Complete spatially resolved gene expression is not necessary for identifying spatial domains.

Spatially resolved transcriptomics (SRT) technologies have revolutionized the study of tissue organization. We introduce a graph convolutional network with an attention and positive emphasis mechanism, termed BINARY, relying exclusively on binarized SRT data to accurately delineate spatial domains. BINARY outperforms existing methods across various SRT data types while using significantly less input information. Our study suggests that precise gene expression quantification may not always be essential, inspiring further exploration of the broader applications of spatially resolved binarized gene expression data.

Improved Denoising of Cryo-Electron Microscopy Micrographs with Simulation-Aware Pretraining.

Cryo-electron microscopy (cryo-EM) has emerged as a potent technique for determining the structure and functionality of biological macromolecules. However, limited by the physical imaging conditions, such as low electron beam dose, micrographs in cryo-EM typically contend with an extremely low signal-to-noise ratio (SNR), impeding the efficiency and efficacy of subsequent analyses. Therefore, there is a growing demand for an efficient denoising algorithm designed for cryo-EM micrographs, aiming to enhance the quality of macromolecular analysis. However, owing to the absence of a comprehensive and well-defined dataset with ground truth images, supervised image denoising methods exhibit limited generalization when applied to experimental micrographs. To tackle this challenge, we introduce a simulation-aware image denoising (SaID) pretrained model designed to enhance the SNR of cryo-EM micrographs where the training is solely based on an accurately simulated dataset. First, we propose a parameter calibration algorithm for simulated dataset generation, aiming to align simulation parameters with those of experimental micrographs. Second, leveraging the accurately simulated dataset, we propose to train a deep general denoising model that can well generalize to real experimental cryo-EM micrographs. Comprehensive experimental results demonstrate that our pretrained denoising model achieves excellent denoising performance on experimental cryo-EM micrographs, significantly streamlining downstream analysis.

Rotating Sonotrode Design for Ultrasonic-Assisted Arc Welding of Metal Materials.

In the process of the ultrasonic-assisted arc welding of metal materials, traditional ultrasonic application methods, such as the low-frequency impact of ultrasonic horns on a base material, can easily cause the non-fusion defect. In order to solve this problem, a rotating sonotrode with a groove and double thin ends was designed in this study. The ultrasonic vibration is transmitted into the weld pool by the rolling of the sonotrode on both sides of the weld. The resonant frequency was set at 50 kHz. Firstly, based on the Mindlin theory, a rotating sonotrode without a groove was designed by solving the frequency equation and by conducting a finite element simulation. Secondly, the effects of the groove, perforation, and transition mode on the resonant frequency, stress distribution, and amplification factor were investigated by finite element simulation. Finally, the optimum rotating sonotrode with a groove was obtained. The results show that the size of a rotating sonotrode that has a small frequency error can be obtained by using the discrete interval solver method combined with finite element simulation. The groove can significantly reduce the resonant frequency. The stress concentration can be effectively reduced by using the elliptical transition mode. The resonant frequency and amplification factor of a rotating sonotrode with a groove could be effectively adjusted by a method of double-position joint perforation. The final resonant frequency was 49.721 kHz and the amplification factor was 3.02. This study provides an effective design method for a sonotrode with double thin ends and a groove structure.

Treatment of L5-S1 Floating Calcified Lumbar Disc Herniation with Percutaneous Endoscopic Interlaminar Discectomy.

OBJECTIVE: The floating calcified tissue in floating calcified lumbar disc herniation (FCLDH) is hard and often adheres to the dura mater, which can easily cause nerve root damage during surgery, making the operation challenging. We proposed the classification of FCLDH and a new technique for removing floating calcified tissue and reported the clinical efficacy and safety of this new technique in clinical practice. METHODS: From January 2019 to October 2021, 24 patients (13 males and 11 females, 46.4 ± 7.72 years) with L5-S1 floating calcified lumbar disc herniation were treated with percutaneous endoscopic interlaminar discectomy (PEID). According to FCLDH classification, a total of Type Ia: nine cases, Type Ib: five cases, Type IIa: four cases, and Type IIa: six cases were included. The visual analogue scale (VAS) and Oswestry disability index (ODI) were recorded pre-operatively and 3 days postoperatively, 6 months postoperatively, and at the last follow-up. The postoperative curative effect was evaluated according to the modified MacNab criteria. Computed tomography (CT) and magnetic resonance imaging (MRI) of the lumbar spine were performed 3 days after surgery to evaluate the efficacy of the surgery. RESULTS: All patients successfully underwent PEID. The VAS and ODI scores at 3 days postoperatively, 6 months postoperatively, and at the last follow-up were significantly improved and statistically significant compared to those of the preoperative period (p < 0.05). All the patients were followed up for 12-24 months (mean, 16.6 ± 4.6 months). At the last follow-up, according to the modified MacNab criteria, 15 cases were excellent, eight were good, and one was fair. The combined excellent and good rate was 95.83% (23/24). Postoperative review revealed that all floating calcified tissues were effectively removed and the nerve roots were adequately decompressed without complications such as cerebrospinal fluid leakage and lumbar spine infection. CONCLUSION: The classification of FCLDH we proposed can well guide the selection of surgical plans. PEID combined with floating calcified tissue removal technology has good efficacy in the treatment of L5-S1 FCLDH, ensuring accurate removal of calcified tissue, reducing complications and improving the quality of life of affected individuals.

MarkerDetector: A method for robust fiducial marker detection in electron micrographs using wavelet-based template.

Fiducial marker detection in electron micrographs becomes an important and challenging task with the development of large-field electron microscopy. The fiducial marker detection plays an important role in several steps during the process of electron micrographs, such as the alignment and parameter calibrations. However, limited by the conditions of low signal-to-noise ratio (SNR) in the electron micrographs, the performance of fiducial marker detection is severely affected. In this work, we propose the MarkerDetector, a novel algorithm for detecting fiducial markers in electron micrographs. The proposed MarkerDetector is built upon the following contributions: Firstly, a wavelet-based template generation algorithm is devised in MarkerDetector. By adopting a shape-based criterion, a high-quality template can be obtained. Secondly, a robust marker determination strategy is devised by utilizing statistic-based filtering, which can guarantee the correctness of the detected fiducial markers. The average running time of our algorithm is 1.67 seconds with promising accuracy, indicating its practical feasibility for applications in electron micrographs.

Effects of vegetation and soil changes on microbial biomass carbon and nitrogen in the Napahai meadow under N deposition.

To explore the responses of soil microorganisms to short-term nitrogen deposition in alpine meadow, we set three treatments of low nitrogen (5 g N·m-2·a-1), medium nitrogen (10 g N·m-2·a-1), and high nitrogen (15 g N·m-2·a-1) addition to investigate the effects of nitrogen-deposition induced alterations in plant diversity and soil physicochemical properties on microbial biomass carbon (MBC) and nitrogen (MBN) in a typical alpine meadow community of Carex nubigena in Napahai. The results showed that nitrogen addition significantly increased soil MBC, MBN, and their quotients, with the increases of MBC being as high as 139.3% under medium nitrogen treatment. Both MBC and MBN showed significant decreases along the soil layer, with a reduction of 24.1% to 75.1%. Nitrogen addition significantly increased aboveground biomass and reduced Shannon and Simpson indices by 6.6%-65.4%. Nitrogen addition significantly decreased soil pH, increased the contents of organic matter, total nitrogen, ammonium nitrogen and nitrate nitrogen, with the highest reduction (7.0%-511.1%) being observed in medium nitrogen treatment. Soil pH increased while other physical and chemical indicators significantly decreased with the increases of soil layer, with a variation range of 19.5%-91.2%. Results of structural equation model showed that microbial biomass was significantly positively correlated with ammonium nitrogen, nitrate nitrogen and organic matter, but negatively correlated with pH and Shannon index. The interaction of plant and soil physicochemical properties explained 55%-77% of the variations in MBC, MBN and their quotient. Soil physicochemical properties had the highest effect value (0.56-0.95) on MBC, MBN and their quotients, followed by plant diversity and aboveground biomass. Therefore, nitrogen deposition increased soil MBC and MBN and their quotient, primarily through improving soil nutrient availability and plant aboveground biomass, whereas MBC and MBN and their quotient were suppressed by high-level nitrogen deposition due to soil acidification and plant diversity losses.

Sparse and Hierarchical Transformer for Survival Analysis on Whole Slide Images.

The Transformer-based methods provide a good opportunity for modeling the global context of gigapixel whole slide image (WSI), however, there are still two main problems in applying Transformer to WSI-based survival analysis task. First, the training data for survival analysis is limited, which makes the model prone to overfitting. This problem is even worse for Transformer-based models which require large-scale data to train. Second, WSI is of extremely high resolution (up to 150,000 x 150,000 pixels) and is typically organized as a multi-resolution pyramid. Vanilla Transformer cannot model the hierarchical structure of WSI (such as patch cluster-level relationships), which makes it incapable of learning hierarchical WSI representation. To address these problems, in this paper, we propose a novel Sparse and Hierarchical Transformer (SH-Transformer) for survival analysis. Specifically, we introduce sparse self-attention to alleviate the overfitting problem, and propose a hierarchical Transformer structure to learn the hierarchical WSI representation. Experimental results based on three WSI datasets show that the proposed framework outperforms the state-of-the-art methods.

[Advances in surgical strategies for ossification of posterior longitudinal ligament involving the C 2 segment].

Objective: To evaluate the application of surgical strategies for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving the C 2 segment. Methods: The literature about the surgery for cervical OPLL involving C 2 segment was reviewed, and the indications, advantages, and disadvantages of surgery were summarized. Results: For cervical OPLL involving the C 2 segments, laminectomy is suitable for patients with OPLL involving multiple segments, often combined with screw fixation, and has the advantages of adequate decompression and restoration of cervical curvature, with the disadvantages of loss of cervical fixed segmental mobility. Canal-expansive laminoplasty is suitable for patients with positive K-line and has the advantages of simple operation and preservation of cervical segmental mobility, and the disadvantages include progression of ossification, axial symptoms, and fracture of the portal axis. Dome-like laminoplasty is suitable for patients without kyphosis/cervical instability and with negative R-line, and can reduce the occurrence of axial symptoms, with the disadvantage of limited decompression. The Shelter technique is suitable for patients with single/double segments and canal encroachment >50% and allows for direct decompression, but is technically demanding and involves risk of dural tear and nerve injury. Double-dome laminoplasty is suitable for patients without kyphosis/cervical instability. Its advantages are the reduction of damage to the cervical semispinal muscles and attachment points and maintenance of cervical curvature, but there is progress in postoperative ossification. Conclusion: OPLL involving the C 2 segment is a complex subtype of cervical OPLL, which is mainly treated through posterior surgery. However, the degree of spinal cord floatation is limited, and with the progress of ossification, the long-term effectiveness is poor. More research is needed to address the etiology of OPLL and to establish a systematic treatment strategy for cervical OPLL involving the C 2 segment.

Divide-and-Attention Network for HE-Stained Pathological Image Classification.

Since pathological images have some distinct characteristics that are different from natural images, the direct application of a general convolutional neural network cannot achieve good classification performance, especially for fine-grained classification problems (such as pathological image grading). Inspired by the clinical experience that decomposing a pathological image into different components is beneficial for diagnosis, in this paper, we propose a Divide-and-Attention Network (DANet) for Hematoxylin-and-Eosin (HE)-stained pathological image classification. The DANet utilizes a deep-learning method to decompose a pathological image into nuclei and non-nuclei parts. With such decomposed pathological images, the DANet first performs feature learning independently in each branch, and then focuses on the most important feature representation through the branch selection attention module. In this way, the DANet can learn representative features with respect to different tissue structures and adaptively focus on the most important ones, thereby improving classification performance. In addition, we introduce deep canonical correlation analysis (DCCA) constraints in the feature fusion process of different branches. The DCCA constraints play the role of branch fusion attention, so as to maximize the correlation of different branches and ensure that the fused branches emphasize specific tissue structures. The experimental results of three datasets demonstrate the superiority of the DANet, with an average classification accuracy of 92.5% on breast cancer classification, 95.33% on colorectal cancer grading, and 91.6% on breast cancer grading tasks.

Light-Induced Synthesis of Oxygen-Vacancy-Functionalized Ni(OH)2 Nanosheets for Highly Selective CO2 Reduction.

Solar-driven CO2 reduction into fuels and chemicals has gained increasing attention in recent years. In this study, oxygen-vacancies-functionalized Ni(OH)2 (OVs-Ni(OH)2 ) nanosheets are synthesized by a photochemical method to serve as a catalyst for CO2 reduction. Characterization reveals that COOH* is the key intermediate for CO2 -to-CO photoreduction. Experimental results and theoretical calculations confirm that OVs modification can greatly modulate the interaction strength between the OVs-Ni(OH)2 and CO2 , while lowering the energy barrier for COOH* formation, thereby preferentially facilitating CO2 reduction. As a result, the OVs-Ni(OH)2 catalyst exhibits outstanding activity and selectivity for CO2 -to-CO photoreduction with visible light. A CO evolution rate of 31.58 µmol h-1 (0.35 mg catalyst, 90228 µmol h-1 g-1 ) with a selectivity of 98 % over OVs-Ni(OH)2 was achieved, outperforming most analogous reported catalysts. Moreover, even under a low CO2 concentration of 0.04 % (representative of the CO2 concentration in air) and low reaction temperature (273 K, 0 °C), this catalyst can still trigger CO2 reduction. This work provides a new method to synthesize OVs-Ni(OH)2 catalysts for efficient CO2 reduction and establishes a relationship between the OVs and the catalytic activity, which may guide the design of highly selective CO2 reduction catalysts.

Noise-Transfer2Clean: denoising cryo-EM images based on noise modeling and transfer.

MOTIVATION: Cryo-electron microscopy (cryo-EM) is a widely used technology for ultrastructure determination, which constructs the 3D structures of protein and macromolecular complex from a set of 2D micrographs. However, limited by the electron beam dose, the micrographs in cryo-EM generally suffer from the extremely low signal-to-noise ratio (SNR), which hampers the efficiency and effectiveness of downstream analysis. Especially, the noise in cryo-EM is not simple additive or multiplicative noise whose statistical characteristics are quite different from the ones in natural image, extremely shackling the performance of conventional denoising methods. RESULTS: Here, we introduce the Noise-Transfer2Clean (NT2C), a denoising deep neural network (DNN) for cryo-EM to enhance image contrast and restore specimen signal, whose main idea is to improve the denoising performance by correctly learning the noise distribution of cryo-EM images and transferring the statistical nature of noise into the denoiser. Especially, to cope with the complex noise model in cryo-EM, we design a contrast-guided noise and signal re-weighted algorithm to achieve clean-noisy data synthesis and data augmentation, making our method authentically achieve signal restoration based on noise's true properties. Our work verifies the feasibility of denoising based on mining the complex cryo-EM noise patterns directly from the noise patches. Comprehensive experimental results on simulated datasets and real datasets show that NT2C achieved a notable improvement in image denoising, especially in background noise removal, compared with the commonly used methods. Moreover, a case study on the real dataset demonstrates that NT2C can greatly alleviate the obstacles caused by the SNR to particle picking and simplify the identifying of particles. AVAILABILITYAND IMPLEMENTATION: The code is available at https://github.com/Lihongjia-ict/NoiseTransfer2Clean/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

YAP derived circ-LECRC functions as a "brake signal" to suppress hyperactivation of oncogenic YAP signalling in colorectal cancer.

Accumulating evidence indicates that circular RNAs (circRNAs) play vital roles in tumorigenesis by modulating gene expression. However, the molecular mechanisms underlying the functions of circRNAs remain largely unknown. Here, we demonstrated that a Yes1 associated transcriptional regulator (YAP1)-derived circRNA, circ-LECRC (circRNA low expressed in CRC), was significantly downregulated in colorectal cancer (CRC). High expression of circ-LECRC positively correlated with a lower TNM stage and good prognosis in CRC patients. Circ-LECRC overexpression significantly inhibited CRC cell proliferation, migration, and invasion and promoted apoptosis (P < 0.05). Additionally, we performed xenograft and lung metastasis experiments by injecting CRC cells into nude mice to mechanistically demonstrate that circ-LECRC directly binds to miR-135b-5p and relieve the suppression of its target, Krüppel-like factor 4 (KLF4). Furthermore, we found that both circ-LECRC and KLF4 inhibited YAP1 hyperactivation, which downregulates the expression of the downstream genes of the YAP1 pathway, such as EGFR, MYC, BIRC5, and CTGF. In summary, circ-LECRC regulates KLF4 expression by functioning as a competing endogenous RNA and serves as a "brake signal" to suppress hyperactivation of oncogenic YAP signalling, leading to tumour growth inhibition in CRC.

Effect of High Rotational-Speed Friction-Stir Welding on Microstructure and Properties of Welded Joints of 6061-T6 Al Alloy Ultrathin Plate.

The butt joint of an Al alloy ultrathin plate with a thickness of 0.5 mm is realized by a high rotational-speed friction-stir welding process. It overcomes the welding difficulty that the ultrathin plate is often torn, and it cannot be formed by conventional friction-stir welding. The results show that the weld surface is well-formed at a high-rotational speed (more than 8000 rpm), and there are no obvious defects in each area of the joint section. The nugget zone (NZ) is a recovery recrystallization structure dominated by large-angle grain boundaries, with a grain size of about 4.9 µm. During grain growth, the texture is randomly and uniformly distributed, and the strength is balanced. The microhardness of the NZ increases significantly with the increase in rotational speed, and the fluctuation range of hardness value is small. The NZ ß-Mg2Si is finer and significantly less than the base metal (BM). The heat dissipation of the thin plate is fast, so a Cu plate is used as the backing plate to slow down the steep temperature-drop process in the weld area. Compared with a low rotational speed, the precipitation amount of brittle phase Al-Cu-Mg-Cr and Al-Fe-Si-Mn is significantly reduced, which is conducive to improving the mechanical properties of the joint. At a high rotational speed, 12,000 rpm, the best tensile strength of the joint is 220 MPa, which is about 76% of the BM (290 MPa), and the highest elongation is 9.3%, which is about 77.5% of the BM (12%). The fracture mode of the joint is a typical plastic fracture.

Influence of bone cement distribution on outcomes following percutaneous vertebroplasty: a retrospective matched-cohort study.

OBJECTIVE: To evaluate the influence of insufficient bone cement distribution on outcomes following percutaneous vertebroplasty (PVP). METHODS: This retrospective matched-cohort study included patients 50-90 years of age who had undergone PVP for single level vertebral compression fractures (VCFs) from February 2015 to December 2018. Insufficient (Group A)/sufficient (Group B) distribution of bone cement in the fracture area was assessed from pre- and post-operative computed tomography (CT) images. Assessments were before, 3-days post-procedure, and at the last follow-up visit (≥12 months). RESULT: Of the 270 eligible patients, there were 54 matched pairs. On post-operative day 3 and at the last follow-up visit, significantly greater visual analogue scale (VAS) pain scores and Oswestry Disability Index (ODI) scores were obtained in Group B over Group A, while kyphotic angles (KAs) and vertebral height (VH) loss were significantly larger in Group A compared with Group B. Incidence of asymptomatic cement leakage and re-collapse of cemented vertebrae were also greater in Group A compared with Group B. CONCLUSIONS: Insufficient cement distribution may relate to less pain relief and result in progressive vertebral collapse and kyphotic deformity post-PVP.

S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic and slowly progressing cholestatic disease, which causes damage to the small intrahepatic bile duct by immuno-regulation, and may lead to cholestasis, liver fibrosis, cirrhosis and, eventually, liver failure. AIM: To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6 (S100A6) messenger ribonucleic acid (mRNA), LINC00312, LINC00472, and LINC01257 in primary biliary cholangitis. METHODS: A total of 145 PBC patients and 110 healthy controls (HCs) were enrolled. Among them, 80 PBC patients and 60 HCs were used as the training set, and 65 PBC patients and 50 HCs were used as the validation set. The relative expression levels of plasma S100A6 mRNA, long noncoding ribonucleic acids LINC00312, LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction. The bile duct ligation (BDL) mouse model was used to simulate PBC. Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice. Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC. RESULTS: The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice. The relative expression levels of plasma S100A6 mRNA, log10 LINC00472 and LINC01257 were up-regulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs (3.01 ± 1.04 vs 2.09 ± 0.87, P < 0.0001; 2.46 ± 1.03 vs 1.77 ± 0.84, P < 0.0001; 3.49 ± 1.64 vs 2.37 ± 0.96, P < 0.0001; 1.70 ± 0.33 vs 2.07 ± 0.53, P < 0.0001, respectively). The relative expression levels of S100A6 mRNA, LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control (2.97 ± 0.43 vs 1.09 ± 0.08, P = 0.0018; 2.70 ± 0.26 vs 1.10 ± 0.10, P = 0.0006; 2.23 ± 0.21 vs 1.10 ± 0.10, P = 0.0011; 1.20 ± 0.04 vs 3.03 ± 0.15, P < 0.0001, respectively). The mean expression of S100A6 in the advanced stage (III and IV) of PBC was up-regulated compared to that in HCs and the early stage (II) (3.38 ± 0.71 vs 2.09 ± 0.87, P < 0.0001; 3.38 ± 0.71 vs 2.57 ± 1.21, P = 0.0003, respectively); and in the early stage (II), it was higher than that in HCs (2.57 ± 1.21 vs 2.09 ± 0.87, P = 0.03). The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs (1.39 ± 0.29 vs 1.56 ± 0.33, P = 0.01; 1.39 ± 0.29 vs 2.07 ± 0.53, P < 0.0001, respectively); in addition, the mean expression of LINC00312 in the early stage was lower than that in HCs (1.56 ± 0.33 vs 2.07 ± 0.53, P < 0.0001). The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs (2.99 ± 0.87 vs 1.81 ± 0.83, P < 0.0001; 2.99 ± 0.87 vs 1.77 ± 0.84, P < 0.0001, respectively). The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs (3.88 ± 1.55 vs 2.37 ± 0.96, P < 0.0001; 3.57 ± 1.79 vs 2.37 ± 0.96, P < 0.0001, respectively). The areas under the curves (AUC) for S100A6, LINC00312, log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759, 0.7292, 0.6942 and 0.7158, respectively. Furthermore, the AUC for these four genes in PBC staging were 0.666, 0.661, 0.839 and 0.5549, respectively. The expression levels of S100A6 mRNA, log10 LINC00472, and LINC01257 in plasma of PBC patients were decreased (2.35 ± 1.02 vs 3.06 ± 1.04, P = 0.0018; 1.99 ± 0.83 vs 2.33 ± 0.96, P = 0.036; 2.84 ± 0.92 vs 3.69 ± 1.54, P = 0.0006), and the expression level of LINC00312 was increased (1.95 ± 0.35 vs 1.73 ± 0.32, P = 0.0007) after treatment compared with before treatment using the paired t-test. Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472 (r = 0.683, P < 0.0001); serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472 (r = 0.482, P < 0.0001); relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV (r = 0.732, P < 0.0001). The AUC for the four biomarkers obtained in the validation set were close to the training set. CONCLUSION: These four genes may potentially act as novel biomarkers for the diagnosis of PBC. Moreover, LINC00472 acts as a potential biomarker for staging in PBC.

Jingshu Keli for treating cervical spondylotic radiculopathy: The first multicenter, randomized, controlled clinical trial.

BACKGROUND: Jingshu Keli (or Jingshu granules), a traditional Chinese medicine, are widely used for treating cervical spondylotic radiculopathy in China; however, no randomized, double-blind, controlled study has verified their effectiveness. PURPOSE: To evaluate the efficacy and safety of Jingshu Keli for the treatment of cervical spondylotic radiculopathy in a randomized controlled trial. DESIGN: From August 2015 to July 2017, a multicenter, randomized, double-blind, placebo-controlled trial was conducted at 13 large- and medium-sized hospitals in China. PATIENT SAMPLE: A total of 360 and 120 patients were initially enrolled in the Jingshu and control groups, respectively; 386 patients completed the study, with 299 in the Jingshu group and 87 in the control group. OUTCOME MEASURES: The main index for evaluating the curative effect was the pain score on a visual analogue scale (VAS; 0-100 points). METHODS: All patients were administered a bag of Jingshu Keli or placebo 3 times a day for 4 weeks, and were interviewed at the second and fourth weeks. The decrease in pain scores and rate of change in pain scores after treatment were calculated, related laboratory indices were reviewed, and adverse reactions were recorded. RESULTS: In the Per Protocol Set (PPS) analysis, the baseline pain VAS scores in the control and Jingshu groups were 49.31 â€‹± â€‹6.97 and 50.06 â€‹± â€‹7.33, respectively, with no significant difference between the groups (P â€‹> â€‹0.05). While there were no differences at 2 weeks between groups, at four weeks the pain VAS scores in the control and Jingshu groups decreased by 12.86 â€‹± â€‹13.45 and 22.72 â€‹± â€‹15.08, respectively relative to the values at baseline, with significant group differences (P â€‹< â€‹0.0001). While there were similar significant differences between the groups (P â€‹< â€‹0.0001) in the Full Analysis Set (FAS) analyses neither group achieved the minimal clinically important difference at any time point. CONCLUSIONS: Jingshu Keli are effective for the treatment of cervical spondylotic radiculopathy. TRANSLATIONAL POTENTIAL STATEMENT: This is the first prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial that confirmed the clinical efficacy and safety of Jingshu Keli for treating cervical spondylotic radiculopathy, which can provide evidence for clinical treatment.

Efficacy of transanal drainage tube and self-expanding metallic stent in acute left malignant colorectal obstruction.

BACKGROUND: The self-expanding metal stent (SEMS) or transanal drainage tube (TDT) methods can be used as a palliative treatment before tumor resection surgery. Studies systematically comparing the efficacy and characteristics between SEMS with TDT are limited, especially in a large-scale Chinese population. This retrospective study aimed to compare the outcomes of these treatment approaches. METHODS: This was a retrospective comparative study of patients with an acute malignant left colorectal obstruction who underwent a preoperative decompressive procedure with SEMS or TDT intervention between December 2014 and October 2017. The indicators after endoscopic treatment and tumor resection surgery between the SEMS and TDT groups were compared. RESULTS: 206 patients underwent endoscopic intervention to relieve obstruction, including 139 patients treated with SEMS and 67 patients treated with TDT. The technical success rates of the SEMS group and TDT group were 97.1% and 95.6%, respectively, and the rates of obstruction relief were 92.8% and 86.6%, respectively. TDT was more easily translocated than SEMS (P=0.02), and there was no significant difference in the incidence of other complications. However, SEMS had a lower complication rate than TDT (P=0.02), and could alleviate the obstruction faster (P<0.01). There were 72 patients and 44 patients who took resection surgery in the SEMS group and TDT group, respectively. The direct anastomosis rates were 73.6% and 63.6% (P=0.26), respectively, and only 1 case in the TDT group had anastomotic leakage. The surgery time of the SEMS group was significantly shorter than that of the TDT group (P=0.01). There was no significant difference between the 2 groups in terms of postoperative hospital stay (P=1.00) or total treatment costs for patients undergoing surgery (P=0.26). CONCLUSIONS: Both TDT and SEMS could effectively relieve acute left malignant colorectal obstruction with safe and reliable results, and they could both reduce the stomas rate compared with traditional surgery. SEMS could alleviate obstruction faster than TDT and had fewer complications.

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs efficacy. The purpose of our current meta-analysis was to clearly evaluated the relationship between BMI and ICIs efficacy for cancer patients receiving immunotherapy. METHODS: A systematic search of Pubmed, EMBASE and conference proceedings was performed to investigate the influence of BMI on ICIs efficacy. Pooled analysis for overall survival (OS), progression-free survival (PFS) and immune-related adverse effects (IRAEs) were analyzed in current study. RESULTS: A total of 13 eligible studies comprising 5279 cancer patients treated with ICIs were included in the analysis. The pooled analysis showed there is positive association between high BMI and improved OS and PFS among patients with ICIs treatment (OS: HR = 0.62, 95% CI 0.55-0.71, P < 0.0001; I2 = 26.3%, P = 0.202); PFS: HR = 0.71, 95% CI 0.61-0.83, P < 0.0001; I2 = 0%, P = 0.591). There is no significant difference between the incidence of all grade IRAEs between obese, overweight patients and normal patients (Overweight vs Normal: pooled RR = 1.28, 95% CI 0.76- 2.18, P = 0.356; Obese vs Normal: pooled RR = 1.36, 95% CI 0.85- 2.17, P = 0.207). CONCLUSION: An improved OS and PFS were observed in patients with high BMI after receiving ICIs treatment compared with patients of low BMI. No significant association between BMI and incidence of IRAEs was found in cancer patients after ICIs treatment.

miR-128 plays a critical role in murine osteoclastogenesis and estrogen deficiency-induced bone loss.

Postmenopausal osteoporosis (PMOP) is a severe health issue faced by postmenopausal women. microRNA-128 (miR-128) is associated with aging, inflammatory signaling, and inflammatory diseases, such as PMOP. It has also been reported to modulate in vitro osteogenic/adipogenic differentiation. However, its function in osteoclast formation is unknown. Methods: First, the expression of miR-128 and nuclear factor of activated T cells 1 (Nfatc1, bone resorption master marker) was investigated in bone tissues derived from PMOP patients, while their correlation to each other was also investigated. The levels of miR-128 and Nfatc1 in bone specimens and bone marrow-derived macrophages (BMMs) from mice subjected to ovariectomy (OVX) were also assayed. Next, we employed mice BMMs modified for overexpression and inhibition of miR-128 levels to determine its effect on osteoclast differentiation. Moreover, we generated osteoclastic miR-128 conditional knockout (miR-128Oc-/- ) mice and isolated miR-128 deletion-BMMs to observe its biological function on bone phenotype and osteoclastogenesis in vivo, respectively. The miR-128Oc-/- BMMs were used to explore the downstream regulatory mechanisms using pull-down, luciferase reporter, and western-blotting assays. Finally, the impact of miR-128 deficiency on OVX-induced bone loss in mice was evaluated. Results: The miR-128 level was found to be positively correlated with the increase in Nfatc1 level in mouse/human bone specimens and mouse primary BMMs. In vitro experiments demonstrated miR-128 levels that were dependent on activity of osteoclast differentiation and miR-128 overexpression or inhibition in BMMs significantly increased or decreased osteoclastogenesis, respectively. In vivo, we revealed that osteoclastic miR-128 deletion remarkedly increased bone mass through the inhibition of osteoclastogenesis. Mechanistically, we identified sirtuin 1 (SIRT1) as the direct target of miR-128 at the post-transcriptional level during osteoclast differentiation. Increased levels of SIRT1 reduced nuclear factor κB (NF-κB) activity by decreasing the level of acetylation of Lysine 310, as well as inhibiting tumor necrosis factor-α (Tnf-α) and interleukin 1 (IL-1) expressions. Lastly, osteoclastic deletion of miR-128 significantly suppressed OVX-triggered osteoclastogenesis and exerted a protective effect against bone loss in mice. Conclusions: Our findings reveal a critical mechanism for osteoclastogenesis that is mediated by the miR-128/SIRT1/NF-κB signaling axis, highlighting a possible avenue for the further exploration of diagnostic and therapeutic target molecules in PMOP.

Exploring prognostic potential of long noncoding RNAs in colorectal cancer based on a competing endogenous RNA network.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent tumors worldwide. Recently, long noncoding RNAs (lncRNAs) have been shown to influence tumorigenesis and tumor progression by acting as competing endogenous RNAs (ceRNAs). It is difficult to extract prognostic lncRNAs and useful bioinformation from most ceRNA networks constructed previously. AIM: To construct a prognostic related ceRNA regulatory network and lncRNA related signature based on risk score in CRC. METHODS: RNA transcriptome profile and clinical information of 506 CRC patients were downloaded from the Cancer Genome Atlas database. R packages and Perl program were used for data processing. Cox regression analysis was used for prognostic model construction. Quantitative real-time polymerase chain reaction was used to detect the expression of lncRNAs. RESULTS: A prognostic-related ceRNA network was constructed, including 9 lncRNAs, 44 mRNAs, and 30 miRNAs. In addition, a four-lncRNA model was constructed using multivariate Cox regression analysis, which could be an independent prognostic model in CRC. The risk score for each patient was calculated, and the 506 patients were divided into high and low-risk groups (253 for each group) based on the median risk score. The results of the survival analysis showed that patients with a high-risk score had a poor survival rate. Furthermore, the predictive value of the four-lncRNA model was evaluated in GSE38832. Patient survival probabilities could be better predicted when combing the risk score and clinical features. Gene Set Enrichment Analysis results verified that a number of cancer-related signaling pathways were enriched with a high-risk score in CRC. Finally, we validated a novel lncRNA (LINC00488) using quantitative real-time polymerase chain reaction in 22 paired CRC patient tumor tissues compared to adjacent non-tumor tissues. CONCLUSION: The four-lncRNA model could give better predictive value for CRC patients. Our understanding of the lncRNA-related ceRNA regulatory mechanism could provide a potential diagnostic indicator for CRC patients.