Curative antitumor immune response is optimal with tumor irradiation followed by genetic induction of major histocompatibility complex class I and class II molecules and suppression of Ii protein

Transfecting genes into tumors, to upregulate major histocompatibility complex (MHC) class I and class II molecules and inhibit MHC class II associated invariant chain (Ii), induces a potent anti-tumor immune response when preceded by tumor irradiation, in murine RM-9 prostate carcinoma. The transfected genes are cDNA plasmids for interferon-gamma (pIFN-gamma), MHC class II transactivator (pCIITA), an Ii reverse gene construct (pIi-RGC), and a subtherapeutic dose of adjuvant IL-2 (pIL-2). Responding mice rejected challenge with parental tumor and demonstrated tumor-specific cytotoxic T lymphocytes (CTLs). We have extended our investigation to determine the relative roles of each one of the four plasmids pIFN-gamma, pCIITA, pIi-RGC, and pIL-2 in conjunction with radiation for the induction of a curative immune response. Upregulation of MHC class I with pIFN-gamma or class II with pCIITA, separately, does not lead to a complete response even if supplemented with pIL-2 or pIi-RGC. An optimal and specific antitumor response is achieved in more than 50% of the mice when, after tumor irradiation, tumor cells are converted in situ to a MHC class I+/class II+/Ii- phenotype with pIFN-gamma, pCIITA, pIi-RGC, and pIL-2. We demonstrate further that both CD4+ helper T cells and CD8+ cytotoxic T cells are essential for induction of an antitumor response because in vivo depletion of either subset abrogates the response. The radiation contributes to the gene therapy by causing tumor debulking and increasing the permeability of tumors to infiltration of inflammatory cells.     

Correlation between Postoperative Weight Loss and Diabetes Mellitus Remission: A Meta-Analysis

Objective

This meta-analysis was conducted to determine the effect of percent excess weight loss (%EWL) after bariatric surgery on diabetes remission.

Methods

The Cochrane Library, PubMed, MEDLINE, Embase, and CINAHL were searched. All reports on %EWL involving humans and published in English between 1 January 1992 and 1 September 2013 were included in the analysis.

Results

Eight studies involving 1,247 patients who underwent bariatric surgery were selected. %EWL was positively associated with remission rate (WMD?=?11.15, 95 % CI: 6.73–15.56, p?Conclusions Patients with extensive weight loss were more likely to achieve T2DM remission after bariatric surgery. Further randomized controlled trials (RCTs) with uniform remission criterion should be performed to provide more reliable evidence.     

一次性根治术治疗高位复杂性肛瘘的临床观察

为观察一次性根治术治疗高位复杂性肛瘘的临床疗效,将37例高位复杂性肛瘘患者采用一次性根治术治疗,均一次性治愈,治愈率100％,无并发症和后遗症。结果表明,采用一次性根治术治疗高位复杂性肛瘘疗效确切,值得推广。     

Morphological and clinical feasibility of C3 pedicle screw instrumentation in patients with congenital C2–3 fusion

Purpose

Congenital C2–3 fusion (C2–3CF) is often involved in patients with atlantoaxial dislocation, and posterior occipitocervical fixation surgery is usually required. Hypoplasia of C2 pedicle is common in such patients, making C2 pedicle screws (PS) instrumentation inapplicable. Because of congenital fusion, C3PS instrumentation would be an ideal alternative for it will not sacrifice an additional motion segment; however, the morphological and clinical feasibility has not been previously reported.

Methods

We included 42 C2–3CF patients to this study and evaluated pedicle trajectories of C2 and C3 using a three-dimensional CT. Clinical applications of C3PS instrumentation were evaluated and followed.

Results

Among the 42 patients, 23 (54.8 %) and 8 (19.0 %) had C2 and C3 pedicle trajectory diameters <4.0 mm, respectively. The bisection line of the fused C2–3 lamina was used to represent the superior border of C3 articular mass; the entry point of C3 pedicle was located at 3 mm inferior to the assumed superior border and 3.2 mm medial to the lateral border. Bilateral C3PS instrumentations were successfully adopted in 22 patients. No spinal cord or vertebral artery injury occurred; postoperative CT showed a trajectory breach rate of 17.4 % for C3PS. After mean of 3.6-year follow-up, no implant failure was documented.

Conclusions

C3PS instrumentation is morphologically and clinically feasible for a large proportion of patients with C2–3CF and can serve as another reliable alternative for C2PS instrumentation. Preoperative evaluation of pedicle trajectory of C2–3CF with three-dimensional CT is highly valuable in the choice of proper fixation methods.     

Radiological studies on the best entry point and trajectory of anterior cervical pedicle screw in the lower cervical spine

Objective

To explore the best entry point and trajectory of anterior cervical transpedicular screws in the lower cervical spine by radiological studies, and provide reference for clinical application.

Methods

Fifty patients were scanned by computed tomography and confirmed no obvious defect of the cervical spine. On horizontal axis, camber angle (α) and axial length (AL) were measured from C₃ to C₇. On sagittal view, the cranial or caudal angle (β) and sagittal length (SL) were also measured from C₃ to C₇. On the sagittal and horizontal planes vertebrae were respectively divided into four areas, ordered 1–4, on the anterior side of the pedicle. The areas and angles of pedicle intersect into the vertebral body were recorded. We inserted six anterior pedicle screws into the lower cervical spine of three patients by this technique.

Results

On transverse plane, camber angle (α) of C₃–C₅ increased gradually, while it decreased from C₅ to C₇. On sagittal view, C₃ and C₄ pedicles showed cranial tilting, while C₅ to C₇ were caudally tilted. AL and SL values increased gradually from C₃ to C₇. The number of the intersections of C₃–C₇ in each area was also different. Six pedicle screws of three cases were inserted into the lower cervical spine with proper placement and no complications.

Conclusion

Anterior transpedicular screw (ATPS) is a theoretically feasible option for internal fixation. The technique described in this paper was subsequently used in three patients without complication. Future improvement of ATPS insertion remains necessary for this technically demanding procedure.     

新型咽鼓管吹张法在儿童分泌性中耳炎的应用

目的探讨新型咽鼓管吹张法对儿童分泌性中耳炎的治疗效果。方法将90例分泌性中耳炎患儿按照随机数字表分为对照组和观察组各45例。观察组采用新型咽鼓管吹张法治疗,对照组采用传统的波氏球咽鼓管吹张法治疗,观察记录治疗3个月后两组患儿声阻抗检测变化及患儿的舒适度。结果治疗3个月后两组患儿的声阻抗检测结果及舒适度比较,差异有统计学意义(P0.05,P0.01)。结论新型咽鼓管吹张法能提高患儿操作时的舒适度,增加患儿治疗的信心,提高疾病治疗效果。     

Characters and influential factors of vascular remolding after native arteriovenous fistula

Objective To finding out the characters of vascular remolding after the establishment of native arteriovenous fistula on the wrist, and exploring the influential factors.MethodsDoppler ultrasound was used to monitor the diameter of cephalic vein, brachial artery, radial artery and ulnar artery at the time before the surgery and one day, one week, two weeks, four weeks and eight weeks after the surgery respectively. The tendency of the diameter change was analyzed. ResultsTwenty eight patients completed the whole monitor session, in which eleven were female. The average age of those patients was (53.68 ± 2.61) years old. Twelve of them were diabetic nephropathy. The diameters of all vessel were increased more rapidly at the first day than any other days after surgery(all P＜0.01). The patients were divided into two groups depending on whether diabetic nephropathy. No significant difference was found between the two groups on the tendency of diameter change in cephalic vein and brachial artery (all P ﹥ 0.05). However, the tendency of diameter change in radial artery and ulnar artery was statistically significant difference between the two groups (all P＜0.05). ConclusionsCephalic vein, brachial artery, radial artery and ulnar artery are all apparently dilated on the first day after the surgery. The vascular dilation and diameter increasing become much slower after the period, the diameter tend to be stable. The primary diseases may affect the tendency of the diameter change in radial artery as well as ulnar artery.     

Expression of NLRP3 inflammasome in the BSA-overloaded rats kidney

Objective To observe NLRP3 inflammasome expression and inflammatory cells infiltration in the BSA-overloaded rats kidney, and to investigate the potential mechanism of renal injury induced by proteinuria. Methods After unilateral right nephrectomy, eighteen healthy male Wistar rats were randomly divided into two groups: protein overload nephropathy model group (n=10), treated with intraperitoneal injections of bovine serum albumin (BSA); control group (n=8), treated with intraperitoneal injections of 0.9% saline for 9 weeks. Body weigh were measured every week and 24 h urine were collected in 0, 2, 5, 7, 9 week. The plasma levels of blood total protein (TP), albumin (Alb), serum creatinine (Scr) and blood urea nitrogen (BUN) were determined by automatic analyzers. Renal pathological changes were evaluated by PAS and Masson stains. Immunohistochemical staining was used to detect the expression of NLRP3, caspase-1, IL-1β, and IL-18, as well as the types of inflammatory cells. The NLRP3, caspase-1, IL-1β, and IL-18 protein and mRNA levels were also analyzed by Western blot and real-time PCR in two groups. Results It was found that there was a significant increase of proteinuria and BUN in model group compare to that in control group (all P＜0.05). However, there were no significant changes in body weight, TP, Alb and Scr between the two groups. Morphological study demonstrated that renal tubular epithelial cell injury, proteinaceous casts in tubular lumen, accompanying with the dominant macrophages and lymphocytes infiltration in interstitium in model group. The immunohistochemistry showed that there were more T (CD3+), B cells (CD20+) and macrophages (CD68+) in renal interstitium in model group than that in control group (P＜0.05). Tubulointerstitial injury score was higher than that of the control group (P＜0.05). Immunohistochemistry, Western blot and real-time PCR all showed that the expression of NLRP3, caspase-1, IL-18 and IL-1 β were significantly increased compared to those in control group (P＜0.05). Furthermore, there were significant correlations between proteinuria and IL-1β/IL-18 expression (P＜0.05). Conclusion NLRP3 inflammasome activation is involved in tubulointerstitial inflammation caused by proteinuria.