Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[Recommendations for the diagnosis and treatment of connective tissue disease-associated interstitial lung disease in China].

Interstitial lung disease (ILD) is a frequent complication of patients with connective tissue disease (CTD) and significantly affects morbidity and mortality. Disease course may vary from stable or mildly progressive to more severe, with rapid loss of lung function. At present, there are great challenges and poor prognosis in the diagnosis and treatment of CTD-ILD. Based on the evidence and guidelines from China and other countries, experts from the Chinese Rheumatology Association developed standardization of diagnosis and treatment of CTD-ILD. The aim is to strengthen the early identification of, standardize the diagnosis and treatment of CTD-ILD, and delay the progress of the disease.

CircABCB10 silencing inhibits the cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis in rectal cancer.

Circular ATP binding cassette subfamily B member 10 (circABCB10) has been identified to have oncological functions in several tumors. However, the roles of circABCB10 in rectal cancer remain unknown. The expression of circABCB10, microRNA (miR)-326 and C-C motif chemokine ligand 5 (CCL5), and apoptosis related-protein was detected using quantitative real-time polymerase chain reaction or western blot, respectively. Cell survival or apoptosis was measured using cell counting kit-8 assay or flow cytometry. The accumulations of intracellular lipid reactive oxygen species (ROS) and Fe2+ were analyzed using C11-BODIP dye or iron kit assay, respectively. In vivo experiments were conducted using the murine xenograft model. The interaction between miR-326 and circABCB10 or CCL5 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircABCB10 and CCL5 were upregulated but miR-326 was downregulated in rectal cancer. The knockdown of circABCB10 promoted rectal cancer cell ferroptosis and apoptosis in vitro as well as inhibited tumor growth in vivo. miR-326 was a target of circABCB10, and the miR-326 inhibition could partially attenuate circABCB10 deletion-induced cell ferroptosis and apoptosis. miR-326 directly interacted with CCL5, and the miR-326 inhibition suppressed cell ferroptosis and apoptosis by targeting CCL5. Besides, we observed that miR-326 was negatively regulated by circABCB10, while CCL5 was positively regulated by it, and circABCB10 served as a sponge of miR-326 to regulate the CCL5 expression in rectal cancer cells. CircABCB10 silence promoted rectal cancer cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis, suggesting a potential therapeutic target for rectal cancer therapy.

[Progress and challenge of vaccine development against 2019-novel coronavirus (2019-nCoV)].

The outbreak of 2019-novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same ß-genus of coronavirus family. Basing on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines covers all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many unknown challenges, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.

[Regulation of m

N^(6)-methyladenosine (m^(6)A) has been identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, and plays important biological roles in the regulation of cellular metabolic processes. However, its role in myogenic differentiation is unclear. Here, we altered the m^(6)A RNA methylation level by overexpression of METTL3, and explored the effect of m^(6)A RNA methylation on myogenic differentiation of murine myoblasts in vitro. The m6A RNA methylation level is regulated by exogenous methylation inhibitor cycloleucine (Cyc) and methyl donor betaine (Bet). Therefore, chemical reagents of Cyc and Bet were used to test the regulatory effect of m^(6)A RNA methylation on myogenic differentiation. Results showed that METTL3 and Bet positively regulated the m^(6)A RNA methylation levels, and Cyc negatively regulated m^(6)A RNA methylation levels. In addition, m^(6)A methylation positively regulated myogenic differentiation in murine myoblasts. These findings provide insight in the mechanisms underlying the effect of m^(6)A RNA methylation on myogenesis.

Differentiation between malignant and benign breast masses: combination of semi-quantitative analysis on DCE-MRI and histogram analysis of ADC maps.

AIM: To investigate the performance of combined semi-quantitative analysis on dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and histogram analysis of diffusion-weighted imaging (DWI) for distinguishing malignant from benign breast masses. MATERIALS AND METHODS: This study included 178 patients with breast masses (benign:malignant=88:9) who underwent both DCE-MRI and DWI. The semi-quantitative parameters, derived from DCE-MRI, included maximum slope of increase (MSI), signal intensity slope (SIslope), initial percentage of enhancement (Einitial), percentage of peak enhancement (Epeak), early signal enhancement ratio (ESER), and second enhancement percentage (SEP). Histogram parameters derived from apparent diffusion coefficient (ADC) maps included ADCmin, ADCmax, ADCmean, ADC10, ADC25, ADC50, ADC75, ADC90, skewness, and kurtosis. All parameters were compared between malignant and benign groups, and their differences were tested using independent-samples t-test or Mann-Whitney test. Receiver operating characteristic (ROC) curves were used to determine the diagnostic value of each significant parameter. RESULTS: Among semi-quantitative parameters, SIslope exhibited the best diagnostic performance in predicting malignancy (cut-off value, 0.096; ROC, 0.756; sensitivity, 86.7%; specificity, 61.4%). Among histogram parameters, ADC10 exhibited the best diagnostic performance in predicting malignancy (cut-off value, 1.051; ROC, 0.885; sensitivity, 86.7%; specificity, 84.1%). The optimal diagnostic performance of combined ADC10 and SIslope (area under curve [AUC], 0.888; sensitivity, 82.2%; specificity, 95.5%) was significantly better than SIslope alone (p<0.001). Moreover, the combination showed higher AUC (0.888 versus 0.885) than ADC10 alone, but the difference was not statistically significant (p=0.914). CONCLUSION: SIslope and ADC10 are significant predictors for breast malignancy. The combination of DCE-MRI and DWI improves differentiating performance.

[Clinical significance of syndecan-1 and syndecan-2 expression in gallbladder squamous cell/adenosquamous carcinoma and adenocarcinoma].

Objective: To investigate the expression of syndecan-1 and syndecan-2 and their clinicopathological significance in patients with gallbladder squamous cell (SC)/adenosquamous carcinoma (ASC) and adenocarcinoma (AC). Methods: A total of 126 patients with SC/ASC (n=46) and AC (n=80) were included in this study. The expression levels of syndecan-1 and syndecan-2 were detected by Envison™ immunohistochemistry assay. The clinical and prognostic significance of syndecan-1 and syndecan-2 were analyzed. Results: In the 46 SC/ASC samples, syndecan-1 and syndecan-2 were positively expressed in 29 (63.0%) and 28 (60.9%) tumor tissues, respectively. (Positive expression was defined based on the staining in the component of squamous cell carcinoma. That is to say, the tissue which adenocarcinoma part was positively stained, but squamous cell carcinoma part was negatively stained is also regarded as negative.) In the 80 AC samples, 47 (58.8%) cases showed syndecan-1 positive expression, and 51 (63.8%) showed syndecan-2 positive expression. There was no significant difference in the positive rates of syndecan-1 and syndecan-2 between SC/ASC and AC groups (P>0.05 for all). The levels of syndecan-1 and syndecan-2 were associated with tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in SC/ASC patients (P<0.05 for all). However, their expression was associated with tumor differentiation, tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in AC patients (P<0.05 for all). The Kaplan-Meier survival analysis of SC/ASC and AC patients revealed that the average survival time for patients with positive syndecan-1 and syndecan-2 expression was significantly shorter than that of those with negative expression (P<0.01 for all). Cox multivariate analysis indicated that syndecan-1 and syndecan-2 expression were independent unfavorable prognostic factors for SC/ASC and AC patients (P<0.05 for all). Conclusion: The syndecan-1 and syndecan-2 expression are associated with the tumor progression and poor prognosis in patients with gallbladder SC/ASC and AC.

Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy.

Presented study aimed to prepare A10 aptamer-modified poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles loaded with triplex forming oligonucleotides(TFO) for targeted prostate cancer therapy. We first synthesized a PLGA-PEG-Apt copolymer. The PLGA-PEG-Apt nanoparticles (NP-Apt) were loaded with TFO using double emulsion solvent evaporation method. Carboxy-fluorescein labeled TFO-NP-Apt, TFO-NP and TFO were prepared for cellular uptake experiments. Cell counting kit-8 (CCK-8) test was used to determine the ability of TFO-NP-Apt to inhibit LNCaP cell proliferation. RT-PCR and Western blot was conducted to analyze AR gene expressing. Then, a mouse model of prostate cancer was used to evaluate the anti-cancer effect of TFO-NP-Apt in vivo. We confirmed that the PLGA-PEG-Apt conjugation was successful. The TFO encapsulation efficiency and drug loading percentage were 46.1± 3.6% and 40.8±5.3%, respectively. TFO-NP-Apt showed a more efficient cellular uptake than TFO-NP or TFO in LNCaP cells. TFO-NP-Apt was significantly more cytotoxic than TFO-NP and TFO in the CCK-8 test (p<0.001). TFO-NP-Apt silenced the AR gene better than unconjugated Apt, naked TFO, NP or saline. TFO-NP-Apt were more effective than TFO-NP, naked TFO, NP and saline at inhibiting prostate cancer growth in vivo (p<0.05). Aptamer-modified TFO-loaded PLGA nanoparticles may prove useful in targeted therapy for advanced prostate cancer.

ERCC1 C118T polymorphism has predictive value for platinum-based chemotherapy in patients with late-stage bladder cancer.

This study aims to investigate the association between ERCC1 codon C118T polymorphism and the response rate of platinum-based chemotherapy in patients with late-stage bladder cancer. A total of 41 eligible patients histologically confirmed as having stage IV muscle-invasive transitional cell carcinoma of the bladder were treated with platinum-based chemotherapy for 2-6 cycles. The genotypes of patients were determined by PCR amplification of genomic DNA followed by restriction enzyme digestion. Positive responses were categorized as complete and partial responses. In addition, progression-free survival (PFS) and overall survival (OS) were also determined as indicators of long-term outcomes. The genotype frequencies of C/C, C/T and T/T genotypes were 56.1, 34.1, and 9.8%, respectively. Positive response was observed in 14 patients (34.1%), while 27 patients (65.9%) were negative responders. As compared with individuals carrying the C/T and T/T genotypes, those with the C/C genotype had significantly improved short-term treatment responses (P = 0.018). The median PFS of patients carrying the C/C genotype was 6.3 months, while that of patients with C/T and T/T genotypes was 4.2 months (P = 0.023). Moreover, the median OS for patients carrying the C/C genotype was also longer as compared with that of patients carrying C/T and T/T (11.7 months vs 8.5 months, P = 0.040). Our results indicated that the ERCC1 codon 118 polymorphism may have predictive potential for chemotherapy treatment responses in late-stage bladder cancer patients.

Analysis of genetic diversity and population structure in a tomato (Solanum lycopersicum L.) germplasm collection based on single nucleotide polymorphism markers.

Knowledge of genetic diversity is important to assist breeders in the selection of parental materials and in the design of breeding programs. In this study, we genotyped 348 inbred tomato lines, representing vintage and contemporary fresh-market varieties, by using 52 single nucleotide polymorphisms (SNPs); 45 of these were found to be polymorphic. The average minor allele frequency and unbiased expected heterozygosity were 0.315 and 0.356, respectively. Population structure analysis revealed that contemporary germplasm could be distinctly divided into six subpopulations representing three market classes and breeding programs (pink, green, and red). Vintage germplasm could be separated into at least two subpopulations, and more admixtures were found in vintage lines than in contemporary lines. These findings indicate that contemporary inbred lines are more diversified than vintage inbred lines. AMOVA of vintage and contemporary lines was performed. A significant difference was found (P < 0.01), which explained 17.4% of the total genetic variance. Subsequently, we constructed a core collection using 45 polymorphic SNP markers. The data showed that all alleles were captured by only 2% of lines, indicating that more alleles, as well as rare alleles, could enable more variation to be captured in the core collection. These data allow us to discard redundant inbred tomato lines and to select elite inbred lines, which will accelerate the breeding process.

Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae. By contrast, in SHR aortae, TRPV4 channels are opened, resulting in endothelial production of acetylcholine, which, in an autocrine manner, activates muscarinic receptors on neighboring cells to elicit endothelium-dependent relaxations in response to mild hypothermia.

Experimental infection of pregnant rabbits with hepatitis E virus demonstrating high mortality and vertical transmission.

A high mortality rate of approximately 20% in pregnant women with hepatitis E has been reported in previous studies. However, other studies showed no difference between pregnant and nonpregnant women in the severity of hepatitis E. To determine the effects of HEV infection on pregnancy, we successfully established HEV infection in six pregnant rabbits (PR) and six nonpregnant rabbits (NPR) with a rabbit HEV isolate, taking three PR and one NPR without HEV infection as controls. Tests for HEV RNA by RT-PCR, anti-HEV antibodies by ELISA and HEV antigen via immunohistochemistry and histopathology were carried out. Two of six infected PR miscarried and three of the remaining four PR died which may be attributed to severe liver necrosis caused by HEV infection. Moreover, vertical transmission was found to be associated with the replication of HEV in placenta, indicated by the presence of HEV RNA and antigen in placenta from the infected PR. Our findings strongly suggest that HEV infection could lead to adverse outcomes in pregnancy and vertical transmission, suggesting the necessity for pregnant women at risk of HEV infection to be vaccinated.

imDC: an ensemble learning method for imbalanced classification with miRNA data.

Imbalances typically exist in bioinformatics and are also common in other areas. A drawback of traditional machine learning methods is the relatively little attention given to small sample classification. Thus, we developed imDC, which uses an ensemble learning concept in combination with weights and sample misclassification information to effectively classify imbalanced data. Our method showed better results when compared to other algorithms with UCI machine learning datasets and microRNA data.

Non-invasive determination of the immune physiological state of reindeer (Rangifer tarandus) in the Greater Khingan Mountains, China.

Immunoglobulin and cortisol levels are good indicators of well-being and living status in animals. In this study, the concentrations of fecal immunoglobulins A ([IgAF]), G ([IgGF]), and M ([IgMF]), and cortisol ([cortisolF]) were examined by enzyme-linked immunosorbent assay in reindeer of the Greater Khingan Mountains of Inner Mongolia, China. [IgAF] was significantly higher than [IgGF] and [IgMF], and [IgGF] was significantly higher than [IgMF] (P < 0.05). Both [IgAF] and [IgGF] were higher in the Adult group than in Aged or Infant groups, and higher in the Young than Infant group (P < 0.05). The four age group [IgMF]s were not significantly different (P > 0.05). [IgAF], [IgGF], and [IgMF] in each age group were higher in females than in males, with a significant difference in the Young group (P < 0.05). The Infant group had the highest [cortisolF], and the Adult group the lowest; [cortisolF] was significantly higher in the Infant group than in other age groups (P < 0.05). In each age group, [cortisolF] was higher in females than males, and there were significant differences among the Infant, Young, and Aged groups (P < 0.05). A significant negative correlation was observed between [cortisolF] and [IgAF] and [IgGF] (P > 0.05). Overall physical condition was better in the Adult and Young groups than in the Aged and Infant groups as determined by the comprehensive analysis of fecal Ig levels in the four age groups, with the Infant group the worst.

Comparative study of clinicopathological significance, BIRC7, and STC2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder.

Gallbladder cancers (GBCs) are uncommon, but highly aggressive cancers. The majority of GBCs are adenocarcinomas (ACs), but rare subtypes of GBCs such as squamous cell carcinoma (SC) and adenosquamous carcinoma (ASC) are observed as well. The clinicopathological characteristics of SC/ASC have not been well documented. Expressions of BIRC7 and STC2 were observed in some tumors. However, BIRC7 and STC2 expressions and clinical significances in gallbladder cancer have not been reported.In this study, the protein expressions of BIRC7 and STC2 in 46 SCs/ASCs and 80 ACs were measured using immunohistochemistry. We demonstrated that positive BIRC7 and STC2 expressions were significantly associated with large tumor mass (>3cm), high TNM stage and lymph node metastasis in SC/ASC and AC (p<0.05). Positive expression of BIRC7 was significantly associated with invasion of around tissues and organs in both SC/ASC and AC. Additionally, negative BIRC7 and STC2 expressions were significantly associated with surgical curability in AC. Univariate Kaplan-Meier analysis showed that BIRC7 and STC2 expressions, differentiation, tumor size, TNM stages, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients(p < 0.001). Multivariate Cox regression analysis showed that positive BIRC7 and STC2 expressions are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive BIRC7 and STC2 expressions are closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer.

cDNA cloning and characterization of two trehalases from Spodoptera litura (Lepidoptera; Noctuidade).

The oriental leafworm moth, Spodoptera litura, is a major agricultural pest in southeast Asia and nearby Pacific regions. Two distinct trehalases have been identified in insects: soluble trehalase (Treh1) and membrane-bound trehalase (Treh2), although there is currently no information on these genes in S. litura. To characterize the distribution and function of treh, cDNAs of Treh proteins were cloned from S. litura. SpoliTreh1 cDNA has an open reading frame of 1758 nucleotides, which encodes a protein of 585 amino acids, with a predicted mass of approximately 67.07 kDa and an isoelectric point of 4.86. SpoliTreh2 cDNA has an open reading frame of 2325 nucleotides, encoding a protein of 645 amino acids, a mass of approximately 73.62 kDa, and an isoelectric point of 5.90. Northern blotting analysis revealed that SpoliTreh1 transcripts are in the midgut, fat body, tracheae, and epidermis, but not in the brain and Malpighian tubules of S. litura larvae, whereas SpoliTreh2 transcripts were found in all 6 tissues. SpoliTreh1 transcripts were highly expressed in the fat body of the pre-pupal stage, and SpoliTreh2 transcripts were highly expressed in the fat body of 3-day-old larvae of the 6th instar and during the 1st 6 days of the pupal stage, except the 2nd day. Both SpoliTreh1 and SpoliTreh2 were highly expressed in third-instar larvae.

[Multi-sequence relation attention network for diagnosing HLA-B27-negative axial spondyloarthritis].

OBJECTIVE: To develop a new 3D multi-sequence relation attention network for exploring the complementary and correlation information of different magnetic resonance imaging (MRI) modalities and improving the diagnostic performance of HLA-B27-negative axial spondyloarthropathy (axSpA). METHODS: We retrospectively collected T1-weighted imaging (T1WI) and fat suppuration MRI (FS-MRI) data and clinical data of 375 HLA-B27-negative patients from the Third Affiliated Hospital of Southern Medical University (including 164 axSpA and 211 non-axSpA patients) and 49 patients from Nanhai Hospital (including 27 axSpA and 22 non-axSpA patients) between January, 2010 and August, 2021.A 3D relation attention network MSFANet based on multi-sequence MRI was used for automatic diagnosis of axSpA against non-axSpA in these patients.MSFANet consisted of a shallow shared feature learning module and a class-aware feature learning module, and latter module used a 3D multi-sequence relation attention mechanism to refine and fuse multi-sequence MRI features.A hybrid loss function was used to enhance the recognition ability of MSFANet by learning the loss weight coefficients of different branches to improve the classification performance. RESULTS: The experimental results demonstrated that MSFANet outperformed several state-of-the-art fusion algorithms (P<0.05) with AUC, accuracy, sensitivity, and specificity of 0.840, 77.93%, 83.70%, and 70.29% in the internal validation set, and of 0.783, 74.47%, 82.43% and 70.40% in the independent external validation set, respectively.The ablation studies showed that under the same architecture, the fusion model was superior to single-sequence models, which confirmed the effectiveness and necessity of fusing multi-sequence MRI.The visualization results demonstrated that MSFANet could focus on learning information from abnormal areas on MRI during the classification. CONCLUSION: We successfully constructed a 3D deep neural network based on multi-sequence MRI for differential diagnosis of HLA-B27-negative axSpA against nonaxSpA and verified the effectiveness of the multisequence relation attention mechanism for promoting classification performance of the network.

Improved method for predicting protein fold patterns with ensemble classifiers.

Protein folding is recognized as a critical problem in the field of biophysics in the 21st century. Predicting protein-folding patterns is challenging due to the complex structure of proteins. In an attempt to solve this problem, we employed ensemble classifiers to improve prediction accuracy. In our experiments, 188-dimensional features were extracted based on the composition and physical-chemical property of proteins and 20-dimensional features were selected using a coupled position-specific scoring matrix. Compared with traditional prediction methods, these methods were superior in terms of prediction accuracy. The 188-dimensional feature-based method achieved 71.2% accuracy in five cross-validations. The accuracy rose to 77% when we used a 20-dimensional feature vector. These methods were used on recent data, with 54.2% accuracy. Source codes and dataset, together with web server and software tools for prediction, are available at: http://datamining.xmu.edu.cn/main/~cwc/ProteinPredict.html.

Benchmark comparison of ab initio microRNA identification methods and software.

MicroRNAs (miRNAs) are short, non-coding RNA molecules that play an important role in the world of genes, especially in regulating the gene expression of target messenger RNAs through cleavage or translational repression of messenger RNA. Ab initio methods have become popular in computational miRNA detection. Most software tools are designed to distinguish miRNA precursors from pseudo-hairpins, but a few can mine miRNA from genome or expressed sequence tag sequences. We prepared novel testing datasets to measure and compare the performance of various software tools. Furthermore, we summarized the miRNA mining methods that study next-generation sequencing data for bioinformatics researchers who are analyzing these data. Because secondary structure is an important feature in the identification of miRNA, we analyzed the influence of various secondary structure prediction software tools on miRNA identification. MiPred was the most effective for classifying real-/pseudo-pre-miRNA sequences, and miRAbela performed relatively better for mining miRNA precursors from genome or expressed sequence tag sequences. RNA-fold performed better than m-fold for extracting secondary structure features of miRNA precursors.