Ultrasound-based radiomics machine learning models for diagnosing cervical lymph node metastasis in patients with non-small cell lung cancer: a multicentre study.

BACKGROUND: Cervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC. METHODS: This study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively. RESULTS: In total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781-0.961) and 0.883 (range: 0.798-0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862-0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837-0.966) and 0.922 (range: 0.872-0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886-0.968). CONCLUSIONS: The ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.

Large regions of homozygosity in prenatal diagnosis.

Chromosomal microarrays (CMA) incorporate single nucleotide polymorphisms to enable the detection of regions of homozygosity (ROH). Here, we retrospectively analyzed 6288 prenatal cases who performed CMA to explored the clinical implications of large ROH in prenatal diagnosis. We analyzed cases with ROH larger than 10 megabases and reviewed the ultrasound findings; karyotype results and pregnancy follow-up data. Cases with possible imprinting disorders were assessed by methylation-specific multiplex ligation-dependent probe amplification. In total, we identified 50 cases with large ROH and chromosomes 1 and 2 were the most affected. About 59.18% of the ROH cases had ultrasound abnormalities, with the most common findings being ultrasound soft-marker abnormalities. There were seven fetuses had ROH which covered almost the entire chromosome and four had terminal ROH that involved almost the entire long arm of the chromosomes, which indicated uniparental disomy (UPD), of which 70% showed abnormal ultrasound findings. Ten cases with multiple ROH on different chromosomes indicated the third to fifth degree of consanguinity. In this study, we highlighted the clinical relevance of large ROH related to UPD. The analysis of ROH allowed us to gain further understanding of complex cytogenetic and disease mechanisms in prenatal diagnosis.

Diagnosis of cutaneous primary nocardiosis in patients with normal immune function by metagenomic next-generation sequencing.

Nocardia primarily affects immunocompromised individuals, and Infection with Nocardia is uncommon and primary cutaneous nocardiosis caused by percutaneous inoculation is even rarer. Primary cutaneous nocardiosis remains a diagnostic challenge and should be considered in the differential diagnosis for any superficial cutaneous infection that arises in patients with normal immune function. We report a case that was diagnosed with primary cutaneous Nocardia by metagenomic next-generation sequencing technology.

Systematic proteomics profiling of lysine crotonylation of the lung at Pseudoglandular and Canalicular phases in human fetus.

Lung tissue is an important organ of the fetus, and genomic research on its development has improved our understanding of the biology of this tissue. However, the proteomic research of developing fetal lung tissue is still very scarce. We conducted comprehensive analysis of two developmental stages of fetal lung tissue of proteomics. It showed the developmental characteristics of lung tissue, such as the down-regulation of metabolism-related protein expression, the up-regulation of cell cycle-related proteins, and the regulation in proteins and pathways related to lung development. In addition, we also discovered some key core proteins related to lung development, and provided some key crotonylation modification sites that regulation during lung tissue development. Our comprehensive analysis of lung proteomics can provide a more comprehensive understanding of the developmental status of lung tissue, and provide a certain reference for future research and epigenetics of lung tissue.

Dermoscopy in Mycobacterium marinum infection and its correlation with clinical and histopathological features: a prospective observational study.

BACKGROUND: Mycobacterium marinum is a nontuberculous mycobacterium and a conditional pathogen to humans, which can be inoculated directly and cause chronic skin granulomas. Dermoscopy has been applied to other granulomatous skin diseases, but not to M. marinum infection. AIM: To explore the dermoscopic features of M. marinum infection, and its correlation with clinical and histopathological features. METHODS: In total, 27 lesions from 27 patients (19 women, 8 men, age range 28-71 years) diagnosed with M. marinum infection were identified by clinical examination, histopathological results, PCR sequencing and mycobacterial culture in the dermatology outpatient department of our hospital from March 2020 to February 2022. The dermoscopy images and pathological characteristics were analysed. RESULTS: Lesions were located on the hands, forearms and upper arms. The following dermoscopic features were observed: yellowish-orange structureless areas (85·2%), white striped structures (59·3%), follicular plugs (29·6%), yellowish oval clods (14·8%) and reddish or pinkish areas (14·8%). Vessel structures were visible in all cases: long hairpin vessels (81·5%), corkscrew vessels (25·9%), comma-shaped vessels (22·2%) and linear vessels (22·2%). CONCLUSION: Yellowish-orange structureless areas, white striped structures and long hairpin vessels are the most common dermoscopic features of M. marinum infection. Thus, dermoscopy could be used as a noninvasive auxiliary diagnostic method to provide a diagnostic basis for this disease.

[Prenatal diagnosis and genetic analysis of a fetus with partial deletion of Yq and mosaicism of 45,X].

OBJECTIVE: To carry out prenatal diagnosis and genetic analysis for a fetus with disorders of sex development (DSDs). METHODS: A fetus with DSDs who was identified at the Shenzhen People's Hospital in September 2021 was selected as the study subject. Combined molecular genetic techniques including quantitative fluorescence PCR (QF-PCR), multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis (CMA), quantitative real-time PCR (qPCR), as well as cytogenetic techniques such as karyotyping analysis and fluorescence in situ hybridization (FISH) were applied. Ultrasonography was used to observe the phenotype of sex development. RESULTS: Molecular genetic testing suggested that the fetus had mosaicism of Yq11.222qter deletion and X monosomy. Combined with the result of cytogenetic testing, its karyotype was determined as mos 45,X[34]/46,X,del(Y)(q11.222)[61]/47,X,del(Y)(q11.222),del(Y)(q11.222)[5]. Ultrasound examination suggested hypospadia, which was confirmed after elective abortion. Combined the results of genetic testing and phenotypic analysis, the fetus was ultimately diagnosed with DSDs. CONCLUSION: This study has applied a variety of genetic techniques and ultrasonography to diagnose a fetus with DSDs with a complex karyotype.

Muti-Frame Point Cloud Feature Fusion Based on Attention Mechanisms for 3D Object Detection.

Continuous frames of point-cloud-based object detection is a new research direction. Currently, most research studies fuse multi-frame point clouds using concatenation-based methods. The method aligns different frames by using information on GPS, IMU, etc. However, this fusion method can only align static objects and not moving objects. In this paper, we proposed a non-local-based multi-scale feature fusion method, which can handle both moving and static objects without GPS- and IMU-based registrations. Considering that non-local methods are resource-consuming, we proposed a novel simplified non-local block based on the sparsity of the point cloud. By filtering out empty units, memory consumption decreased by 99.93%. In addition, triple attention is adopted to enhance the key information on the object and suppresses background noise, further benefiting non-local-based feature fusion methods. Finally, we verify the method based on PointPillars and CenterPoint. Experimental results show that the mAP of the proposed method improved by 3.9% and 4.1% in mAP compared with concatenation-based fusion modules, PointPillars-2 and CenterPoint-2, respectively. In addition, the proposed network outperforms powerful 3D-VID by 1.2% in mAP.

Macrophages Rapidly Seal off the Punctured Zebrafish Larval Brain through a Vital Honeycomb Network Structure.

There is accumulating evidence that macrophages play additional important roles in tissue damage besides their typical phagocytosis. Although the aggregation of macrophages on injured sites has long been observed, few researchers have focused on the role of the overall structure of macrophage aggregation. In this study, we developed a standardized traumatic brain injury (TBI) model in zebrafish larvae to mimic edema and brain tissue spillage symptoms after severe brain trauma. Using time-lapse imaging, we showed that macrophages/microglia in zebrafish larvae responded rapidly and dominated the surface of injured tissue, forming a meaningful honeycomb network structure through their compact aggregation and connection. Disrupting this structure led to fatal edema-like symptoms with severe loss of brain tissue. Using the RNA-Seq, together with the manipulation of in vitro cell lines, we found that collagen IV was indispensable to the formation of honeycomb network structures. Our study thus revealed a novel perspective regarding macrophages forming a protective compact structure with collagen IV. This honeycomb network structure acted as a physical barrier to prevent tissue loss and maintain brain homeostasis after TBI. This study may provide new evidence of macrophages' function for the rapid protection of brain tissue after brain injury.

Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia.

Preeclampsia (PE) is a dangerous hypertensive disorder that occurs during pregnancy. The specific aetiology and pathogenesis of PE have yet to be clarified. To better reveal the specific pathogenesis of PE, we characterized the proteome and acetyl proteome (acetylome) profile of placental tissue from PE and normal-term pregnancy by label-free quantification proteomics technology and PRM analysis. In this research, 373 differentially expressed proteins (DEPs) were identified by proteome analysis. Functional enrichment analysis revealed significant enrichment of DEPs related to angiogenesis and the immune system. COL12A1, C4BPA and F13A1 may be potential biomarkers for PE diagnosis and new therapeutic targets. Additionally, 700 Kac sites were identified on 585 differentially acetylated proteins (DAPs) by acetylome analyses. These DAPs may participate in the occurrence and development of PE by affecting the complement and coagulation cascades pathway, which may have important implications for better understand the pathogenesis of PE. In conclusion, this study systematically analysed the reveals critical features of placental proteins in pregnant women with PE, providing a resource for exploring the contribution of lysine acetylation modification to PE.

Rapid orderly migration of neutrophils after traumatic brain injury depends on MMP9/13.

Macrophages and granulocytes play an important role in various injuries and post-traumatic repair. Due to the limited number of neutrophils in the brain, their role in traumatic brain injury has rarely been mentioned. Here, neutrophils were found to take over the role of macrophages after brain injury in the absence of macrophages. Neutrophils have the characteristics of long residence time and number advantage to actively remove the apoptotic debris. The number of neutrophils recruited was effectively reduced by inhibiting IL-1ß. Interestingly, neutrophils migrated regularly and rapidly to the wound during the early stages of brain injury through three paths. They first infiltrated the wound mainly through blood circulation around the eyes, then became unscrupulous and began to move directly across the brain. In addition, MMP9 and MMP13 were found to be related to the migration of neutrophils, and inhibition of MMP could significantly inhibit the number and speed of neutrophils' migration. Our study showed that neutrophils rely on MMP9 and MMP13 for a rapid and orderly response to brain injury to maintain central nervous system stability in the absence or decrease of macrophages.

Exosomal miR-146a-5p from Treponema pallidum-stimulated macrophages reduces endothelial cells permeability and monocyte transendothelial migration by targeting JAM-C.

Exosomal microRNAs (miRNAs) transferred between cells have been implicated in modulating the host immune response in microbial infections. In this study, we isolated exosomes from Treponema pallidum (T. pallidum)-stimulated macrophages and detected differential exosomal miRNA expression using both microarrays, and RT-qPCR. A total of 65 differentially expressed miRNAs (35 upregulated and 30 downregulated) were identified. Of all identified miRNAs, miR-146a-5p was one of the most significantly changed miRNAs with high expression in exosomes from T. pallidum-stimulated macrophages. Furthermore, we isolated plasma exosomes from early syphilis patients and healthy controls, and confirmed miR-146a-5p upregulation in the former group. We also show that exosomal miR-146a-5p is efficiently transported into endothelial cells, reducing monocyte transendothelial migration and endothelial permeability by targeting junctional adhesion molecule C (JAM-C). Luciferase reporter assays confirmed binding of exosomal miR-146a-5p to the 3'untranslated region (3'UTR) of JAM-C. We then demonstrated that also exosomes derived from macrophages stimulated by T. pallidum expressed high levels of miR-146a-5p which could be delivered to endothelial cells, and decreased monocyte transendothelial migration by targeting JAM-C. Overall, this work provides novel insights into the mechanism by which T. pallidum hampers inflammatory reactions of the host via a blockade of leukocytes transendothelial migration and endothelial permeability.

[Genetic analysis of a family with 9q34.3 microdeletion and microduplication caused by abnormal chromosome balance structure].

OBJECTIVE: To perform prenatal diagnosis, pedigree analysis, and genetic counseling of a pregnant woman who gave birth to a child with Kleefstra syndrome. METHODS: Karyotype analysis, chromosomal microarray analysis (CMA), multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were used of peripheral blood and amniotic fluid to find causes. Recurrence risk assessment was performed later. RESULTS: The amniotic fluid sample showed a 9q34.3 microduplication of arr (hg19) 9q34.3 (140 168 806-141 020 389)× 3, which overlapped the 9q34.3 microdeletion region of proband. The pregnant woman was detected with a balanced translocation of ish, t(9;17)(9q34.3; qter) (9p+; 17p+,9q+, 17q+). No other abnormal results were found in the family. CONCLUSION: Offspring who share the same chromosome segment deletion or duplication are always from parent who carries balanced chromosomal structural aberration.

Decreased blood natural killer cells in serofast patients: a systematic review and meta-analysis.

Currently, increasing attention has been paid to the association of the serofast status with natural killer (NK) cells. Remarkable diversity among the results of different studies has been observed. We conducted this meta-analysis to evaluate the variation of the proportion of NK cells in serofast patients compared with that of healthy controls and cured patients. Through the designed retrieval methods, 631 serofast patients, 562 healthy controls and 160 patients whose serology turned negative following treatment were derived from 16 publications for further analysis. The established items were used for the standard selection and quality assessment. The Stata software was used for meta-analysis. The final results indicated that serofast patients exhibited a dramatic decrease in the number of NK cells in the peripheral blood compared with that noted in healthy control subjects [standardized mean difference (SMD) = -0.63, 95% CI (-1.08, -0.17), p = 0.007]. The proportion of NK cells was significantly lower in serofast patients than that noted in cured patients [SMD = -0.25, 95% CI (-0.48, -0.02), p = 0.033] and no significant difference was noted in the proportion of NK cells between cured patients and healthy controls [SMD = -0.39, 95% CI (-0.93, 0.14), p = 0.148]. The present meta-analysis indicated that the proportion of NK cells in the peripheral blood was significantly lower in serofast patients compared with that of the healthy controls and cured patients, indicating that the reduction in the number of NK cells may be closely associated with the syphilis serofast status.

[FOXO4 maintains senescence in human umbilical cord mesenchymal stem cells by repressing apoptosis].

The purpose of the present study was to investigate the effects of forkhead box O4 (FOXO4) on the senescence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSCs were induced to senescence by natural passage, and FOXO4 expression was inhibited by lentiviral shRNA transfection. The hallmark of cell senescence was analyzed by ß-galactosidase staining, and the cell viability was assayed by CCK-8 method. Flow cytometry was used to investigate the apoptosis of hUC-MSCs. The expression levels of Bcl-2, Bax, FOXO4, interleukin 6 (IL-6) and cleaved Caspase-3 were detected by qPCR and Western blot. Immunofluorescence staining was used to detect FOXO4 expression. The amount of IL-6 secreted by hUC-MSCs was detected by ELISA. The results showed that, compared with the passage 1, senescent hUC-MSCs showed up-regulated expression levels of Bax and FOXO4, down-regulated expression levels of Bcl-2 and cleaved Caspase-3, and increased IL-6 mRNA expression and secretion. FOXO4 inhibition in senescent hUC-MSCs promoted cell apoptosis, reduced cell viability, and inhibited the mRNA expression and secretion of IL-6. These results suggest that FOXO4 maintains viability and function of senescent hUC-MSCs by repressing their apoptosis response, thus accelerating senescence of the whole cell colony.

Successful Treatment of Eczema-Like Mucormycosis in a Child by Combination of Intravenous Drip and Percutaneous Injection Amphotericin B.

We report a case of eczema-like cutaneous mucormycosis caused by Rhizopus arrhizus. A 4-year-old child was presented to our hospital with a history of gradually enlarging papule and plaque in the periumbilical area for nearly 4 years since 2 weeks after his birth, and it has been misdiagnosed as eczema for nearly 3 years. Based on histopathology examination, the fungus culture test and DNA sequencing, it was revealed that R. arrhizus should be the responsible fungus for skin infection. The patient was successfully cured by combination of intravenous drip and percutaneous injection amphotericin B for nearly 3 months, and no recrudescence was seen during a follow-up of 6-month observation.

Evaluation of IL-17A, IL-17F, IL-23R, VDR, CCL2, CCL5, CCR2, and CCR5 gene polymorphisms and expression in Chinese individuals with syphilis.

Syphilis is a sexually transmitted disease caused by the infection of Treponema pallidum subspecies pallidum. T-helper type 17-related genes, vitamin D receptor (VDR) gene, and chemokine/chemokine receptor genes are crucial in microbial infection. A total of 16 single-nucleotide polymorphisms (SNPs) in eight genes (interleukin [IL]-17A, IL-17F, IL-23R, VDR, C-C motif chemokine ligand [CCL] 2, CCL5, C-C chemokine receptor [CCR] 2, and CCR5) were analyzed in 188 patients with syphilis and 216 healthy controls. The results showed a strong correlation of IL-17A rs2275913 (AA vs AG + GG: odds ratio [OR], 1.78; 95% confidence interval [CI], 1.09 to 2.92; P = 0.020; A vs G: OR, 1.33; 95% CI, 1.01 to 1.76; P = 0.043) and rs3819024 (GG vs AA + GA: OR, 1.76; 95% CI, 1.06 to 2.91; P = 0.028; G vs A: OR, 1.36; 95% CI, 1.03 to 1.80; P = 0.030) with syphilis. In haplotype analysis, IL-17A rs2275913A/rs3819024G showed a risk effect (OR, 1.38; 95% CI, 1.04 to 1.82; P = 0.026), whereas IL-17A rs2275913G/rs3819024A showed a protective effect (OR, 0.76; 95% CI, 0.57 to 0.998; P = 0.048). The expression levels of IL-17A messenger RNA (mRNA) in peripheral blood mononuclear cells and IL-17A secretion in plasma were further examined. No significant differences were found between patients with syphilis and healthy controls. The study also explored whether IL-17A rs2275913 and rs3819024 were associated with the expression of IL-17A mRNA and IL-17A secretion in patients with syphilis. Similar negative results were found. In conclusion, the polymorphisms of IL-17A rs2275913 and rs3819024 and the haplotype containing these two SNPs influenced the susceptibility to syphilis in a Han Chinese population.

A Quality Assessment Method Based on Common Distributed Targets for GF-3 Polarimetric SAR Data.

The GaoFen-3 (GF-3) satellite, launched on 10 August 2016, is the first C-band polarimetric synthetic aperture radar (PolSAR) satellite in China. The PolSAR system of GF-3 can collect a significant wealth of information for geophysical research and applications. Being used for related applications, GF-3 PolSAR images must be of good quality. It is necessary to evaluate the quality of polarimetric data and achieve the normalized quality monitoring during 8-year designed life of GF-3. In this study, a new quality assessment method of PolSAR data based on common distributed targets is proposed, and the performance of the method is analyzed by simulations and GF-3 experiments. We evaluate the quality of GF-3 PolSAR data by this method. Results suggest that GF-3 antenna is highly isolated, and the quality of calibrated data satisfies the requests of quantitative applications.

A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as Treatment Agents for Early Syphilis in Jiangsu, China.

BACKGROUND: The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early syphilis because there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an human immunodeficiency virus coinfection. METHODS: A randomized, open-label controlled study evaluating the efficacy of ceftriaxone and BPG was conducted in 4 hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, given intravenously, once daily for 10 days) or BPG (2.4 million units, given intramuscularly, once weekly for 2 weeks). A serological response was defined as a ≥4-fold decline in the rapid plasma reagin (RPR) titer. RESULTS: In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The serological response at 6 months of follow up was observed in 90.2% in ceftriaxone group and 78.0% in BPG group (P = .01). There was no significant difference between treatment groups in patients with primary or early latent syphilis, but among patients with secondary syphilis the difference was highly significant (95.8% vs 76.2%; P < .01). Moreover, patients exhibiting a Jarisch-Herxheimer reaction after treatment might have a shorter period before a serological response (P = .03). CONCLUSIONS: In this study, ceftriaxone regimen was noninferior to the BPG regimen in nonpregnant, immunocompetent patients with early syphilis. CLINICAL TRIALS REGISTRATION: ChiCTR-TQR-13003624.