Deep-learning features based on F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to predict preoperative colorectal cancer lymph node metastasis.

AIM: The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features. MATERIALS AND METHODS: In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis. RESULTS: The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884-0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769-1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673-0.998) in the test cohort. CONCLUSION: We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients.

Optical response of Higgs mode in superconductors at clean limit: formulation through Eilenberger equation and Ginzburg-Landau Lagrangian.

Both macroscopic Ginzburg-Landau Lagrangian and microscopic gauge-invariant kinetic equation suggest a finite Higgs-mode generation in the second-order optical response of superconductors at clean limit, whereas the previous derivations through the path-integral approach and Eilenberger equation within the Matsubara formalism failed to give such generation. The crucial treatment leading to this controversy lies at an artificial scheme that whether the external optical frequency is taken as continuous variable or bosonic Matsubara frequency to handle the gap dynamics within the Matsubara formalism. To resolve this issue, we derive the effective action of the superconducting gap nearTcin the presence of the vector potential through the path-integral approach, to fill in the long missing gap of the microscopic derivation of the Ginzburg-Landau Lagrangian in superconductors. It is shown that only by taking optical frequency as continuous variable within the Matsubara formalism, can one achieve the fundamental Ginzburg-Landau Lagrangian, and in particular, the finite Ginzburg-Landau kinetic term leads to a finite Higgs-mode generation at clean limit. To further eliminate the confusion of the Matsubara frequency through a separate framework, we apply the Eilenberger equation within the Keldysh formalism, which is irrelevant to the Matsubara space. By calculating the gap dynamics in the second-order response, it is analytically proved that the involved optical frequency is a continuous variable rather than bosonic Matsubara frequency, causing a finite Higgs-mode generation at clean limit.

[Functional analysis of laparoscopic intracorporeal Xing's neobladder in long-term follow-up].

Evaluation of neobladder function in patients with long-term survival and no recurrence after laparoscopic radical cystectomy and intracorporeal Xing's neobladder. The clinical data of laparoscopic radical cystectomy and intracorporeal Xing's neobladder in long-term survival patients with bladder cancer treated in Beijing Chaoyang Hospital from July 2013 to July 2018 were analyzed retrospectively. All 17 patients underwent the surgery by the same surgical team, including 15 males and 2 females, whose mean age at the time of operation was (55.9±7.6) years. Thepostoperative urinary function and renal function were summarized. All operations were successfully completed. The mean operative time was (340±62) min. All patients were followed up for a long time, with a median follow-up time of 80(70, 96) months, Urinary continence was achieved in 17 (100%)casesduring the day and 13 (76.5%) cases at night, with a median bladder volume of 350 (200, 400) ml. All patients had good urinary control after surgery, and no hydronephrosis or creatinine increase was found in reexamination.After the application of Xing's neobladder operation, the patient maintained acceptable urinary control status after the operation, and the long-term follow-up effect was satisfactory.

[Progress of schistosomiasis control in People's Republic of China in 2023].

To understand the progress of national schistosomiasis elimination program of China in 2023 and summarize the lessons and experiences, data on the endemic status of schistosomiasis and national schistosomiasis surveillance results in the People's Republic of China were collected and analyzed at a national level. By the end of 2023, Shanghai Municipality, Zhejiang Province, Fujian Province, Guangdong Province and Guangxi Zhuang Autonomous Region continued to consolidate the achievements of schistosomiasis elimination, and Sichuan and Jiangsu provinces maintained the criteria of transmission interruption, while Yunnan and Hubei provinces were identified to achieve the criteria of transmission interruption in 2020, and Anhui, Jiangxi and Hunan provinces achieved the criteria of transmission interruption in 2023. A total of 451 counties (cites, districts) were found to be endemic for schistosomiasis in China in 2023, including 26 250 endemic villages covering 73 034 500 residents at risk of infections. Among the 451 endemic counties (cities, districts), 78.49% (354/451) achieved the criteria of schistosomiasis elimination and 21.51% (97/451) achieved the criteria of transmission interruption, respectively. In 2023, a total of 4 216 643 individuals received immunological tests, with 47 794 sero-positives identified, and a total of 184 216 individuals received parasitological examinations, with 4 egg-positives detected. A total of 27 768 cases with advanced schistosomiasis were documented in China by the end of 2023. In 2023, 539 548 bovines were raised in schistosomiasis-endemic areas of China, and 125 440 bovines received immunological tests, with 124 sero-positives detected, while no egg-positives were identified among the 133 508 bovines receiving parasitological examinations. In 2023, snail survey was performed at an area of 641 339.53 hm2 and 184 819.77 hm2 snail habitats were identified, including 51.53 hm2 emerging snail habitats and 642.25 hm2 reemerging snail habitats. In 2023, there were 20 198 schistosomiasis patients receiving praziquantel chemotherapy, and 598 183 person-time individuals and 283 954 herdtime bovines were given expanded chemotherapy. In 2023, snail control with chemical treatment was performed in 116 347.95 hm2 snail habitats, and the actual area of chemical treatment was 65 690.89 hm2, while environmental improvements were performed in snail habitats covering an area of 1 334.62 hm2. The national schistosomiasis surveillance results showed that the mean prevalence of Schistosoma japonicum infections were both zero among humans and bovines in 2023, and no S. japonicum infection was detected in snails. These data demonstrated that transmission interruption of schistosomiasis had been achieved across all endemic provinces in China in 2023, and the endemic status of schistosomiasis tended to be stable, while advanced cases were predominant among all schistosomiasis cases. However, the areas of snail habitats remained high and cattle re-raising was very common in some regions. Intensified schistosomiasis surveillance and forecast and snail control in high-risk areas are needed.

Integrating genomics and transcriptomics to identify candidate genes for high-altitude adaptation and egg production in Nixi chicken.

1. This study combined genome-wide selection signal analysis with RNA-sequencing to identify candidate genes associated with high altitude adaptation and egg production performance in Nixi chickens (NXC).2. Based on the whole-genome data from 20 NXC (♂:10; ♀:10), the population selection signal was analysed by sliding window analysis. The selected genes were screened by combination with the population differentiation statistic (FST). The sequence diversity statistic (θπ). RNA-seq was performed on the ovarian tissues of NXC (n = 6) and Lohmann laying hens (n = 6) to analyse the differentially expressed genes (DEGs) between the two groups. The functional enrichment analysis of the selected genes and differentially expressed genes was performed.3. There were 742 genes under strong positive selection and 509 differentially expressed genes screened in NXC. Integrated analysis of the genome and transcriptome revealing 26 overlapping genes. The candidate genes for adaptation to a high-altitude environment, as well as for egg production, disease resistance, vision and pigmentation in NXC were preliminarily screened.4. The results provided theoretical guidance for further research on the genetic resource protection and utilisation of NXC.

Multimode ultrasound imaging of an anal canal gastrointestinal stromal tumour (GIST).

Gastrointestinal stromal tumours (GISTs) can develop throughout the entire gastrointestinal tract, but these tumours are usually found in the stomach and small intestine. In this case, a rare GIST arising from the anal canal was investigated using high-frequency endoanal ultrasound and external three-dimensional ultrasound with tomographic ultrasound imaging. The endoanal approach revealed the inner structure of the tumour. External ultrasound was used to determine the relationship between the lesion and surrounding tissues. In the limited reports of anal canal GISTs, no other lesions have been correctly diagnosed preoperatively or displayed in detail on imaging. The multilayer structure of the anal sphincter and these lesions can be clearly displayed by a variety of ultrasound imaging methods, which are nonradiative, low-cost and easily accessible. Modern ultrasound has the potential for broad application in anal canal tumour diagnosis and surveillance.

[Clinical and electrophysiological characteristics and treatment outcomes of anti-neutrophil cytoplasmic antibody ANCA-associated vasculitic neuropathy].

Objective: To investigate the clinical and electrophysiological characteristics of ANCA-associated vasculitic neuropathy (VN) and analyze the predictors of treatment outcomes. Methods: Retrospective case series. In all, 652 consecutive patients with ANCA-associated vasculitis were admitted to the First Medical Center of the Chinese PLA General Hospital between January 2006 and December 2022. Peripheral neuropathy occurred in 91 patients. Patients were excluded if other known causes of neuropathy were present. Sixty-one patients were eventually enrolled, including 17 with eosinophilic granulomatosis with polyangiitis (EGPA), 11 with granulomatosis polyangiitis (GPA), and 33 with microscopic polyangiitis (MPA). Their clinical data were collected and clinical characteristics, VN manifestations, electrophysiological findings (including interside amplitude ratio [IAR]), and treatment outcomes were compared among the three subsets of AAV. Then, factors influencing the treatment outcomes were analyzed using multivariable logistic regression analysis. Results: Peripheral neuropathy occurred in 62.1%(18/29) of EGPA, 8.3%(15/180) of GPA, and 13.1%(58/443) of MPA patients. The age at onset and examination was higher in patients with MPA than those with EGPA or GPA (P<0.01). The occurrence of VN was later in patients with GPA than those with EGPA (P<0.01), and the GPA group had fewer affected nerves than the other two groups (P<0.016). The abnormal IARs of motor nerves in lower limbs were more detected in the EGPA than the MPA group (P<0.01). Logistic regression analysis suggested that higher Birmingham vasculitis activity score-version 3 (BVAS-V3) (OR=6.85, 95%CI 1.33-35.30) was associated with better treatment outcomes of VN. However, central nervous system involvement was a risk factor for poor treatment outcomes (OR=0.13, 95%CI 0.02-0.89). Conclusions: The clinical and electrophysiological characteristics of VN were slightly different among subsets of AAV. Patients with GPA often presented with polyneuropathy and had fewer nerves affected; mononeuritis multiplex was more common in EGPA than GPA and MPA. Higher BVAS-V3 and central nervous system involvement might predict the treatment outcome of VN.

[Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors].

Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.

The top 100 most cited articles on intramedullary nail fixation from 2018-2022: a bibliometric and visualized analysis.

OBJECTIVE: Intramedullary nails are commonly used for the purposes of internal fixation in the repair of tubular bone fractures, allowing for optimal fixation while minimizing intraoperative bleeding, surgical incision size, and associated stress. These nails are thus often utilized to repair hip and peripheral fractures, femur fractures, tibial fractures, humerus fractures, and clavicle fractures. Recent life expectancy increases, rising economic standards, and technological innovations have led to the application of a wider range of materials and techniques in the context of orthopedic device production, further expanding the clinical indications for intramedullary nailing. Despite the growing importance of this technique, there is currently a lack of any bibliometric or visual analyses that provide a robust overview of recent progress in the intramedullary nailing research space. Accordingly, this study was developed to succinctly and comprehensively summarize the current research status and major hotspots in this field through a bibliometric review of major relevant scientific articles focused on intramedullary nailing published in recent years. MATERIALS AND METHODS: For this analysis, the top 100 most-cited articles focused on intramedullary nails published between 2018 and 2022 were identified through a search of the Web of Science Core Collection database. Countries, institutions, journals, and other specific parameters associated with these articles were then analyzed using tools including CiteSpace, VOS-viewer, Origin, and SCImago Graphica in an effort to more clearly define the latest trends in the intramedullary nail-related research space. RESULTS: The top 3 most-cited articles related to intramedullary nailing over the past five years were "Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium", "Diaphyseal long bone nonunions - types, etiology, economics, and treatment recommendations", and "Epidemiology, treatment, and mortality of trochanteric and subtrochanteric hip fractures: data from the Swedish fracture register", all of which were published in 2018, respectively exhibiting 93, 83, and 81 citations. Of the 100 most-cited intramedullary nailing-related articles, 38, 20, and 12 were respectively published by researchers from the USA, China, and the UK, while research groups from Italy and Spain each published 7 articles. Four of this field's most highly cited articles were published by individuals affiliated with the US-based University of California System and the University System of Ohio. Of the 15 journals that published the largest number of these top 100 articles, the "Injury International Journal of The Care of The Injured" and the "Journal of Orthopaedic Trauma" published 9 manuscripts each, which was more than any other journal, while the "Journal of Orthopaedic Surgery" and the "Journal of Pediatric Orthopaedics" published 7 each. In total, 73 highly cited articles focused on utilizing intramedullary nailing in orthopedic applications. Rozbruch SR from the USA published 3 high-quality articles in this research space, while the Chinese researchers Chang Shi Min, Du Shou Chao, Hou Zhi Yong, and Hu Sun Jun exhibited a total linkage strength of 21 in global interaction analyses. The most common keywords associated with intramedullary nail-related research identified in these analyses included "Hip fracture", "Nonunion", "Limb lengthening", "Proximal humeral fractures", "Additive manufacturing", "Induced membrane", and "Endoprosthetic replacement". Promising areas of potential future research focus may include "Limb reconstruction", "Pediatric deformity", and "Congenital femoral deficiency". CONCLUSIONS: This analysis revealed that the highest volume of high-impact research output focused on intramedullary nailing over the past 5 years has been produced by the USA, followed by China and the UK. The most influential journals in this research space were Injury International Journal of The Care of The Injured and the Journal of Orthopaedic Trauma, while the institutions associated with the most highly cited articles were the University of California System and the University System of Ohio. Intramedullary nailing is commonly utilized to treat intertrochanteric fractures and other tubular bone fractures. In the future, the application of augmented and virtual reality technologies may help shorten the learning curve for orthopedic surgeons and trauma surgeons who are learning intramedullary nailing-related techniques, and the combination of intramedullary nailing with antibacterial drugs, metal alloys, 3D navigation, and sensor devices may help improve patient outcomes.

Subsurface hydrological connectivity controls nitrate export flux in a hilly catchment.

Subsurface runoff represents the main pathway of nitrate transport in hilly catchments. The magnitude of nitrate export from a source area is closely related to subsurface hydrological connectivity, which refers to the linkage of separate regions of a catchment via subsurface runoff. However, understanding of how subsurface hydrological connectivity regulates catchment nitrate export remains insufficient. This study conducted high-frequency monitoring of shallow groundwater in a hilly catchment over 17 months. Subsurface hydrological connectivity of the catchment over 38 rainfall events was analyzed by combining topography-based upscaling of shallow groundwater and graph theory. Moreover, cross-correlation analysis was used to evaluate the time-series similarity between subsurface hydrological connectivity and nitrate flux during rainfall events. The results showed that the maximum subsurface hydrological connectivity during 32 out of 38 rainfall events was below 0.5. Although subsurface flow paths (i.e., the pathways of lateral subsurface runoff) exhibited clear dynamic extension and contraction during rainfall events, most areas in the catchment did not establish subsurface hydrological connectivity with the stream. The primary pattern of nitrate export was flushing (44.7%), followed by dilution (34.2%), and chemostatic behavior (21.1%). A threshold relationship between subsurface hydrological connectivity and nitrate flux was identified, with nitrate flux rapidly increasing after the subsurface connectivity strength exceeded 0.121. Moreover, the median value of cross-correlation coefficients reached 0.67, which indicated subsurface hydrological connectivity exerts a strong control on nitrate flux. However, this control effect is not constant and it increases with rainfall amount and intensity as a power function. The results of this study provide comprehensive insights into the subsurface hydrological control of catchment nitrate export.

[High-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou].

Objective: To explore high-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou. Methods: A cross-sectional survey was conducted in 5 different types of Guangzhou colleges by convenience sampling with minimum number of classes per grade and 600 samples per school from September to November 2021. The R 4.2.2 software was used to consolidate databases. Simultaneously, a logistic regression model and a decision tree algorithm model, stratifying by whether sexual behaviors had occurred before, were constructed. In each layer, the prediction performance of the two models was evaluated through area under receiver operating characteristic and the confusion matrix, and then the model with high prediction performance was retained. Results: A total of 7 346 students were surveyed. The proportion of the respondents reporting sexual experience were 9.08% (667/7 346), in whom 26.24% (175/667) had risky sexual activity in the past year. The decision tree algorithm model performs well in predicting whether high-risk sexual behaviors have occurred in the past year. When the complexity parameter value is 0.018, and nsplit reaches 4, which means there are 5 leaf nodes in the model, the cross error of the tree will be the smallest. The first best grouping variable in the decision tree was whether to use condoms throughout the first sexual behavior. If condoms were used at their sexual debut, but homosexual practices have occurred in the past year, the probability of risky sexual behavior will increase. If homosexual practices have not occurred in the past year, but the age of sexual debut was below 18 years old while the period of HIV education was after high school, the probability of risk sexual behavior will also increase. Conclusions: AIDS-related risky behaviors of young students still deserved attention. The experience of sexual debut and whether AIDS-related health education has been received before the sexual debut were significant predictors for the occurrence of high-risk sexual behavior. The decision tree algorithm model has particular applicability for predicting and screening potential risk populations.

[Ultrasonographic features of thyroid carcinoma of different sizes: comparison between medullary thyroid carcinomas and papillary thyroid carcinomas].

Objective: To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods: There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results: In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference (P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant (P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference (P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions: Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

The Impact of Testosterone on Alzheimer's Disease Are Mediated by Lipid Metabolism and Obesity: A Mendelian Randomization Study.

BACKGROUND: To investigate the causal relationship between testosterone (BT) levels and Alzheimer's disease (AD) risk and to quantify the role of obesity and lipid metabolism as potential mediators. METHODS: We used a two-sample, two-step MR to determine:1) the causal effect of BT levels on AD; 2) the causal effect of two lipid metabolites, obesity and LDLc on AD; and 3) the mediating effects of these metabolites. Pooled data for BT levels and lipid metabolism were obtained from the UK Biobank. AD data were obtained from the Alzheimer's Disease Project International Genomics Consortium, FinnGen Consortium, and UK Biobank study. Effect estimates from external genome-wide association study (GWAS) pooled statistics were obtained using inverse variance-weighted (IVW) MR analysis. RESULTS: Higher levels of BT were associated with a reduced risk of AD (odds ratio [OR] 0.9992, 95% CI 0.9985-0.9998, P = 0.019), and there was a negative correlation with LDLc (OR 0.9208, 95% CI 0.8569-0.9895, P = 0.024) and obesity class 2 (OC2) (OR 0.7445, 95% CI 0.5873-0.9437, P = 0.014). Conversely, there was a positive correlation between LDLc (OR 1.0014, 95% CI 1.0000-1.0029, P = 0.043) and OC2 (OR 1.0005, 95% CI 1.0001-1.0009, P = 0.003) and AD. Mediation analysis showed that the indirect effect of BT levels on AD was achieved through LDLc and OC2, which accounted for 17% and 17% of the total effect, respectively. CONCLUSION: Our study identified a causal role of BT levels in LDLc and OC2. BT levels may affect AD through LDLc and OC2 metabolic processes.

Integrated Bioinformatic Analysis and Validation Identifies Immune Microenvironment-Related Potential Biomarkers in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, accompanied by cognitive and memory impairment, accounting for about 60% - 80% of dementia types. The pathogenesis of AD has not been clarified, and there is no effective therapy to prevent or treat AD. In this study, we aimed to identify the potential biomarkers involved in the brain immune microenvironment in AD. METHODS: AD datasets from GEO database were obtained to identify the differentially expressed disease-related genes (DEDRGs) in AD through weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Functional Enrichment analysis was performed to explore the potential biological function of DEDRGs. The hub DEDRGs were identified through the protein-protein interaction (PPI) network. Furthermore, the CIBERSORT algorithm was employed to bulk gene expression profiles of AD to depict the immune microenvironment characteristics in AD. Pearson's correlation analysis was utilized to depict the correlation between each of immune cells and hub DEDRGs. RESULTS: A total of 27 DEDRGs were identified through WGCNA and differential expression analysis. Functional enrichment analysis of 27 DEDRGs indicated that chemokine signaling pathway was the most significantly enriched KEGG pathway, response to biotic stimulus was the most significantly enriched GO term, and most of DEDRGs were enriched into urinary system cancer in DO analysis. 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were screened through PPI network and all of them were up-regulated in AD. Immune infiltration analysis revealed that there were higher infiltration levels of T cells CD4 memory activated, T cells gamma delta, NK cells resting and macrophages M0, and lower infiltration level of NK cell activated in AD, and macrophages M2 owned the highest positively association with VCAM1 and CXCR4, but VCAM1 was statistically and negatively correlated to T cells CD8. CONCLUSION: Our study identified 6 hub DEDRGs, ANGPT1, CCL2, CD44, CXCR4, GJA1 and VCAM1, were statistically associated with immune infiltrating cells, and were significantly related to the pathological development of AD, which may provide a theoretical basis for developing potential biomarkers and implementing effective therapies against AD.

Determinants of depressive symptoms at individual, school and province levels: a national survey of 398,520 Chinese children and adolescents.

OBJECTIVES: The aims of this study were to describe the national distribution of depressive symptoms in Chinese children and adolescents, to examine the determinants of depressive symptoms at individual, school and province levels and to assess the gender and age differences in the effect of school factors on depressive symptoms. STUDY DESIGN: This was a national cross-sectional study. METHODS: A school-based online survey was conducted in mainland China from between December 1, 2021, and January 1, 2022. A total of 398,520 eligible participants were included in the analysis. School-level data were drawn from students, headteachers and Baidu Maps, and province-level data were obtained from the national human development report. The Patient Health Questionnaire-2 was used to measure depressive symptoms. RESULTS: Areas with the highest mean scores for depressive symptoms were in the northeastern, inner central and southwestern regions of China. At the individual level, younger age, male sex, being an only child, Han ethnicity, lower body mass index, more days of exercise, less drinking and smoking behaviours, higher subjective family socio-economic status (SES) and popularity in school were related to fewer depressive symptoms; however, objective family SES and maternal education were not related to fewer depressive symptoms. The school-level variables of public status, psychological activities and psychological courses and province-level variable of higher Human Development Index were associated with fewer depressive symptoms. The effect of psychological courses and activities on depressive symptoms was greater in females. CONCLUSIONS: The results showed multilevel factors related to depressive symptoms and emphasised the importance of implementing school-based psychological activities to ameliorate depressive symptoms in Chinese children and adolescents across age and gender.

Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-κB/IRF7/JAK-STAT signalling pathway and apoptosis.

1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells.2. The half toxic concentration (CC50) of palmatine was 672.92 µM, the half inhibitory concentration (IC50) of palmatine against IBV was 7.76 µM and the selection index (SI) was 86.74.3. Mode of action assay showed that palmatine was able to directly inactivate IBV and inhibited the adsorption, penetration and intracellular replication of IBV.4. Palmatine significantly upregulated TRAF6, TAB1 and IKK-ß compared with the IBV-infected group, leading to the increased expressions of pro-inflammatory cytokines IL-1ß and TNF-α in the downstream NF-κB signalling pathway.5. Palmatine significantly up-regulated the levels of MDA5, MAVS, IRF7, IFN-α and IFN-ß in the IRF7 pathway, inducing type I interferon production. It up-regulated the expression of 2'5'-oligoadenylate synthase (OAS) in the JAK-STAT pathway.6. IBV infection induced cell apoptosis and palmatine-treatment delayed the process of apoptosis by regulation of the expression of apoptosis-related genes (BAX, BCL-2, CASPASE-3 and CASPASE-8).7. Palmatine could exert anti-IBV activity through regulation of NF-κB/IRF7/JAK-STAT signalling pathways and apoptosis, providing a theoretical basis for the utilisation of palmatine to treat IBV infection.