Conditional survival of male breast cancer.

BACKGROUND: The incidence of male breast cancer has been increasing in recent years; however, the long-term survival outcomes of diagnosed patients remain uncertain. This study was designed to evaluate the conditional survival of male breast cancer patients and to predict the future survival of patients through the conditional nomogram, to provide important suggestions for clinical decision-making. METHODS: Retrospective data from the SEER database included 3600 male breast cancer patients, divided into training and validation groups (7 : 3 ratio). Overall survival rates were calculated using Kaplan-Meier analysis. Conditional survival analysis described survival at specific years. Time-dependent multivariate Cox analysis identified prognostic factors' impact. The conditional survival nomogram model predicted real-time survival rates. RESULTS: Over time, the 5-year real-time survival rate of patients gradually improved, increasing from 70.5 to 74.8, 79.4, 85.8, and 92.9% (respectively, representing 5-year survival rates of 1-4 years after diagnosis). In addition, the improvement in conditional survival rate CS5 showed a nonlinear trend. After 5 years of diagnosis, age, tumor size, and tumor stage had a sustained impact on patient prognosis. Finally, a conditional survival nomogram was constructed to predict the 10-year survival rate in real time. CONCLUSION: Five years after diagnosis, the conditional survival rate of male patients with breast cancer has improved, but it is not nonlinear. In the first 5 years after diagnosis, patients with older age, larger tumor size, poorer tumor stage, and distant metastasis should be actively followed up and treated to improve their long-term survival.

Paradoxical psoriasis induced by IL-17 antagonists.

Background The paradoxical occurrence of psoriasis triggered by Interleukin-17 (IL-17) inhibitors is notable due to its prominent symptoms and the therapeutic dilemma it presents for follow-up care. Objective To describe cases in our clinic, perform an in-depth literature review, and suggest the most probable mechanisms of action. Method We conducted a literature review on published cases of IL-17 inhibitor-induced psoriasis. Results We found 22 articles reporting 30 cases of IL-17 inhibitor-induced paradoxical psoriasis, primarily observed in patients with a previous psoriasis history. Almost 60% of cases showed a change in lesion morphology, with the plaque or pustular type being prevalent. About 73.3% of patients had to discontinue the implicated drug, leading to partial or complete symptom resolution. The mechanism behind this response seemed to involve IL-17 inhibitors downregulating Tumour Necrosis Factor alpha (TNF-α), subsequently upregulating plasmacytoid dendritic cells and triggering unopposed IFN-alpha (IFN-α) production. Limitation Data are confined to case reports and case series. Conclusion More assertive measures are recommended for treating paradoxical psoriasis induced by IL-17 inhibitors than those caused by TNF-α inhibitors. Reintroducing an IL-17 inhibitor is not advised, as patients did not show improvement.

[Mechanism of dexamethasone combined with glutamine in reducing lung inflammation and pulmonary edema in rats with acute lung injury].

Objective To investigate the effect of dexamethasone (DEX) combined with glutamine (Gln) on lung inflammation and pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS) and its related mechanisms. Methods Fifty Wistar rats were randomly divided into control group, model group, dexamethasone group (DEX) and DEX combined with Gln group. Except for the control group, rats in other groups were injected with 6 mg/kg LPS intraperitoneally to induce an acute lung injury. The mRNA expression of p38 MAPK, NLRP3, and NF-κB in lung tissue were detected by real-time quantitative PCR. The protein expressions of p-p38 MAPK, NLRP3, phosphorylated inhibitor of nuclear factor κB (p-IκB), NF-κB p65, aquaporin 1 (AQP1) and AQP5 in lung tissue were detected by Western blot analysis. ELISA was used to detect the content of serum tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß). Spectrophotometer was employed to detect the content of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in lung tissue. Results Compared with the control group, the lung index of the model group decreased, the content of the serum inflammatory factors TNF-α, IL-6 and IL-1ß significantly increased, and the protein expression of p38 MAPK, NLRP3, NF-κB mRNA, p-p38 MAPK, NLRP3, p-IκB and NF-κB p65 in the lung tissue significantly increased, while that of AQP1, AQP5 decreased, and the content of SOD and GSH-Px in lung tissue decreased, while that of MDA increased; Compared with the model group, the above mentioned symptoms and indicators in each treatment group were significantly improved, among which the DEX combined with Gln group was the most significant. Conclusion DEX combined with Gln can inhibit inflammation, resist oxidative damage, relieve pulmonary edema, and prevent acute lung injury. Its mechanism is related to inhibiting the activation of p38 MAPK, NLRP3, and NF-κB signaling pathways, promoting the expression of AQP1 and AQP5, and promoting the activity of antioxidant products.

S100A5 Attenuates Efficiency of Anti-PD-L1/PD-1 Immunotherapy by Inhibiting CD8+ T Cell-Mediated Anti-Cancer Immunity in Bladder Carcinoma.

Although immune checkpoint blockade (ICB) therapies have been approved for bladder cancer (BLCA), only a minority of patients respond to these therapies, and there is an urgent need to explore combined therapies. Systematic multi-omics analysis identified S100A5 as a novel immunosuppressive target for BLCA. The expression of S100A5 in malignant cells inhibited CD8+ T cell recruitment by decreasing pro-inflammatory chemokine secretion. Furthermore, S100A5 attenuated effector T cell killing of cancer cells by inhibiting CD8+ T cell proliferation and cytotoxicity. In addition, S100A5 acted as an oncogene, thereby promoting tumor proliferation and invasion. Targeting S100A5 synergized with the efficacy of anti-PD-1 treatment by enhancing infiltration and cytotoxicity of CD8+ T cells in vivo. Clinically, there was a spatially exclusive relationship between S100A5+ tumor cells and CD8+ T cells in tissue microarrays. Moreover, S100A5 negatively correlated with immunotherapy efficacy in our real-world and several public immunotherapy cohorts. In summary, S100A5 shapes a non-inflamed tumor microenvironment in BLCA by inhibiting the secretion of pro-inflammatory chemokines and the recruitment and cytotoxicity of CD8+ T cells. Targeting S100A5 converts cold tumors into hot tumors, thus enhancing the efficacy of ICB therapy in BLCA.

ATXN3 promotes prostate cancer progression by stabilizing YAP.

BACKGROUND: Prostate cancer (PC) is the most common neoplasm and is the second leading cause of cancer-related deaths in men worldwide. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in PC remains to be characterized. METHODS: Western blot was used to measure the protein expression of ATXN3 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect cell viability; transwell invasion assay was used to measure the invasion ability of PC. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between YAP and ATXN3. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP. RESULTS: In the present study, we identified ATXN3, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of YAP in PC. ATXN3 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. Depletion of ATXN3 decreased the YAP protein level and the expression of YAP/TEAD target genes in PC, including CTGF, ANKRD1 and CYR61. Further mechanistic study revealed that the Josephin domain of ATXN3 interacted with the WW domain of YAP. ATXN3 stabilized YAP protein via inhibiting K48-specific poly-ubiquitination process on YAP protein. In addition, ATXN3 depletion significantly decreased PC cell proliferation, invasion and stem-like properties. The effects induced by ATXN3 depletion could be rescued by further YAP overexpression. CONCLUSIONS: In general, our findings establish a previously undocumented catalytic role for ATXN3 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of PC. Video Abstract.

Competing risks analysis of external versus internal radiation in patients with hepatocellular carcinoma after controlling for immortal time bias.

PURPOSE: In cohort studies on liver cancer, there are often immortal time bias and interference of competing risk events. This study proposes to explore the role of internal and external radiotherapy for hepatocellular carcinoma using SEER data, using a competing risk model and controlling immortal time bias. METHODS: Data of SEER from 2004 till 2015 was included. To analyze whether there was a difference in survival between HCC (hepatocellular carcinoma) patients receiving external radiation and internal radiation, we used a competing risk analysis after excluding immortal time bias, and created a nomogram to assess the risk of cancer-specific death (CSD) in hepatocellular carcinoma patients receiving radiotherapy. RESULTS: Potential confounding factors adjusted, there was no significant difference in CSD between external and internal radiation therapy [HR and its 95% CI = 1.098 (0.874-1.380)]. The constructed nomogram performed better than the traditional AJCC model. The AUC and calibration curve results showed that this well-calibrated nomogram could be used to make clinical decisions regarding the prognosis and personalized treatment of hepatocellular carcinoma treated. There was no difference in the cumulative risk of death between patients with liver cancer treated with external radiation therapy and internal radiation therapy. CONCLUSION: There is no difference in the cumulative risk of death between patients with liver cancer treated with external radiation therapy and internal radiation therapy. The nomogram predicts the results more accurately. These results can be used to guide the choice of treatment options for patients with HCC and to predict their survival prognosis.

Evaluation of Haplo-Paraspinal-Muscle-Preserving Technique to Prevent Postoperative Axial Pain in Cervical Laminoplasty.

BACKGROUND: The present study aimed to assess the efficacy of a new haplo-paraspinal-muscle-preserving (HMP) laminoplasty technique in the treatment of cervical myelopathy. METHODS: The medical records of 68 patients diagnosed with multisegmental cervical myelopathy were retrospectively reviewed. Of these, 22 patients who underwent HMP laminoplasty were defined as the muscle-preserved group (MP), and 46 patients who underwent traditional open-door laminoplasty were enrolled and defined as the traditional open-door laminoplasty group (LP). Patient demographic data and surgical parameters like clinical and radiological parameters, operation duration, blood loss, and spinal canal expansion distance were compared. RESULTS: Average surgical time and blood loss were significantly reduced in the MP group when compared with the LP group (P < 0.05). Both groups demonstrated significant improvements in neurological function and spinal canal expansion (P > 0.05). However, the visual analog scale score in the MP group was significantly lower compared with the LP group at the 6-month follow-up (P < 0.05), but no differences were found at the 1-year follow-up. The loss of lordosis was more prominent in the LP group when compared with the MP group at 1-year follow-up (P < 0.05). Lower events of persistent axial pain were found in the MP group but with no statistical significance. More hinge side laminae fractures could be found in the MP group, but more hinge side displacements were found in the LP group. CONCLUSIONS: The HMP laminoplasty technique is relatively safe, effective, easier to perform, and better for lordosis maintenance and complication control compared with the traditional open-door technique. CLINICAL RELEVANCE: Although traditional open-door laminoplasty is an efficient approach in treating multisegmental cervical myelopathy, the complications could significantly affect the clinical outcome. Our new HMP laminoplasty technique has a lower complication rate and a better lordosis maintenance ability; therefore, it could be a better choice in treating multisegmental cervical myelopathy.

Methionine enkephalin inhibited cervical carcinoma via apoptosis promotion and reduction of myeloid derived suppressor cell infiltrated in tumor.

Immunotherapy for cervical carcinoma is becoming increasingly important recently. In these studies methionine enkephalin (menk) is shown to inhibit cervical tumor cell proliferation in vitro in association with an increase in the expression of apoptosis markers and mediators, including an increase in fas, caspase 8, and caspase 3 expression and intrinsic expression of the signaling pathway mediator bax. In vivo, tumor growth was restrained in mice xenotransplant model with typical pathological features of apoptosis. Furthermore, myeloid derived suppressor cells (MDSCs) had a significant decrease in circulation and in tumor site. In brief, these findings showed menk could inhibit tumor growth in vitro and in vivo, providing direction of further research and clinical application prospect.

Clinical implications of 3D printing technology in preoperative evaluation of partial nephrectomy. / 3D打印技术应用于肾部分切除术术前评估中的临床意义.

OBJECTIVES: Renal cancer is a common malignancy of the urinary system, and the partial nephrectomy is a common surgical modality for early renal cancer. 3D printing technology can create a visual three-dimensional model by using 3D digital models of the patient's imaging data. With this model, surgeons can perform preoperative assessment to clarify the location, depth, and blood supply of the tumor, which helps to develop preoperative plans and achieve better surgical outcomes. In this study, the R.E.N.A.L scoring system was used to stratify patients with renal tumors and to explore the clinical application value of 3D printing technology in laparoscopic partial nephrectomy. METHODS: A total of 114 renal cancer patients who received laparoscopic partial nephrectomy in Xiangya Hospital from June 2019 to December 2020 were enrolled. The patients were assigned into an experimental group (n=52) and a control group (n=62) according to whether 3D printing technology was performed, and the differences in perioperative parameters between the 2 groups were compared. Thirty-nine patients were assigned into a low-complexity group (4-6 points), 32 into a moderate-complexity group (7-9 points), and 43 into a high-complexity group (10-12 points) according to R.E.N.A.L score, and the differences in perioperative parameters between the experimental group and the control group in each score group were compared. RESULTS: The experimental group had shorter operative time, renal ischemia time, and postoperative hospital stay (all P<0.05), less intraoperative blood loss (P=0.047), and smaller postoperative blood creatinine change (P=0.032) compared with the control group. In the low-complexity group, there were no statistically significant differences between the experimental group and the control group in operation time, renal ischemia time, intraoperative blood loss, postoperative blood creatinine changes, and postoperative hospital stay (all P>0.05). In the moderate- and high- complexity groups, the experimental group had shorter operative time, renal ischemia time, and postoperative hospital stay (P<0.05 or P<0.001), less intraoperative blood loss (P=0.022 and P<0.001, respectively), and smaller postoperative blood creatinine changes (P<0.05 and P<0.001, respectively) compared with the control group. CONCLUSIONS: Compared with renal tumor patients with R.E.N.A.L score<7, renal cancer patients with R.E.N.A.L score≥7 may benefit more from 3D printing assessment before undergoing partial nephrectomy.

Intervertebral-spreader-assisted anterior cervical discectomy and fusion prevents postoperative axial pain by alleviating facet joint pressure.

OBJECTIVE: To evaluate the relationship of postoperative cervical axial pain with different vertebral distraction methods used during ACDF procedures in cervical spondylosis patients. METHODS: Ninety-four single-level cervical spondylotic myelopathy patients with significantly loss of intervertebral disc height who underwent ACDF surgery in our institute between January 2018 and January 2020 were enrolled. Cervical spine lateral radiographs were taken preoperatively, 3 days, 1-month, 2-month and 6-month after the surgery. The intervertebral disc height (IDH), interfacet distance (IFD), JOA (Japanese Orthopaedic Association) score, NDI (Neck Disability Index) score, nVAS (Neck Visual Analogue Scale) score and aVAS (Arm Visual Analogue Scale) score were measured. The correlation of clinical parameters and intervertebral disc height was evaluated. Then the correlation of clinical outcomes and different distraction method was evaluated. The patients were randomly divided into two groups, one uses Casper pin distractor system alone for distraction (Caspar alone group) and the other uses spreader assisted distraction method (Casper + spreader group). In biomechanical study, four cervical spine cadavers were selected for facet pressure measurements under different vertebral distraction methods, and the facet joint pressure was measured using force sensors. RESULTS: Satisfactory cervical fusion and neurological recovery were achieved in all patients. No significant correlation of IDH, IFD, JOA, NDI or aVAS with nVAS score was found. No significant difference between the change in disc height and clinical outcomes was found. However, by comparing the clinical parameters of patients in different vertebral distraction groups, we found significant changes in the early nVAS and NDI scores (P = 0.11, P = 0.48) of the Casper + spreader group (3 days postoperation), and was associated with a better nVAS score at 2 months postoperation (P < 0.05). The biomechanical study in cervical cadavers also showed significantly and continuously decreased facet joint pressure in the spreader assisted vertebral distraction group (P < 0.01). CONCLUSIONS: Spreader-assisted vertebral distraction method effectively alleviates postoperative neck pain in degenerative cervical spondylosis patients treated with ACDF. The mechanism may be related to the transient relief of facet joint pressure during the vertebral distraction procedure in ACDF.

PD-L1: Can it be a biomarker for the prognosis or a promising therapeutic target in cervical cancer?

Cervical cancer is one of the most common in the female genital tract and remains a leading cause that threatens the health and lives of women worldwide, although preventive vaccines and early diagnosis have reduced mortality. While treatment by operation and chemoradiotherapy for early-stage patients achieve good outcomes, the great majority of cervical cancers caused by the human papilloma virus (HPV) make immunotherapy realizable for patients with advanced and recurrent cervical cancer. To date, some clinical trials of checkpoint immunotherapy in cervical cancer have indicated significant benefits of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors, providing strong evidence for PD-1/PD-L1 as a therapeutic target. In this review article, we discuss the role of PD-L1 and the application of PD-L1 inhibitors in cervical cancer, with the aim of providing direction for future research.

Anterior cervical discectomy and fusion, open-door laminoplasty, or laminectomy with fusion: Which is the better treatment for four-level cervical spondylotic myelopathy?

Four-level cervical spondylotic myelopathy (CSM) is a common disease affecting a large number of people, with the optimal surgical strategy remaining controversial. This study compared the clinical outcomes, radiological parameters, and postoperative complications of primarily performed surgical procedures such as anterior cervical discectomy and fusion (ACDF), open-door laminoplasty (LAMP), and laminectomy with fusion (LF) in treating four-level CSM. A total of 116 patients who received ACDF (38 cases), LAMP (45 cases), and LF (33 cases) were followed up for a minimum of 24 months were enrolled in this study and retrospectively analyzed. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) scoring system, the Neck Disability Index (NDI), and the Visual Analogue Scale (VAS). Changes in the curvature of the cervical spine were determined using the cervical curvature index (CCI) and the C2-C7 Cobb angle. Cervical mobility was evaluated using the C2-C7 range of motion (ROM) and active cervical ROM (aROM). Complications were recorded and compared among the three groups. All patients achieved significant improvement in JOA, NDI, and VAS scores at the final follow-up (P < 0.05), whereas no remarkable difference was found among the groups (P > 0.05). In addition, both C2-7 ROM and aROM were significantly reduced in the three groups and LAMP showed the least reduction relatively. As for complications, LAMP showed the lowest overall incidence of postoperative complications, and patients in the ACDF group were more susceptible to dysphagia, pseudoarthrosis than LAMP and LF. Considering improvements in clinical symptoms and neurological function, no remarkable difference was found among the groups. Nevertheless, LAMP had advantages over the other two surgical procedures in terms of preserving cervical mobility and reducing postoperative complications.

LncRNA HCP5 Promotes Cell Invasion and Migration by Sponging miR-29b-3p in Human Bladder Cancer.

BACKGROUND: Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. In this study, the roles of lncRNA HCP5 (human major histocompatibility complex p5) and miR-29b-3p in human BC were investigated. Their regulations involved in cell invasion and migration were also evaluated. METHODS: Luciferase reporter assay was performed to detect the binding between miR-29b-3p and HCP5 or high-mobility group box 1 (HMGB1). Cell viability, migration, invasion and apoptosis were assessed by CCK-8, colony formation, transwell assay and flow cytometry, respectively. Expression levels of HMGB1/toll-like receptor 4 (TLR4) proteins were measured by Western blot. Xenograft model was built, and tumor volumes and weights were calculated. RESULTS: The results revealed dysregulation of HCP5 and miR-29b-3p in BC samples and cells. HCP5 negatively regulated the expression of miR-29b-3p and enhanced cell viability, migration and invasion. MiR-29b-3p mediated the effect of HCP5 on cell viability, proliferation, migration and invasion in RT4 cells. In addition, miR-29b-3p could regulate the expression of HMGB1 through interaction with HMGB1. CONCLUSION: The findings in this study supported that lncRNA HCP5 could promote cell invasion and migration by sponging miR-29b-3p in human BC.

MicroRNA-181 regulates the development of Ossification of Posterior longitudinal ligament via Epigenetic Modulation by targeting PBX1.

Objectives: Ossification of the posterior longitudinal ligament (OPLL) presents as the development of heterotopic ossification in the posterior longitudinal ligament of the spine. The etiology of OPLL is genetically linked, as shown by its high prevalence in Asian populations. However, the molecular mechanism of the disease remains obscure. In this study, we explored the function and mechanism of OPLL-specific microRNAs. Methods: The expression levels of the ossification-related OPLL-specific miR-181 family were measured in normal or OPLL ligament tissues. The effect of miR-181a on the ossification of normal or pathogenic ligament cells was tested using real-time polymerase chain reaction (PCR), Western blot, alizarin red staining and alkaline phosphatase (ALP) staining. The candidate targets of miR-181 were screened using a dual luciferase reporter assay and functional analysis. The link between miR-181a and its target PBX1 was investigated using chromatin immunoprecipitation, followed by real-time PCR detection. Histological and immunohistochemical analysis as well as micro-CT scanning were used to evaluate the effects of miR-181 and its antagonist using both tip-toe-walking OPLL mice and in vivo bone formation assays. Results: Using bioinformatic analysis, we found that miR-181a-5p is predicted to play important roles in the development of OPLL. Overexpression of miR-181a-5p significantly increased the expression of ossification-related genes, staining level of alizarin red and ALP activity, while the inhibition of miR-181a-5p by treatment with an antagomir had the opposite effects. Functional analysis identified PBX1 as a direct target of miR-181a-5p, and we determined that PBX1 was responsible for miR-181a-5p's osteogenic phenotype. By chromatin immunoprecipitation assay, we found that miR-181a-5p controls ligament cell ossification by regulating PBX1-mediated modulation of histone methylation and acetylation levels in the promoter region of osteogenesis-related genes. Additionally, using an in vivo model, we confirmed that miR-181a-5p can substantially increase the bone formation ability of posterior ligament cells and cause increased osteophyte formation in the cervical spine of tip-toe-walking mice. Conclusions: Our data unveiled the mechanism by which the miR-181a-5p/PBX1 axis functions in the development of OPLL, and it revealed the therapeutic effects of the miR-181a-5p antagomir in preventing OPLL development both in vivo and in vitro. Our work is the first to demonstrate that microRNA perturbation could modulate the development of OPLL through epigenetic regulation.

Low-dose naltrexone inhibits the epithelial-mesenchymal transition of cervical cancer cells in vitro and effects indirectly on tumor-associated macrophages in vivo.

The metastasis of cervical cancer has always been a clinical challenge. We investigated the effects of low-dose naltrexone (LDN) on the epithelial mesenchymal transition of cervical cancer cells in vitro as well as its influence on macrophage polarization and associated cytokines in vivo. The results suggested that LDN supressed the proliferation, migration and invasion abilities and promote their apoptosis in Hela cells, whereas the opioid growth factor receptor (OGFr) silenced significantly reversed these effects in vitro. Knockdown the expression of OGFr, the inhibitory of LDN on EMT was weakened. LDN could inhibit cervical cancer progression in nude mice. In additon, LDN indirectly reduced the number of tumor-associated macrophages (TAMs), mainly M2 macrophages, and decreased expression of anti-inflammatory factor IL-10 in the serum of nude mice. These findings demonstrate that LDN could be a potential treatment for cervical cancer.

Inflammatory-sensitive CHI3L1 protects nucleus pulposus via AKT3 signaling during intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the main cause of low back pain and the mechanism of which is far from fully revealed. Although inflammation directed nucleus pulposus (NP) extracellular matrix metabolism dysregulation is known to be the main cause of the degeneration process, few is known about the protective factors. Using high-throughput label-free proteomics, we found that inflammation-related autocrine factor Chitinase-3-like protein 1 (CHI3L1, or YKL-40) is highly expressed in the NP cells during degeneration. Immunohistochemical analysis show that the expression of CHI3L1 is NP tissue specific, and increase significantly during degeneration. Overexpression of CHI3L1 significantly decrease the catabolism, and increase the anabolism of extracellular matrix. Knockdown of CHI3L1 using siRNAs show the opposite results, which imply that the protective role of CHI3L1 in IDD. Using high-throughput RNA sequencing and functional analyses, we find that AKT3 expression and its phosphorylation is mainly regulated by CHI3L1. And lastly, the mechanism of which is also validated using human and mouse degenerated NP tissues. In summary, our findings show that the inflammation-related autocrine factor CHI3L1 is NP specific, and it protects IDD by promoting the AKT3 signaling, which may serve as a potential therapeutic target in intervertebral disc degeneration.

Neoadjuvant Chemotherapy Benefits Survival in High-Grade Upper Tract Urothelial Carcinoma: A Propensity Score-Based Analysis.

BACKGROUND: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for survival in high-grade upper tract urothelial carcinoma (UTUC), a propensity score-based analysis was performed with high-grade UTUC patients from multiple urologic centers. METHODS: From three urologic centers, 48 high-grade UTUC patients who received chemotherapy followed by surgery (NAC group) and 72 high-grade UTUC patients who underwent initial surgery (no-NAC group) were involved in a propensity score-based analysis. After propensity score-based (1:1) matching, 37 patients receiving NAC and 37 patients not receiving NAC were followed. RESULTS: The patients who received NAC had improved disease-free survival (DFS) and overall survival (OS), with a 3-year DFS rate of 78.4% and an OS rate of 86.5% versus a 3-year DFS rate of 51.4% and an OS rate of 62.2% for those treated with initial surgery (P = 0.018 and P = 0.02, respectively). In the multivariate analysis, the NAC group had a lower risk for mortality [DFS hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.10-0.62; P = 0.003; OS HR 0.22; 95% CI 0.085-0.57; P = 0.002]. The analysis of patient survival in matched subgroups showed that NAC was beneficial in terms of the 3-year DFS for the group with a cT of 3 or higher (DFS HR 0.37; 95% CI 0.14-0.94; P = 0.036) and the group that had tumor with hydronephrosis (DFS HR 0.31; 95% CI 0.11-0.87; P = 0.026). CONCLUSION: The study showed that NAC may be considered as an effective addition to surgery for the treatment in high-grade UTUC patients.

Holmium laser enucleation of the prostate versus thulium laser enucleation of the prostate for the treatment of large-volume prostates > 80 ml: 18-month follow-up results.

PURPOSE: To compare the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) for the treatment of large-volume benign prostatic hyperplasia (BPH) (> 80 ml). METHODS: A total of 116 consecutive patients with BPH were randomized to be treated surgically with either HoLEP (n = 58) or ThuLEP (n = 58), following the classical three-lobe enucleation technique. Follow-up was assessed at 1, 3, 6, 12 and 18 months after surgery. RESULTS: At 18 months, the lower urinary tract symptom index was improved significantly in both groups compared with the baseline values. The operative time (78.4 ± 8.0 vs. 71.4 ± 6.4 min) and enucleation time (61.2 ± 5.4 vs. 56.4 ± 8.4 min) were significantly shorter for ThuLEP compared to HoLEP (both p < 0.001). There were no significant differences between the two groups regarding morcellation time, resected weight, hemoglobin decrease, catheter time and hospital stay (p > 0.05). The HoLEP and ThuLEP groups had equivalent International Prostate Symptom Scores (3 [3-3] vs. 3 [3-3], p = 0.776), quality of life (1 [1-2] vs. 2 [1-2], p = 0.809), Qmax (25.3 ± 4.8 ml/s vs. 24.7 ± 4.4 ml/s, p = 0.470), postvoid residual urine (PVR) (6.1 [2.6-20.8] vs. 7.7 [3.1-22.8] ml, p = 0.449) and PSA (0.84 ± 0.32 vs. 0.90 ± 0.34 ml, p = 0.309) at 18 months postoperatively. CONCLUSION: Both HoLEP and ThuLEP relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLEP was statistically superior to HoLEP in operation time and enucleation time, although the differences were clinically negligible.

Long noncoding RNA DNM3OS promotes prostate stromal cells transformation via the miR-29a/29b/COL3A1 and miR-361/TGFß1 axes.

Transforming growth factor-ß1 (TGFß1)-induced differentiation into and the activation of myofibroblasts have been regarded as critical events in benign prostatic hyperplasia (BPH); however, the underlying mechanisms of BPH pathogenesis remain unclear. Microarray profiling, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Gene Ontology (GO) enrichment analysis were performed to confirm the candidate genes and long non-coding RNA (lncRNAs) related to BPH. Collagen Type III (COL3A1) was significantly upregulated by TGFß1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGFß1 stimulation. Upon TGFß1 stimulation, COL3A1 protein was decreased by DNM3OS silencing. miR-29a and miR-29b could directly bind to the DNM3OS and COL3A1 3' untranslated region (UTR)s to negatively regulate their expression, and by serving as a competing endogenous RNAs (ceRNA), DNM3OS competed with COL3A1 for miR-29a/29b binding, therefore counteracting miR-29a/29b-mediated COL3A1 suppression. The effect of DNM3OS silencing on ECM components and TGFß1 downstream signaling was similar to that of the TGFß1 inhibitor SB431542. miR-361 could target DNM3OS and TGFß1; DNM3OS competed for miR-361 binding to counteract miR-361-mediated TGFß1 suppression. In conclusion, we identified DNM3OS as a specifically-upregulated lncRNA upon TGFß1 stimulation in PrSCs; by serving as a ceRNA for the miR-29a/29b cluster and miR-361, DNM3OS eliminated miRNA-mediated suppression of COL3A1 and TGFß1, thereby promoting TGFß1-induced PrSC transformation into myofibroblasts.

Glioblastoma Treatment Modalities besides Surgery.

Glioblastoma multiforme (GBM) is commonly known as the most aggressive primary CNS tumor in adults. The mean survival of it is 14 to 15 months, following the standard therapy from surgery, chemotherapy, to radiotherapy. Efforts in recent decades have brought many novel therapies to light, however, with limitations. In this paper, authors reviewed current treatments for GBM besides surgery. In the past decades, only radiotherapy, temozolomide (TMZ), and tumor treating field (TTF) were approved by FDA. Though promising in preclinical experiments, therapeutic effects of other novel treatments including BNCT, anti-angiogenic therapy, immunotherapy, epigenetic therapy, oncolytic virus therapy, and gene therapy are still either uncertain or discouraging in clinical results. In this review, we went through current clinical trials, underlying causes, and future therapy designs to present neurosurgeons and researchers a sketch of this field.