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Babesia orientalis, a protozoan parasite transmitted by the tick Rhipicephalus haemaphysaloides, holds significant economic importance along the Yangtze River. Key factors in the host invasion process include rhoptry neck proteins (RON2, RON4, and RON5) and apical membrane antigen 1 (AMA1). However, the intricacies of the interaction between AMA1 and RONs remain incompletely elucidated in B. orientalis. To better understand these crucial invasion components, the RON4 gene of B. orientalis (BoRON4) was cloned and sequenced. RON4 is 3468 base pairs long, encodes 1155 amino acids, and has a predicted molecular weight of 130 kDa. Bioinformatics analysis revealed a unique region (amino acid residues 109–452) in BoRON4, which demonstrates higher sensitivity to epitope activity. The BoRON4 gene was strategically truncated, amplified, and cloned into the pGEX-6p-1 vector for fusion expression. We successfully used the mouse polyclonal antibody to identify native BoRON4 in B. orientalis lysates. Furthermore, the corresponding BoRON4 protein band was detected in the water buffalo serum infected with B. orientalis, while no such band was observed in the control. Additionally, I-TASSER and Discovery Studio software were used to predict the tertiary structures of BoRON4 and its ligands, CH-PKA and CH-complex. These ligands can serve as lead compounds for the development of anti-babesiosis drugs. In conclusion, BoRON4 emerges as a promising candidate antigen for distinguishing water buffalo infected with B. orientalis from their normal counterparts. This study positions BoRON4 as a potential diagnostic antigen for babesiosis in water buffalo, contributing valuable insights to the field of parasitology. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) significantly contributes to cancer-related mortality in women, underscoring the criticality of early detection for optimal patient outcomes. Mammography is a key tool for identifying and diagnosing breast abnormalities; however, accurately distinguishing malignant mass lesions remains challenging. To address this issue, we propose a novel deep learning approach for BC screening utilizing mammography images. Our proposed model comprises three distinct stages: data collection from established benchmark sources, image segmentation employing an Atrous Convolution-based Attentive and Adaptive Trans-Res-UNet (ACA-ATRUNet) architecture, and BC identification via an Atrous Convolution-based Attentive and Adaptive Multi-scale DenseNet (ACA-AMDN) model. The hyperparameters within the ACA-ATRUNet and ACA-AMDN models are optimized using the Modified Mussel Length-based Eurasian Oystercatcher Optimization (MML-EOO) algorithm. The performance is evaluated using a variety of metrics, and a comparative analysis against conventional methods is presented. Our experimental results reveal that the proposed BC detection framework attains superior precision rates in early disease detection, demonstrating its potential to enhance mammography-based screening methodologies. [ABSTRACT FROM AUTHOR]

Background: Babesia orientalis is an intra-erythrocytic protozoan parasite that causes babesiosis in water buffalo. The genome of B. orientalis has been reported and various genes have been accurately annotated, including heat shock proteins (HSP). Three B. orientalis HSPs (HSP90, HSP70 and HSP20) have been previously identified as potential antigenic targets. Here, a new validation strategy for the chaperone activities and cell protection characteristics of the three HSPs was developed in vitro. Methods: BoHSP20, BoHSP70 and BoHSP90B were amplified from cDNA, followed by cloning them into the pEGFP-N1 vector and transfecting the vector plasmid separately into 293T and Hela mammalian cells. Their expression and localization were determined by fluorescence microscopy. The biological functions and protein stability were testified through an analysis of the fluorescence intensity duration. Their role in the protection of cell viability from heat-shock treatments was examined by MTT assay (cell proliferation assay based on thiazolyl blue tetrazolium bromide). Results: Fusion proteins pEGFP-N1-BoHSP20, pEGFP-N1-BoHSP70, and pEGFP-N1-BoHSP90B (pBoHSPs: pBoHSP20; pBoHSP70 and pBoHSP90B) were identified as 47 kDa/97 kDa/118 kDa with a 27 kDa GFP tag, respectively. Prolonged fluorescent protein half-time was observed specifically in pBoHSPs under heat shock treatment at 55 °C, and BoHSP20 showed relatively better thermotolerance than BoHSP70 and BoHSP90B. Significant difference was found between pBoHSPs and controls in the cell survival curve after 2 h of 45 °C heat shock. Conclusion: Significant biological properties of heat stress-associated genes of B. orientalis were identified in eukaryote by a new strategy. Fusion proteins pBoHSP20, pBoHSP70 and pBoHSP90B showed good chaperone activity and thermo-stability in this study, implying that BoHSPs played a key role in protecting B. orientalis against heat-stress environment during parasite life cycle. In conclusion, the invitro model explored in this study provides a new way to investigate the biological functions of B. orientalis proteins during the host–parasite interaction. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic bone disease characterized by low bone mineral density and bone microstructure damage, resulting in increased bone fragility and fracture risk. The present study aimed to identify key genes and functionally enriched pathways in osteoporotic patients. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to microarray datasets of blood samples of osteoporotic patients from the Sao Paulo Ageing & Health [SPAH] study (26 osteoporotic samples and 31 normal samples) to construct co-expression networks and identify hub gene. The results showed that HDGF, AP2M1, DNAJC6, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, IGKV3-7, IGKV3D-11, and IGKV1D-42 are genes which were associated with the disease status of osteoporosis. Differentially expressed genes are enriched in proteasomal protein catabolic process, ubiquitin ligase complex, and ubiquitin-like protein transferase activity. Functional enrichment analysis demonstrated that genes in the tan module were enriched in immune-related functions, indicating that the immune system plays a critical role in osteoporosis. Validation assay demonstrated that the HDGF, AP2M1, TMEM183B, and MFSD2B levels were decreased in osteoporosis samples compared with healthy controls, while the levels of IGKV1-5, IGKV1-8, and IGKV1D-42 were increased in osteoporosis samples compared with healthy controls. In conclusion, our data identified and validated the association of HDGF, AP2M1, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, and IGKV1D-42 with osteoporosis in elderly women. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of osteoporosis. [ABSTRACT FROM AUTHOR]

Mitochondrial transcription termination factor 3 (MTERF3) negatively regulates mitochondrial DNA transcription. However, its role in hepatocellular carcinoma (HCC) progression remains elusive. Here, we investigate the expression and function of MTERF3 in HCC. MTERF3 is overexpressed in HCC tumor tissues and higher expression of MTERF3 positively correlates with poor overall survival of HCC patients. Knockdown of MTERF3 induces mitochondrial dysfunction, S-G2/M cell cycle arrest and apoptosis, resulting in cell proliferation inhibition. In contrast, overexpression of MTERF3 promotes cell cycle progression and cell proliferation. Mechanistically, mitochondrial dysfunction induced by MTERF3 knockdown promotes ROS accumulation, activating p38 MAPK signaling pathway to suppress HCC cell proliferation. In conclusion, ROS accumulation induced by MTERF3 knockdown inhibits HCC cell proliferation via p38 MAPK signaling pathway suggesting a promising target in HCC patients. Targeting mitochondrial transcription termination factor MTERF3 induces mitochondrial dysfunction and inhibits the proliferation via activating ROS-dependent p38 MAPK pathway in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets. Methods: An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry. Results: Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline. Conclusion: Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings. Key Points • Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging. • This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM. • Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels. [ABSTRACT FROM AUTHOR]

Objective: The stratification of microsatellite instability (MSI) status assists clinicians in making treatment decisions for colorectal cancer (CRC) patients. This study aimed to establish a CT-based radiomics signature to predict MSI status in patients with CRC. Methods: A total of 837 CRC patients who underwent preoperative enhanced CT and had available MSI status data were recruited from two hospitals. Radiomics features were extracted from segmented tumours, and a series of data balancing and feature selection strategies were used to select MSI-related features. Finally, an MSI-related radiomics signature was constructed using a genetic algorithm–enhanced artificial neural network model. Combined and clinical models were constructed using multivariate logistic regression analyses by integrating the clinical factors with or without the signature. A Kaplan–Meier survival analysis was conducted to explore the prognostic information of the signature in patients with CRC. Results: Ten features were selected to construct a signature which showed robust performance in both the internal and external validation cohorts, with areas under the curves (AUC) of 0.788 and 0.775, respectively. The performance of the signature was comparable to that of the combined model (AUCs of 0.777 and 0.767, respectively) and it outperformed the clinical model constituting age and tumour location (AUCs of 0.768 and 0.623, respectively). Survival analysis demonstrated that the signature could stratify patients with stage II CRC according to prognosis (HR: 0.402, p = 0.029). Conclusions: This study built a robust radiomics signature for identifying the MSI status of CRC patients, which may assist individualised treatment decisions. Key Points: • Our well-designed modelling strategies helped overcome the problem of data imbalance caused by the low incidence of MSI. • Genetic algorithm–enhanced artificial neural network–based CT radiomics signature can effectively distinguish the MSI status of CRC patients. • Kaplan–Meier survival analysis demonstrated that our signature could significantly stratify stage II CRC patients into high- and low-risk groups. [ABSTRACT FROM AUTHOR]

Objectives: To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. Methods: In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). Results: iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759–0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647–0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206–0.546, p < 0.001), Resec4 (0.199, 0.040–1.000, p < 0.001), and TCIA (0.303, 0.098–0.944, p = 0.001). Conclusions: iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. Key Points: • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing spondylitis. Methods: This multicenter, randomized, double-blind, positive-controlled phase III clinical trial was conducted in 19 centers across China. Chinese adults with active ankylosing spondylitis despite being treated with non-steroidal anti-inflammatory drugs for ≥ 4 weeks were randomized in a 1:1 ratio to subcutaneously receive 40 mg of TQ-Z2301 or adalimumab every other week for 24 weeks. The primary endpoint was the percentage of patients who achieved at least 20% improvement according to the Assessment of Spondyloarthritis International Society criteria (ASAS20) at week 24. The equivalence was established if the 90% CI for RR of ASAS20 between two groups at week 24 fell within (0.80, 1.25). Secondary endpoints included efficacy measures of disease activity, spinal mobility, physical function and quality of life, immunogenicity, and pharmacokinetic parameters. Safety analysis was done for all patients who received at least one study drug. Results: A total of 380 patients were enrolled in the study between September 2018 and October 2019, including 188 in the TQ-Z2301 group and 192 in the adalimumab group. In the full analysis population, the ASAS20 response rate at week 24 was 86.70% in the TQ-Z2301 group, and 80.73% in the adalimumab group, the RR of ASAS20 for TQ-Z2301 versus adalimumab was 1.074, 90% CI (0.997, 1.157), fell within the predefined equivalence boundary (0.80, 1.25). Except for the SF-36 at week 12, there was no statistical difference between the two groups for all the secondary endpoints (P>0.05). The incidence of adverse events group was 82.45% in the TQ-Z2301, and 83.85% in the adalimumab group, the safety profile of the two groups was similar. The profiles of immunogenicity and pharmacokinetics were also similar between the two groups. Conclusion: TQ-Z2301 is equivalent to adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. The safety, immunogenicity, and pharmacokinetic characteristics of both drugs are similar. Trial registration: The study (CTR20181863) was registered in the Chinese Clinical Trial Registry on 19 October 2018. Key Points • TQ-Z2301 showed the equivalence of efficacy compared with the reference adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. • The safety, immunogenicity, and pharmacokinetics profiles of TQZ-2301 were similar to those of the reference adalimumab. [ABSTRACT FROM AUTHOR]

Introduction: Biomarkers of bone and cartilage metabolism were proposed as early diagnosis indicators for knee osteoarthritis (OA), however, which were influenced by disease stage, age, and menopause state. Accurate diagnosis indicators are eagerly awaited. The current study aims to investigate associations of joint metabolism biomarkers and bone mineral density (BMD) with early knee OA in males and premenopausal females before age 50 years. Method: A total of 189 patients aged before 50 years with early knee OA and 152 healthy participants were enrolled. Levels of bone biomarkers (PINP, OC, and CTX-I) and cartilage biomarkers (PIIANP, COMP, CTX-II, and MMP-3) were assessed. BMD was measured at the lumbar, femoral neck, and hip. Multivariate regression analyses were performed to evaluate the relationship between biomarkers, BMD, and early knee OA. Results: Serum COMP, urine CTX-II and BMD at femoral neck and hip were increased in premenopausal patients as compared to control; with serum PINP and OC reduced. Meanwhile, serum COMP, urine CTX-II, and BMD at femoral neck and hip showed positive associations with premenopausal early knee OA, while serum PINP had negative association. However, in male patients, only serum COMP was higher than control, and no association of biomarkers or BMD was found with early knee OA. Conclusions: The joint metabolism biomarkers and BMD showed multiple associations with early knee OA in premenopausal females, but not in males aged before 50 years. It was suggested that sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. Key Points • The joint metabolism biomarkers and BMD are associated with early knee OA in premenopausal females, but not in males aged before 50 years. • Sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. [ABSTRACT FROM AUTHOR]

Objective: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. Methods: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. Results: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. Conclusion: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. Trial registration: http://www.chictr.org.cn/enindex.aspx, ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. Methods: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. Results: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. Conclusion: HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883) [ABSTRACT FROM AUTHOR]

Babesia orientalis, belonging to the phylum Apicomplexa, is mainly accountable for water buffalo babesiosis, which adversely affected the livestock industry in China. Variant erythrocyte surface antigen-1 (VESA1), an antigen that helps infected erythrocytes to escape from host immune responses, was first reported in Babesia bovis. Various VESA1 proteins have also been characterized in other Babesia species. Nevertheless, there is no research on the identification and characterization of VESA1 proteins in Babesia orientalis. In this study, the BoVESA1 gene was amplified from both gDNA and cDNA. The results revealed that it is an intronless gene with a full length of 753 bp, encoding a protein of 250 amino acids with a predicted molecular weight of 28 kDa. The coding sequence (CDS) was cloned into the pGEX-6p-1 vector using a homologous recombination kit and expressed as a glutathione-S-transferase (GST)-fusion protein with a molecular weight of 53 kDa. The tertiary structure of BoVESA1 was predicted using the I-TASSER software. The recombinant protein was subjected to western blotting; the immunogenicity of recombinant BoVESA1 (rBoVESA1) was identified by incubating it with B. orientalis-positive serum. The native BoVESA1 was identified using the lysates of B. orientalis-infected water buffalo erythrocytes incubated with the anti-rBoVESA1 mouse serum. The results showed a band of ~ 28 kDa, which is similar to the predicted size. Immunofluorescence assay (IFA) using anti-rBoVESA1 serum probed indicated a strong signal in the infected RBCs, while the negative control showed no signal. In conclusion, the VESA1 protein was first identified in B. orientalis. This study facilitated further investigation of B. orientalis, and the results indicated that BoVESA1 may serve as a potential candidate antigen for diagnosis and detection of B. orientalis infection. [ABSTRACT FROM AUTHOR]

Background: Although laparoscopic common bile duct exploration (LCBDE) is considered the best treatment and has the advantages of being minimally invasive for common bile duct (CBD) stones, the choice of T-tube drainage (TTD) or primary duct closure (PDC) after LCBDE is still controversial. Therefore, the aim of the study was to compare the superiority of PDC versus TTD after LCBDE for choledocholithiasis. Methods: All potential studies which compare the surgical effects between PDC with TTD were electronically searched for in PubMed, Web of Science, and the Cochrane library databases up to November 2019. Data synthesis and statistical analysis were carried out using RevMan 5.3 software. Results: In total, six randomized controlled trials with 604 patients (307 in the PDC group and 297 in the TTD group) were included in the current meta-analysis. As compared with the TTD group, the pooled data showed that PDC group had shorter operating time (WMD = −24.30; 95% CI = −27.02 to −21.59; p < 0.00001; I2 = 0%; p < 0.88), less medical expenditure (WMD = −2255.73; 95% CI = −3330.59 to −1180.86; p < 0.0001; I2 = 96%; p < 0.00001), shorter postoperative hospital stay (OR = −2.88; 95% CI = −3.22 to −2.54; p < 0.00001; I2 = 60%; p < 0.03), and lower postoperative complications (OR = 0.49; 95% CI = 0.31 to 0.78; p = 0.77; I2 = 0%; p = 0.003). There were no significant differences between the two groups concerning bile leakage (OR = 0.74; 95% CI = 0.36 to 1.53; p = 0.42; I2 = 0%; p = 0.90) and retained stones (OR = 0.96; 95% CI = 0.36 to 2.52; p < 0.93; I2 = 0%; p < 0.66). Conclusions: LCBDE with PDC should be performed as a priority alternative compared with TTD for choledocholithiasis. [ABSTRACT FROM AUTHOR]

Due to its wide presence in apicomplexan parasites as well as high polymorphism and antigenic diversity, the variable merozoite surface antigen (VMSA) family in Babesia sp. has attracted increasing attention of researchers. Here, all the reported VMSA genes of Babesia spp. were obtained from GenBank, and multiple alignments were performed by using conserved regions to blast the Babesia orientalis genome database (unpublished data). Five MSA genes (named MSA-2a1, MSA-2a2, MSA-2c1, MSA-1, and MSA-2c2, respectively) were identified, sequenced, and cloned from B. orientalis, which were shown to encode proteins with open reading frames ranging in size from 266 (MSA-2c1) to 317 (MSA-1) amino acids. All the five proteins contain an MSA-2c superfamily conserved domain, with an identical signal peptide and glycosyl phosphatidyl inositol (GPI)-anchor for each of them. The five proteins were also predicted to contain B cell epitopes, with only three for BoMSA-2c1, the smallest protein in the BoVMSA family, while at least six for each of the others. Notably, BoMSA-2a1 has 2 identical copies, a specific phenomenon only present in B. orientalis. This research has determined the MSA genes of B. orientalis and provides a genetic basis for further research of functional genes in B. orientalis. [ABSTRACT FROM AUTHOR]

Using king grass (Pennisetum purpureum Schumach. × Pennisetum glaucum (L.) R.Br.) for phytoextraction is a promising technology for producing large amounts of biomass fuel while remediating contaminated soil. To assess the practical phytoextraction capacity of king grass, we conducted a field experiment with three different soil types (loam, sandy loam, clay loam) and cadmium (Cd) concentrations (0, 0.25, 0.5, 1, 2, 4, 8, and 16 mg kg−1, aged stably for 6 years). King grass were harvested at two different periods (elongation and maturity) to identify the optimal harvest time for extraction efficiency. The results showed that all treatments had bioconcentration factor (BCF) > 1 and translocation factor (TF) < 1; Cd is mainly stored in the roots. However, due to a high shoot biomass, the highest quantity of Cd extracted from shoots was 2.75 mg plant−1, from the experimental group with 16 mg kg−1 Cd added in sandy loam. A significant positive relationship (P < 0.05) was observed between the amount of Cd extracted from king grass stems, leaves, and roots from soil with the diethylene triamine pentacetate acid (DTPA) extractable Cd concentration. The Cd concentration in shoots at the maturity stage is lower than at the elongation stage, mainly due to the effect of biological dilution. Meanwhile, there is significantly more biomass (P < 0.05) at the maturity stage than at the elongation stage. At the latter, the extraction efficiency of the three soils was loam > sandy loam > clay loam, while at maturity it was sandy loam > clay loam > loam. This change in extraction efficiency can be attributed mainly to differences in soil DTPA-extractable Cd concentration and growth rate caused by differences in soil physical and chemical properties. According to calculations from multiple harvests using three types of soil, remediating contaminated soil with 0–16 mg kg−1 Cd would take 13.9–224.5 and 19.5–250.6 years, extracting 7.21–265.23 and 4.96–330.52 g ha−1 Cd while producing 33.62–66.50 and 73.8–110.5 t ha−1 dry biomass at the elongation (90 days) and maturity (120 days) stages, respectively. In summary, king grass has major potential for remediating Cd-contaminated soil while producing large volumes of biofuel. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a messenger molecule in organisms, participating in the regulation of many biological processes. The abnormal expression of NO is often observed in a variety of diseases, including cerebral ischemia, atherosclerosis, and cancer. However, a suitable tool that can directly and sensitively detect NO in vitro and in vivo is important for understanding its various biological functions. In this report, a new fluorescent probe for nitric oxide, DHP-4, was prepared, based on dihydropyridine-coumarin. DHP-4 was able to greatly enhance the fluorescence of NO, but did not affect the fluorescence emissions of other reactive oxygen species and nitrogen species, demonstrating its highly selective and sensitive response to NO. The probe generated stable optical signals in a buffer solution at pH values ranging from 3 to 10. In addition, DHP-4 could detect NO directly, showed low cellular toxicity, and was successfully applied to determine NO in Raw 264.7 cells, indicating its great potential as a tool for investigating the biological roles of NO in vivo. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the efficacy and safety of the biosimilar candidate of adalimumab (HS016) compared with adalimumab (Humira) for the treatment of active ankylosing spondylitis. Methods: A multicenter, randomized, double-blind, parallel, positive control, phase III clinical trial was conducted at 28 locations in China. Patients with active ankylosing spondylitis were randomized in a 2:1 ratio to subcutaneously receive 40 mg of either HS016 or adalimumab every other week for 24 weeks. The primary endpoint was to achieve at least a 20% improvement (ASAS20) in patients at 24 weeks according to the Assessment of Spondyloarthritis International Society criteria. The secondary endpoint included other efficacy assessment parameters, health evaluations, safety, pharmacokinetic, and immunogenicity parameters. Results: Following the random assignment of 648 patients into HS016 (n = 416) and adalimumab (n = 232) groups, no significant difference was found in the ASAS20 response rates at 24 weeks between the HS016 (364/416, 87.5%) and adalimumab (209/232, 90.1%) treatments and the difference between the response rates (− 2.59%; 90% confidence interval [CI] − 6.77 to 1.60) was within the predefined equivalence margin (± 15%). There were also no significant differences when the secondary endpoints were compared (all p > 0.05). Similarly, the rates of treatment-emergent adverse events (TEAEs) were not significantly different between the two groups, with most TEAEs being mild to moderate. Only nine severe cases were found, including seven within the HS016 group, three (0.7%) of which were tuberculosis cases. Plasma concentrations of HS016 and adalimumab from weeks 12 to 14 were similar during the steady-state period and steady-state maximal concentration (Cmax,ss) was equivalent for HS016 (7356.6 ng/mL) and adalimumab (7600.3 ng/mL). The accumulated proportion of patients with positive human anti-human antibodies (HAHAs) at week 24 was 326/412 (79.1%) in the HS016 group and 183/229 (79.9%) in the adalimumab group (p > 0.05), while the accumulated proportion of patients with positive neutralizing antibody (NAb) tests were 72/412 (17.5%) in the HS016 group and 43/229 (18.8%) in the adalimumab group (p > 0.05). Conclusion: HS016 resembled adalimumab in efficacy and safety over the 24-week treatment period. Trial registration number: ChiCTR1900022520. [ABSTRACT FROM AUTHOR]

Background: Protein arginine methyltransferase 1 (PRMT1) is the founding member of the PRMT family of proteins, whose members catalyze methylation of arginine residues in various proteins. Although several studies have reported upregulation of PRMT1 in various cancer types, the expression pattern and the underlying mechanism of PRMT1 action in pancreatic ductal adenocarcinoma (PDAC) are still unclear. Methods: Immunohistochemistry staining as well as RT-PCR was used to determine the expression pattern of PRMT1 in clinical PDAC samples. Lentivirus packaging and transfection were employed to construct cell lines with PRMT1 overexpression or knockdown. MTT and crystal violet assays were used to determine the proliferation rates of PDAC cells. β-catenin transcription activity was measured using a TOPFlash assay. PRMT1 binding to the promoter region of CTNNB1 was determined by ChIP-qPCR assay. Results: Elevated PRMT1 expression was found in PDAC tissue samples compared to noncancerous normal tissues in 41 patients using a real-time PCR assay and in 90 patients using a tissue microarray (TMA) in conjunction with immunohistochemistry. Analysis of the PRMT1 expression data and PDAC clinical features revealed that PRMT1 expression was significantly correlated with PDAC tumor size and prognosis in postoperative patients. Additional functional experiments revealed that PRMT1 expression promoted the growth of pancreatic cancer-derived cells, both in vitro and in vivo. Mechanistically, we found that PRMT1 increased the cellular β-catenin level. We also found that PRMT1 and β-catenin were co-expressed in TCGA and GTEx datasets containing 370 samples. Conclusions: Collectively, our study provides novel insight into the expression and function of PRMT1 in PDAC and indicates that PRMT1 may serve as a therapeutic target for treating patients with pancreatic ductal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot.To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM).Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed.The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p < 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p < 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value.Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as “delayed wash-in, delayed wash-out, and weak enhancement” on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions.Objective: Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot.To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM).Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed.The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p < 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p < 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value.Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as “delayed wash-in, delayed wash-out, and weak enhancement” on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions.Methods: Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot.To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM).Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed.The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p < 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p < 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value.Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as “delayed wash-in, delayed wash-out, and weak enhancement” on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions.Results: Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot.To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM).Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed.The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p < 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p < 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value.Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as “delayed wash-in, delayed wash-out, and weak enhancement” on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions.Conclusions: Diabetic foot is one of the most serious complications of type 2 diabetes mellitus (T2DM), and its incidence is increasing in China. Early detection of abnormal microcirculation in the foot is very important for the prevention and treatment of diabetic foot.To investigate the value of contrast-enhanced ultrasound (CEUS) in diagnosing microcirculatory alterations in the dorsum of the foot for patients with type 2 diabetes mellitus (T2DM).Eighty-eight T2DM patients were included, among them 30 patients sustained diabetes mellitus without complications (group A), 28 with lesions in the dorsum of the foot (no acute infection) that can be classified as Wagner grade 0 ~ 1 (group B), and 30 with lesions in the dorsum of the foot that can be classified as Wagner grade 2–5 (group C). Another 30 healthy adults were included as the control group. All subjects underwent CEUS to examine the dorsalis pedis arteries and blood perfusion to the underlying soft tissues. Parameters of the time-intensity curve (TIC), including rise time (RT), ascending slope (AS), time to peak (TTP), peak intensity (PI), area under the curve (AUC), and half of drop time (DT/2) were analyzed.The analysis of TIC data of the dorsalis pedis arteries showed that group C had decreased AS, PI, and AUC and increased TTP, RT, and DT/2 compared with groups A, B, and the control group; the differences were statistically significant (p < 0.05). The analysis of TIC data of the perfusion to the underlying soft tissues showed that AS, PI, and AUC decreased from the control group through group A, B, and then C; the differences were all statistically significant (p < 0.05). The TIC data were correlated with the severity of microcirculatory impairment in the dorsum of the foot and among them the AUC, PI, and AS had higher predictive value.Microcirculatory impairment in the dorsum of the foot in T2DM patients presents itself as “delayed wash-in, delayed wash-out, and weak enhancement” on CEUS images. CEUS can provide quantification of the microcirculatory changes in the soft tissues in the dorsum of the foot and reflect the differences of microcirculatory perfusion across different grades of lesions. [ABSTRACT FROM AUTHOR]

Ixodid ticks are ectoparasites responsible for the transmission of a large number of bacterial, viral, and protozoan pathogens to animals and humans. As long-term blood-pool feeders, the digestion of host blood is critical to their development as well as to the establishment of the sexual cycle of hemoparasites such as Babesia parasites, the agents of human and animal babesiosis. Previous studies have demonstrated that cysteine proteases are involved in blood digestion, embryogenesis, and pathogen transmission in other species of ticks, but their characteristics and functions are still unidentified in Haemaphysalis flava. Here, we describe the characterization of a cysteine protease HfCL from H. flava. We show that HfCL belongs to the L-like papain family of proteases, exhibits high expression in nymphs and adults, and localizes to both the midgut and salivary glands. Biochemical assays using purified recombinant enzyme reveal that rHfCL can hydrolyze the fluorogenic substrate Z-phe-Arg-MCA with optimal activity detected at pH 6. Furthermore, the short-term growth assay indicates that rHfCL can inhibit the intraerythrocytic development of Babesia microti and Babesia gibsoni in vitro. [ABSTRACT FROM AUTHOR]

Babesia gibsoni (B. gibsoni), an intracellular apicomplexan protozoan, poses great threat to canine health. Currently, little information is available about the B. gibsoni (WH58) endemic to Wuhan, China. Here, the mitochondrial (mt) genome of B. gibsoni (WH58) was amplified by five pairs of primers and sequenced and annotated by alignment with the reported mt genome sequences of Babesia canis (B. canis, KC207822), Babesia orientalis (KF218819), Babesia bovis (AB499088), and Theileria equi (AB499091). The evolutionary relationships were analyzed with the amino acid sequences of cytochrome c oxidase I (cox1) and cytochrome b (cob) genes in apicomplexan parasite species. Additionally, the mt genomes of Babesia, Theileria, and Plasmodium spp. were compared in size, host infection, form, distribution, and direction of the protein-coding genes. The full size of the mt genome of B. gibsoni (WH58) was 5865 bp with a linear form, containing terminal-inverted repeats on both ends, six large subunit ribosomal RNA fragments, and three protein-coding genes: cox1, cob, and cytochrome c oxidase III (cox3). Babesia, Theileria, and Plasmodium spp. had a similar mt genome size of about 6000 bp. The mt genomes of parasites that cause canine babesiosis showed a slightly smaller size than the other species. Moreover, Babesia microti (R1 strain) was about 11,100 bp in size, which was twice larger than that of the other species. The mt form was linear for Babesia and Theileria spp. but circular for Plasmodium falciparum and Plasmodium knowlesi. Additionally, all the species contained the three protein-coding genes of cox1, cox3, and cob except Toxoplasma gondii (RH strain) which only contained the cox1 and cob genes. The phylogenetic analysis indicated that B. gibsoni (WH58) was more identical to B. gibsoni (AB499087), B. canis (KC207822), and Babesia rossi (KC207823) and most divergent from Babesia conradae in Babesia spp. Despite the highest similarity to B. gibsoni (AB499087) reported in Japan, B. gibsoni (WH58) showed notable differences in the sequence of nucleotides and amino acids and the property in virulence to host and in vitro cultivation. This study compared the mt genomes of the two B. gibsoni isolates and other parasites in the phylum Apicomplexa and provided new insights into their differences and evolutionary relationships. [ABSTRACT FROM AUTHOR]

Babesia gibsoni is a protozoan parasite responsible for the majority of reported cases of canine babesiosis in China. Currently, microscopic examination of the Giemsa-stained thin blood smears is the main diagnosis method in clinic. Here, we report the recombinase polymerase amplification-lateral flow (LF-RPA) dipstick detection method for targeting B. gibsoni cytochrome c oxidase subunit I (cox I) gene. The reaction takes only 20-30 min under isothermal temperatures between 30 and 45 °C. Specificity was evaluated using DNA from related apicomplexan parasites and their host, while the sensitivity was calculated based on the DNA from the experimental B. gibsoni-infected dogs. Results indicated that the LF-RPA method is 20 times more sensitive than the conventional PCR based on 18S rRNA and has no cross reaction with any other test DNAs. The applicability of the LF-RPA method was further evaluated using 15 samples collected from clinic. Thirteen of the 15 samples (86.67%) were detected as positive by LF-RPA, while 10 of them (66.67%) were found positive by conventional PCR. Overall, the novel LF-RPA assay is effective for the detection of B. gobsini and has considerable advantages over the conventional PCR in sensitivity, specificity, simplicity in operation, less time consumption, and visual detection. The LF-RPA method may facilitate the surveillance and early detection of B. gibsoni infection in dogs. [ABSTRACT FROM AUTHOR]

Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet β cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic β cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9-fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-β (TGF-β) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, characterized by B cell hyperactivity and pathogenic autoantibodies formation. The objective of this study is to evaluate the distribution of B cell subsets in patients with SLE. We included patients with SLE followed in First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, China. Flow cytometry was used to measure frequencies of B cell subsets, including memory B cells, switched memory B cells, non-switched memory B cells, double-negative memory B cells, and naïve B cells in 130 patients with SLE and 55 healthy controls. The different distributions of B cell subsets were further evaluated by their associations with disease activity and clinical manifestation. SLE patients showed significant alteration of B cell subsets, including lower frequency of non-switched memory B cells and higher double-negative memory B cells. The frequencies of B cell subsets also varied between new-onset SLE patients and chronic SLE patients. Frequencies of total memory B cells, switched memory B cells, and non-switched memory B cells were lower in new-onset SLE patients and frequency of naïve B cells was higher compared with healthy controls. Chronic SLE patients showed increased switched memory B cells and double-negative memory B cells. In addition, switched memory B cells and double-negative B cells were higher in patients with lupus nephritis (LN) regardless of disease activity. Our findings suggested that abnormalities of the B cell subsets homeostasis might contribute to the pathogenesis of SLE. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency may be associated with depression in the general population. This study aimed to describe the prevalence of depression and anxiety in rheumatoid arthritis (RA) patients from Northwestern China and identify associations of Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores with serum vitamin D level in these patients. We recruited 161 RA patients inform the First Affiliated Hospital of Xi'an Jiaotong University during Nov. 2016 to Feb. 2017. All patients completed a survey including HAMD and HAMA scales. RA activity (DAS28) was scored by a rheumatologist, and serum 25-OH-D3 levels were measured by electrochemiluminescence immunoassay. The data were analyzed using the SPSS16.0 based on 'possible and probable' cut points for HAMD and HAMA. About 62 and 60% of patients had some degrees of depression and anxiety, respectively. The mean of serum 25-OH-D3 levels in RA patients with depression was 15.24 ± 8.78 ng/mL, which was significantly lower than those without depression (24.68 ± 10.98 ng/mL, p = 0.009). Despite negative correlations between serum 25-OH-D3 level and the score of HAMD ( r = − 0.520, p < 0.001) or HAMA ( r = − 0.469, p < 0.001), there was a positive correlations between DAS28and the score of HAMD ( r = 0.459, p = 0.001) or HAMA ( r = 0.486, p < 0.001). The multivariate logistic regression showed that disease duration, serum 25-OH-D3 level, and treatment of tumor necrosis factor inhibitor were associated with depression/anxiety in RA patients. Our study shows a high prevalence of depression and anxiety in RA patients from Northwestern China. Both disease activity of RA and low serum 25-OH-D3 level are associated with the severity of depression and anxiety. It is imperative for clinicians to screen hypovitaminosis of vitamin D and depression/anxiety in RA patients. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether multiphasic dynamic CT can preoperatively predict lymphovascular invasion (LVI) in advanced gastric cancer (AGC).Methods: 278 patients with AGC who underwent preoperative multiphasic dynamic CT were retrospectively recruited. Tumour CT attenuation difference between non-contrast and arterial (ΔAP), portal (ΔPP) and delayed phase (ΔDP), tumour-spleen attenuation difference in the portal phase (ΔT-S), tumour contrast enhancement ratios (CERs), tumour-to-spleen ratio (TSR) and tumour volumes were obtained. All CT-derived parameters and clinicopathological variables associated with LVI were analysed by univariate analysis, followed by multivariate and receiver operator characteristics (ROC) analysis. Associations between CT predictors for LVI and histopathological characteristics were evaluated by the chi-square test.Results: ΔPP (OR, 1.056; 95% CI: 1.032-1.080) and ΔT-S (OR, 1.043; 95% CI: 1.020-1.066) are independent predictors for LVI in AGC. ΔPP, ΔT-S and their combination correctly predicted LVI in 74.8% (AUC, 0.775; sensitivity, 88.6%; specificity, 54.1%), 68.7% (AUC, 0.747; sensitivity, 68.3%; specificity, 69.4%) and 71.7% (AUC, 0.800; sensitivity, 67.6%; specificity, 77.8%), respectively. There were significant associations between CT predictors for LVI with tumour histological differentiation and Lauren classification.Conclusion: Multiphasic dynamic CT provides a non-invasive method to predict LVI in AGC through quantitative enhancement measurement.Key Points: • Lymphovascular invasion rarely can be evaluated preoperatively in advanced gastric cancer (AGC). • Δ PP and Δ T-S were independent predictors for LVI in patients with AGC. • Δ PP and Δ T-S showed acceptable predictive performance for LVI. • Combination of Δ PP and Δ T-S improved predictive performance for LVI. • Multiphasic dynamic CT may be a useful adjunct for detecting LVI preoperatively. [ABSTRACT FROM AUTHOR]

Purpose: To develop a CT-based radiomics signature and assess its ability for preoperatively predicting the early recurrence (≤1 year) of hepatocellular carcinoma (HCC). Methods: A total of 215 HCC patients who underwent partial hepatectomy were enrolled in this retrospective study, and all the patients were followed up at least within 1 year. Radiomics features were extracted from arterial- and portal venous-phase CT images, and a radiomics signature was built by the least absolute shrinkage and selection operator (LASSO) logistic regression model. Preoperative clinical factors associated with early recurrence were evaluated. A radiomics signature, a clinical model, and a combined model were built, and the area under the curve (AUC) of operating characteristics (ROC) was used to explore their performance to discriminate early recurrence. Results: Twenty-one radiomics features were chosen from 300 candidate features to build a radiomics signature that was significantly associated with early recurrence ( P < 0.001), and they presented good performance in the discrimination of early recurrence alone with an AUC of 0.817 (95% CI: 0.758-0.866), sensitivity of 0.794, and specificity of 0.699. The AUCs of the clinical and combined models were 0.781 (95% CI: 0.719-0.834) and 0.836 (95% CI: 0.779-0.883), respectively, with the sensitivity being 0.784 and 0.824, and the specificity being 0.619 and 0.708, respectively. Adding a radiomics signature into conventional clinical variables can significantly improve the accuracy of the preoperative model in predicting early recurrence ( P = 0.01). Conclusions: The radiomics signature was a significant predictor for early recurrence in HCC. Incorporating radiomics signature into conventional clinical factors performed better for preoperative estimation of early recurrence than with clinical variables alone. [ABSTRACT FROM AUTHOR]

The aims of this study are to characterize the biological disease-modifying antirheumatic drug (bDMARD) usage patterns in real-life and examine the remission rate of rheumatoid arthritis (RA) patients receiving bDMARDs in routine clinical practice in China. Consenting RA patients (≥18 years) from 15 teaching hospitals and receiving marketed bDMARDs were included. In total, 802 patients (81.3 % women, 49.0 ± 13.9 years) were included; 89.5 % were receiving a combination of bDMARDs and conventional synthetic DMARDs (csDMARDS), whereas 10.5 % were receiving bDMARD monotherapy. Etanercept (including Enbrel® and local brand Yi Sai Pu® and Qiangke®), tocilizumab, adalimumab, and infliximab were used by 66.6 %, 17.0 %, 7.5 %, and 6.6 % patients, respectively. Etanercept was used at a mean weekly dose of 38.2 ± 15.6 mg for 25.5 ± 47.0 weeks and tocilizumab at 94.5 ± 21.9 mg for 4.7 ± 7.5 weeks. Overall rate of remission was 12.6 %, 5.4 % , and 3.5 % based on DAS28, CDAI, and SDAI scores, respectively. Compared with patients receiving bDMARDs for <3 months, those receiving bDMARDs for ≥3 months exhibited significantly lower DAS28 scores ( p < 0.0001), and a significantly higher proportion of patients who received bDMARDs for ≥12 months achieved the treatment goal (remission or low disease activity, 62.5 % vs. 18.3 %, p < 0.0001). Patients receiving combination therapy with csDMARDs exhibited lower DAS28 scores than patients receiving bDMARD monotherapy (4.3 vs. 4.8, p = 0.011). This large-scale real-world study showed that bDMARD usage patterns in routine clinical practice in China were in accordance with international guidelines for RA management despite the short treatment duration. Longer duration of bDMARD usage and combination therapy showed a favored outcome of RA. [ABSTRACT FROM AUTHOR]

Several rhoptry proteins (ROPs) have been confirmed to be critical virulence factors of Toxoplasma gondii strains from North America and Europe. The two active kinases ROP17 and ROP18, and pseudokinase ROP5 were thought to be the key determinants of parasites' virulence in laboratory mice. Given the genetic diversity of Toxoplasma strains from different geographical regions, the virulence determinants in other strains, particularly the ones that are phylogenetically distant to the North American and European strains, are yet to be elucidated. In this study, we sought to examine the contribution of three known virulence factors to the virulence of a type I strain (T.gHB1) isolated from Central China. We deleted ROP17 and ROP18 individually, as well as in combination with GRA7 by the CRISPR-Cas9 system in this local isolate. Subsequent virulence tests in mice indicated that deletion of GRA7, ROP17, or ROP18 in T.gHB1showed similar attenuation in mice as the type I RH strain lacking the corresponding proteins. However, in contrast to the reported double knockouts in RH, double deletions of GRA7 plus ROP17 or GRA7 plus ROP18 in T.gHB1 did not show significant further virulence attenuation compared to the ROP17 or ROP18 single knockouts. These results indicated that GRA7, ROP18 and ROP17 may play different roles in virulence determination in genetically diverse strains of Toxoplasma. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a leading cause of acquired heart disease predominantly affecting infants and young children. Intravenous immunoglobulin (IVIG) is applied as the most favorable treatment against KD, but IVIG resistant remains exist. Although several clinical scoring systems have been developed to identify children at highest risk of IVIG resistance, there is a need to identify sufficiently sensitive biomarkers for IVIG treatment. Some differentially expressed genes (DEGs) could be the promising potential biomarkers for IVIG-related sensitivity diagnosis. We employed a systematic and integrative bioinformatics framework to identify such kind of genes. The performance of the candidate genes was evaluated by hierarchical clustering, ROC analysis and literature mining. By analyzing three datasets of KD patients, 34 DEGs of the three groups have been found to be associated with IVIG-related sensitivity. A module of 12 genes could predict resistant group patients with high accuracy, and a module of ten genes could predict responsive group patients effectively with accuracy of 96 %. And three of them are most likely to serve as drug targets or diagnostic biomarkers in the future. Compared with unsupervised hierarchical clustering analysis, our modules could distinct IVIG-resistant patients efficiently. Two groups of DEGs could predict IVIG-related sensitivity with high accuracy, which are potential biomarkers for the clinical diagnosis and prediction of IVIG treatment response in KD patients, improving the prognosis of patients. [ABSTRACT FROM AUTHOR]

High stress response is an important factor impeding the breeding of wild animals in captivity. Experimental fawn manipulation is considered a suitable approach to reduce the negative effects of behavioral and physiological stress. The forest musk deer ( Moschus berezovskii) is classified as 'endangered' by the IUCN Red List due to over-exploitation for musk production. Musk is highly valued for its cosmetic and alleged pharmaceutical properties and has stimulated the enthusiasm of captive musk deer breeding in recent years. This study attempts to reduce behavioral and physiological stress responses in juvenile musk deer using experimental fawn manipulation. Habituation started 5 days after birth and lasted until weaning age (90 days). We determined the behavioral stress response at the age of 30, 60, 90, 150, and 360 days by measuring acceptance or rejection of three treatment intensities (i.e., stroking, embracement) and quantified behavioral responses (urination, approaching the investigator). At the same time, physiological stress parameters were established, measuring the fecal glucocorticosteroid metabolite (FGM) concentration. Our results indicate that fawn manipulation initially reduced the behavioral stress, but after termination of treatments, stress symptoms reoccurred. We detected no difference in the FGM concentrations between treatment and control groups, suggesting that the experimental fawn manipulation did not decrease the physiological stress response. This implies that behavioral stress reduction cannot be sustained if the physiological stress remains unaltered. We argue that the socio-positive reactions of musk deer fawns to humans could be phenotypic and that the physiological stress response rather reflects their intrinsic characteristics than a successful manipulation. [ABSTRACT FROM AUTHOR]

This paper describes a simple, sensitive, and selective spectrofluorimetric method to determine trace amount of nitrite in food products using 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM DA) as a fluorescent probe. The reaction of DAF-FM DA with nitrite in acidic medium resulted in triazolofluorescein (DAF-FM T), a highly fluorescent reagent in neutral medium. The fluorescence enhancement was proportional to nitrite concentration in the range of 5.0 × 10 to 1.5 × 10 mol L with a detection limit of 3.3 × 10 mol L (S/ N = 3). The proposed method has been applied to the determination of nitrite in real food samples, with relative standard deviation (RSD) ( n = 6) less than 5.1 % and recoveries in the range of 86.4 ~ 102.9 %. [ABSTRACT FROM AUTHOR]

Background: Congenital intrahepatic shunts in children are rare and precise treatment strategies have not been established.Objective: The purpose of this study was to present our experience with transcatheter embolization in a descriptive case series of congenital intrahepatic shunts in children.Materials and Methods: We retrospectively studied 10 children with symptomatic congenital intrahepatic shunts who were treated with embolization at our institute between January 2008 and December 2014.Results: Seven children had arteriovenous shunts in association with hepatic hemangiomas, two had arterioportal shunts and one had portosystemic shunts. The major presentations were congestive heart failure and severe anemia in the groups with arteriovenous and arterioportal shunts, respectively. Following embolization, two children died in the arteriovenous group, one from progressive liver dysfunction and the other from abdominal compartment syndrome. One child in the arterioportal group required liver transplantation after initial embolization. With mean post-procedure follow-up of 15 months (range 4-54 months), all the remaining children were well, with resolution of the symptoms.Conclusion: Interventional embolization provides an alternative to surgical ligation or hepatic resection in children with clinically significant intrahepatic shunts. For lesions with complex morphology, embolization may be inadequate and liver transplantation might be the only therapeutic option. [ABSTRACT FROM AUTHOR]

Currently, advanced glycation end product (RAGE) is receiving much attention in carcinogenesis research due to its involvement in cancer progression and metastasis. We therefore sought to examine the association of circulating soluble RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE databases were searched before March 1, 2014. Data and study quality were assessed in duplicate. Effect estimates were expressed as weighted mean difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible articles including 1,337 cancer patients and 1,839 controls were analyzed. The overall analysis indicated that circulating sRAGE was remarkably reduced by 222.07 pg/ml in cancer patients compared with controls (95 % CI: −373.77 to −70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup analyses, this reduction was weakened yet still significant in prospective studies (WMD = −87.62; 95 % CI: −138.60 to −36.63; P = 0.001) with improved heterogeneity ( I = 56.5 %; P = 0.056). Restricting analyses to the large studies (total number of subjects ≥200) identified significant reduction of circulating sRAGE in cancer patients relative to controls (WMD = −231.34; 95 % CI: −450.10 to −12.58; P = 0.038). Further meta-regression analysis showed that smoking status explained some part of heterogeneity for the association of circulating sRAGE with cancer risk (regression coefficient: −67.02; P = 0.046). Our findings demonstrate a protective role of circulating sRAGE in the development of cancer, especially in patients without diabetes mellitus or with normal renal function. [ABSTRACT FROM AUTHOR]

We have developed an unlabeled sensing strategy for tetracycline (TET) detection in aqueous solutions and milk by using an aptamer-gold nanoparticle (AuNP)-based colorimetric method. Aptamers were found to be absorbed on the Au surface which stabilizes the AuNPs against conditions of high poly(diallyldimethylammonium) strength. The introduction of TET had reduced aptamers to form a TET-aptamer complex, so that the following cationic polymers could aggregate AuNPs and cause a remarkable change in color. Through this phenomenon, TET can be detected qualitatively and quantitatively by means of absorbance. This unlabeled strategy saves both the time and cost for detection, which could selectively detect TET at concentrations as low as 1 μM and 45.8 nM for the naked eyes and colorimetric detector, respectively. In addition, this biosensor exhibited high selectivity over other antibiotics with an excellent recovery in the detection of milk. Because of the advantages of this sensor, we hope this will be the basis for an assay for the sensitive, colorimetric detection of a wide range of molecular analytes. [ABSTRACT FROM AUTHOR]

Fasciolosis is an economically important disease for livestock, as well as being zoonotic. Recent figures on the prevalence of this disease have caused alarm concerning its potential for an increased prevalence in the future. The prevalence of fascioliosis has been documented from different regions of the world, helping us identify areas where future research needs to be focused. This manuscript is a review of the current status of the disease, the pathogenic species involved, diagnostic techniques (with new modifications and comparative specificity, sensitivity, and rapidity of these tests), chemotherapy, and vaccination. This also encompasses inaccurate reports on vaccination and drug development as well as the latest technologies to find promising candidates for drugs and vaccines. Drugs with lower efficacy have been used on some farms which lead to exacerbation of the clinical disease, presumably due to the development of drug resistance. Future studies should be focused on (1) the use of the most reliable diagnostic tests for periodic monitoring of the disease, (2) insights of the ecobiology and transmission dynamics of the snail intermediate host and the best possible methods of their control, (3) in vitro and in vivo testing of chemotherapeutic compounds using sensitive methods, and (4) the identification of novel drug and vaccine candidates using modern molecular markers. This approach may help increase the reliability of chemotherapeutic agents and control nuisance, ultimately reducing the economic losses attributable to the livestock industry around the world. [ABSTRACT FROM AUTHOR]

Vascular peroxidase 1 (VPO1) can utilize reactive oxygen species (ROS) generated from NADPH oxidase (NOX) to catalyze peroxidative reactions. This study was performed to identify a novel pathway of NOX/VPO1 in mediating the oxidative injury following myocardial ischemia reperfusion (IR). In a rat model of myocardial IR, the infarct size, serum creatine kinase (CK) activity, apoptosis, NOX activity, NOX2 and VPO1 expression were measured. In a cell (rat heart-derived H9c2 cells) model of hypoxia/reoxygenation (HR), the apoptosis, NOX activity, NOX2 and VPO1 expression, and HO and HOCl levels were examined. In vivo, IR caused 54.8 ± 1.7 % infarct size in myocardium accompanied by elevated activities of CK, caspase-3 and NOX, up-regulated VPO1 expression and high numbers of myocardial apoptotic cells; these effects were attenuated by pretreatment with the inhibitor of NOX. In vitro, inhibition of NOX or silencing of NOX2 or VPO1 expression significantly suppressed HR-induced cellular apoptosis concomitantly with decreased HOCl production. Inhibition of NOX or silencing of NOX2 led to a decrease in HO production accompanied by a decrease in VPO1 expression and HOCl production. However, silencing of VPO1 expression did not affect NOX2 expression and HO production. HO-induced VPO1 expression was partially reversed by JNK or p38 MAPK inhibitor. Our results demonstrate a novel pathway of NOX2/VPO1 in myocardium, where VPO1 coordinates with NOX2 and amplifies the role of NOX-derived ROS in oxidative injury following IR. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy and safety of sphenopalatine ganglion needling in treating patients with primary trigeminal neuralgia (PTN) of Liver (Gan)-yang upsurge syndrome (LYUS) type. Methods: Sixty-five PTN patients of LYUS type were assigned by a random number table to two groups and treated by deep-needling (33 patients, DN group) and superficial-needling (32 patients, SN group), respectively. The main-acupoint used for both groups was Xiaguan (ST7) of affected side, on which needle was deeply inserted to reach spheno-palatine ganglion in the DN group, but was inserted conventionally in the SN group; the auxiliary acupoints used were the local points Cuanzhu (BL2), Sibai (ST2), Chengjiang (CV24) of affected side, as well as the remote points, bilateral Hegu (LI4) and Taichong (LR3). The needling was implemented every other day, with electric stimulation applied to all the punctured acupoints for 30 min, 10 days treatment as one therapeutic course. Each patient received 2 courses of needling with 1 week interval in between. The clinical efficacy, pain control and adverse reaction were evaluated and compared after the treatment. Results: Rank-sum test showed that the efficacy in the DN group was significantly better than that in the SN group ( Z =2.30, P=0.021); the pain was alleviated in both groups in frequency, intensity and sustained time (evaluated by visual analogue scale) significantly ( P<0.01), but deep needling showed a superiority over superficial needling in reducing the frequency and intensity of episode ( Z=9.55, Z=5.50, both P=0.00). No adverse reaction occurred during the treatment course of both groups. Conclusion: Spheno-palatine ganglion needling is highly effective, safe and reliable for the treatment of PTN. [ABSTRACT FROM AUTHOR]

This longitudinal study addressed the sequential events and metabolic consequences of lipid partitioning following uninephrectomy. Adult male Sprague-Dawley rats were randomized into sham operation ( n = 15) or left uninephrectomy (UNX, n = 18). At 1 and 3 months post nephrectomy, three rats from each group were killed for histopathological examination of adipocyte differentiation and lipid accumulation. Renal protein expression of the lipogenic peroxisome proliferator-activated receptor-γ (PPAR-γ), HMG-CoA reductase (HMGCR), and adiponectin receptor was detected by Western blot and immunofluorescence microscopy. Blood lipids, glucose, insulin, and renal functions were longitudinally measured up to 10 months after operation. The UNX rats progressively developed lipodystrophy of subcutaneous and visceral adipose depots with failure of adipocyte differentiation and lipid storage, followed by blood lipid elevation and ectopic lipid deposition with cellular lipid peroxidation, and renal adipogenesis with chronic inflammatory infiltration. Despite having standard diet, normal food consumption and normal body weight, the uninephrectomized rats with defective lipid partitioning manifested a myriad of homeostatic disturbances including insulin resistance, hyperglycemia, adiponectin resistance, and upregulation of PPAR-γ and HMGCR. Abnormal lipid partitioning from adipose depots to circulation and non-adipose tissues and non-adipocytic cells contributes to homeostatic disturbances and lipogenic activation. [ABSTRACT FROM AUTHOR]

The properties of absorption of infrared light for collagen, hemoglobin, bivine serum albumen (BSA) protein molecules with α- helix structure and water in the living systems as well as the infrared transmission spectra for person's skins and finger hands of human body in the region of 400-4000 cm (i.e., wavelengths of 2-20 μm) have been collected and determined by using a Nicolet Nexus 670 FT-IR Spectrometer, a Perkin Elmer GX FT-IR spectrometer, an OMA (optical multichannel analysis) and an infrared probe systems, respectively. The experimental results obtained show that the protein molecules and water can all absorb the infrared lights in the ranges of 600-1900 cm and 2900-3900 cm, but their properties of absorption are somewhat different due to distinctions of their structure and conformation and molecular weight. We know from the transmission spectra of person's finger hands and skin that the infrared lights with wavelengths of 2 μm-7 μm can not only transmit over the person's skin and finger hands, but also be absorbed by the above proteins and water in the living systems. Thus, we can conclude from this study that the human beings and animals can absorb the infrared lights with wavelengths of 2 μm-7 μm. [ABSTRACT FROM AUTHOR]

The authors would like to correct the following panels in Figures [ABSTRACT FROM AUTHOR]

Pediatric patients with coronary artery lesions (CALs) after Kawasaki disease (KD) may be complicated with myocardial ischemia. Although previous studies in adults have proven the diagnostic value of 99mTc-MIBI myocardial perfusion imaging (MPI) for ischemic heart disease, its feasibility and accuracy in this pediatric population remain uncertain. In this retrospective study, we collected data of 177 pediatric patients (Age range: 6 months to 14 years) who had undergone MPI and coronary artery angiography (CAG) between July 2019 and February 2023. Using the positive result of CAG as the reference standard of myocardial ischemia, we compared the results of 99mTc-MIBI MPI with other non-invasive examinations, including cardiac magnetic resonance imaging (CMRI), echocardiogram, and comprehensive electrocardiogram-related examinations. All patients finished adenosine triphosphate stress MPI without major side effects. The sensitivity of MPI was 79.17%, which was greater than CMRI and echocardiogram (P < 0.05). The negative predictive value and the accuracy of MPI were 89.9% and 71.75%, indicating the advantages over others. Composite monitoring strategy of MPI and CMRI effectively improved the diagnostic performance (P < 0.001). In 4 cases diagnosed with myocardial ischemia by “MPI + CMRI,” despite the absence of significant stenosis, multiple giant coronary artery aneurysms (GCAA) were all observed in CAG. 99mTc-MIBI MPI is the preferred non-invasive examination for detecting myocardial ischemia in pediatric patients with CAL after KD. When combined with CMRI, it can enhance diagnostic accuracy. Multiple GCAAs without stenosis may be an isolated risk factor of myocardial ischemia. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ.Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi’an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software.A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ.Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Methods: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ.Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi’an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software.A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ.Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Results: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ.Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi’an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software.A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ.Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Conclusion: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ.Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi’an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software.A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ.Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.Key Points• Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases.• PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia.• It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency. [ABSTRACT FROM AUTHOR]