Rupture process of the 2021 M7.4 Maduo earthquake and implication for deformation mode of the Songpan-Ganzi terrane in Tibetan Plateau.

The deformation mode of the Tibetan Plateau is of crucial importance for understanding its construction and extrusion processes, as well as for the assessment of regional earthquake potential. Block motion and viscous flow models have been proposed to describe the deformation field but are not fully supported by modern geophysical observations. The 2021 Mw 7.4 Maduo earthquake, which occurred inside the Songpan-Ganzi terrane (SGT) in central-east Tibet, provides a chance to evaluate the associated deformation mode of the region. We conduct a joint inversion for this earthquake and resolve a bilateral rupture process, which is characterized by super- and subshear rupture velocities, respectively. We interpret this distinct rupture behavior to be the result of the respective slip concentration depths of the two ruptured segments. We analyze geological, seismic, and geodetic evidence and find that the SGT upper crust shows distributed shear deformation and distinct transverse anisotropy, which are associated with folded structures originating from compression of the paleo-Tethys ocean accretional prism realigned by following shear deformation. The SGT receives lateral shear loading from its NS boundary and accommodates a right-step sinistral motion across the terrane boundary faults. The unique tectonic setting of the SGT defines locations and behaviors of internal faulting and strong earthquakes such as the 2021 Maduo earthquake, with the latter occurring on slow-moving faults at intervals of several thousands of years.

Characterization of Bacillus amyloliquefaciens PM415 as a potential bio-preserving probiotic.

Animal feed is vulnerable to fungal infections, and the use of bio-preserving probiotics has received increasing attention. In contrast to Lactobacillus and Bifidobacteria spp., fewer Bacillus spp. have been recognized as antifungal probiotics. Therefore, our objective was to screen antifungal strains and provide more Bacillus candidates to bridge this gap. Here, we screened 56 bacterial strains for cyclic lipopeptide genes and conducted an antifungal assay with Aspergillus niger as a representative fungus. We found that a Bacillus strain Bacillus amyloliquefaciens PM415, isolated from pigeon manure, exhibited the highest fungal inhibition activity as demonstrated by the confrontation assay and morphological observation under scanning electron microscope (SEM). Preliminary safety assessment and probiotic characterization revealed its non-pathogenic feature and stress tolerance capability. Whole genome sequencing of Bacillus amyloliquefaciens PM415 revealed a genome size of 4.16 Mbp and 84 housekeeping genes thereof were used for phylogenetic analysis showing that it is most closely related to Bacillus amyloliquefaciens LFB112. The in silico analysis further supported its non-pathogenic feature at the genomic level and revealed potential biosynthetic gene clusters responsible for its antifungal property. RNA-seq analysis revealed genome-wide changes in transportation, amino acid metabolism, non-ribosomal peptides (NRPs) biosynthesis and glycan degradation during fungal antagonism. Our results suggest that Bacillus amyloliquefaciens PM415 is a safe and effective probiotic strain that can prevent fungal growth in animal feeds.

Dual-source dual-energy CT and deep learning for equivocal lymph nodes on CT images for thyroid cancer.

OBJECTIVES: This study investigated the diagnostic performance of dual-energy computed tomography (CT) and deep learning for the preoperative classification of equivocal lymph nodes (LNs) on CT images in thyroid cancer patients. METHODS: In this prospective study, from October 2020 to March 2021, 375 patients with thyroid disease underwent thin-section dual-energy thyroid CT at a small field of view (FOV) and thyroid surgery. The data of 183 patients with 281 LNs were analyzed. The targeted LNs were negative or equivocal on small FOV CT images. Six deep-learning models were used to classify the LNs on conventional CT images. The performance of all models was compared with pathology reports. RESULTS: Of the 281 LNs, 65.5% had a short diameter of less than 4 mm. Multiple quantitative dual-energy CT parameters significantly differed between benign and malignant LNs. Multivariable logistic regression analyses showed that the best combination of parameters had an area under the curve (AUC) of 0.857, with excellent consistency and discrimination, and its diagnostic accuracy and sensitivity were 74.4% and 84.2%, respectively (p < 0.001). The visual geometry group 16 (VGG16) based model achieved the best accuracy (86%) and sensitivity (88%) in differentiating between benign and malignant LNs, with an AUC of 0.89. CONCLUSIONS: The VGG16 model based on small FOV CT images showed better diagnostic accuracy and sensitivity than the spectral parameter model. Our study presents a noninvasive and convenient imaging biomarker to predict malignant LNs without suspicious CT features in thyroid cancer patients. CLINICAL RELEVANCE STATEMENT: Our study presents a deep-learning-based model to predict malignant lymph nodes in thyroid cancer without suspicious features on conventional CT images, which shows better diagnostic accuracy and sensitivity than the regression model based on spectral parameters. KEY POINTS: Many cervical lymph nodes (LNs) do not express suspicious features on conventional computed tomography (CT). Dual-energy CT parameters can distinguish between benign and malignant LNs. Visual geometry group 16 model shows superior diagnostic accuracy and sensitivity for malignant LNs.

Risk factors for delayed extubation after pediatric perineal anaplasty in patients less than 1 year of age: a retrospective study.

BACKGROUND: Anorectal malformation is a common congenital problem occurring in 1 in 5,000 births and has a spectrum of anatomical presentations, requiring individualized surgical treatments for normal growth. Delayed extubation or reintubation may result in a longer intensive care unit (ICU) stay and hospital stay, increased mortality, prolonged duration of mechanical ventilation, increased tracheostomy rate, and higher hospital costs. Extensive studies have focused on the role of risk factors in early extubation during major infant surgery such as Cardiac surgery, neurosurgery, and liver surgery. However, no study has mentioned the influencing factors of delayed extubation in neonates and infants undergoing angioplasty surgery. MATERIALS AND METHODS: We performed a retrospective study of neonates and infants who underwent anorectal malformation surgery between June 2018 and June 2022. The principal goal of this study was to observe the incidence of delayed extubation in pediatric anorectal malformation surgery. The secondary goals were to identify the factors associated with delayed extubation in these infants. RESULTS: We collected data describing 123 patients who had anorectal malformations from 2019 to 2022. It shows that 74(60.2%) in the normal intubation group and 49(39.8%) in the longer extubation. In the final model, anesthesia methods were independently associated with delayed extubation (P < 0.05). CONCLUSION: We found that the anesthesia method was independently associated with early extubation in neonates and infants who accepted pediatric anorectal malformation surgery.

Clinical Analysis of Atorvastatin Calcium, Fenofibrate, and Acipimox in the Treatment of Hypertriglyceridemia-induced Acute Pancreatitis.

Background: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is an increasingly recognized and potentially severe form of acute pancreatitis. The effective management of HTG-AP is critical due to its association with significant morbidity and mortality. HTG-AP poses a considerable burden on affected individuals and healthcare systems. It can result in persistent upper abdominal pain, nausea, vomiting, abdominal distension, fever, and in severe cases, hypotension or shock and multiple organ dysfunction. Standard treatment strategies often involve lipid-lowering agents, but the optimal therapeutic approach remains a subject of ongoing research. This study aims to evaluate the efficacy of atorvastatin calcium, fenofibrate, and acipimox, either individually or in combination, in the treatment of HTG-AP, providing insights into more effective management strategies. Methods: 150 HTG-AP patients admitted to the first hospital of Putian from June 2020 to December 2022 were selected. The age range of the patients included in the study was between 30 and 70 years, with an average age of approximately 48 years. The cohort consisted of 90 males and 60 females, resulting in a male-to-female ratio of 3:2. The patients were grouped: atorvastatin calcium, acipimox, fenofibrate, fenofibrate + Atorvastatin calcium, fenofibrate + acipimox, and no drug. The therapeutic effects and clinical indicators of the six groups were compared. Results: Patients in the fenofibrate + acipimox and fenofibrate groups experienced significantly reduced hospitalization duration compared to the other groups. They also had shorter abdominal pain relief time and gastrointestinal function relief time. Additionally, these groups had lower peak levels of amylase (an enzyme) and cholesterol compared to the other groups. In terms of neutrophil (NEUT) increase, the fenofibrate + acipimox, atorvastatin calcium, and fenofibrate groups had significantly lower peak levels compared to the other groups, indicating a less pronounced increase in NEUT. Furthermore, the fenofibrate and acipimox groups exhibited significantly lower peak levels of C-reactive protein (CRP) compared to the other groups. CRP is an indicator of inflammation. On the other hand, the atorvastatin calcium group had higher levels of procalcitonin (a marker of infection) and a higher peak score on the acute physiology and chronic health evaluation II (APACHE II) scale, which assesses the severity of acute pancreatitis, compared to the other groups (all P < .05). Conclusion: The findings of this study highlight the effectiveness of combining fenofibrate and acipimox in the treatment of HTG-AP, leading to rapid disease recovery and significant improvement in clinical symptoms. These results have important implications for clinical practice, as the combination therapy can be widely adopted as an effective treatment strategy for HTG-AP patients. Moreover, this study provides valuable insights into the management of HTG-AP and suggests that lipid-lowering agents, such as atorvastatin calcium and fenofibrate, play a crucial role in the treatment of this condition. However, further research is needed to explore the optimal dosages, treatment durations, and potential side effects of these medications in HTG-AP patients.

Analysis of Relevant Predictive Indicators for Postoperative Condition Change in Brain Tumor Patients.

BACKGROUND: Novice nurse need more guidance and professional confidence. This study aimed to explore early relevant predictive indicators for postoperative condition changes in brain tumor patients, which can be used to map patients' condition changes for novice nurses. METHODS: The authors prospectively collected clinical data, including nursing records of cerebral tumor patients after operation from July 2020 to June 2021 in the Department of Neurosurgery. Univariant analysis and multivariable logistic regression analysis were performed to identify independent predictors, the satisfaction questionnaire for teaching nurses is used to evaluate the new nurse's performance during perioperative period, psychometric scale is used to assess nurses' psychological stress. RESULTS: Nine hundred ninety-five cerebral tumor patients were enrolled in this study, and 115 (11.6%) patients' conditions were changed. Relevant predictive indicators, including vision, myodynamia, urine volume, nausea, vomit, pain, Glasgow Coma Scale (GCS), and Modified Early Warning System (MEWS), among them GCS, MEWS, and vision can basically cover the above indicators through simulation and calculation of the integrated model was set as Z=22*vision+1*GCS+3*MEWS. The satisfaction rate of teaching nurses has increased from 78.125 to 86.25%. Novice nurses' psychological stress was dropped from 30.637% to 19.844%. CONCLUSIONS: GCS and MEWS. GCS, MEWS and vision can map patients' condition change after cerebral tumor operation. The warning model has reduced their psychological stress, and the teaching nurse expressed that the effective evaluation of postoperative patient conditions by novice nurses reduces their nursing and teaching work greatly.

Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

Postoperative outcomes of pediatric patients with perioperative COVID-19 infection: a systematic review and meta-analysis of observational studies.

OBJECTIVE: To quantify the risk of adverse postoperative outcomes in pediatric patients with COVID-19 infection. METHODS: We searched PubMed, Embase, Cochrane Library from December 2019 to 21 April 2023. Observational cohort studies that reported postoperative early mortality and pulmonary complications of pediatric patients with confirmed COVID-19-positive compared with COVID-19-negative were eligible for inclusion. We excluded pediatric patients underwent organ transplantation or cardiac surgery. Reviews, case reports, letters, and editorials were also excluded. We used the Newcastle-Ottawa Scale to assess the methodological quality and risk of bias for each included study. The primary outcome was postoperative early mortality, defined as mortality within 30 days after surgery or during hospitalization. The random-effects model was performed to assess the pooled estimates, which were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). RESULTS: 9 studies involving 23,031 pediatric patients were included, and all studies were rated as high quality. Compared with pediatric patients without COVID-19, pediatric patients with COVID-19 showed a significantly increased risk of postoperative pulmonary complications (PPCs) (RR = 4.24; 95% CI 2.08-8.64). No clear evidence was found for differences in postoperative early mortality (RR = 0.84; 95% CI 0.34-2.06), postoperative intensive care unit (ICU) admission (RR = 0.80; 95% CI 0.39-1.68), and length of hospital stay (MD = 0.35, 95% CI -1.81-2.51) between pediatric patients with and without COVID-19. CONCLUSION: Perioperative COVID-19 infection was strongly associated with increased risk of PPCs, but it did not increase the risk of postoperative early mortality, the rate of postoperative ICU admission, and the length of hospital stay in pediatric patients. Our preplanned sensitivity analyses confirmed the robustness of our study findings.

Analysis of m7G-Related signatures in the tumour immune microenvironment and identification of clinical prognostic regulators in breast cancer.

BACKGROUND: Breast cancer is a malignant tumour that seriously threatens women's life and health and exhibits high inter-individual heterogeneity, emphasising the need for more in-depth research on its pathogenesis. While internal 7-methylguanosine (m7G) modifications affect RNA processing and function and are believed to be involved in human diseases, little is currently known about the role of m7G modification in breast cancer. METHODS AND RESULTS: We elucidated the expression, copy number variation incidence and prognostic value of 24 m7G-related genes (m7GRGs) in breast cancer. Subsequently, based on the expression of these 24 m7GRGs, consensus clustering was used to divide tumour samples from the TCGA-BRCA dataset into four subtypes based on significant differences in their immune cell infiltration and stromal scores. Differentially expressed genes between subtypes were mainly enriched in immune-related pathways such as 'Ribosome', 'TNF signalling pathway' and 'Salmonella infection'. Support vector machines and multivariate Cox regression analysis were applied based on these 24 m7GRGs, and four m7GRGs-AGO2, EIF4E3, DPCS and EIF4E-were identified for constructing the prediction model. An ROC curve indicated that a nomogram model based on the risk model and clinical factors had strong ability to predict the prognosis of breast cancer. The prognoses of patients in the high- and low-TMB groups were significantly different (p = 0.03). Moreover, the four-gene signature was able to predict the response to chemotherapy. CONCLUSIONS: In conclusion, we identified four different subtypes of breast cancer with significant differences in the immune microenvironment and pathways. We elucidated prognostic biomarkers associated with breast cancer and constructed a prognostic model involving four m7GRGs. In addition, we predicted the candidate drugs related to breast cancer based on the prognosis model.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

Impact of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease: study protocol of a randomized controlled trial.

BACKGROUND: Literature regarding the advantages of gasless vNOTES is insufficient. The aim of our study is to compare gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. We hypothesize that compared with those in the traditional vNOTES group, hemodynamic profiles will be changed less during gasless vNOTES, while safety can be promised. METHODS: This is a single-center, prospective, single-blind, randomized controlled clinical trial, which has been approved by the Institutional Review Board of Chengdu Women's and Children's Hospital on September 27, 2022. One hundred and twenty patients will be recruited and randomly assigned to either the traditional vNOTES group or the gasless vNOTES group in a 1:1 ratio. For patients allocated to the traditional vNOTES group, after insertion of one port through the vagina, CO2 gas is infused with a pressure of 12-14 mmHg; while for those allocated to the gasless vNOTES group, a special device is used as an abdominal wall-lifting device to facilitate gasless surgery. CO2 pneumoperitoneum will not be used during the whole gasless vNOTES procedure. The primary outcome is vital signs at different time points. The secondary outcomes include surgical conversion rate, duration of surgery and anesthesia, anesthetic consumption, intraoperative estimated blood loss, VAS and PONV scores at postoperative 2 h and 24 h, administration of vasopressor drugs from the beginning of general anesthesia induction to 15 min after endotracheal intubation, including times, dosage, and type, intraoperative and postoperative complications, time of first getting out of bed after surgery, and time of first eating after surgery, including light drink. DISCUSSION: This is the first randomized controlled trial to compare the impacts of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. If a favorable effect and safety of gasless vNOTES for hemodynamic profiles and outcomes in patients are shown, gasless vNOTES would be an optimal treatment option for patients with benign gynecological disease. TRIAL REGISTRATION: The trial was registered at https://www.chictr.org.cn/showproj.html?proj=182441 with registration No. ChiCTR2200064779 on Oct 17, 2022.

Urinary N-acetyl-ß-d-glucosaminidase-creatine ratio is a valuable predictor for advanced diabetic kidney disease.

BACKGROUND: Many biomarkers show high diagnostic values for diabetic kidney disease (DKD), but fewer studies focus on the predictive assessment of DKD progression by blood and urinary biomarkers. AIM: This study aims to find powerful risk predictors and identifying biomarkers in blood and urine for DKD progression. METHODS: A total of 117 patients with type 2 DKD including early and advanced stages and their laboratory parameters were statistically assessed. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the significance of discriminating between early and advanced DKD, and the predictive power for advanced DKD was analyzed by regression analysis and trisector grouping. RESULTS: N-acetyl-ß-d-glucosaminidase-creatine (NAG/CR) level in advanced DKD was statistically higher than that in early DKD (p < 0.05), and there was a higher incidence of advanced DKD (72% vs. 56%) and high odds ratio (OR: 3.917, 95% CI: 1.579-10.011) of NAG/CR with ≥2.79 U/mmol compared with <2.79 U/mmol (p < 0.05). NAG/CR ratio also showed a higher area under the ROC curve of 0.727 (95% CI: 0.616-0.828, p = 0.010) with a high sensitivity (0.75) and a moderate specificity (0.66) when 1.93 U/mmol was set as the optimal cutoff value. The adjusted-multivariable analysis revealed that NAG/CR had an OR of 1.021 (95% CI: 1.024-1.038) and 2.223 (95% CI: 1.231-4.463) based on a continuous and categorical variable, respectively, for risk of advanced DKD. Moreover, the prevalence of advanced DKD exhibited an increasing tendency by an increment of the trisector of NAG/CR. CONCLUSIONS: This study suggests that NAG/CR ratio is an independent predictor for advanced DKD, and it also can be used as a powerful identifying marker between early and advanced DKD.

Three-Dimensional Digital Technology: A Powerful Assistant for the Reconstruction of Complex Craniofacial Deformities.

Three-dimensional digital technology has been widely applied in craniofacial surgeries, particularly in conventional procedures such as facial contouring and orthognathic surgery. To some extent, the process has already been standardized. As to reconstruction surgeries of complex craniofacial deformity, however, surgical plans need to be patient-specific. Traditionally, individualized surgical treatment largely relies on the surgeon's clinical experience. The application of digital technology mainly focuses on preoperative planning and postoperative evaluation of surgical outcomes rather than intraoperative patient-specific implants or osteotomy guides. For patients with complex craniofacial deformities, requirements for accurate 3-dimensional digital technology can be much higher. This study presents a favorable surgical reconstruction of the severe craniofacial deformity using 3-dimensional digital technology, providing references for craniofacial surgeons, which could be beneficial to clinical practice and treatment efficacy.

Comprehensive Serial Treatment of Treacher Collins Syndrome.

OBJECTIVE: To discuss and summarize the comprehensive serial surgical treatment of Treacher Collins syndrome. MATERIALS AND METHODS: From September 2012 to January 2020, 12 patients with Treacher Collins syndrome were treated by autologous fat graft, mandibular distraction osteogenesis, orbitozygomatic reconstruction with calvarial external lamina, orthognathic surgery combined with postoperative orthodontics, transplantation of upper eyelid orbicularis myocutaneous flap, lateral canthal ligament reduction, and other methods. The authors evaluated the postoperative improvement, summarized experiences, and reviewed literatures about the comprehensive serial treatment of Treacher Collins syndrome. RESULTS: All patients showed significant improvement in appearance and function, and no complications were found during the follow-up period of 5 months to 3 years. CONCLUSIONS: The deformities of Treacher Collins syndrome involves multiple craniofacial region, and only by formulating comprehensive serial treatment strategies according to the malformation characteristics of different patients can the best effect be achieved.

Treatment of Asymmetric Crying Face by Fascia lata Grafting.

OBJECTIVE: To evaluate and discuss the plastic surgery treatment of asymmetric crying face. METHODS: From 2019 to 2022, 60 patients with asymmetric crying face were treated by fascia lata grafting. We evaluated the postoperative improvement, summarized experiences and reviewed literatures about the treatment of asymmetric crying face. RESULTS: 59 patients showed varying degrees of improvement in the movement of the affected corner of mouth, and no complications were found during the follow-up period of 6 months to 24 months. CONCLUSIONS: The cause of asymmetric crying face is still uncertain. Fascia lata grafting has shown a certain effect in the treatment of asymmetric crying face. This study evaluated this method with quite large sample. More researches are needed to explore the most appropriate treatment for asymmetric crying face.

Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors.

BACKGROUND/AIMS: This study explores the relationship between the E3 ubiquitin ligase Ring finger protein 126 (RNF126) and early breast cancer metastasis and tests the hypothesis that RNF126 determines the efficacy of inhibitors targeting Ataxia telangiectasia mutated and Rad3-related kinase (ATR). METHODS: Various metastasis-related genes were identified by univariable Cox proportional hazards regression analysis based on the GSE11121 dataset. The RNF126-related network modules were identified by WGCNA, whereas cell viability, invasion, and migration assays were performed to evaluate the biological characteristics of breast cancer cells with or without RNF126 knockdown. MTT, immunoblotting, immunofluorescence, and DNA fiber assays were conducted to determine the efficiency of ATR inhibitor in cells with or without RNF126 knockdown. RESULTS: RNF126 was associated with early breast cancer metastasis. RNF126 promoted breast cancer cell proliferation, growth, migration, and invasion. ATR inhibitors were more effective at killing breast cancer cells with intact RNF126 due to replication stress compared with the corresponding cells with RNF126 knockdown. Cyclin-dependent kinase 2 (CDK2) was involved in regulating replication stress in breast cancer cells with intact RNF126. CONCLUSION: A high level of expression of RNF126 in early breast cancer patients without lymph node metastases may indicate a high-risk type of metastatic disease, possibly due to RNF126, which may increase breast cancer cell proliferation and invasion. RNF126-expressing breast cancer cells exhibit CDK2-mediated replication stress that makes them potential targets for ATR inhibitors.

Circular RNA circPDSS1 promotes osteosarcoma progression by sponging miR-502-3p and miR-4436a.

Osteosarcoma (OS) is a highly aggressive bone cancer. Patients with OS frequently develop drug resistance in clinical treatment, and the prognosis has not been improved significantly. There is an urgent need to identify novel markers and therapeutic targets. In this study, we focused on the highly expressed noncoding circular RNA circPDSS1 in OS, and studied its functional roles and downstream targets in OS cells by CCK-8, clone formation assay, transwell assays. Additionally, we performed luciferase reporter assay, RNA pull-down experiment and qRT-PCR to validate the micoRNA targets of circPDSS1. The involvement of circPDSS1 in tumorigenesis was also investigated in mouse xenografts model. The expression of circPDSS1 was significantly upregulated in OS tissues and cell lines. Patients with high circPDSS1 expression were associated with poorer progression-free survival (PFS) and overall survival (OS) as compared to those with low circPDSS1 expression. CircPDSS1 knockdown significantly inhibited the viability, clone formation ability and invasion ability of OS cells, and induced cell apoptosis, which were associated with the upregulation of proapoptotic proteins and the impairment of prosurvival signaling. Molecular mechanism study further demonstrated that circPDSS1 modulates OS cell functions by regulating the expression of miR-502-3p and miR-4436a. Our data suggest that circPDSS1 acts as a molecular sponge of miR-502-3p and miR-4436a regulates the proliferation and invasion of OS cells and promote the malignant progression of OS.

Diagnostic efficacy of FibroScan for liver inflammation in patients with chronic hepatitis B: a single-center study with 1185 liver biopsies as controls.

BACKGROUND: Noninvasive diagnostic technologies that can dynamically monitor changes in liver inflammation are highly important for the management of chronic hepatitis B (CHB) patients and thus warrant further exploration. This study assessed the diagnostic efficacy of FibroScan for liver inflammation in CHB patients. METHODS: A total of 1185 patients were selected, and ultrasound-guided liver biopsy was performed within 1 month after the FibroScan test. The liver stiffness measurement (LSM), the reliability criteria (IQR/M) of LSM, the quality of liver biopsy (complete portal area, PA), and the liver inflammation grades were the main observation items of this study. With liver biopsy as the control, the diagnostic efficacy of FibroScan for liver inflammation in CHB patients was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The grade of liver inflammation was positively correlated with the stage of fibrosis (rho = 0.829, P < 0.001). Different grades of inflammation will have significant rise in LSM values within the same fibrosis stage, and LSM values were positively correlated with liver inflammation grade and fibrosis stage, and the rho is 0.579 and 0.593 respectively (P < 0.001). Significant differences in the LSM of FibroScan were observed among different grades of liver inflammation (P < 0.0001). Liver biopsy (PA > 10) served as the control, and the cutoff point and the area under ROC curves (AUCs) of the LSMs for different inflammation grades were as follows: G2, 8.6 kPa, 0.775; G3 9.8 kPa, 0.818; and G4, 11.0 kPa; 0.832. With LSM cutoff values of 8.6 kPa, 9.8 kPa and 11.0 kPa, FibroScan showed certain diagnostic value for CHB patients with G2, G3 and G4 liver inflammation, especially those with G4 inflammation. CONCLUSIONS: The grade of liver inflammation was positively correlated with the stage of fibrosis, different grades of inflammation will have significant rise in LSM values within the same fibrosis stage. In addition to liver fibrosis, FibroScan could evaluate liver inflammation in CHB patients in a noninvasive manner.

Inferring subgroup-specific driver genes from heterogeneous cancer samples via subspace learning with subgroup indication.

MOTIVATION: Detecting driver genes from gene mutation data is a fundamental task for tumorigenesis research. Due to the fact that cancer is a heterogeneous disease with various subgroups, subgroup-specific driver genes are the key factors in the development of precision medicine for heterogeneous cancer. However, the existing driver gene detection methods are not designed to identify subgroup specificities of their detected driver genes, and therefore cannot indicate which group of patients is associated with the detected driver genes, which is difficult to provide specifically clinical guidance for individual patients. RESULTS: By incorporating the subspace learning framework, we propose a novel bioinformatics method called DriverSub, which can efficiently predict subgroup-specific driver genes in the situation where the subgroup annotations are not available. When evaluated by simulation datasets with known ground truth and compared with existing methods, DriverSub yields the best prediction of driver genes and the inference of their related subgroups. When we apply DriverSub on the mutation data of real heterogeneous cancers, we can observe that the predicted results of DriverSub are highly enriched for experimentally validated known driver genes. Moreover, the subgroups inferred by DriverSub are significantly associated with the annotated molecular subgroups, indicating its capability of predicting subgroup-specific driver genes. AVAILABILITY AND IMPLEMENTATION: The source code is publicly available at https://github.com/JianingXi/DriverSub. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p.

BACKGROUND: Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. METHODS: Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. RESULTS: Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. CONCLUSIONS: Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.