Prevalence and risk factors for kidney disease among hospitalized PLWH in China.

BACKGROUND: Kidney disease is an important comorbidity in people living with HIV(PLWH), and is associated with poor outcomes. However, data on renal function of PLWH are limited in China so far. In this study we assessed the prevalence of kidney disease in patients either on antiretroviral therapy (ART) or not respectively in a single center in China and explored the possible risk factors associated. METHODS: In the cross-sectional study, we recruited hospitalized adult PLWH. Demographic characteristics, clinical information and laboratory variables were collected. Kidney disease was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and/or isolated hematuria, proteinuria, microalbuminuria. We calculated the prevalence of kidney disease and used logistic regression to assess its associated risk factors. RESULTS: A total of 501 adult PLWH were enrolled, 446 (89.0%) males and 55 (11.0%) females. The median age was 39 (IQR 30-50) years old. The prevalence of kidney disease was 19.0%, 22 (4.4%) patients with eGFR < 60 mL/min/1.73 m2, 53 (10.6%) patients with hematuria, 11 (2.2%) patients with proteinuria, and 40 (8.0%) patients with microalbuminuria. 297 (59.3%) patients were receiving ART. The patients on ART had a higher prevalence of renal disease than those had not been administrated with ART (22.6% vs. 13.7%, P = 0.013). On the multivariate logistic regression analysis among patients not on ART, lower haemoglobin (OR 0.994, 95%CI: 0.902-0.988, P = 0.013) were significantly associated with kidney disease. While among those on ART, older age (OR 1.034, 95%CI: 1.003-1.066, P = 0.032), lower haemoglobin (OR 0.968, 95%CI: 0.948-0.988, P = 0.002) and lower albumin (OR 0.912, 95%CI: 0.834-0.997, P = 0.044) were significantly associated with kidney disease. CONCLUSIONS: The prevalence of kidney disease among hospitalized PLWH in China is high, especially in patients on ART. A larger scale study on Chinese outpatient PLWH should be conducted, so as to precisely assess prevalence of kidney disease in general Chinese PLWH.

Development of a nomogram model for prediction of new adjacent vertebral compression fractures after vertebroplasty.

BACKGROUND: Vertebroplasty is the main minimally invasive operation for osteoporotic vertebral compression fracture (OVCF), which has the advantages of rapid pain relief and shorter recovery time. However, new adjacent vertebral compression fracture (AVCF) occurs frequently after vertebroplasty. The purpose of this study was to investigate the risk factors of AVCF and establish a clinical prediction model. METHODS: We retrospectively collected the clinical data of patients who underwent vertebroplasty in our hospital from June 2018 to December 2019. The patients were divided into a non-refracture group (289 cases) and a refracture group (43 cases) according to the occurrence of AVCF. The independent predictive factors for postoperative new AVCF were determined by univariate analysis, least absolute shrinkage and selection operator (LASSO) logistic regression, and multivariable logistic regression analysis. A nomogram clinical prediction model was established based on relevant risk factors, and the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effect and clinical value of the model. After internal validation, patients who underwent vertebroplasty in our hospital from January 2020 to December 2020, including a non-refracture group (156 cases) and a refracture group (21 cases), were included as the validation cohort to evaluate the prediction model again. RESULTS: Three independent risk factors of low bone mass density (BMD), leakage of bone cement and "O" shaped distribution of bone cement were screened out by LASSO regression and logistic regression analysis. The area under the curve (AUC) of the model in the training cohort and the validation cohort was 0.848 (95%CI: 0.786-0.909) and 0.867 (95%CI: 0.796-0.939), respectively, showing good predictive ability. The calibration curves showed the correlation between prediction and actual status. The DCA showed that the prediction model was clinically useful within the whole threshold range. CONCLUSION: Low BMD, leakage of bone cement and "O" shaped distribution of bone cement are independent risk factors for AVCF after vertebroplasty. The nomogram prediction model has good predictive ability and clinical benefit.

Emodin inhibits invasion and migration of hepatocellular carcinoma cells via regulating autophagy-mediated degradation of snail and ß-catenin.

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/ß-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 bolt results show that emodin-induced autophagy promotes Snail and ß-catenin degradation. We also found that blocking autophagic flux after emodin treatment caused EMT reversal. Furthermore, the PI3K agonist Y-P 740 significantly reversed the phosphorylation levels of GSK3ß and mTOR. These results indicated that emodin induced autophagy and inhibited the EMT in part through suppression of the PI3K/AKT/mTOR and Wnt/ß-catenin pathways. CONCLUSION: Our study indicated that emodin inhibited cell metastasis in HCC via the crosstalk between autophagy and EMT.

Cabin1 involves in renal tubular epithelial cells mitochondrial dysfunction through SIRT1/p53 pathway.

Background: Angiotensin II (AngII) induced Calcineurin binding protein 1 (Cabin1) protein expression significantly increased during Renal tubular epithelial cells (RTEC) injury. However, the detailed function of Cabin1 protein in RTEC was not characterized well. In this study, we aimed to explore the downstream target of Cabin1 in vitro model.Methods: Rat kidney epithelial cells were cultured and stimulated with AngII. Electron microscopy was performed to observe mitochondrial morphology change. Immunofluorescence staining was detected to observe the distribution of cytoskeleton and Cabin1. Mitochondrial morphology change and protein expression were detected by electrical microscopy and western blot.Results: AngII induced the disruption of cytoskeleton at 24 and 48 h. Western blot analysis showed AngII significantly induced the overexpression of Cabin1. AngII induced a great deal of small, long and irregular mitochondria in RTEC, aspect ratio which reflects the length-to-width ratio of mitochondria remarkably increased at 12 and 24 h. Knocking down Cabin1 aggravated mitochondrial morphological abnormality in AngII treated RTEC. In comparison with control, Cabin1, p53 and cyto C level were significantly increased in AngII treated cells, while SIRT1 level was obviously decreased. Knocked down Cabin1 plus AngII stimulated, SIRT1 was further decreased, while p53 and cyto C were significantly increased.Conclusions: Cabin1 involves in RTEC mitochondrial dysfunction through SIRT1/p53 pathway. Cabin1 may be used as a new marker for the mechanisms of RTEC injury.

Increased E2F2 predicts poor prognosis in patients with HCC based on TCGA data.

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 AFP<20, p = 2.16E-04; OR = 2.50 for 20 ≤ AFP<400 vs AFP<20, p = 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.

Distinct fusion intersegmental parameters regarding local sagittal balance provide similar clinical outcomes: a comparative study of minimally invasive versus open transforaminal lumbar interbody fusion.

BACKGROUND: Most contemporary studies suggested that intersegmental parameters including disc height and local lordosis contribute to the sagittal balance of fused lumbar. Although similar clinical outcomes following MIS- and Open-TLIF were reported essentially at the early postoperative time, the comparison of local balance variables after these two different techniques was lack. The radiological differences maybe not relevant to the postoperative efficacy at an earlier post-operation stage. But during the long-term follow-up, the complications with regards to the sagittal imbalance might occur due to the distinct biomechanical properties of fusion level after MIS- and Open-TLIF. METHODS: The patients who underwent a single-level MIS- and Open-TLIF were reviewed retrospectively. The anterior disc height (ADH), posterior disc height (PDH), and segmental lordosis (SL) of the fusion segment were measured using recognition technical fluoroscopy. The mean disc height (MDH) was calculated by (ADH + PDH)/2. The relative DH was normalized by the anterior height of the upper vertebrae. The body mass index (BMI), the pain score of low back and leg visual analogue scale (VAS), Oswestry disability index (ODI), estimated blood loss, and hospital stay length was collected. RESULTS: A total of 88 patients undergoing a single-level TLIF (MIS and Open) were included. The pre- and post-operative ADH, PDH, MDH, and SL of MIS-TLIF group were 1.57 ± 0.33 cm, 0.79 ± 0.20 cm, 1.18 ± 0.21 cm, 7.36 ± 3.07 and 1.63 ± 0.30 cm, 1.02 ± 0.28 cm, 1.32 ± 0.24 cm, 10.24 ± 4.79 respectively. Whereas, the pre- and post-operative ADH, PDH, MDH, and SL of Open-TLIF group were 1.61 ± 0.40 cm, 0.77 ± 0.21 cm, 1.19 ± 0.24 cm, 9.05 ± 5.48 and 1.81 ± 0.33 cm, 0.98 ± 0.24 cm, 1.39 ± 0.24 cm, 12.34 ± 4,74 respectively. MIS- and Open-TLIF group showed no significant differences in low back VAS, leg VAS, and ODI both in pre-operation and post-operation (P > 0.05). The estimated blood loss and hospital stay length in the MIS-TLIF group were significantly lower than those in the Open-TLIF group (P < 0.05). CONCLUSION: MIS- and Open-TLIF provided similar clinical outcomes as the respect of low back VAS, leg VAS, and ODI. MIS-TLIF significantly reduced the blood loss and length of hospital stay though. The intervertebral parameters of DH and SL were both increased significantly, Open-TLIF group presented better sagittal balance in term of ADH and SL variables. The contrast investigation of intersegmental parameters may help the surgeons to figure out the further advantages of MIS-TLIF technique, and then better manage the rehabilitation and prevent the reoperation.

[Clinical outcomes of single-level minimally invasive transforaminal lumbar interbody fusion with tube work channel system].

OBJECTIVE: To evaluate the clinical effectiveness of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in single-level lumbar degeneration disease treatment. METHODS: We retrospectively analyzed the clinical data of 32 patients who underwent the MIS-TLIF surgery from Nov. 2013 to Oct. 2014 in Shanghai Tongji Hospital.Clinical and radiological outcomes including operation time, X-ray exposure, surgical blood loss, drainage blood loss, complications, visual analogue scores (VAS), Oswestry disability index (ODI) scores, average intervertebral space and fusion rate. VAS scores of low back and leg pain, ODI scores were recorded before and after surgery to evaluate the functional recovery, average intervertebral space height, lumbar and surgical Cobb angle were measured by X-rays before and after surgery to assess recovery of intervertebral space height and the change of lumbar kyphosis. The Bridwell criterion was used for evaluating the interbody fusion and the MacNab criterion was used for assessment after surgery. RESULTS: All the patients received successful surgery. The mean operative time was (171.9±31.1) min with (36.7±16.4) seconds radiation exposure, and mean blood loss was (153.3±64.8) ml, drainage blood loss was (58.9±49.2) ml. All cases were followed up for (11.6±3.3) months. Compared with preoperation, VAS score of low back and leg pain, ODI score and average intervertebral space showed significant improvements after surgery. There were 26 (81.3%) cases were grade I and II 3 months after surgery according to the Bridwell criteria while the number was 31 (96.9%) at the last follow-up. The clinical results were excellent in 22 cases, good in 8 cases and fair in 2 cases according to the MacNab criteria at the final follow-up. CONCLUSION: MIS-TLIF under Spotlight work channel system is a safe and effective procedure for single segment lumbar degenerative disease and it may offer patients additional advantages in less trauma and reduction of hospital stay.

VoxelMorph-Based Deep Learning Motion Correction for Ultrasound Localization Microscopy of Spinal Cord.

Accurate assessment of spinal cord vasculature is important for the urgent diagnosis of injury and subsequent treatment. Ultrasound localization microscopy (ULM) offers super-resolution imaging of microvasculature by localizing and tracking individual microbubbles across multiple frames. However, a long data acquisition often involves significant motion artifacts caused by breathing and heartbeat, which further impairs the resolution of ULM. This effect is particularly pronounced in spinal cord imaging due to respiratory movement. We propose a VoxelMorph-based deep learning motion correction method to enhance ULM performance in spinal cord imaging. Simulations were conducted to demonstrate the motion estimation accuracy of the proposed method, achieving a mean absolute error of 8 µm. Results from in vivo experiments show that the proposed method efficiently compensates for rigid and nonrigid motion, providing improved resolution with smaller vascular diameters and enhanced microvessel reconstruction after motion correction. Nonrigid deformation fields with varying displacement magnitudes were applied to in vivo data for assessing the robustness of the algorithm.

The improvement of modified Si-Miao granule on hepatic insulin resistance and glycogen synthesis in type 2 diabetes mellitus involves the inhibition of TNF-α/JNK1/IRS-2 pathway: network pharmacology, molecular docking, and experimental validation.

BACKGROUND: Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown. METHODS: Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells. RESULTS: 50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experimental validation proved that mSMG ameliorated hyperglycemia, IR, and TNF-α, enhanced glucose consumption and glycogen synthesis, relieved the phosphorylation of JNK1 and IRS-2 (Ser388), and elevated the phosphorylation of Akt (Ser473) and GSK-3ß (Ser9) and GLUT2 expression in KK-Ay mice. Molecular docking further showed berberine from mSMG had excellent binding capacity with TNF-α. Then, in vitro validation experiments, we found that 20% mSMG-MS or 50 µM berberine had little effect in IR-HepG2 cell viability, but significantly increased glucose consumption and glycogen synthesis and regulated TNF-α/JNK1/IRS-2 pathway. CONCLUSION: Network pharmacology and molecular docking help us predict potential mechanism of mSMG and further guide experimental validation. mSMG and its representative compound berberine improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway.

[Unilateral versus bilateral pedicle fixation at the level of fracture in the treatment of thoracolumbar fractures with mild to moderate instability].

OBJECTIVE: To evaluate the efficacies of unilateral versus bilateral pedicle screw fixation through the pedicle of fractured vertebra plus short-segment pedicle instrumentation (SSPI) in the treatment of thoracolumbar fractures. METHODS: Between June 2008 and September 2010, a total of 46 patients with fractures of thoracolumbar junction, whose scores of load sharing classification (LSC) ranging from 5 to 7, underwent the combined treatment of SSPI and fracture level pedicle screw at our department. They were divided into 2 groups. Group I included 25 patients undergoing SSPI plus unilateral pedicle screw fixation through the pedicle of fractured vertebra (5 screws) while Group II included 21 patients had SSPI plus bilateral pedicle screw fixation through the pedicle of fractured vertebra (6 screws). The data of anterior body height compression (AVHC), sagittal Cobb's angle, internal fixation failure, restoration of nervous function, visual analogue score (VAS) and Oswestry disability index (ODI) were analyzed. RESULTS: The groups were similar with regards to age, gender, LSC, AVHC and sagittal Cobb's angle preoperatively. Blood loss volume and operative duration were less in the Group I (109.2 ± 30.68 vs 110.0 ± 32.06 min, t = -0.086, P > 0.05 and 376.0 ± 303.1 vs 409.5 ± 361.1 ml, t = -0.342, P > 0.05). They were followed up for a minimum period of 12 months. In follow-up period was 17.48 ± 4.14 months in Group I versus 18.33 ± 4.31 months in Group II (t = -0.683, P > 0.05). All patients with initial partial neurologic deficits improved at the final follow-up. Radiographic parameters and clinical outcomes were similar in both groups. CONCLUSIONS: Pedicle screw fixation through the pedicle of fractured vertebra plus SSPI is an excellent surgical therapeutic choice for patients with a LSC range of 5-7 thoraclumbar fractures. The efficacies of unilateral and bilateral pedicle screw fixation at fracture level are the same.

[Efficacy analysis of intermediate screws technique plus injectable calcium sulfate for thoracolumbar fracture in postmenopausal patients].

OBJECTIVE: To explore the clinical efficacies of intermediate screws plus injectable calcium sulfate MIIGX3 for thoracolumbar fracture in postmenopausal patients. METHODS: A total of 21 postmenopausal patients with vertebral compression fractures reconstructed with posterior internal fixation of intermediate screws technique and anterior vertebral augmentation of MIIGX3 technique in three dimension were retrospectively analyzed. The changes of fracture vertebral height and Cobb's angle were compared.Visual analogue scale (VAS) was performed to evaluate their symptoms. All patients were followed up. RESULTS: Intermediate screws surgical technique plus MIIGX3 was successfully performed. The average injection dose was 4.6 ml.Leakage occurred intraoperatively in two cases. The average follow-up period was 15 (6-36) months. The VAS system demonstrated that pain decreased significantly (preoperative:7.8, postoperative:2.2). The height and Cobb's angle of fractured vertebra improved greatly. The preoperative values were 45.0 ± 6.4% and 19.4 ± 4.5° and postoperative ones 15.4 ± 3.9% and 8.64 ± 3.18° respectively. There was no occurrence of severe complications related with treatment.Except for 2 patients with a loss of 15% of vertebral height, the average heights of fractured vertebra in other 19 patients recovered to 85% of normal ones. CONCLUSION: Thoracolumbar fracture in postmenopausal patients may be managed satisfactorily by intermediate screws and injectable calcium sulfate technique.Such a technique is both safe and effective. And its stable and durable reduction offers significant improvement.

Correlation between direction of pedicle screw and restoration of lumbar degenerative scoliosis in degenerative lumbar spondylolisthesis: a retrospective study.

Background: Inferior clinical outcomes have been reported in patients with degenerative lumbar spondylolisthesis (DLS) accompanied by lumbar degenerative scoliosis, but little attention has been paid to its radiologic assessment or preoperative planning. The aim of this study was to analyze the effect of transforaminal lumbar interbody fusion on patients with DLS and lumbar degenerative scoliosis and explore the surgical aspects benefiting the restoration of lumbar degenerative scoliosis. Methods: All patients with DLS and lumbar degenerative scoliosis undergoing single-level unilateral transforaminal lumbar interbody fusion surgery between July 1, 2015, and April 30, 2021, were screened in this retrospective cohort study. Clinical outcomes including visual analog scale (VAS), Oswestry disability index (ODI), and radiographic parameters of sagittal and coronal alignment, cage spatial locations, and angle of pedicle screw (parallel, cranial, and caudad angle) were assessed. Coronal asymmetry was demonstrated by the intervertebral height difference between the medial and lateral margins of indexed intersegmental space. The correlations between Δintervertebral height difference (postoperative intervertebral height difference-preoperative intervertebral height difference) and radiographic parameters and clinical outcomes were analyzed by univariable, multivariable, mediation, and correlation analyses. Significance was set at a bilateral P<0.05. Results: A total of 57 included patients were followed up for a minimum of 1 year. Reduction of VAS, ODI, and improvement of radiographic parameters were found after surgery. The cranial angle of the lower pedicle screw positively correlated with Δintervertebral height difference restoration (b=0.54; standard error=0.11; P<0.001). Conclusions: Transforaminal lumbar interbody fusion surgery appears to be an effective approach to improving the radiographic and clinical outcomes of patients with DLS and lumbar degenerative scoliosis. The cranial direction of the lower pedicle screws in single-level unilateral transforaminal lumbar interbody fusion surgery may be associated with a better postoperative restoration of lumbar degenerative scoliosis.

Shentao Ruangan formula promotes apoptosis via the E2F2-p53 pathway in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rates. E2F2 is an independent predictor of poor prognosis in HCC; however, The mechanism by which E2F2 promotes the progression of HCC remains unclear. The Shentao Ruangan (STR) formula exhibits antitumor efficacy against HCC; however, the underlying antitumor mechanisms remain unknown. PURPOSE: To explore the regulatory effect of E2F2 on the p53 signaling pathway and reveal the role and mechanism of STR in promoting cell apoptosis via the E2F2-p53 signaling pathway in HCC. METHODS: E2F2 overexpression or silencing by lentivirus in HepG2 cells were used to explore their influence on apoptosis and the p53 pathway. An H22 tumor-bearing mice model was used to determine the therapeutic efficacy of STR and its effects on the E2F2-p53 pathway. STR-mediated serum (STR-MS) was prepared, and its chemical constituents were identified using mass spectrometry. The effects of STR-MS on viability and apoptosis of HepG2 cells and the E2F2-p53 pathway were investigated and validated using rescue experiments. RESULTS: E2F2 overexpression significantly inhibited apoptosis and the p53 pathway in HepG2 cells, whereas E2F2-silenced HepG2 cells showed the reverse. This increased apoptosis was rescued by the addition of a p53 inhibitor (PFT-α) to E2F2-silenced HepG2 cells. In vivo, high doses of STR could remarkably inhibit the growth of xenografts, promote the apoptosis of hepatoma cells, downregulate E2F2, and activate the p53-dependent mitochondrial apoptotic pathway with good safety. In vitro, STR-MS exhibited similar effectiveness, and the best effect was achieved at 30% STR-MS concentration for 48 h. When 30% STR-MS was added to E2F2-overexpressing cells, the increased apoptosis and expression of key proteins in the p53-dependent mitochondrial apoptosis pathway were significantly rescued. CONCLUSION: Our findings demonstrate, for the first time, that E2F2 inhibits hepatoma cell apoptosis in a p53-dependent manner and that STR may promote apoptosis by regulating the E2F2-p53 pathway in HCC.

Spinal cord injury-activated C/EBPß-AEP axis mediates cognitive impairment through APP C586/Tau N368 fragments spreading.

Spinal cord injury (SCI) leads to mental abnormalities such as dementia and depression; however, the molecular mechanism of SCI-induced dementia remains a matter of debate. Asparagine endopeptidase (AEP) mediated dementia by enhancing amyloid plaque and Tau hyperphosphorylation, indicating that it played an important role in neurodegeneration. Here we revealed that SCI stimulated AEP activation in mice with T9 contusion injury. Activated-AEP cleaved APP and Tau, resulting in APP C586 and Tau N368 formations, and consequentially accelerated Aß deposit and Tau hyperphosphorylation, respectively. At 9 months following injury, mice demonstrated a severe deterioration in cognitive-behavioral function, which was corroborated by the presence of accumulated AD-specific pathologies. Surprisingly, activated AEP was found in the brains of mice with spinal cord injury. In contrast, AEP knockout reduced SCI-induced neuronal death and neuroinflammation, resulting in cognitive-behavioral restoration. Interestingly, compared to the full-length proteins, truncated Tau N368 and APP C586 were easier to bind to each other. These AEP-processed fragments can not only be induced to pre-formed fibrils, but also amplified their abilities of spreading and neurotoxicity in vitro. Furthermore, as a critical transcription factor of AEP, C/EBPß was activated in injured spinal cord. Elevated C/EBPß level, as well as microglia population and inflammatory cytokines were also noticed in the cortex and hippocampus of SCI mice. These neuroinflammation pathologies were close related to the amount of Tau N368 and APP C586 in brain. Moreover, administration with the AEP-specific inhibitor, compound #11, was shown to decelerate Aß accumulation, tauopathy and C/EBPß level in both spinal cord and brain of SCI mice. Thus, this study highlights the fact that spinal cord injury is a potential risk factor for dementia, as well as the possibility that C/EBPß-AEP axis may play a role in SCI-induced cognitive impairment.

[Unilateral pedicle screw fixation through the pedicle of fractured vertebra in combination with the short segment of pedicle screw in the treatment of thoracolumbar fracture of mild to moderate instability].

OBJECTIVE: To evaluate the efficacy of unilateral pedicle screw fixation through the pedicle of fractured vertebra in combination with the short segment of pedicle screw in the treatment of thoracolumbar fracture of mild to moderate instability. METHODS: Twenty-six patients with single segment thoracolumbar fracture received unilateral pedicle screw fixation through the pedicle of fractured vertebra in combination with the short segment of pedicle screw from January 2008 to December 2009. There were 16 patients were male and 10 were female with an average age of 47.3 years (range from 39 to 60 years). Fracture severity score was constructed by using the load-sharing classification (4 points for 2 cases, 5 points for 14 cases, 6 points for 10 cases). By Frankel assessment system, 2 cases were in grade C, 3 in grade D, 21 in grade E. The assessment included anterior vertebral body height, the sagittal Cobb angle, the restoration of nervous function, visual analogue score (VAS) and Oswestry disability index (ODI). RESULTS: The follow-up after the surgery was 13 - 26 months, with an average of 18.6 months. There were no fixation failure, defined as implant failure or ≥ 10° correction loss. The neurological status of 4 patients, who had an associated neurologic deficit preoperatively, was completely recovered. The Frankel grade of another case was re-rated D from the original C. The mean anterior vertebral body height increased from 57.0% ± 6.3% before the surgery to 93.1% ± 1.7% at the last follow-up(F = 455.276, P < 0.05). The sagittal Cobb angle decreased from 15.6° ± 4.7° before the surgery to 2.6° ± 5.2° at the last follow-up (F = 34.623, P < 0.05). VAS and ODI were 1.0 ± 0.7 and 17.0 ± 5.9 at the last follow-up. CONCLUSION: Unilateral pedicle screw fixation through the pedicle of fractured vertebra combined with the short segment of pedicle screw is effective for thoracolumbar fracture with mild to moderate instability.

[Building an effective nonlinear three-dimensional finite-element model of human thoracolumbar spine].

OBJECTIVE: To build an effective nonlinear three-dimensional finite-element (FE) model of T(11)-L(3) segments for a further biomechanical study of thoracolumbar spine. METHODS: The CT (computed tomography) scan images of healthy adult T(11)-L(3) segments were imported into software Simpleware 2.0 to generate a triangular mesh model. Using software Geomagic 8 for model repair and optimization, a solid model was generated into the finite element software Abaqus 6.9. The reasonable element C3D8 was selected for bone structures. Created between bony endplates, the intervertebral disc was subdivided into nucleus pulposus and annulus fibrosus (44% nucleus, 56% annulus). The nucleus was filled with 5 layers of 8-node solid elements and annulus reinforced by 8 crisscross collagenous fiber layers. The nucleus and annulus were meshed by C3D8RH while the collagen fibers meshed by two node-truss elements. The anterior (ALL) and posterior (PLL) longitudinal ligaments, flavum (FL), supraspinous (SSL), interspinous (ISL) and intertransverse (ITL) ligaments were modeled with S4R shell elements while capsular ligament (CL) was modeled with 3-node shell element. All surrounding ligaments were represented by envelope of 1 mm uniform thickness. The discs and bone structures were modeled with hyper-elastic and elasto-plastic material laws respectively while the ligaments governed by visco-elastic material law. The nonlinear three-dimensional finite-element model of T(11)-L(3) segments was generated and its efficacy verified through validating the geometric similarity and disc load-displacement and stress distribution under the impact of violence. Using ABAQUS/ EXPLICIT 6.9 the explicit dynamic finite element solver, the impact test was simulated in vitro. RESULTS: In this study, a 3-dimensional, nonlinear FE model including 5 vertebrae, 4 intervertebral discs and 7 ligaments consisted of 78 887 elements and 71 939 nodes. The model had good geometric similarity under the same conditions. The results of FEM intervertebral disc load-displacement curve were similar to those of in vitro test. The stress distribution results of vertebral cortical bone, posterior complex and cancellous bone were similar to those of other static experiments in a dynamic impact test under the observation of stress cloud. CONCLUSION: With the advantages of high geometric and mechanical similarity and complete thoracolumbar, hexahedral meshes, nonlinear finite element model may facilitate the impact loading test for a further dynamic analysis of injury mechanism for thoracolumbar burst fracture.

A Retrospective Analysis of Superior Facet Joint Violation Between Open and Minimally Invasive Transforaminal Lumbar Interbody Fusion and its Relation to Adjacent Segment Disease.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim was to analyze the superior facet joint violation (SFV) between open transforaminal lumbar interbody fusion (open-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and its effect on the superior and inferior adjacent segment disc height, segmental lordosis, lumbar lordosis, and facet joint degeneration. SUMMARY OF BACKGROUND DATA: We compared SFV between open-TLIF and MIS-TLIF and its correlation with different factors as well as its effect on adjacent segment disease. MATERIALS AND METHODS: We retrospectively studied data of patients undergoing single level TLIF surgery from January 2013 to February 2016 in single institutional hospital. Axial and coronal postoperative computed tomography scan images were used to analyze SFV. In secondary analysis patients were divided into nonfacet violation group (NSFVG) and facet violation group (SFVG) and compared the changes on the superior and inferior adjacent level disc height, segmental lordosis, lumbar lordosis, and facet joint degeneration. RESULTS: Mean SFV grade was significantly greater in MIS-TLIF compared with open-TLIF (odds ratio: 0.638, confidence interval: 0.431-0.944; P=0.025). There was more grade 2 (10.71% vs. 5.60%) and grade 3 (4.46% vs. 1.29%) SFV in MIS-TLIF. Patient with age below 60 and body mass index (BMI) >30 kg/m2 in MIS-TLIF were more prone to high-grade SFV compared with open-TLIF. Further, logistic regression showed patients with BMI ≥30 kg/m2 has 7.137 increased odds of high-grade SFV (95% confidence interval: 3.261-15.618; P=0.000) compared with patients with BMI <30 kg/m2. Compared with NSFVG, SFVG has more SFV (0.096±0.244 vs. 0.177±0.317; P=0.012) and less improvement in lumbar visual analog scale scores -0.65±0.073 versus -0.67±0.074 (P=0.006). CONCLUSION: MIS-TLIF has more high-grade SFV as well as overall mean SFV in comparison to open-TLIF with BMI >30 kg/m2 and location of pedicle screw as an independent risk factor for SFV and risk of adjacent segment disease increases with SFV. LEVEL OF STUDY: Level III.

Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data.

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.

Identification of potential bioactive compounds and mechanisms of GegenQinlian decoction on improving insulin resistance in adipose, liver, and muscle tissue by integrating system pharmacology and bioinformatics analysis.

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.

Estimation of Incubation Period and Serial Interval for SARS-CoV-2 in Jiangxi, China, and an Updated Meta-Analysis.

INTRODUCTION: This paper aims to estimate the incubation period and serial intervals for SARS-CoV-2 based on confirmed cases in Jiangxi Province of China and meta-analysis method. METHODOLOGY: Distributions of incubation period and serial interval of Jiangxi epidemic data were fitted by "fitdistrplus" package of R software, and the meta-analysis was conducted by "meta" package of R software. RESULTS: Based on the epidemic data of Jiangxi, we found the median days of incubation period and serial interval were 5.9 days [IQR: 3.8 - 8.6] and 5.7 days [IQR: 3.6 - 8.3], respectively. The median days of the infectivity period at pre-symptomatic was 1.7 days [IQR: 1.1 - 2.4]. The meta-analysis based on 64 papers showed the pooled means of the incubation period and serial interval were 6.25 days (95% CrI: 5.75 - 6.75) and 5.15 days (95% CrI: 4.73 - 5.57), respectively. CONCLUSIONS: Our results contribute to a better understanding of COVID-19 and provide useful parameters for modelling the dynamics of disease transmission. The serial interval is shorter than the incubation period, which indicates that the patients are infectious at pre-symptomatic period, and isolation of detected cases alone is likely to be difficult to halt the spread of SARS-CoV-2.