[Risk factors of visceral leishmaniasis in the world: a review].

Visceral leishmaniasis is a zoonotic parasitic disease caused by viscerotropic Leishmania species and transmitted by bites of infected phlebotomine sandflies, which is predominantly prevalent in the Indian subcontinent, eastern Africa and South America. Currently, visceral leishmaniasis is the second most fatal parasitic disease in the world. Because of climate changes, urban development and individual conditions, there are changes in the density of visceral leishmaniasis vector sandflies and the likelihood of contact with humans, resulting in a visceral leishmaniasis transmission risk. The review summarizes natural, social and biological factors affecting the transmission of visceral leishmaniasis, so as to provide insights into formulation of targeted control measures for visceral leishmaniasis.

[Construction and application of a risk index of Echinococcus infection based on the classification of echinococcosis lesions].

OBJECTIVE: To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. METHODS: The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. RESULTS: A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = -0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). CONCLUSIONS: The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

[Epidemiological characteristics of leptospirosis in China from 2010 to 2022].

OBJECTIVE: To analyze the epidemiological characteristics of leptospirosis in China from 2010 to 2022, so as to provide insights into formulation of the leptospirosis control strategy. METHODS: All data pertaining to clinically diagnosed cases and confirmed cases of leptospirosis reported in China from January 1, 2010 to December 31, 2022 was collected from Chinese Disease Prevention and Control Information Management System. The spatial, temporal and population distributions, and report and diagnosis institutions of leptospirosis cases were analyzed using a descriptive epidemiological method. RESULTS: A total of 4 559 leptospirosis cases were reported in China from 2010 to 2022, with an annual average number of 351 cases, and the number of reported leptospirosis cases reduced from 679 cases in 2010 to 158 cases in 2018. A total of 4 276 leptospirosis cases were reported in Sichuan Province, Yunnan Province, Guangdong Province, Hunan Province, Fujian Province, Zhejiang Province, Guangxi Zhuang Autonomous Region, Anhui Province, Jiangxi Province and Guizhou Province, accounting for 93.79% of the total number of leptospirosis cases in China. The number of leptospirosis cases had recently appeared a remarkable decline in Yunnan Province, while a significant rise was seen in the number of leptospirosis cases in two provinces of Zhejiang and Guangdong. No leptospirosis cases were reported in Henan Province from 2010 to 2020; however, there were 5 cases and 2 cases reported in 2021 and 2022, respectively. There was only one leptospirosis case reported in Shaanxi Province from 2010 to 2017; however, leptospirosis cases were reported in the province for 5 consecutive years since 2018. Leptospirosis cases were reported throughout the year in China from 2010 to 2022, with the peak of incidence found during the period between August and October, and the peak of leptospirosis incidence varied in provinces. A higher number of leptospirosis cases was seen among men than among women, with a male to female ratio of 2.3:1, and the median age of leptospirosis cases was 50 years (interquartile range, 23 years), with the highest proportion of leptospirosis cases reported at ages of 51 to 60 years (23.21%). Among all reported leptospirosis cases, 53.28% were confirmed cases, and the proportion of confirmed cases increased from 35.05% in 2010 to 61.66% in 2022. In addition, there were 67.22% of leptospirosis cases (2 937 cases) reported by comprehensive hospitals, 20.44% (893 cases) by disease control and prevention institutions, 7.23% (316 cases) by grassroots healthcare institutions and 5.10% (223 cases) by other healthcare and medical institutions, and the mortality of reported leptospirosis cases was 1.07% in China from 2010 to 2022, with a higher mortality seen among men than among women (1.39% vs. 0.36%; χ2 = 9.52, P = 0.002). CONCLUSIONS: The incidence of leptospirosis remained at a low level in China from 2010 to 2022, and southern China was still the main endemic area for leptospirosis. The epidemiological characteristics of leptospirosis cases varied in endemic provinces, and leptospirosis cases had been continued to be reported in Shaanxi and Henan provinces, which should be paid much attention to. Intensified surveillance of leptospirosis, improved diagnosis and treatment capability of leptospirosis cases and leptospirosis control with adaptations to local circumstance are recommended.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Study on liver tissue derived-extracellular vesicles regulating the osteogenic differentiation ability of mesenchymal stem cells and promoting the healing of jaw bone defects].

Objective: To explore the biological process of liver tissue-derived extracellular vesicle (LT-EV) in promoting osteogenic differentiation of mesenchymal stem cells and healing of jaw defects to provide a feasible treatment method for the clinical treatment of jaw bone defects. Methods: Enzymatic hydrolysis and differential centrifugation were used to extract LT-EV, scanning electron microscopy, Western blotting, and nanoparticle tracking analyzers were used to identify and characterize LT-EV, and further to explore the biological functions of LT-EV through proteomics and Kyoto Encyclopedia of Genes and Genomes. Flow cytometry was used to detect LT-EV plasma concentration and to calculate the plasma half-life of LT-EV. Small animal in vivo imaging system was used to detect the biological distribution of LT-EV 24 hours after injection. Six C57BL/6 mice were divided into control group and LT-EV group (3 mice in each group) by simple random sampling method. All mice underwent jaw bone defect surgery and tail vein injection every 7 days (the control group was injected with phosphoric buffer saline, LT-EV group was injected with LT-EV), micro-CT was used to evaluate the degree of mouse jaw bone healing 28 days after surgery, HE staining was used to analyze the multi-organ biosafety of LT-EV, and immunofluorescence staining was used to detect the jaw bone expression of osteogenic marker proteins in the defect area. Human jaw bone mesenchymal stem cells (hJBMSC) induced by osteogenic differentiation were treated with LT-EV (obtained from orthognathic surgery patients provided by the Department of Traumatology and Orthognathic Surgery of School of Stomatology of The Fourth Military Medical University resected normal jaw bone fragments), and the difference in osteogenic differentiation ability between the hJBMSC group and the control group (phosphate buffer saline treatment) was compared, and the in vitro bone differentiation promoting effect of LT-EV was verified through alkaline phosphatase (ALP) staining and real-time fluorescence quantitative PCR. Results: The yield of LT-EV was high, and proteomics and Kyoto Encyclopedia of Genes and Genomes showed that LT-EV contained a series of proteins that regulated cell biological functions. LT-EV injected into the tail vein could reach the mouse jaw bone defect area and promote the regeneration and repair of the jaw bone defect [the bone volume fractions of the LT-EV group and the control group were (36.06±4.20)% and (18.58±5.61)%, respectively; t=4.32, P=0.013], and had good biosafety. LT-EV could promote osteogenic differentiation of hJBMSC in vitro. Compared to the control group, ALP staining and osteogenic gene expression levels were significantly enhanced after osteogenic differentiation of hJBMSC (P<0.05). Conclusions: LT-EV exhibits a high yield, ease of acquisition, high biological safety, and excellent bone-promoting effects. It holds promise as a novel cell-free therapy strategy for regenerating craniofacial bone defects.

Structural performance of detachable precast concrete column-column joint.

A novel type of detachable precast concrete column-column joint (DPC) is proposed in this study to solve the problems in current column-column dry connections including complex load path, uncertainty of structural stiffness of beam-column joints and inconvenience for disassembly. The dry connection technology is applied by composing of steel plate and concrete. Finite element models of DPC were created to study its structural performance including hysteresis curve, skeleton curve, ductility, and energy dissipation capacity. The benchmark models are firstly established and validated against the test data and after that a small-scale parametric study is prepared. The effect of axial pressure ratio and eccentricity distance size on the seismic performance of DPC was studied. Results indict that the optimal value of axial pressure ratio ranges from 0.5 to 0.7. With increase of the axial pressure ratio, the ductility coefficient shows a decreasing trend in general. The eccentricity has little effect on the energy dissipation capacity of the joint.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

[Analysis of the differences in the characteristics of mesenchymal stem cells derived from jaw and long bones based on single-cell RNA-sequencing].

Objective: To study the whole bone marrow cellular composition of jaw and long bones, and further analyze the heterogeneity of mesenchymal stem cells (MSCs) derived from these two tissue, aiming at exploring the differences in functional characteristics of bone MSCs from different lineage sources. Methods: The Seurat package of R language was used to analyze the mandibular and femur whole bone marrow single-cell RNA-sequencing (scRNA-seq) datasets in the literature, and the subpopulations were annotated by reference to the marker genes reported by previous studies. The differentially expressed genes between mandible-derived MSCs (M-MSCs) and femur-derived MSCs (F-MSCs) were calculated, and cell-cell communication analysis between M-MSCs or F-MSCs with other cell populations was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on up-regulated and down-regulated differentially expressed genes of M-MSCs, and Gene Set Enrichment Analysis (GSEA) was performed on M-MSCs or F-MSCs. Results: cRNA-seq analysis showed that the mandible and femur had the same bone marrow cell composition, but there were differences in the proportion of specific cell populations. Also, there were significantly differentially expressed genes between M-MSCs and F-MSCs. In addition, cell-cell communication analysis revealed differences in numbers of ligand-receptor pairs between M-MSCs or F-MSCs with other cell populations. Furthermore, GO, KEGG and GSEA analysis showed that M-MSCs had higher extracellular matrix production potential than F-MSCs, but had lower ability to regulate other cells in the bone marrow, especially immune cells. Conclusions: M-MSCs and F-MSCs showed distinct differences in the gene expression pattern and up-regulated signaling pathways, which may be closely related to the developmental sources and functional characteristics of jaw and long bones.

Remarkable undercooling capability and metastable thermophysical properties of liquid Nb84.1Si15.9 alloy revealed by electrostatic levitation in outer space.

The stable manipulation, high undercooling, and thermophysical property measurement of the liquid Nb84.1Si15.9 refractory alloy were successfully achieved by the electrostatic levitation technique on board the China Space Station. By controlling the superheating temperature, a maximum liquid undercooling up to 421 K (0.18 TL) was obtained in the space environment, and two distinct solidification paths with different recalescence features were realized at metastable undercooled states. The liquid density and the ratio of specific heat to emissivity were measured in a wide temperature range from 1841 to 2346 K, which displayed linear and quadratic relations vs temperature, respectively. The liquid emissivity was further deduced from the specific heat of the liquid alloy calculated by molecular dynamics simulation. In addition, both the density and structural characteristics of the undercooled liquid alloy were also analyzed by MD calculations.

Beyond Vision: A View from Eye to Alzheimer's Disease and Dementia.

With the aging of the global population, the health care burden of Alzheimer's disease (AD) and dementia is considered to increase dramatically in the coming decades. Given the insufficiency of effective interventions for AD and dementia, clinical research on identifying potentially modifiable risk factors and early diagnostic biomarkers becomes a public health priority. Currently, extracerebral manifestations with a large proportion of ocular involvement are usually recognized to precede the symptoms of AD and dementia. Growing epidemiologic evidence also suggests that eye disorders, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy, and so on, are closely associated with and even have a higher incidence of AD and dementia. The eye, as an extension of the central nervous system, therefore has the potential to provide a feasible approach to detecting structural and functional abnormalities of the brain. Numerous new imaging modalities are developed and give novel insights into the detection of several neurodegenerative, vascular, neuropathological, and other ocular abnormalities of AD and dementia in scientific research and clinical application. This review provides an overview of the epidemiologic associations between eye disorders and AD or dementia and summarizes the recent advances in ocular examinations and techniques employed for the detection of AD and dementia. With more brain-and-eye interconnections being identified, the eye is becoming a noninvasive and easily accessible window for the early diagnosis and prevention of AD and dementia.

Fine-mapping of a major locus for Fusarium wilt resistance in flax (Linum usitatissimum L.).

KEY MESSAGE: Fine-mapping of a locus on chromosome 1 of flax identified an S-lectin receptor-like kinase (SRLK) as the most likely candidate for a major Fusarium wilt resistance gene. Fusarium wilt, caused by the soil-borne fungal pathogen Fusarium oxysporum f. sp. lini, is a devastating disease in flax. Genetic resistance can counteract this disease and limit its spread. To map major genes for Fusarium wilt resistance, a recombinant inbred line population of more than 700 individuals derived from a cross between resistant cultivar 'Bison' and susceptible cultivar 'Novelty' was phenotyped in Fusarium wilt nurseries at two sites for two and three years, respectively. The population was genotyped with 4487 single nucleotide polymorphism (SNP) markers. Twenty-four QTLs were identified with IciMapping, 18 quantitative trait nucleotides with 3VmrMLM and 108 linkage disequilibrium blocks with RTM-GWAS. All models identified a major QTL on chromosome 1 that explained 20-48% of the genetic variance for Fusarium wilt resistance. The locus was estimated to span ~ 867 Kb but included a ~ 400 Kb unresolved region. Whole-genome sequencing of 'CDC Bethune', 'Bison' and 'Novelty' produced ~ 450 Kb continuous sequences of the locus. Annotation revealed 110 genes, of which six were considered candidate genes. Fine-mapping with 12 SNPs and 15 Kompetitive allele-specific PCR (KASP) markers narrowed down the interval to ~ 69 Kb, which comprised the candidate genes Lus10025882 and Lus10025891. The latter, a G-type S-lectin receptor-like kinase (SRLK) is the most likely resistance gene because it is the only polymorphic one. In addition, Fusarium wilt resistance genes previously isolated in tomato and Arabidopsis belonged to the SRLK class. The robust KASP markers can be used in marker-assisted breeding to select for this major Fusarium wilt resistance locus.

Autonomic neural regulation in mediating the brain-bone axis: mechanisms and implications for regeneration under psychological stress.

Efficient regeneration of bone defects caused by disease or significant trauma is a major challenge in current medicine, which is particularly difficult yet significant under the emerging psychological stress in the modern society. Notably, the brain-bone axis has been proposed as a prominent new concept in recent years, among which autonomic nerves act as an essential and emerging skeletal pathophysiological factor related to psychological stress. Studies have established that sympathetic cues lead to impairment of bone homeostasis mainly through acting on mesenchymal stem cells (MSCs) and their derivatives with also affecting the hematopoietic stem cell (HSC)-lineage osteoclasts, and the autonomic neural regulation of stem cell lineages in bone is increasingly recognized to contribute to the bone degenerative disease, osteoporosis. This review summarizes the distribution characteristics of autonomic nerves in bone, introduces the regulatory effects and mechanisms of autonomic nerves on MSC and HSC lineages, and expounds the crucial role of autonomic neural regulation on bone physiology and pathology, which acts as a bridge between the brain and the bone. With the translational perspective, we further highlight the autonomic neural basis of psychological stress-induced bone loss and a series of pharmaceutical therapeutic strategies and implications toward bone regeneration. The summary of research progress in this field will add knowledge to the current landscape of inter-organ crosstalk and provide a medicinal basis for the achievement of clinical bone regeneration in the future.

Construction of prediction model for fetal growth restriction during first trimester in an Asian population.

OBJECTIVE: To construct a prediction model for fetal growth restriction (FGR) during the first trimester of pregnancy and evaluate its screening performance. METHODS: This was a prospective cohort study of singleton pregnancies that underwent routine ultrasound screening at 11 to 13 + 6 weeks at the Affiliated Suzhou Hospital of Nanjing Medical University between January 2019 and April 2022. Basic clinical information, ultrasound indicators and serum biomarkers of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve for the Southern Chinese population. FGR was diagnosed according to Delphi consensus criteria. Least absolute shrinkage and selection operator (lasso) regression was used to select variables for inclusion in the model. Discrimination, calibration and clinical effectiveness of the model were evaluated in training and validation cohorts. RESULTS: A total of 1188 pregnant women were included, of whom 108 had FGR. Lasso regression identified seven predictive features, including history of maternal hypertension, maternal smoking or passive smoking, gravidity, uterine artery pulsatility index, ductus venosus pulsatility index and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The nomogram prediction model constructed from these seven variables accurately predicted FGR, and the area under the receiver-operating-characteristics curve in the validation cohort was 0.82 (95% CI, 0.74-0.90). The calibration curve and Hosmer-Lemeshow test demonstrated good calibration, and the clinical decision curve and clinical impact curve supported its practical value in a clinical setting. CONCLUSION: The multi-index prediction model for FGR has good predictive value during the first trimester. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of bimatoprost sustained-release intracameral implant on intraocular pressure and medication burden in patients with prior glaucoma surgery.

The present retrospective study evaluated intraocular pressure (IOP) and medication burden after bimatoprost sustained-release (bimatoprost SR, Durysta, Allergan) implantation in patients with glaucoma. A secondary objective was to examine an effect of bimatoprost SR in a subset of patients with prior minimally invasive and incisional glaucoma surgery. A retrospective chart review of 122 eyes that received bimatoprost SR by 6 glaucoma specialists at Wills Eye Hospital between March 2020 and September 2021 was performed. One hundred and eighteen eyes from 84 patients had a reduction in IOP (18.5±5.7mmHg vs. 16.0±5.4mmHg, P<0.01) and required fewer glaucoma medications (2.1±1.4 vs. 1.2±1.2, P<0.01) after bimatoprost SR implantation. In 41 eyes from 31 patients who previously underwent glaucoma surgery (including iStent, goniotomy, trabeculectomy, Xen Gel Stent, or tube shunt surgery), medication burden was decreased after bimatoprost SR implantation (1.9±1.3 vs. 1.0±1.0, P<0.001). These data suggest that bimatoprost SR is an efficacious treatment modality for glaucoma, even in post-surgical patients.

Single-cell and bulk RNA sequencing reveal heterogeneity and diagnostic markers in papillary thyroid carcinoma lymph-node metastasis.

PURPOSE: Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing (RNA-seq) to find diagnostic markers and therapeutic targets. METHODS: ScRNA-seq data were clustered and malignant cells were identified. Differentially expressed genes (DEGs) were identified in malignant cells of scRNA-seq and bulk RNA-seq, respectively. PTC LNM diagnostic model was constructed based on intersecting DEGs using glmnet package. Next, PTC samples from 66 patients were used to validate the two most significant genes in the diagnostic model, S100A2 and type 2 deiodinase (DIO2) by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC). Further, the inhibitory effect of DIO2 on PTC cells was verified by cell biology behavior, western blot, cell cycle analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay, and xenograft tumors. RESULTS: Heterogeneity of PTC LNM was demonstrated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. A total of 19 differential genes were used to construct the diagnostic model. S100A2 and DIO2 differ significantly at the RNA (p < 0.01) and protein level in LNM patient tissues (p < 0.001). And differed in PTC tissues with different pathologic typing (p < 0.001). Further, EdU (p < 0.001) and cell biology behavior revealed that PTC cells overexpressed DIO2 had reduced proliferative capacity. Cell cycle proteins were reduced and cells are more likely to be stuck in G2/M phase (p < 0.001). CONCLUSIONS: This study explored the heterogeneity of PTC LNM using scRNA-seq. By combining with bulk RNA-seq data, diagnostic markers were explored and the model was established. Clinical diagnostic efficacy of S100A2 and DIO2 was validated and the treatment potential of DIO2 was discovered.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Anomalous staged hot-electron acceleration by two-plasmon decay instability in magnetized plasmas.

We present a staged hot-electron acceleration mechanism of the two-plasmon decay (TPD) instability in the transverse magnetic field under the parameters relevant to inertial confinement fusion experiments. After being accelerated by the forward electron plasma wave (FEPW) of TPD, the hot-electrons can be anomalously accelerated again by the backward electron plasma wave (BEPW) of TPD and then obtain higher energy. Moreover, the surfatron acceleration mechanism of TPD in the magnetic field is also confirmed, the electrons trapped by the TPD daughter EPWs are accelerated in the direction along the wave front. Interestingly, the velocity of electrons accelerated by surfing from the FEPW is quite easily close to the BEPW phase velocity, which markedly enhances the efficiency of the staged acceleration. The coexistence of these two acceleration mechanisms leads to a significant increase of energetic electrons generated by TPD in the magnetic field. Meanwhile the EPWs are dissipated, TPD instability is effectively suppressed, and the laser transmission increases.

Dietary non-phytate phosphorus requirements for optimal productive and reproductive performance, and egg and tibial quality in egg-type duck breeders.

Optimal dietary non-phytate phosphorus (NPP) is essential in poultry to maximise productive and reproductive performance, along with indices of egg and bone quality. This study aimed to establish the NPP requirements of egg-type duck breeders aged from 54 to 80 weeks on the following traits: egg production, egg incubation, egg quality, tibial characteristics, reproductive organ, plasma indices, and the expression of genes related to phosphorus absorption. Longyan duck breeders aged 54 weeks (n = 300) were randomly allotted to five treatments, each containing six replicates of 10 individually caged birds. Birds were fed corn-soybean meal-based diets containing 0.18, 0.25, 0.32, 0.38, and 0.45% NPP/kg for 27 weeks. The tested dietary NPP levels did not affect egg production or egg quality indices. The hatchling weight of ducklings increased (quadratic, P < 0.01) as dietary NPP level increased, and the highest value occurred with 0.25% NPP. The number of large yellow follicles (LYF), and the relative weights of LYF and ovary showed linear and quadratic responses to dietary NPP levels; the lowest number and relative weight of LYF occurred with 0.38% NPP, and the lowest ovarian weight was obtained with 0.25% NPP. There were no differences in tibial length, breaking strength, and mineral density in response to dietary NPP levels. In contrast, tibial content of Ca increased (linear, P < 0.01) with dietary NPP levels increasing from 0.18 to 0.45%, and the tibial content of P increased at 0.32% NPP and the higher dietary NPP levels. Plasma concentration of P showed a quadratic (P < 0.05) response to the dietary NPP levels, where the highest value was seen at 0.38% NPP. In conclusion, dietary NPP levels from 0.18 to 0.45% had no effects on egg production, and egg and tibial quality of duck breeders. The duck breeders fed a diet with 0.25% NPP showed the highest hatchling weight of their offspring, while those fed 0.38% NPP had the lowest number and relative weight of LYF. These results indicated that the diet with 0.25% NPP can be used in egg-type duck breeders to improve the hatchling weight of their offspring, without adverse effects on their productivity. The regression model indicated that the maximal hatchling weight of ducklings was obtained from duck breeders fed the diet with 0.30% NPP.