[Clinical characteristics in gout patients with different body mass index].

Objective: Obesity is one of the risk factors for gout. The aim of the present study was to evaluate clinical characteristics of gout patients with different BMI. Methods: A total of 5 104 patients with gout were enrolled and divided into three groups according to the BMI. The clinical information was collected and relevant biochemical indices were detected. SPSS software was applied for the statistical analyses. Results: There were significant differences in the ratios of gender, regular exercise, hypertension, tophus, renal insufficiency, hyperlipidemia, impaired glucose metabolism, liver dysfunction among the three groups (all P<0.01). The onset age in overweight [45(36, 55) years] and obese subjects [40(31, 50) years] were earlier than that of the normal weight subjects [50(38, 61) years]. Moreover, waist circumstances [103(99, 108) cm and 94 (90, 98) cm vs 87 (82, 91) cm], systolic pressure [130 (120, 145) mmHg (1 mmHg=0.133 kPa)and 130(120, 140)mmHg vs 128(115, 140) mmHg], diastolic pressure [90 (80, 100) mmHg and 85 (80, 92) mmHg vs 80 (79, 90) mmHg], fasting blood glucose [5.77 (5.30, 6.44) mmol/L and 5.65 (5.19, 6.26) mmol/L vs 5.55 (5.10, 6.15) mmol/L], TG [2.10 (1.46, 3.04) mmol/L and 1.88 (1.35, 2.78) mmol/L vs 1.52 (1.07, 2.39) mmol/L], TC [5.20 (4.55, 5.93) mmol/L and 5.07 (4.46, 5.75) mmol/L vs 4.95 (4.27, 5.65) mmol/L], serum uric acid [483(418, 552) µmol/L and 461(395, 524) µmol/L vs 440 (368, 517) µmol/L], ALT [30 (21, 46) U/L and 25 (18, 36) U/L vs 21 (14, 29) U/L], AST [21(17, 28) U/L and 20 (17, 26) U/L vs 20 (6, 25) U/L], the number of joints involved [2(1, 3)joints and 2(1, 2) joints vs 1(1, 2) joints] in the overweight and obese groups were higher than those in the normal weight group ( all P<0.01). There were no statistical differences in family history, involvement of upper limb joints, kidney stones and coronary heart disease among the three groups (all P>0.05). Conclusions: Obesity is associated with an earlier age of gout onset.With the increase of BMI, the blood pressures, glucose, lipid, serum uric acid, liver transaminase levels and the number of involved joints increased gradually. Cautions should be taken in treating patients with different BMI.

Molecular identification and genetic variation of varieties of Styphnolobium japonicum (Fabaceae) using SRAP markers.

Thirty-four Styphnolobium japonicum varieties were analyzed using sequence-related amplified polymorphism (SRAP) markers, to investigate genetic variation and test the effectiveness of SRAP markers in DNA fingerprint establishment. Twelve primer pairs were selected from 120 primer combinations for their reproducibility and high polymorphism. We found a total of 430 amplified fragments, of which 415 fragments were considered polymorphic with an average of 34.58 polymorphic fragments for each primer combination. The percentage of polymorphic fragments was 96.60%, and four primer pairs showed 100% polymorphism. Moreover, simple matched coefficients ranged between 0.68 and 0.89, with an average of 0.785, indicating that the genetic variation among varieties was relatively low. This could be because of the narrow genetic basis of the selected breeding material. Based on the similarity coefficient value of 0.76, the varieties were divided into four major groups. In addition, abundant and clear SRAP fingerprints were obtained and could be used to establish DNA fingerprints. In the DNA fingerprints, each variety had its unique pattern that could be easily distinguished from others. The results demonstrated that 34 varieties of S. japonicum had a relatively narrow genetic variation. Hence, a broadening of the genetic basis of breeding material is necessary. We conclude that establishment of DNA fingerprint is feasible by means of SRAP markers.

Midline preperitoneal repair for incarcerated and strangulated femoral hernia.

OBJECTIVE: Femoral hernias constantly present as incarceration or strangulation and require emergency surgery. Incarcerated and strangulated femoral hernia repair remains challenging and controversial. The aim of our study was to analyze the efficacy of preperitoneal tension-free hernioplasty via lower abdominal midline incision for incarcerated and strangulated femoral hernia. METHODS: Data of 47 patients who underwent emergency surgery for incarcerated or strangulated femoral hernias from January 2009 to December 2017 were retrospectively analyzed. According to the surgical incisions, they were divided into two groups: the observation group (21 cases) had a lower abdominal midline incision, and the control group (26 cases) had a traditional inguinal incision. General data of patients, intraoperative findings, operative time and postoperative complications were compared. RESULTS: Patient characteristics showed that the two groups were comparable.15 cases (31.9%) underwent intestinal resection, and 32 cases (68.1%) underwent first-stage tension-free repair in total. The rate of first-stage tension-free hernioplasty was significantly higher in the observation group (18/21, 85.7% vs 14/26 53.8%, P = 0.020). No additional incision was required in the observation group, while six cases of the control group (23.1%) had an additional incision for intestinal resection and anastomosis (P = 0.026). Mean operative time (53.6 ± 24.7 min vs 77.9 ± 36.5 min, P = 0.012) and the length of hospital stay (6.3 ± 4.2 days vs 10.3 ± 6.9 days, P = 0.020) were significantly shorter in the observation group. The time of return to normal physical activity resulted significantly reduced compared to the control group (9.2 ± 4.1 days vs 13.3 ± 6.6 days, P = 0.017). The total incidence of postoperative complication (including chronic pain, foreign body sensation, hernia recurrence, wound infection and seroma/hematomas) in the observation group was lower (14.3% vs 42.3% P = 0.037). There were two recurrences in the control group. No mesh-related infection and no mortalities in two groups. CONCLUSIONS: Midline preperitoneal approach for incarcerated and strangulated femoral hernia is a convenient and effective technique. It can improve the rate of first-stage tension-free repair of incarcerated femoral hernia and allow intestinal resection through the same incision, and with lower rate of postoperative complications.

[Molecular mechanisms and relationship of M2-polarized macrophages with early response in multiple myeloma].

Objective: To investigate the relationship between M2-polarized macrophages and early response in multiple myeloma and its molecular mechanism. Methods: Two hundred and forty bone marrow biopsy tissue were collected and M2-polarized macrophages were stained by anti-CD163 monoclonal antibody. In vitro M2-polarized macrophages were derived from human peripheral blood mononuclear cell or THP-1 cells and identified by flow cytometry. Two myeloma cell lines RPMI 8226 and U266 were co-cultured with M2 macrophages using a transwell system. We measured myeloma cells proliferation through CCK-8 method and the pro-inflammatory cytokines expression (TNF-α and IL-6) by ELISA. Real time PCR was applied to measure chemokines (CCL2 and CCL3) , chemokine receptors (CCR2, CCR5) , VEGF and their receptors. In addition, flow cytometry was used to analyze the apoptosis of myeloma cells induced by dexamethasone. Results: ①Patients with high percentage of M2 macrophage involvement in bone marrow showed poorer response (23.9% versus 73.0%, χ(2)=60.31, P<0.001). ② In vitro the proliferation of RPMI 8226 cells (P=0.005 at 24 h, P=0.020 at 36 h) or U266 myeloma cells (P= 0.030 at 24h, P=0.020 at 36h) co-cultured with M2-polarized macrophages was higher than control group. ③In vitro the apoptotic rate of RPMI 8226 cells (29.0% versus 71.0%, t=4.97, P=0.008) or U266 myeloma cells (24.9% versus 67.7%, t=6.99, P=0.002) co-cultured with M2-polarized macrophages was lower than control group. ④ In vitro M2-polarized macrophages promoted myeloma cells secreting higher level of IL-6, TNF-α and higher expression of CCL2, CCL3, CCR2, CCR5, VEGFA, VEGFR-1,-2 compared with the non-macrophage co-culture system. Conclusion: M2-polarized macrophages promote myeloma cells proliferation and inhibit apoptosis through a very complex mechanism involving pro-inflammatory cytokines IL-6 and TNF-α, chemokines and related receptors such as CCL2, CCL3, CCR2, CCR3, and VEGF as well as related VEGFR.

[Intratympatic budesonide injection for treatment of refractorysudden sensorineural hearing loss].

Objective:To investigate intratympanic steroid injection for treatment of sudden sensorineural hearing loss after failure of initial systemic therapy,and discuss the role of steroid in refractory sudden sensorineural hearing loss.Method:We included 90 patients who did not response to initial systemic therapy of sudden hearing loss.This research adopted the randomized,controlled trial of clinical research.Ninety qualified patients were divided into 3 groups,30 for each group,intratympanic budesonide for experimental group,dexamethasone for control group-1 while control group-2 did not take intratympanic steroid injection but continue another round of systemic therapy.Intratympanic injection was performed 3 times a week and last for 2 weeks.Alprostadil,mecobalamin,ginkgo biloba extract injection,PNS injection and intravenous hyperbaric oxygen fluid were used for consecutive 10 days in the control group-2.Pure tone audiometry and speech Discrimination Score was retaken at the end of each therapy.Result:The results show that the average PTA of damaged frequencies improved more than 10 dB was considered significant,we had 26.7%(8/30) patients meet this criteria in experiment group,30.0%(9/30) in the control group-1 and 6.7%(2/30) in the control group-2.And the recovery rate between these 3 groups is statistically significant(P<0.05),the average PTA improvement in the experimental group,control group-1 and control-2 was(5.0±11.1)dB,(4.2±12.5)dB and (0±3.33)dB respectively,P<0.05,control group-2 was significantly different from control group-1 and experimental group.The Speech Discrimination Score improvement rates in the experimental group,control group-1 and control-2 was 16.7%,12.0% and 4.2% respectively,but the difference in those 3 groups was not significant.Conclusion:Budesonide intratympanic injection is a save method in treating refractory sudden hearing loss ,and it is as effective as dexamethasone.Intratympanic steroids could be an option for refractory sudden sensorineural hearing loss patients.

Field homogeneity improvement of maglev NdFeB magnetic rails from joints.

An ideal magnetic rail should provide a homogeneous magnetic field along the longitudinal direction to guarantee the reliable friction-free operation of high temperature superconducting (HTS) maglev vehicles. But in reality, magnetic field inhomogeneity may occur due to lots of reasons; the joint gap is the most direct one. Joint gaps inevitably exist between adjacent segments and influence the longitudinal magnetic field homogeneity above the rail since any magnetic rails are consisting of many permanent magnet segments. To improve the running performance of maglev systems, two new rail joints are proposed based on the normal rail joint, which are named as mitered rail joint and overlapped rail joint. It is found that the overlapped rail joint has a better effect to provide a competitive homogeneous magnetic field. And the further structure optimization has been done to ensure maglev vehicle operation as stable as possible when passing through those joint gaps. The results show that the overlapped rail joint with optimal parameters can significantly reduce the magnetic field inhomogeneity comparing with the other two rail joints. In addition, an appropriate gap was suggested when balancing the thermal expansion of magnets and homogenous magnetic field, which is considered valuable references for the future design of the magnetic rails.

Large scale and clinical grade purification of syndecan-1+ malignant plasma cells.

For cancer immunotherapy, it is usually necessary to obtain a large number of tumor cells from patients. We have previously reported that syndecan-I is present only on malignant plasma cells in samples from patients with multiple myelomatosis. We report here that this antigen is cleaved by chymopapain. This makes it possible to develop a rapid and clinical grade procedure to purify large numbers of myeloma cells using anti-syndecan-1 mAb, magnetic beads and chymopapain.

Inhibitory effects of synthetic beta peptide on invasion and metastasis of liver cancer.

PURPOSE: To study the inhibitory effects of synthetic beta peptide on invasion and metastasis of liver cancer. METHODS: Membrane-type intercellular adhesion molecule-1 (ICAM-1) expression of SMMC-7721 cultured hepatoma cells (7721 cells) was detected by immunofluorescence cell flowmeter. The adhesion of 7721 cells to fibronectin (FN) was assayed by the MTT method. The adhesion of 7721 cells to 7721 cells, 7721 cells to endothelial cells, and 7721 cells to lymphocyte cells was detected by adhesion assay. LCI-D20 human liver cancer metastasis model in nude mice was used in this experiment. One hundred micrograms of beta peptide per mouse were injected subcutaneously after tumor was resected premetastatically or postmetastatically to observe its effect on liver cancer metastasis after hepatectomy. RESULTS: Membrane-type ICAM-1 expression of SMMC-7721 cells treated by beta peptide was lower than that of the untreated cells. The adhesion of 7721 cells to FN, 7721 cells to 7721 cells, 7721 cells to endothelial cells, and 7721 cells to lymphocyte cells was also lower in the beta peptide group than in the untreated group. CONCLUSIONS: beta Peptide can block the adhesion of 7721 cells to FN, 7721 cells to some host cells in vitro, and inhibit HCC metastasis of LCI-D20 model posthepatectomy in vivo, so it could potentially act as an antimetastasis drug.

Interleukin-6 receptor antagonists inhibit interleukin-11 biological activity.

The IL-6 receptor system comprises two functionally different chains: a binding chain (IL-6R) and a signal-transducing chain (gp130). The IL-6/IL-6R complexes associate with gp130, induce its dimerization and signal transduction. When IL-6 is complexed to IL-6R, two distinct sites of IL-6 are able to bind gp130. Other cytokines-oncostatin M (OM), leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF) also use the gp130 transducer and induce its heterodimerization with LIF receptor (LIFR). A series of IL-6 mutants have been generated which function as IL-6 receptor antagonists (IL-6RA). These IL-6RA carried substitutions that increased their affinity with IL-6R and abolished 1 or the 2 sites of interaction with gp130. All the IL-6RA inhibited wild-type IL-6. The IL-6RA with one mutated binding site to gp130 inhibited IL-11 activity. They did not affect those of CNTF, LIF and OM, even when used at a very high concentration at which virtually all membrane IL-6R were bound to IL-6RA. IL-6RA with two mutated gp130 binding sites did not affect IL-11, CNTF, LIF or OM activities. The results indicate that the interaction of one gp130 chain with IL-6R/IL-6R complexes inhibited further the dimerization of gp130 induced by IL-11/IL-11R but not its heterodimerization with LIFR. Thus these IL-6RA can also function as IL-11 antagonists.

Specific inhibition of IL-6 signalling with monoclonal antibodies against the gp130 receptor.

A family of cytokines [IL-6, IL-11, oncostatin M (OM), leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and cardiotrophin-1] involved in various inflammatory or tumoral diseases share the same gp130 signal transducer chain. The complex formed with their specific receptors associates with a common transducing gp130 membrane protein (gp130) resulting in the formation of high avidity receptor and activation of tyrosine kinases. With the view of identifying gp130 domains specifically involved in IL-6 signalling, the authors prepared 37 new anti-gp130 mAb and analysed the structure-function relationship of the molecule. By cross-competition ELISA, the mAb were classified in 10 subgroups called A to J. By ELISA and BIAcore analysis, the mAb were found to recognize at least 18 antigenic specificities of the gp130 chain. The mAb reacted against the soluble and the membrane forms of gp130 as well. Their ability to inhibit the proliferation of the human myeloma cell line XG-4 of which the growth is strictly dependent on the presence of either exogenous IL-6, or LIF, or OM, or CNTF was studied. Besides mAb with no evident neutralizing effect (G and H) and mAb which neutralized equally well the activity of all tested cytokines (all mAb of groups A, I and J), some showed a selective effect. Those of group F inhibited also the proliferation induced by the 4 cytokines, but more specifically that dependent on the CNTF. mAb of groups B and E specifically inhibited the growth induced by IL-6, whereas those of group C inhibited that induced by LIF and OM. These results show the presence of different gp130 epitopes specifically involved in the signaling induced by the cytokines of the gp130 family. In ELISA, only mAb of group B and E were found to inhibit the binding of the IL-6-IL-6R complex to gp130, showing that they identified one or two domains of gp130 involved in its interaction with the IL-6-IL-6R complex. Precise identification of this(ese) epitope(s) would be useful to better understand the mechanisms of the IL-6 signalling.

MBR rearrangement and P-glycoprotein expression are not independent prognostic factors like p53 protein in malignant lymphoma.

Non-Hodgkin's lymphomas (NHL) are B-cell malignancies which generally present molecular abnormalities, such as bcl-2 translocation t(14; 18) predominantly in the follicular subgroup. Other molecular events have been described in NHL, including p53 gene mutation and overexpression of one chemoresistance mechanism, the multidrug resistance system, P-glycoprotein (MDR 1/P-gp). In this study, we analysed samples from 44 NHL patients with the presence of the bcl-2 major breakpoint region (MBR) rearrangement in 29 and without in 15. Immunochemical analysis revealed that 39 samples were positive for bcl-2 protein expression in tumoral cells (88.6%). Seventeen (38.6%) patients expressed P-gp and 9 (20.5%) expressed p53 proteins. Eleven patients expressed both bcl-2 and P-gp proteins, four expressed bcl-2 and p53 proteins whereas four expressed bcl-2, p53 and P-gp proteins. Our results confirm the importance of p53 expression as a key prognostic factor, and no objective response (OR) was found in patients with p53 positivity. MBR rearrangement was not associated with poor response to chemotherapy (62.1% OR in MBR positive patients v. 60% OR in MBR negative patients). The clinical impact of P-gp cannot be identified because no relationship was observed between P-gp expression and prognosis (58.8% OR in P-gp positive patients v. 63% OR in P-gp negative patients).

Human interleukin-6 receptor super-antagonists with high potency and wide spectrum on multiple myeloma cells.

Interleukin-6 (IL-6) is the major growth factor for myeloma cells and is believed to participate in the pathogenesis of chronic autoimmune diseases and postmenopausal osteoporosis. IL-6 has been recently shown to possess three topologically distinct receptor binding sites: site 1 for binding to the subunit specific chain IL-6R alpha and sites 2 and 3 for the interaction with two subunits of the signaling chain gp130. We have generated a set of IL-6 variants that behave as potent cytokine receptor super-antagonists carrying substitutions that abolish interaction with gp130 at either site 2 alone (site 2 antagonist) or at both sites 2 and 3 (site 2 + 3 antagonist). In addition, substitutions have been introduced in site 1 that lead to variable increases in binding for IL-6R alpha up to 70-fold. IL-6 super-antagonists inhibit wild-type cytokine activity with efficacy proportional to the increase in receptor binding on a variety of human call lines of different origin, and the most potent molecules display full antagonism at low molar excess to wild-type IL-6. When tested on a representative set of IL-6-dependent human myeloma cell lines, although site 2 super-antagonists were in general quite effective, only the site 2 + 3 antagonist Sant7 showed antagonism on the full spectrum of cells tested. In conclusion, IL-6 super-antagonists are a useful tool for the study of myeloma in vitro and might constitute, in particular Sant7, effective IL-6 blocking agents in vivo.

A plasmocyte selective monoclonal antibody (B-B4) recognizes syndecan-1.

We developed a new monoclonal antibody. B-B4, which specifically identifies human plasma cells. It strongly reacts with all multiple myeloma cell lines and with malignant plasma cells of all tumour samples of the multiple myeloma patients tested. B-B4 does not react with any peripheral blood, bone marrow or tonsil cells. Cloning of the B-B4 antigen reveals that the monoclonal antibody recognizes syndecan-1. It appears that the monoclonal antibody B-B4 is a suitable marker for human plasmocyte identification among haemopoietic cells and a useful probe for the diagnosis of haematological malignancies. Furthermore, this monoclonal antibody can be used for depletions prior to CD34 grafting.