Lipopolysaccharide promotes cancer cell migration and invasion through METTL3/PI3K/AKT signaling in human cholangiocarcinoma.

Purpose: As a major structural component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) has been detected in the blood circulation and tissues in patients with chronic diseases and cancers, which plays a critical role in the tumor formation and progression. However, the biological role of LPS in human intrahepatic cholangiocarcinoma remains unclear. The aims of this study were to investigate the role of LPS in the malignant progression of intrahepatic cholangiocarcinoma. Methods: The cell migration and invasion capacities of cholangiocarcinoma cell lines were evaluated by Boyden chamber assays. Expression levels of the key molecules involved in the PI3K/AKT signaling and METTL3 were detected by qPCR and western blot. The molecular mechanism by which LPS promotes the malignant behaviors was investigated by using siRNAs, plasmids and small molecule inhibitors. Results: In vitro experiments showed that exogenous LPS treatment promoted cell migration and invasion capacities in both QBC939 and HUCCT1 cell lines, while did not affect cell proliferation and apoptosis. Mechanistically, exogenous LPS treatment had been proved to induce the increased expression of METTL3 and activate the downstream PI3K/AKTsignaling pathway. In addition, suppression of METTL3 expression reduced cell proliferation, migration and invasion capacities in both cell lines. Furthermore, inhibition of METTL3 expression or inhibition of PI3K/AKT signaling decreased LPS-induced cell migration and invasion capacities. Moreover, knockdown of METTL3 or inhibition of METTL3 significantly inhibited LPS-induced activation of the PI3K/AKT signaling. Conclusion: In general, these results suggest that the LPS-METTL3-PI3K/AKT signal axis promotes cell migration and invasion in ICC, which contributes to a reduced overall survival in patients with ICC. It may broaden the horizon of cancer therapy with potential therapeutic targets.

Heart failure classification using deep learning to extract spatiotemporal features from ECG.

BACKGROUND: Heart failure is a syndrome with complex clinical manifestations. Due to increasing population aging, heart failure has become a major medical problem worldwide. In this study, we used the MIMIC-III public database to extract the temporal and spatial characteristics of electrocardiogram (ECG) signals from patients with heart failure. METHODS: We developed a NYHA functional classification model for heart failure based on a deep learning method. We introduced an integrating attention mechanism based on the CNN-LSTM-SE model, segmenting the ECG signal into 2 to 20 s long segments. Ablation experiments showed that the 12 s ECG signal segments could be used with the proposed deep learning model for superior classification of heart failure. RESULTS: The accuracy, positive predictive value, sensitivity, and specificity of the NYHA functional classification method were 99.09, 98.9855, 99.033, and 99.649%, respectively. CONCLUSIONS: The comprehensive performance of this model exceeds similar methods and can be used to assist in clinical medical diagnoses.

[Comparative analysis of clinical efficacy between posterior percutaneous endoscopic discectomy and anterior cervical discectomy and fusion in the treatment of cervical spondylotic radiculopathy].

OBJECTIVE: To explore the clinical efficacy of posterior percutaneous endoscopic discectomy(PPECD) in the treatment of cervical spondylotic radiculopathy. METHODS: A total of 56 patiens with single segment cervical spondylotic radiculopathy from December 2017 to October 2020, were randomly divided into observation group and control group. In observation group, there were 16 males and 11 females, including 8 cases of C4,5, 13 cases of C5,6 and 6 cases of C6,7 performed posterior percutaneous endoscopic discectomy, aged from 34 to 61 years old with an average of (51.15±6.29) years old. In control group, there were 19 males and 10 females with single segment cervical spondylotic radiculopathy including 10 cases of C4,5, 14 cases of C5,6 and 5 cases of C6,7 performed anterior cervical discectomy and fusion, aged from 40 to 65 years old with an average of (53.24±5.31) years old. The operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were recorded. Visual analogue scale(VAS) and neck disability index(NDI) were used to evaluate the clinical efficacy. Cervical plain films or MRIs, CTs were taken for re-visiting patients. RESULTS: All patients were followed up more than 2 years. The observation group patients were followed up, the duration ranged from 24 to 42 months with an average of (30.48±4.91) months. The control group patients were followed up, the duration ranged from 25 to 47 months, with an average of (32.76±4.53) months. Compared with control group, operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were decreased(P<0.05). Compared with pre-operation, VAS of neck and upper limb and NDI at the latest follow-up between two groups were significantly improved(P<0.05). Compared with control group, VAS of neck and upper limb at 1 day after operation in observation group were significantly reduced(P<0.05). There was no significant difference in VAS of neck and upper limb and NID at 1, 3 months and the latest follow-up after operation between two groups(P>0.05). In the observation group, one patient's deltoid muscle strength was weakened to grade 4 after operation, and returned to normal after 12 weeks of conservative treatment. In control group, there was 1 case of postoperative adjacent spondylosis with symptoms of spinal compression after 2 years operation, then underwent cervical artificial intervertebral disc replacement. And there was 1 case of dysphagia after operation in control group and improved after 1 year. There was no significant difference in incidence of complications between two groups. CONCLUSION: PPECD has advantages of shortening operative time, decreasing intraoperative blood loss, reducing postoperative time of lying in bed and length of postoperative hospital stay. However, applicable age range of patients and long-term clinical efficacy needs further study.

A Comparison of Co-expression Networks in Silk Gland Reveals the Causes of Silk Yield Increase During Silkworm Domestication.

Long-term domestication and selective breeding have increased the silk yield of the domestic silkworm (Bombyx mori) by several times the amount of the silk yield of its wild ancestor (Bombyx mandarina). However, little is known about the molecular mechanisms behind the increase in silk yield during domestication. Based on dynamic patterns of functional divergence in the silk gland between domestic and wild silkworms, we found that at early and intermediate stages of silk gland development, the up-regulated genes of the domestic silkworm were mainly involved in DNA integration, nucleic acid binding, and transporter activity, which are related to the division and growth of cells. This has led to the posterior silk gland (PSG) of the domestic silkworm having significantly more cells ("factories" of fibroin protein synthesis) than that of the wild silkworm. At the late stage of silk gland development, the up-regulated genes in the domestic silkworm was enriched in protein processing and ribosome pathways, suggesting protein synthesis efficiency is greatly improved during silkworm domestication. While there was an increase in fibroin protein synthesis, the production of sericin protein was simultaneously reduced in the silk gland of the domestic silkworm. This reflects that domestic and wild silkworms have been under different selection pressures. Importantly, we found that the network co-expressed with the silk-coding genes of the domestic silkworm was larger than that of the wild silkworm. Furthermore, many more genes co-expressed with silk-coding genes in the domestic silkworm were subjected to artificial selection than those in the wild silkworm. Our results revealed that the increase of silk yield during silkworm domestication is involved in improvement of a biological system which includes not only expansion of "factories" (cells of PSG) of protein synthesis, but also a high expression of silk-coding genes and silk production-related genes such as biological energy, transport, and ribosome pathway genes.

An adaptive enhancement method for breast X-ray images based on the nonsubsampled contourlet transform domain and whale optimization algorithm.

We propose a new method for breast X-ray image adaptive enhancement that combines nonsubsampled contourlet transform (NSCT) with the whale optimization algorithm (WOA). First, the mammography X-ray image was processed by histogram equalization to ensure global image contrast. The processed image was then decomposed into three layers in the NSCT domain. Each layer was each decomposed into two, four, and eight directions. A median filter was used to remove noise in the first and second layers. Then, a special edge filter was adopted to enhance each sub-band image, and two parameters are involved. WOA is used to automatically search the optimal two parameters. Blind image quality index (BIQI) adaptive function was used as an objective function of WOA. Then, inverse NSCT was employed to reconstruct the processed image, generating the final adaptive enhancement image. The digital database for screening mammography (DDSM) was used to verify the performance of the proposed method. Five objective evaluation indexes, including information entropy, average gradient, standard deviation, contrast improvement index (CII), and BIQI, are combined together to construct a new comprehensive index to evaluate the visual quality of the enhanced image. The results show that the proposed method has a good enhancement effect for mammography X-ray images. The overall performance of the proposed method is better than some existing similar methods. Graphical abstract .

MRI denoising by NeighShrink based on chi-square unbiased risk estimation.

NeighShrink is an efficient image denoising algorithm for the reduction of additive white Gaussian noise. However, it does not perform well in terms of Rician noise removal for MRI (Magnetic Resonance Imaging). Allowing for the characteristics of squared-magnitude MR (Magnetic Resonance) images, which follow a non-central chi-square distribution, the CURE (Chi-Square Unbiased Risk Estimation) is used to determine an optimal threshold for NeighShrink. Therefore, we propose the NeighShrinkCURE denoising algorithm. Bilateral filtering and cycle spinning are used to further improve denoising performance. Experimental results show that the proposed algorithm is simple and efficient, and provides good noise reduction while preserving edges and details well. Compared with some similar MRI denoising algorithms, the proposed algorithm has improvements in PSNR (Peak Signal-to-Noise Ratio) and SSIM (Structural Similarity). Although running time of the proposed algorithm has some increment compared with some current MRI denoising algorithms, the comprehensive performance of the proposed algorithm is superior to several current MRI denoising algorithms.

[Comparison of early clinical effects between Activ C cervical disc replacement and anterior cervical discectomy and fusion for single-level cervical spondylosis].

OBJECTIVE: To compare the early clinical effects of Activ C cervical disc replacement (ACDR) and anterior cervical discectomy and fusion (ACDF) in treating single-level cervical spondylosis. METHODS: The clinical data of 76 patients with single-level cervical spondylosis underwent surgery from July 2009 to September 2012 were retrospectively analyzed. Among them, 28 patients were treated with ACDR (ACDR group), including 18 males and 10 females, aged from 32 to 62 years old with an average of (45.2±6.2) years; and 48 patients were treated with ACDF (ACDF group), including 28 males and 20 females, aged from 33 to 60 years old with an average of (45.8±6.4) years. Visual analogue scale (VAS), Japanese Orthopedics Association (JOA) score, Short Form-36 (SF-36), imaging data were used to assess the clinical effects after operation. RESULTS: A total of 76 patients were followed up from 6 to 24 months with an average of 13.2 months. VAS of neck pain and brachialgia were improved in all patients after operation (P<0.05), there was no significant difference between two group (P>0.05). Somato-score and psycho-score of SF-36 of two groups were obviously increased (P<0.05), ACDR group was better than that of ACDF group (P<0.05). In ACDR group, there was no significant difference in the range of motion of surgical segments and adjacent segments between preoperative and postoperative (P>0.05); heterotopic ossification around the edge of vertebral body occurred in 1 case on the 6th month after operation, no fusion was found on the 1st year after operation. In ACDF group, the adjacent vertebral disease occurred in 1 case and the patient underwent the reoperation. CONCLUSION: Activ C cervical disc replacement can reduce the degeneration of adjacent segments and its early outcomes for the treatment of single-level cervical spondylosis are satisfactory, but the long-term effects still need study.

[Long-term assessment of relapse and associated risk factors in chronic hepatitis C patients treated with interferon and ribavirin].

OBJECTIVE: To investigate viral relapse and the associated risk factors during a long-term follow-up study of chronic hepatitis C (CHC) patients who achieved end-of-treatment response (ETR) after interferon and ribavirin therapy. METHODS: This retrospective study was conducted on 146 CHC patients treated with a combination of ribavirin and pegylated (PEG) interferon-alpha (IFNa) (n=126) or conventional IFNa (n=20) for 24 (hepatitis C virus (HCV) non-genotype 1b) or 48 (HCV genotype 1b) weeks. The main outcome measure was serum HCV RNA load. The risk factors analyzed included age, sex, HCV genotype, baseline HCV RNA load, and IFN type. RESULTS: The mean follow-up time for all patients was 33.45+/-16.41 months (range: 12-85 months). The cumulative relapse rate during follow-up was 14.80%. The relapse rate within six months (8.90%) was significantly higher than other periods during two years of follow-up, and no relapse occurred after 30 months. Of all relapsers (n=20), 65% occurred within six months, followed by 35% within 7-24 months after antiviral therapy. The relapse rates in patients with HCV genotype 1b and non-1b were not significantly different (20.37% vs. 12.12%, X2 =1.517, P=0.315). The mean baseline HCV RNA load was significantly higher in the relapsers than that in the non-relapsers (t=0.915, P=0.362). Relapse rates were similar in patients treated with PEG-IFNa-2b, PEG-IFNa-2a and IFNa (12.12% vs. 13.97% vs. 15.00%, respectively; X2=0.104, p=0.949). The mean age of relapsers was significantly higher than that of non-relapsers (P less than 0.005). CONCLUSION: The maximum probability of relapse for CHC patients exists within six months from when ETR is achieved by interferon and ribavirin therapy. A lower risk for relapse persists past this period. Thus, ETR CHC patients, especially older patients, should be carefully monitored during the two years after cessation of antiviral therapy. Standard antiviral therapy based on HCV genotype eliminates the influence of viral factors on treatment-response.

[Positive selection analysis of hepatitis C virus genotype 1b envelope 2 gene and its significance during natural chronic infection].

AIM: To elucidate adaptive evolution patterns and perform a positive selection analysis of hepatitis C virus(HCV) genotype 1b envelope 2 gene(E2) during natural chronic infection by a longitudinal study. METHODS: HCV E2 quasispecies profiles were derived from partially sequenced domains of 6 000 bp recombinant clones. Phylogenetic trees for HCV E2 gene were constructed by MEGA software and the specific codons undergoing diversifying positive selection were identified by FEL method. RESULTS: HCV phylogenies, coupled with the number and distribution of selected sites were differed markedly between patients. HCV quasispecies complexity during chronic infection was not associated with the evolutionary time and the dominant viriant alternation of HCV quasispecies may occur after more than six months apart. Five sites under positive selection were identified within the ectodomain of the E2 protein. CONCLUSION: A series of serum specimens for studies based on dominant viriant of HCV dynamic quasispecies is recommended to be collected at every six months. Several individual sites of HCV E2 gene are under a strong host immune pressure, position aa384, aa399 and aa410 may be involved in escape from neutralizing antibodies, while position aa475, aa522 may correlate to modulate the virus-receptor interaction which result in evading immunity.

[Identification of Papaver somni ferum L. and Papaver rhoeas using DSWT-FTIR-RBFNN].

Infrared spectra of Papaver somniferum L. and Papaver rhoeas were obtained directly, quickly and accurately by Fourier transform infrared spectroscopy (FTIR)with OMNI sampler. Discrete stationary wavelet transform was used to extrude local region of infrared spectra of Papaver somniferum L. and Papaver rhoeas. The difference of infrared spectra between Papaver somniferum L. and Papaver rhoeas was extruded. Accurate identification rate is improved greatly. One dimensional discrete stationary wavelet transform was implemented to the infrared spectra of Papaver somniferum L. and Papaver rhoeas. The difference between Papaver somniferum L. and Papaver rhoeas was observed at all scales in wavelet domain. Two scales, at which the difference between Papaver somniferum L and Papaver rhoeas is the most obvious, were selected to extract the features of Papaver somniferum L. and Papaver rhoeas. A feature vector including eight feature parameters was constructed. The feature vector was input to RBFNN for training in order to accurately identify Papaver somniferum L. and Papaver rhoeas. In experiment, the authors used one hundred and twenty-eight couples of data of Papaver somniferum L. and Papaver rhoeas (including seventy-eight couples of training samples and fifty couples of testing samples). The experimental results show that it is effective to apply discrete stationary wavelet transform on the basis of FTIR to identify the Papaver somniferum L. and Papaver rhoeas. The accurate identification rate of Papaver somniferum L and Papaver rhoeas is 99.8% and 99.9% respectively.

[Identification of semen celosiae and semen celosiae cristatae using continuous wavelet transform with FTIR].

Infrared spectra of semen celosiae and semen celosiae cristatae were obtained directly, quickly and accurately by Fourier transform infrared spectroscopy (FTIR) with OMNI sampler. Continuous wavelet transform was used to extrude local region of infrared spectra of semen celosiae and its confusable varieties. The difference of infrared spectra between semen celosiae and semen celosiae cristatae was extruded greatly. Accurate identification rate was improved greatly. Morlet wavelet, which can detect singular values of signal effectively, was selected as the mother wavelet. One-dimensional continuous wavelet transform was implemented for the infrared spectra of semen celosiae and its confusable varieties. The difference between semen celosiae and semen celosiae cristatae was observed at all scales in the wavelet domain. An optimal scale, at which the difference between semen celosiae and semen celosiae cristatae was the most obvious, was selected to identify semen celosiae and semen celosiae cristatae. The results show that it is effective to apply continuous wavelet transform on the basis of FTIR to identify the traditional Chinese medicinal materials, which are the same genus but different species.

[Application of wavelet transform to infrared analysis].

In the present article the FTIR spectra of the xylems of Smilax glabra Roxb. and its three kinds of counterfeits were obtained by Fourier transform infrared spectroscopy (FTIR) with OMNI-sampler directly, fast and accurately. By adopting wavelet transform analytical method the samples were studied in detail. The results showed that wavelet transform could remove the noises and condense variable, and have the advantages of fast operating speed, high degree of accuracy, and no noise disposal. It will have a good application prospect in infrared spectroscopic analysis.