Multiparameter spectral CT-based radiomics in predicting the expression of programmed death ligand 1 in non-small-cell lung cancer.

AIM: To explore the value of radiomics for predicting the expression of programmed death ligand 1 (PD-L1) in non-small-cell lung cancer (NSCLC) based on multiparameter spectral computed tomography (CT) images. MATERIALS AND METHODS: A total of 220 patients with NSCLC were enrolled retrospectively and divided into the training (n=176) and testing (n=44) cohorts. The radiomics features were extracted from the conventional CT images, mono-energy 40 keV images, iodine density (ID) maps, Z-effective maps, and electron density maps. The logistic regression (LR) and support vector machine (SVM) algorithms were employed to build models based on radiomics signatures. The prediction abilities were qualified by the area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. Internal validation was performed on the independent testing dataset. RESULTS: The combined model for PD-L1 ≥1%, which consisted of the radiomics score (rad-score; p<0.0001), white blood cell (WBC; p=0.027) counts, and air bronchogram (p=0.003), reached the highest performance with the AUCs of 0.873 and 0.917 in the training and testing dataset, respectively, which was better than the radiomics model with the AUCs of 0.842 and 0.886. The combined model for PD-L1 ≥50%, which consisted of rad-score (p<0.0001) and WBC counts (p=0.027), achieved the highest performance in the training and testing dataset with AUCs of 0.932 and 0.903, respectively, which was better than the radiomics model with AUCs of 0.920 and 0.892, respectively. CONCLUSION: The radiomics model based on the multiparameter images of spectral CT can predict the expression level of PD-L1 in NSCLC. The combined model can obtain higher prediction efficiency and serves as a promising method for immunotherapy selection.

[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

[Application of the blastomere count variations "skip value" in the embryo AI assessment].

Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the ß values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number (ß=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate (OR=0.97, 95%CI: 0.93-0.99, P=0.034; OR=0.96, 95%CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age (OR=0.91, 95%CI: 0.88-0.93; P<0.001), D3 general score (OR=0.77, 95%CI: 0.59-0.99; P=0.045) and order selection of skip values (OR=0.98, 95%CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred (OR=1.08, 95%CI:1.05-1.11, P<0.001; OR=1.09, 95%CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.

Redisposition of acremonium-like fungi in Hypocreales.

Acremonium is acknowledged as a highly ubiquitous genus including saprobic, parasitic, or endophytic fungi that inhabit a variety of environments. Species of this genus are extensively exploited in industrial, commercial, pharmaceutical, and biocontrol applications, and proved to be a rich source of novel and bioactive secondary metabolites. Acremonium has been recognised as a taxonomically difficult group of ascomycetes, due to the reduced and high plasticity of morphological characters, wide ecological distribution and substrate range. Recent advances in molecular phylogenies, revealed that Acremonium is highly polyphyletic and members of Acremonium s. lat. belong to at least three distinct orders of Sordariomycetes, of which numerous orders, families and genera with acremonium-like morphs remain undefined. To infer the phylogenetic relationships and establish a natural classification for acremonium-like taxa, systematic analyses were conducted based on a large number of cultures with a global distribution and varied substrates. A total of 633 cultures with acremonium-like morphology, including 261 ex-type cultures from 89 countries and a variety of substrates including soil, plants, fungi, humans, insects, air, and water were examined. An overview phylogenetic tree based on three loci (ITS, LSU, rpb2) was generated to delimit the orders and families. Separate trees based on a combined analysis of four loci (ITS, LSU, rpb2, tef-1α) were used to delimit species at generic and family levels. Combined with the morphological features, host associations and ecological analyses, acremonium-like species evaluated in the present study are currently assigned to 63 genera, and 14 families in Cephalothecales, Glomerellales and Hypocreales, mainly in the families Bionectriaceae, Plectosphaerellaceae and Sarocladiaceae and five new hypocrealean families, namely Chrysonectriaceae, Neoacremoniaceae, Nothoacremoniaceae, Pseudoniessliaceae and Valsonectriaceae. Among them, 17 new genera and 63 new combinations are proposed, with descriptions of 65 new species. Furthermore, one epitype and one neotype are designated to stabilise the taxonomy and use of older names. Results of this study demonstrated that most species of Acremonium s. lat. grouped in genera of Bionectriaceae, including the type A. alternatum. A phylogenetic backbone tree is provided for Bionectriaceae, in which 183 species are recognised and 39 well-supported genera are resolved, including 10 new genera. Additionally, rpb2 and tef-1α are proposed as potential DNA barcodes for the identification of taxa in Bionectriaceae. Taxonomic novelties: New families: Chrysonectriaceae L.W. Hou, L. Cai & Crous, Neoacremoniaceae L.W. Hou, L. Cai & Crous, Nothoacremoniaceae L.W. Hou, L. Cai & Crous, Pseudoniessliaceae L.W. Hou, L. Cai & Crous, Valsonectriaceae L.W. Hou, L. Cai & Crous. New genera: Bionectriaceae: Alloacremonium L.W. Hou, L. Cai & Crous, Gossypinidium L.W. Hou, L. Cai & Crous, Monohydropisphaera L.W. Hou, L. Cai & Crous, Musananaesporium L.W. Hou, L. Cai & Crous, Paragliomastix L.W. Hou, L. Cai & Crous, Proliferophialis L.W. Hou, L. Cai & Crous, Proxiovicillium L.W. Hou, L. Cai & Crous, Ramosiphorum L.W. Hou, L. Cai & Crous, Verruciconidia L.W. Hou, L. Cai & Crous, Waltergamsia L.W. Hou, L. Cai & Crous; Clavicipitaceae: Subuliphorum L.W. Hou, L. Cai & Crous; Neoacremoniaceae: Neoacremonium L.W. Hou, L. Cai & Crous; Nothoacremoniaceae: Nothoacremonium L.W. Hou, L. Cai & Crous; Plectosphaerellaceae: Allomusicillium L.W. Hou, L. Cai & Crous, Parafuscohypha L.W. Hou, L. Cai & Crous; Pseudoniessliaceae: Pseudoniesslia L.W. Hou, L. Cai & Crous; Sarocladiaceae: Polyphialocladium L.W. Hou, L. Cai & Crous. New species: Bionectriaceae: Alloacremonium ferrugineum L.W. Hou, L. Cai & Crous, Al. humicola L.W. Hou, L. Cai & Crous, Acremonium aerium L.W. Hou, L. Cai & Crous, A. brunneisporum L.W. Hou, L. Cai & Crous, A. chlamydosporium L.W. Hou, L. Cai & Crous, A. ellipsoideum L.W. Hou, Rämä, L. Cai & Crous, A. gamsianum L.W. Hou, L. Cai & Crous, A. longiphialidicum L.W. Hou, L. Cai & Crous, A. multiramosum L.W. Hou, Rämä, L. Cai & Crous, A. mycoparasiticum L.W. Hou, L. Cai & Crous, A. stroudii K. Fletcher, F.C. Küpper & P. van West, A. subulatum L.W. Hou, L. Cai & Crous, A. synnematoferum L.W. Hou, Rämä, L. Cai & Crous, Bulbithecium ammophilae L.W. Hou, L. Cai & Crous, B. ellipsoideum L.W. Hou, L. Cai & Crous, B. truncatum L.W. Hou, L. Cai & Crous, Emericellopsis brunneiguttula L.W. Hou, L. Cai & Crous, Gliomastix musae L.W. Hou, L. Cai & Crous, Gossypinidium sporodochiale L.W. Hou, L. Cai & Crous, Hapsidospora stercoraria L.W. Hou, L. Cai & Crous, H. variabilis L.W. Hou, L. Cai & Crous, Mycocitrus odorus L.W. Hou, L. Cai & Crous, Nectriopsis ellipsoidea L.W. Hou, L. Cai & Crous, Paracylindrocarpon aurantiacum L.W. Hou, L. Cai & Crous, Pn. foliicola Lechat & J. Fourn., Paragliomastix rosea L.W. Hou, L. Cai & Crous, Proliferophialis apiculata L.W. Hou, L. Cai & Crous, Protocreopsis finnmarkica L.W. Hou, L. Cai, Rämä & Crous, Proxiovicillium lepidopterorum L.W. Hou, L. Cai & Crous, Ramosiphorum echinoporiae L.W. Hou, L. Cai & Crous, R. polyporicola L.W. Hou, L. Cai & Crous, R. thailandicum L.W. Hou, L. Cai & Crous, Verruciconidia erythroxyli L.W. Hou, L. Cai & Crous, Ve. infuscata L.W. Hou, L. Cai & Crous, Ve. quercina L.W. Hou, L. Cai & Crous, Ve. siccicapita L.W. Hou, L. Cai & Crous, Ve. unguis L.W. Hou, L. Cai & Crous, Waltergamsia alkalina L.W. Hou, L. Cai & Crous, W. catenata L.W. Hou, L. Cai & Crous, W. moroccensis L.W. Hou, L. Cai & Crous, W. obpyriformis L.W. Hou, L. Cai & Crous; Chrysonectriaceae: Chrysonectria crystallifera L.W. Hou, L. Cai & Crous; Nectriaceae: Xenoacremonium allantoideum L.W. Hou, L. Cai & Crous; Neoacremoniaceae: Neoacremonium distortum L.W. Hou, L. Cai & Crous, N. flavum L.W. Hou, L. Cai & Crous; Nothoacremoniaceae: Nothoacremonium subcylindricum L.W. Hou, L. Cai & Crous, No. vesiculophorum L.W. Hou, L. Cai & Crous; Myrotheciomycetaceae: Trichothecium hongkongense L.W. Hou, L. Cai & Crous; Plectosphaerellaceae: Brunneomyces polyphialidus L.W. Hou, L. Cai & Crous, Parafuscohypha proliferata L.W. Hou, L. Cai & Crous; Sarocladiaceae: Chlamydocillium acaciae L.W. Hou, L. Cai & Crous, C. antarcticum L.W. Hou, L. Cai & Crous, C. guttulatum L.W. Hou, L. Cai & Crous, C. lolii L.W. Hou, L. Cai & Crous, C. soli L.W. Hou, L. Cai & Crous, C. terrestre L.W. Hou, L. Cai & Crous, Parasarocladium chondroidum L.W. Hou, L. Cai & Crous,Polyphialocladium fusisporum L.W. Hou, L. Cai & Crous, Sarocladium agarici L.W. Hou, L. Cai & Crous, S. citri L.W. Hou, L. Cai & Crous, S. ferrugineum L.W. Hou, L. Cai & Crous, S. fuscum L.W. Hou, L. Cai & Crous,S. theobromae L.W. Hou, L. Cai & Crous; Valsonectriaceae: Valsonectria crystalligena L.W. Hou, L. Cai & Crous, V. hilaris L.W. Hou, L. Cai & Crous. New combinations: Bionectriaceae: Acremonium purpurascens (Sukapure & Thirum.) L.W. Hou, L. Cai & Crous, Bulbithecium arxii (Malloch) L.W. Hou, L. Cai & Crous, Bu. borodinense (Tad. Ito et al.) L.W. Hou, L. Cai & Crous, Bu. pinkertoniae (W. Gams) L.W. Hou, L. Cai & Crous, Bu. spinosum (Negroni) L.W. Hou, L. Cai & Crous, Emericellopsis exuviara (Sigler et al.) L.W. Hou, L. Cai & Crous, E. fimetaria (Pers.) L.W. Hou, L. Cai & Crous, E. fuci (Summerb. et al.) L.W. Hou, L. Cai & Crous, E. moniliformis (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, E. salmonea (W. Gams & Lodha) L.W. Hou, L. Cai & Crous, E. tubakii (Gams) L.W. Hou, L. Cai & Crous, Fusariella arenula (Berk. & Broome) L.W. Hou, L. Cai & Crous, Hapsidospora chrysogena (Thirum. & Sukapure) L.W. Hou, L. Cai & Crous, H. flava (W. Gams) L.W. Hou, L. Cai & Crous, H. globosa (Malloch & Cain) L.W. Hou, L. Cai & Crous, H. inversa (Malloch & Cain) L.W. Hou, L. Cai & Crous, Hydropisphaera aurantiaca (C.A. Jørg.) L.W. Hou, L. Cai & Crous, Lasionectria atrorubra (Lechat & J. Fourn.) L.W. Hou, L. Cai & Crous, L. bisepta (W. Gams) L.W. Hou, L. Cai & Crous, L. castaneicola (Lechat & Gardiennet) L.W. Hou, L. Cai & Crous, L. cerealis (P. Karst.) L.W. Hou, L. Cai & Crous, L. olida (W. Gams) L.W. Hou, L. Cai & Crous, Lasionectriopsis dentifera (Samuels) L.W. Hou, L. Cai & Crous, Lasionectriella arenuloides (Samuels) L.W. Hou, L. Cai & Crous, La. marigotensis (Lechat & J. Fourn.) L.W. Hou, L. Cai & Crous, Monohydropisphaera fusigera (Berk. & Broome) L.W. Hou, L. Cai & Crous, Musananaesporium tectonae (R.F. Castañeda) L.W. Hou, L. Cai & Crous, Mycocitrus zonatus (Sawada) L.W. Hou, L. Cai & Crous, Nectriopsis microspora (Jaap) L.W. Hou, L. Cai & Crous, Ovicillium asperulatum (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, O. variecolor (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, Paracylindrocarpon multiloculatum (Samuels) L.W. Hou, L. Cai & Crous, Pn. multiseptatum (Samuels)L.W. Hou, L. Cai & Crous, Paragliomastix chiangraiensis (J.F. Li et al.) L.W. Hou, L. Cai & Crous, Px. luzulae (Fuckel) L.W. Hou, L. Cai & Crous, Px. znieffensis (Lechat & J. Fourn.) L.W. Hou, L. Cai & Crous, Protocreopsis rutila (W. Gams) L.W. Hou, L. Cai & Crous, Proxiovicillium blochii (Matr.)L.W. Hou, L. Cai & Crous, Stanjemonium dichromosporum (Gams & Sivasith.) L.W. Hou, L. Cai & Crous, Verruciconidia persicina (Nicot) L.W. Hou, L. Cai & Crous, Ve. verruculosa (W. Gams & Veenb.-Rijks) L.W. Hou, L. Cai & Crous, Waltergamsia citrina (A. Giraldo et al.) L.W. Hou, L. Cai &Crous, W. dimorphospora (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, W. epimycota (Samuels) L.W. Hou, L. Cai & Crous, W. fusidioides (Nicot) L.W. Hou, L. Cai & Crous, W. hennebertii (W. Gams) L.W. Hou, L. Cai & Crous, W. parva (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, W. pilosa (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, W. zeylanica (Petch) L.W. Hou, L. Cai & Crous; Cephalothecaceae: Phialemonium thermophilum (W. Gams & J. Lacey) L.W. Hou, L. Cai & Crous; Clavicipitaceae: Subuliphorum camptosporum (W. Gams) L.W. Hou, L. Cai & Crous; Coniochaetaceae: Coniochaeta psammospora (W. Gams) L.W. Hou, L. Cai & Crous; Nothoacremoniaceae: Nothoacremonium exiguum (W. Gams) L.W. Hou, L. Cai & Crous; Neoacremoniaceae: Neoacremonium minutisporum (Sukapure & Thirum.) L.W. Hou, L. Cai & Crous; Ne. taiwanense (K.L. Pang et al.) L.W. Hou, L. Cai & Crous; Ne. vitellinum (W. Gams) L.W. Hou, L. Cai & Crous; Plectosphaerellaceae: Allomusicillium domschii (W. Gams) L.W. Hou, L. Cai & Crous, Brunneomyces pseudozeylanicus (W. Gams) L.W. Hou, L. Cai & Crous; Pseudoniessliaceae: Pseudoniesslia minutispora (W. Gams et al.) L.W. Hou, L. Cai & Crous; Sarocladiaceae: Chlamydocillium curvulum (W. Gams) L.W. Hou, L. Cai & Crous, Parasarocladium funiculosum (Sukapure & Thirum.) L.W. Hou, L. Cai & Crous; Valsonectriaceae: Valsonectria inflata (C.H. Dickinson) L.W. Hou, L. Cai & Crous, V. roseola (G. Sm.) L.W. Hou, L. Cai & Crous. Epitype (basionym): Sphaeria violacea J.C. Schmidt ex Fr. Neotype (basionym): Mastigocladium blochii Matr. Citation: Hou LW, Giraldo A, Groenewald JZ, Rämä T, Summerbell RC, Zang P, Cai L, Crous PW (2023). Redisposition of acremonium-like fungi in Hypocreales. Studies in Mycology 105: 23-203. doi: 10.3114/sim.2023.105.02.

A factorial-analysis-based Bayesian neural network method for quantifying China's CO2 emissions under dual-carbon target.

Energy-structure transformation and CO2-emission reduction are becoming particularly urgent for China and many other countries. Development of effective methods that are capable of quantifying and predicting CO2 emissions to achieve carbon neutrality is desired. This study advances a factorial-analysis-based Bayesian neural network (abbreviated as FABNN) method to reflect the complex relationship between inputs and outputs as well as reveal the individual and interactive effects of multiple factors affecting CO2 emissions. FABNN is then applied to analyzing CO2 emissions of China (abbreviated as CEC), where multiple factors involve in energy (e.g., the consumption of natural gas, CONG), economic (e.g., Gross domestic product, GDP) and social (e.g., the rate of urbanization, ROU) aspects are investigated and 512 scenarios are designed to achieve the national dual carbon targets (i.e., carbon peak before 2030 and carbon neutrality by 2060). Comparing to the conventional machine learning methods, FABNN performs better in calibration and validation results, indicating that FABNN is suitable for CEC simulation and prediction. Results disclose that the top three factors affecting CEC under the dual­carbon target are GDP, CONG, and ROU; energy, economic and social contributions are 43.5 %, 34.6 % and 21.9 %, respectively. CEC reaches its carbon peak during 2027-2032 and achieve carbon neutrality during 2053-2057 under all scenarios. Under the optimal scenario (S195), the CO2-emission reduction potential is about 772.2 million tonnes and the consumptions of coal, petroleum and natural gas can be respectively reduced by 3.1 %, 9.9 % and 23.0 % compared to the worst scenario (S466). The results can provide solid support for national energy-structure transformation and CO2-emission reduction to achieve carbon-peak and carbon-neutrality targets.

Neovascularization by DPSC-ECs in a Tube Model for Pulp Regeneration Study.

The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used. Human microvascular endothelial cells (hMVECs) were used as a positive control. DPSC-ECs formed tubules on Matrigel similar to hMVECs. Cells were mixed in fibrinogen/thrombin or mouse blood and seeded into wells of 96-well plates or injected into a tapered plastic tube (14 mm in length and 1 or 2 mm diameter of the apex opening) with the larger end sealed with MTA to simulate root canal space. Cells/gels in wells or tubes were incubated for various times in vitro and observed under the microscope for morphological changes. Samples were then fixed and processed for histological analysis to determine vessel formation. Vessel-like networks were observed in culture from 1 to 3 d after cell seeding. Cells/gels in 96-well plates were maintained up to 25 d. Histologically, both hMVECs and DPSC-ECs in 96-well plates or tubes showed intracellular vacuole formation. Some cells showed merged large vacuoles indicating the lumenization. Tubular structures were also observed resembling blood vessels. Cells appeared healthy throughout the tube except some samples (1 mm apical diameter) in the coronal third. Histological analysis also showed pulp-like soft tissue throughout the tube samples with vascular-like structures. hMVECs formed larger vascular lumen size than DPSC-ECs while the latter tended to have more lumen and tubular structure counts. We conclude that DPSC-ECs can form vascular structures and sustained in the 3-dimensional fibrin gel system in vitro. The tube model appears to be a proper and simple system simulating the root canal space for vascular formation and pulp regeneration studies.

Effects of rumen-protected 5-hydroxytryptophan on circulating serotonin concentration, behaviour, and mammary gland involution in goats.

The risk of acquiring new intramammary infections is high at the end of lactation, especially for the high milk-producing dairy animals. Resistance to bacterial infection increases following the completion of mammary gland involution after milking cessation. The serotonin precursor 5-hydroxytryptophan (5-HTP) could accelerate involution by increasing circulating serotonin levels, but ruminal microbes may degrade 5-HTP if orally administered to adult ruminants. It is unclear whether rumen-protected 5-HTP could effectively mediate circulating serotonin (5-hydroxytryptamine, 5-HT) and therefore accelerate mammary gland involution in ruminants. Goats were used as a model in the current study to investigate the effects of rumen-protected 5-HTP on behaviour, 5-HT metabolism, and mammary involution in ruminants. In the first experiment, 16 female Dazu black goats were assigned to one of four groups in a randomised block design. The treatments included a basal diet plus 0, 4, 20, or 100 mg/kg BW of rumen-protected 5-HTP. Serum was collected at 0, 3, 6, 12, and 24 h after offering the rumen-protected 5-HTP in the morning feed, and the behaviours were monitored. In the second experiment, 12 female Dazu black goats (Somatic cell count < 250 000) were randomly assigned to the control (basal diet) or rumen-protected 5-HTP group (basal diet plus 20 mg/kg BW). Milk or mammary secretions were manually collected aseptically on d -1, 1, 2, 3, 4, and 5 around weaning. The results depicted that rumen-protected 5-HTP supplementation elevated circulating 5-HTP and 5-hydroxyindole acetic acid concentrations, while 20 mg/kg BW of rumen-protected 5-HTP supplementation lowered the goats' locomotive activity. A high concentration of rumen-protected 5-HTP (100 mg/kg BW) increased serum alkaline phosphatase and gamma-glutamyl transpeptidase concentrations. Moreover, oral supplementation with 20 mg/kg BW of rumen-protected 5-HTP accelerated mammary gland involution and reduced feed intake in goats after weaning. These results demonstrate that oral supplementation with rumen-protected 5-HTP influences 5-HT metabolism and accelerates mammary gland involution after milking cessation in ruminants.

[Analysis on the use of HIV post-exposure prophylaxis and related factors in men who have sex with men in Qingdao].

Objective: To understand the use of post-exposure prophylaxis (PEP) and analyze related factors among men who have sex with men (MSM) in Qingdao, and provide a reference for the AIDS prevention and control in this population. Methods: A cross-sectional survey conducted from April 2022 to February 2023. Relying on MSM social groups in Qingdao, a snowball sampling method was applied to recruit research subjects who met the inclusion criteria of age ≥18 years old, having had homosexual anal or oral sex in the past six months, and HIV-negative or infection status unknown. The sample size was estimated at 566. Data on demographic characteristics, sexual behavior characteristics, PEP use, and others of the research subjects was collected through on-site questionnaires. The logistic regression model was used to analyze the factors associated with using PEP. Results: A total of 811 participants were recruited, mainly aged 25-34 (53.6%, 435/811), unmarried (74.7%, 606/811), with an average monthly income of ≥5 000 yuan (52.2%, 423/811), and having lived in Qingdao for ≥10 years (75.6%, 613/811). The proportion of those who knew the HIV status of their sexual partners in the last six months was 67.1% (544/811), and those with HIV-positive partners were 3.6% (29/811). In the last six months, the proportion of participants who had group sex (86.4%, 701/811), unprotected anal sex (98.2%, 796/811), and use of club drugs (80.3%, 651/811) was high. Moreover, 28.4% (230/811) had used PEP. The multivariate logistic regression analysis showed that the factors related to the use of PEP included divorced or widowed (aOR=5.46,95%CI:1.96-15.17), average monthly income ≥5 000 yuan (aOR=2.04,95%CI:1.44-2.89), same-sex sexual orientation (aOR=0.40,95%CI:0.22-0.71), having HIV-positive sexual partners in the last six months (aOR=2.54,95%CI:1.13-5.71) and having been tested for HIV ≥3 times in the last six months (aOR=1.46,95%CI:1.04-2.06). Conclusions: The prevalence of risk behaviors among MSM in Qingdao was high, and the use of PEP was low. In the future, it is essential to increase HIV/AIDS prevention education among MSM, promote MSM to know the HIV status of their sexual partners, and reduce the prevalence of risk behaviors among this population. Additionally, explore medical insurance reimbursement plans for PEP to reduce utilization costs and promote the use of PEP by MSM after HIV exposure occurs as soon as possible.

[Current status of pubertal sexual characteristics development of 2 704 girls aged 6-18 years in Tongzhou District of Beijing].

Objective: To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese. Methods: A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ2 test was applied to compare the counting data between two or multiple groups. Results: A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95%CI 8.9-9.1), 10.5 (95%CI 10.4-10.6), and 11.4 (95%CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95%CI 4.6-4.8) years, between P2 and P5 was 4.5 (95%CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95%CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95%CI 9.5-10.6), 9.3 (95%CI 9.2-9.4), and 8.6 (95%CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95%CI 12.4-13.7), 11.6 (95%CI 11.4-11.7), and 11.1 (95%CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions: The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Critical Values of Daily Sedentary Time and Its Longitudinal Association with Mild Cognitive Impairment Considering APOE ε4: A Prospective Cohort Study.

BACKGROUND: Long sedentary time and physical inactivity are negatively related to cognition, but the cut-off value remains unclear, and apolipoprotein E polymorphism ε4 (APOE ε4) is a known genetic risk factor of mild cognitive impairment (MCI). OBJECTIVES: To explore longitudinal association of sedentary time and MCI, and to identify a cutoff value that increases the risk of developing MCI, taking into account APOE ε4 stratification and its interactions. DESIGN: A prospective cohort study. SETTING: Population-based study. PARTICIPANTS: We included 4932 older adults from Tianjin Elderly Nutrition and Cognition (TENC) cohort study recruited from March 2018 to June 2021 with 3.11 years of median follow-up time. MEASUREMENTS: The primary outcome was newly diagnosed MCI, which was diagnosed by a modified version of the Petersen's criteria. The information of sedentary time (hours/day) and physical activity (MET-h/week) were obtained by questionnaire. Cox proportional hazard regression models and restricted spline curve were conducted. RESULTS: A total of 4932 participants were included (mean [SD] age, 67.85 [4.96] years; 2627 female [53.3%] and 2305 male [46.7%]), 740 newly onset MCI patients were identified. Longer sedentary time was associated with higher risk of MCI for all participants (HR:1.069, 95%CI: 1.034, 1.105), especially in APOE ε4 non-carriers (HR:1.083, 95%CI: 1.045, 1.123) whether adjusted potential confounders. Sedentary time had synergistic interactions with APOE ε4 (ß:1.503, 95%CI: 1.163, 1.942) and physical activities (ß: 1.495, 95%CI: 1.210, 1.846). Restricted spline curve showed a cut-off value of 3.03 hours/day. CONCLUSIONS: Long sedentary time (≥3.03 hours/day) could increase MCI risk, especially in APOE ε4 non-carriers, people with higher PA, aged 65 and above.

[Periconceptional maternal homocysteine and birth weight outcomes in offspring: a prospective cohort study].

Objective: To quantify the associations between periconceptional maternal homocysteine (HCY) and offspring's birth weight and risk of small for gestational age (SGA) infant. Methods: The 19 984 mother-child pairs in this prospective cohort study were recruited from the Shanghai preconception cohort; the infants were delivered from 1st September 2016 to 11th November 2022. A standardized questionnaire was used to collect the mothers' demographic information, medical history, dietary supplement use, and maternal complications during pregnancy, and their serum samples were collected. Serum HCY, folate, and vitamin B12 were measured using chemiluminescent microparticle immunoassay based on serum sample drawn at enrollment. Birth weight data were obtained from medical records. Multiple imputation methods were applied to handle missing data in key variables. Multivariable linear regression and Poisson regression models were used to analyze the relationship between maternal HCY concentration during the periconceptional period and the birth weight and SGA risk of the offspring. Results: A total of 9 452 pairs were enrolled preconceptionally and the remaining 10 532 pairs were enrolled in early pregnancy. The proportion of mothers whose pregnancy age was greater than 35 years was 9.2% (1 832/19 984), the proportion of primiparous women was 76.5% (15 283/19 984), the proportion of pre-pregnancy overweight and obesity was 14.0% (2 804/19 984), the proportion of using folic acid supplements before pregnancy was 21.4% (4 272/19 984), and the proportion of those who supplemented with folic acid during early pregnancy was 85.2% (8 976/10 532); gestational diabetes mellitus was in 6.2% (1 245/19 984), gestational hypertensive syndrome in 3.6% (711/19 984). The birth weight of the offspring was (3 297±468) g, and there were 1 962 SGA children (9.8%). The HCY concentration in the overall population in appropriate for gestational age during the periconceptional period was (7.9±3.2) µmol/L, with (8.3±3.7) µmol/L in the preconception subgroup and (7.3±2.4) µmol/L in the early pregnancy subgroup. After adjustment for the covariates of perinatal demographic information, adverse pregnancy outcomes, serum folate and vitamin B12, increased maternal periconceptional HCY was significantly associated with lower offspring birth weight (ß=-2.30, 95%CI -4.43--0.16, P=0.035). Only the early pregnancy subgroup was significantly associated with lower offspring birth weight (ß=-7.39, 95%CI-11.50--3.21, P<0.001). No association was found between peripregnancy HCY and offspring SGA risk. However, elevated HCY in early pregnancy was associated with an increased risk of SGA in the offspring (RR=1.05, 95%CI 1.01-1.08, P=0.002). Periconceptional vitamin B12 was a mediator of the association between HCY and offspring birth weight, accounting for 16.5%, 41.2% and 5.4% of its total effect in the overall periconceptional population, the pre-pregnancy subgroup and the early pregnancy subgroup, respectively. Conclusions: Maternal periconceptional HCY level is associated with lower birth weight in offspring, but not with the risk of SGA. Elevated maternal HCY in early pregnancy subgroup may be associated with increased risk of SGA in offspring.

[Effect of information-knowledge-attitude-practice theory-based health education on clonorchiasis control among community residents and primary school students in Zhongshan City].

OBJECTIVE: To evaluate the effect of information-knowledge-attitude-practice (IKAP) theory-based health education interventions on clonorchiasis control among community residents and primary school students in Torch High-tech Development Zone of Zhongshan City, so as to provide insights into formulation of clonorchiasis control strategies among different types of populations. METHODS: Residents were randomly sampled from two communities and students from two primary schools using a random cluster sampling method in Torch High-tech Development Zone, Zhongshan City from 2019 to 2021, and health education pertaining to clonorchiasis control was performed based on the IKAP theory. The changes in the awareness of basic clonorchiasis control knowledge and belief, self-reported risk of Clonorchis sinensis infections and dietary behaviors were compared among community residents and primary school students before and after health education interventions. RESULTS: The participants included 146 male and 151 female community residents and 158 male and 153 female primary school students, with no significant difference detected in gender distribution (χ2 = 0.16, P > 0.05). The mean awareness of basic clonorchiasis control knowledge increased by 44.71% and 43.28% among primary school students and community residents 6 months following health education, and there were significant differences in the awareness of each item of basic clonorchiasis control knowledge before and after health education (χ2 = 41.53 to 284.44, all P values < 0.05). The proportions of primary school students and community residents thinking very high and high risks of C. sinensis infections increased from 9.35% and 6.71% before health education to 22.15% and 37.75% after health education, but only the difference of the attitudes in community residents achieve statistical significance (χ2 = 92.18, P < 0.05). The frequency of separation of raw and cooked foods with chopping board and knife significantly increased among community residents and primary school students following health education (χ2 = 16.04 to 62.65, all P values < 0.05). The frequency of eating raw freshwater fish (χ2 = 32.85, P < 0.05), fish congee (χ2 = 7.02, P < 0.05) and fish fillet hot pot (χ2 = 4.88, P < 0.05) significantly reduced among primary school students following health education, while only the frequency and proportions of eating raw freshwater fish have significantly reduced in community residents (χ2 = 11.77, P < 0.05). CONCLUSIONS: Health education interventions based on the IKAP theory are effective to increase the awareness of clonorchiasis control knowledge and improve dietary behaviors associated with C. sinensis infections among community residents and primary school students in Zhongshan City.

[Evaluating the efficiency of endoscope-assisted septo-rhinoplasty via intranasal approach].

Objective: To observe the functional and esthetic results of endoscope-assisted septo-rhinoplasty via intranasal approach. Methods: The clinical data of 12 patients with septal deviation and nasal deformity in the University of Hong Kong-Shenzhen Hospital from June 2021 to June 2022 were analyzed, including 8 males and 4 females, aging 28 to 58 years. All patients were operated under general anesthesia. The septal deviation was corrected by hemitransfixion incision, combined with intercartilaginous incision and other intranasal or extranasal incisions to perform osteotomy, hump resection and saddle nose correction. Patient satisfaction with postoperative functional and aesthetic improvements was assessed through Nasal Obstruction Symptom Evaluation (NOSE), Rhinoplasty Outcome Evaluation (ROE), and Visual Analogue Scale (VAS).SPSS 25 software was used for statistical analysis. Results: The correction of nasal septum deviation was satisfactory in all 12 patients. Nasal obstruction was relieved, with NOSE score and VAS score of nasal ventilation decreased [(21.67±10.30) vs (70.83±14.12), (1.83±1.03) vs (8.33±0.89), t value was 9.49 and 16.30, respectively, both P<0.05]. The nasal appearance of 10 patients with crooked nose deformity was improved, with ROE score and VAS score of nasal appearance increased [(21.30±2.31) vs (8.10±3.31), (8.90±0.99) vs (3.80±1.62), t value was -11.85 and -9.33, respectively, both P<0.05];The nasal vestibule morphology of 2 patients with abnormal nasal vestibule was improved. During the follow-up of 12 to 24 months, no postoperative complication such as nasal septum perforation, nasal cavity adhesion or nasal dorsal collapse occurred in all patients. Conclusion: Endoscope-assisted septo-rhinoplasty via intranasal approach can resolve both functional and esthetic problems at the same time, improving outcomes while reducing surgical trauma.

[A cohort study of HIV infection in club drug abusers among men who have sex with men in Qingdao].

Objective: To understand and analyze the incidence of HIV infection in club drug abusers among men who have sex with men (MSM) in Qingdao and provide a reference for the prevention and intervention of this population. Methods: From March 2017 to July 2022, club drug abusers among MSM who are HIV-negative were recruited by snowball sampling of MSM social organizations in Qingdao, a prospective cohort was established, and a follow-up survey was conducted every six months, with the sample size estimated to be 436. The survey contents included demographic characteristics, sexual characteristics, AIDS knowledge awareness, club drug abuse, HIV testing, and other information. HIV infection was the outcome-dependent variable, and the interval between the recruitment into the cohort and the HIV infection was the time-dependent variable. Cox proportional hazards regression analysis was conducted to identify the related factors for HIV infection. Results: A total of 987 participants of club drug abusers among MSM were recruited during the baseline survey and 826 eligible participants were enrolled in this cohort. A total of 46 HIV infection cases were found, and the cumulative follow-up time was 1 960.68 person-years. The incidence of HIV infection was 2.35/100 person-years. The multivariate Cox regression analysis showed that <30 (aHR=3.04, 95%CI: 1.62-5.71) non-Shandong residents (aHR=2.29,95%CI:1.20-4.39) found their partners through offline (aHR=4.62,95%CI:2.05-10.41), homosexual sexual partners >4 (aHR=3.06,95%CI:1.59-5.88), condom broken during sex (aHR=2.24,95%CI:1.21-4.17) and hemorrhage sexual intercourse (aHR=2.56,95%CI:1.31-5.03) were significantly associated with HIV infection in this cohort. Conclusions: The incidence of HIV infection in club drug abusers among MSM in Qingdao is generally low, but knowledge and practice have separated, and the risk of HIV infection is high. The related factors of HIV infection included younger age, non-Shandong residents, finding their partners offline, multiple sexual partners, condom break during sex, and hemorrhage sexual intercourse; HIV-related behavioral intervention should be strengthened.

Clinical and radiographic outcomes of upper thoracic versus lower thoracic upper instrumented vertebrae for adult scoliosis: a meta-analysis

The aim of this study was to evaluate the clinical and radiographic outcomes of upper thoracic (UT) versus lower thoracic (LT) upper instrumented vertebrae (UIV) for adult scoliosis by meta-analysis. We conducted a literature search in three databases to retrieve related studies up to March 15, 2017. The preliminary screened studies were assessed by two reviewers according to the selection criteria. All analyses were carried out using the statistical software package R version 2.31. Odds ratios (OR) with 95% confidence intervals (CI) were used to describe the results. The I2 statistic and Q statistic test were used for heterogeneity assessment. Egger's test was performed to detect publication bias. To assess the effect of each study on the overall pooled OR or standardized mean difference (SMD), sensitive analysis was conducted. Ten trials published between 2007 and 2015 were eligible and included in our study. Meta-analysis revealed that the UT group was associated with more blood loss (SMD=0.4779, 95%CI=0.3349-0.6209, Z=6.55, P<0.0001) and longer operating time (SMD=0.5780, 95%CI=0.1971-0.958, Z=2.97, P=0.0029) than the LT group. However, there was no significant difference in Oswestry Disability Index, Scoliosis Research Society (SRS) function subscores, radiographic outcomes including sagittal vertical axis, lumbar lordosis, and thoracic kyphosis, length of hospital stay, and revision rates between the two groups. No evidence of publication bias was found between the two groups. Fusion from the lower thoracic spine (below T10) has as advantages a shorter operation time and less blood loss than upper thoracic spine (above T10) in posterior long-segment fixation for degenerative lumbar scoliosis.

MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer

This study aimed to investigate the function and mechanism of microRNA-143 (miR-143) in the occurrence and development of breast cancer (BC). A total of 30 BC tissues, 30 corresponding noncancerous tissues, and 10 normal control (NC) breast tissues were obtained to detect the levels of miR-143, extracellular signal-regulated kinase 5 (ERK5) and mitogen-activated protein 3 kinase 7 (MAP3K7) using RT-qPCR, western blotting or immunohistochemistry. The correlation of miR-143 with ERK5 or MAP3K7 was evaluated using Pearson correlation analysis. MCF-7 cells were transiently transfected with miR-143 mimic, miR-143 inhibitor, miR-143 mimic/inhibitor + si-ERK5, si-MAP3K7 or si-cyclin D1. Then, cell growth was evaluated by MTT assay and the expressions of phospho-ERK5 (p-ERK5), ERK5, p-MAP3K7, MAP3K7 and cyclin D1 were detected by western blotting. Results showed that, compared with noncancerous tissues or NC breast tissues, miR-143 level was decreased, while p-ERK5, ERK5, p-MAP3K7 and MAP3K7 expressions were increased in BC tissues (all P<0.01). The miR-143 level was negatively correlated with the mRNA level of ERK5 or MAP3K7 (r=-4.231 or r=-4.280, P<0.01). In addition, up-regulated miR-143 significantly decreased the expressions of p-ERK5, ERK5, p-MAP3K7, MAP3K7 and cyclin D1 (all P<0.01), as well as cell viability in MCF-7 cells (all P<0.05) while the effect of down-regulated miR-143 was the opposite. In conclusion, both ERK5 and MAP3K7 may be the target genes of miR-143. Increased expression of miR-143 can inhibit cell growth, which may be associated with ERK5 and MAP3K7 expressions in BC.