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Abstract Objectives This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. Methods We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. Results Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. Conclusion Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Abstract Background To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion. Results Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes. Conclusions Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.

Abstract Background Chromosomal microarray analysis (CMA) is a valuable tool in prenatal diagnosis for the detection of chromosome uniparental disomy (UPD). This retrospective study examines fetuses undergoing invasive prenatal diagnosis through Affymetrix CytoScan 750 K array analysis. We evaluated both chromosome G-banding karyotyping data and CMA results from 2007 cases subjected to amniocentesis. Results The detection rate of regions of homozygosity (ROH) ≥ 10 Mb was 1.8% (33/2007), with chromosome 11 being the most frequently implicated (17.1%, 6/33). There were three cases where UPD predicted an abnormal phenotype based on imprinted gene expression. Conclusion The integration of UPD detection by CMA offers a more precise approach to prenatal genetic diagnosis. CMA proves effective in identifying ROH and preventing the birth of children affected by imprinting diseases.

Abstract Background Vascular invasion is a major route for intrahepatic and distant metastasis in hepatocellular carcinoma (HCC) and is a strong negative prognostic factor. Circular RNAs (circRNAs) play important roles in tumorigenesis and metastasis. However, the regulatory functions and underlying mechanisms of circRNAs in the development of vascular invasion in HCC are largely unknown. Methods High throughput sequencing was used to screen dysregulated circRNAs in portal vein tumor thrombosis (PVTT) tissues. The biological functions of candidate circRNAs in the migration, vascular invasion, and metastasis of HCC cells were examined in vitro and in vivo. To explore the underlying mechanisms, RNA sequencing, MS2-tagged RNA affinity purification, mass spectrometry, and RNA immunoprecipitation assays were performed. Results circRNA sequencing followed by quantitative real-time PCR (qRT-PCR) revealed that circRNA pleckstrin and Sect. 7 domain containing 3 (circPSD3) was significantly downregulated in PVTT tissues. Decreased circPSD3 expression in HCC tissues was associated with unfavourable characteristics and predicted poor prognosis in HCC. TAR DNA-binding protein 43 (TDP43) inhibited the biogenesis of circPSD3 by interacting with the downstream intron of pre-PSD3. circPSD3 inhibited the intrahepatic vascular invasion and metastasis of HCC cells in vitro and in vivo. Serpin family B member 2 (SERPINB2), an endogenous bona fide inhibitor of the urokinase-type plasminogen activator (uPA) system, is the downstream target of circPSD3. Mechanistically, circPSD3 interacts with histone deacetylase 1 (HDAC1) to sequester it in the cytoplasm, attenuating the inhibitory effect of HDAC1 on the transcription of SERPINB2. In vitro and in vivo studies demonstrated that circPSD3 is a promising inhibitor of the uPA system. Conclusions circPSD3 is an essential regulator of vascular invasion and metastasis in HCC and may serve as a prognostic biomarker and therapeutic target.

Abstract Background Abdominal pregnancy, a rare form of ectopic pregnancy, is associated with high morbidity and adverse consequences for future fertility. Early recognition and management reduce mortality and allow minimal invasive and conservative treatment. In modern medicine, primitive prevention to unexpected fatal pregnancies is crucial. Case presentation A divorced 33-year-old “self-identified” infertile polycystic ovary woman diagnosed as repeated implantation failure in previous in vitro fertilization with her ex-husband ever presented in surgery department with a history of 15-day abdominal pain, nausea, and vomiting and 3-h worsening abdominal pain. The serum beta-human chorionic gonadotropin value was more than 10,000 m-international units per milliliter. Sonogram findings were significant for the absence of intrauterine gestation; a placenta and well-formed living fetus of second-trimester gestation were seen in the abdomen, accompanied by hemoperitoneum. A unique spontaneously second-trimester tubo-abdominal pregnancy was confirmed in emergent laparotomy by gynecologists, she received a removing of the living fetus, a right total salpingectomy, resection of partial omentum and blood transfusion. The patient recovered uneventfully and her serum beta-human chorionic gonadotropin returned to normal range on the 30th postoperative day, till now, she has weak fertility awareness because of her catastrophic experiences in the unexpected abdominal pregnancy. Conclusions This case highlights woman with a previous in vitro fertilization history may be in is a high risk to be delayed or missed in diagnosis in an intended ectopic pregnancy due to a fixed belief in infertility. Educational interventions and contraceptive care should be provided by fertility and healthcare practitioner. The possibility of abdominal pregnancy must always be suspected and dealt with promptly and appropriately by the astute clinician.

Abstract Background Genome-wide sequencing may extensively identify potential pathogenic variants, which helps to understand mechanisms of tumorigenesis, but such study has not been reported in benzene-induced leukemia (BIL). Methods We recruited 10 BIL patients and conducted the whole-exome sequencing on their peripheral blood samples. The obtained sequencing data were screened for potential pathogenic and novel variants, then the variants-located genes were clustered to identify cancer-related pathways. Shared or recurrent variants among the BIL cases were also identified and evaluated for their potential functional impact. Results We identified 48,802 variants in exons in total, 97.3% of which were single nucleotide variants. After filtering out variants with minor allele frequency ≥ 1%, we obtained 8667 potentially pathogenic variants, of which 174 were shared by all the BIL cases. The identified variants located in genes that could be significantly enriched into certain cancer-related pathways such as PI3K-AKT signaling pathway and Ras signaling pathway. We also identified 1010 novel variants with no record in the Genome Aggregation Database and in dbSNP, and one of them was shared by 90% cases. The recurrent and novel variant caused a missense mutation in SESN3. Conclusions We examined variations of the whole exome in BIL patients for the first time. The commonly shared variants implied a relation with BIL, and the recurrent and novel variant might be specifically related to BIL. The related variants may help unravel the carcinogenic mechanisms of BIL.

Abstract Background Leprosy is a chronic infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that is mainly transmitted through droplets from the nose and mouth of untreated patients. Owing to the lack of specific serological markers and clinical manifestations, leprosy can be easily confused with other skin lesion-related diseases and is difficult to distinguish. Case presentation This study introduces and summarises the diagnosis and treatment process of a case of leprosy misdiagnosed as erythema multiforme for a long time. A 43-year-old female was admitted to our hospital because of “repeated fever with superficial lymphadenopathy and systemic rash in May”. The diagnosis of the patient was based on the two main clinical characteristics of superficial lymphadenopathy and systemic pleomorphic erythema by using a combination of multiple samples of lymph nodes and skin, routine pathological examination, immunohistochemistry, acid-fast, silver hexamine, periodic acid-Schiff (PAS) staining, and second-generation gene sequencing of fresh biopsy tissue. The patient was treated with dapsone, rifampicin, and clofazimine at the Institute of Dermatology and Venereal Diseases. After treatment for 1 year, her temperature returned to normal, the area of facial erythema decreased, and the volume of axillary lymph nodes had gradually reduced. Conclusions In conclusion, special pathological staining and second-generation gene sequencing show promising advantages in distinguishing leprosy from other skin lesion-related diseases.

Abstract Background Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. Methods Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. Results In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. Conclusions The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.

Abstract Background Canine distemper caused by canine distemper virus that belongs to the Morbillivirus genus of the Paramyxoviridae family is still a global epidemic significant infectious disease, especially in pet dogs in China and serious harm to the development of the dog industry. It has been known that apoptosis caused by the canine distemper virus can show in culture cells, lymphoid tissues, and the cerebellum. However, its occurrence in brain tissue cells remains unclear. To investigate the relationship among canine distemper infecting brain tissues, apoptosis in brain tissue cells, and demyelinating pathogenesis was investigated. Methods 16 naturally infected dogs that exhibited clinical signs of CD and tested positive for the anti-CDV monoclonal antibody and six healthy dogs that served as the control, were used in the research. Brain specimens were divided into the cerebrum, brain stem, and cerebellum embedded in paraffin and made the sections respectively. Approximately 5 µm-thick sections were stained by hematoxylin–eosin, methyl green pyronin, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique, and immunohistochemistry. CDV nucleocapsid protein was detected by immune streptavidin-biotinylated peroxidase complex. Results Alterations in the brain tissues of CDV-infected dogs involved both various cells and nerve fibers. CDV had varying degrees of cytotropism to all brain tissue cells; apoptosis also occurred in all brain cells, especially in the endothelia of cerebral vessels, astrocytes, oligodendrocytes, and ependymal cells, the more serious infection, the more obvious apoptosis. Serious infections also involved the pyramidal and Purkinje cells. The nervous fibers exhibited demyelinating lesions (showed small multifocal vacuole), and some axonal neuron atrophy gradually disappeared (formed large vacuole). Conclusions Apoptosis in brain tissue cells was mainly related to the propagation path and cytotropism of CDV. The apoptosis of astrocytes, oligodendrocytes, and some neurons may play a significant role in the demyelinating pathogenesis in dogs with acute canine distemper. A lot of diverse nervous signs shown in the clinic may be related to different neuron apoptosis.

Abstract Background Trichloroethylene (TCE) hypersensitivity syndrome (THS) is a dose-independent and potentially life-threatening disease. In this study, we sought to identify THS-related miRNAs and evaluate its potential clinical value. Methods Serum samples of five patients and five matched TCE contacts were used for screening differential miRNAs. Another 34 patients and 34 matched TCE contacts were used for verifying significantly differential miRNAs with SYBR™ Green PCR and MGB PCR. The diagnostic model based on these miRNAs was established via the support vector machine (SVM) algorithm. Correlation between differential miRNAs and liver function was analyzed via the Spearman correlation test. Results A total of 69 miRNAs was found to be differentially expressed. MiR-21-5p and miR-339-5p were verified to have significant higher expressions in patients. The sensitivity, specificity and accuracy of disease model were 100, 75 and 86%, respectively. The two miRNAs showed significant correlations with liver function. Conclusion These findings suggested that miRNAs profiles in serum of THS patients had changed significantly, and miR-21-5p and miR-339-5p were associated with THS.

Abstract Background The World Health Organization (WHO) in 2015 stated that every effort should be made to provide cesarean delivery (CD) for women in need. In China, the two-child policy largely prompts the number of advanced age childbirth, which raises the possibility of an increasing number of women who need a c-section. The aim of this study was to assess the trends in the overall and medical indication-classified CD rates in the era of the two-child policy in Jiangsu, China. Methods A retrospective cross-sectional study of 291,448 women who delivered in 11 hospitals in Jiangsu province between 2012 and 2019 was conducted. Medical cesarean indication for each woman was ascertained by manually reviewing the medical records. The 291,448 women were divided into two subgroups according to the presence of the indications: the indicated group (7.80%) and the non-indicated group (92.20%). We then fitted joinpoint regression and log-binomial regression models to estimate trends in the CD rates across the study period. Results The overall CD rate was observed with a declining trend from 52.51% in 2012–2015 to 49.76% in 2016–2019 (adjusted RR, 0.92; 95% CI, 0.91–0.93; P

Abstract Background Circular RNAs (circRNAs) play important roles in tumourigenesis and tumour progression. However, the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC) are largely unclear. Methods The expression profiles of circRNAs in HCC were identified through microarray analysis and were validated through quantitative reverse transcription polymerase chain reaction (qRT-PCR). Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. The circular structure of candidate circRNA was confirmed through Sanger sequencing, divergent primer PCR, and RNase R treatments. Proliferation of HCC cells was evaluated in vitro and in vivo. The microRNA (miRNA) sponge mechanism of circRNAs was demonstrated using dual-luciferase reporter and RNA immunoprecipitation assays. Results CircSETD3 (hsa_circRNA_0000567/hsa_circRNA_101436) was significantly downregulated in HCC tissues and cell lines. Low expression of circSETD3 in HCC tissues significantly predicted an unfavourable prognosis and was correlated with larger tumour size and poor differentiation of HCC in patients. In vitro experiments showed that circSETD3 inhibited the proliferation of HCC cells and induced G1/S arrest in HCC cells. In vivo studies revealed that circSETD3 was stably overexpressed in a xenograft mouse model and inhibited the growth of HCC. Furthermore, we demonstrated that circSETD3 acts as a sponge for miR-421 and verified that mitogen-activated protein kinase (MAPK)14 is a novel target of miR-421. Conclusion CircSETD3 is a novel tumour suppressor of HCC and is a valuable prognostic biomarker. Moreover, circSETD3 inhibits the growth of HCC partly through the circSETD3/miR-421/MAPK14 pathway.