Effects of 1α, 25-dihydroxyvitamin D3 on memory CD4+ T cells of focal proliferative IgA nephropathy

Objective To explore the effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on memory CD4+ T cells of focal proliferative IgA nephropathy (IgAN）patients. Methods (1) Total of twenty incipient focal proliferative IgAN patients (Lee classification: Ⅲ level) were chosen as IgAN group and 20 healthy volunteers were chosen as healthy control group. The level of serum 1,25(OH)2D3 was measured by radioimmunoassay (RIA). Peripheral blood mononuclear cells (PBMCs) were separated by the method of Ficoll density gradient centrifugation and were stimulated with anti-CD3/anti-CD28 in the absence or presence of various concentrations of 1,25(OH)2D3, Dexamethasone(DEX) and 1,25(OH)2D3 and DEX combined. PBMCs were cultured for 72 hours and the levels of IFN-γ, IL-4, IL-17A, Foxp3 were measured by flow cytometry(FCM), standing for the levels of Th1, Th2, Th17, Treg. (2) IgAN group was divided into two subgroups (proteinuria＜1 g/24 h subgroup, proteinuria≥1 g/24 h subgroup), then the serum levels of 1,25(OH)2D3, IFN-γ, IL-4, IL-17A, Foxp3 were compared. Results Compared with healthy control group, serum 1,25(OH)2D3 level of IgAN group was significantly lower (P＜0.05). Serum 1,25(OH)2D3 level in proteinuria≥1 g/24 h subgroup was significantly lower than proteinuria＜1 g/24 h subgroup and healthy control group (P＜0.05). The level in proteinuria＜1 g/24 h subgroup was lower than healthy control group, but the difference was not statistically significant (P＞0.05). (2) The levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4, IL-17A/Foxp3 in IgAN group increased significantly compared with healthy control group (all P＜0.05), and the level of Foxp3 decreased significantly (P＜0.05). The level of IL-4 also increased, but the difference was not statistically significant (P＞0.05). The levels of IFN-γ and IL-17A and the ratio of IL-17A/Foxp3 in proteinuria≥1 g/24 h subgroup increased significantly, and the level of Foxp3 decreased significantly, compared with urinary protein＜1 g/24 h subgroup and healthy control group (P＜0.05). The ratio of IFN-γ/IL-4 in proteinuria≥1 g/24 h subgroup and proteinuria＜1 g/24 h subgroup all increased, compared with healthy control group, and the ratio in proteinuria≥1 g/24 h subgroup increased significantly (P＜0.05). There was no significant difference in the level of IL-4 among all groups. (3) After treatment with 1,25(OH)2D3, the levels of IFN-γ and IL-17A and the ratios of IFN-γ/IL-4 and IL-17A/Foxp3 decreased significantly, and the level of Foxp3 increased significantly (P＜0.05), and these effects were more obvious as the increase of the drug concentration. The level of IL-4 did not change significantly. The combination of 1,25(OH)2D3 and DEX had a synergistic inhibition on the production of IFN-γ, IL-4, IL-17A, and the ratios of IFN-γ/IL-4 and IL-17A/Foxp3, and had a synergistic promotion on the production of Foxp3. Conclusions There is a certain extent of vitamin D deficiency in focal proliferative IgAN patients, which may be associated with the severity of proteinuria. The disorder of immunomodulatory effects of memory CD4+ T cell might exist in the patients of focal proliferative IgAN. 1α,25-dihydroxyvitamin D3 might have beneficial effects on the immunoregulation of memory CD4+T cells of focal proliferative IgAN patients.     

Association between nutrition and peripheral artery disease in continuous ambulatory peritoneal dialysis patients

Objective To investigate the association between nutrition and peripheral artery disease (PAD) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods One hundred and two stable CAPD patients from a single center were enrolled in this cross-sectional study. Automatic ankle-brachial index (ABI) measuring system was applied to examine ABI. Patients were divided into PAD group (ABI＜0.9) and non-PAD group (ABI≥0.9). Clinical data were collected. Biochemical parameters were detected. Nutritional status was evaluated by serum albumin, handgrip strength (HGS) and subjective global assessment (SGA). Logistic regression analysis was performed to estimate the association of PAD with each nutritional marker as well as other potential risk factors. Results The incidence of PAD was 23.53% (24/102). ABI was significantly lower in patients with malnutrition as compared to those without malnutrition [(0.72±0.21) vs (1.04±0.14), P＜0.01]. Compared with non-PAD patients, serum albumin (P＜0.01), HGS (P＜0.01), diastolic blood pressure (P＜0.05), serum creatine (P＜0.05)、blood urine nitrogen (P＜0.01) were significantly decreased, but age (P＜0.01), the incidence of malnutrition [SGA, P＜0.01], diabetic status (P＜0.01), cardiovascular disease history (P＜0.01) were significantly increased in PAD patients. Logistic regression analysis showed that serum albumin (OR=0.762, 95％CI：0.611-0.948, P=0.015), HGS (OR=0.988, 95％CI：0.979-0.997, P=0.013) were independent protective factors for PAD, malnutrition [(SGA), OR=21.101, 95％CI：5.008-88.901, P＜0.01] was independent risk factor for PAD in CAPD patients. Conclusions The PAD incidence of CAPD patients in our center is 23.53%. Nutrition is independent factor associated with PAD in CAPD patients.     

DC-SIGN expression on podocytes and its role in immune and inflammatory responses of lupus nephritis

Objective To explore the expression of DC-SIGN, the phenotype of dendritic cells (DCs), on podocytes, and its role in immune and inflammatory responses of lupus nephritis (LN). Methods DC-SIGN and IgG1 expression in renal tissues of lupus nephritis patients were observed by immunohistochemistry and immunofluorescence. The 4-week old LN mice were randomly divided into the experimental group and the intervention group. C57BL/6J mice were used as normal control group. Mice of the intervention group were injected anti-DC-SIGN antibody at 6-week old. Mice were sacrificed at 16, 20, 24, 28-week old respectively, to observe the mice renal function and pathological changes. And DC-SIGN and IgG1 expression in renal tissue were observed by immunohistochemistry and immunofluorescence. In addition, mice podocytes were treated with serum of LN mice. Flow cytometry was used to investigate the expression of MHC II, CD80 and DC-SIGN expression on podocytes. Mixed lymphocyte reaction was used to detect the ability of stimulating T cells proliferation. IFN-gamma and IL-4 in supernatant were determined by ELISA. Results (1) Expression of DC-SIGN and IgG1 was found in glomeruli of lupus nephritis patients. (2) Accompanied by increased proteinuria of LN mice from 20-week old (P＜0.01), DC-SIGN and IgG1 expression was found in glomeruli, and the renal function deteriorated up to 24 week-old (P＜0.01). Mice with anti-DC-SIGN antibody intervention appeared reduced proteinuria and remission of renal function (P＜0.01). (3) After stimulated by serum of LN mice, the expression of DC-SIGN, MHC II and CD80 was up-regulated, stimulation of T cell proliferation was enhanced (P＜0.01), and IFN-gamma/IL-4 ratio increased (P＜0.01). Anti-DC-SIGN antibody treatment down-regulated the expressions of DC-SIGN, MHC II and CD80 on podocytes, decreased the ability of stimulating T cell proliferation and lowered the ratio of IFN-gamma/IL-4 (P＜0.01). Conclusions Podocytes in lupus nephritis can play DC-like function through the expression of DC-SIGN, which may be involved in immune and inflammatory responses of renal tissue. However, inhibiton of DC-SIGN can depress immune function of podocytes and have prevention and treatment effect.     

Metacarpal fractures: treatment and complications

Metacarpal fractures comprise between 18–44 % of all hand fractures. Non-thumb metacarpals account for around 88 % of all metacarpal fractures, with the fifth finger most commonly involved [19]. The majority of metacarpal fractures are isolated injuries, which are simple, closed, and stable. While many metacarpal fractures do well without surgery, there is a paucity of literature and persistent controversy to guide the treating physician on the best treatment algorithm. The purpose of this article is to review non-thumb metacarpal anatomy and treatment protocols for nonoperative management of stable fractures, and compare existing literature on surgical techniques for treatment of acute fractures and complications.     

A comparative study between local bone graft with a cage and with no cage in single posterior lumbar interbody fusion (PLIF): a multicenter study

Objective

A retrospective study was performed to compare the clinical and radiological results between local bone graft with a cage and without using a cage in patients treated with posterior lumbar interbody fusion surgery.

Methods

A total of 115 consecutive patients who underwent PLIF in three institutions were evaluated from December 2005 to December 2010. 53 patients received PLIF with local bone graft combined with using one PEEK cage, and 62 patients received the PLIF with local bone graft without using a cage. The clinical data and perioperative complications of the patients in the two groups were recorded. Preoperative and postoperative radiographs were taken to calculate the disc height and the interbody bony fusion rate. Functional outcome was assessed using the Kirkaldy-Willis criteria at the follow-up time. The results between the cage group and no cage group were compared.

Results

The mean follow-up time was 19 months in no cage group and 18.5 months in cage group (P = 0.716). 20.9 % of patients (13 cases) in no cage group and 20.7 % of patients (11 cases) in cage group developed surgical complications perioperatively (P = 0.978). 51.6 % patients in no cage group got excellent functional outcome at the final follow-up while 54.7 % patients in cage group (P = 0.944). The mean interbody bony fusion time was 7.5 ± 4.5 months in no cage group and 8 ± 3.5 months in cage group (P = 0.841). According to the radiographs measurement, no significant difference was found for the disc height at each level between the two groups at the final follow-up.

Conclusion

Local bone graft without a cage is as beneficial as that with a cage for PLIF. Comparing with local bone graft using a single cage, we believe that the purely local bone graft is a more ideal way in single PLIF.     

Epsilon-aminocaproic Acid Improves Postrecirculation Hemodynamics by Reducing Intraliver Activated Protein C Consumption in Orthotopic Liver Transplantation

Background

Activated protein C (APC) is related to regulating the inflammatory response and hemodynamic stability upon reperfusion in cardiac operations and orthotopic liver transplantation (OLT). Epsilon-aminocaproic acid (EACA) is frequently used to treat fibrinolysis during OLT. It also has inhibitory effects related to the inflammatory response. However, it remains to be determined whether EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion during OLT.

Methods

Fifty-nine recipients were randomized to receive either EACA (150 mg kg^?1 given intravenously prior to incision, followed by 15 mg kg^?1 h^?1 infusion until 2 h after the graft reperfusion) or the same volume of saline. Blood samples to assess plasma APC and protein C were obtained immediately before and after reperfusion from the inferior caval effluent or the portal veins for calculation of transliver differences (Δ). Hemodynamics and vasoactive medication use during the reperfusion period were observed in both groups.

Results

No transhepatic changes in protein C were found in either group. Immediately after reperfusion, a marked intraliver consumption of APC was noted in all recipients (P < 0.001), and intraliver consumption of APC in the control group was greater than that in the EACA-treated group (P < 0.05). Fewer requirements for vasoactive medication use after reperfusion and better initial graft function were noted in the EACA-treated group (P < 0.05).

Conclusions

EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion and initial graft function during OLT.     

Lymph Node Counts and Ratio in Axillary Dissections Following Neoadjuvant Chemotherapy for Breast Cancer: A Better Alternative to Traditional pN Staging

Background

Neoadjuvant chemotherapy (NCT) for breast cancer might change the number of involved and detected nodes in axillary lymph node dissections (ALND). In this study, we analyzed whether the number of dissected nodes and the lymph node ratio (LNR, defined as the proportion of involved nodes in dissected nodes) would have a better prognostic value than traditional pN staging.

Methods

A total of 569 patients with stage II, III breast cancer were included in this retrospective study. All patients underwent a median of three cycles of NCT followed by mastectomy and ALND. Clinical and pathological variables were investigated using univariate and multivariate survival analyses.

Results

In post-NCT node-negative (LN?) patients, those with 4–9 dissected nodes experienced a significantly lower relapse-free survival (RFS) compared with those with 10 or more dissected nodes (hazard ratio = 0.19, 0.41, for 10–19 nodes, 20+ nodes, respectively; 4–9 nodes as the reference; P = 0.002). In post-NCT node-positive (LN+) patients, a lower LNR was correlated with a better RFS on multivariate analysis, and pN staging failed to show independent prognostic significance when the LNR was included in the Cox regression model (hazard ratio = 4.2, 2.97, 2.24, and 1.68 for LNR 81–100, 61–80, 41–60; and 21–40 %, respectively; LNR 0–20 % as the reference. P < 0.001). In addition, there were significant differences in the estimated 5-year RFS for pN1 (P = 0.043) and pN3 patients (P = 0.03) among the different LNR subgroups.

Conclusions

Our study has provided new evidence that the number of dissected nodes (in LN? patients) and the LNR (in LN+ patients) might be a complementary or alternative method to traditional pN staging when evaluating disease after primary treatment.     

Significance of the mass-compression effect of postlaminectomy/laminotomy fibrosis on histological changes on the dura mater and nerve root of the cauda equina: an experimental study in rats

Purpose The precise mechanism and pathological role of postlaminectomy/laminotomy fibrosis (PLF) in postoperative neurological deficits have not been established. Many studies use magnetic resonance imaging (MRI) to prove that there is no consistent correlation between PLF and postoperative neurological deficits and back pain (PNDBP). Therefore, we assumed that the direct-compression effect may not be the only factor but that other neurological deficits associated with pathological mechanisms should exist and need more investigation. The purpose of this study was to compare over time the differences and changes in histopathological properties of PLF in rats.Methods We used a rat model with walking-track analysis for neurologic evaluation, grading scale to evaluate PLF, histomorphometric measurements of dura sac diameter, and histological tissue reactions (dura mater and spinal rootlets) juxtaposed to the postlaminectomy/laminotomy defect. The 54 adult Sprague–Dawley rats were divided into laminotomy (n = 18), laminectomy (n = 18), and sham-operation groups (n = 18). All groups were subdivided into three equal subgroups based on different postoperative time points (1, 2, and 3 months). All sections of vertebral column were stained with hematoxylin and eosin and with Masson’s trichrome.Results The results showed that only a slight compression effect reflected by nonsignificant changes in the maximum anterior-posterior diameters within the dura sac, in the walking tract test, and increased grades of PLF over time. In addition, significant pathological inflammatory changes, such as thickening of the dura mater, axonal swelling, and neovascularization, were found in the post-laminectomy/laminotomy groups at each time point.Conclusion Laminectomy-/laminotomy-related inflammation may lead to PLF, and these pathological changes may be the main cause of postoperative neurological deficits. These findings show that research on preventing PLF should include perioperative modulation of inflammatory reactions induced by laminectomy/laminotomy.     

模拟高空跳伞着陆状态下踝关节动态角速度与垂直反作用力的测定

 目的 通过模拟高空跳伞着陆训练环境测定不同高度半蹲式跳伞着陆状态下的踝关节角速度、地面垂直反作用力,为预防跳伞着陆踝部损伤提供生物力学依据。方法 募集18名健康志愿者,包括空军地勤人员9名、职业跳伞人员9名。两组受试者身高、体重的差异无统计学意义。受试者分别从30 cm和60 cm高的跳台以半蹲式跳伞着陆并腿姿势跳落到测力台上。高速摄像机记录着陆过程,测定踝关节跖屈角位移及时间、地面垂直反作用力,计算角速度,分析踝关节动态角位移、角速度、垂直作用力与不同高度的相关性。结果 30 cm高度：地勤人员组与跳伞运动员组踝关节角位移分别为25.73°±8.13°、20.05°±12.27°,垂直反作用力分别为（3 372.4±748.6） N、（5 181.5±1 726.2） N,受力时间分别为（0.049±0.015） s、（0.012±0.004） s,缓冲时间分别为（1.397±0.746） s、（1.737±0.451） s,差异均有统计学意义。60 cm高度：地勤人员组与跳伞运动员组踝关节角速度分别为（25.45±15.01） °/s、（16.51±4.18） °/s,垂直反作用力分别为（4 616.0±1124.7） N、（7 119.5±2 307.4） N,受力时间分别为（0.048±0.013） s、（0.015±0.006） s,缓冲时间分别为（0.922±0.347） s、（1.617±0.547） s,差异均有统计学意义。结论 从不同的测试高度跳下,跳伞运动员组的地面垂直反作用力大于地勤人员组,但角速度及角位移小于地勤人员组。对比地勤人员组,跳伞运动员组的受力时间短而缓冲时间更长。