Asymmetric segregation of maternal mRNAs and germline-related determinants in Cephalochordate embryos: implications for the evolution of early patterning events in chordates.

How animal embryos determine their early cell fates is an important question in developmental biology. In various model animals asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification. Cephalochordates (amphioxus), which have three living genera (Asymmetron, Epigonichthys, Branchiostoma), are an early branching chordate lineage and thus occupy a key phylogenetic position for understanding the evolution of chordate developmental mechanisms. It has been shown that in the zygote of Brachiostoma amphioxus, which possess bilateral gonads flanking both sides of their trunk region, maternal transcripts of germline determinants form a compact granule. During early embryogenesis this granule is inherited by a single blastomere that subsequently gives rise to a cluster of cells displaying typical characteristics of primordial germ cells (PGC). These PGCs then come to lie in the tailbud region and proliferate during posterior elongation of the larva to join in the gonad anlagen at the ventral tip of the developing myomeres in amphioxus larvae. However, in Asymmetron and Epigonichthys amphioxus, whose gonads are present only on the right side of their body, nothing is known about their PGC development or the cellular/morphogenetic processes resulting in the asymmetric distribution of gonads. Using conserved germline determinants as markers, we show that similarly to Brachiostoma amphioxus, Asymmetron also employ a preformation mechanism to specify their PGCs, suggesting that this mechanism represents an ancient trait dating back to the common ancestor of Cephalochordates. Surprisingly, we found that Asymmetron PGCs are initially deposited on both sides of the body during early larval development; however, the left side PGCs cease to exist in young juveniles, suggesting that PGCs are eliminated from the left body side during larval development or following metamorphosis. This is reminiscent of the PGC development in the sea urchin embryo, and we discuss the implications of this observation for the evolution of developmental mechanisms.

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study.

BACKGROUND: To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). METHODS: This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected. RESULTS: A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories. CONCLUSION: SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

Global trends in research of melanoma differentiation-associated gene 5: a bibliometric analysis from 2002 to 2022.

BACKGROUND: Melanoma differentiation-associated gene 5 (MDA5), as a cytoplasmic sensor for viral double-stranded RNAs, has received increasing attention in recent years. Although considerable headway has been made on the functional role of MDA5 in antiviral immunity and autoimmune disease, the available literature is insufficient to assess the vast field. METHODS: This study performed a bibliometric analysis to investigate current hotspots in the global scientific output of MDA5 over the past two decades. Related publications and recorded information from 2002 to 2022 in the Web of Science Core Collection (WoSCC) database were retrieved. VOSviewer and CiteSpace were used for quantitative evaluation and visualization. RESULTS: A total of 2267 original articles and reviews were obtained, and the annual number of publications related to MDA5 was increasing rapidly. China has published the most papers, while the USA was the most influential country with the most citations and the highest H-index. The Chinese Academy of Sciences, the United States Department of Health and Human Services, and the Journal of Virology were the most prolific research affiliation, funding source, and journal, respectively. Fujita T (Kyoto University) was the most productive author with the highest H-index and had close cooperation with Kato H and Yoneyama M. The keywords "RIG-I," "MDA5," "innate immunity," "double-stranded-RNA," and "recognition" had the highest frequency, while "dermatomyositis" as well as "autoantibody" seemed to be the emerging hotspots. CONCLUSION: This study comprehensively demonstrated the research frontiers of MDA5 and will provide a useful resource for scholars to conduct future decisions. KEY POINTS: We conducted the first in-depth survey of the research frontiers on melanoma differentiation-associated gene 5 (MDA5) over the past two decades via bibliometric analysis. We found that many early breakthroughs have been made in the mechanism of MDA5-mediated antiviral immune responses, and the role of MDA5 in autoimmune and autoinflammatory diseases has raised the recent concern. We identified that the virus infection-associated pathogenesis and effective therapeutic strategy of anti-MDA5 antibody-positive dermatomyositis will remain the hotspots in the future.

CD24+ decidual stromal cells: a novel heterogeneous population with impaired regulatory T cell induction and potential association with recurrent miscarriage.

OBJECTIVE: To explore the heterogeneity of CD24+ decidual stromal cells (DSCs) in patients with recurrent miscarriages (RMs). DESIGN: We have discerned that the expression of CD24 serves to differentiate two stable and functionally distinct lineages of DSCs. The heterogeneity of CD24+ DSCs has been scrutinized, encompassing variances in stromal markers, transcriptional profiles, metabolic activity, and immune regulation. SETTING: Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University; Shanghai Institute of Immunity and Infection, Chinese Academy of Science. PATIENTS: A total of 129 early decidual samples were obtained, comprising 36 from healthy donors and 93 from patients with RMs. Blood samples were collected before the surgical procedure. Paraffin-embedded segments from 20 decidual samples of patients with RMs were obtained. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The flow cytometry was used to quantify the expression of CD24+ DSCs in both healthy donors and patients with RMs, although it also evaluated the cellular heterogeneity. To ascertain the transcriptomic profiles of CD24+ DSCs by reanalyzing our single-cell transcriptomic data. Additionally, to measure the metabolomic activity of CD24+ DSCs from patients with RMs, ultraperformance liquid chromatography-mass spectrometry was employed. Through the implementation of a coculture system, we unraveled the role of CD24+ DSCs in immune regulation. RESULTS: Patients with RMs exhibit a notable enrichment of CD24+ DSCs, revealing a pronounced heterogeneity characterized by variations in stromal markers and transcriptional profiles. The heightened enrichment of CD24+ DSCs may play a pivotal role in triggering decidual inflammation and dysfunction in decidualization. Furthermore, CD24+ DSCs showed diverse metabolic activities and impeded the induction of naïve CD4+ T cells into regulatory T cells through the abundant secretion of 3-hydroxyisovaleric acid. Finally, our investigations have revealed that intraperitoneal administration of 3-hydroxyisovaleric acid in mouse models can elevate the risk of RM. CONCLUSION: We have successfully identified a disease-associated subset of CD24+ decidual stromal cells that could potentially contribute to the development of RM through the impairment of decidual immune tolerance. Targeting these specific CD24+ DSCs might hold promising prospects for therapeutic interventions in the clinical management of RM.

Successful pregnancy and delivery after premature ovarian insufficiency combined with undifferentiated connective tissue disease: a case report.

BACKGROUND: Premature ovarian insufficiency (POI) is extremely rare in the early stage of undifferentiated connective tissue disease. Patients with POI find it difficult to achieve successful pregnancy and delivery. CASE PRESENTATION: A 27-year-old female visited an outpatient department for premature ovarian insufficiency (POI) and infertility. She had regular menstrual periods since she was 14 years old and had no history of systemic disease. Laboratory tests showed low estrogen (15 ng/L, range 19.6-144.2 ng/L), elevated follicle-stimulating hormone (34 U/L), low anti-Mullerian hormone (0.1 µg/L), normal prolactin (11.48 ng/mL), and thyroid stimulating hormone (TSH) levels (0.97 mU/L). She demonstrated smaller bilateral ovarian volume and positivity to antinuclear and antiphospholipid antibodies. After the failure of conventional drug therapy and in vitro fertilization, the patient became pregnant naturally after treatment with glucocorticoids. CONCLUSION: Immunosuppression could help improve ovarian function and pregnancy outcomes in POI patients, but the therapeutic mechanisms are not clear and should be elucidated with more clinical studies.

Efficacy and safety of Janus kinase inhibitors in systemic and cutaneous lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence regarding their efficacy and safety in systemic and cutaneous lupus erythematosus. METHODS: We searched for systemic and cutaneous lupus erythematosus patients who were treated with JAK inhibitors in PubMed, Embase, Web of Science, and the Cochrane Library until February 28, 2023. The quality of clinical trials was assessed using the Cochrane risk-of-bias tool. Meta-analysis was conducted when at least three studies had comparable measures of outcome. If meta-analysis was not feasible, a descriptive review was carried out. RESULTS: We included 30 studies, consisting of 10 randomized controlled trials and 20 case series or reports, with a total of 2,460 patients. JAK inhibitors were found to be more effective than placebo in systemic lupus erythematosus (SLE) based on the percentage of achieving SLE Responder Index (SRI)-4 response (RR = 1.18; 95% CI 1.07 to 1.31; p = 0.001), British Isles Lupus Assessment Group -based Composite Lupus Assessment (BICLA) response (RR = 1.16; 95% CI 1.02 to 1.31; p = 0.02), Lupus Low Disease Activity State (LLDAS) (RR = 1.28; 95% CI 1.07 to 1.54; p = 0.008), and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) remission of arthritis or rash (RR = 1.09; 95% CI 1.00 to 1.18; p = 0.04), particularly in treating musculoskeletal and mucocutaneous involvement. However, the effect of JAK inhibitors on cutaneous lupus erythematosus was uncertain. JAK inhibitors and placebo had a similar incidence of adverse events (RR = 1.01; 95% CI 0.97 to 1.04; p = 0.65). CONCLUSION: JAK inhibitors could be a potential treatment option for systemic and cutaneous lupus erythematosus, particularly in treating cutaneous and musculoskeletal lesions of SLE. JAK inhibitors had a safe profile.

Screening ester-producing yeasts to fortify the brewing of rice-flavor Baijiu for enhanced aromas.

To enhance the aromas in Guangdong rice-flavor Baijiu, ester-producing yeast was selected to fortify Baijiu brewing. Among eight kinds of ester-producing yeasts selected, Saccharomyces cerevisiae CM15 (CM15) that showed both the stronger ability to utilize substrates to produce esters and the excellent tolerance to industrially relevant stress factors was chosen. When CM15 was synergistically fermented with six kinds of Kojis from distilleries of rice-flavor liquor in Guangdong, the enhanced total esters had happened to the liquors brewing with the fortified four kinds of Kojis, especially with Koji F. When Koji F was fortified with CM15, the resultant Baijiu showed a higher esters proportion and a lower higher alcohol ratio than that of Baijiu brewed only with Koji F, with the content of ethyl acetate and ethyl lactate increasing by 25% and 214%, respectively. This study suggested that CM15 can be used as a functional microorganism to fortify Baijiu brewing, which might also be suitable for other traditional fermented foods.

Artificial Intelligence Iterative Reconstruction in Computed Tomography Angiography: An Evaluation on Pulmonary Arteries and Aorta With Routine Dose Settings.

OBJECTIVE: The objective of this study is to investigate whether a newly introduced deep learning-based iterative reconstruction algorithm, namely, the artificial intelligence iterative reconstruction (AIIR), has a clinical value in computed tomography angiography (CTA), especially for visualizing vascular structures and related lesions, with routine dose settings. METHODS: A total of 63 patients were retrospectively collected from the triple rule-out CTA examinations, where both pulmonary and aortic data were available for each patient and were taken as the example for investigation. The images were reconstructed using the filtered back projection (FBP), hybrid iterative reconstruction (HIR), and the AIIR. The visibility of vasculature and pulmonary emboli and the general image quality were assessed. RESULTS: Artificial intelligence iterative reconstruction resulted in significantly (P < 0.001) lower noise as well as higher signal-to-noise ratio and contrast-to-noise ratio compared with FBP and HIR. Besides, AIIR achieved the highest subjective scores on general image quality (P < 0.05). For the vasculature visibility, AIIR offered the best vessel conspicuity, especially for the small vessels (P < 0.05). Also, >90% of emboli on the AIIR images were graded as sharp (score 5), whereas <15% of emboli on FBP and HIR images were scored 5. CONCLUSION: As demonstrated for pulmonary and aortic CTAs, AIIR improves the image quality and offers a better depiction for vascular structures compared with FBP and HIR. The visibility of the pulmonary emboli was also increased by AIIR.

Prognosis of post-neoadjuvant therapy patients who underwent immediate breast reconstruction: a SEER-based, propensity-matched study.

OBJECTIVE: The application of immediate breast reconstruction (IBR) for post-neoadjuvant therapy (NAT) patients was controversial. The aim of this study was to investigate the long-term survival outcomes of IBR for these patients. METHODS: Data between January 2010 and November 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce the influence of confounding factors between the mastectomy alone group (MA) and the mastectomy with IBR group (IBR). The rates of 5 year breast cancer-specific survival (BCSS) were compared by Kaplan-Meier curves with log-rank test. RESULTS: The IBR was associated with improved 5-year BCSS in the IBR group before PSM (88.5 vs. 79.1%, P < 0.001). The proportion of IBR increased from 21.5% in 2010 to 28.2% in 2017. After PSM, a total of 9,610 patients were enrolled for survival analysis (4,805 in each group). In the complete response (CR) group, the 5-year BCSS rates did not differ (93.4 vs. 95.6%, P = 0.16). In the non-CR group, the 5-year BCSS rate was higher in patients who received IBR (82.5% 79.4%, P = 0.034). CONCLUSION: In general, the application of IBR among post-NAT patients has steadily increased from 2010 to 2017. In the CR group, survival outcomes of post-NAT patients who received IBR were similar to those who received mastectomy alone. In the non-CR group, IBR was associated with potential survival benefits. More studies are expected to validate our findings.

Effects of ultra-high-temperature processes on metabolite changes in milk.

Processing can affect milk properties and alter the composition of milk metabolites, which has corresponding effects on milk flavor and quality. It is quite important to study the safe quality control of milk processing. Therefore, the purpose of this study was to identify metabolites at different steps of ultra-high-temperature-sterilized (UHT) milk processing using gas chromatography-mass spectrometry (GC-MS). These steps included raw milk, pasteurized milk (80°C for 15 s), semi-finished milk (after pasteurizing, it was homogenized at 75°C with pressure of 250 bar), UHT milk (at 140°C for 10 s), and finished milk (homogenized UHT milk). A total of 66 metabolites were identified across all samples, including 30 metabolites in the chloroform layers of the milk samples and 41 metabolites in the water layers; 5 metabolites were found in both layers. The metabolites were primarily fatty acids, amino acids, sugars, and organic acids. For example, pasteurized and ultra-high-temperature-sterilized kinds of milk had lactose contents similar to those of raw milk, with increases in saturated fatty acids such as hexadecanoic acid and octadecanoic acid. Additionally, these findings indicated that these methods of processing can affect the contents of some components of milk. Therefore, from the perspective of milk's nutritional value and consumer health, the excessive heating of dairy products should be avoided and the milk heat treatment process should be standardized from the source.

Biological characteristics of microRNAs secreted by exosomes of periodontal ligament stem cells due to mechanical force.

BACKGROUND: Orthodontic tooth movement (OTM) has previously been considered an inflammatory process. However, recent studies suggest that exosomes may play an important role in the cellular microenvironment of OTM. microRNAs (miRNAs) are one of the major constituents of exosomes. This study aims to investigate the biological characteristics of miRNAs secreted by exosomes of periodontal ligament stem cells (PDLSCs) due to mechanical forces. MATERIALS AND METHODS: First, we established a mechanical stress model. The PDLSCs were loaded under different force values and exosomes were extracted after 48 h. High-throughput sequencing of exosomal miRNAs was performed to further evaluate their biological functions and underlying mechanisms. RESULTS: The morphology and functions of exosomes were not significantly different between the loading and non-loading PDLSC groups. The optimal loading time and force were 48 h and 1 g/cm2, respectively. After sequencing, gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) pathway and network analyses were performed and 10 differentially expressed miRNAs were identified according to a literature search. These are miR-99a-5p, miR-485-3P, miR-29a-3p,miR-21-5p, miR-146a-5p, miR140-3p, miR-1306-5p, miR-126-5p, miR-125a-5p, and miR-23a-3p. LIMITATIONS: Extracting exosomes needs a large amount of PDLSCs. More functional experiments need to be done to confirm the exact mechanism of exosomal miRNAs of PDLSCs due to mechanical force. CONCLUSIONS: The expression levels of miRNAs secreted by PDLSC-derived exosomes due to mechanical force were very different compared to PDLSC-derived exosomes under nonmechanical stress. The function of many of the identified exosomal miRNAs was found to be related to osteoblasts and osteoclasts. Further validation is required. A functional investigation of these miRNA could provide novel insights into their mechanism.

Survival Nomogram for Patients With Locally Advanced Breast Cancer Undergoing Immediate Breast Reconstruction: A SEER Population-Based Study.

INTRODUCTION/BACKGROUND: This study aimed to construct a nomogram to provide prognostic references for patients with locally advanced breast cancer (LABC) to receive immediate breast reconstruction (IBR). MATERIALS AND METHODS: All data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and best subset regression (BSR), separately followed by backward stepwise multivariable Cox, were used to construct the nomogram. Risk stratification was established after validation. RESULTS: A total of 6,285 patients were enrolled to generate the training group (n = 3,466) and the test group (n = 2,819) by geographical split. Age, marital status, grade, T staging, N staging, radiotherapy, chemotherapy, estrogen receptor status (ER), progesterone receptor status (PR) and human epidermal growth factor receptor type 2 status (HER2) were used to fit the nomogram. The overall Harrell's concordance index (C-index) was 0.772 in the training group and 0.762 in the test group. The area under the receiver operator characteristic curves (AUC) at 3-year and 5-year were respectively 0.824 and 0.720 in the training group, 0.792 and 0.733 in the test group. The calibration curves showed great consistency in both groups. A dynamic nomogram (https://dcpanfromsh.shinyapps.io/NomforLABCafterIBR/) was developed. CONCLUSION: A nomogram was developed and validated that predicts prognosis more accurately than the AJCC 7th stage and can be used as a reference for decision-making in LABC patients receiving IBR.

Do intravitreal anti-vascular endothelial growth factor agents lead to renal adverse events? A pharmacovigilance real-world study.

Purpose: Intravitreal vascular endothelial growth factor (VEGF) blockade is essential in many macular edema diseases treatment. However, intravitreal VEGF treatment has been reported to lead to deteriorated proteinuria and renal function. This study aimed to explore the relationship between renal adverse events (AEs) and the intravitreal use of VEGF inhibitors. Method: In the FDA's Adverse Event Reporting System (FAERS) database, we searched for renal AEs of patients receiving various anti-VEGF drugs. We performed statistics on renal AEs in patients treated with Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab (from January 2004 to September 2022) using disproportionate and Bayesian analysis. We also investigated the time to onset, fatality, and hospitalization rates of renal AEs. Results: We identified 80 reports. Renal AEs were most frequently associated with Ranibizumab (46.25%) and Aflibercept (42.50%). However, the association between intravitreal anti-VEGFs and renal AEs was insignificant since the reporting odds ratio of Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab were 0.23 (0.16, 0.32), 0.24 (0.11, 0.49), 0.37 (0.27, 0.51) and 0.15 (0.04, 0.61), respectively. The median time to renal AEs onsets was 37.5 (interquartile range 11.0-107.3) days. The hospitalization and fatality rates in patients who developed renal AEs were 40.24 and 9.76%, respectively. Conclusion: There are no clear signals for the risk of renal AEs following various intravitreal anti-VEGF drugs based on FARES data.

Distribution, source identification and ecological effects of aerosol dissolved nutrients in the Bohai Bay.

The atmospheric aerosols around the Bohai Bay are affected intensively by the surrounding industrial, shipping and other human activities. Although atmospheric dry deposition is an important way for nutrients to enter the Bohai Bay, few studies explore the distribution patterns, source and deposition fluxes of typical nutrients in aerosols and their impacts on the marine ecosystem. This paper explored the spatial-temporal distribution of typical aerosol nutrients in summer and autumn, and their source and ecological effects were illustrated further. The mean concentration of dissolved total phosphorus (DTP), dissolved total nitrogen (DTN), dissolved organic nitrogen (DON), dissolved inorganic nitrogen (DIN), ammonium (NH4-N), nitrate (NO3-N), nitrite (NO2-N), silicate (SiO3-Si), phosphate (PO4-P), and dissolved organic phosphorus (DOP) were 31.22, 847.22, 288.19, 559.77, 288.19, 304.00, 253.65, 2.12, 15.74 and 15.48 nmol/m3, respectively, while their fluxes were corresponding to 0.61, 8.36, 2.52, 4.90, 1.41, 2.49, 0.02, 0.04, 0.19 and 0.26 mmol/(m2 month). Typical aerosol nutrient concentrations in autumn were mostly higher than those in summer, with high values occurring mainly in the central region. The potential sources of pollution were mainly concentrated in Shandong and Mongolia, and the sources of pollution were mainly agriculture, dust and industry. The large N:P and N:Si ratios in the dry deposition likely exacerbated Si and P limitation in the water column. These results provided the data basis for evaluating the pollution status and revealed that the dry deposition of aerosol nutrients should not be neglected by the ecological environment in the Bohai Bay.

Accuracy of additive manufacturing in stomatology.

With the rapid development of the three-dimensional (3D) printing technology in recent decades, precise and personalized manufacturing has been achieved gradually, bringing benefit to biomedical application, especially stomatology clinical practice. So far, 3D printing has been widely applied to prosthodontics, orthodontics, and maxillofacial surgery procedures, realizing accurate, efficient operation processes and promising treatment outcomes. Although the printing accuracy has improved, further exploration is still needed. Herein, we summarized the various additive manufacturing techniques and their applications in dentistry while highlighting the importance of accuracy (precision and trueness).

Research progress on ANXA5 in recurrent pregnancy loss.

The incidence of recurrent pregnancy loss (RPL) in fertile women ranges from 1% to 5%, of which about 50% of them are due to unknown causes. The possible pathogenesis of RPL is an urgent problem to be solved in the clinical. Mutations or polymorphisms of certain genes in the coagulation mechanism are associated with susceptibility to thrombotic diseases and are one of the main reasons for the occurrence of RPL. Among them, the ANXA5 gene was newly studied and some single nucleotide polymorphisms (SNPs) in the promoter region of ANXA5 have been reported to be associated with RPL in multiple races. In this review, we summarized the research progress on the correlation between the SNPs in ANXA5 and RPL, hoping to provide some valuable guidance for the future studies.