Molecular epidemiology of Brucella abortus isolated from the environment in Ningxia Hui autonomous region, China.

Brucellosis is among the key zoonotic infectious diseases in China, and The Ningxia Hui Autonomous Region represents a major endemic area, and it is one of the main causes of poverty in the region due to illness. In Ningxia, there is substantial research on Brucella melitensis, studies on the molecular epidemiology of Brucella abortus are notably scarce. Consequently, this study aims to undertake pathogenic isolation and molecular epidemiological research on Brucella abortus isolated from the environment in Ningxia, providing insights and evidence to advance the prevention and control measures for brucellosis in the region. Building on traditional pathogenic detection methods, this research employs whole-genome sequencing(WGS) techniques and bioinformatics software to conduct a phylogenetic comparison of Ningxia strains and strains of Brucella abortus from various geographical origins. The results indicate that four Brucella abortus strains are classified as biovar 3 and MLST type ST2. It is shown that the local strains were closer phylogenetic relationships with strains from Asian and European countries. The presence of Brucella abortus in certain environmental sectors of Ningxia indicates a risk of transmission from the environment to animals and subsequently to humans. In conclusion, the Brucella abortus exists in some farming environments in Ningxia, and exists for a long time. Therefore, it is necessary to strengthen the monitoring of the disinfection effect of the farming environment to provide a basis for the forward movement of the gate of brucellosis prevention and control.

Whole Genome-Sequencing and Phylogenetic Analysis of Bacillus anthracis from 2019-2023 in Ningxia Hui Autonomous Region, China.

BACKGROUND: Since 2019, the incidence of anthrax in the Ningxia Hui Autonomous Region has increased significantly compared with previous years, so in this situation the anthrax in the Ningxia region not only had a detrimental impact on public health, but also inflicted significant economic repercussions. Therefore, we conducted a molecular epidemiological study of 20 strains from 2019-2023 isolates. This study investigated the origin of Bacillus anthracis and its genetic diversity. METHODS: We conducted canonical single-nucleotide polymorphisms (CanSNPs) typing and whole genome sequencing based on the extracted nucleic acid of Bacillus anthracis. Based on the whole genome drafts, we studied the genomic characteristics of 20 isolates. Meanwhile, we performed phylogenetic studies based on genome-wide core single-nucleotide polymorphisms (SNPs) using MEGA's Maximum Likelihood (ML) method and core-genome-based multilocus sequence typing (cgMLST) of the core genomes of these strains using BioNumerics' minimum spanning tree (MST) model. RESULTS: The 20 isolates were categorized into sub-lineages A.Br.001/002, and comparative genomic analyses of these strains with other isolates from other parts of the world showed that the strains from Ningxia were correlated with isolates from Europe, Indonesia, Georgia (USA), and Beijing (China). For the 20 isolates in Ningxia, the genetic relationship of the isolates isolated from the same year or region was relatively close. CONCLUSION: The A.Br.001/002 subgroup was the dominant endemic strain in Ningxia. The genetic relationship and phylogenesis between isolates from Ningxia and strains from Europe and Indonesia suggest that anthrax spread around the globe through ancient trade routes.

Arthroscopic Medial Bi-portal Extra-articular Debridement for Recalcitrant Medial Epicondylitis.

Medial epicondylitis, or golfer's elbow, is characterized by pain and tenderness at the tendon insertion points of the pronator teres and flexor carpi radialis. Conservative treatment is sufficient for most patients, whereas surgical treatment is the best choice for intractable medial epicondylitis. With open surgery or arthroscopic surgery, good clinical results have been reported. However, there is still no consensus on which surgical technique is more ideal. We describe our technique of arthroscopic medial bi-portal extra-articular debridement, which is a safe and effective technique that allows more accurate debridement and maximum protection of the ulnar nerve while reducing surgical scars, relieving postoperative pain, reducing the probability of elbow infection and ankylosis, and shortening the recovery time.

Catalytic performance and mechanism study of the isomerization of 2,5-dichlorotoluene to 2,4-dichlorotoluene.

This work investigates the influence of catalyst HZSM-5 on the isomerization of 2,5-dichlorotoluene (2,5-DCT) to produce 2,4-dichlorotoluene (2,4-DCT). We observe that hydrothermal treatment leads to a decrease in total acidity and Brønsted/Lewis ratio of HZSM-5 while generating new secondary pores. These characteristics result in excellent selectivity for post-hydrothermal modified HZSM-5 in the isomerization reaction from 2,5-DCT to 2,4-DCT. Under atmospheric pressure at 350 °C, unmodified HZSM-5 achieves a selectivity of 66.4% for producing 2,4-DCT, however after hydrothermal modification the selectivity increases to 78.7%. Density Functional Theory (DFT) calculations explore the thermodynamic aspects of adsorption between the HZSM-5 surface and 2,4-DCT. The kinetic perspective investigates the mechanism involving proton attack on the methyl group of 2,5-DCT followed by rearrangement leading to formation of 2,4-DCT during isomerization. The consistency between simulation and experimental results provides evidence for the feasibility of isomerizing 2,5-DCT to 2,4-DCT. This work fills the gap in the low value-added product 2,5-DCT isomer conversion, indicating its significant practical application potential and provides a valuable reference and guidelines for industrial research in this field.

Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling.

BACKGROUND: Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), a flavonoid phytochemical, plays a critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts in postmenopausal osteoporosis (PMOP) has not been elucidated. PURPOSE: This research aimed to determine the effect of Lut in ameliorating PMOP by alleviating osteoblast pyroptosis and sustaining osteogenesis. STUDY DESIGN: This research was designed to investigate the novel mechanism of Lut in alleviating PMOP both in cell and animal models. METHODS: Ovariectomy-induced PMOP models were established in mice with/without daily gavaged of 10 or 20 mg/kg body weight Lut. The impact of Lut on bone microstructure, metabolism and oxidative stress was evaluated with 0.104 mg/kg body weight Estradiol Valerate Tablets daily gavaged as positive control. Network pharmacological analysis and molecular docking were employed to investigate the mechanisms of Lut in PMOP treatment. Subsequently, the impacts of Lut on the PI3K/AKT axis, oxidative stress, mitochondria, and osteoblast pyroptosis were assessed. In vitro, cultured MC3T3-E1(14) cells were exposed to H2O2 with/without Lut to examine its effects on the PI3K/AKT signaling pathway, osteogenic differentiation, mitochondrial function, and osteoblast pyroptosis. RESULTS: Our findings demonstrated that 20 mg/kg Lut, similar to the positive control drug, effectively reduced systemic bone loss and oxidative stress, and enhanced bone metabolism induced by ovariectomy. Network pharmacological analysis and molecular docking indicated that the PI3K/AKT axis was a potential target, with oxidative stress response and nuclear membrane function being key mechanisms. Consequently, the effects of Lut on the PI3K/AKT axis and pyroptosis were investigated. In vivo data revealed that the PI3K/AKT axis was deactivated following ovariectomy, and Lut restored the phosphorylation of key proteins, thereby reactivating the axis. Additionally, Lut alleviated osteoblast pyroptosis and mitochondrial abnormalities induced by ovariectomy. In vitro, Lut intervention mitigated the inhibition of the PI3K/AKT axis and osteogenesis, as well as H2O2-induced pyroptosis. Furthermore, Lut attenuated ROS accumulation and mitochondrial dysfunction. The effects of Lut, including osteogenesis restoration, anti-pyroptosis, and mitochondrial maintenance, were all reversed with LY294002 (a PI3K/AKT pathway inhibitor). CONCLUSION: In summary, Lut could improve mitochondrial dysfunction, alleviate GSDME-mediated pyroptosis and maintain osteogenesis via activating the PI3K/AKT axis, offering a new therapeutic strategy for PMOP.

Unravelling cancer subtype-specific driver genes in single-cell transcriptomics data with CSDGI.

Cancer is known as a heterogeneous disease. Cancer driver genes (CDGs) need to be inferred for understanding tumor heterogeneity in cancer. However, the existing computational methods have identified many common CDGs. A key challenge exploring cancer progression is to infer cancer subtype-specific driver genes (CSDGs), which provides guidane for the diagnosis, treatment and prognosis of cancer. The significant advancements in single-cell RNA-sequencing (scRNA-seq) technologies have opened up new possibilities for studying human cancers at the individual cell level. In this study, we develop a novel unsupervised method, CSDGI (Cancer Subtype-specific Driver Gene Inference), which applies Encoder-Decoder-Framework consisting of low-rank residual neural networks to inferring driver genes corresponding to potential cancer subtypes at the single-cell level. To infer CSDGs, we apply CSDGI to the tumor single-cell transcriptomics data. To filter the redundant genes before driver gene inference, we perform the differential expression genes (DEGs). The experimental results demonstrate CSDGI is effective to infer driver genes that are cancer subtype-specific. Functional and disease enrichment analysis shows these inferred CSDGs indicate the key biological processes and disease pathways. CSDGI is the first method to explore cancer driver genes at the cancer subtype level. We believe that it can be a useful method to understand the mechanisms of cell transformation driving tumours.

Genomic analysis of two rare human G3P[9] rotavirus strains in Ningxia, China.

G3P (Matthijnssens et al., 2008b [9]) is a rare combination of human rotavirus VP7/VP4 genotypes with a complex evolutionary pattern but limited related studies. Detailed genomic characterisation and genetic evolutionary analyses of G3P (Matthijnssens et al., 2008b [9]) rotaviruses have helped to enhance our understanding of rotavirus diversity. For the first time, we detected two human G3P (Matthijnssens et al., 2008b [9]) Rotavirus A (RVA) strains, RVA/Human-tc/CHN/2020999/2020/G3P (Matthijnssens et al., 2008b [9]) and RVA/Human-wt/CHN/23582009/2023/G3P (Matthijnssens et al., 2008b [9]), in diarrhoea patients from the Ningxia region of China, and carried out a whole-genome analysis of these strains. 2,020,999 and 23,582,009 have identical gene constellations: G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3, and this genotypic constellation was reported first time in China. They are closely related in 11 genome segments. The genotypes of these two strains are different from the human RVA strains L621 and E2451, which are only G3P (Matthijnssens et al., 2008b [9]) strains reported so far in China, but are identical to those of the Thai feline strain Meesuk and the Korean human strain CAU12-2-51.Phylogenetic analysis showed that the VP6, VP1-VP3, and NSP2 genes of the two strains in this study clustered with human/bovine and feline/bovine rotavirus strains to form a sublineage distinct from the common DS-1-like G2 human rotavirus. In contrast, the VP7, VP4, NSP1, and NSP3-NSP5 gene segments were closely associated with human/feline rotavirus and feline rotavirus strains. These findings suggest that the evolutionary origin of the G3P (Matthijnssens et al., 2008b [9]) human rotavirus found in Ningxia, China, is consistent with the Meesuk and CAU12-2-51 strains， may have arisen through reassortment between uncommon human/bovine， feline/bovine rotavirus strains and human/feline， feline rotaviruses. However, VP1-VP2 gene segments did not have the same lineage as strains Meesuk and CAU12-2-51, suggesting that these genes might be derived from additional reassortment event.

Determination and analysis of whole genome sequence of recombinant GII.6[P7] norovirus in Ningxia, China.

While the GII.4 norovirus was the predominant genotype, non-GII.4 genotype was increasingly focused since the non-GII.4 genotype caused regional epidemics. In this study, the detection rate was16.51% (183/1108) in Ningxia from January to December 2020. Among identified genotypes, GII.4[P31] and GII.4[P16] were the dominant genotypes (n = 20 and 18, respectively) while GII.6[P7] was the main type (n = 6) in non-GII.4 strains which was mainly detected in from May to July. The whole genome sequences of the norovirus diarrhea samples identified as GII.6 [P7] with Ct ≤ 30 collected in 2020 were determined. In this study, the complete genome sequences of norovirus strains PL20-044 and QTX20-071 were identified and analyzed phylogenetically. Phylogenetic analysis of the ORF1and ORF2 regions showed that these strains evolved from the GII·P7-GII.6 strains detected in recent years from different country. The results showed that PL20-044 had intra-type recombination with GII·P7-GII.6c and GII·P7-GII.6a, while QTX20-071 had intre-type recombination within GII·P7-GII.6a. The evolutionary rates of the RdRp gene region of the GII·P7 genotype and the VP1 gene region of the GII.6 genotype were 2.91 × 10-3 (95%HPDs2.32-3.51 × 10-3) and 2.61 × 10-3 (95%HPDs2.14-3.11 × 10-3) substitutions/site/year, respectively. Comparative analysis of the amino acid mutation sites in VP1 with the GII·P7-GII.6a strains before 1997, the later detected strains have changed in aa131 and aa354. Moreover, PL20-044 strains showed special mutations at aa316 and aa395. These results help to understand the norovirus genotype circulating in the human population in Ningxia, and discover the evolutionary characteristics of the GII·P7-GII.6 strain.

Surveillance of human Group A rotavirus in Ningxia, China (2015-2021): Emergence and prevalence of G9P[8]-E2 and G3P[8]-E2 genotypes.

BACKGROUND: Group A rotaviruses (RVA) are the primary pathogens of acute gastroenteritis. Currently, two live attenuated RVA vaccines, LLR and RotaTeq, have been introduced into mainland China but are not included in the national immunization program. Because of the unknown genetic evolution of group A rotavirus in an all-age population in Ningxia, China, we monitored the epidemiological characteristics and circulating genotypes of RVA as a reference for developing vaccine strategies. METHODS: We conducted seven years of consecutive surveillance of RVA based on stool samples from patients with acute gastroenteritis in sentinel hospitals in Ningxia, China, from 2015 to 2021. Reverse transcription quantitative polymerase chain reaction(RT-qPCR) was used to detect RVA in stool samples. Genotyping and phylogenetic analysis of VP7, VP4 and NSP4 genes were performed by reverse transcription-polymerase chain reaction(RT-PCR) and nucleotide sequence determination. RESULTS: RVA was detected in 16.58% (1436/8662) of 8662 stool samples. The positive rates were 7.17% (201/2805) and 21.09% (1235/5857) in adults and children, respectively. The most affected age group was infants and children aged 12-23 months, with a positive rate of 29.53% (p < 0.05). A significant winter/spring seasonality was observed. 23.29% positive rate in 2020 was the highest in 7 years (p < 0.05). The region with the highest positive rate in the adult group was Yinchuan, and the children's group was Guyuan. A total of 9 genotype combinations were found to be distributed in Ningxia. The dominant genotype combinations in this region gradually changed from G9P[8]-E1, G3P[8]-E1, G1P[8]-E1 to G9P[8]-E1, G9P[8]-E2, and G3P[8]-E2 during these seven years. Rare strains (e.g., G9P[4]-E1, G3P[9]-E3 and G1P[8]-E2) were occasionally detected during the study. CONCLUSIONS: During the study period, changes in the significant RVA circulating genotype combinations and the emergence of reassortment strains were observed, particularly the emergence and prevalence of G9P[8]-E2, G3P[8]-E2 reassortants in the region. These results indicate the importance of continuous monitoring of the molecular evolution and recombination characteristics of RVA, and should not be limited to G/P genotyping but should consider multi-gene fragment co-analysis and whole genome sequencing.

Delivery of AntagomiR-7 through polymer nanoparticles for assisting B Cell to alleviate systemic lupus erythematosus.

An autoimmune condition known as systemic lupus erythematosus (SLE) is characterized by B cell hyperresponsiveness and persistent generation of pathogenic autoantibodies that cause damage to various organs and tissues. The treatments available today are either ineffective or have adverse effects. The dysregulation of B cell activation is crucial for the emergence of SLE. MiR-7 explicitly targeted PTEN mRNA in B cells. Treatment with antagomiR-7 reduced B cell hyperresponsiveness and prevented the onset of lupus. As a result, inhibiting miR-7 may be used therapeutically to treat SLE. We developed a SA (sialic acid)-poly (D, L-lactide-co-glycolide) (SA-PLGA) nano delivery system to deliver antagomiR-7 into splenic B cells since the stability and targeted delivery of miRNA remain significant challenges in vivo. Results show that SA-PLGA nanoparticles (SA-PLGA@antagomiR-7) loaded with antagomiR-7 display good biocompatibility and shield antagomiR-7 from degradation, extending the miRNA's duration in circulation in vivo. Additionally, in MRL/Ipr lupus mice, SA-PLGA@antagomiR-7 is successfully delivered to the splenic B cells and preferentially enriched in the diseased spleen in MRL/Ipr lupus mice. The SA-PLGA@antagomiR-7 NPs therapy effectively decreases immunological abnormalities, normalizes splenic B cell subtypes, and suppresses B cell activation. The antagomiR-7 NPs exhibit excellent therapeutic efficiency and high biosafety collectively, which may result in a more effective treatment for SLE.

AAFL: automatic association feature learning for gene signature identification of cancer subtypes in single-cell RNA-seq data.

Single-cell RNA-sequencing (scRNA-seq) technologies have enabled the study of human cancers in individual cells, which explores the cellular heterogeneity and the genotypic status of tumors. Gene signature identification plays an important role in the precise classification of cancer subtypes. However, most existing gene selection methods only select the same informative genes for each subtype. In this study, we propose a novel gene selection method, automatic association feature learning (AAFL), which automatically identifies different gene signatures for different cell subpopulations (cancer subtypes) at the same time. The proposed AAFL method combines the residual network with the low-rank network, which selects genes that are most associated with the corresponding cell subpopulations. Moreover, the differential expression genes are acquired before gene selection to filter the redundant genes. We apply the proposed feature learning method to the real cancer scRNA-seq data sets (melanoma) to identify cancer subtypes and detect gene signatures of identified cancer subtypes. The experimental results demonstrate that the proposed method can automatically identify different gene signatures for identified cancer subtypes. Gene ontology enrichment analysis shows that the identified gene signatures of different subtypes reveal the key biological processes and pathways. These gene signatures are expected to bring important implications for understanding cellular heterogeneity and the complex ecosystem of tumors.

Rasburicase-Induced Falsely Low Measurement of Uric Acid in Tumor Lysis Syndrome: A Report of Two Cases.

Rasburicase, a recombinant urate-oxidase enzyme, can significantly catalyze the oxidation of uric acid to allantoin. It was approved by the US Food and Drug Administration (FDA) to control blood uric acid levels in both pediatric and adult patients especially those with tumor lysis syndrome. It is quite important to realize that rasburicase can continue to be effective ex vivo and cause falsely low results if the blood sample is not contained and transported in ice water immediately. We presented two cases of falsely low measurement of blood uric acid caused by rasburicase and elaborated the proper method for collecting and transporting blood samples from patients using rasburicase.

Molecular evolution and antigenic drift of type 3 iVDPVs excreted from a patient with immunodeficiency in Ningxia, China.

A 2.5-year-old pediatric patient with acute flaccid paralysis was diagnosed with primary immunodeficiency (PID) in Ningxia Province, China, in 2011. Twelve consecutive stool specimens were collected from the patient over a period of 10 months (18 February 2011 to 20 November 2011), and 12 immunodeficiency vaccine-derived poliovirus (iVDPV) strains (CHN15017-1 to CHN15017-12) were subsequently isolated. Nucleotide sequencing analysis of the plaque-purified iVDPVs revealed 2%-3.5% VP1-region differences from their parental Sabin 3 strain. Full-length genome sequencing showed they were all Sabin 3/Sabin 1 recombinants, sharing a common 2C-region crossover site, and the two key determinants of attenuation (U472C in the 5' untranslated region and T2493C in the VP1 region) had reverted. Temperature-sensitive experiments demonstrated that the first two iVDPV strains partially retained the temperature-sensitive phenotype's nature, while the subsequent ten iVDPV strains distinctly lost it, possibly associated with increased neurovirulence. Nineteen amino-acid substitutions were detected between 12 iVDPVs and the parental Sabin strain, of which only one (K1419R) was found on the subsequent 10 iVDPV isolates, suggesting this site's potential as a temperature-sensitive determination site. A Bayesian Monte Carlo Markov Chain phylogenetic analysis based on the P1 coding region yielded a mean iVDPV evolutionary rate of 1.02 × 10-2 total substitutions/site/year, and the initial oral-polio-vaccine dose was presumably administered around June 2009. Our findings provide valuable information regarding the genetic structure, high-temperature growth sensitivity, and antigenic properties of iVDPVs following long-term evolution in a single PID patient, thus augmenting the currently limited knowledge regarding the dynamic changes and evolutionary pathway of iVDPV populations with PID during long-term global replication.

Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway.

Background: Postmenopausal osteoporosis (PMOP) is the most common primary osteoporosis, which is prone to fractures and affect the health and quality of life of the elderly and even shorten their lifetime. Traditional Chinese medicine can not only effectively improve osteoporosis and reduce fracture rate, but also have tonifying and analgesic effects. The purpose of this study was to investigate the effects of Zhuanggu Zhitong (ZGZT) Capsule on autophagy related genes and proteins in PMOP rats, so as to elucidate the molecular mechanism of tonifying deficiency and regulating stasis in the treatment of osteoporosis and analgesia. Methods: The PMOP rat model was established by bilateral oophorectomy, and then the rats were randomly divided into control group, PMOP group, PMOP + ZGZT group and PMOP + E2 group. The changes of mechanical pain threshold of rats were detected by von Frey filaments, and the changes of mechanical pain threshold of rats in each group were compared. Computed tomography (CT) and dual-energy X-ray were used to measure the bone mineral density of lumbar bone tissue. Enzyme-linked immunosorbent assay (ELISA) and tartrate-resistant acid phosphatase (TRAP) staining were used to detect inflammatory factors and bone metabolism related indicators. Hematoxylin-eosin (HE) staining was used to observe the tissue morphology of lumbar vertebra tissue. Western blot (WB) and quantitative polymerase chain reaction (qPCR) were used to detect AMPK/mTOR pathway- and autophagy-related factor expression. Results: ZGZT can effectively restore the bone mineral density (BMD) of PMOP rats, improve the microstructure of lumbar vertebra of PMOP rats, restore the balance of bone metabolism, promote the expression of AMPK and autophagy related factors, inhibit the expression of mTOR and the release of inflammatory factors, and increase the mechanical pain threshold of PMOP rats, so as to effectively improve osteoporosis and relieving osteoporosis pain in PMOP rats. Conclusions: ZGZT affects autophagy by regulating AMPK/mTOR pathway, restores the homeostasis of bone metabolism and inhibits the release of inflammatory factors. Moreover, the regulation of feedback pathways between bone metabolism and inflammatory factors finally plays the role of "bone strengthening" and "pain relieving". ZGZT may be a new treatment for PMOP and relieving osteoporotic pain.

Differences in actionable genomic alterations between brain metastases and non­brain metastases in patients with non­small cell lung cancer.

Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non­small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture­based next­generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non­BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel­Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co­enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non­BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma­derived circulating tumor DNA (ctDNA) in the non­BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non­BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.

Combined strategy of knowledge-based rule selection and historical data percentile-based range determination to improve an autoverification system for clinical chemistry test results.

BACKGROUND: Current autoverification, which is only knowledge-based, has low efficiency. Regular historical data analysis may improve autoverification range determination. We attempted to enhance autoverification by selecting autoverification rules by knowledge and ranges from historical data. This new system was compared with the original knowledge-based system. METHODS: New types of rules, extreme values, and consistency checks were added and the autoverification workflow was rearranged to construct a framework. Criteria for creating rules for extreme value ranges, limit checks, consistency checks, and delta checks were determined by analyzing historical Zhongshan laboratory data. The new system's effectiveness was evaluated using pooled data from 20 centers. Efficiency improvement was assessed by a multicenter process. RESULTS: Effectiveness was evaluated by the true positive rate, true negative rate, and overall consistency rate, as compared to manual verification, which were 77.55%, 78.53%, and 78.3%, respectively for the new system. The original overall consistency rate was 56.2%. The new pass rates, indicating efficiency, were increased by 19%-51% among hospitals. Further customization using individualized data increased this rate. CONCLUSIONS: The improved system showed a comparable effectiveness and markedly increased efficiency. This transferable system could be further improved and popularized by utilizing historical data from each hospital.

Incidence and risk factors of preoperative deep venous thrombosis in closed tibial shaft fracture: a prospective cohort study.

OBJECTIVE: To investigate the preoperative morbidity of deep venous thrombosis (DVT) and predictive risk factors associated with DVT after closed tibial shaft fracture. METHODS: Ultrasonography and blood analyses were performed preoperatively in patients who sustained tibial shaft fracture between October 2014 and December 2018. Univariate analyses were used in the data of demographics, comorbidities, mechanism of injury, concomitant fractures and laboratory biomarkers. Multivariate logistic regression analyses were conducted to determine the independent risk factors associated with DVT. RESULTS: In total, 918 patients with an operatively treated tibial shaft fracture were included, among whom 122 patients had preoperative DVTs, indicating a crude morbidity of 13.3%. Ninety-two of 758 (12.1%) patients with isolated tibial shaft fracture developed DVT, while 30 of 160 (18.8%) patients with concurrent fracture presented with DVT. The average interval between fracture and initial diagnosis of DVT was 3.1 days (median, 2 days), ranging from 0 to 33 days. Among DVT-positive patients, 16 (13.1%) patients presented with proximal DVT and 106 (86.9%) patients had distal DVT. Multivariate logistic regression analysis showed four independent risk factors were significantly correlated to the development of DVT, including increased age (OR = 1.17, p = 0.003), diabetes (OR = 1.99, p = 0.009), serum hydroxybutyrate dehydrogenase > 182 U/L (OR = 1.83, p = 0.008), and delay to DUS (in each day) (OR = 1.13, p < 0.001). CONCLUSION: In the present cohort study, the incidence of DVT was 12.1% in patients with isolated tibial shaft fracture. We suggest individualized risk stratification and early anticoagulation for patients with high risk factors including pre-existing diabetes, HBDH > 182 U/L, delay to DUS and older age. LEVEL OF EVIDENCE: Level III, a prospective cohort study.

Inferring cell developmental stage-specific lncRNA regulation in the developing human neocortex with CDSlncR.

Noncoding RNAs (ncRNAs) occupy ~98% of the transcriptome in human, and are usually not translated into proteins. Among ncRNAs, long non-coding RNAs (lncRNAs, >200 nucleotides) are important regulators to modulate gene expression, and are involved in many biological processes (e.g., cell development). To study lncRNA regulation, many computational approaches or tools have been proposed by using bulk transcriptomics data. Nevertheless, previous bulk data-driven methods are mostly limited to explore the lncRNA regulation regarding all of cells, instead of the lncRNA regulation specific to cell developmental stages. Fortunately, recent advance in single-cell sequencing data has provided a way to investigate cell developmental stage-specific lncRNA regulation. In this work, we present a novel computational method, CDSlncR (Cell Developmental Stage-specific lncRNA regulation), which combines putative lncRNA-target binding information with single-cell transcriptomics data to infer cell developmental stage-specific lncRNA regulation. For each cell developmental stage, CDSlncR constructs a cell developmental stage-specific lncRNA regulatory network in the cell developmental stage. To illustrate the effectiveness of CDSlncR, we apply CDSlncR into single-cell transcriptomics data of the developing human neocortex for exploring lncRNA regulation across different human neocortex developmental stages. Network analysis shows that the lncRNA regulation is unique in each developmental stage of human neocortex. As a case study, we also perform particular analysis on the cell developmental stage-specific lncRNA regulation related to 18 known lncRNA biomarkers in autism spectrum disorder. Finally, the comparison result indicates that CDSlncR is an effective method for predicting cell developmental stage-specific lncRNA targets. CDSlncR is available at https://github.com/linxi159/CDSlncR.

Epidemiological Characteristics of Major Joints Fracture-Dislocations.

OBJECTIVE: To describe the epidemiological features of major joints fracture-dislocations between 2015 and 2019. METHODS: This retrospective study enrolled patients with majorintra-articular fracture-dislocations who were treated in the third hospital of Hebei Medical University from January 2015 to December 2019. A total of 582 patients (389 [66.84%] males and 193 [33.16%] females) were identified. The distribution characteristics of intra-articular fracture-dislocations involving shoulder, elbow, wrist, hip, knee, and ankle joints were included. The potential associations between fractures with concomitant dislocations and related factors, such as age, gender and sites were explored. RESULTS: There were 92 cases (15.81%) of shoulder joints, 67 cases (11.51%) of elbow joints, 45 cases (7.73%) of wrist joints, 181 cases (31.10%) of hip joints, 42 cases (7.22%) of knee joints, and 155 cases (26.63%) of ankle joints. The overall male-to-female ratio was 2.02:1.The highest proportion age group of the six types intra-articular fracture-dislocations included the ages 25-34 years. For males, the highest proportion age group was 25-34 years, for females, it was 45-54 years. For male patients, hip was the most common, accounted for 35.48%, but ankle fracture-dislocation was the most common for females, accounted for 30.57%. The highest proportion age group of shoulder fracture-dislocation included the ages 55-64 years(22.83%), with a male to female ratio of 1.24:1. While the age group with the highest risk of elbow, wrist, hip, knee and ankle fracture- dislocation was 25-34 years (28.36%) with a male to female ratio of 2.19:1, 25-34 years (31.11%) with a male to female ratio of 8:1, 45-54 years (27.07%) with a male to female ratio of 3.21:1, 15-24 years (45.24%) with a male to female ratio of 0.75:1, 25-44 years (43.87%) with a male to female ratio of 1.63:1, respectively. The most common site of joint fracture-dislocation in different age groups was corresponding as follows, 0-14 years(elbow), 15-24 years(knee), 25-34 years(hip), 35-44 years(hip), 45-54 years(hip), 55-64 years(ankle), 65-74 years(shoulder), ≥75 years(shoulder). CONCLUSION: Major joints fracture-dislocations were most common in the hip and the least common in the knee, and there were more men than women. Hip was the most common affected joint in men while ankle in women. Age and sex factors can significantly affect the location of intra articular fracture and dislocation. The current study could aid orthopaedic surgeons in a better understanding of this injury and help to implement targeted preventive measures.

A Knowledge Graph Entity Disambiguation Method Based on Entity-Relationship Embedding and Graph Structure Embedding.

The purpose of knowledge graph entity disambiguation is to match the ambiguous entities to the corresponding entities in the knowledge graph. Current entity ambiguity elimination methods usually use the context information of the entity and its attributes to obtain the mention embedding vector, compare it with the candidate entity embedding vector for similarity, and perform entity matching through the similarity. The disadvantage of this type of method is that it ignores the structural characteristics of the knowledge graph where the entity is located, that is, the connection between the entity and the entity, and therefore cannot obtain the global semantic features of the entity. To improve the Precision and Recall of entity disambiguation problems, we propose the EDEGE (Entity Disambiguation based on Entity and Graph Embedding) method, which utilizes the semantic embedding vector of entity relationship and the embedding vector of subgraph structure feature. EDEGE first trains the semantic vector of the entity relationship, then trains the graph structure vector of the subgraph where the entity is located, and balances the weights of these two vectors through the entity similarity function. Finally, the balanced vector is input into the graph neural network, and the matching between the entities is output to achieve entity disambiguation. Extensive experimental results proved the effectiveness of the proposed method. Among them, on the ACE2004 data set, the Precision, Recall, and F1 values of EDEGE are 9.2%, 7%, and 11.2% higher than baseline methods.