Thioredoxin-1 Protects Neurons Through Inhibiting NLRP1-Mediated Neuronal Pyroptosis in Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease all over the world. In the last decade, accumulating proofs have evidenced that neuroinflammation is intimately implicated in the pathogenesis of AD and activation of NOD-like receptor family pyrin domain-containing 1 (NLRP1) inflammasome can induce neuronal pyroptosis and in turn lead to neuronal loss in AD. Thioredoxin-1 (Trx-1), a multifunctional molecule with anti-inflammation in human tissues, displays crucial neuroprotective roles in AD. Our previous research preliminarily found that Trx-1 inhibition enhanced the expression of NLRP1, caspase-1, and gasdermin D (GSDMD) in Aß25-35-treated PC12 cells. However, it is largely unknown if Trx-1 can inhibit NLRP1-mediated neuronal pyroptosis in AD neurons. In this study, it was verified that the protein levels of NLRP1, caspase-1, and GSDMD were significantly increased in Aß25-35-treated mouse HT22 and primary hippocampal neurons. Suppression of Trx-1 with PX-12, a selective inhibitor of Trx-1, or Trx-1 knockdown further activated NLRP1-mediated neuronal pyroptosis. On the contrary, lentivirus infection-mediated Trx-1 overexpression in differentiated PC12 cells dramatically reversed expression of NLRP1, caspase-1, and GSDMD. Furthermore, Trx-1 overexpression mediated by adeno-associated virus in the hippocampal tissues of APP/PS1 mice likewise attenuated the activation of NLRP1-mediated neuronal pyroptosis, as well as reduced the hippocampal deposition of Aß and ameliorated the cognitive function of APP/PS1 mice. In conclusion, this article predicates a novel molecular mechanism by which Trx-1 exploits neuroprotection through attenuating NLRP1-mediated neuronal pyroptosis in AD models, suggesting that Trx-1 may be a promising therapeutic target for AD.

Application of 3D­printed porous titanium interbody fusion cage vs. polyether ether ketone interbody fusion cage in anterior cervical discectomy and fusion: A systematic review and meta­analysis update.

The present study aimed to compare the differences between 3D-printed porous titanium and polyether ether ketone (PEEK) interbody fusion cages for anterior cervical discectomy and fusion (ACDF). Literature on the application of 3D-printed porous titanium and PEEK interbody fusion cages for ACDF was searched in the PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang and VIP databases. A total of 1,181 articles were retrieved and 12 were finally included. The Cochrane bias risk assessment criteria and Newcastle-Ottawa scale were used for quality evaluation and Review Manager 5.4 was used for data analysis. The 3D cage group was superior to the PEEK cage group in terms of operative time [mean difference (MD): -7.68; 95% confidence interval (CI): -11.08, -4.29; P<0.00001], intraoperative blood loss (MD: -6.17; 95%CI: -10.56, -1.78; P=0.006), hospitalization time (MD: -0.57; 95%CI: -0.86, -0.28: P=0.0001), postoperative complications [odds ratio (OR): 0.35; 95%CI: 0.15, 0.80; P=0.01], C2-7 Cobb angle (MD: 2.85; 95%CI: 1.45, 4.24; P<0.0001), intervertebral space height (MD: 1.20; 95%CI: 0.54, 1.87; P=0.0004), Japanese Orthopaedic Association Assessment of Treatment (MD: 0.69; 95%CI: 0.24, 1.15; P=0.003) and visual analogue scale score (MD: -0.43; 95%CI: -0.78, -0.07; P=0.02). The difference was statistically significant, while there was no significant difference between the two groups in terms of fusion rate (OR: 1.74; 95%CI: 0.71, 4.27; P=0.23). The use of 3D-printed porous titanium interbody fusion cage in ACDF has the advantages of short operation time, less bleeding loss, shorter hospitalization time and fewer postoperative complications. It can better maintain the cervical curvature and intervertebral height, relieve pain and accelerate postoperative functional recovery.

A child With Diphallia, Duplicate Bladder, Bladder Exstrophy, and Anorectal Malformation.

Congenital true diphallia, complete duplicate bladder, bladder exstrophy, and anorectal malformation in a child are uncommon. Here, we present the case of a 3-year-old boy with multiple genitourinary malformation, including true diphallia, complete duplicate bladder, bladder exstrophy, epispadias, and anorectal malformation. Multi-departmental collaborative treatment for complex conditions ultimately achieved an ideal appearance for this patient. All vital signs were stable after the surgery and they remained consistent during follow-up. In such cases, surgical correction is individualized to achieve adequate urinary continence and erection with adequate esthetics.

Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis. OBJECTIVES: We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility. METHODS: All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI). RESULTS: The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population. CONCLUSION: We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.

A rare presentation of Maffucci syndrome: A case report and literature review.

Maffucci syndrome is an extremely rare disease which can manifest symptoms as early as childhood. It is estimated that there have been <300 cases reported globally; however, this number is likely to be an underestimate. Maffucci syndrome is characterized by multiple enchondromas and soft tissue hemangiomas, which can cause growth and developmental malformations. In addition to bone deformities, pathological fractures and a loss of mobility, patients with Maffucci syndrome may develop secondary central chondrosarcoma and have a higher risk of developing non-skeletal malignant tumors, such as gliomas and mesenchymal ovarian tumors. The present study provides information for clinicians about this disease through the use of imaging, physical examinations, clinical manifestations and the treatment strategy used. There is need to summarize the existing cases of this disease around the world and produce an effective framework for the diagnosis, treatment and prevention of Maffucci syndrome, in order to better understand this disease. The present study reports on a 15-year-old male diagnosed with Maffucci syndrome. . Due to the risk of malignant tumor development in the absence of effective treatment, regular and careful observation through monitoring of tumor markers and imaging studies is important for patients with Maffucci syndrome. As cases of this disease are rare and case data is limited, it is difficult to create a clear treatment plan. There is an urgent need to establish a case database of Maffucci syndrome patients and explore its pathogenesis for early diagnosis, treatment and prevention of disease.

The development and application of pediatric complicated appendicitis prediction model.

BACKGROUND: Acute appendicitis in children refers to the acute inflammation of the appendix, which accounts for 20% ∼ 30% of cases of acute abdomen in pediatric surgery. OBJECTIVE: This study aimed to establish a decision tree model of complicated appendicitis in children using appendiceal ultrasound combined with an inflammatory index and evaluated its clinical efficacy in pediatric patients. METHODS: A total of 395 children admitted to the Emergency Department of the Shanghai Children's Hospital from January 2018 to December 2021 and diagnosed with appendicitis by postoperative pathology were retrospectively analyzed. According to the postoperative pathology, the children were divided into a complicated and non-complicated appendicitis group, respectively. Routine laboratory inflammatory indicators, including white blood cell count, N(%), neutrophil (Neu) count, Neu/lymphocyte ratio (NLR), C-reactive protein (CRP), and procalcitonin were collected from the two groups. Collecting data on ultrasound examination of the appendix includes whether the appendix diameter is thickened, whether the echogenicity of the mesenteric rim surrounding the appendix is enhanced, whether there is rich blood supply in the appendix, and whether there are fecaliths in the appendix lumen. The risk factors for complicated appendicitis were screened out by univariate and multivariate logistic regression analyses, the binary logistic regression prediction and decision tree models were established, respectively, and the receiver operating characteristic (ROC) curve was used to verify the accuracy of the two prediction models. RESULTS: Binary logistic regression analysis showed that CRP, NLR, the presence of an appendicolith, and peripheral retina echo enhancement were independent risk factors for complicated appendicitis in children (P< 0.05). The decision tree model had an overall accuracy of 79%, an area under the ROC curve (AUC) of 0.809 (95% confidence interval [CI] 0.780-0.865), and sensitivity and specificity of 71.3% and 77.7%, respectively. The logistic regression model had an overall accuracy of 74.9%, an AUC value of 0.823 (95% CI, 0.765-0.853), a sensitivity value of 80.3%, and a specificity of 71.8%. CONCLUSION: This predictive model, based on ultrasound of the appendix combined with inflammatory markers, provides a useful method to assist pediatric emergency physicians in diagnosing childhood appendicitis. The decision tree model reflected the interaction of various indexes, and the model was simple, intuitive, and effective.

Efficacy and safety of unilateral biportal endoscopy compared with microscopic decompression in the treatment of lumbar spinal stenosis: A systematic review and updated meta­analysis.

The incidence of lumbar spinal stenosis is increasing annually, and with an ever-aging population and longer life expectancies, this trend will further continue. It is hoped that a more effective treatment can be found so that the patients can be relieved of their pain. The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of unilateral biportal endoscopic surgery (UBE) and microscopic decompression surgery (MD) for the treatment of lumbar spinal stenosis. A literature search of related studies published until April 2022 was performed using PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, Google Scholar, China National Knowledge Infrastructure (CNKI), and other databases. After filtering of references, 12 eligible studies were identified that compared UBE with MD as a treatment for lumbar spinal stenosis. Data were extracted and analysed using R. A total of 12 articles (four randomized controlled and eight cohort studies) were included, with a total of 1,067 patients: 250 men and 249 women in the UBE group and 290 men and 278 women in the MD group. The meta-analysis showed that the mean intraoperative blood loss in the UBE group [standardized mean difference (SMD)=-2.10, 95% confidence interval (CI) (-3.97, -0.23), P=0.03] was lower than that in the MD group. The postoperative Visual analogue scale (VAS) score for back pain [SMD=-0.52, 95% CI (-0.76, -0.27), P<0.01], leg pain [SMD=-0.30, 95% CI (-0.51, -0.08), P<0.01], postoperative Oswestry disability index [(ODI); SMD=-0.25, 95% CI (-0.48, -0.03), P=0.03], and postoperative C-reactive protein [(CRP); odds ratio (OR)=-0.92, 95% CI (-1.80, 0.03), P=0.04] were lower than those in the MD group. Complications (OR=0.60, 95% CI (0.37, 0.98), P=0.04) and hospital stay (SMD=-1.84, 95% CI (-2.85, 0.83), P <0.01] were also lesser in the UBE group than in the MD group. UBE was preferable to that in the MD group according to the modified MacNab score [OR=2.28, 95% CI (1.28, 4.06), P<0.01]. No significant differences were observed in the operation times between the groups. UBE surgery was found to be a better option for the treatment of lumbar spinal stenosis than MD surgery.

KCNQ1OT1 sponges miR-34a to promote malignant progression of malignant melanoma via upregulation of the STAT3/PD-L1 axis.

BACKGROUND: Malignant melanoma is a leading cause of skin cancer-related death. In over 30% of cases, the melanoma is invasive and has a metastatic phenotype. KCNQ1 overlapping transcript 1 (KCNQ1OT1) was previously identified as an oncogenic long noncoding RNA (lncRNA). Our study intends to uncover the mechanism of KCNQ1OT1 functioning in melanoma. METHODS: qRT-PCR, immunohistochemical analysis, and Western blotting were used to investigate mechanisms of the lncRNA KCNQ1OT1, on its downstream genes in melanoma tissues, cells as well as the impact on CD8+ T cells. Proliferation, apoptosis, and migration/invasion were assessed in melanoma cells to evaluate the effects of KCNQ1OT1, miR-34a, and signal transducer and activator of transcription 3 (STAT3). The RNA interactions were determined by dual-luciferase reporter, and melanoma cells were co-cultured with CD8+ T cells to study immune evasion. A lactate dehydrogenase (LDH) cytotoxicity assay was used to investigate the cytotoxicity of CD8+ T cells toward melanoma cells. The in vivo tumorigenic potential of KCNQ1OT1 was defined using xenograft models. RESULTS: KCNQ1OT1 was upregulated in melanoma tissues leading to a poor prognosis, and knocking down it inhibited melanoma cell proliferation, migration, and invasion. KCNQ1OT1 regulated the progression of the melanoma via its action as a miR-34a sponge. STAT3 was found to be a downstream target of miR-34a, resulting in transcriptional regulation of Programmed cell death 1 ligand 1 (PD-L1). KCNQ1OT1 regulated STAT3 by targeting miR-34a. Knockdown of KCNQ1OT1 reduced PD-L1 level, enhanced CD8+ T cell cytotoxicity, and proliferation and inhibited apoptosis of CD8+ T cells. CONCLUSION: Melanoma cells overexpressed KCNQ1OT1, which influenced the miR-34a/STAT3 axis, to promote proliferation, migration, and invasion of melanoma cells. In addition, KCNQ1OT1 inhibited CD8+ T cell function, also via the miR-34a/STAT3/PD-L1 axis, thus promoting immune evasion of melanoma cells. The current findings expose a potential therapeutic target of melanoma.

Prognostic significance of metastatic lymph node ratio in patients with gastric cancer after curative gastrectomy: a single-center retrospective study.

BACKGROUND: The objective of this study was to evaluate the prognostic value of Metastatic lymph node ratio (MLNR) after curative gastrectomy in patients with gastric cancer (GC) and the potential for new indicators to strengthen the current guidelines. METHODS: We retrospectively researched 3864 GC patients with curative gastrectomy between February 2011 and February 2016. The following clinical data were collected from the included patients: gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, TNM stage, survival time and survival status. Patients were divided into low-MLNR (L-MLNR), and high-MLNR (H-MLNR) groups based on adjusted the X-tile cutoff-value of 0.25 for MLNR, the survival rates and clinicopathological characteristics of each group were compared. For the assessment of significant associations between clinicopathological characteristics and patients' survival, univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazards analysis. The log-rank test was used to examine the statistical significance of differences among different survival curves. Clinicopathological features significantly associated with MLNR were assessed by the Chi-square test and multinomial logistic regression. The discriminative ability was measured by calculating the Bayesian Information Criterion (BIC) values for each category. Assessment of the effect of clinicopathological features on MLNR for predicting prognosis of GC patients used stratum analysis through Kaplan-Meier analysis and Cox proportional risk Analysis. RESULTS: Survival analysis indicated that MLNR was negatively associated with overall survival (OS) (p < .001) and was an independent prognostic predictor in 3864 GC patients (p < .001). MLNR had significant prognostic significance in various subgroups with clinicopathological characteristics (gender, type of gastrectomy, tumor location, T stage, N stage, ELN, tumor size, age at surgery, perineural invasion, vascular invasion, and TNM stage) (p < .001). CONCLUSIONS: The MLNR may become a new indicator to assess the prognosis of GC patients who underwent curative gastrectomy. The results may have potential clinical implications that should be considered when developing clinical practice guidelines or the design of the future investigation.

The lncRNA HOXA11-AS acts as a tumor promoter in breast cancer through regulation of the miR-125a-5p/TMPRSS4 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) play vital roles in tumorigenesis. Here, we explored how lncRNA HOXA11-AS functions in the progression of breast cancer (BC). METHODS: HOXA11-AS and miR-125a-5p levels were measured by a quantitative real-time polymerase chain reaction, whereas western blotting determined TMPRSS4 levels in BC tumor tissues, adjacent normal tissues and BC cell lines. The roles of HOXA11-AS, miR-125a-5p and TMPRSS4 in BC proliferation were investigated using cell counting kit-8, colony formation and flow cytometry assays, whereas scratch and transwell assays were used to measure metastasis. RNA pull-down assays and dual-luciferase assays assessed direct interactions between HOXA11-AS and miR-125a-5p. The effects of HOXA11-AS in vivo were investigated in a BC xenograft model. RESULTS: HOXA11-AS was upregulated in tumor tissues of 56 BC patients compared to adjacent non-tumor tissues, with high levels being associated with worse overall survival. Silencing of HOXA11-AS inhibited the proliferation and metastasis of BC cells, leading to cell cycle arrest in G0/G1 and induction of apoptosis. We identified miR-125a-5p as a target of HOXA11-AS, with miR-125a-5p inhibitors partially restoring the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. We also determined that miR-125a-5p targeted TMPRSS4 mRNA, with HOXA11-AS knockdown and miR-125a-5p mimics suppressing TMPRSS4. Overexpression of TMPRSS4 partially compensated for the reduction of cell proliferation and metastasis induced by HOXA11-AS silencing. Finally, we confirmed the mechanism of HOXA11-AS in the regulation of tumorigenesis in the mouse model. CONCLUSIONS: HOXA11-AS regulates the tumorigenic ability of BC via the miR-125a-5p/TMPRSS4 axis. This provides insights for regulatory mechanisms involved in BC progression, and may enable new treatment strategies in the clinical setting.

KCNQ1OT1 affects cell proliferation, invasion, and migration through a miR-34a / Notch3 axis in breast cancer.

BACKGROUND: Breast cancer (BC) accounts for a significant share of cancer-related deaths worldwide. Ongoing investigations have shown that long non-coding RNAs (lncRNAs) drive BC progression but their underlying mechanisms remain largely undescribed. LncRNA KCNQ1OT1 was previously identified in BC but its functional significance remained to be fully investigated. METHODS: KCNQ1OT1 and its downstream target genes were analyzed in breast cancer tissues and cell lines using methods including RT-qPCR, immunohistochemistry and Western blotting. The effects of KCNQ1OT1, miR-34a and Notch3 on BC cells were investigated using assays measuring proliferation (CCK-8, colony formation), apoptosis, and migration/invasion (scratch and Transwell assays). MS2-RIP and dual-luciferase reporter assays were used to study RNA interactions. Xenograft studies were employed to define the tumorigenic potential of KCNQ1OT1 in vivo. RESULTS: KCNQ1OT1 expression was up-regulated in BC tissues and high levels were associated with poorer prognosis. ShRNA inhibition of KCNQ1OT1 expression in BC cell lines retarded proliferation, migration and invasion in vitro and tumor growth in vivo. Up-regulation of KCNQ1OT1 was shown to inhibit miR-34a which was associated with blocking the inhibitory effect of miR-34a on BC cell proliferation, migration and invasion. Notch3 was found to be a downstream target of miR-34a with KCNQ1OT1 markedly inducing Notch3 expression in BC. Evidence for KCNQ1OT1/miR-34a/Notch3 axis was further established in clinical BC samples. CONCLUSION: We identified a KCNQ1OT1/miR-34a/Notch3 axis which promotes BC progression through effects on cell proliferation and metastasis that was further associated with poor patient prognosis. These results propose targeting this axis as novel treatment approach for BC.

Monitoring of postoperative neutrophil-to-lymphocyte ratio, D-dimer, and CA153 in: Diagnostic value for recurrent and metastatic breast cancer.

Objective: This stydy aims to assess the value of monitoring of postoperative neutrophil-to-lymphocyte ratio (NLR), D-dimer, and carbohydrate antigen 153 (CA153) for diagnosis of breast cancer (BC) recurrence and metastasis. Materials/Methods: A cohort of 252 BC patients who underwent surgery at the First Affiliated Hospital of Anhui Medical University between August 2008 and August 2018 were enrolled in this retrospective study. All patients were examined during outpatient follow-ups every 3 months for 5 years postoperation and every 6 months thereafter. Recurrence or metastasis was recorded for 131 patients but not for the remaining 121. Retrospective analysis of hematological parameters and clinicopathological characteristics allowed comparison between the two groups and evaluation of these parameters for the recurrent and metastatic patients. Results: Lymph node metastasis, higher tumor node metastasis (TNM) staging, and higher histological grade correlated with BC recurrence and metastasis (p < 0.05). Statistical differences were found in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), CEA, CA153, D-dimer, NLR, platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) between the recurrent and metastatic and control groups (p < 0.05). Logistic regression analysis showed that CA153, D-dimer, NLR, and TNM staging were risk factors for BC recurrence and metastasis (p < 0.05). Combined values for the NLR, D-dimer, and CA153 had good diagnostic values, giving the highest area under the curve (AUC) of 0.913. High NLR, D-dimer, and CA153 values were significantly associated with recurrence and metastasis at multiple sites, lymph node metastasis, and higher TNM staging (p < 0.05). Patients with high CA153 were more likely to have bone metastases (p < 0.05), and those with high D-dimer were prone to lung metastasis (p < 0.05). With the increasing length of the postoperative period, the possibility of liver metastases gradually decreased, while that of chest wall recurrence gradually increased (p < 0.05). Conclusion: Monitoring postoperative NLR, D-dimer, and CA153 is a convenient, practical method for diagnosing BC recurrence and metastasis. These metrics have good predictive value in terms of sites of recurrence and metastasis and the likelihood of multiple metastases.

YY1-induced long non-coding RNA PSMA3 antisense RNA 1 functions as a competing endogenous RNA for microRNA 214-5p to expedite the viability and restrict the apoptosis of bladder cancer cells via regulating programmed cell death-ligand 1.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. Our research aimed to explore the function and underlying mechanisms of long noncoding RNA (lncRNA) PSMA3-AS1 in BC. RT-qPCR was utilized to detect the levels of PSMA3-AS1, miR-214-5p, and PD-L1. ChIP assay was employed to confirm the transcription factor of PSMA3-AS1. Luciferase reporter assay was carried out to demonstrate the relationships between miR-214-5p and PSMA3-AS1 or PD-L1. The diagnostic value of PSMA3-AS1 was evaluated by the ROC curve. CCK-8, wound healing, transwell, and flow cytometry assays were applied to analyze cell viability, migration, invasion, and apoptosis. Western blotting was used to confirm the expression of cleaved caspase-3. The present study revealed that BC tissues and cells exhibited an increased expression in PSMA3-AS1. High expression of PSMA3-AS1 was related to poor prognosis in BC patients. Then, the area under the ROC curve for PSMA3-AS1 was up to 0.8954. Moreover, ChIP assay elaborated that YY1 could bind to the PSMA3-AS1 promoter region. Furthermore, it was found that that PSMA3-AS1 knockdown repressed BC cell viability and metastasis, and promoted apoptosis. In addition, miR-214-5p was inversely correlated with PSMA3-AS1 or PD-L1 levels. MiR-214-5p deletion reversed the impacts of PSMA3-AS1 deletion on BC progression, and PD-L1 inhibition also abrogated the influence of miR-214-5p deletion in BC development. In conclusion, YY1-induced PSMA3-AS1 exerted an oncogenic function in BC cells via targeting miR-214-5p and enhancing PD-L1, providing potential biomarkers for BC therapy.

Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma.

BACKGROUND: Cumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment. METHODS: We compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n = 60) and TCGA (n = 411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan-Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY. RESULTS: We identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC.ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application. CONCLUSIONS: We investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

Antibacterial Activity and Mechanism of Coenzyme Q0 Against Escherichia coli.

Coenzyme Q0 (CoQ0) is a natural compound found in Antrodia cinnamomea, which has a variety of biological activities. Here, the antibacterial activity and possible antibacterial mechanism of CoQ0 against Escherichia coli were investigated. The antibacterial effect was evaluated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, and by assessing bacterial survival and the effect on the growth of E. coli after CoQ0 treatment in Luria-Bertani (LB) broth. To reveal the antibacterial mechanism of CoQ0, changes in intracellular adenosine triphosphate (ATP) concentration, membrane potential, and bacterial protein content, as well as effects on cell morphology and membrane integrity, were investigated. Both the MICs and MBCs of CoQ0 against E. coli were 0.1 mg/mL. After treatment of E. coli (6.5 log colony-forming units/mL) with 0.1 mg/mL of CoQ0 in LB broth for 3 h, the number of viable cells dropped below the detection limit. In addition, CoQ0 treatment resulted in the reduction in intracellular ATP concentration, cell membrane hyperpolarization, decreased bacterial protein concentrations, and damage to cell membrane integrity and cellular morphology. These results indicated that CoQ0 has effective antibacterial activity against E. coli, suggesting potential applications in food industry safety.

[Ultrasonographic and clinical features of common testicular germ cell tumors in children].

OBJECTIVE: To study the ultrasonographic manifestations and clinical features of common pediatric testicular germ cell tumors (TGCT) in children. METHODS: We retrospectively analyzed the laboratory, ultrasonographic and clinical data on 92 children with TGCT diagnosed in Shanghai Children's Hospital from March 2013 to January 2019, and investigated the values of the serum alpha-fetoprotein (AFP) level and maximum diameter of tumors in the diagnosis of benign and malignant tumors using the ROC curve. RESULTS: Of the 92 cases of pediatric TGCT, 64 (69.6%) were pathologically confirmed as benign tumors, including 40 cases of teratoma (62.5%), 18 cases of epidermoid cyst (28.1%) and 6 cases of dermoid cyst (9.4%), and the other 28 (30.4%) as malignant neoplasms, including 26 cases of yolk sac tumor (YST, 92.9%) and 2 cases of mixed germ cell tumor (MGCT, 7.1%). Ultrasonography showed that 62.5% of the teratomas were cystic-solid mixed (25/40) and 32.5% solid masses (12/40), that 33.3% of the epidermoid cysts exhibited a typical sign of "onion ring" (6/18) and 22.2% that of capsular calcification (4/18), and that 42.3% of the YSTs displayed isoechoic (11/26), 30.9% hypoechoic (8/26) solid masses without calcium and 26.9% cystic anechoic lesions (7/26). Color Doppler blood flow imaging manifested abundant blood flow signals in most of the YSTs (25/26, 96.2%) but none in either the epidermoid or the dermoid cysts. The area under the ROC curve (AUC) of the serum AFP value was 0.985, with an optimal cutoff value of 124.2 ng/ml, and the sensitivity and specificity of AFP in the diagnosis of benign and malignant tumors were 92.9% and 93.7%, respectively. The AUC of the maximum diameter of the tumors was 0.796, with an optimal cutoff value of 2.7 cm, and the sensitivity and specificity of the maximum diameter of the tumors in the diagnosis of benign and malignant neoplasms were 57.1% and 93.7%, respectively. CONCLUSIONS: Ultrasonographic images have different characteristic manifestations for different pathological types of pediatric TGCT. Pediatric TGCT has a good prognosis and radical orchiectomy should be considered for the treatment of the tumors with serum AFP ≥ 124.2 ng/ml and a diameter ≥ 2.7 cm.

Effects of humus on the mobility of arsenic in tailing soil and the thiol-modification of humus.

The ability of thiol-modified humic acids (HAs) to release arsenic in tailings soil after being modified with different sulfur-containing reagents were significantly improved. The structure and physicochemical properties of humic acid (HA) before and after thiol-modification were characterized. The 3-MPTS-HA treated with 3-mercaptopropyltrimethoxysilane (3-MPTS) effectively improved the mobility of arsenic, and its reducing ability was increased from 2 mmol g-1 to 3.54 mmol g-1. The S content of humic acids were also significantly increased after treatment with sulfur-containing reagents, in which the oxygen-containing functional group (e.g., C = O, C-O) on the surface of HA may be the active sites for binding with sulfur-containing reagents. It was found in the XPS spectrum that because the thiol group is easily oxidized, there are many S forms in thiol-modified HA. The -SH content in Na2S·9H2O-HA, l (+)-Cysteine-HA (Cys-HA), thioglycolic acid (TGA-HA) and 3-MPTS-HA was determined by fluorescence method to be 13.9, 78.45, 90.34, and 192.29 µmol g-1, respectively. The study demonstrated that surface thiol modification can increase the abundance of thiol in HA and enhance reactivity, which will further promote the application of HA in the treatment of heavy metal contaminated tailing soil.

Superior-segment Bilateral Facet Violation in Lumbar Transpedicular Fixation, Part I: A Biomechanical Study of Blocking Superior Facets.

STUDY DESIGN: This is an in vitro biomechanical study. OBJECTIVES: The aim of this study was to investigate the biomechanical variations of lumbar spine motor units and that under different moments after screw heads blocking superior-adjacent bilateral facets through the cadaver specimen biomechanical experiment. SUMMARY OF BACKGROUND DATA: Facet joint violation by pedicle screws is not a rare adverse event in instrumented lumbar fusion surgery, and one of the most common types is the screw head blocking the superior-adjacent facet. However, its contribution to biomechanical instability at the supradjacent level is unknown. METHODS: The range of motion (ROM) of 12 lumbar spines (L4-S1) were measured in flexion-extension, lateral bending, and axial rotation for L4/5. All specimens were randomly divided into two groups: the control group and the blocking group, each with 6 specimens. Spine were tested on intact and instrumented specimens, respectively. The relative ROM changes were compared between the blocking and control groups. RESULTS: In the blocking group, the supradjacent-level flexion-extension ROM significantly decreased under all moments (7.5, 6.0, 4.5 Nm) relative to the intact spine and a significant decrease in the lateral bending relative ROM was found at 4.5 Nm. In the control group, no significant change of supradjacent-level ROM was found relative to the intact noninstrumented spine at each moment. When performing flexion-extension, the relative ROM change between the 2 groups was significantly different at 4.5 Nm. When performing lateral bending, the relative ROM change between the 2 groups was significantly different at moments of 6.0 and 4.5 Nm. CONCLUSION: When screw heads blocked superior-adjacent bilateral facets, the supradjacent-level flexion-extension ROM and lateral bending ROM decreased. In the long run, this may be a risk of persistent low-back pain due to frequent impingement. LEVEL OF EVIDENCE: N/A.

Incidence and Risk Factors of Superior Facet Joint Violation in Percutaneous and Open Instrumentation Using Cortical Bone Trajectory Technique: A Comparison of Different Techniques.

STUDY DESIGN: A retrospective study evaluating cranial facet joint violation (FJV) by cortical bone trajectory (CBT) screw. OBJECTIVE: To determine the incidence and risk factors of FJV following CBT screw placement for different techniques. SUMMARY OF BACKGROUND DATA: CBT is a novel technique for lumbar fusion, and FJV is one of the most common complications, leading to poor prognosis. No studies have investigated the incidence and risk factors of FJV for the CBT technique during different methods. METHODS: The authors reviewed 91 consecutive patients who underwent CBT screw instrumentation from June 2015 to August 2018. In the fluoroscopic-open group (FOG), 42 patients received an open procedure. In the navigation-open group (NOG), 24 patients underwent open instrumentation. In the navigation-percutaneous group, 25 patients underwent percutaneous instrumentation. Postoperative computed tomography scans were obtained to determine the degree and incidence of FJV. Clinical and imaging data were analyzed to clarify the risk factors of FJV. RESULTS: The incidence of FJV occurred in 35.7% of patients and 16.9% of screws in the FOG, 4.2% of patients and 3.8% of screws in the NOG, and 8.0% of patients and 8.0% of screws in the navigation-percutaneous group. Open instrumentation using navigation led to a lower risk of FJV compared with the conventional approach. There was no difference in the rate of FJV between percutaneous and open surgery with navigation assistance. Risk factors affecting FJV include: (1) left-side screw, facet angle ≥45 degrees, and scoliosis for fluoroscopy-assisted CBT instrumentation; (2) body mass index ≥30 kg/m, facet angle ≥45 degrees, and scoliosis for navigation-assisted CBT instrumentation. CONCLUSIONS: Lumbar fusion through CBT instrumentation would reduce FJV. Computer-assisted navigation resulted in a lower incidence of FJV. Percutaneous instrumentation with navigation assistance is not a risk factor for FJV. Special care should be taken in patients with body mass index ≥30 kg/m, left-side screw, facet angle ≥45 degrees, and scoliosis. LEVEL OF EVIDENCE: Level III.