Search

Aims: Emerging evidence suggests that the pathogenesis of osteoporosis, characterized by impaired osteogenesis, is shifting from estrogen centric to oxidative stress. Our previous studies have show...

Although bone morphogenetic protein-2 (BMP-2) is widely used for spinal fusion, some concerns cannot be ignored. The combination of growth factor with composite scaffolds represent a promising approach to promote bone regeneration and spinal fusion. Recent studies have demonstrated that the growth differentiation factor-5 (GDF-5) variant BB-1, combining the osteogenic activity of BMP-2 with the angiogenic features of GDF-5, enhanced bone regeneration during long-bone healing in lower-order animals. The study aimed to investigate the efficacy and safety of BB-1 loading on composite scaffolds on spinal fusion in nonhuman primates. Six healthy rhesus monkeys were used to establish a clinically relevant two-segment spinal fusion model. Blank scaffolds or BB-1-loaded scaffolds were implanted into each animal and distributed in a blinded way. Imageological and histological examinations as well as bone histomorphometry were performed after euthanization at 6 months post-operation. BB-1 led to a higher spinal fusion rate (5/6) compared to the negative control (1/6). Mechanically, BB-1 stimulated bone formation and vessel formation. Furthermore, we found that BB-1 increased the density of H-type vessels in the newly formed bone tissues for the first time. Moreover, 500 ​μg BB-1 triggered no local inflammation response in each spine segment and no systematic toxicity in liver and kidney. These results suggest that BB-1 promotes spinal fusion in rhesus monkeys by coupling of angiogenesis and osteogenesis and that local usage of 500 ​μg BB-1 should be effective and safe, facilitating translation of BB-1 from bench to bedside.

Summary: Background: The end plate plays an important role in intervertebral disc degeneration progression. The aim of the study was to examine the compositional and structural changes of the end plate with age and to investigate the correlation between end plate and disc degeneration by T1ρ and T2 map magnetic resonance imaging. Methods: There were 12 young monkeys (6-7 years old), 20 aged monkeys (14-17 years old) and 12 human participants (30-50 years old) in this study. T1ρ or T2 map values of the nucleus pulposus and end plate cartilage were analyzed according to Pfirrmann grades and age. Afterwards, micro computed tomography and histological analysis were used to confirm the end plate changes in monkeys. Pearson’s correlation was performed to investigate the relationship between end plate and disc degeneration. Results: In monkeys, T1ρ (r=-0.794, P

Summary Background Colonoscopy with computer-aided detection (CADe) has been shown in non-blinded trials to improve detection of colon polyps and adenomas by providing visual alarms during the procedure. We aimed to assess the effectiveness of a CADe system that avoids potential operational bias. Methods We did a double-blind randomised trial at the endoscopy centre in Caotang branch hospital of Sichuan Provincial People's Hospital in China. We enrolled consecutive patients (aged 18–75 years) presenting for diagnostic and screening colonoscopy. We excluded patients with a history of inflammatory bowel disease, colorectal cancer, or colorectal surgery or who had a contraindication for biopsy; we also excluded patients who had previously had an unsuccessful colonoscopy and who had a high suspicion for polyposis syndromes, inflammatory bowel disease, and colorectal cancer. We allocated patients (1:1) to colonoscopy with either the CADe system or a sham system. Randomisation was by computer-generated random number allocation. Patients and the endoscopist were unaware of the random assignment. To achieve masking, the output of the system was shown on a second monitor that was only visible to an observer who was responsible for reporting the alerts. The primary outcome was the adenoma detection rate (ADR), which is the proportion of individuals having a complete colonoscopy, from caecum to rectum, who had one or more adenomas detected. The primary analysis was per protocol. We also analysed characteristics of polyps and adenomas missed initially by endoscopists but detected by the CADe system. This trial is complete and is registered with http://www.chictr.org.cn , ChiCTR1800017675. Findings Between Sept 3, 2018, and Jan 11, 2019, 1046 patients were enrolled to the study, of whom 36 were excluded before randomisation, 508 were allocated colonoscopy with polyp detection using the CADe system, and 502 were allocated colonoscopy with the sham system. After further excluding patients who met exclusion criteria, 484 patients in the CADe group and 478 in the sham group were included in analyses. The ADR was significantly greater in the CADe group than in the sham group, with 165 (34%) of 484 patients allocated to the CADe system having one or more adenomas detected versus 132 (28%) of 478 allocated to the sham system (odds ratio 1·36, 95% CI 1·03–1·79; p=0·030). No complications were reported among all colonoscopy procedures. Polyps initially missed by the endoscopist but identified by the CADe system were generally small in size, isochromatic, flat in shape, had an unclear boundary, were partly behind colon folds, and were on the edge of the visual field. Interpretation Polyps initially missed by the endoscopist had characteristics that are sometimes difficult for skilled endoscopists to recognise. Such polyps could be detected using a high-performance CADe system during colonoscopy. The effect of CADe during colonoscopy on the incidence of interval colorectal cancer should be investigated. Funding None.

Adoptive cell therapy using TCR-engineered T cells (TCR-T cells) represents a promising strategy for treating relapsed and metastatic cancers. We previously established methods to identify neoantigen-specific TCRs based on patients’ PBMCs. However, in clinical practice isolation of PBMCs from advanced-stage cancer patients proves to be difficult. In this study, we substituted blood-derived T cells for tumor-infiltrating lymphocytes (TILs) and used an HLA-matched cell line of antigen-presenting cells (APCs) to replace autologous dendritic cells. Somatic mutations were determined in head and neck squamous cell carcinoma resected from two patients. HLA-A*02:01-restricted neoantigen libraries were constructed and transferred into HLA-matched APCs for stimulation of patient TILs. TCRs were isolated from reactive TIL cultures and functionality was tested using TCR- T cells in vitro and in vivo. To exemplify the screening approach, we identified the targeted neoantigen leading to recognition of the minigene construct that stimulated the strongest TIL response. Neoantigen peptides were used to load MHC-tetramers for T cell isolation and a TCR was identified targeting the KIAA1429D1358E mutation. TCR-T cells were activated, exhibited cytotoxicity, and secreted cytokines in a dose-dependent manner, and only when stimulated with the mutant peptide. Furthermore, comparable to a neoantigen-specific TCR that was isolated from the patient’s PBMCs, KIAA1429D1358E-specific TCR T cells destroyed human tumors in mice. The established protocol provides the required flexibility to methods striving to identify neoantigen-specific TCRs. By using an MHC-matched APC cell line and neoantigen-encoding minigene libraries, autologous TILs can be stimulated and screened when patient PBMCs and/or tumor material are not available anymore. Abbreviations: Head and neck squamous cell carcinoma (HNSCC); adoptive T cell therapy (ACT); T cell receptor (TCR); tumor-infiltrating lymphocytes (TIL); cytotoxic T lymphocyte (CTL); peripheral blood mononuclear cell (PBMC); dendritic cell (DC); antigen-presenting cells (APC)

ObjectiveThe effect of colonoscopy on colorectal cancer mortality is limited by several factors, among them a certain miss rate, leading to limited adenoma detection rates (ADRs). We investigated the effect of an automatic polyp detection system based on deep learning on polyp detection rate and ADR.DesignIn an open, non-blinded trial, consecutive patients were prospectively randomised to undergo diagnostic colonoscopy with or without assistance of a real-time automatic polyp detection system providing a simultaneous visual notice and sound alarm on polyp detection. The primary outcome was ADR.ResultsOf 1058 patients included, 536 were randomised to standard colonoscopy, and 522 were randomised to colonoscopy with computer-aided diagnosis. The artificial intelligence (AI) system significantly increased ADR (29.1%vs20.3%, pConclusionsIn a low prevalent ADR population, an automatic polyp detection system during colonoscopy resulted in a significant increase in the number of diminutive adenomas detected, as well as an increase in the rate of hyperplastic polyps. The cost–benefit ratio of such effects has to be determined further.Trial registration numberChiCTR-DDD-17012221; Results.

Chemotherapy is one of the main options for the treatment of a variety of malignant tumors. However, the severe side effects resulting from the killing of normal proliferating cells limit the application of cancer-targeting chemotherapeutic drugs. To improve the efficacy of classic systemic chemotherapy, the local delivery of high-dose chemotherapeutic drugs was developed as a method to enhance local drug concentrations and minimize systemic toxicity. Studies have demonstrated that chemotherapy is often accompanied by cancer-associated immunogenic cell death (ICD) and that autophagy is involved in the induction of ICD. To improve the efficacy of local cancer chemotherapy, we hypothesized that the local delivery of chemotherapeutic plus autophagy-enhancing agents would enhance the promotive effects of ICD on the antitumor immune response. Here, we report that a low-dose chemotherapy/autophagy enhancing regimen (CAER) not only resulted in the increased death of B16F10 and 4T1 tumor cells, but also induced higher levels of autophagy in vitro. Importantly, the local delivery of the CARE drugs significantly inhibited tumor growth in B16F10 and 4T1 tumor-bearing mice. Systemic antitumor T-cell immunity was observed in vivo, including neoantigen-specific T-cell responses. Furthermore, bioinformatic analysis of human breast cancer and melanoma tissues showed that autophagy-associated gene expression was upregulated in tumor samples. Increased autophagy and immune cell infiltration in tumor tissues were positively correlated with good prognosis of tumor patients. This work highlights a new approach to improve the effects of local chemotherapy and enhance systemic antitumor immunity.

With the aging of the population and the extension of life expectancy, osteoporosis is becoming a global epidemic. Although there are several drugs used to treat osteoporosis in clinical practice, such as parathyroid hormone or bisphosphonates, they all have some serious side effects. Therefore, a safer drug is called for osteoporosis, especially for the prevention in the early stage of the disease, not only the treatment in the later stage. Panax notoginseng saponin (PNS), a traditional Chinese herb, has been used as anti-ischemic drug due to its function on improving vascular circulation. In order to verify whether Panax notoginseng saponins (PNS) could be used to prevent osteoporosis, ovariectomy (OVX) was induced in female C57BL/C6J mice, followed by orally administration with 40 mg/kg/d, 80 mg/kg/d, and 160 mg/kg/d of three different dosages of PNS for 9 weeks. Serum biochemical analysis, micro-CT, histological evaluation, and immunostaining of markers of osteogenesis and angiogenesis were performed in the sham, osteoporotic (OVX), and treatment (OVX+PNS) groups. Micro-CT and histological evaluation showed that compared to sham group, the bone mass of OVX group reduced significantly, while it was significantly restored in the moderate-dose PNS (40 mg/kg and 80 mg/kg) treatment groups. The expression of CD31 and osteocalcin (OCN) in the bone tissue of treatment group also increased, suggesting that PNS activated osteogenesis and angiogenesis, which subsequently increased the bone mass. These results confirmed the potential function of PNS on the prevention of osteoporosis. However, in the high dose of PNS (160 mg/kg) group, the antiosteoportic effect had been eliminated, which also suggested the importance of proper dose of PNS for the prevention and treatment of osteoporosis in postmenopausal women.

Background: Computer-aided detection (CADe) of colon polyps has been demonstrated to improve colon polyp and adenoma detection during colonoscopy by indicating the location of a given polyp on a parallel monitor. The aim of this study was to investigate whether embedding the CADe system into the primary colonoscopy monitor may serve to increase polyp and adenoma detection, without increasing physician fatigue level. Methods: Consecutive patients presenting for colonoscopies were prospectively randomized to undergo routine colonoscopy with or without the assistance of a real-time polyp detection CADe system. Fatigue level was evaluated from score 0 to 10 by the performing endoscopists after each colonoscopy procedure. The main outcome was adenoma detection rate (ADR). Results: Out of 790 patients analyzed, 397 were randomized to routine colonoscopy (control group), and 393 to a colonoscopy with computer-aided diagnosis (CADe group). The ADRs were 20.91% and 29.01%, respectively (OR = 1.546, 95% CI 1.116–2.141, p = 0.009). The average number of adenomas per colonoscopy (APC) was 0.29 and 0.48, respectively (Change Folds = 1.64, 95% CI 1.299–2.063, p Conclusions: A real-time CADe system employed on the primary endoscopy monitor may lead to improvements in ADR and polyp detection rate without increasing fatigue level during colonoscopy. The integration of a low-latency and high-performance CADe systems may serve as an effective quality assurance tool during colonoscopy. www.chictr.org.cn number, ChiCTR1800018058.

Cancer immunotherapies, including immune checkpoint blockage and adoptive transfer of CAR-T cells, have achieved historical successes for many kinds of malignancy. However, a minority of patients survive long term over 5 years without relapse, perhaps owing to tumor heterogeneity and potent immunosuppression in the tumor microenvironment. Here, using an established mouse tumor model of triple-negative 4T1 breast cancer, we show that local immunochemotherapy triggers powerful local and systemic antitumor immunity. Paraneoplastic injection of CpG, α-OX40, and anthracycline completely eliminated both local and distant large established 4T1 breast cancer without obvious relapse. Analysis of the immune cells at tumor tissues, draining lymph nodes, and spleens revealed that the local treatment increased the infiltration of CD4+ and CD8+ T cells in all three tissues and inhibited the accumulation of myeloid-derived suppressor cells in the spleen in a delayed response. Most importantly, this treatment triggered systemic T cell response against 4T1 tumors and some of their neoantigen epitopes as detected by IFN-γ ELISpot and intracellular cytokine assays in splenocytes. Furthermore, T cells showed specific cytotoxic activity against 4T1 tumor cells in vitro. In general, this local immunochemotherapy provides a new approach to target highly diverse neoantigens in various types of cancers without complicated and expensive antigen identification via next-generation sequencing.

L.P. Li, L. Venkataraman, S. Chen, and H.J. Fu. Function of WFS1 and WFS2 in the Central Nervous System: Implications for Wolfram Syndrome and Alzheimer's Disease. NEUROSCI BIOBEHAV REVXXX-XXX,2020.-Wolfram syndrome (WS) is a rare monogenetic spectrum disorder characterized by insulin-dependent juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, progressive neurodegeneration, and a wide spectrum of psychiatric manifestations. Most WS patients belong to Wolfram Syndrome type 1 (WS1) caused by mutations in the Wolfram Syndrome 1 (WFS1/Wolframin) gene, while a small fraction of patients belongs to Wolfram Syndrome type 2 (WS2) caused by pathogenic variants in the CDGSH Iron Sulfur Domain 2 (CISD2/WFS2) gene. Although currently there is no treatment for this life-threatening disease, the molecular mechanisms underlying the pathogenesis of WS have been proposed. Interestingly, Alzheimer's disease (AD), an age-dependent neurodegenerative disease, shares some common mechanisms with WS. In this review, we focus on the function of WFS1 and WFS2 in the central nervous system as well as their implications in WS and AD. We also propose three future directions for elucidating the role of WFS1 and WFS2 in WS and AD.

ObjectivesFBXO6, a component of the ubiquitin E3 ligases, has been shown to bind high mannose N-linked glycoproteins and act as ubiquitin ligase subunits. Most proteins in the secretory pathway, such as matrix metalloproteinases, are modified with N-glycans and play important roles in the development of osteoarthritis (OA). However, whether FBXO6 exerts regulatory effects on the pathogenesis of OA remains undefined.MethodsThe expression of FBXO6 was examined in the cartilage of human and multiple mouse OA models. The role of FBXO6 in cartilage degeneration was analysed withglobal FBXO6-/-mice, transgenicCol2a1-CreERT2;FBXO6f/fmice. The FBXO6 interacting partner MMP14 and its regulatory transcriptional factor SMAD2/3 were identified and validated in different pathological models as well asSMAD2-/-mice.ResultsThe expression of FBXO6 decreased in the cartilage from human OA samples, anterior cruciate ligament transaction (ACLT) -induced OA samples, spontaneous OA STR/ort samples and aged mice samples. Global knockout or conditional knockout of FBXO6 in cartilage promoted experimental OA process. The molecular mechanism study revealed that FBXO6 decreased MMP14 by ubiquitination and degradation, leading to inhibited proteolytic activation of MMP13. Interestingly, FBXO6 expression is regulated by transforming growth factor β (TGFβ)-SMAD2/3 signalling pathway. Therefore, the overexpression of FBXO6 protected mice from post-injury OA development.ConclusionsTGFβ-SMAD2/3 signalling pathway suppressed MMP13 activation by upregulating of FBXO6 transcription and consequently promoting MMP14 proteasomal degradation. Inducement of FBXO6 expression in OA cartilage might provide a promising OA therapeutic strategy.

BackgroundEvidence has shown that deep learning computer aided detection (CADe) system achieved high overall detection accuracy for polyp detection during colonoscopy.AimThe detection performance of CADe system on non-polypoid laterally spreading tumors (LSTs) and sessile serrated adenomas/polyps (SSA/Ps), with higher risk for malignancy transformation and miss rate, has not been exclusively investigated.MethodsA previously validated deep learning CADe system for polyp detection was tested exclusively on LSTs and SSA/Ps. 1451 LST images from 184 patients were collected between July 2015 and January 2019, 82 SSA/Ps videos from 26 patients were collected between September 2018 and January 2019. The per-frame sensitivity and per-lesion sensitivity were calculated.Results(1) For LSTs image dataset, the system achieved an overall per-image sensitivity and per-lesion sensitivity of 94.07% (1365/1451) and 98.99% (197/199) respectively. The per-frame sensitivity for LST-G(H), LST-G(M), LST-NG(F), LST-NG(PD) was 93.97% (343/365), 98.72% (692/701), 85.71% (324/378) and 85.71% (6/7) respectively. The per-lesion sensitivity of each subgroup was 100.00% (71/71), 100.00% (64/64), 98.31% (58/59) and 80.00% (4/5). (2) For SSA/Ps video dataset, the system achieved an overall per-frame sensitivity and per-lesion sensitivity of 84.10% (15883/18885) and 100.00% (42/42), respectively.ConclusionsThis study demonstrated that a local-feature-prioritized automatic CADe system could detect LSTs and SSA/Ps with high sensitivity. The per-frame sensitivity for non-granular LSTs and small SSA/Ps should be further improved.

The detection and removal of precancerous polyps via colonoscopy is the gold standard for the prevention of colon cancer. However, the detection rate of adenomatous polyps can vary significantly among endoscopists. Here, we show that a machine-learning algorithm can detect polyps in clinical colonoscopies, in real time and with high sensitivity and specificity. We developed the deep-learning algorithm by using data from 1,290 patients, and validated it on newly collected 27,113 colonoscopy images from 1,138 patients with at least one detected polyp (per-image-sensitivity, 94.38%; per-image-specificity, 95.92%; area under the receiver operating characteristic curve, 0.984), on a public database of 612 polyp-containing images (per-image-sensitivity, 88.24%), on 138 colonoscopy videos with histologically confirmed polyps (per-image-sensitivity of 91.64%; per-polyp-sensitivity, 100%), and on 54 unaltered full-range colonoscopy videos without polyps (per-image-specificity, 95.40%). By using a multi-threaded processing system, the algorithm can process at least 25 frames per second with a latency of 76.80 ± 5.60 ms in real-time video analysis. The software may aid endoscopists while performing colonoscopies, and help assess differences in polyp and adenoma detection performance among endoscopists.

Non-alcoholic fatty liver disease (NAFLD) has been considered as a multi-factorial metabolic syndrome. MicroRNA-375 (MiR-375) was significantly up-regulated in serum of NAFLD patients and the role of miR-375 was addressed as a putative biomarker of NAFLD progression. However, the specific function of miR-375 in the progression of NAFLD is still unclear and the molecular mechanisms underlying NAFLD have yet to be elucidated. Our study aimed at investigating the regulatory role of miR-375 in the molecular mechanisms of the pathogenic progression of NAFLD and to find out whether miR-375 regulates the expression level of adipokines and inflammatory cytokines in NAFLD. We found that miR-375 expression was increased in the serum of high fat diet (HFD)-feeding mice comparing to that in healthy controls, whereas the expression of Adiponectin receptor 2 (AdipoR2) was decreased in mice fed with HFD. Moreover, inhibiton of miR-375 up-regulated the expression of Adiponectin, inhibited the lipid accumulation and down-regulated both the level of Leptin and inflammatory cytokines including tumour necrosis factor (TNF)-α and interleukin (IL)-6 in palmiticacid (PA)-induced human hepatocellular carcinoma HepG2 cells. In addition, we also found that AdipoR2 was a target of miR-375 by binding directly to the 3'UTR of it. Of note, the reduced level of TNF-α, IL-6 as well as Leptin and the production of Adiponectin by miR-375 inhibitors was significantly reversed by silencing of AdipoR2 in PA-induced HepG2 cells. Our findings bring new insight into understanding the complex mechanisms underlying the pathogenesis of NAFLD and provide evidence that miR-375 might represent a novel therapeutic target for NAFLD.

Systematic review and meta-analysis.Posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) were widely used in the treatment of lumbar isthmic spondylolisthesis (IS). There was a great controversy over the preferred fusion method.The purpose of this study is to evaluate the clinical outcomes between PLF and PLIF for the treatment of IS.Related studies that compared the clinical effectiveness of PLIF and PLF for the treatment of IS were acquired by a comprehensive search in 4 electronic databases (PubMed, EMBASE, Cochrane Controlled Trial Register, and MEDLINE) from January 1950 through December 2014. Included studies were performed according to eligibility criteria. The main endpoints included: improvement of clinical satisfaction, complication rate, reoperation rate, fusion rate, and reoperation rate.A total of 9 studies were included in the meta-analysis; 6 were low-quality evidence and 2 were high-quality evidence as indicated by the Jadad scale. Compared with PLIF, PLF patients showed lower fusion rates [P=0.005, odds ratio (OR)=0.29 (0.14, 0.58)] and shorter operation times [P0.00001, weighted mean difference (WMD)=-0.5(-0.61, -0.39)]. No significant difference was found in the term of postoperative visual analogue scale leg score [P=0.92, WMD=0.02 (-0.39, 0.44)] and visual analogue scale back score [P=0.41, WMD=0.20 (-0.28, 0.68)], blood loss [P=0.39, WMD=121.17 (-152.68, 395.01)], complication rate [P=0.42, OR=1.50 (0.56, 4.03)], postoperative Oswestry Disability Index [P=0.3, WMD=1.09 (-0.97, 3.15)], and postoperative clinical satisfaction [P=0.84, OR=1.06 (0.60, 1.86)].In conclusion, our meta-analysis suggested that PLF shows significant lower fusion rate compared with PLIF. Although PLIF had more operation time than PLF, there was no significant difference in global assessment of clinical outcome between the 2 fusion procedures. However, future well-designed, randomized-controlled trials are still needed to further confirm our results.

Because of endoscopist fatigue, the time of colonoscopy have been shown to influence adenoma detection rate (ADR). Computer-aided detection (CADe) provides simultaneous visual alerts on polyps during colonoscopy and thus to increase adenoma detection rate. This is attributable to the strengthening of endoscopists diagnostic level and alleviation of fatigue. The aim of the study was to investigate whether CADe colonoscopy could eliminate the influence of the afternoon fatigue on ADR. We retrospectively analyzed the recorded data of patients who were performed CADe colonoscopy from September 2017 to February 2019 in Endoscopy Center of Sichuan Provincial People's Hospital. Patients demographic as well as baseline data recorded during colonoscopy were used for the analysis. Morning colonoscopy was defined as colonoscopic procedures starting between 8:00 am and 12:00 noon. Afternoon colonoscopy was defined as procedures starting at 2:00 pm and thereafter. The primary outcome was ADR. Univariate analysis and multivariate regression analysis were also performed. A total of 484 CADe colonoscopies were performed by 4 endoscopists in the study. The overall polyp detection rate was 52% and overall ADR was 35.5%. The mean number of adenomas detected per colonoscopy (0.62 vs 0.61, P > .05) and ADR (0.36 vs 0.35, P > .05) were similar in the am and pm group. Multivariable analysis shows that the ADR of CADe colonoscopy was influenced by the age (P

Background Owing to the small sample sizes in individual studies reported to date, whether or not mini-plate fixation is better than suture suspensory fixation in unilateral open-door laminoplasty is unclear. Thus, we conducted a meta-analysis to evaluate which fixation method is superior in cervical laminoplasty for patients with multilevel cervical spondylotic myelopathy (MCSM). Methods Several electronic databases were selected to search the related studies. The main endpoints included operation time, blood loss, preoperative Japanese Orthopedic Association (JOA) score, postoperative JOA score, JOA recovery rate, postoperative anteroposterior diameter, open angle, and the incidence of axial symptoms or C5 palsy after surgery. The results are presented as mean difference (MD) for continuous outcomes and odds ratio (OR) with 95% confidence interval (CI) for dichotomous outcomes. Results Six studies, including a total of 436 patients, were included in this review. The postoperative JOA score was higher in patients receiving suture suspensory fixation (group B) than in those receiving mini-plate fixation (group A) (MD, 0.51; 95% CI, 0.07–0.96; P = 0.002), as was the incidence of C5 palsy (OR, 0.37; 95% CI, 0.15–0.92; P = 0.03). In 5 of the 6 studies, including 282 patients, the incidence of axial symptoms was lower in group A (OR, 0.37; 95% CI, 0.21–0.67; P = 0.0009). There were no significant differences ( P > 0.05) between groups A and B in terms of operation time, blood loss, JOA recovery rate, postoperative anteroposterior diameter, or open angle after surgery. Conclusions Although suture suspensory fixation was associated with better postoperative JOA scores, mini-plate fixation was superior in reducing the incidence of surgical complications. To avoid severe surgical complications, mini-plate fixation is a good choice for laminoplasty for patients with MCSM. Valid evidence depends on more high-quality, randomized controlled trials in the future.

Background and Aims Up to 30% of adenomas might be missed during screening colonoscopy—these could be polyps that appear on-screen but are not recognized by endoscopists or polyps that are in locations that do not appear on the screen at all. Computer-aided detection (CADe) systems, based on deep learning, might reduce rates of missed adenomas by displaying visual alerts that identify precancerous polyps on the endoscopy monitor in real time. We compared adenoma miss rates of CADe colonoscopy vs routine white-light colonoscopy. Methods We performed a prospective study of patients, 18–75 years old, referred for diagnostic, screening, or surveillance colonoscopies at a single endoscopy center of Sichuan Provincial People's Hospital from June 3, 2019 through September 24, 2019. Same day, tandem colonoscopies were performed for each participant by the same endoscopist. Patients were randomly assigned to groups that received either CADe colonoscopy (n=184) or routine colonoscopy (n=185) first, followed immediately by the other procedure. Endoscopists were blinded to the group each patient was assigned to until immediately before the start of each colonoscopy. Polyps that were missed by the CADe system but detected by endoscopists were classified as missed polyps. False polyps were those continuously traced by the CADe system but then determined not to be polyps by the endoscopists. The primary endpoint was adenoma miss rate, which was defined as the number of adenomas detected in the second-pass colonoscopy divided by the total number of adenomas detected in both passes. Results The adenoma miss rate was significantly lower with CADe colonoscopy (13.89%; 95% CI, 8.24%–19.54%) than with routine colonoscopy (40.00%; 95% CI, 31.23%–48.77%, P Conclusions CADe colonoscopy reduced the overall miss rate of adenomas by endoscopists using white-light endoscopy. Routine use of CADe might reduce the incidence of interval colon cancers. chictr.org.cn study no: ChiCTR1900023086

Iodine-rich groundwater is a cause for concern because it is harmful to human health, and determining the sources of groundwater iodine in coastal urbanized areas is complicated. This study aims to delineate the spatial distribution of groundwater iodide in various shallow and unconfined aquifers, as well as in areas with different urbanization levels in the Pearl River Delta (PRD), and to identify the origins of iodide-rich (>0.08 mg/L) groundwater in this region. Approximately 400 groundwater samples, 10 surface water samples, and 9 leachate samples were collected, and a total of 17 chemicals were analyzed. The result showed that iodide-rich groundwater was present in 13.95% of shallow granular aquifers and 6.82% of shallow fissured aquifers; however, it was not present in karst aquifers. In shallow granular aquifers, the proportions of iodide-rich groundwater in areas with different urbanization levels were similar. On the other hand, in shallow fissured aquifers, iodide-rich groundwater mostly appeared in urbanized areas, and its proportion was more than three times that of non-urbanized areas; however, it was not present in peri-urban areas. The reductive dissolution of iodine-loaded Fe/Mn (oxy)hydroxides and decomposition of iodine-rich organic matter in sediments were likely the main sources of iodide-rich groundwater in shallow granular aquifers. Urbanization accompanied by wastewater leakage was also a significant source for iodide-rich groundwater in granular aquifers of urbanized areas. In contrast, the degradation of organic matter in carbonate-rich rocks and urbanization accompanied by leakage of reductive sewage were most likely responsible for the occurrence of iodide-rich groundwater in shallow fissured aquifers. The leakage of landfill leachate was also a significant source for iodide-rich groundwater in the fissured aquifers of non-urbanized areas.

Urbanization and industrialization have increased groundwater resource demands, and may drive the change of heavy metal(loid)s and organic chemicals in groundwater in the Pearl River Delta (PRD), southern China. Thus, a comprehensive understanding of the distributions, sources, and driving forces of heavy metal(loid)s and organic chemicals in groundwater in the PRD is vital for water resource management in this region. In this study, eight heavy metal(loid)s and fifty-five organic chemicals in groundwater across the PRD were investigated. The results show that undrinkable groundwater related to heavy metal(loid)s was mainly due to high concentrations of Fe (19.3%) and As (6.8%). Eighteen organic contaminants were detected in groundwater in the PRD, where the most frequently detected organic contaminant was naphthalene, and its detection rate was 2.51%. In 5.3% of all groundwater samples, one or more organic contaminants were found. All detected organic contaminants, except ones without allowable limits, in groundwater were at concentrations below allowable limits of China. The mean concentrations of heavy metal(loid)s in granular aquifers were higher than those in fissured and karst aquifers, especially for Fe and As. Except Se, the mean concentrations of other heavy metal(loid)s and the frequency of detection of organic contaminants in groundwater in urbanized and peri-urban areas were higher than those in non-urbanized areas, especially for Hg, Co, and organic contaminants. Fe, As, and Se in groundwater mainly originated from the release of Fe/As/Se rich sediments. The former two were driven by reduction reactions, while the latter was driven by oxidation resulting from the infiltration of NO3-. In contrast, other five heavy metal(loid)s and organic contaminants in groundwater mainly originated from the anthropogenic sources, such as the infiltration of industrial sewage. It is evident that urbanization and industrialization are two powerful driving forces for heavy metal(loid)s and organic contaminants in groundwater in the PRD.

Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated, for the first time, that miR-425 was significantly up-regulated in peripheral blood mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th) 17 cells were found to be the major source of miR-425 expression. Using gain-of-function approaches, we demonstrated that miR-425 could facilitate the differentiation of CD4+ T cells into Th17 lineage. In addition, forkhead box O1 (Foxo1) was identified as a novel target gene of miR-425, which was able to inhibit Th17 cell differentiation, and it was observed to be markedly decreased in PBMC and mucosa of patients with IBD. Notably, in vivo inhibition of miR-425 significantly alleviated the disease severity of TNBS-induced colitis in mice, with down-regulated levels of IL-17A. Our data reveal a novel mechanism in which the elevated miR-425 in IBD mediates pathogenic Th17 cell generation through down-regulation of Foxo1. In vivo blockade of miR-425 may serve as a novel therapeutic approach in the treatment of IBD.

The purpose of this study is to evaluate the clinical outcomes, complications, and surgical trauma between anterior and posterior approaches for the treatment of multilevel cervical spondylotic myelopathy (CSM).Systematic review and meta-analysis.Randomized controlled trials or non-randomized controlled trials published up to November 2014 that compared the clinical effectiveness of anterior and posterior surgical approaches for the treatment of multilevel CSM were acquired by a comprehensive search in four electronic databases (PubMed, EMBASE, Cochrane Controlled Trial Register and MEDLINE). Exclusion criteria were non-controlled studies, combined anterior and posterior surgery and cervical myelopathy caused by ossification of the posterior longitudinal ligament. The main end points included: recovery rate; Japanese Orthopedic Association (JOA) score; complication rate; reoperation rate; blood loss; operation time and length of stay.A total of ten studies were included in the meta-analysis; none of which were randomized controlled trials. All of the selected studies were of high quality as indicated by the Newcastle-Ottawa scale. In six studies involving 467 patients, there was no significant difference in the preoperative JOA score between the anterior surgery group and the posterior group [P0.05, WMD -0.00 (-0.50, 0.50)]. In four studies involving 268 patients, the postoperative JOA score was significantly higher in the anterior surgery group compared with the posterior surgery group [P0.05, WMD 0.79 (0.16, 1.42)]. In five studies involving 420 patients, there was no statistically significant difference in recovery rate between the anterior and posterior surgery groups [P0.05, WMD 2.73 (-8.69, 14.15)]. In nine studies involving 804 patients, the postoperative complication rate was significantly higher in the anterior surgery group compared with the posterior surgery group [P = 0.009, OR 1.65 (1.13, 2.39)]. In five studies involving 294 patients, the reoperation rate was significantly higher in the anterior surgery group compared with the posterior surgery group [P = 0.0001, OR 8.67 (2.85, 26.34)]. In the four studies involving 252 patients, the intraoperative blood loss and operation time was significantly higher in the anterior surgery group compared with the posterior surgery group [P0.05, WMD -40.25 (-76.96, -3.53) and P0.00001, WMD 61.3 (52.33, 70.28)]. In the three studies involving 192 patients, the length of stay was significantly lower in the anterior surgery group compared with the posterior surgery group [P0.00001, WMD -1.07 (-2.23, -1.17)].In summary, our meta-analysis suggested that a definitive conclusion could not be reached regarding which surgical approach is more effective for the treatment of multilevel CSM. Although anterior approach was associated with better postoperative neural function than posterior approach in the treatment of multilevel CSM, there was no apparent difference in the neural function recovery rate between the two approaches. Higher rates of surgery-related complication and reoperation should be taken into consideration when anterior approach is used for patients with multilevel CSM.

Colorectal cancer has high incidence and mortality. Early diagnosis could increase patient survival, but early diagnosis has been poor in China for the past decades. The purpose of this study is to assess the polyp detection rate (PDR) and adenoma detection rate (ADR) by colonoscopy in a Chinese population, and to determine the risk factors for adenoma. This prospective study at Sichuan Provincial People's Hospital evaluated patients who underwent colonoscopy in September 2017 to February 2018. Basic information, exact insertion and withdrawal times, PDR, and ADR were assessed. Risk factors for colorectal adenoma in the adenoma-positive and adenoma-negative groups (based on pathology) were assessed by multivariable logistic regression analysis. A total of 1058 procedures with 767 polyps were analyzed. The overall PDR and ADR were 36.96% (391/1058) and 24.67% (261/1058), respectively. Occurrence of adenoma was associated with age, gender, body mass index (BMI), family history of colon cancer, personal history of adenoma, diabetes mellitus, and tobacco use. There was a significant association between withdrawal time and ADR (P

Inverse modeling is an essential step for reliable modeling of subsurface flow and transport, which is important for groundwater resource management and aquifer remediation. Multiple-point statistics (MPS) based reservoir modeling algorithms, beyond traditional two-point statistics-based methods, offer an alternative to simulate complex geological features and patterns, conditioning to observed conductivity data. Parameter estimation, within the framework of MPS, for the characterization of conductivity fields using measured dynamic data such as piezometric head data, remains one of the most challenging tasks in geologic modeling. We propose a new local global pattern matching method to integrate dynamic data into geological models. The local pattern is composed of conductivity and head values that are sampled from joint training images comprising of geological models and the corresponding simulated piezometric heads. Subsequently, a global constraint is enforced on the simulated geologic models in order to match the measured head data. The method is sequential in time, and as new piezometric head become available, the training images are updated for the purpose of reducing the computational cost of pattern matching. As a result, the final suite of models preserve the geologic features as well as match the dynamic data. This local global pattern matching method is demonstrated for simulating a two-dimensional, bimodally-distributed heterogeneous conductivity field. The results indicate that the characterization of conductivity as well as flow and transport predictions are improved when the piezometric head data are integrated into the geological modeling. (C) 2015 Elsevier Ltd. All rights reserved., The authors gratefully acknowledge the financial support by DOE through projects DE-FE0004962 and DE-SC0001114. The last author acknowledges the support of the Spanish Ministry of Economy and Competitiveness through project CGL2011-23295. We greatly thank the three anonymous reviewers for their comments, which substantially improved the manuscript.

Anterior cervical discectomy and fusion (ACDF) is a widely accepted surgical procedure for the treatment of cervical degenerative disk diseases (CDDD). The purpose of our study was to investigate the reliability and efficacy of ACDF using self-locking stand-alone polyetheretherketone (PEEK) cages, with two anchoring clips placed in the upper and lower vertebrae, respectively. Twenty-six patients who underwent ACDF using a stand-alone PEEK cage packed with local osteophytes and cancellous allograft bone from January 2010 to January 2012 were enrolled in this study. Clinical findings were assessed using a visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), and Odom criteria. Intervertebral height and cervical fusion status were assessed on X-ray. Twenty-six patients underwent ACDF using a stand-alone PEEK cervical cage. All patients had a minimum 2 years of follow-up. The operative levels were C3/4, C4/5 in seven patients, C4/5, C5/6 in 13 patients, and C4/5, C6/7 in six patients. At 3 days, 6 months, and 2 years of follow-ups, the JOA scores were 10.41 ± 1.67, 13.78 ± 1.91, 14.42 ± 2.09, respectively, which was significantly higher (p

[EN] The normal-score ensemble Kalman filter (NS-EnKF) is tested on a synthetic aquifer characterized by the presence of channels with a bimodal distribution of its hydraulic conductivities. This is a clear example of an aquifer that cannot be characterized by a multiGaussian distribution. Fourteen scenarios are analyzed which differ among them in one or various of the following aspects: the prior random function model, the boundary conditions of the flow problem, the number of piezometers used in the assimilation process, or the use of covariance localization in the implementation of the Kalman filter. The performance of the NS-EnKF is evaluated through the ensemble mean and variance maps, the connectivity patterns of the individual conductivity realizations and the degree of reproduction of the piezometric heads. The results show that (i) the localized NS-EnKF can characterize the non-multiGaussian underlying hydraulic distribution even when an erroneous prior random function model is used, (ii) localization plays an important role to prevent filter inbreeding and results in a better logconductivity characterization, and (iii) the NS-EnKF works equally well under very different flow configurations. © Author(s) 2012., The authors gratefully acknowledge the financial support by the Spanish Ministry of Science and Innovation through project CGL2011-23295. The two anonymous reviewers are gratefully acknowledged for their comments which helped improving the final version of the manuscript.