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Background Hepatocellular carcinoma (HCC) is characterized by rapid progression, high recurrence rate and poor prognosis. Early prediction for the prognosis and immunotherapy efficacy is of great significance to improve the survival of HCC patients. However, there is still no reliable predictor at present. This study is aimed to explore the role of centromere protein L (CENPL) in predicting prognosis and its association with immune infiltration in HCC. Methods The expression of CENPL was identified through analyzing the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data. The association between CENPL expression and clinicopathological features was investigated by the Wilcoxon signed-rank test or Kruskal Wallis test and logistic regression. The role of CENPL in prognosis was examined via Kaplan-Meier method and Log-rank test as well as univariate and multivariate Cox regression analysis. Besides, in TIMER and GEPIA database, we investigated the correlation between CENPL level and immunocyte and immunocyte markers, and the prognostic-related methylation sites in CENPL were identified by MethSurv. Results CENPL had a high expression in HCC samples. Increased CENPL was prominently associated with unfavorable survival, and maybe an independent prognostic factor of worse overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), progression-free interval (PFI). Additionally, CENPL expression was significantly correlated with immune cell infiltration and some markers. CENPL also contained a methylation site that was notably related to poor prognosis. Conclusions Elevated CENPL may be a promising prognostic marker and associate with immune infiltration in HCC.

Introduction Based on the results of long-term clinical and radiological follow-up studies of decompression and fusion with internal fixation for degenerative lumbar spondylolisthesis (DLS), we recognized that the direction of the pedicle screw affects the stability of the fixation. However, few studies have analyzed the role of pedicle screw insertion trajectory in disc height recovery after fusion. We therefore analyzed patients’ general information, clinical efficacy and sagittal, coronal and implant parameters to determine whether there is a correlation between the insertion trajectory of screws and the recovery of intervertebral space height, with the ultimate aim to provide a basis for improving the clinical efficacy and radiological outcomes of patients with DLS and to identify an optimal technique for spine surgeons that would benefit patients with spondylolisthesis. Methods From May 2015 to October 2019, patients who underwent single-segment decompression and fusion with internal fixation for DLS at our department were screened for enrollment in the study. The clinical history, pre- and post-operative lumbar sagittal parameters, intervertebral height, rate of recovery from spondylolisthesis and pedicle screw angle of inpatients were recorded and followed up for at least 6 months. Clinical assessments included the Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for lower back and leg pain. Data on screw angle, fusion segment intervertebral space height and clinical outcome were the primary outputs. Pearson correlation and multivariate regression analyses were performed to investigate the relationship between the pedicle screw angle, the sagittal parameters of the fusion segment and clinical efficacy. Results A total of 50 patients were initially enrolled, two patients were lost to follow-up after 6 months, 48 patients (17 men, 31 women) were eventually enrolled, and the follow-up rate was 96%. At least 6 months after the operation, vertebral spondylolisthesis improved to varying degrees [> 80% in 17 cases (35.4%) and > 20% in 43 cases (87.5%), respectively]. Changes in disc height (DH) were significantly associated with lower pedicle screw angle, while lumbar lordosis and segment lordosis remained the same. Multivariate regression analysis showed a significant negative correlation between the upper and lower pedicle screw angles and the change in DH (P

What is known about this topic? Dengue fever is an acute febrile illness caused by four types of dengue virus (DENV 1–4), and is a mosquito-borne infectious disease. The incidence of dengue has increased dramatically around the world in recent decades. An estimated of 3.9 billion people in 128 countries are at risk of infection with dengue viruses, 70% of whom are in Asia. In 2017, the first local infections of dengue virus (DENV-2) in Jiangxi Province was reported in Zhanggong District, Ganzhou City. What is added by this report? From August to September 2019, the first dengue outbreak happened in Xin’gan County, where 81 local dengue fever cases were reported, 35 were laboratory-confirmed cases, and 46 were clinically-diagnosed cases; all cases were dengue virus type 1. The DENV-virus strains isolated from the cases of Xin’gan County were close to the strains isolated in Singapore (MF033254|25657|Singapore|2016) and Henan (MK905537|Henan201903|China: Henan Province|2019). What are the implications for public health practice? The outbreak might have been caused by imported cases or covert infections. The outbreak in Xin’gan County indicated that more proactive countermeasures should be taken during the dengue epidemic period such as intensifying surveillance for dengue cases, virus serotype, and Aedes vector density and strengthening cooperation with customs and tourism departments. Moreover, the outbreak should prompt training in medical institutions and improved ability for doctor’s to diagnose dengue fever, which is very important for early detection of dengue cases and taking preventive measures.

Background: Previous studies reported that emodin extracted from Rheum palmatum L. exerts antiproliferation and antimetastatic effects in a variety of human cancer types. However, the role of emodin in hepatocellular carcinoma (HCC) remain unknown.Methods: EdU and colony formation assays were performed to evaluate the effects of emodin on proliferation. The mobility capacities of HCC treated with emodin were evaluated using wound healing assay. Transwell invasion and migration assays were performed to evaluate anti-migratory and anti-invasive effects of emodin on HCC. Annexin V-FITC/PI was performed to analyze the apoptosis. PI stain was performed to analyze cell cycle. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) induced by emodin in HCC. The impact of emodin on autophagic flux in HepG2 cells was examined by mCherry-GFP-LC3 analysis. Western blot was used to assess the protein expressions of epithelial-mesenchymal transition (EMT), autophagy, PI3K/AKT/mTOR and Wnt/β-catenin signaling pathway.Results: We found that emodin inhibited the growth of HepG2 cells in a dose- and time-dependent manner. In addition, emodin inhibited cell proliferation, induced S and G2/M phases arrest, and promoted apoptosis in HepG2 cells. The migration and invasion of HepG2 cells were also suppressed by emodin. Enrichment analysis revealed that DEGs involved in cell adhesion, cancer metastasis and cell cycle arrest. Moreover, western blot and bioinformatics analysis indicated that emodin induced autophagy and inhibited the EMT in part through suppression of the PI3K/AKT/mTOR and Wnt/β-catenin pathways. Conclusion: Our study indicated that emodin inhibited cell metastasis in HCC via the crosstalk between autophagy and EMT.

Assessing renal function accurately is important for human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) patients. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recommended three equations to calculate estimated glomerular filtration rate (eGFR). There is evidence that eGFR based on the combination of serum creatinine and cystatin C is the most accurate of the three equations. But there is limited data on the comparison of three CKD-EPI equations in Chinese HIV/AIDS patients. The aim of our study was to compare the three CKD-EPI equations in Chinese HIV/AIDS population and assess renal function. Cross-sectional, single center, prospective study. One hundred seventy two Chinese adult HIV/AIDS patients were enrolled, including 145 (84.3%) males and 27 (15.7%) females. Mean age was 40(±12) years old. Overall mean eGFR based on serum creatinine, cystatin C and the combination of the 2 markers was 112.6(±19.0) mL/min/1.73 m2, 92.0(±24.2)mL/min/1.73 m2, and 101.7(±21.8)mL/min/1.73 m2, respectively (P = .000). The eGFR calculated by serum creatinine alone is higher than eGFR calculated by combination of serum creatinine and cystatin C, and eGFR calculated by cystatin C individual is lower than eGFR calculated by combination of the 2 markers. Of the 3 CKD-EPI equations, the CKD-EPIscr-cys equation may have the most accuracy in evaluating renal function in Chinese HIV/AIDS patients while the CKD-EPIscr equation may overestimate renal function and the CKD-EPIcys equation may underestimate renal function.

Background: Hepatocellular carcinoma (HCC) is a malignant tumor with rapid progression, high recurrence rate and poor prognosis. The objective of our investigation was to explore the prognostic value of CDK5R1 in HCC. Methods: The raw data of HCC raw data were downloaded from The Cancer Genome Atlas (TCGA) database. The Wilcoxon signed-rank test, Kruskal–Wallis test and logistic regression were applied to investigate the relevance between the CDK5R1 expression and clinicopathologic characteristics in HCC. Kaplan–Meier and Cox regression analysis were employed to examine the association between clinicopathologic features and survival. Gene set enrichment analysis (GSEA) was applied to annotate the biological function of CDK5R1. Results: CDK5R1 was highly expressed in HCC tissues. The high expression of CDK5R1 in HCC tissues was significantly associated with tumor status (P=0.00), new tumor event (P=0.00), clinical stage (P=0.00) and topography (P=0.00). Elevated CDK5R1 had significant correlation with worse overall survival (OS; P=7.414e−04), disease-specific survival (DSS; P=5.642e−04), disease-free interval (DFI; P=1.785e−05) and progression-free interval (PFI; P=2.512e−06). Besides, univariate and multivariate Cox regression analysis uncovered that increased CDK5R1 can independently predict adverse OS (P=0.037, hazard ratio [HR]= 1.7 (95% CI [1.0–2.7])), DFI (P=0.007, hazard ratio [HR]= 3.0 (95% CI [1.4–6.7])), PFI (P=0.007, hazard ratio [HR]= 2.8 (95% CI [1.3–5.9])). GSEA disclosed that notch signaling pathway and non-small cell lung cancer were prominently enriched in CDK5R1 high expression phenotype. Conclusions: Increased CDK5R1 may act as a promising independent prognostic factor of poor survival in HCC.

Primary liver cancer is a rapidly progressing neoplasm with high morbidity and mortality rates. The present study aimed to identify potential diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus (HBV)-associated early stage hepatocellular carcinoma (HCC). The gene expression profiles were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), hub genes and the enrichment of signaling pathways were filtered out via a high-throughput sequencing method. The association between hub genes and the effects of the abnormal expression of hub genes on the rate of genetic variation, overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DSS) of patients with HCC, as well as pathological stage and grade, were analyzed using different databases. A total of 1,582 DEGs were identified. Gene Ontology analysis revealed that the DEGs were mainly involved in the 'oxidation-reduction process', 'steroid metabolic process', 'metabolic process' and 'fatty acid beta-oxidation'. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways revealed that the DEGs were mainly associated with 'metabolic pathways', 'PPAR signaling pathway', 'fatty acid degradation' and the 'cell cycle'. A total of 8 hub genes were extracted. Additionally, the abnormal expression levels of hub genes were closely associated with the OS, RFS, PFS and DSS of patients, the pathological stage and the grade. Furthermore, abnormal expression levels of the 8 hub genes were found in >30% of all samples. Several small molecular compounds that may reverse the altered DEGs were identified based on Connectivity Map analysis, including phenoxybenzamine, GW-8510, resveratrol, 0175029-0000 and daunorubicin. In conclusion, the dysfunction of fat metabolic pathways, the cell cycle, oxidation-reduction processes and viral carcinogenesis may serve critical roles in the occurrence of HBV-associated early stage HCC. The identified 8 hub genes may act as robust biomarkers for diagnosis and prognosis. Some small molecular compounds may be promising targeted agents against HBV-associated early stage HCC.

Background The E2F family of transcription factor 2 (E2F2) plays an important role in the development and progression of various tumors, but its association with hepatocellular carcinoma (HCC) remains unknown. Our study aimed to investigate the role and clinical significance of E2F2 in HCC. Methods HCC raw data were extracted from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test, Kruskal-Wallis test and logistic regression were applied to analyze the relationship between the expression of E2F2 and clinicopathologic characteristics. Cox regression and Kaplan-Meier were employed to evaluate the correlation between clinicopathologic features and survival. The biological function of E2F2 was annotated by Gene Set Enrichment Analysis (GSEA). Results The expression of E2F2 was increased in HCC samples. The expression of elevated E2F2 in HCC samples was prominently correlated with histologic grade (OR = 2.62 for G3–4 vs. G1–2, p = 1.80E-05), clinical stage (OR = 1.74 for III-IV vs. I-II, p = 0.03), T (OR = 1.64 for T3–4 vs.T1–2, p = 0.04), tumor status (OR = 1.88 for with tumor vs. tumor free, p = 3.79E-03), plasma alpha fetoprotein (AFP) value (OR = 3.18 for AFP ≥ 400 vs AFPp = 2.16E-04; OR = 2.50 for 20 ≤ AFPp = 2.56E-03). Increased E2F2 had an unfavorable OS (p = 7.468e− 05), PFI (p = 3.183e− 05), DFI (p = 0.001), DSS (p = 4.172e− 05). Elevated E2F2 was independently bound up with OS (p = 0.004, hazard ratio [HR] = 2.4 (95% CI [1.3–4.2])), DFI (P = 0.029, hazard ratio [HR] = 2.0 (95% CI [1.1–3.7])) and PFI (P = 0.005, hazard ratio [HR] = 2.2 (95% CI [1.3–3.9])). GSEA disclosed that cell circle, RNA degradation, pyrimidine metabolism, base excision repair, aminoacyl tRNA biosynthesis, DNA replication, p53 signaling pathway, nucleotide excision repair, ubiquitin-mediated proteolysis, citrate cycle TCA cycle were notably enriched in E2F2 high expression phenotype. Conclusions Elevated E2F2 can be a promising independent prognostic biomarker and therapeutic target for HCC. Additionally, cell cycle, pyrimidine metabolism, DNA replication, p53 signaling pathway, ubiquitin-mediated proteolysis, the citrate cycle TCA cycle may be the key pathway by which E2F2 participates in the initial and progression of HCC.

Facetectomy is an important intervention for spinal stenosis but may lead to spinal instability. Biomechanical knowledge for facetectomy can be beneficial when deciding whether fusion is necessary. Therefore, the aim of this study was to investigate the biomechanical effect of different grades of facetectomy. A three-dimensional nonlinear finite element model of L3–L5 was constructed. The mobility of the model and the intradiscal pressure (IDP) of L4-L5 for standing were inside the data from the literature. The effect of graded facetectomy on intervertebral rotation, IDP, facet joint forces, and maximum von Mises equivalent stresses in the annuli was analyzed under flexion, extension, left/right lateral bending, and left/right axial rotation. Compared with the intact model, under extension, unilateral facetectomy increased the range of intervertebral rotation (IVR) by 11.7% and IDP by 10.7%, while the bilateral facetectomy increased IVR by 40.7% and IDP by 23.6%. Under axial rotation, the unilateral facetectomy and the bilateral facetectomy increased the IVR by 101.3% and 354.3%, respectively, when turned to the right and by 1.1% and 265.3%, respectively, when turned to the left. The results conclude that, after unilateral and bilateral facetectomy, care must be taken when placing the spine into extension and axial rotation posture from the biomechanical point of view.

Background Compared to other risk factors, adjacent facet joint degeneration (AFD) is the main contributor to adjacent segment disease (ASD). The interbody cage may be a potential indirect risk of AFD. This study investigated the correlations among the lumbar sagittal balance parameters, the inter-body cage's intraoperative positioning variables, and adjacent facet joint degeneration following the transforaminal lumbar interbody fusion (TLIF) technique. Methods Patients who accepted single-level TLIF for symptomatic lumbar degenerative disease and were followed up for at least six months were enrolled in this study. According to the inclusive and exclusive criteria, 93 patients were included (44 males and 49 females). X-ray and computed tomography (CT) images were obtained before and six months after surgery. The vertebral contour and the center of the marker mass in the cage were calculated using a geometric algorithm. Orthopedic surgeons measured the disc height, lordosis angle, and facet joint degeneration. Patient-reported outcomes, including the Oswestry Disability Index (ODI) and the visual analog scale (VAS), were used to assess the clinical outcomes. The Student's t-test, Wilcoxon rank-sum test, and Chi-square test were used for the statistical analyses. Results The average age was 53.7 years old (range, 27-84 years). The average functional disability outcome assessed by the ODI was 61.2, and the average back and leg pain assessed by the VAS was 6.2 and 6.9, respectively. The patients were categorized into a normal group and an abnormal (AFD) group according to whether the facet joint degeneration was aggravated. The abnormal group had a higher back pain VAS score (P=0.031) and lower sagittal vertical position (P=0.027). The other parameters were similar at baseline (P>0.05). The cage's sagittal vertical position decreased significantly with AFD aggravation (OR, 0.737; 95% CI, 0.561-0.969). Conclusions In patients with AFD aggravation, the preoperative VAS and postoperative ODI scores were significantly higher. The cage position parameters were related to AFD. A lower cage center was associated with a greater incidence of AFD.

Ethnopharmacological relevance GegenQinlian Decoction (GQD), a classical formula in traditional Chinese medicine, is widely used in the treatment of diabetes. While studies have demonstrated that GQD is an efficacious treatment for insulin resistance (IR) in type 2 diabetes mellitus (T2DM), the potential bioactive compounds and mechanisms remain unclear. Aim of the study To further investigate the potential bioactive compounds, targets, and pathways of GQD on improving IR in T2DM for adipose, liver, and muscle tissue using an integrated strategy of system pharmacology and bioinformatics analysis. Materials and methods We screened the candidate compounds and targets of GQD and identified IR-associated differentially expressed genes (DEGs) of adipose, liver, and muscle tissue, respectively. Then the intersecting target genes between candidate targets and DEGs were used for “GQD-compounds-targets-tissue” network construction in each type of tissue. The top 10 bioactive compounds acting on each type of tissue were intersected and consequently identified as potential bioactive compounds of GQD. Furthermore, pathway enrichment, protein-protein interaction (PPI) network construction, and hub target identification were performed based on the targets of GQD and the targets of quercetin in each type of tissue, respectively. Finally, to further confirm the role of quercetin, we intersected the hub targets of quercetin and the hub targets of GQD, and the pathways were intersected as well. Results 132 compounds and 119 potential targets of these compounds were obtained. 1,765, 3,206, and 3594 DEGs were identified between IR and insulin sensitivity (IS) tissue in adipose, liver, and muscle, respectively. There were 21, 23, 45 targets and 103, 73, 123 compounds in the “GQD-compounds-targets-tissue” network of adipose, liver, and muscle tissue, respectively. Then compounds such as quercetin, kaempferol, baicalein, wogonin, isorhamnetin, beta-sitosterol and licochalcone A, were identified as the potential bioactive compounds of GQD, and quercetin had the highest degree among the compounds. Moreover, based on the targets of GQD, hub targets like PPARG, RELA, EGFR, CASP3, VEGFA, AR, ESR1 and CCND1, and signaling pathways such as insulin signaling pathway, endocrine resistance, TNF signaling pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, MAPK signaling pathway, NF-κB signaling pathway, HIF-1 signaling pathway, apoptosis, and VEGF signaling pathway, were filtered out as the underlying mechanisms of GQD on improving diabetic IR. In addition, the hub targets and pathways of quercetin coincided with most of the hub targets and pathways of GQD in each type of tissue, respectively, suggesting that quercetin may be a potential representative compound of GQD. Conclusions Our analysis identifies the potential bioactive compounds, targets, and pathways of GQD on improving IR in T2DM for adipose, liver, and muscle tissue, which shows the characteristics of multi-compounds, multi-targets, multi-pathways, and multi-mechanisms of GQD and lays a solid foundation for further experimental research and clinical application.

Spinal cord injury (SCI) leads to several neurologic damages to patients with sensory and motor function loss. Although some inspiring results were reported in animal, even in non-human primate models, the clinical translation of these research achievements barely move forward for the SCI patients. This review mainly focused on the pathogenesis of the primary and secondary injury, the clinical therapies and the new technologies in spinal cord injury. Moreover, the key scientific issues on this field were discussed in the review. Finally, some suggestions were proposed for the scientific and clinical researches.

PURPOSE: There is still some controversy regarding the optimal biomechanical concept for spinopelvic stabilization following total sacrectomy for malignancy. Strains at specific anatomical sites at pelvis/sacrum and implants interfaces have been poorly investigated. Herein, we compared and analyzed the strains applied at key points at the bone-implant interface in four different spinopelvic constructs following total sacrectomy; consequently, we defined a balanced architecture for spinopelvic fusion in that situation. METHODS: Six human cadaveric specimens, from second lumbar vertebra to proximal femur, were used to compare the partial strains at specific sites in a total sacrectomy model. Test constructs included: (1) intact pelvis (control), (2) sacral-rod reconstruction (SRR), (3) bilateral fibular flap reconstruction (BFFR), (4) four-rods reconstruction (FRR), and (5) improved compound reconstruction (ICR). Strains were measured by bonded strain gauges onto the surface of three specific sites (pubic rami, arcuate lines, and posterior spinal rods) under a 500 N axial load. RESULTS: ICR caused lower strains at specific sites and, moreover, on stress distribution and symmetry, compared to the other three constructs. Strains at pubic rami and arcuate lines following BFFR were lower than those following SRR, but higher at the posterior spinal rod construct. The different modes of strain distribution reflected different patient's parameter-related conditions. FRR model showed the highest strains at all sites because of the lack of an anterior bracing frame. CONCLUSIONS: The findings of this investigation suggest that both anterior bracing frame and the four-rods load dispersion provide significant load sharing. Additionally, these two constructs decrease the peak strains at bone-implant interface, thus determining the theoretical surgical technique to achieve optimal stress dispersion and balance for spinopelvic reconstruction in early postoperative period following total sacrectomy.