To explore the effect of low intensity pulsed ultrasound stimulation (LIPUS) on the maturation of regenerate bone in a rabbit limb lengthening model.Sixty skeletal mature female New Zealand white rabbits were randomly divided into an LIPUS treatment group and a control group. All rabbits were underwent mid-diaphyseal tibial osteotomy and immobilized in an Orthofix M103 Mini lengther. Gradual distraction at 0.5 mm every 12 h for 10 d was performed at day 7 postoperatively. A 4-week course of LIPUS treatment group was applied over the distraction site for 20 min daily starting immediately after the completion of the distraction only for the treatment group. Rabbits were euthanized and the mid-diaphyseal tibia was harvested for evaluation at 4, 8, and 12 wk after the completion of the bone lengthening protocol. Radiographic analysis was performed to study the formation of bone callus using the ImageJ software at 12 wk after the completion of the bone lengthening protocol. Bone mineral density (BMD) of regenerate bone was measured by Dual energy X-ray absorptiometry (DEXA). Torsional testing to failure was performed on the tibia specimens at 8 and 12 wk after the completion of the bone lengthening protocol.Radiographic measurement showed higher relative gray scale of bone callus in the LIPUS group than that in the control group at 12 wk (P<0.05). BMD in the LIPUS group was significantly higher than that in control group at 8 and 12 wk (P<0.05). Biomechanical testing showed that the ultimate torque, ultimate torsional stiffness, and energy absorption at failure of regenerated bone at 8 and 12 wk in the LIPUS treatment group were better than those in the control group (P<0.05).LIPUS as a biophysical stimulation may accelerate the formation and maturation of regenerate bone in rabbit tibia lengthening model.
Abstract Tumor progression locus 2 (TPL2; also known as MAP3K8) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that phosphorylates the MAPK kinases MEK1 and MEK2 (MEK1/2), which, in turn, activates the MAPKs extracellular signal–regulated kinase 1 (ERK1) and ERK2 (ERK1/2). We describe an additional conserved and critical role for TPL2 in mediating the effector functions of myeloid cells including neutrophils, macrophages, and microglia through the activation of the p38 MAPK signaling pathway. Gene expression profiling and functional studies of neutrophils and monocytes revealed a MEK1/2-independent branch point downstream of TPL2 in neutrophils. Genetic ablation of the catalytic activity of TPL2 or therapeutic intervention with TPL2-specific inhibitors reduced inflammatory responses in vitro and in vivo. Besides myeloid cells, TPL2 also plays critical roles in fibroblast synoviocytes, indicating a potential role in rheumatoid arthritis via stromal cells.
To compare the effectiveness of microdiscectomy and macrodiscectomy on the single-level lumbar disc protrusion (LDP).Between November 2002 and October 2005, 241 patients with LDP underwent 2 surgical procedures: microdiscectomy (group A, 93 cases) and macrodiscectomy (group B, 148 cases). All patients had single-level LDP. In group A, there were 51 males and 42 females with an average age of 32.3 years (range, 18-47 years); there were 23 cases of protrusion, 52 cases of prolapse, and 18 cases of sequestration with an average disease duration of 8.5 months (range, 1-18 months), including 8 cases at L2,3 level, 11 cases at L3,4 level, 35 cases at L4,5 level, and 39 cases at L5, S1 level. In group B, there were 81 males and 67 females with an average age of 31.8 years (range, 16-50 years); there were 37 cases of protrusion, 85 cases of prolapse, and 26 cases of sequestration with an average disease duration of 9.3 months (range, 1-20 months), including 9 cases at L2,3 level, 15 cases at L3,4 level, 63 cases at L4,5 level, and 61 cases at L5, S1 level. There was no significant difference in age, sex, segment level, type, or disease duration between 2 groups (P > 0.05).Immediate back and sciatic pain relief was achieved in 225 (93.4%) patients after operation. The satisfactory rates were 91.4% in group A and 87.8% in group B at 1 week after operation, showing no significant difference (P > 0.05). The length of incision, amount of bleeding, amount of drainage, and hospitalization time in group A were significantly fewer than those in group B (P < 0.05); while the operative time in group A was longer than that in group B, but showing no significant difference (P > 0.05). Dural laceration occurred in 4 cases of group A and 5 cases of group B, superficial infections of incision occurred in 5 cases of group B and intervertebral space infections occurred in 4 cases of group B, and epidural hematoma occurred in 1 case of group A. The perioperative complication rate (5.4%, 5/93) in group A was significantly lower (P < 0.05) than that in group B (9.5%, 14/148). LDP recurred in 4 cases (4.3%) of group A and in 9 cases (6.1%) of group B postoperatively, showing no significant difference (P > 0.05); of them, 11 cases received second operation and 2 cases were treated conservatively. All cases were followed up 36-77 months (mean, 51.4 months). There were significant differences in visual analog scale (VAS) and Oswestry disability index (ODI) between 2 groups at the last follow-up and preoperation (P > 0.05), but there was significant difference in VAS at 1 week postoperatively between 2 groups (P < 0.05). VAS and ODI were obviously improved at 1 week and last follow-up when compared with preoperation (P < 0.05). There was no significant difference in the improvement rates of VAS and ODI between 2 groups at last follow-up (P > 0.05). According to clinical evaluation of Modified Macnab criteria, the excellent and good rate was 90.3% in group A and 86.5% in group B at final follow-up (P > 0.05).Both macrodiscectomy and microdiscectomy are effective for LDP, furthermore microdiscectomy is less invasive than macrodiscectomy. Microdiscectomy is recommended to treat single-level LDP.
Previous research has shown that the effectiveness of selecting filter set from a large set of commercial broadband filters by vector analyzing method based on maximum linear independence (MLI). However, the traditional MLI is suboptimal due to predefining the first filter of the selected filter set being the maximum ℓ2 norm among all those of the filters. An exhaustive imaging simulation is conducted to investigate the features of the most competent filter set. In the simulation, every filter in a subset of all the filters is selected serving as the first filter in turn. From the results of the simulation, we found there are remarkable characteristics for the most competent filter set. Besides smaller condition number, the geometric features of the best-performed filter set comprise the distinct peak of the transmittance of the first filter, the generally uniform distributing of the peaks of the transmittance curve of the filters, the substantial overlapping of the transmittance curves with those of the adjacent filer sets. Therefore, the best-performed filter sets can be decided intuitively by simple vector analyzing and just a few experimental verifications. This work would be useful for optimizing spectral sensitivity of broadband multispectral imaging sensors or SFA sensors.
Abstract CD8 tissue-resident memory T (TRM) cells provide front-line protective immunity at barrier tissues. Understanding TRM cell development will provide significant insights for vaccine design targeting infections and cancers at barrier tissues. Here, we demonstrate that pathogen-induced inflammation and pathogen-derived cognate antigen had minimal impact on intestinal CD103+ TRM cell differentiation. Instead, T cell priming in the mesenteric lymph nodes (MLN) was the principal determinant of CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were incapable of differentiating into intestinal CD103+ TRM cells. Foodborne rechallenge of spleen-primed memory T cells was unable to induce intestinal CD103+ TRM cell differentiation, suggesting initial priming promoted a lasting fate. Moreover, both CD103− and CD103+ naïve T cells were highly efficient in differentiating into CD103+ TRM cells in the intestine after priming in the MLN, suggesting preconditioning of naïve T cells by TGF-b during homeostasis had little impact on intestinal CD103+ TRM cell differentiation. We further demonstrate that MLN priming initiated a CD103+ TRM cell program before effector T cell migration to the intestine and promoted CD103+ TRM cell differentiation in situ in part by promoting CCR9 expression and the ability to respond to TGF-b in a cell-extrinsic manner. Thus, mesenteric lymph node priming is specialized to license intestinal CD103+ CD8 TRM cell development.
The repair of rotator cuff injury is affected by lifestyle and metabolic factors. Intermittent fasting (IF) can promote repair of damaged tissue by regulating intestinal flora, which provides an idea of therapy for rotator cuff injury. The aim of this study was to investigate the effects of fasting on rotator cuff repair after injury, and the role of intestinal flora or a single strain in this process.Mice underwent rotator cuff injury were treated with intermittent fasting or fed ad libitum. Fasting began one month before surgery and continued until euthanasia. Fresh feces were collected at 2 weeks before surgery, on the day of surgery, and 2, 4, 8 weeks postoperatively for 16S rRNA microbiome sequencing. Supraspinatus tendon-humerus (SSTH) complex was collected at 2, 4 and 8 weeks after surgery. Live parabacteroides distasonis (Parabacteroides distasonis) was used for repair of rotator cuff injury, with equal amount of pasteurized P. distasonis (KPD) or sterile anaerobic phosphate buffer saline (PBS) as control. Biomechanical, radiological, histological analysis were used to assess the effect of rotator cuff repair.Biomechanical, radiological and histological analysis indicated that intermittent fasting significantly promoted the repair of rotator cuff injury in the early postoperative period (P ＜ 0.05), but significantly inhibited the repair of rotator cuff injury at 4 weeks postoperatively (P ＜ 0.05). 16S rRNA Microbiome sequencing result showed that P. distasonis was the species with the most obvious changes in intestinal flora of mice after fasting. The results of tensile test, X-ray analysis and histological analysis indicated that the live P. distasonis (LPD) significantly impaired the biomechanical properties, bone regeneration and fibrocartilage regeneration of enthesis postoperatively (P ＜ 0.05).Intermittent fasting promoted repair of rotator cuff injury in the early postoperative period by regulating the gut microbiota, in which P. distasonis played an important role.Intermittent fasting (IF) may be a beneficial lifestyle for the repair of rotator cuff injury in the early postoperative period in clinical, and the influence of a certain strain on the repair of rotator cuff injury may also provide an idea for the treatment of rotator cuff injury in the future.
Anterior talofibular ligament (ATFL) injury is one of the most common injuries in sports medicine, resulting in chronic lateral ankle instability (CLAI). The patients' daily life may be seriously affected by ankle osteoarthritis and other irreversible damages, if the ATFL injury is not treated in time and drags on. Patients with ATFL injury who show no significant recovery after 3-6 months of conservative treatment should consider surgical treatment as soon as possible to restore ankle stability and function. This study aims to investigate the effect of double-bands anatomical reconstruction of the ATFL's fibular enthesis for the treatment of CLAI.
Abstract Listeria monocytogenes (Lm) is a common foodborne pathogen which causes mild gastrointestinal distress in healthy hosts, and systemic listeriosis in immunocompromised individuals. While immune responses have been rigorously examined after intravenous Lm infection, less is understood about Lm dissemination from the intestines or the induction of adaptive immune responses after physiologic infection through the consumption of contaminated food. Consequently, this study focused on the cells involved in early immune responses in the intestinal mucosa using foodborne Lm infection in mice. After foodborne infection, Lm trafficked intracellularly from the intestines to the mesenteric lymph nodes (MLN) and were associated with Batf3-independent dendritic cells (DC) in the lymphatics. Consistent with this observation, dissemination of Lm from the gut to the MLN occurred normally in Batf3−/− mice. Activated migratory DC accumulated in the MLN by 3 days post-infection (dpi) where they surrounded Lm foci. At this time, Lm burden in the MLN was reduced in Batf3−/− mice implicating Batf3-DC in the maximal accumulation of Lm. While both conventional type 1 DC (cDC1) and type 2 DC in the MLN contained Lm by 3 dpi, Batf3−/− mice exhibited a profound defect in the induction and gut homing of Lm-specific CD8 T cells. Surprisingly, restoration of pathogen burden was unable to restore CD8 T cell responses in Batf3−/− mice. Thus, cDC1 play a critical role in the generation of potent anti-Lm immunity following foodborne infection. Collectively, these data demonstrate that DC play diverse and dynamic roles in the early events that follow foodborne Lm infection, and in the establishment of protective, anti-Lm intestinal immunity.
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