Time series analysis of COVID-19 infection curve: A change-point perspective.

In this paper, we model the trajectory of the cumulative confirmed cases and deaths of COVID-19 (in log scale) via a piecewise linear trend model. The model naturally captures the phase transitions of the epidemic growth rate via change-points and further enjoys great interpretability due to its semiparametric nature. On the methodological front, we advance the nascent self-normalization (SN) technique (Shao, 2010) to testing and estimation of a single change-point in the linear trend of a nonstationary time series. We further combine the SN-based change-point test with the NOT algorithm (Baranowski et al., 2019) to achieve multiple change-point estimation. Using the proposed method, we analyze the trajectory of the cumulative COVID-19 cases and deaths for 30 major countries and discover interesting patterns with potentially relevant implications for effectiveness of the pandemic responses by different countries. Furthermore, based on the change-point detection algorithm and a flexible extrapolation function, we design a simple two-stage forecasting scheme for COVID-19 and demonstrate its promising performance in predicting cumulative deaths in the U.S.

Proteomic comparison between physiological degeneration and needle puncture model of disc generation disease.

BACKGROUND: The completeness of the intervertebral disc proteome is fundamental to the integrity and functionality of the intervertebral disc. METHODS: The 20 experimental rats were placed into two groups randomly, normal group (NG) and acupuncture pathological degeneration group-2 weeks (APDG-2w). The ten 24-month-old rats were grouped into physiological degeneration group (PDG). Magnetic resonance imaging, X-ray examination, histological staining (hematoxylin & eosin, safranin-O cartilage, and alcian blue staining), and immunohistochemical examination were carried out for assessing the degree of disc degradation. Intervertebral disc was collected, and protein composition was determined by LC- MS, followed by bioinformatic analysis including significance analysis, subcellular localization prediction, protein domain prediction, GO function and KEGG pathway analysis, and protein interaction network construction. LC-PRM was done for protein quantification. RESULTS: Physiological degeneration and especially needle puncture decreased T2 signal intensity and intervertebral disc height. Results from hematoxylin & eosin, safranin-O, and alcian blue staining revealed that the annulus fibrosus apparently showed the wavy and collapsed fibrocartilage lamellas in APDG-2w and PDG groups. The contents of the nucleus pulposus were decreased in physiological degeneration group and APDG-2w group compared with NG. Results from immunohistochemical analysis suggested the degeneration of intervertebral disc and inflammation in APDG-2w and PDG groups. The protein composition and expression between needle puncture rat models and the physiological degeneration group showed significant difference. CONCLUSIONS: Our studies produced point-reference datasets of normal rats, physiological degeneration rats, and needle puncture rat models, which is beneficial to subsequent pathological studies. There is differential expression of protein expression in degenerative discs with aging and acupuncture, which may be used as a potential discriminating index for different intervertebral degenerations.

A retrospective comparative study of postoperative sagittal balance in isthmic L5-S1 spondylolisthesis using single segment or two-segment pedicle screw fixation.

OBJECTIVE: To compare the radiographic parameters and clinical outcomes of isthmic L5-S1 spondylolisthesis with single segment or two-segment pedicle screw fixation. METHODS: Between January 2018 and January 2019, a total of 76 patients with isthmic L5-S1 spondylolisthesis were included in this study. All patients were treated with varying numbers of pedicle screw fixation with single-segment fusion during posterior lumbar interbody fusion (PLIF). Patients were divided into two groups, based on the number of pedicle screws placed during fixation, namely, 4 screws (4S) group and 6 screws (6S) group. Subsequently, the sagittal balance parameters were measured, which included slippage degree (SD), lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. RESULTS: The 4S group comprised of 10 males and 27 females, with a median age of 55.2 ± 10.8 years old and a mean follow-up of 16.95 ± 4.16 months. The 6S group comprised of 14 males and 25 females, with a median age of 58.1 ± 7.5 years old and a median follow-up of 17.33 ± 3.81 months. No significant differences were evident in all preoperative parameters between both groups. In contrast, the postoperative LL, SL, PT, SS, and SD values increased significantly, compared to the preoperative values in both groups (all P < 0.05). At the last follow-up, the 6S group exhibited better correction in LL, SL, and PT, relative to the 4S group (all P < 0.05). A significant SD difference was observed between both groups at all points post surgery (P < 0.05). The postoperative slip correction rate was significantly larger in the 6S group, compared to the 4S group (P < 0.05). The postoperative VAS and ODI scores of both groups improved significantly, when compared to the preoperative scores (both P < 0.05). However, there were no significant differences in the ODI and VAS scores between the two groups at all time points. CONCLUSIONS: The clinical outcomes of both approaches appeared to be satisfactory. In terms of short-term outcomes, the 6S group exhibited better spinal sagittal restoration and stability than the 4S group.

Should adjacent asymptomatic lumbar disc herniation of L5-S1 isthmic spondylolisthesis be simultaneously rectified? Evaluation of postoperative spino-pelvic sagittal balance and functional outcomes.

BACKGROUND: This study aimed to analyze the efficacy of the simultaneous rectification of adjacent asymptomatic lumbar disc herniation (asLDH) of L5-S1 isthmic spondylolisthesis (IS). METHODS: One hundred and forty-eight patients with L5-S1 IS, and simultaneous L4-5 asLDH, were recruited between January 2012 and December 2017, for this study. Group A: seventy-two patients received PLIF at L5-S1. Group B: seventy-six patients received PLIF at L4-S1. The radiographic outcomes were assessed via the lumbar lordosis (LL), segmental lordosis (SL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), PI-LL and slip degree (SD). The functional outcomes were evaluated via the visual analog scale (VAS), Oswestry disability index (ODI), and reoperation rate. The potential risk hazards for reoperation were identified using both uni- and multivariate logistic regression analyses. RESULTS: The postoperative LL, SL, PT, SS, SD, VAS, and ODI exhibited vast improvements (P < 0.05). Relative to Group A, Group B exhibited markedly better LL, SL, PT, PI-LL,VAS and ODI scores at the final follow-up (P < 0.05). Group B also achieved better SD values post surgery than Group A (P < 0.05). The reoperation rate was remarkably elevated in Group A, compared to Group B (P < 0.05). The multivariate logistic regression analysis showed the L4-5 asLDH grade was a stand-alone risk hazard for reoperation, whereas, pre-SL and pre-LL offered protection against reoperation (P < 0.05). CONCLUSIONS: L4-S1 PLIF is recommended to correct asLDH in L5-S1 IS patients, with high-grade disc herniation and abnormal sagittal alignment.

A retrospective comparative study of clinical efficacy of percutaneous short segment pedicle screw fixation with or without screwing of the fractured vertebra with O-arm navigation.

OBJECTIVE: To retrospectively analyze the short and long-term efficacies of O-arm-navigated percutaneous short segment pedicle screw fixation, with or without screwing of the fractured vertebra. METHODS: A total of 42 patients who underwent O-arm-navigated percutaneous short segment pedicle screw fixation for the treatment of thoracolumbar fractures from February 2015 to December 2018 were selected for analysis. The patients were divided into two groups according to the surgical intervention they received: Group A received percutaneous short segment pedicle screw fixation with screwing of the fractured vertebra and Group B received percutaneous short segment pedicle screw fixation without screwing of the fractured vertebra. Radiographic analysis included Cobb angles and percentage of anterior vertebral height (AVH%). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. RESULTS: No significant differences were observed in the operation time and intraoperative blood loss between the two groups (P > 0.05). The length of incision was statistically significantly different between the two groups (P < 0.05). There was no significant difference in Cobb angle and AVH% between the two groups before and after the surgery (P > 0.05). However, the Cobb angle and AVH% were both significantly larger in Group A than Group B at the final follow-up (P < 0.05). In terms of clinical outcomes, there were no statistically significant differences in VAS and ODI scores between the two groups (P > 0.05). CONCLUSION: In the short term, both minimally invasive treatments were safe and effective in treating thoracolumbar fracture. Although there was significant difference between the two groups in Cobb angle and vertebral body height at the last follow-up, the difference was small. Therefore, these specific parameters will be an important outcome measure in further investigations.

Comparison of Clinical Outcomes Following Anterior Cervical Discectomy and Fusion with Zero-Profile Anchored Spacer-ROI-C-Fixation and Combined Intervertebral Cage and Anterior Cervical Discectomy and Fusion: A Retrospective Study from a Single Center.

BACKGROUND The aim of this study was to compare the outcomes following anterior cervical discectomy and fusion with zero-profile anchored spacer-ROI-C-fixation (ROI-C) vs combined intervertebral cage and anterior cervical discectomy and fusion (ACDF). MATERIAL AND METHODS We retrospectively analyzed 87 patients who underwent operations between January 2015 and January 2019, including 42 patients that underwent ROI-C treatment (group A) and 45 that were treated by the ACDF approach (group B). Operative duration, blood loss, dysphagia, Neck Disability Index scores (NDI), Japanese Orthopaedic Association scores (JOA), and other complications were compared between these groups. In addition, implant settlement, fusion, and cervical Cobb angle were assessed via imaging analyses. RESULTS Patients in group A and group B were followed for 22.6±3.3 months and 27.1±3.5 months, respectively (range: 13-30 months). Relative to preoperative values, JOA scores were increased and NDI scores were reduced in both groups following treatment (P<0.05), with comparable outcomes between groups (P>0.05). However, operative duration, intraoperative blood loss, and postoperative complications did differ significantly between these groups (P<0.05). Specifically, rates of short-term dysphagia were lower and recovery time was faster in group A relative to group B (P<0.05). CONCLUSIONS The findings from this study showed that ROI-C fixation achieved satisfactory outcomes, improved cervical curvature, restored intervertebral height, and was associated with shorter operative duration, reduced blood loss, and less dysphagia.

Metal-free N-doped carbon nanofibers as an efficient catalyst for oxygen reduction reactions in alkaline and acid media.

The development of metal-free catalysts to replace the use of Pt has played an important role in relation to its application to fuel cells. We report N-doped carbon nanofibers as the catalyst of an oxygen reduction reaction, which were synthesized via carbonizing bacterial cellulose-polypyrrole composites. The as-prepared material exhibited remarkable catalytic activity toward the oxygen reduction reaction with comparable onset potential and the ability to limit the current density of commercial Pt/C catalysts in both alkaline and acid media due to the unique porous three-dimensional network structure and the doped nitrogen atoms. The effect of N functionalities on catalytic behavior was systematically investigated. The results demonstrated that pyridinic-N was the dominating factor for catalytic performance toward the oxygen reduction reaction. Additionally, N-doped carbon nanofibers also demonstrated excellent cycling stability (93.2% and 89.4% retention of current density after chronoamperometry 20 000 s in alkaline and media, respectively), obviously superior to Pt/C.

Enhanced Recovery After Surgery Protocol for Oblique Lumbar Interbody Fusion.

Background: Enhanced recovery after surgery (ERAS) attempts to decrease the surgical stress response to minimize postoperative complications and improve functional rehabilitation after major surgery, but it has not been widely utilized in spinal surgery. The study reported the development and implementation of an ERAS pathway for patients with lumbar spondylolisthesis undergoing oblique lumbar interbody fusion (OLIF). Methods: Seventy-six patients underwent OLIF surgery from January 2018 to December 2019 were enrolled. Thirty-seven patients were included in pre-ERAS group and 39 patients were included in ERAS group. Major outcomes that were collected included demographics, comorbidities, blood loss, operative time, length of hospital stay (LOS), cost, time to walk, blood transfusion, complications, Visual analogue scale (VAS) scores, Oswestry Disability Index (ODI) and factors affecting LOS were also recorded. The ERAS pathway and compliance with pathway elements were also recorded. Results: After ERAS implementation, the blood loss, LOS, the financial costs, and the time to walk were significantly lower in the ERAS group compared to the pre-ERAS group (all P < 0.05). There was no significant difference in operative time, complications, and blood transfusion between both groups. VAS and ODI between the two groups showed a significant difference during postoperative 3 days and postoperative 1 month (both P < 0.05). The preoperative time to walk was significant factors for hospital stay at the final follow-up. Conclusion: Institution of an ERAS protocol for OLIF surgery appears to accelerate functional recovery, reduce length of stay and financial costs.

Percutaneous Kyphoplasty in Patients with Severe Osteoporotic Vertebral Compression Fracture with and without Intravertebral Cleft: A Retrospective Comparative Study.

Purpose: To comparatively analyze the clinical and radiographic outcomes of percutaneous kyphoplasty (PKP) in patients with severe osteoporotic vertebral compression fracture (sOVCF) with or without intravertebral cleft (IVC). Methods: We enrolled a total of 75 patients with sOVCF receiving PKP between January 2016 and December 2018. The patients were divided into the following two groups based on their radiographic findings: with IVC (IVC group) and without IVC (NIVC group). The following radiographic outcomes were determined: anterior vertebral height (AVH), kyphotic angle (KA), lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), and pelvic tilt (PT). The clinical functional assessment included Oswestry disability index (ODI) and visual analog scale (VAS) scores. Results: No significant difference was found between the demographic data of the two groups (P > 0.05). AVH, KA, and LL in both groups were significantly corrected one month after surgery (P < 0.05). There was statistical difference between the two groups in AVH and KA one year and three years after surgery, and in LL and PT three years after surgery (P < 0.05). Compared with the results one month after surgery, AVH, KA, and LL of the IVC group deteriorated significantly one year and three years after surgery, whereas AVH, KA, and LL of the NIVC group deteriorated significantly three years after surgery (P < 0.05). The VAS and ODI scores in both groups decreased significantly one month, one year, and three years after surgery than preoperative results (P < 0.05), and a statistical difference was observed between the two groups three years after surgery (P < 0.05). Conclusion: PKP can give satisfactory outcomes for the treatment of sOVCF with or without IVC. However, the NIVC group showed better clinical outcomes and could maintain spinal sagittal balance better than the IVC group during long-term follow-up.

Bone Cement and Pedicle Screw for the Treatment of Spinal Tumors with Spinal Cord Compression and Posterior Wall Defects.

OBJECTIVE: To compare the safety and efficacy of posterior internal fixation with open vertebroplasty (VP) and posterior internal fixation with open kyphoplasty (KP) in the treatment of metastatic epidural spinal cord compression (MESCC) with posterior wall destruction. METHODS: This retrospective study, conducted between January 2016 and May 2019, equally divided 60 patients with MESCC and posterior wall destruction into two groups based on the surgical method: open vertebroplasty with pedicle screw fixation (VP group) and open kyphoplasty with pedicle screw fixation (KP group). Visual analogue scale (VAS), SF-36 scores, middle vertebral height (MVH), and posterior vertebral height (PVH) were evaluated for the two groups preoperatively, postoperatively, and 1 year after surgery. Spinal Instability Neoplastic Score, Frankel grades and complications were recorded and evaluated. RESULTS: Five patients were excluded from the analysis, and our study cohort consisted of 55 adult patients who met the inclusion criteria. The VAS and SF-36 scores of these two groups of patients significantly improved, when compared with those before the surgery (P < 0.05). There were significant differences in total cost (8835 ± 1468 vs 9540 ± 053 USD) and cement volume (4.51 ± 0.96 ml vs 6.35 ± 1.09 ml) between two groups (P < 0.05). The MVH and PVH of these two groups of patients significantly improved, when compared with those before the surgery (P < 0.05). The MVH was significantly larger in the KP group than in the VP group postoperatively (20.15 ± 4.86 vs 17.70 ± 3.78, P < 0.05) and at the final follow-up (20.42 ± 5.59 vs 17.28 ± 3.23, P < 0.05). However, the PVH of the two groups did not significantly differ at the two postoperative follow-ups (P > 0.05). No significant differences were found in surgery time, time from surgery to discharge, blood loss and complications between both groups postoperatively (P > 0.05). CONCLUSION: In the short term, both approaches are effective and safe in patients with MESCC and posterior wall destruction. The posterior internal fixation with open VP may be a good choice of surgical method in patients with MESCC and posterior wall defects.

Comparing the Bridge-Type Zero-Profile Anchored Spacer (ROI-C) Interbody Fusion Cage System and Anterior Cervical Discectomy and Fusion (ACDF) with Plating and Cage System in Cervical Spondylotic Myelopathy.

OBJECTIVE: To compare the clinical efficacy and radioactivity of the bridge-type zero-profile anchored spacer (ROI-C) interbody fusion cage and anterior cervical discectomy and fusion with plating and cage system (ACDF) for cervical spondylotic myelopathy (CSM). METHODS: This is a retrospective contrastive study. We recruited 35 patients who received ROI-C (ROI-C group) and 34 patients who received ACDF (ACDF group), between January 2014 to January 2019, at our treatment center. The ROI-C group comprised of 11 males and 24 females with a mean age of 61.59 ± 8.21 years (range, 51-71 years). The ACDF group comprised of 12 males and 22 females with a mean age of 60.15 ± 7.52 years (range, 52-74 years). Neck Disability Index (NDI), Japanese Orthopaedic Association score (JOA), Odom's score, cervical Cobb angle, fusion rate, adjoining ossification, and dysphagia. RESULTS: A total of 69 patients met the inclusion criteria, and these patients received more than two years of follow-up. There were significant differences in surgical duration (101 ± 22 min vs. 118 ± 29 min) and blood loss (102 ± 46 ml vs. 145 ± 58 ml) between two groups (P < 0.05). The JOA and NDI of these two groups of patients significantly improved, when compared with those before the operation (P < 0.05). Twenty-nine of 35 patients in the ROI-C group and 27 of 34 patients in ACDF group achieved good or excellent outcomes according to Odom's criteria. The cervical lordosis of both two groups significantly increased, when compared with those before the operation (P < 0.05). In the ROI-C group, the postoperative fusion rate was 85.7% at the 3-month follow-up and 100% at the final follow-up. In the ACDF group, the postoperative fusion rate was 82.4% at the 3-month follow-up and 100% at the final follow-up. The dysphagia incidence of the ACDF group was higher than that of the ROI-C group postoperatively and at the one month after surgery (P < 0.05), but no significant difference was found in the incidence of dysphagia at final follow-up (P > 0.05). CONCLUSION: Both ROI-C and ACDF achieved good therapeutic effects. However, ROI-C can reduce the operation time and postoperative complications.

Similarity and difference between aging and puncture-induced intervertebral disc degeneration.

The purpose of our study was to investigate the changes in micromorphology and mechanical properties of intervertebral discs degeneration induced by aging and puncture. Normal group (NG), 2 weeks post-puncture degeneration group (PDG) and aging degeneration group (ADG) each included 10 rats. Plain film, magnetic resonance imaging, and histological testing were utilized to assess intervertebral disc degeneration. Atomic force microscope was utilized to analyze the microstructure and elastic modulus of the intervertebral disc, while immunohistochemistry was employed to assess alterations in the cell matrix using collagen I, collagen II, matrix metalloproteinase-3 (MMP-3), and tumour necrosis factor-α (TNF-α). The results showed that the disc height ratio between PDG and ADG decreased. In the PDG and ADG group, histological scores both increased, the gray value of the T2 signal decreased, the proportion of MMP-3 and TNF-positive cells in intervertebral disc tissues was higher (p < 0.05) and the IOD values of COL-2 lower in intervertebral disc tissues (p < 0.05). The elastic modulus of PDG and ADG annulus fibers (AF) increased compared to the NG (p < 0.05); when compared to PDG, the elastic modulus of ADG AF decreased (p < 0.05). The elastic modulus of PDG and ADG collagen increased in the nucleus pulposus (NP, p < 0.05); ADG had a greater AF diameter than NG and PDG (p < 0.05). The results indicated that ADG fiber diameter thickens, and chronic inflammation indicators rise; PDG suffers from severe extracellular matrix loss. The degeneration of the ADG and PDG intervertebral discs is different. The results provide foundation for clinical research.

Identification of osteoporosis based on gene biomarkers using support vector machine.

Osteoporosis is a major health concern worldwide. The present study aimed to identify effective biomarkers for osteoporosis detection. In osteoporosis, 559 differentially expressed genes (DEGs) were enriched in PI3K-Akt signaling pathway and Foxo signaling pathway. Weighted gene co-expression network analysis showed that green, pink, and tan modules were clinically significant modules, and that six genes (VEGFA, DDX5, SOD2, HNRNPD, EIF5B, and HSP90B1) were identified as "real" hub genes in the protein-protein interaction network, co-expression network, and 559 DEGs. The sensitivity and specificity of the support vector machine (SVM) for identifying patients with osteoporosis was 100%, with an area under curve of 1 in both training and validation datasets. Our results indicated that the current system using the SVM method could identify patients with osteoporosis.

Comparison of clinical outcomes and spino-pelvic sagittal balance in degenerative lumbar spondylolisthesis: Minimally invasive oblique lumbar interbody fusion (OLIF) versus transforaminal lumbar interbody fusion (TLIF).

ABSTRACT: Spino-pelvic sagittal parameters are closely related to the lumbar degenerative diseases. The present study aims to compare clinical results and spino-pelvic sagittal balance treated with oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in patients with degenerative lumbar spondylolisthesis at single segment.We retrospectively reviewed and compared 28 patients who underwent OLIF (OLIF group) and 35 who underwent TLIF (TLIF group). Radiological results were evaluated with disc height (DH), foraminal height (FH), fused segment lordosis (FSL), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), and sacral slope (SS). Clinical results were evaluated with the Oswestry Disability Index (ODI) and VAS for back and leg pain.The OLIF group showed higher improvement of DH and FH than the TLIF group at all time points after surgery (P < .05). No significant differences were found in PT, PI, and SS between the 2 groups (P > .05). Significant restoration of spino-pelvic sagittal balance was observed in the 2 groups after surgery. Significant differences in postoperative lumbar lordosis and fused segment lordosis were found between the 2 groups (P < .05). Significant difference in the improvement of symptoms was observed between the 2 groups. The OLIF group had lower VAS scores for back pain and ODI compared after surgery (P < .05).It can be concluded that there are exactly differences in improvement of radiographic parameters between 2 approaches, which confirmed that OLIF is better in restoring spinal alignment. Besides, due to the unique minimally invasive approach, OLIF did exhibit a greater advantage in early recovery after surgery.

LncRNA NONHSAT114552 Sponges miR-320d to Promote Proliferation and Invasion of Chordoma Through Upregulating NRP1.

Chordoma is a relatively rare malignant bone tumor with high local recurrence. To date, the mechanism remains unclear. lncRNAs play a pivotal role in tumorigenesis by acting as competitive endogenous RNAs of microRNAs. However, the biological role of lncRNA is still unclear in chordoma. In this research, our aim is to investigate the roles and regulation mechanisms of lncRNA NONHSAT114552 in chordoma development. The expression level of NONHSAT114552 and miR-320d in chordoma tissues was determined by qRT-PCR. Meantime, the correlation between NONHSAT114552 and clinical prognosis was also studied. Bioinformatics analysis and luciferase reporter assays were used to verify the relationship between NONHSAT114552 and miR-320d, and between miR-320d and Neuropilin 1 (NRP1). In addition, effects of NONHSAT114552 on chordoma cells (U-CH1 and U-CH2) proliferation and invasion and its regulation on miR-320d were also evaluated. Furthermore, the influences of NONHSAT114552/miR-320d/NRP1 axis on chordoma tumorigenesis were investigated in vivo. NONHSAT114552 was overexpressed while miR-320d was down-regulated in chordoma tissue compared to fetal nucleus pulposus. Kaplan-Meier survival analysis showed that NONHSAT114552 overexpression was associated with patients' poor prognosis. Knockdown of NONHSAT114552 significantly suppressed chordoma cell proliferation and invasion. In vitro studies confirmed that NONHSAT114552 acted as ceRNA to regulate NRP1 by directly sponging miR-320d, thus facilitating chordoma cell proliferation and invasion. In vivo study demonstrated that NONHSAT114552 moderated chordoma growth by sponging miR-320d to regulating NRP1. Our findings indicate that lncRNA NONHSAT114552 exhibits a critical role in the tumorigenesis and development of chordoma and it may become one potential prognostic marker and therapeutic target for this disease. .

LncRNA-NONHSAT024778 promote the proliferation and invasion of chordoma cell by regulating miR-1290/Robo1 axis.

Chordoma is a malignant bone tumor originating from the embryonic remnants of the notochord. lncRNAs act as competing endogenous RNAs (ceRNAs) and play a critical role in tumor pathology. However, the biological role of lncRNA-NONHSAT024778 and the underlying molecular mechanism in chordoma remains unknown. qRT-PCR was used to analyze the expression changes of NONHSAT024778 and miR-1290 in chordoma tissues and cell lines. Bioinformatics analysis and luciferase reporter assay were applied to detect the targeting binding effect between NONHSAT024778 and miR-1290, and between Robo1 and miR-1290. The effect of NONHSAT024778 on chordoma cell proliferation and invasion and its regulation of miR-1290 by acting as a ceRNA were also investigated. An increased NONHSAT024778 expression was correlated with a decreased miR-1290 level in chordoma tissues. NONHSAT024778 knockdown suppressed the proliferation and invasion of chordoma cells. miR-1290 restored expression rescued the carcinogenic function of NONHSAT024778. Bioinformatics analysis showed that NONHSAT024778 acted as ceRNA to regulate Robo1 via sponging miR-1290 in chordoma cells, thereby promoting chordoma cell malignant progression. In vivo results confirmed the anti-tumor effects of NONHSAT024778 knockdown activating miR-1290 to inhibit the oncogene Robo1. NONHSAT024778 is substantially overexpressed, whereas miR-1290 is decreased in chordoma tissue. NONHSAT024778-miR-1290-Robo1 axis plays a critical role in chordoma tumorigenesis and might be a potential predictive biomarker for the diagnosis and therapeutic target among patients with chordoma.

Long Non-Coding RNA MDFIC-7 Promotes Chordoma Progression Through Modulating the miR-525-5p/ARF6 Axis.

BACKGROUND: Chordoma, an extremely rare malignant tumor, remains difficult to be cured because of its strong local invasiveness and high recurrence rate. Long non-coding RNAs (lncRNAs) have been demonstrated to play multiple roles in various cancers. The purpose of this study was to investigate the modulatory function of lncRNA MDFIC-7 in chordoma and to elucidate its underlying mechanisms. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of lncRNA MDFIC-7 in tumor tissues and adjacent nontumorous tissues collected from 15 chordoma patients, as well as in chordoma cell lines. Gene silencing and overexpression experiments were carried out by RNA interference and lentiviral transduction. The effect of lncRNA MDFIC-7 on the proliferation of chordoma cells was evaluated by cell counting kit-8 assay, colony formation assay and xenograft tumor experiments. RNA immunoprecipitation and dual luciferase reporter assays were conducted to evaluate the binding between lncRNA MDFIC-7 and miRNA-525-5p and the interaction between miR-525-5p and the 3' untranslated region of ADP-ribosylation factor 6 (ARF6) mRNA. The glycolytic capacity and mitochondrial function of chordoma cells were measured by the Seahorse Bioscience XF96 Extracellular Flux Analyzer. RESULTS: The expression of lncRNA MDFIC-7 was higher in chordoma tumor tissues than in adjacent non-tumor tissues. Downregulation of lncRNA MDFIC-7 reduced colony formation and cell proliferation in chordoma cells and decreased xenograft tumor growth in a nude mouse model. Moreover, lncRNA MDFIC-7 knockdown attenuated the Warburg effect in chordoma cells and xenograft tumors. LncRNA MDFIC-7 knockdown elevated miR-525-5p levels and decreased ARF6 expressions. Overexpression of ARF6 reversed the inhibitory effect of lncRNA MDFIC-7 knockdown on cell proliferation and the Warburg effect in chordoma cells and xenograft tumors. Mechanistically, lncRNA MDFIC-7, as a molecular sponge of miR-525-5p, negatively regulated miR-525-5p expression and promoted the gene expression of ARF6, a miR-525-5p target. CONCLUSION: Our findings demonstrate that lncRNA MDFIC-7 acts as a molecular sponge to competitively bind to miR-525-5p and promote expression of ARF6. The lncRNA MDFIC-7/miR-525-5p/ARF6 axis regulates chordoma progression and the Warburg effect in chordoma, suggesting that lncRNA MDFIC-7 and miR-525-5p could be promising therapeutic targets for the treatment of chordoma.

The Implementation of Patient-Centered Humanistic Care for COVID-19 Closely Contacted Hemodialysis Patients Under the Hospital-Based Group Medical Quarantine: A Brief Research Report.

In February 2020, an inpatient in Peking University People's Hospital (PKUPH), China, was confirmed positive for the novel coronavirus. In this case, 143 hemodialysis patients were labeled as close contacts and required to be placed under the hospital-based group medical quarantine (HB-GMQ) for 2 weeks by the authorities. After the case was reported, false or misleading information about the case flourished on social media platforms, which led to infodemic. Under this context, PKUPH adopted patient-centered humanistic care to implement the HB-GMQ, through the synergy of administrative, healthcare, logistical, and other measures under the model of patient-centered care of the Massachusetts Medical Society (MMS). As a result, all the patients tided over the HB-GMQ with no COVID-19 infection and no unanticipated adverse events, and all met the criteria for lifting the HB-GMQ. According to the questionnaires taken during the HB-GMQ, a high level of satisfaction was found among the quarantined and no symptomatic increase of anxiety and depression in the patients before and during the HB-GMQ, by comparing the Zung self-rating anxiety scale (SAS) and self-rating depression scale (SDS) conducted in December 2019 and on the 12th day of the HB-GMQ. This article is to brief on PKUPH's experience in implementing patient-centered humanistic care tailored to hemodialysis patients under the HB-GMQ, and to validate the hypothesis that patient-centered humanistic care is effective and helpful to help them tide over the HB-GMQ, so as to shed light on how to implement the HB-GMQ and cope with the HB-GMQ-induced problems in other hospitals.

Improvement of tumor targeting and antitumor activity by a disulphide bond stabilized diabody expressed in Escherichia coli.

We have generated an anti-Pgp/anti-CD3 diabody which can effectively inhibit the growth of multidrug-resistant human tumors. However, the two chains of the diabody are associated non-covalently and are therefore capable of dissociation. Cysteine residues were introduced into the V-domains to promote disulphide cross-linking of the dimer as secreted by Escherichia coli. Compared with the parent diabody, the ds-Diabody obtained was more stable in human serum at 37 degrees C, without loss of affinity or cytotoxicity activity in vitro. Furthermore, the ds-Diabody showed improved tumor localization and a twofold improved antitumor activity over the parent diabody in nude mice bearing Pgp-overexpressing K562/A02 xenografts. Our data demonstrate that ds-Diabody may be more useful in therapeutic applications than the parent diabody.

[Related factors of systemic lupus erythematosus: clinical analysis of 203 cases].

OBJECTIVE: To investigate the related factors of systemic lupus erythematosus (SLE) and the situation of diagnosis and treatment after onset. METHODS: 203 SLE patients, 11 males and 192 females, with a male/female ratio of 1:17, average onset age of (32 +/- 14), and average course of 3 years, were followed up and the related factors such as risk factors, family history and the situation of diagnosis and treatment were studied. RESULTS: 63 patients (31%) had the history of overworking before falling ill; 47 patients (23.2%) had suffered from infection before SLE onset. Other risk factors, such as solarization, emotional fluctuation, menstrual disorder, abortion, dyeing, and chemical drug contacting accounted for 14.3%, 14.3%, 9.4%, 6.9% , 4.9%, and 1.5% respectively. 16 patients (7.9%) had positive family history. 120 patients got the correct diagnosis at the first visit. 83 patients had been misdiagnosed for less than 1 year to 14 years. 47 of the 83 patients (23.2%) failed to get the correct diagnosis for more than one year. 140 of the 203 patients (69.0%) were given glucocorticoid and/or immunosuppressant as the first choice treatment measures after the diagnosis was confirmed. 39 of the 203 patients (19.2%) chose traditional Chinese medicine or folk prescription as the first choice. And 24 of the 203 patients (11.8%) used anti-inflammatory, and antipyretic drugs. 128 patients (63.1%) failed to continue to work. CONCLUSION: Overworking, infection, solarization, and emotional fluctuation may be related to the onset of SLE. A great part of SLE patients can not be diagnosed early and treated promptly. SLE brings bad influence on the life quality of patients.