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Background The purpose of this study was to analyze the efficacy of U-shaped internal fixation for calcaneal tubercle fracture after nearly 3 years of case follow-up and data collection. Method We retrospectively analyzed the collected data from 16 patients with avulsion fracture of calcaneal tubercle between December 2018 and February 2021 at our institute. All patients were required to conform to regular follow up postoperatively. X-ray film was applied to all cases. The American Orthopaedic Foot and Ankle Association (AOFAS) score, Cedell score and the visual analog scale (VAS) were used to evaluate functional results. Results All patients achieved bone union. The preoperative AOFAS score was 26.34 ± 3.34, which was significantly different from 91.38 ± 6.15 half a year after operation (p = 0.003). The preoperative Cedell score was 31.05 ± 4.18 and the score half a year after operation was 92.17 ± 5.39(p = 0.011). The VAS score was 8.91 ± 1.51 before operation and decreased to 0.58 ± 1.31 half a year after operation (p = 0.014). Conclusions In the treatments of calcaneal tubercle fracture, U-shaped internal fixation is a new attempt. Through the short-term follow-up study, we found that its therapeutic effect is excellent, which is a recommended treatment in clinic.

Cell degeneration in the retina leads to several ocular diseases and vision loss. Considerable research efforts focus on reprogramming Muller glia (MG) into functional cells to rescue vision as a promising therapeutic strategy, although whether MG can convert into functional bipolar cells, retinal ganglia cells (RGCs), rods or cones in mammals remains controversial. The broad applicability of tracking MG differentiation thus presents a need for improved labeling efficiency and specificity. Here, we compared AAV-based labeling strategies with conventional lineage-tracking by crossing transgenic mouse lines. We found that reporter expression was weak and not MG-specific in mGFAP-Cre transgenic mice. Different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the WPRE (WPRE, woodchuck hepatitis virus post-transcriptional regulatory element) removed. The hGFAP-Cre- ΔWPRE reporter could label 20-73.8% MGs, with non-specific RGC labeling rates ranging from 0-0.08% at doses of 1 × 108 to 1010 vector genomes (vg) per eye, an approximate 40-fold reduction compared with the AAV9-hGFAP-Cre-WPRE labeling system. Furthermore, we validated the availability of the label system to trace MG reprogramming and also detected false-positive results reported previously. The AAV9-hGFAP-Cre-ΔWPRE system thus represents a highly efficient and specific labeling system for MG, providing a valuable tool for tracking cell fate in vivo.

Recently, a human mutation of OPG was identified to be associated with familial forms of osteoarthritis. This missense mutation (c.1205A = > T; p.Stop402Leu) occurs on the stop codon of OPG, which results in a 19-residue appendage to the C-terminus (OPG+19). The biochemical consequence of this unusual sequence alteration remains unknown. Here we expressed OPG+19 in 293 cells and the mutant OPG was purified to homogeneity by heparin affinity chromatography and size exclusion chromatography. We found that in sharp contrast to wildtype OPG, which mainly exists in dimeric form, OPG+19 had a strong tendency to form higher-order oligomers. To our surprise, the hyper-oligomerization of OPG+19 had no impact on how it binds cell surface heparan sulfate, how it inhibits RANKL-induced osteoclastogenesis and TRAIL-induced chondrocytes apoptosis. Our data suggest that in biological contexts where OPG is known to play a role, OPG+19 functions equivalently as wildtype OPG. The disease-causing mechanism of OPG+19 likely involves an unknown function of OPG in cartilage homeostasis and mineralization. By demonstrating the biochemical nature of this disease-causing OPG mutant, our study will likely help elucidating the biological roles of OPG in cartilage biology.

Trauma hemorrhage (TH) and subsequent sepsis are well known to frequently result in severe organ damage. Although macrophage-activating lipopeptide-2 (MALP-2) has been described to exert beneficial effects on organ damage, and further clinical course after both isolated trauma and sepsis, little is known about the impact of MALP-2 in a clinically realistic two-hit scenario of TH and subsequent sepsis. As the liver represents a key organ for the posttraumatic immune response and development of complications, the effects of MALP-2 on the posttraumatic hepatic immunologic response and tissue damage were investigated in a murine “two-hit” model. In C57BL/6 mice, blood pressure-controlled (35 ± 5 mm Hg) TH was induced. Cecal ligation and puncture (CLP) was performed 48 h after TH. Mice were divided into two control groups (control 1, TH and laparotomy without CLP; control 2, TH and CLP) and three experimental groups (TH + CLP) treated with MALP-2 at different timepoints (ETH, end of TH; ECLP, end of CLP; 6CLP, 6 h after CLP). The observation time lasted for 168 h after induction of TH. Kupffer cells (KC) were isolated and cultured, and MPO activity was analyzed. Cell culture supernatants were taken for cytokine analysis (TNF-α, IL-6, MCP-1, GM-CSF, IL-10). Histological analysis was performed using the Hepatic Injury Severity Scoring (HISS). Statistical evaluation was carried out using SPSS (version 24.0.0; IBM, Armonk, NY, USA). MPO activity of control 1 group was lowest compared with all the other groups (p

To evaluate the recovery of early urinary continence in patients with prostate cancer using a suprapubic catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy. From January 2018 to January 2019, 223 patients diagnosed with prostate cancer who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy in Diakonie Klinikum Stuttgart were involved in our study. From January 2018 to June 2018, patients (112 cases) only had an indwelling urinary catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy, while from July 2018 to January 2019, patients (111 cases) were offered an extra suprapubic catheter during operation. The recovery of early urinary continence of patients was mainly investigated one month later. The overall early urinary continence rate was 81.61%. Patients with suprapubic catheter had better urinary control results, compared to patients with only indwelling urinary catheter (87.39% vs 75.89%, p = 0.027). In addition, International Prostate Symptom Score and irritative subscore in patients with good urinary control were significantly lower than that in patients with urinary incontinence. Suprapubic catheter insertion (OR 0.395; 95% CI 0.190–0.821) and advanced pathological tumor stage (T3a–T4) (OR 2.061; 95% CI 1.008–4.217) were two independent influencing factors for early urinary continence recovery in patients who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy through multivariate logistic regression analysis. Suprapubic catheter insertion may be helpful for early urinary continence recovery in patients with Retzius-sparing Robotic-assistant laparoscopic prostatectomy. Advanced pathological tumor stage (T3a–T4) before Retzius-sparing robotic-assistant laparoscopic prostatectomy might be associated with poor urinary control.

Pulmonary complications after severe trauma and sepsis remain to be the main cause for adverse outcome. MALP-2 has been described to exert beneficial effects on organ damage and the further course after isolated trauma and sepsis. However, the impact of MALP-2 on a clinically realistic two-hit scenario of trauma and subsequent sepsis remains unknown. We, therefore, investigated if the systemic inflammatory response and pulmonary immune response and damage are beneficially modulated by MALP-2 in a murine two-hit model. Blood pressure-controlled trauma-hemorrhage (TH) and cecal ligation and puncture (CLP) were induced in C57/BL6 mice. Mice were divided into 2 control groups (control 1: TH without CLP; control 2: TH and CLP) and 3 experimental groups treated with MALP-2 at different time points (ETH, end of TH; ECLP, end of CLP; and 6CLP 6 h after CLP). Survival rates were assessed over the observation period of 168 h after the induction of TH. Concentrations of plasma inflammatory cytokines and chemokines (TNF-α, IL-6, MIP-1α, IFN-γ, and IL-10) were assessed, and bacterial clearance of the lungs was determined. Furthermore, pulmonary MPO activity assay to evaluate the infiltration of polymorphonuclear neutrophils (PMN) and histological evaluation were performed. Survival rates were evaluated. Compared with control group 1, the level of TNF-α in the ECLP group showed a significant increase (ECLP, 2.27 pg./ml ± 1.39 vs. control 1: 0.16 pg./ml ± 0.11, p = 0.021). In contrast, levels of IFN-γ were significantly reduced in groups ETH and 6CLP compared with control group 1 (control 1: 8.92 pg./ml ± 4.38 vs. ETH: 1.77 pg./ml ± 4.34, p = 0.026 resp. vs. 6CLP: 1.83 pg./ml ± 4.49, p = 0.014). While systemic concentrations of inflammatory mediators were not affected by MALP-2 treatment, the lung tissue presented with significant alterations. Reduced MPO activity was lowest in group ECLP (ECLP 11,196.77 ± 547.81 vs. ETH 12,773.94 ± 1011.76; p = 0.023 resp. vs. 6CLP 13,155.19 ± 423.99, p = 0.016) in experimental groups. Also, histological damage after MALP-2 application was lowest in ECLP animals (ECLP 0.50 ± 0.08 vs. ETH 0.71 ± 0.05, p = 0.034 resp. vs. 6CLP 0.64 ± 0.08, p = 0.021). Furthermore, MALP-2 treatment was associated with a trend towards improved survival in the ECLP group (ECLP 83.3% vs. ETH 66.7 and 6CLP 58.3%, p > 0.05). Based on our results, MALP-2 might have beneficial effects on the clinical course after hemorrhage and sepsis by reducing pulmonary damage and PMN infiltration. This might also affect survival. According to our data, MALP-2 should be given at the earliest possible time point after the onset of sepsis. However, the optimal dosage and confirmation of our results in larger cohorts need to be the focus of further research.

To investigate the beneficial effects of oridonin, a diterpenoid compound isolated from Rabdosia rubescens, on the inflammatory response in TNBS-induced post-inflammatory irritable bowel syndrome (PI-IBS) model and the underlying mechanism. Using the PI-IBS rat model and Caco-2 cell lines, we found that intestinal barrier function reflected by lactulose/mannitol (L/M) ratio and tight junction protein level was significantly ameliorated by oridonin. We also demonstrated that oridonin abrogated inflammation through inhibiting the phosphorylation of NF-κBp65 as well as its downstream gene (iNOS, COX-2, IL-1β, and IL-6) level. Molecular docking studies confirmed the good binding activity between oridonin and PXR. In Caco-2 cell lines, oridonin markedly inhibited LPS-induced NF-κB activation in a PXR-dependent manner. Meanwhile, PXR and its target genes CYP3A4 and P-gp were induced by oridonin, which was associated with the decreased expression of NF-κB and the recovery of intestinal barrier. This study indicated that the therapeutic effect of oridonin on experimental PI-IBS through repairing intestinal barrier function may be closely associated with the regulatory role of PXR/NF-κB signaling pathway. Oridonin may serve as a PXR ligand for the development of drugs in the therapy for PI-IBS.

The tumor immune microenvironment (TIME) is now considered as an important factor during gastric cancer (GC) development. This study identified a novel immune-related risk model for predicting prognosis and assessing the immune status of GC patients. Transcriptomic data were obtained from the TCGA database. The differential expressed immune-related genes (IRGs) were identified through the ImmPort portal. Enrichment analysis was performed to explore the potential molecular mechanism of these IRGs. By the Cox regression analysis, we constructed the immune prognostic model. Then, the association between the model and the immune microenvironment was estimated. The model was validated in the GSE84433 dataset. Totally, we identified 222 differentially expressed IRGs. These IRGs were closely correlated with immune response and immune signaling pathways. Through the Cox regression analysis, we developed the immune prognostic model based on the expression of seven IRGs (CXCL3, NOX4, PROC, FAM19A4, RNASE2, IGHD2-15, CGB5). Patients were stratified into two groups according to immune-related risk scores. Survival analysis indicated that the prognosis of high-risk patients was poorer than low-risk patients. Moreover, the immune-related risk score was an independent prognostic biomarker. More importantly, we found that the infiltration level of immunosuppressive cells and the expression of inhibitory immune checkpoints were higher in high-risk patients. The immune microenvironment tended to be a suppressive status in patients with high-risk scores. This study demonstrated that our model had predictive value for prognosis and the TIME in GC. It might be a robust tool to improve personalized patient management.

Background The activation degree of the orbitofrontal cortex (OFC) functional area in drug abusers is directly related to the craving for drugs and the tolerance to punishment. Currently, among the clinical research on drug rehabilitation, there has been little analysis of the OFC activation in individuals abusing different types of drugs, including heroin, methamphetamine, and mixed drugs. Therefore, it becomes urgently necessary to clinically investigate the abuse of different drugs, so as to explore the effects of different types of drugs on the human brain. Methods Based on prefrontal high-density functional near-infrared spectroscopy (fNIRS), this research designs an experiment that includes resting and drug addiction induction. Hemoglobin concentrations of 30 drug users (10 on methamphetamine, 10 on heroin, and 10 on mixed drugs) were collected using fNIRS and analyzed by combining algorithm and statistics. Results Linear discriminant analysis (LDA), Support vector machine (SVM) and Machine-learning algorithm was implemented to classify different drug abusers. Oxygenated hemoglobin (HbO2) activations in the OFC of different drug abusers were statistically analyzed, and the differences were confirmed. Innovative findings: in both the Right-OFC and Left-OFC areas, methamphetamine abusers had the highest degree of OFC activation, followed by those abusing mixed drugs, and heroin abusers had the lowest. The same result was obtained when OFC activation was investigated without distinguishing the left and right hemispheres. Conclusions The findings confirmed the significant differences among different drug abusers and the patterns of OFC activations, providing a theoretical basis for personalized clinical treatment of drug rehabilitation in the future.

Cystatin C (Cst-3) is a potent inhibitor of cysteine proteases with diverse biological functions. As a secreted protein, the potential interaction between Cst-3 and extracellular matrix components has not been well studied. Here we investigated the interaction between Cst-3 and heparan sulfate (HS), a major component of extracellular matrix. We discovered that Cst-3 is a HS-binding protein only at acidic pH. By NMR and site-directed mutagenesis, we identified two HS binding regions in Cst-3: the highly dynamic N-terminal segment and a flexible region located between residue 70-94. The composition of the HS-binding site by two highly dynamic halves is unique in known HS-binding proteins. We further discovered that HS-binding severely impairs the inhibitory activity of Cst-3 towards papain, suggesting the interaction could actively regulate Cst-3 activity. Using murine bone tissues, we showed that Cst-3 interacts with bone matrix HS at low pH, again highlighting the physiological relevance of our discovery., Zhang et al. identify Cystatin C as a new heparan sulfate (HS) binding protein, however only at acidic pH (≤6.5). They further identify two isolated HS binding motifs on Cystatin C that are required to come together to form a complete HS-binding site, which is a unique property among known HS binding proteins.

Reduced Cu/ZnO catalyst was synthesized through solid phase grinding of the mixture of oxalic acid, copper nitrate and zinc nitrate, followed by subsequent calcination in N2 atmosphere without further H2 reduction. The catalysts were characterized by various techniques, such as XRD, TG-DTA, TPR and N2O chemisorption. Characterization results suggested that during the calcination in N2, as-ground precursor (oxalate complexes) decomposed to CuO and ZnO, releasing considerable amount of CO, which could be used for in situ reduction of CuO to Cuo. The in situ reduced O/I-Cu/ZnO catalyst was evaluated in CO2 hydrogenation to methanol, which exhibited superior catalytic performance to its counterpart O/H-Cu/ZnO catalyst obtained through conventional H2 reduction. The decomposition of precursor and reduction of CuO happened simultaneously during the calcination in N2, preventing the growth of active Cu0 species and aggregation of catalyst particles, which was inevitable during conventional H2 reduction process. This method is simple and solvent-free, opening a new route to prepare metallic catalysts without further reduction.

Hook plate fixation is widely used to treat acromioclavicular joint dislocation. However, there are many post-operative complications affecting the effect of treatment. The aim of this study is to evaluate the efficacy of the clavicular hook plate with different hook angles as a method of treatment in AC joint dislocation, and to guide the clinical application of hook plate.We prospectively analysed 54 patients who were diagnosed with AC joint dislocation and treated with hook plate fixation by different hook angles. The patients were randomised into three groups: the -20° AHP 0° group, the 20° AHP 0° group and the 40° AHP 20° group. All patients were required to conform to regular follow-up post-operatively. Routine imaging to the shoulder was obtained to evaluate maintenance of the dislocation and the implant. Constant-Murley criteria were used to evaluate functional results.There were 19 patients in the -20° AHP 0° group, with one lost to follow-up, 22 patients in the 20° AHP 0° group, with two male patients lost to follow-up, and one female patient excluded because of no follow-up consent, and 19 patients in the 40° AHP 20° group, with one female and one male patient lost to follow-up. The Constant score was 61.8 ± 12.8, 74.7 ± 9.2 and 70.7 ± 9.4 before implant removal, and 78.8 ± 8.3, 87.1 ± 6.4 and 85.0 ± 6.1 after implant removal in the -20° AHP 0°, 20° AHP 0° and 40° AHP 20° groups, respectively. The functional results of the 20° AHP 0° and 40° AHP 20° groups were significantly better than the -20° AHP 0° group (P 0.05), but the functional results of the 20° AHP 0° and 40° AHP 20° groups were not statistically significant. The CCD was 98.1 ± 4.8%, 107.5 ± 5.1% and 105.5 ± 4.1% before implant removal, and 98.8 ± 4.6%, 108.3 ± 4.8% and 107.2 ± 3.3% after implant removal in the three groups, respectively. The CCD of the 20° AHP 0° and 40° AHP 20° groups were statistically significantly different from the -20° AHP 0° group (P 0.001). However, there was no statistical difference between the 20° AHP 0° group and the 40° AHP 20° group. Post-operative persistent pain occurred in 18.5% of all patients, post-operative stiffness occurred in 25.9% of all patients and 24.0% of patients had subacromial erosion.Hook plate treatment for AC joint dislocation can achieve the desired results, but the efficacy was significantly different depending on the different angles of the hook plate. AHP should be controlled within the range of 0-40° as much as possible when making clinical decisions.