SPSS 17.0 software.Results There were 9 known resistance site mutations found in 87 samples (61.3 %) among 142 samples,including 21 mutation patterns.Forty-three samples (49.4%) showed multi-site mutation,in which 9 samples (10.3%) were multidrug resistant mutation.In the patients treated with lamivudine (LAM) alone,there were 2 samples of A181T mutation and 1 sample of M204V + L180M + A194T mutation (tenofovir-related mutation).M204I mutation was found in 2 patients treated with adefovir dipivoxil (ADV) alone.These mutations were relatively rare.It suggested that LAM and ADV cross-resistance might exist in some circumstances.Conclusions By the further research of clinical practice,the patterns of mutation in the RT region of HBV polymerase will be more complex including multi-site mutation and multidrug resistant mutation.The clinician should pay great attention.
替比夫定是口服L核苷类似物,是一种特异性的HBV DNA多聚酶的强效抑制剂[1].国内外临床试验结果显示,替比夫定比拉米夫定具有更强的病毒抑制作用,更高的HBeAg血清学转换率,且2年耐药率更低[2-4].本研究观察单用替比夫定与胸腺肽序贯替比夫定的抗HBV疗效,现将观察结果报道如下.
Objective To evaluate the clinical value of desmopressin in reducing blood loss following total hip arthroplasty (THA) .Methods From September 2007 to June 2009, 62 patients (28 males and 34 females) underwent THA.They were randomly divided into 2 even groups.Group A (desmopressin group) received intravenous administration of desmopressin(0.3 μg/kg diluted in 100 mL normal saline) at 30 minutes preoperatively and in 2 consecutive days postoperatively.Instead Group B (control group) received intravenous administration of normal saline of the same volume and in the same manner.The amounts of calculated total blood loss, intraoperative blood loss, postoperative wound blood loss and blood transfusion were recorded.The hemoglobin concentration (Hb) , hematocrit (Hot), platelet (Plt),fibrinogen (Fib), prothrombin time (PT), activated partial thromboplastin time (APTT) were also examined one day before and one day after operation for comparison.The patients were examined for occurrence of deep vein thrombosis(DVT) by Color Doppler Flow Imaging.Results The intraoperative blood loss was 375 ±43 mL in Group A and 392 ± 55 mL in Group B, without significant difference between the 2 groups ( P >0.05 ).The postoperative drainage volume was 276 ± 49 mL in Group A and 294 ± 52 mL in Group B with no significant difference either ( P > 0.05).The total blood loss was 920 ±80 mL in Group A and 1150 ±99 mL in Group B, with a significant difference between the 2 groups ( P < 0.05) .There were also significant differences between the 2 groups in average amount of blood transfusion, patients needing blood transfusion and postoperative Hb, Hct, Plt levels and APTT( P < 0.05).No DVP event was found 14 days postoperation in either group.Conclusion During and following THA, a short-term use of desmopressin can significantly decrease blood loss and transfusion required.
拉米夫定是第一个被用于口服治疗慢性乙型肝炎(CHB)的抗病毒药物,近期疗效较满意[1-2].拉米夫定治疗过程中随着HBV-DNA转阴,ALT恢复正常,也可出现HBeAg转阴或血清转换,常显示有良好的治疗应答,同时其也是停药的参考指标之一.
拉米夫定治疗慢性乙型肝炎(CHB)已积累了大量的临床数据,近期疗效良好,但是长期治疗易发生HBV变异和耐药[1].若能够在治疗的早期预测患者的远期疗效,将有利于对患者进行优化治疗.我们通过对拉米夫定治疗成人HBeAg阳性CHB患者的临床资料进行了分析,以期探索实际有用的疗效预测指标.
Objective To investigate the etiology and clinical types of sporadic virus hepatitis in wenling city and to provide the base for the preventive strategy. Methods The data of 3317 sporadic viral hepatitis cases in the Affiliated Wenling Hospital of Wenzhou Medical College were analysed retrorespectively. Results Of the 3317 cases, the rates of hepatitis A, B,C,D, E,G, coinfection and infection of uncertain type were 1.63% ,64.97% ,0.66% ,0.12% ,9.52%,0.06%,16.79% and 6.24% respectively.The clinical types included 1181 eases of chronic hepatitis (35.60%),965cases of hepatocirrhosis(29.09% ) ,904 cases of acute hepatitis(27.25% ), 175 cases d liver cancer(5.28% ) ,56 cases of serious hepatitis( 1.69% ),36 cases of cholestatic hepatitis( 1.09% ). The rates of hepatitis B in chronic hepatitis,hepatocirrhosis, serious hepatitis, liver cancer and coinfection were 74.68% ,82.80% ,71.43% ,97.71% and 88.51%respectively. The incidence of hepatitis A reduced, while the incidence of hepatitis B and E increased in acute hepatitis. The rate of uncertain type hepatitis was 18.03% in acute hepatitis. Conclusions Most patients are infected with hepatitis B virus in Wenling city, especially in adults. Extended vaccination and strengthening the management of volunteer donors and blood transfusion are effective measures to prevent the transmission. Meanwhile, the hepatitis E epidemic should be controlled strictly, and the study of new hepatitis virus should be strengthened.
AIM:To investigate the clinical character of patients who had achieved complete or partial response relapsed after withdrawal with lamivudine therapy.METHODS:160 patients with complete response and 35 patients with partial response continue to be monitored after withdrawal with lamivudine therapy.The liver function was checked once a month,the levels of HBV DNA,HBsAg,anti-HBs,HBeAg,anti-HBe and anti-HBc were tested once every 3 months.And detailed record of the condition and re-treatment outcomes.RESULTS:The relapse rates of HBV-DNA were 30.6% in the complete response group and 85.7% in the partial response group.The difference was statistically significant(χ2=36.164,P0.001).ALT recurrence rate were 28.75%(46/160) and 82.9%(29/35),the difference was statistically significant(χ2=32.645,P0.001).In 6 months after withdrawal,the relapse rates of the patients were 80% in the complete response group and 53.1% in the partial response group.With a long course,the recurrence rate was relatively low.The relapsed patients who had achieved complete response were mild.Lamivudine withdrawal with the long-term follow-up,timely treatment,prognosis was good.CONCLUSION:The relapse rate of the patients who had achieved complete response is lower.The state of illness is better in the patients who had achieved complete response,whereas,the treatment of the patients who had achieved partial response with lamivudine should not be discontinue.
<正>笔者于2009年2月收治铰链式全膝关节置换术后股骨假体周围骨折1例。报告如下。1病例报告患者,男性,74岁。因跌倒后右大腿剧烈疼痛,不能活动近2h入院。患者于6年前因右膝骨性关节炎伴外翻畸形于本院