[Short-term effectiveness of unilateral biportal endoscopy technique in treatment of lumbar lateral saphenous fossa combined with intervertebral foramina stenosis via contralateral sublaminar approach].

Objective: To investigate the short-term effectiveness of unilateral biportal endoscopy (UBE) in treatment of lumbar lateral saphenous fossa combined with intervertebral foramina stenosis via contralateral sublaminar approach. Methods: A clinical data of 15 patients with lumbar lateral saphenous fossa combined with intervertebral foramina stenosis, who were admitted between September 2021 and December 2023 and met selective criteria, was retrospectively analyzed. There were 5 males and 10 females with an average age of 70.3 years (range, 46-83 years). Surgical segment was L 4, 5 in 12 cases and L 5, S 1 in 3 cases. The disease duration was 12-30 months (mean, 18.7 months). All patients were treated by UBE via contralateral sublaminar approach. The operation time, intraoperative blood loss, postoperative hospital stay, and the occurrence of complications were recorded. The visual analogue scale (VAS) score was used to evaluate the degree of lower back and leg pain before and after operation; the Japanese Orthopaedic Association (JOA) score and the Oswestry disability index (ODI) were used to evaluate the lumbar function; and the clinical outcome was evaluated using the MacNab criteria at 6 months after operation. Postoperative MRI and CT were taken to observe whether the lateral saphenous fossa and intervertebral foramen stenosis were removed or not, and the cross-sectional area of the spinal canal (CSA-SC), cross-sectional area of the intervertebral foramen (CSA-IVF), and cross-sectional area of the facet joint (CSA-FJ) were measured. Results: The operation time was 55-200 minutes (mean, 127.5 minutes); the intraoperative blood loss was 10-50 mL (mean, 27.3 mL); the length of postoperative hospital stay was 3-12 days (mean, 6.8 days). All patients were followed up 6-12 months (mean, 8.9 months). At 1 day, 1 month, 3 months, and 6 months after operation, the VAS scores of low back and leg pain and ODI scores after operation were significantly lower than preoperative scores and showed a gradual decrease with time; the JOA scores showed a gradual increase with time; the differences in the above indexes between different time points were significant ( P<0.05). The clinical outcome was rated as excellent in 10 cases, good in 4 cases, and poor in 1 case according to the MacNab criteria at 6 months after operation, with an excellent and good rate of 93.33%. Imaging review showed that the compression on the lateral saphenous fossa and intervertebral foramina had been significantly relieved, and the affected articular process joint was preserved to the maximum extent; the CSA-SC and CSA-IVF at 3 days after operation significantly increased compared to the preoperative values ( P<0.05), and the CSA-FJ significantly reduced ( P<0.05). Conclusion: The UBE via contralateral sublaminar approach can effectively reduce pressure in the lateral saphenous fossa and the intervertebral foramina of the same segment while preserving the bilateral articular process joints. The short-term effectiveness is good and it is expected to avoid fusion surgery caused by iatrogenic instability of the lumbar spine. However, further follow-up is needed to clarify the mid- and long-term effectiveness.

IGF2BP3/NCBP1 complex inhibits renal tubular senescence through regulation of CDK6 mRNA stability.

Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852-1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence in vitro. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing m6A modification. Specifically, IGF2BP3 recognizes m6A motif "GGACU" at nucleotides 110-114 in the 5' untranslated region (UTR) field of CDK6 mRNA. The involvement of IGF2BP3/CDK6 in alleviating tubular senescence was confirmed in a cisplatin-induced acute kidney injury (AKI)-to-chronic kidney disease (CKD) model. Clinical data also suggests an age-related decrease in IGF2BP3 and CDK6 levels in renal tissue or serum samples from patients. These findings suggest that IGF2BP3/CDK6 may be a promising target in cisplatin-induced tubular senescence and renal failure.

Long noncoding RNA UCA1 promotes the chondrogenic differentiation of human bone marrow mesenchymal stem cells via regulating PARP1 ubiquitination.

Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) urothelial carcinoma associated 1 (UCA1) has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms of these processes. The expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull-down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminish the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.

[Prospective comparative study of unilateral biportal endoscopic transforaminal lumbar interbody fusion and endoscopic transforaminal lumbar interbody fusion for treatment of single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis].

Objective: To compare the effectiveness of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) and endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) in the treatment of single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis. Methods: Between November 2019 and May 2023, a total of 81 patients with single-segment degenerative lumbar spinal stenosis with lumbar spondylolisthesis who met the selection criteria were enrolled. They were randomly divided into UBE-TLIF group (39 cases) and Endo-TLIF group (42 cases). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, body mass index, surgical segment, and preoperative visual analogue scale (VAS) scores for low back and leg pain, Oswestry Disability Index (ODI), and serum markers including creatine kinase (CK) and C reactive protein (CRP). Total blood loss (TBL), intraoperative blood loss, hidden blood loss (HBL), postoperative drainage volume, and operation time were recorded and compared between the two groups. Serum markers (CK, CRP) levels were compared between the two groups at 1 day before operation and 1, 3, and 5 days after operation. Furthermore, the VAS scores for low back and leg pain, and ODI at 1 day before operation and 1 day, 3 months, 6 months, and 12 months after operation, and intervertebral fusion rate at 12 months after operation were compared between the two groups. Results: All surgeries were completed successfully without occurrence of incision infection, vascular or nerve injury, epidural hematoma, dural tear, or postoperative paraplegia. The operation time in UBE-TLIF group was significantly shorter than that in Endo-TLIF group, but the intraoperative blood loss, TBL, and HBL in UBE-TLIF group were significantly more than those in Endo-TLIF group ( P<0.05). There was no significant difference in postoperative drainage volume between the two groups ( P>0.05). The levels of CK at 1 day and 3 days after operation and CRP at 1, 3, and 5 days after operation in UBE-TLIF group were slightly higher than those in the Endo-TLIF group ( P<0.05), while there was no significant difference in the levels of CK and CPR between the two groups at other time points ( P>0.05). All patients were followed up 12 months. VAS score of low back and leg pain and ODI at each time point after operation significantly improved when compared with those before operation in the two groups ( P<0.05); there was no significant difference in VAS score of low back and leg pain and ODI between the two groups at each time point after operation ( P>0.05). There was no significant difference in the intervertebral fusion rate between the two groups at 12 months after operation ( P>0.05). Conclusion: UBE-TLIF and Endo-TLIF are both effective methods for treating degenerative lumbar spinal stenosis with lumbar spondylolisthesis. However, compared to Endo-TLIF, UBE-TLIF requires further improvement in minimally invasive techniques to reduce tissue trauma and blood loss.

A comprehensive meta-analysis comparing the effectiveness and safety of cold snare polypectomy and hot snare polypectomy in removing colorectal polyps ≤ 10 mm.

OBJECTIVE: The optimal methods for removing polyps remain controversial especially for polyps ≤10mm. We aim to combine the latest evidence to evaluate and compare the effectiveness and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP) in the removal of colorectal polyps ≤10mm in size. METHODS: We performed an extensive search across multiple databases, including PubMed, Embase, Cochrane, and Web of Science, with the search period ending in April 2023 for randomized controlled trials comparing the effectiveness and/or safety of CSP and HSP for the removal of ≤10mm colorectal polyps.The final outcomes included complete resection rate, operation time, and postoperative adverse events (including immediate bleeding, delayed bleeding, and perforation) rates. RESULTS: A total of 14 eligible randomized controlled trials were included, involving 7,460 patients and 15,829 polyps. The incidence of immediate bleeding was observed to be more prevalent in CSP in contrast to HSP, and the disparity was statistically notable (OR=2.18, 95% CI: 1.43-3.30, I2=36%, P=0.0003). The incidence of delayed bleeding was observed to be lower in CSP in contrast to HSP, and this difference was statistically significant (OR=0.30, 95% CI: 0.15-0.58, I2=0%, P=0.0003). Procedure time: both the total colonoscopy time and specific polypectomy time were shorter in CSP than in HSP (MD=-5.92, 95% CI: -9.70 to -2.14, I2=96%, P=0.002; MD=-0.56, 95% CI: -0.91 to -0.20, I2=77%, P=0.002). There were no statistically significant differences in complete resection and the polyp retrieval rate between CSP and HSP. CONCLUSION: CSP is as effective and safe as HSP for ≤10mm colorectal polyps, while effectively reducing the risk of delayed bleeding and shortening the procedure time.

Chemokines and Their Receptors: Predictors of Therapeutic Potential in Tumor Microenvironment on Esophageal Cancer.

Esophageal carcinoma (ESCA) is an aggressive solid tumor. The 5-year survival rate for patients with ESCA is estimated to be less than 20%, mainly due to tumor invasion and metastasis. Therefore, it is urgent to improve early diagnostic tools and effective treatments for ESCA patients. Tumor microenvironment (TME) enhances the ability of tumor cells to proliferate, migrate, and escape from the immune system, thus promoting the occurrence and development of tumor. TME contains chemokines. Chemokines consist of four major families, which are mainly composed of CC and CXC families. The main purpose of this review is to understand the CC and CXC chemokines and their receptors in ESCA, to improve the understanding of tumorigenesis of ESCA and determine new biomarkers for the diagnosis and prognosis of ESCA. We reviewed the literature on CC and CXC chemokines and their receptors in ESCA identified by PubMed database. This article introduces the general structures and functions of CC, CXC chemokines and their receptors in TME, as well as their roles in the progress of ESCA. Chemokines are involved in the development of ESCA, such as cancer cell invasion, metastasis, angiogenesis, and radioresistance, and are key determinants of disease progression, which have a great impact on patient prognosis and treatment response. In addition, a full understanding of their mechanism of action is essential to further verify that these chemokines and their receptors may serve as biomarkers or therapeutic targets of ESCA.

miR-133b Promotes Esophageal Squamous Cell Carcinoma Metastasis.

Background: Evaluation of biological changes at the molecular level has important clinical implications for improving the survival rate of esophageal squamous cell carcinoma (ESCC). Therefore, we plan to analyze and elucidate the expression of microRNA-133b (miR-133b), M2 pyruvate kinase (PKM2), and signal transducer and activator of transcription 3 (STAT3) in ESCC and their associated clinicopathological significance. Methods: The 72 patients with ESCC were selected as the experimental study group. Normal adjacent tissues (NAT) were matched as the control group. In this study, in situ hybridization was used to detect the expression of miR-133b in ESCC, and tissue expressions of PKM2 and STAT3 were detected by immunohistochemistry, and literature review was conducted. Results: Studies had shown that the positive expression of miR-133b in NAT was significantly higher than that in ESCC (χ2 = 9.007, P = .003). PKM2 and STAT3 in ESCC had a significantly higher positive expression levels than those of NAT (χ2 = 56.523, P = .000; χ2 = 72.939, P = .000). From correlation analysis, there was a negative correlation between miR-133b and PKM2(r = -0.515, P < .001), a negative correlation between miR-133b and STAT3(r = -0.314, P = .007), and a positive correlation between PKM2 and STAT3(r = 0.771, P < .001). Conclusions: In ESCC, our study demonstrated that downregulation of miR-133b and upregulation of PKM2 and STAT3. We predict that miR-133b may inhibit the STAT3 pathway by downregulating PKM2.

SPI1-Mediated Upregulation of the CST1 Gene as an Independent Poor Prognostic Factor Accelerates Metastasis in Esophageal Squamous Cell Carcinoma (ESCC) by Interacting with MMP2.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal tumor type, but studies on the ESCC tumor microenvironment are limited. We found that cystatin SN (CST1) plays an important role in the ESCC tumor microenvironment. CST1 has been reported to act as an oncogene in multiple human cancers, but its clinical significance and underlying mechanism in ESCC remain elusive. METHODS: We performed ESCC gene expression profiling with data from RNA-sequencing and public databases and found CST1 upregulation in ESCC. Then, we assessed CST1 expression in ESCC by RT‒qPCR and Western blot analysis. In addition, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to estimate the expression of CST1 in ESCC tissue and serum. Moreover, further functional experiments were conducted to verify that the gain and loss of CST1 in ESCC cell lines significantly influenced the proliferation and metastasis of ESCC. Mass spectrometry, coimmunoprecipitation, and gelatin zymography experiments were used to validate the interaction between CST1 and matrix metalloproteinase 2 (MMP2) and the mechanism of CST1 influence on metastasis in ESCC. RESULTS: Here, we found that CST1 expression was significantly elevated in ESCC tissues and serum. Moreover, compared with patients with low CST1 expression, patients with high CST1 expression had a worse prognosis. Overall survival (OS) and disease-free survival (DFS) were significantly unfavorable in the high CST1 expression subgroup. Likewise, the CST1 level was significantly increased in ESCC serum compared with healthy control serum, indicating that CST1 may be a potential serum biomarker for diagnosis, with an area under the curve (AUC) = 0.9702 and p < 0.0001 by receiver operating curve (ROC) analysis. Furthermore, upregulated CST1 can promote the motility and metastatic capacity of ESCC in vitro and in vivo by influencing epithelial mesenchymal transition (EMT) and interacting with MMP2 in the tumor microenvironment (TME). CONCLUSIONS: Collectively, the results of this study indicated that high CST1 expression mediated by SPI1 in ESCC may serve as a potentially prognostic and diagnostic predictor and as an oncogene to promote motility and metastatic capacity of ESCC by influencing EMT and interacting with MMP2 in the TME.

Associations between immune-mediated diseases (IMDs) and the risk of HPV-associated diseases: a UK Biobank cohort analysis.

OBJECTIVES: To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases. DESIGN: Retrospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 500 371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex. EXPOSURE: Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively. RESULTS: During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p<0.001; male: HR=1.66, 95% CI=1.41 to 1.97, p<0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95% CI=1.47 to 2.11, p<0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95% CI=3.32 to 11.04, p<0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups. CONCLUSION: In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases.

Genomic full-length sequence of the HLA-B*13:64 allele was identified in a Chinese bone marrow donor.

Genomic full-length sequence of HLA-B*13:64 was identified in a Chinese individual by sequence-based typing.

[Research progress of different minimally invasive spinal decompression in lumbar spinal stenosis].

Objective: To review the application and progress of different minimally invasive spinal decompression in the treatment of lumbar spinal stenosis (LSS). Methods: The domestic and foreign literature on the application of different minimally invasive spinal decompression in the treatment of LSS was extensively reviewed, and the advantages, disadvantages, and complications of different surgical methods were summarized. Results: At present, minimally invasive spinal decompression mainly includes microscopic bilateral decompression, microendoscopic decompression, percutaneous endoscopic lumbar decompression, unilateral biportal endoscopy, and so on. Compared with traditional open surgery, different minimally invasive spinal decompression techniques can reduce the operation time, intraoperative blood loss, and postoperative pain of patients, thereby reducing hospital stay and saving treatment costs. Conclusion: The indications of different minimally invasive spinal decompression are different, but there are certain advantages and disadvantages. When patients have clear surgical indications, individualized treatment plans should be formulated according to the symptoms and signs of patients, combined with imaging manifestations.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

LncRNA MEG3 alleviates interstitial cystitis in rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

PURPOSE: Interstitial cystitis (IC), a chronic pain syndrome characterized by urinary frequency, urgency, and bladder or pelvic floor pain, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of long noncoding RNA Maternally Expressed Gene3 (lncRNA MEG3) in IC. METHODS: An IC rat model was established by intraperitoneal injection of cyclophosphamide combined with bladder perfusion of fisetin and tumor necrosis factor-α (TNF-α) to mimic IC. An in vitro model was established using TNF-α-induced rat bladder epithelium cells. H&E staining was used to assess bladder tissue damage and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine Nrf2, Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-NF-κB and NF-κB protein expression levels. RNA immunoprecipitation and RNA pull-down assays were used to examine the interaction between MEG3 and Nrf2. RESULTS: MEG3 levels were upregulated in IC tissues and bladder epithelial cells, whereas Nrf2 expression was found to be downregulated. Knockdown of MEG3 reduced bladder tissue injury, inflammation, oxidative stress and apoptosis. MEG3 was negatively correlated with Nrf2. Downregulation of MEG3 alleviated IC inflammation and injury by upregulating Nrf2 and inhibiting the p38/NF-κB pathway. CONCLUSION: Downregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

Novel long noncoding RNA LINC02820 augments TNF signaling pathway to remodel cytoskeleton and potentiate metastasis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. However, there are no targets to treat ESCC because the molecular mechanism behind the cancer is still unclear. Here, we found a novel long noncoding RNA LINC02820 was upregulated in ESCC and associated with the ESCC clinicopathological stage. Through a series of functional experiments, we observed that LINC02820 only promoted the migration and invasion capabilities of ESCC cell lines. Mechanically, we found that LINC02820 may affect the cytoskeletal remodeling, interact with splice factor 3B subunit 3 (SF3B3), and cooperate with TNFα to amplify the NF-κB signaling pathway, which can lead to ESCC metastasis. Overall, our findings revealed that LINC02820 is a potential biomarker and therapeutic target for the diagnosis and treatment of ESCC.

The relationship between processed meat, red meat, and risk of types of cancer: A Mendelian randomization study.

Background: Observational studies have suggested processed and red meat may increase the risk of cancer. However, the causal effects and direction between them were still unclear. We conducted two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of processed meat and red meat on the risk of nine common types of cancer, namely, lung, ovarian, endometrial, breast, kidney, gastric, prostate, skin, and oropharyngeal cancer. Methods: Genome-wide association studies (GWAS) for processed meat and red meat (pork, beef, and mutton) were obtained from the UK Biobank. GWAS of types of cancer in this study were extracted from the genetic consortia and the FinnGen consortium. The inverse variance weighted (IVW) was carried out as the main method for two-sample MR analysis. Sensitivity analyses were used to assess the robustness of the results. Results: Genetically predicted processed meat intake was causally associated with increased risk of lung cancer (OR [odds ratio] = 1.923, 95% CI = 1.084-3.409, P = 0.025). There is no convincing evidence for the associations between genetically determined processed meat, red meat, and the risk of other cancers we studied. Conclusion: Our results suggested that intake of processed meat may increase the risk of lung cancer. These findings provided no evidence to support that consumption of processed and red meat has a large effect on the risk of other cancers we studied. Further research is needed to clarify the results.

Prediction of the therapeutic efficacy of epirubicin combined with ifosfamide in patients with lung metastases from soft tissue sarcoma based on contrast-enhanced CT radiomics features.

OBJECTIVE: To investigate the value of contrast-enhanced computed tomography (CECT) radiomics features in predicting the efficacy of epirubicin combined with ifosfamide in patients with pulmonary metastases from soft tissue sarcoma. METHODS: A retrospective analysis of 51 patients with pulmonary metastases from soft tissue sarcoma who received the chemotherapy regimen of epirubicin combined with ifosfamide was performed, and efficacy was evaluated by Recist1.1. ROIs (1 or 2) were selected for each patient. Lung metastases were used as target lesions (86 target lesions total), and the patients were divided into a progression group (n = 29) and a non-progressive group (n = 57); the latter included a stable group (n = 34) and a partial response group (n = 23). Information on lung metastases was extracted from CECT images before chemotherapy, and all lesions were delineated by ITK-SNAP software manually or semiautomatically. The decision tree classifier had a better performance in all radiomics models. A receiver operating characteristic curve was plotted to evaluate the predictive performance of the radiomics model. RESULTS: In total, 851 CECT radiomics features were extracted for each target lesion and finally reduced to 2 radiomics features, which were then used to construct a radiomics model. Areas under the curves of the model for predicting lesion progression were 0.917 and 0.856 in training and testing groups, respectively. CONCLUSION: The model established based on the radiomics features of CECT before treatment has certain predictive value for assessing the efficacy of chemotherapy for patients with soft tissue sarcoma lung metastases.

Prognostic factors of primary neuroendocrine breast cancer: A population-based study.

BACKGROUND: Primary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial. METHODS: In this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki-67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67-15.60], p = 0.004; HR = 57.70 [6.36-523.40], p < 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33-7570.21], p = 0.037; HR = 31.47 [1.05-945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04-1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01-1.14], p = 0.015; HR = 0.10 [0.02-0.44], p = 0.003, respectively). CONCLUSIONS: Tumor grade and Ki-67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.

Evaluation of fecal SYPL1 as a diagnostic biomarker in colorectal cancer.

BACKGROUND: At present, there is still no ideal non-invasive biomarker for colorectal cancer (CRC) screening. Previously, we foundserum synaptophysin like 1 (SYPL1) served as a potential biomarker for CRC diagnosis. However, whether fecal SYPL1 (fSYPL1) are more sensitive and specific for CRC remains unclear. METHODS: We analyzed fSYPL1 in controls (n = 70), adenoma patients (n = 80), CRC patients (n = 150) and postoperative CRC patients (n = 25) by ELISA. RESULTS: SYPL1 was stable in feces. The fSYPL1 levels were significantly higher in CRC patients than in either controls or adenoma patients (P < 0.0001). ROC curves showed that fSYPL1 performed superbly in distinguishing CRC patients from controls (AUC = 0.947; 95% CI: 0.920-0.974, P < 0.0001, sensitivity: 80.67%, specificity: 100.00%), which showed much stronger performance than the traditional biomarkers (FOBT, CEA and CA19-9). Meanwhile, the fSYPL1 level positively correlated with tumor size, tumor invasion, lymph node invasion and clinical stage (P < 0.05). In addition, the detection rate of fSYPL1 was high in early CRC (75.00% in stage I and II). The fSYPL1 levels in CRC patients declined substantially after surgery (P = 0.0002). By means of a lower cut off level, 73.58% of high-risk adenomas were detected. The combination of fSYPL1 and FOBT performed better than the combination of plasma SYPL1, CEA and CA199 in distinguishing CRC patients from controls. CONCLUSION: The fSYPL1 might be a potential biomarker for CRC screening, early diagnosis, prognosis prediction and therapeutic effect monitoring.

Circular RNA_0000326 promotes bladder cancer progression via microRNA-338-3p/ETS Proto-Oncogene 1/phosphoinositide-3 kinase/Akt pathway.

Circular RNAs (circRNAs) play a pivotal regulatory role in bladder cancer (BC) occurrence and progression. The expression level, role and mechanism of circ_0000326 in BC remain unknown. In the present study, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to evaluate the expressions of circ_0000326, microRNA-338-3p (miR-338-3p) and ETS Proto-Oncogene 1(ETS1) mRNA in BC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, wound healing assay and flow cytometry were used to detect the impacts of circ_0000326 on BC cell growth, migration and apoptosis. Western blot was used to detect the expressions of ETS1, phospho-phosphoinositide-3 kinase (p-PI3K), phospho-AKT, PI3K and AKT protein. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the biological function of ETS1 in BC. Here, we found that circ_0000326 expression was significantly elevated in BC cell lines and tissues, and circ_0000326 could promote BC cell growth and migration, and inhibit apoptosis. Dual-luciferase reporter gene assay confirmed that circ_0000326 and ETS1 could bind directly to miR-338-3p. Furthermore, circ_0000326 sponged miR-338-3p and up-regulated ETS1 expression. ETS1 was associated with the activation of PI3K/AKT pathway. Moreover, circ_0000326 could activate PI3K/AKT pathway by miR-338-3p/ETS1 axis. Collectively, circ_0000326/miR-338-3p/ETS1/PI3K/AKT pathway is involved in regulating BC progression.

Bone mesenchymal stem cell-derived exosome-loaded injectable hydrogel for minimally invasive treatment of spinal cord injury.

Aim: Bone mesenchymal stem cell-derived exosomes (Exos) have been shown to exert therapeutic effects in spinal cord injury (SCI). In this study, we aimed to apply bioengineering approaches to promote Exo retention and their sustained release for SCI repair. Materials & methods: 3D gelatin methacrylate hydrogel (GelMA) was used as a transplanted Exo delivery system (GelMA-Exos). The viability, proliferation, and differentiation of neural stem cells cultured on hydrogel were assessed. Further, GelMA-Exos was injected into the damaged lesions to assess its repair potential. Results: GelMA hydrogel enhanced the retention of Exos, which promoted the neuronal differentiation and extension in vitro. Furthermore, GelMA-Exos promoted neurogenesis and attenuated glial scars in the damaged lesions. Conclusion: The injectable Exo-loaded 3D hydrogel induced neurological functional recovery post SCI.