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Abstract Background The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. Results We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. Conclusions Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.

Abstract Background & aims Pyogenic liver abscess (PLA) is a common hepatobiliary infection that has been shown to have an increasing incidence, with biliary surgery being identified as a trigger. Our aim was to investigate the clinical characteristics and treatments of PLA patients with and without a history of biliary surgery (BS). Methods The study included a total of 353 patients with PLA who received treatment at our hospital between January 2014 and February 2023. These patients were categorized into two groups: the BS group (n = 91) and the non-BS group (n = 262). In the BS group, according to the anastomosis method, they were further divided into bilioenteric anastomoses group (BEA, n = 22) and non-bilioenteric anastomoses group (non-BEA, n = 69). Clinical characteristics were recorded and analyzed. Results The percentage of PLA patients with BS history was 25.78%. The BS group exhibited elevated levels of TBIL and activated APTT abnormalities (P = 0.009 and P = 0.041, respectively). Within the BS group, the BEA subgroup had a higher prevalence of diabetes mellitus (P

Abstract Background Secondary immunodeficiency can arise from various clinical conditions that include HIV infection, chronic diseases, malignancy and long-term use of immunosuppressives, which makes the suffering patients susceptible to all types of pathogenic infections. Other than HIV infection, the possible pathogen profiles in other aetiology-induced secondary immunodeficiency are largely unknown. Methods Medical records of the patients with secondary immunodeficiency caused by various aetiologies were collected from the First Affiliated Hospital of Nanchang University, China. Based on these records, models were developed with the machine learning method to predict the potential infectious pathogens that may inflict the patients with secondary immunodeficiency caused by various disease conditions other than HIV infection. Results Several metrics were used to evaluate the models’ performance. A consistent conclusion can be drawn from all the metrics that Gradient Boosting Machine had the best performance with the highest accuracy at 91.01%, exceeding other models by 13.48, 7.14, and 4.49% respectively. Conclusions The models developed in our study enable the prediction of potential infectious pathogens that may affect the patients with secondary immunodeficiency caused by various aetiologies except for HIV infection, which will help clinicians make a timely decision on antibiotic use before microorganism culture results return.

Abstract Background Oils are important sources of energy in pig diets. The combination of oils with different degree of saturation contributes to improve the utilization efficiency of the mixed oils and may reduce the cost of oil supplemented. An experiment was conducted to evaluate the effects of oils with different degree of saturation on the fat digestibility and corresponding additivity and bacterial community in growing pigs. Methods Eighteen crossbred (Duroc × Landrace × Yorkshire) barrows (initial body weight: 29.3 ± 2.8 kg) were surgically fitted with a T-cannula in the distal ileum. The experimental diets included a fat-free basal diet and 5 oil-added diets. The 5 oil-added diets were formulated by adding 6% oil with different ratio of unsaturated to saturated fatty acids (U:S) to the basal diet. The 5 oils were palm oil (U:S = 1.2), canola oil (U:S = 12.0), and palm oil and canola oil were mixed in different proportions to prepare a combination of U:S of 2.5, 3.5 and 4.5, respectively. Results The apparent and standardized ileal digestibility (AID and SID) of fat and fatty acids increased linearly (P

Abstract The devastating impact of youth mental health concerns is increasingly evident on a global scale. This crisis calls for innovative solutions that are sufficiently accessible, scalable, and cost-effective to support diverse communities around the world. One such solution involves engagement in the arts: incorporating and building upon existing local resources and cultural practices to bolster youth mental health. In this article, we describe the global youth mental health crisis and note major gaps in the knowledge and resources needed to address it. We then discuss the potential for arts- and culture-based strategies to help meet this challenge, review the mounting evidence regarding art’s ability to support mental health, and call for action to undertake critical research and its translation into accessible community practices. Four steps are suggested: (1) elevate and prioritize youth voice, (2) develop core outcome measures, (3) identify and analyze successful models around the globe, and (4) generate clear funding pathways for research and translational efforts. Worldwide implementation of arts- and culture-based strategies to address youth mental health will provide critical resources to support the health, wellbeing and flourishing of countless youth across the globe.

Abstract Background Uncut Roux-en-Y (URY) effectively alleviates the prevalent complexities connected with RY, such as Roux-en-Y stasis syndrome (RSS). Nevertheless, for gastric cancer (GC) patients, it is still controversial whether URY has an impact on long-term prognosis and whether it has fewer afferent loop recanalization. Therefore, compare whether URY and RY have differences in prognosis and long-term complications of GC patients undergoing totally laparoscopic gastrectomy (TLG). Methods We analyzed the data of patients who underwent TLG combined with digestive tract reconstruction from dual-center between 2016 and 2022. Only patients undergoing URY and RY were selected for analysis. Relapse-free survival (RFS) and overall survival (OS) were estimated. Bias between the groups was reduced by propensity score matching (PSM). The Cox proportional hazard regression model was used to further analyze the influence of URY on prognosis. Results Two hundred forty two GC patients were enrolled. The URY had significantly shorter operation time, liquid food intake time, and in-hospital stays than the RY (P

Abstract Gallstone disease is a prevalent biliary disease worldwide, and bacteria play vital roles in the disease development and progression, as well as the prognosis after endoscopic surgery. However, there have been limited studies to explore the key taxa involved. In this study, bile samples from healthy controls (HCs, liver donors without hepatobiliary disease) and three diseased groups, namely patients with gallbladder stones (GBS), patients with common bile duct stones (CBDS), and patients with stricture in the common bile duct (SCBD), were collected and analyzed. Bacterial community characterization based on 16S rRNA amplicon sequencing showed that bacterial diversities did not change significantly alongside gallstone disease development and progression. The predominant phyla in each group were Proteobacteria, Firmicutes, Bacteroidota, and Fusobacteriota, representing over 80% in abundance of the biliary bacteria community. Specifically, the abundance of Proteobacteria decreased greatly while that of Firmicutes and Bacteroidota increased greatly in the diseased groups when compared to that in HCs. Moreover, linear discriminant analysis identified several genera highly represented in the diseased groups. Among them, Klebsiella, Prevotella, Pseudomonas and Veillonella are persistent in both the HCs group and the diseased groups, indicating an enrichment of local bile bacteria in the diseased bile; while Lachnoanerobaculum, Atopobium, Oribacterium, and Stomatobaculum, those aligned to oral cavity taxa, are persistent in the diseased groups but are transient in the HCs group, and their abundances sequentially increased with the disease development and progression (HCs→GBS→CBDS→SCBD), implying a translocation and colonization of the oral cavity bacteria in the diseased bile. Moreover, co-occurrence network analysis revealed that bacterial infection (e.g., Photobacterium and Plesiomonas) from the intestine was developed during endoscopic surgery with reduced bile bacteria diversity. The results of this study revealed that the bile bacterial community is relatively stable and dominated by a few persistent taxa. Moreover, we hypothesized that translocation and colonization of specific bacteria from the oral cavity happens alongside gallstone disease development and progression, and bacterial infection from the intestinal tract results in poor outcomes after endoscopic surgery.

Abstract Objective To explore the return-to-work adaptation experience and coping resources used by cancer patients. Methods With the help of the Nantong Cancer Friends Association, from June 2019 to January 2020, this study recruited 30 cancer patients who had returned to work using purpose sampling, snowball sampling and theoretical sampling. The researchers analyzed the data using initial-, focusing-, and theoretical coding. Results The adaptation of cancer patients to return-to-work is a rebuilding process by taking advantage of the available personal and external coping resources. The adaptation experience includes: focusing on rehabilitation, rebuilding self-efficacy, and adjusting plans. Conclusion Medical staff should help patients mobilize coping resources to adapt to return to work.

Abstract Hypoimmunogenic human pluripotent stem cells (hPSCs) are expected to serve as an unlimited cell source for generating universally compatible “off-the-shelf” cell grafts. However, whether the engineered hypoimmunogenic hPSCs still preserve their advantages of unlimited self-renewal and multilineage differentiation to yield functional tissue cells remains unclear. Here, we systematically studied the self-renewal and differentiation potency of three types of hypoimmunogenic hPSCs, established through the biallelic lesion of B2M gene to remove all surface expression of classical and nonclassical HLA class I molecules (B2Mnull), biallelic homologous recombination of nonclassical HLA-G1 to the B2M loci to knockout B2M while expressing membrane-bound β2m-HLA-G1 fusion proteins (B2MmHLAG), and ectopic expression of soluble and secreted β2m-HLA-G5 fusion proteins in B2MmHLAG hPSCs (B2Mm/sHLAG) in the most widely used WA09 human embryonic stem cells. Our results showed that hypoimmunogenic hPSCs with variable expression patterns of HLA molecules and immune compromising spectrums retained their normal self-renewal capacity and three-germ-layer differentiation potency. More importantly, as exemplified by neurons, cardiomyocytes and hepatocytes, hypoimmunogenic hPSC-derived tissue cells were fully functional as of their morphology, electrophysiological properties, macromolecule transportation and metabolic regulation. Our findings thus indicate that engineered hypoimmunogenic hPSCs hold great promise of serving as an unlimited universal cell source for cell therapeutics.

Abstract Background The aim of this study is to investigate the association of retinal age gap with the risk of incident stroke and its predictive value for incident stroke. Methods A total of 80,169 fundus images from 46,969 participants in the UK Biobank cohort met the image quality standard. A deep learning model was constructed based on 19,200 fundus images of 11,052 disease-free participants at baseline for age prediction. Retinal age gap (retinal age predicted based on the fundus image minus chronological age) was generated for the remaining 35,917 participants. Stroke events were determined by data linkage to hospital records on admissions and diagnoses, and national death registers, whichever occurred earliest. Cox proportional hazards regression models were used to estimate the effect of retinal age gap on risk of stroke. Logistic regression models were used to estimate the predictive value of retinal age and well-established risk factors in 10-year stroke risk. Results A total of 35,304 participants without history of stroke at baseline were included. During a median follow-up of 5.83 years, 282 (0.80%) participants had stroke events. In the fully adjusted model, each one-year increase in the retinal age gap was associated with a 4% increase in the risk of stroke (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.00–1.08, P = 0.029). Compared to participants with retinal age gap in the first quintile, participants with retinal age gap in the fifth quintile had significantly higher risks of stroke events (HR = 2.37, 95% CI: 1.37–4.10, P = 0.002). The predictive capability of retinal age alone was comparable to the well-established risk factor-based model (AUC=0.676 vs AUC=0.661, p=0.511). Conclusions We found that retinal age gap was significantly associated with incident stroke, implying the potential of retinal age gap as a predictive biomarker of stroke risk.

Abstract Background Dual sensory impairment is affecting over 10% of older adults worldwide. However, the long-term effect of dual sensory impairment (DSI) on the risk of mortality remains controversial. We aim to investigate the impact of single or/and dual sensory impairment on the risk of mortality in a large population-based sample of the adult in the UK with 14-years of follow-up. Methods This population-based prospective cohort study included participants aged 40 and over with complete records of visual and hearing functions from the UK Biobank study. Measurements of visual and hearing functions were performed at baseline examinations between 2006 and 2010, and data on mortality was obtained by 2021. Dual sensory impairment was defined as concurrent visual and hearing impairments. Cox proportional hazards regression models were employed to evaluate the impact of sensory impairment (dual sensory impairment, single visual or hearing impairment) on the hazard of mortality. Results Of the 113,563 participants included in this study, the mean age (standard deviation) was 56.8 (8.09) years, and 61,849 (54.5%) were female. At baseline measurements, there were 733 (0.65%) participants with dual sensory impairment, 2,973 (2.62%) participants with single visual impairment, and 13,560 (11.94%) with single hearing impairment. After a follow-up period of 14 years (mean duration of 11 years), 5,992 (5.28%) participants died from all causes. Compared with no sensory impairment, dual sensory impairment was significantly associated with an estimated 44% higher hazard of mortality (hazard ratio: 1.44 [95% confidence interval, 1.11–1.88], p = 0.007) after multiple adjustments. Conclusions Individuals with dual sensory impairment were found to have an independently 44% higher hazard of mortality than those with neither sensory impairment. Timely intervention of sensory impairment and early prevention of its underlying causes should help to reduce the associated risk of mortality.

Abstract Background Hepatectomy is currently the most effective modality for the treatment of intrahepatic cholangiocarcinoma (ICC). The status of the lymph nodes directly affects the choice of surgical method and the formulation of postoperative treatment plans. Therefore, a preoperative judgment of lymph node status is of great significance for patients diagnosed with this condition. Previous prediction models mostly adopted logistic regression modeling, and few relevant studies applied random forests in the prediction of ICC lymph node metastasis (LNM). Methods A total of 149 ICC patients who met clinical conditions were enrolled in the training group. Taking into account preoperative clinical data and imaging features, 21 indicators were included for analysis and modeling. Logistic regression was used to filter variables through multivariate analysis, and random forest regression was used to rank the importance of these variables through the use of algorithms. The model’s prediction accuracy was assessed by the concordance index (C-index) and calibration curve and validated with external data. Result Multivariate analysis shows that Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), and lymphadenopathy on imaging are independent risk factors for lymph node metastasis. The random forest algorithm identifies the top four risk factors as CEA, CA19-9, and lymphadenopathy on imaging and Aspartate Transaminase (AST). The predictive power of random forest is significantly better than the nomogram established by logistic regression in both the validation group and the training group (Area Under Curve reached 0.758 in the validation group). Conclusions We constructed a random forest model for predicting lymph node metastasis that, compared with the traditional nomogram, has higher prediction accuracy and simultaneously plays an auxiliary role in imaging examinations.

Abstract Background HIV prevention, diagnosis, treatment and care services might be hampered by inaccurate risk assessment. This study aimed to investigate the extent of and factors associated with the discordance between perceived risk and actual risky sexual behaviors among undergraduates in mainland China, guided by the Anderson's behavioral model. Methods This study involved a secondary analysis of cross-sectional data collected during the fall semester of 2018–2019 academic year. The present analysis was restricted to 8808 undergraduates with low risk perception. Those who had low perceived risk but actually engaged in risky sexual behaviors were categorized as risk discordance (RD). Univariate and multivariate Logistic regression analyses were conducted to identify factors associated with RD. Results Overall, the discordance rate between perceived and actual risk was 8.5% (95% CI: 7.9%-9.1%). Multivariate Logistic regression analysis indicated that non-heterosexual women (AOR = 0.41, 95% CI:0.27–0.60), heterosexual men (AOR = 0.45, 95% CI:0.33–0.61) and women (AOR = 0.26, 95% CI:0.19–0.35) were less likely to exhibit RD, when compared with non- heterosexual men. Furthermore, non-freshmen (AOR = 1.57, 95% CI:1.30–1.90), early initiators of sexual intercourse (AOR = 5.82, 95% CI:4.10–8.26), and those who had lower levels of HIV knowledge (AOR = 1.28, 95% CI:1.08–1.51), displayed higher levels of stigma against PLHIV (AOR = 1.50, 95% CI:1.26–1.77) and had ever been tested for HIV (AOR = 1.36, 95% CI:1.04–1.77) were more prone to reporting RD. Those with more enabling resources [i.e., displaying high levels of condom use self-efficacy (AOR = 0.70, 95% CI:0.59–0.84) and being knowledge of local testing center (AOR = 0.71, 95% CI:0.60–0.83)] were less likely to report RD. However, spending more than 2000 Yuan a month on basic needs (AOR = 2.55, 95% CI:2.07–3.14), residing in urban areas (AOR = 1.35, 95% CI:1.15–1.59) and being knowledgeable of the national AIDS policy (AOR = 1.40,95% CI:1.18–1.66) increased the chance of exhibiting RD. Conclusions Comprehensive interventions, including targeting students with high-risk characteristics, improving the acceptability of PrEP and PEP, conducting health education, enhancing self-efficacy for using condoms and making opt-out HIV testing routine in college campus, should be taken to reduce the discordance between perceived and actual HIV risk and finally to reach the goal of Zero AIDS.

Abstract Background and objectives Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC. Methods One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA). Results The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69–0.85) and 0.76 (95% CI: 0.66–0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. Conclusions Our model demonstrated favorable performance in predicting VER in cHCC patients.

Abstract Background At present, hepatectomy is still the most common and effective treatment method for intrahepatic cholangiocarcinoma (ICC) patients. However, the postoperative prognosis is poor. Therefore, the prognostic factors for these patients require further exploration. Whether microvascular invasion (MVI) plays a crucial role in the prognosis of ICC patients is still unclear. Moreover, few studies have focused on preoperative predictions of MVI in ICC patients. Methods Clinicopathological data of 704 ICC patients after curative resection were retrospectively collected from 13 hospitals. Independent risk factors were identified by the Cox or logistic proportional hazards model. In addition, the survival curves of the MVI-positive and MVI-negative groups before and after matching were analyzed. Subsequently, 341 patients from a single center (Eastern Hepatobiliary Hospital) in the above multicenter retrospective cohort were used to construct a nomogram prediction model. Then, the model was evaluated by the index of concordance (C-Index) and the calibration curve. Results After propensity score matching (PSM), Child-Pugh grade and MVI were independent risk factors for overall survival (OS) in ICC patients after curative resection. Major hepatectomy and MVI were independent risk factors for recurrence-free survival (RFS). The survival curves of OS and RFS before and after PSM in the MVI-positive groups were significantly different compared with those in the MVI-negative groups. Multivariate logistic regression results demonstrated that age, gamma-glutamyl transpeptidase (GGT), and preoperative image tumor number were independent risk factors for the occurrence of MVI. Furthermore, the prediction model in the form of a nomogram was constructed, which showed good prediction ability for both the training (C-index = 0.7622) and validation (C-index = 0.7591) groups, and the calibration curve showed good consistency with reality. Conclusion MVI is an independent risk factor for the prognosis of ICC patients after curative resection. Age, GGT, and preoperative image tumor number were independent risk factors for the occurrence of MVI in ICC patients. The prediction model constructed further showed good predictive ability in both the training and validation groups with good consistency with reality.

Abstract Background The purpose of the present study is to evaluate the prevalence of temporomandibular disorders (TMD) and their associated biological and psychological factors in Chinese university students. Methods A total of 754 students were included from Zunyi Medical University, each participant completed questionnaires and clinical examinations according to the Diagnostic Criteria for Temporomandibular Disorders. Results The overall prevalence of TMD was 31.7% among medical students. Subjects with TMD had a high prevalence of bruxism, empty chewing, unilateral chewing, chewing gum, anterior teeth overbite, anterior teeth overjet, depression, anxiety, and sleep disturbance. Moreover, sleep bruxism, empty chewing, unilateral chewing, anterior teeth overbite, depression, and anxiety were the strongest risk factors for TMD. Conclusions Individuals with TMD have a high prevalence of psychological distress and oral parafunctional habits. Except for the psychological factors associated with TMD, bruxism, abnormal chewing, and malocclusion also shared similar risks for TMD.

Abstract Background Neoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM, and the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. We presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals. Results We first derived intrinsic features for each neoantigen associated with survival, followed by applying neoDL in TCGA data cohort(AUC = 0.988, p value

Abstract Background The objective of this study was to investigate the survival outcomes of surgical margin width in intrahepatic cholangiocarcinoma (ICC). Methods Between November 2011 and August 2017, patients who underwent hepatectomy for ICC were collected from 13 major hepatopancreatobiliary centers in China. The survival outcomes for patients who underwent wide margin hepatectomy (WMH) were compared with those who underwent narrow margin hepatectomy (NMH) using the 1:1 propensity score matching (PSM). Results Among 478 included patients, 195 (40.8%) underwent WMH whereas 283 (59.2%) underwent NMH. PSM yielded 79 matched patients with similar baseline characteristics. Patients underwent WMH had a significant better OS and DFS compared with those underwent NMH (before PSM: median OS 27 vs 17 months, P

Abstract Background The present study investigated the influence of ischemic postconditioning (I-postC) on the adjustment of renal injury after limb ischemia-reperfusion (I/R) injury, to elucidate the mechanisms of the Toll-like receptor 4 (TLR 4)/NF-κB signaling pathway using histopathological and immunohistochemical methods. Methods Male Sprague-Dawley rats were randomly assigned to five groups (numbered from 1 to 5): the sham group (Group 1, only the anesthesia procedure was conducted without limb I/R), the I/R group (Group 2, 4 h of reperfusion was conducted following 4 h limb ischemia under anesthesia), the I/R + I-postC group (Group 3, 4 h of ischemia and 4 h of reperfusion was conducted; before perfusion, 5 min of limb ischemia and 5 min of reperfusion were performed in the rats and repeated 3 times), the I/R + TAK group (Group 4, rats were injected with TLR4 antagonist TAK through the caudal vein before limb ischemia and reperfusion under anesthesia), the TAK group (Group 5, rats were injected with TAK, and the anesthesia procedure was conducted without limb I/R). Histological changes in the kidney in different groups were observed, and the extent of tubular injury was assessed. Changes in biochemical indexes and the expression of inflammatory factors, TLR4, and NF-κB were also evaluated. Results Compared with rats in the I/R group, the secretion of inflammatory factors and the expression levels of TLR4 and NF-κB were decreased in rats in the I/R + I-postC group. Histological analysis revealed renal injury, including inflammatory cell infiltration, dilatation of the tubuli lumen, congestion in glomerular capillaries, degeneration of tubuli epithelial cells, and necrosis was ameliorated by I-postC. Immunohistochemical studies showed that I/R-induced elevation in TLR4 and NF-κB expression was reduced by I-postC treatment. Moreover, the expression levels of TLR4, NF-κB, and inflammatory factors in rats in the I/R + TAK group were also decreased, and the renal pathological lesion was alleviated, which was similar to that in rats in the I/R + I-postC group. Conclusions The present findings suggest that I-postC can reduce tissue injury and kidney inflammation induced by limb I/R injury, possibly via inhibition of the TLR4 and NF-κB pathways.

Abstract Background Tumor-associated macrophages (TAMs) promote key processes in the modulation of tumor microenvironment (TME). However, the clinical significance of heterogeneous subpopulations of TAMs in hepatocellular carcinoma (HCC) remains unknown. Methods HCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas were obtained and analyzed. Immunohistochemistry and flow cytometry were performed to detect the characteristics of sialic acid-binding immunoglobulin-like lectin 10high (Siglec-10hi) TAMs and explore their impact on the TME of HCC. The effect of Siglec-10 blockade was evaluated in vitro based on fresh human tumor tissues. Results Our data revealed that Siglec-10 was abundant in a large proportion of HCC specimens and prominently distributed on macrophages. Kaplan–Meier curves and Cox regression analysis showed that intratumoral Siglec-10+ cell enrichment was associated with unfavorable prognosis in patients with HCC. Notably, multiple anti-inflammatory cytokines and inhibitory receptors were enriched in Siglec-10hi TAMs. RNA sequencing data also revealed that numerous M2-like signaling pathways were significantly upregulated in Siglec-10hi TAMs. High infiltration of Siglec-10hi TAMs was associated with impaired CD8+ T cell function in HCC. Of note, blocking Siglec-10 with the competitive binding antibody Siglec-10 Fc led to decreased expression of immunosuppressive molecules and increased the cytotoxic effects of CD8+ T cells against HCC cells. Moreover, blocking Siglec-10 promoted the anti-tumor efficacy of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab. Conclusions Siglec-10hi TAMs are associated with immune suppression in the TME, and indicate poor prognosis in patients with HCC. Targeting Siglec-10hi TAMs may serve as a promising immunotherapy approach for HCC.

Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality worldwide. The effect of socioeconomic factors on cause-specific mortality and burden of CVD is rarely evaluated in low- and middle-income countries, especially in a rapidly changing society. Methods Original data were derived from the vital registration system in Yangpu, a representative, population-stable district of urban Shanghai, China, during 1974–2015. Temporal trends for the mortality rates and burden of CVD during 1974–2015 were evaluated using Joinpoint Regression Software. The burden was evaluated using age-standardized person years of life loss per 100,000 persons (SPYLLs). Age-sex-specific CVD mortality rates were predicted by using age-period-cohort Poisson regression model. Results A total of 101,822 CVD death occurred during 1974–2015, accounting for 36.95% of total death. Hemorrhagic stroke, ischemic heart disease, and ischemic stroke were the 3 leading causes of CVD death. The age-standardized CVD mortality decreased from 144.5/100,000 to 100.7/100,000 in the residents (average annual percentage change [AAPC] -1.0, 95% confidence interval [CI] -1.7 to − 0.2), which was mainly contributed by women (AAPC -1.3, 95% CI − 2.0 to − 0.7), not by men. Hemorrhagic stroke, the major CVD death in the mid-aged population, decreased dramatically after 1991. The crude mortality of ischemic heart disease kept increasing but its age-adjusted mortality decreased continually after 1997. SPYLLs of CVD death increased from 1974 to 1986 (AAPC 2.1, 95% CI 0.4 to 3.8) and decreased after 1986 (AAPC 1.8, 95% CI − 2.3 to − 1.3). These changes were in concert with the implementation of policies including extended medical insurance coverage, pollution control, active prophylaxis of CVD including lifestyle promotion, and national health programs. The mortality of CVD increased in those born during 1937–1945, a period of the Japanese military occupation, and during 1958–1965, a period including the Chinese Famine. Sequelae of CVD and ischemic heart disease are predicted to be the leading causes of CVD death in 2029. Conclusions Exposure to serious malnutrition in early life might increase CVD mortality in later life. Improvements in medical services, pollution control, and lifestyle could decrease CVD death. New strategy is needed to prevent the aging-related CVD death and burden in the future.

Abstract Background The established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies. Methods The HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level. Results mRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TCGA data are previously reported in the literature and overlap in regulation and function, new pairs have been identified that may contribute to the discovery of novel targets. Conclusion The results strongly support the hypothesis that miRNAs are important regulators of mRNAs in HCC. Furthermore, these results emphasize the biological relevance of studying miRNA-mRNA pairs.

Abstract Background This cross-sectional study aims to validate the Chinese version of Zelaya’s HIV-related Stigma Scale (CVZHSS) among a large undergraduate sample in mainland China, and apply it to measure the level of different dimensions of stigma and their respective determinants. Methods From September 10, 2018, to January 9, 2019, a total of 10,665 eligible undergraduates conveniently drawn from 30 provinces in mainland China (except for Tibet) completed the self-designed online questionnaire distributed via sojump.com voluntarily, anonymously and confidentially. Both exploratory and confirmatory factor analyses (EFA and CFA) were first performed to test its construct validity, Cronbach’s alpha was then used to assess its internal consistency, and Logistic regression analyses were finally carried out to identify predictors of various dimensions of stigma. Results As expected from the original model, four factors (i.e., “fear of casual transmission”, “moral judgment”, “personal stigma” and “perceived community stigma”) were extracted using principal component analysis with varimax rotation, accounting for 63.26% of the total variance. The CFA further confirmed the four-factor construct (CFI = 0.92, GFI = 0.91, RMSEA = 0.07). In addition, all the four factors demonstrated acceptable internal consistency with Cronbach’s alpha ranging from 0.83 to 0.92. Stigma as measured by “fear of casual transmission” (74.4%), “moral judgement” (61.6%), “personal stigma” (79.0%) and “perceived community stigma”(36.5%) is highly prevalent among undergraduates. Except for non-freshmen, less knowledge about HIV and unsafe sex which were consistently associated with higher levels of stigma in all four dimensions, other eight variables including gender, residential area, major, sexual orientation, having ever being tested perception of HIV risk, willingness to utilize HTC service and awareness of the national AIDS policy played differential roles in affecting different dimensions of stigma. Conclusions The CVZHSS is a reliable and valid measurement tool and can be used to identify undergraduates with high levels of stigma. However, the four dimensions (Fear, moral judgement, personal stigma and perceived community stigma) were respectively influenced by different determinants, and thus should be treated independently when designing, implementing and evaluating stigma reduction programs.

Abstract Background Determination of the endogenous loss of fat (ELF) is used to adjust for the estimation of true total tract digestibility (TTTD) of fat in diets and ingredients. Any factor which affected ELF may further affect the digestibility of fat, including sources and concentrations of fat and fiber in the diet. There are some reports of determining the ELF using regression methods based on different levels of fat intake, while reports on effects of dietary fiber content and different fiber-rich ingredients in pig diets on ELF are very limited. Therefore, the objective of this study was to determine the effects of dietary fiber content and different fiber-rich ingredients on endogenous losses of fat and fatty acids at the end of ileum and throughout the entire intestinal tract in growing pigs. Methods In Exp. 1, the effect of fiber content on endogenous loss of fat was determined using six growing pigs (Duroc × Landrace × Yorkshire; 27.6 ± 2.4 kg), fitted with a T-cannula at the end of ileum. The experimental design was a 6 × 6 complete Latin square design with six periods of feeding and six diets. The six experimental fat-free diets were formulated to include graded levels of neutral detergent fiber (NDF) (0, 40, 80, 120, 160 and 200 g/kg) and soybean hull (SH) was the only fiber source, providing 0, 75, 150, 225, 300 and 375 g/kg, respectively. Chromic oxide was included at 4 g/kg in all diets as an indigestible marker. In Exp. 2, six crossbred growing barrows (27.6 ± 1.6 kg) were used and the experimental design was the same as for Exp. 1. The six fat-free diets were formulated to include six common fiber-rich ingredients and the concentration of NDF was 100 g/kg. The six fiber-rich ingredients were defatted rice bran (DRB), sugar beet pulp (SBP), rice hull (RH), corn germ meal (CGM), SH and wheat bran (WB) and they were fed at represented 250, 270, 145, 250, 170 and 280 g/kg in the diet, respectively. Results In Exp. 1, the endogenous loss of fatty acids profile did not change as dietary NDF increased in growing pigs. The endogenous losses of fat, C16:0, C18:0, C18:1, C18:2, total unsaturated fatty acids (UFA) and total saturated fatty acids (SFA) in growing pigs at the end of ileum and throughout the entire intestinal tract increased linearly as NDF content of diets increased. The endogenous losses of fat, as well as C16:0 and C18:0 throughout the entire intestinal tract also increased quadratically as NDF content of diets increased. The ELF increased from 0.71 to 3.14 g/kg of dry matter intake (DMI) and 0.56 to 8.21 g /kg DMI at the end of ileum and throughout the entire intestinal tract in growing pigs, respectively. The ELF occurred in the hindgut except for the growing pigs fed 0 and 4% NDF in their diets. The endogenous losses of C16:0 and UFA occurred primarily in the upper regions of the gut and the greatest endogenous losses of C18:0 occurred in the hindgut. The endogenous losses of fat, individual SFA and total SFA throughout the entire intestinal tract were much greater than that at the end of ileum. However, the endogenous losses of individual UFA and total UFA were less throughout the intestinal tract than at the end of ileum. In Exp. 2, the endogenous losses of fat at the end of ileum were greater in growing pigs fed CGM or WB diets. The endogenous loss of fatty acids profile changed to a slight degree at the end of ileum that the endogenous loss of UFA (particularly C18:1 and C18:2) in growing pigs fed CGM or WB diets were greater (P

Abstract Background Fasting is a simple metabolic strategy that is used to estimate the maintenance energy requirement where the energy supply for basic physiological functions is provided by the mobilization of body reserves. However, the underlying metabolic components of maintenance energy expenditure are not clear. This study investigated the differences in heat production (HP), respiratory quotient (RQ) and plasma metabolites in pigs in the fed and fasted state, using the techniques of indirect calorimetry and metabolomics. Methods Nine barrows (45.2 ± 1.7 kg BW) were fed corn-soybean based meal diets and were kept in metabolism crates for a period of 14 d. After 7 d adaptation, pigs were transferred to respiratory chambers to determine HP and RQ based on indirect calorimetry. Pigs were fed the diet at 2,400 kJ ME/(kg BW0.6·d) during d 8 to 12. The last 2 d were divided into 24 h fasting and 48 h fasting treatment, respectively. Plasma samples of each pig were collected from the anterior vena cava during the last 3 d (1 d while pigs were fed and 2 d during which they were fasted). The metabolites of plasma were determined by high-resolution mass spectrometry using a metabolomics approach. Results Indirect calorimetry analysis revealed that HP and RQ were no significant difference between 24 h fasting and 48 h fasting, which were lower than those of fed state (P

Abstract Background The cranial-caudal-medial approach (CCMA) has been proposed for laparoscopic right hemicolectomy nowadays. This study aimed to investigate the safety and oncological efficacy of CCMA in the treatment of right-sided colon cancer compared to the medial–lateral approach (MLA). Methods Patients diagnosed with right-sided colon cancer were included from February 2015 to June 2018, retrospectively, dividing into the CCMA group and the MLA group. We compared the basic characteristics and the short-term and long-term outcomes in two groups. Results Two hundred and ninety-six patients were included in this study. The baseline characteristics were similar in two groups. Compared with MLA group, CCMA group exhibited shorter operation time (136.3 ± 25.3 min vs. 151.6 ± 21.5 min, P

Abstract Background Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association. Methods We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran’s Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings. Results No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892–0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888–0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy. Conclusion While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.

Abstract Background The experiences and challenges associated with breastfeeding multiple births can be considerably more complex than those of singletons. Multiple births refer to the delivery of more than one offspring in a single birth event. Emphasizing the needs and experiences of mothers with multiple births during breastfeeding can enable healthcare providers to design targeted interventions that enhance breastfeeding rates. However, existing breastfeeding and health education resources and practices do not fully meet the needs of women who breastfeed multiples. This review aimed to review and synthesize qualitative studies on the breastfeeding experiences of women with multiple births. Methods A systematic search was conducted in 10 electronic databases for papers published from the inception of the database to March 2024. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research was utilized to evaluate the methodological quality of the studies included. The thematic synthesis method of Thomas and Harden was employed to integrate and analyze the included literature to derive new categories and conclusions. Findings Eight studies met the inclusion criteria and quality assessment criteria for this study. Through the integration of their results, four themes were identified: the choice and willingness to breastfeed multiple births; the challenges of breastfeeding multiple births; stage management and individualised adaptation of breastfeeding; and the experience of support. Conclusion Throughout the feeding process from pregnancy to the postpartum period, mothers with multiple births often have predominantly negative experiences with breastfeeding. Consequently, hospitals should create a multidisciplinary follow-up team comprising obstetrics, neonatology, psychology, and community services to offer specialized and personalized support to these women at various stages. Systematic review registration [ https://www.crd.york.ac.uk/PROSPERO/ ], identifier [PROSPERO 2024 CRD42024520348].

Abstract Background Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. Methods A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. Results Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). Conclusions Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.

Abstract Background Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood. Methods We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice. Results Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice. Conclusion Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages.

Abstract Background Combining conventional radiomics models with deep learning features can result in superior performance in predicting the prognosis of patients with tumors; however, this approach has never been evaluated for the prediction of metachronous distant metastasis (MDM) among patients with retroperitoneal leiomyosarcoma (RLS). Thus, the purpose of this study was to develop and validate a preoperative contrast-enhanced computed tomography (CECT)-based deep learning radiomics model for predicting the occurrence of MDM in patients with RLS undergoing complete surgical resection. Methods A total of 179 patients who had undergone surgery for the treatment of histologically confirmed RLS were retrospectively recruited from two tertiary sarcoma centers. Semantic segmentation features derived from a convolutional neural network deep learning model as well as conventional hand-crafted radiomics features were extracted from preoperative three-phase CECT images to quantify the sarcoma phenotypes. A conventional radiomics signature (RS) and a deep learning radiomics signature (DLRS) that incorporated hand-crafted radiomics and deep learning features were developed to predict the risk of MDM. Additionally, a deep learning radiomics nomogram (DLRN) was established to evaluate the incremental prognostic significance of the DLRS in combination with clinico-radiological predictors. Results The comparison of the area under the curve (AUC) values in the external validation set, as determined by the DeLong test, demonstrated that the integrated DLRN, DLRS, and RS models all exhibited superior predictive performance compared with that of the clinical model (AUC 0.786 [95% confidence interval 0.649–0.923] vs. 0.822 [0.692–0.952] vs. 0.733 [0.573–0.892] vs. 0.511 [0.359–0.662]; both P

Abstract Purpose This study aims to evaluate the pain relief function of chemical sphincterotomy in patients undergoing haemorrhoid surgery and compare, through a meta-analysis, the different drugs used to treat this condition. Methods We conducted a search in databases including PubMed, EMBASE and Web of Science. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (ROB2). The pain score was assessed using a visual analogue scale (VAS) on day 1, day 2, and day 7, and a meta-analysis was conducted based on the use of random effects models. In addition, the subgroup analysis was evaluated based on the kind of experimental drugs. Heterogeneity and publication bias were assessed. Results Fourteen studies with a total of 681 patients were included in this meta-analysis, and all studies were randomized controlled trials RCTs. Chemical sphincterotomy showed better pain relief function than placebo on day 1 (SMD: 1.16, 95% CI 0.52 to 1.80), day 2 (SMD: 2.12, 95% CI 1.37 to 2.87) and day 7 (SMD: 1.97, 95% CI 1.17 to 2.77) after surgery. In the subgroup meta-analysis, we found that different drugs for chemical sphincterotomy provided different pain relief. Conclusion Chemical sphincterotomy effectively relieves pain after haemorrhoidectomy, and calcium channel blockers have the best effect.

Abstract Background We evaluated the value of electrophysiological indicators by external anal sphincter electromyography (EAS-EMG), sympathetic skin response (SSR), R-R interval variation (RRIV), and Bulbocavernosus Reflex (BCR) in differential diagnosis of multiple system atrophy (MSA) and Parkinson’s disease (PD). Methods A total of 41 patients with MSA and 32 patients with PD were enrolled. The electrophysiological changes of autonomic dysfunction were assessed with BCR, EAS-EMG, SSR, and RRIV, and the abnormal rate of each indicator was calculated. The diagnostic value of each indicator was analyzed with ROC curve. Results The incidence rate of autonomic dysfunction in MSA group was significantly higher than that in PD group (p 0.05). The sensitivity of BCR combined with EAS-EMG indicators in differential diagnosis of MSA and PD were 92.3% in males and 86.7% in females, respectively, and the specificity was 72.7% in males and 90% in females, respectively. Conclusions Combined analysis of BCR and EAS-EMG has high sensitivity and specificity for differential diagnosis of MSA and PD.

Abstract In the last few decades, YAP has been shown to be critical in regulating tumor progression. YAP activity can be regulated by many kinase cascade pathways and proteins through phosphorylation and promotion of cytoplasmic localization. Other factors can also affect YAP activity by modulating its binding to different transcription factors (TFs). Programmed cell death (PCD) is a genetically controlled suicide process present with the scope of eliminating cells unnecessary or detrimental for the proper development of the organism. In some specific states, PCD is activated and facilitates the selective elimination of certain types of tumor cells. As a candidate oncogene correlates with many regulatory factors, YAP can inhibit or induce different forms of PCD, including apoptosis, autophagy, ferroptosis and pyroptosis. Furthermore, YAP may act as a bridge between different forms of PCD, eventually leading to different outcomes regarding tumor development. Researches on YAP and PCD may benefit the future development of novel treatment strategies for some diseases. Therefore, in this review, we provide a general overview of the cellular functions of YAP and the relationship between YAP and PCD.

Abstract The role of PLAC8 in tumorigenesis has been gradually elucidated with the development of research. Although there are common molecular mechanisms that enforce cell growth, the impact of PLAC8 is varied and can, in some instances, have opposite effects on tumorigenesis. To systematically understand the role of PLAC8 in tumors, the molecular functions of PLAC8 in cancer will be discussed by focusing on how PLAC8 impacts tumorigenesis when it arises within tumor cells and how these roles can change in different stages of cancer progression with the ultimate goal of suppressing PLAC8-relevant cancer behavior and related pathologies. In addition, we highlight the diversity of PLAC8 in different tumors and its functional output beyond cancer cell growth. The comprehension of PLAC8’s molecular function might provide new target and lead to the development of novel anticancer therapies.