METTL3 Modulates Ctsk+ Lineage Supporting Cranial Osteogenesis via Hedgehog.

N6-methyladenosine (m6A) modification, a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), plays a pivotal role in stem cell fate determination. Calvarial bone development and maintenance are orchestrated by the cranial sutures. Cathepsin K (CTSK)-positive calvarial stem cells (CSCs) contribute to mice calvarial ossification. However, the role of m6A modification in regulating Ctsk+ lineage cells during calvarial development remains elusive. Here, we showed that METTL3 was colocalized with cranial nonosteoclastic Ctsk+ lineage cells, which were also associated with GLI1 expression. During neonatal development, depletion of Mettl3 in the Ctsk+ lineage cells delayed suture formation and decreased mineralization. During adulthood maintenance, loss of Mettl3 in the Ctsk+ lineage cells impaired calvarial bone formation, which was featured by the increased bone porosity, enhanced bone marrow cavity, and decreased number of osteocytes with the less-developed cellular outline. The analysis of methylated RNA immunoprecipitation sequencing and RNA sequencing data indicated that loss of METTL3 reduced Hedgehog (Hh) signaling pathway. Restoration of Hh signaling pathway by crossing Sufufl/+ alleles or by local administration of SAG21 partially rescued the abnormity. Our data indicate that METTL3 modulates Ctsk+ lineage cells supporting calvarial bone formation by regulating the Hh signaling pathway, providing new insights for clinical treatment of skull vault osseous diseases.

[Research progress in methylation modification in tooth root development].

Methylation modification is one of the most common epigenetic modification regulation in eukaryotes, including histone methylation, DNA methylation, RNA methylation, etc., which plays an important regulatory role in physiological processes and pathologic occurrence and development. Tooth root development is carried out by both epithelial and mesenchymal cells and involves a variety of cell-molecular interactions. In recent years, a large number of studies have found that methylation plays a key role in the regulation of tooth root development and expands the mechanism network of tooth root development. In this paper, we review the role and mechanism of methylation modification during root development.

[Comparative study of percutaneous transfacet screw and pedicle screw in oblique lumbar interbody fusion for the treatment of single-level lumbar spinal stenosis].

Objective: To conduct a comparative study of radiological and clinical outcomes between percutaneous transfacet screw (TFS) and pedicle screw (BPS) in oblique lateral lumbar interbody fusion (OLIF) for single-level lumbar spinal stenosis. Methods: A retrospective cohort study. Patients who underwent OLIF with TFS or BPS for the treatment of single-level lumbar spinal stenosis at Beijing Jishuitan Hospital from January 2019 to June 2022 were retrospectively analyzed. Radiological parameters and clinical indicators were compared between the two groups. Radiological parameters included preoperative, immediate postoperative (within 5 days), and 1-year postoperative measurements of disc height and segmental lordosis angle, as well as interbody fusion status at 1 year postoperatively. Clinical indicators included operative time, blood loss, length of hospital stay, complications, and Oswestry Disability Index (ODI), visual analogue scale (VAS) scores for back pain, and leg pain before and 1 year after surgery. Results: Four male and 10 female patients with an average age of (61.0±11.2) years underwent OLIF with TFS, while 9 male and 12 female patients underwent OLIF with BPS, with a mean age of (60.9±6.7) years. There was no statistically significant difference in preoperative disc height between the TFS and BPS groups (P>0.05). The immediate postoperative disc height was (12.9±2.1) mm and it was (10.4±1.7) mm at 1-year follow-up in the TFS group; in the BPS group, it was (12.9±2.1) mm immediately postoperatively and (11.9±2.1) mm at 1-year follow-up; there was statistically significant difference between the two groups at 1-year follow-up (P=0.037). The segmental lordosis angle showed no significant differences within each group or between the two groups at preoperative, immediate postoperative, or 1-year postoperative follow-up (all P>0.05). At 1-year postoperative follow-up, the fusion rates was 92.9%(13/14) in the TFS group and 95.2%(20/21) in the BPS group, with no statistically significant difference between the two groups (P>0.05). The TFS group had a significantly shorter operative time and less blood loss compared to the BPS group [(164.3±33.9) minutes vs (191.7±31.8) minutes and (74.3±46.9) ml vs (124.8±54.0) ml, respectively] (both P<0.05). Both groups showed significant improvement in ODI and VAS scores at 1 year postoperatively compared to those preoperatively, but with no statistically significant difference was found between the groups (both P>0.05). Conclusions: OLIF with TFS fixation can effectively restore disc height and alleviate back and leg pain in patients with single-level lumbar spinal stenosis. Compared to the OLIF with BPS procedure, OLIF with TFS has shorter operative time and less blood loss.

[Spermidine alleviates lipopolysaccharide-induced myocardial injury in mice by suppressing apoptosis, ROS production and ferroptosis].

OBJECTIVE: To investigate the protective effect of spermidine against lipopolysaccharide (LPS)-induced myocardial injury in mice and the underlying mechanism. METHODS: C57BL/6 mice subjected to intraperitoneal LPS injection with or without pretreatment with daily gavage of spermidine for 2 weeks were examined for myocardial pathologies using HE staining and transmission electron microscopy. In the cell experiment, cultured rat cardiomyocytes (H9c2 cells) were pretreated with 10 or 20 µmol/L spermidine before LPS exposure for 2 h, and the changes in cell viability and levels of lactate dehydrogenase (LDH) and cardiac troponin Ⅰ (cTNI) were assessed using CCK-8 kit, LDH detection kit and ELISA, respectively. Western blotting was performed to detect the changes in the expressions of Bax, Bcl-2, cleaved caspase-3, SLC7A11 and GPX4; the changes in reactive oxygen species (ROS) and Fe2+ levels were detected using fluorescent probes, and mitochondrial membrane potential of the cells was measured using JC-1 staining. RESULTS: Treatment of the mice with LPS induced obvious myocardial and mitochondrial damages, which were significantly alleviated by pretreatment with spermidine. In H9c2 cells, LPS exposure significantly lowered the cell viability, increased LDH and cTNI levels and expressions of Bax and cleaved caspase-3 levels, decreased expressions of Bcl-2, SLC7A11 and GPX4, increased ROS production and Fe2+ level (P < 0.05), and lowered mitochondrial membrane potential (all P < 0.05). These effects were significantly alleviated by SPD pretreatment of the cells prior to LPS exposure. CONCLUSION: Spermidine alleviates LPS-induced myocardial injury by suppressing cell apoptosis and inhibiting cellular ROS production and ferroptosis.

Serum human epidermal growth factor receptor-2 extracellular domain, carcinoma embryonic antigen and carbohydrate antigen 15-3 combined detection in early diagnosis of breast cancer.

The multi-markers combined detection can make up for the deficiency of single marker detection and significantly increase the positive detection rates of tumors. This study aimed to assess the performance of serum HER-2 extracellular domain (HER-2/neu ECD), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA15-3) in early screening and auxiliary diagnosis of breast cancer. The HER-2, CEA, and CA15-3 serum levels were measured in 164 healthy volunteers, 111 patients with benign nodules (BN), 123 with early breast cancer (EBC), and 25 with advanced breast cancer. In distinguishing health and EBC, the sensitivity and specificity of joint detection of HER-2, CEA, and CA15-3 were 96.75% and 96.95%, respectively; the accuracy was up to 96.19%, and the AUC was 0.994. In the cohort for distinguishing BN from EBC, serum HER-2, CEA, and CA15-3 sensitivities were 77.03%, 75.27%, and 48.65%, respectively. Combined with three markers, the sensitivity was increased to 84.46%, the AUC was 0.834. All in all, through the combined detection of serum HER-2, CEA and CA15-3 levels in healthy volunteers, BN and EBC, our study found that this method can significantly improve the diagnosis level of breast cancer, suggesting that the three markers panel can be used as an effective tool to improve the early screening level, early diagnosis, and clinical intervention of breast cancer.

Meta-analysis exploring the effectiveness and safety of different doses of estrogen in the treatment of osteoporosis in perimenopausal women in China.

OBJECTIVE: This study aims to systematically evaluate the effectiveness and safety of using different doses of estrogen in the treatment of perimenopausal osteoporosis in China. MATERIALS AND METHODS: Computer searches of the Cochrane Library, PubMed, Embase, CBM, CNKI, WanFang Date, and VIP databases were conducted. Randomized Controlled Trials (RCTs) on different doses of estrogen for the treatment of osteoporosis in Chinese perimenopausal women were searched for the period 01/01/2000-06/09/2022. Document screening and data extraction were completed independently by 2 researchers and assessed using the Cochrane recommended risk bias assessment tool for RCTs. The software used for analysis in this study was Stata, version 16.0. RESULTS: A total of 10 RCTs with a cumulative total of 804 patients were included. Meta-analysis results showed that low doses of estrogen were more effective in improving patient outcomes [OR=0.521, 95% CI (0.300-0.907), z = 2.31, p ≤ 0.05] and bone mineral density [SMD = -0.218, 95% CI (-0.42,-0.016), z = 2.11, p ≤ 0.05] was not superior. For bone metabolism and sex hormone indicators, the standard dose group had a slight advantage, but the difference was small (p > 0.05) and not statistically significant. With regard to safety, the incidence of adverse reactions was higher with the standard dose of estrogen. CONCLUSIONS: In China, standard doses of estrogen are used for clinical effectiveness. However, vigilance must be maintained for potential safety concerns that may arise during treatment.

[Prognostic significance and immune cell infiltration analysis of differentially expressed genes in malignant pleural mesothelioma].

Objective: To explore and analyze differential expressed genes in malignant pleural mesothelioma (MPM) by bioinformatics method, and to study their prognostic value in MPM and their potential role in immunotherapy. Methods: In January 2022, the dataset GSE51024 was downloaded from the GEO database, and MPM (55 cases) and normal tissue (41 cases) samples were obtained. Using R software and HMDD and miRNet database, MPM-related differential genes were screened and co-expressed genes were identified. Co-expressed genes were enriched and functionally annotated, and protein-protein interaction (PPI) networks were constructed and key genes were identified using the STRING database and Cytoscape software. TRRUST and GEPIA databases were used to predict transcription factors of key genes and to analyze prognosis and survival. The correlation between key genes and the degree of infiltration of immune cells was analyzed using TIMER. Results: A total of 435 co-expressed genes were obtained, which were mainly concentrated in the extracellular matrix tissue and the signaling pathways of cell adhesion molecules. Combined with PPI and TRRUST database, seven key MPM prognostic genes were identified. Among them, cyclin 20 (CDC20) , cell cycle checkpoint kinase 1 (CHEK1) , enhancer of Zeste homolog 2 (EZH2) , ribonucleotide reductase subunit M2 (RRM2) , topoisomerase 2A (TOP2A) , ubiquitin like plant homeodomain and ring finger domain 1 (UHRF1) were significantly up-regulated in MPM, while cyclin A1 (CCNA1) was significantly down-regulated. The expressions of CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 genes were significantly associated with MPM overall survival (P<0.05) . The expressions of CDC20, CHEK1, EZH2, RRM2 and TOP2A genes were positively correlated with B cells and dendritic cells (P<0.05) , and negatively correlated with neutrophils (P<0.05) . Conclusion: CCNA1, CDC20, CHEK1, EZH2, RRM2, TOP2A and UHRF1 may be potential prognostic markers in MPM patients, and their expressions may be related to MPM tumor immunity.

[Epidemiological characteristics of incident cases and risk factors of hepatitis C infection in Beijing City from 2004 to 2021].

Objective: To analyze the epidemiological characteristics and related factors of hepatitis C in Beijing City from 2004 to 2021. Methods: Descriptive epidemiological method and Joinpoint regression were used to analyze the trend and other epidemiological characteristics of hepatitis C in Beijing City from 2004 to 2021 in National Notifiable Disease Reporting System. According to a 1∶1 matched case-control study design, logistic regression was used to investigate the risk factors of hepatitis C infection in 2021. Results: From 2004 to 2021, the reported incidence of hepatitis C in Beijing City ranged from 2.37/100 000 to 10.46/100 000. The reported cases were mainly aged 30-60 years, and most of them were chronic. The reported incidence of hepatitis C showed an initial increase from 2004 to 2006 (APC=45.37%, 95%CI:-1.56%-114.69%), and declined after 2006 (APC=-9.21%, 95%CI:-10.70%-7.70%). Logistic analysis showed that history of surgery (OR=1.84, 95%CI: 1.08-3.14) and previous blood transfusion (OR=34.22, 95%CI: 8.05-145.41) were risk factors for hepatitis C infection. Conclusion: The reported incidence of hepatitis C in Beijing City increases first and decreases later. It currently remains at a low level. The risk factors of infection are surgery and blood transfusion history. Safe blood supply and preventing iatrogenic transmission should be focused on the prevention of hepatitis C transmission.

Mass Measurement of Upper fp-Shell N=Z-2 and N=Z-1 Nuclei and the Importance of Three-Nucleon Force along the N=Z Line.

Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.

[Study on the related factors of antiviral treatment in previously reported hepatitis C patients based on the Andersen model].

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

Identification of novel characteristic biomarkers and immune infiltration profile for the anaplastic thyroid cancer via machine learning algorithms.

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and lethal malignant cancer. In recent years, the application of molecular-driven targeted therapy and immunotherapy has markedly improved the prognosis of ATC. This study aimed to identify characteristic genes for ATC diagnosis and revealed the role of ATC characteristic genes in drug sensitivity and immune cell infiltration. METHODS: We downloaded ATC RNA-sequencing data from the GEO database. Following the combination and normalization of the dataset, we first divided the combined datasets into the training cohort and the validation cohort. We identified differentially expressed genes (DEGs) in ATC by differential expression analysis in the training cohort. We used two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) to identify ATC characteristic genes. The CIBERSORT algorithm was performed to calculate the abundance of various immune cells in ATC. Finally, we validated the expression of ATC characteristic genes by quantitative RT-PCR (RT-qPCR) in ATC cell lines and immunohistochemistry (IHC). RESULTS: A total of 425 DEGs were identified in the training cohort, including 240 upregulated genes and 185 downregulated genes. Four ATC characteristic genes (ADM, PXDN, MMP1, and TFF3) were identified, and their diagnostic value was validated in the validation cohort (AUC in ROC analysis > 0.75). We established a practical gene expression-based nomogram to accurately predict the probability of ATC. We also found that ATC characteristic biomarkers are associated with the tumor immune microenvironment and drug sensitivity. CONCLUSION: ADM, PXDN, MMP1, and TFF3 might serve as potential ATC diagnostic biomarkers and may be helpful for ATC molecular targeted therapy and immunotherapy.

[Astragalus polysaccharide protects against blood-brain barrier damage in MCAO rats by inhibiting P2X7R channel].

OBJECTIVE: To investigate the protective effect of astragalus polysaccharide (APS) against blood-brain barrier in a rat model of middle cerebral artery occlusion (MCAO) and the role of P2X7R channel in the protective mechanism. METHODS: In rat microglial cell models of oxygen and glucose deprivation (OGD) or ATP treatment, the formation of blood-brain barrier in vitro was assessed using the leak test, and the effect of APS on the permeability of the blood-brain barrier was determined using LC-MS. In 12 SD rats, MCAO model was established followed by treatment with intraperitoneal injection of normal saline (n= 6) or APS (45 mg/kg, n=6) for 3 consecutive days, with another 6 rats without MCAO receiving saline injections as the control group. The permeability of the blood-brain barrier of the rats was evaluated by determining Evans blue (EB) extravasation, and ATP content in the brain tissue was detected using ELISA; the expression levels of matrix metalloproteinase-9 (MMP-9) and P2X7R in the brain tissue were detected with Western blot. RESULTS: In the in vitro cell model of OGD or ATP treatment, APS treatment obviously promoted the repair of blood-brain barrier integrity. In the rat models, the EB content in the brain tissue and the blood-brain barrier permeability increased significantly in MCAO+saline group and MCAO+APS group as compared with those in the control group (P < 0.01). Compared with saline treatment, APS treatment significantly decreased EB content in the brain tissue and improved the blood-brain barrier permeability in the MCAO rats (P < 0.05). MCAO caused a significant reduction of ATP content and obviously increased the expression levels of MMP-9 and P2X7R in the brain tissue of the rats (P < 0.01), and these changes were significantly alleviated after APS treatment (P < 0.01 or 0.05). CONCLUSION: APS can protect the brain tissue of MCAO rats by stabilizing the internal environment, down-regulating the expression of MMP-9 and improving the permeability of blood-brain barrier under cerebral ischemia and hypoxia, and its mechanism may involve the inhibition of P2X7R channel.

[A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China].

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ2=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ2=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ2=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ2=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.

[Accuracy and retention of denture bases fabricated by injection molding, milling, and three-dimensional printing].

Objective: To compare the accuracy and retention of denture bases fabricated by injection molding, milling, and three-dimensional (3D) printing fabricating, in order to provide some references for clinical practice. Methods: A maxillary edentulous jaw model made was used to duplicated 10 working casts. The casts were numbered and scanned. The wax pattern was designed by digital ways and conventional methods and then the denture bases were fabricated by injection molding, milling, and 3D printing. The tissue surface of experimental denture base was obtained using a dental laboratory scanner. The deviation between the tissue surface of the fabricated denture bases and the working model was evaluated. A digital force gauge was used to measure the traction force. Results: The milling group [(0.076±0.026) mm] was more accurate than the 3D printing group [(0.117±0.041) mm] (P<0.05) and the injection group [(0.120± 0.025) mm] (P<0.05). The accuracy of 3D printing group and that of injection group were not statistically significant (P>0.05). The milling group [(9.55±2.44) N] demonstrated greater retentive force than 3D printing group [(5.19±0.06) N] and injection molding group [(1.52±0.52) N] (P<0.05). Conclusions: The denture base fabricated by milling was more accurate and showed the greatest retentive force than the other groups. And 3D printing group showed better retentive force than the injection molding group. Both digital manufacturing methods can meet the requirements of clinical application.

Retraction Note: The carcinogenic complex lncRNA FOXP4-AS1/EZH2/LSD1 accelerates proliferation, migration and invasion of gastric cancer.

The article "The carcinogenic complex lncRNA FOXP4-AS1/EZH2/LSD1 accelerates proliferation, migration and invasion of gastric cancer, by R.-Y. Chen, Q. Ju, L.-M. Feng, Q. Yuan, L. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8371-8376-DOI: 10.26355/eurrev_201910_19148-PMID: 31646567" has been retracted by the authors. After publication, the authors raised concerns about the reliability of the data used to conduct the study by stating that some data cannot be repeated by further research. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19148.

Evaluation of the protective efficacy of virus-like particles based on PCV 2b and 2d subtypes against mixed challenge in mice.

Porcine circovirus type 2 (PCV2) is an economically important swine pathogen and, although small, it has the highest evolution rate among DNA viruses. Commercial PCV2 commercial vaccines are inactivated PCV2 isolates or a subunit vaccine based on the Cap protein of PCV2. Currently, PCV2 VLPs of individual subtype vaccines are available. Although the main prevalent genotype worldwide is PCV2b, the emerging subtype PCV2d subtype is also increasingly associated with PCV disease. The aim of the study was to evaluate the protective efficacy of VLP based on the PCV2b and 2d subtypes against the mixed challenge of two hypotype PCV2 in mice. Thirty-six female SPV Kunming mice were immunized twice with PCV2b and 2d VLPs, then challenged with PCV2b and PCV2d, to assess the immunogenicity and effectiveness of the VLPs. Vaccination of the mice with PCV2b and 2d VLPs elicited a robust antibody response specific for the PCV2. The virus load detected in the 2b and 2d spleen vaccine group was the lowest compared to other groups. Furthermore, there was no pathological damage in the HE stained sections of the 2b and 2d spleen vaccine, and no virus was detected in the immunohistochemical sections. Our data suggest that the mixed PCV2b and 2d VLP vaccine could protect mice from challenge with the mixed infection of PCV2b and PCV2d..

Single-Cell Transcriptomic Atlas of Gingival Mucosa in Type 2 Diabetes.

The oral gingival barrier is a constantly stimulated and dynamic environment where homeostasis is often disrupted, resulting in inflammatory periodontal diseases. Type 2 diabetes (T2D) has been reported to be associated with gingival barrier dysfunction, but the effect and underlying mechanism are inconclusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) of gingiva from leptin receptor-deficient mice (db/db) to examine the gingival heterogeneity in the context of T2D. Periodontal health of control mice is characterized by populations of Krt14+-expressing epithelial cells and Col1a1+-fibroblasts mediating immune homeostasis primarily through the enrichment of innate lymphoid cells. The db/db gingiva exhibited decreased epithelial/stromal ratio and dysfunctional barrier. We further observed stromal, particularly fibroblast immune hyperresponsiveness, linked to the recruitment of myeloid-derived cells at the db/db gingiva. Both scRNA-seq and histological analysis suggested the inflammatory signaling between fibroblasts and neutrophils as a potential driver of diabetes-induced periodontal damage. Notably, the "immune-like" stromal cells were wired toward the induction of gingival IL-17A hyperresponsiveness in db/db mice. Our work reveals that the "immune-like" fibroblasts with transcriptional diversity are involved in the innate immune homeostasis at the diabetic gingiva. It highlights a potentially significant role of these cell types in its pathogenesis.

[Identification and preservation of arm lymphatics in axillary lymph node dissection to prevent arm lymphedema: a single center randomized controlled trial].

Objective: To evaluate the feasibility of identification and preservation of arm lymphatics (DEPART) in axillary lymph node dissection (ALND) for breast cancer to prevent arm lymphedema. Methods: A randomized controlled study method was used. Two hundred and sixty-five patients who underwent breast cancer surgery at the Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University from November 2017 to June 2018 were included, and the patients were randomly divided into ALND+ DEPART group (132 patients) and standard ALND group (133 patients) by random number table method. In the ALND+ DEPART group, indocyanine green and methylene blue were injected as tracers before surgery, and the arm sentinel nodes was visualized by staged tracing during intraoperative dissection of axillary lymph nodes. Partial frozen sections were made of arm lymph nodes >1 cm in length and hard and suspicious of metastasis, and arm lymph nodes and lymphatic vessels were selectively preserved. Patients in the standard ALND group underwent standard ALND. Objective and subjective indexes of arm lymphedema were evaluated by 5-point circumference measurement and Norman questionnaire. Results: Among 132 breast cancer patients in the ALND+ DEPART group, 121 (91.7%) completed DEPART. There were no statistically significant differences in age, body mass index, pathological type, dissection number of axillary lymph node, N stage, TNM stage, molecular typing, and regional radiotherapy between the ALND+ DEPART and standard ALND groups (P>0.05). At a median follow-up of 24 months, assessment by the 5-point circumference measurement showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.0% (6/121) and 15.8% (21/133), respectively, with statistically significant differences (P=0.005). Assessment by the Norman questionnaire showed that the incidence rates of lymphedema in the ALND+ DEPART and standard ALND groups were 5.8% (7/121) and 21.8% (29/133), respectively, with a statistically significant difference (P<0.001). No local regional recurrence was observed in either group during the follow-up period. Conclusion: For breast cancer patients with positive axillary lymph nodes, the administration of DEPART during ALND can reduce or avoid the occurrence of arm lymphedema without compromising oncology safety.

Safety and tolerance of Lacticaseibacillus paracasei N1115 in caesarean-born young children: a randomised, placebo-controlled trial.

The administration of probiotics may help to improve dysbiosis and related health problems in children delivered by caesarean section. However, the effects are strain specific, and safety combined tolerance are considered a priority. The aim of this study was to evaluate the safety and tolerance of Lacticaseibacillus paracasei N1115 in caesarean-born children aged 6-24 months via a randomised, placebo-controlled intervention study. In total, 101 children were included and randomised to receive either a sachet of L. paracasei N1115 (2×1010 cfu/g, 2 g/day) or placebo (maltodextrin, 2 g/day) per day for 12 weeks. Anthropometric parameters were measured by trained nurses, and defecation characteristics, gastrointestinal symptoms, (serious) adverse events ((s)AEs), crying patterns and lifestyle behaviours were recorded by parents or guardians. Neurocognitive development was assessed by the Ages and Stages Questionnaires-3 (ASQ-3) before and after the intervention. The only difference between groups regarding defecation characteristics was a significant treatment × time effect on stool frequency (P=0.007), as the number of defecations was significantly higher in the probiotic group (around 1.2-1.3 times/day) than in the placebo group (around 1.0 times/day) in the later intervention period (P=0.035 at week 9; P=0.048 at week 10; P=0.026 at week 12). The use of L. paracasei N1115 also reduced the incidence rate of constipation (Incidence rate ratio (IRR): 0.120; 95% confidence interval (CI): 0.015, 0.967; P=0.046) and abdominal pain (IRR: 0.562; 95% CI: 0.358, 0.882; P=0.012). Changes in anthropometric parameters, including weight, height and head circumference, did not differ significantly between groups, nor did measures of crying, sleep, outdoor activity, temper, appetite or the ASQ-3 scores. No adverse events associated with consumption of the probiotic were reported. Thus, the administration of L. paracasei N1115 is safe and well-tolerated in caesarean-born children aged 6-24 months. Furthermore, it may ameliorate gastrointestinal function to some extent.

Development of a radiomic-clinical nomogram for prediction of survival in patients with serous ovarian cancer.

AIM: To develop and validate a radiomic-clinical nomogram to evaluate overall survival (OS) postoperatively in patients with serous ovarian cancer. MATERIALS AND METHODS: Eighty serous ovarian cancer patients from The Cancer Imaging Archive (TCIA) database were used as the training set, and 39 eligible patients treated at Affiliated Huadu Hospital were used as the independent validation set. In total, 1,301 radiomics features were extracted from ovarian cancer lesions on venous-phase computed tomography (CT) images. Then, a radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm in the training set. Moreover, a radiomic-clinical nomogram was constructed incorporating the radiomics signature and clinical predictors based on a multivariable Cox regression analysis. The performance of the nomogram was evaluated. RESULTS: Consisting of three selected features, the radiomics signature showed good discrimination in the training and validation sets with C-indexes of 0.694 (95% confidence interval [CI]: 0.613-0.775) and 0.709 (95% CI: 0.517-0.901), respectively. The radiomic-clinical nomogram contained the radiomics signature and four clinical predictors, including age, tumour size, pathological staging, and tumour grade. The nomogram showed favourable discrimination in the training set (C-index [95% CI], 0.754 [0.678-0.830]), which was confirmed in the validation set (C-index [95% CI], 0.727 [0.569-0.885]). According to the model, all patients were classified into high-risk and low-risk groups. Kaplan-Meier curves showed that there was a significant distinction between the OS of the high-risk and low-risk patients. CONCLUSIONS: The proposed radiomic-clinical nomogram can increase the predictive accuracy of OS in patients with serous ovarian cancer after surgery, which may aid in clinical decision-making.