Search

Abstract Background The association between MicroRNAs (miRNAs) and diseases is crucial in treating and exploring many diseases or cancers. Although wet-lab methods for predicting miRNA-disease associations (MDAs) are effective, they are often expensive and time-consuming. Significant advancements have been made using Graph Neural Network-based methods (GNN-MDAs) to address these challenges. However, these methods still face limitations, such as not considering nodes’ deep-level similarity associations and hierarchical learning patterns. Additionally, current models do not retain the memory of previously learned heterogeneous historical information about miRNAs or diseases, only focusing on parameter learning without the capability to remember heterogeneous associations. Results This study introduces the K-means disentangled high-level biological similarity to utilize potential hierarchical relationships fully and proposes a Graph Attention Heterogeneous Biological Memory Network architecture (DiGAMN) with memory capabilities. Extensive experiments were conducted across four datasets, comparing the DiGAMN model and its disentangling method against ten state-of-the-art non-disentangled methods and six traditional GNNs. DiGAMN excelled, achieving AUC scores of 96.35%, 96.10%, 96.01%, and 95.89% on the Data1 to Data4 datasets, respectively, surpassing all other models. These results confirm the superior performance of DiGAMN and its disentangling method. Additionally, various ablation studies were conducted to validate the contributions of different modules within the framework, and’s encoding statuses and memory units of DiGAMN were visualized to explore the utility and functionality of its modules. Case studies confirmed the effectiveness of DiGAMN’s predictions, identifying several new disease-associated miRNAs. Conclusions DiGAMN introduces the use of a disentangled biological similarity approach for the first time and successfully constructs a Disentangled Graph Attention Heterogeneous Biological Memory Network model. This network can learn disentangled representations of similarity information and effectively store the potential biological entanglement information of miRNAs and diseases. By integrating disentangled similarity information with a heterogeneous attention memory network, DiGAMN enhances the model’s ability to capture and utilize complex underlying biological data, significantly outperforming many existing models. The concepts used in this method also provide new perspectives for predicting miRNAs associated with diseases.

Abstract Background Unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) is a minimally invasive procedure for treating lumbar degenerative diseases. However, the use of endoscopic lumbar interbody fusion does not completely eliminate the risk of dural and nerve root injuries. This study has refined UBE-TLIF to incorporate en bloc resection of the ligamentum flavum for bilateral decompression and aim to detail the surgical procedure and evaluate the clinical outcomes of this modification. Methods This study analyzes the outcomes of 109 consecutive patients treated by a single surgeon for lumbar degenerative disease using UBE-TLIF. Patients were divided into two groups: Group A (51 patients) underwent en bloc resection of the ligamentum flavum, while Group B (58 patients) underwent routine piecemeal resection. Assessed outcomes included surgery-related complications, operation time, estimated blood loss, postoperative stay, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). The surgical technique is detailed within the study. Results In Group A, no nerve root or dura injuries were observed, whereas Group B reported one case of nerve root injury and three dura tears. The average operation time for Group A was shorter than that for Group B; however, the difference was not statistically significant (P > 0.05). No significant differences were found in the VAS score, ODI, estimated blood loss, or postoperative stay between the groups during follow-up. Conclusions En bloc resection of the ligamentum flavum for bilateral decompression in UBE-TLIF demonstrates satisfactory clinical outcomes and low perioperative complications rates, offering a safe and innovative alternative for the treatment of lumbar degenerative disease.

Abstract Background There is no regulation in the current guidelines on the sequence of ligation of the inferior mesenteric artery and vein during rectal cancer surgery owing to a lack of sufficient evidence. Circulating tumor cells (CTCs) in peripheral blood can be used as potential indicators for predicting prognosis in colorectal cancer patients. This study aims to explore the feasibility of different ligation sequences for the inferior mesenteric vessels and their potential influence on CTCs. Methods This pilot study involved 29 stage I-III rectal adenocarcinoma patients undergoing laparoscopic surgery. Patients were allocated into two groups based on the sequence of vascular ligation: vein-first (V-first) and artery-first (A-first). The primary objective was to assess the impact of the ligation sequence on peripheral blood CTC levels pre- and post-operatively. Secondary outcomes included intraoperative complications, surgical duration, blood loss, and number of lymph nodes harvested, and postoperative complications. The study was approved by the ethics committee of our hospital (SCCHEC-02-2024-102), and all patients provided informed consent. Results No significant differences were found between the two groups regarding surgical duration, blood loss, lymph nodes harvested, or postoperative complications. A reduction in CTCs postoperatively was observed in 36% of patients in the V-first group, in comparison to 20% in the A-first group. Conclusion Both A-first and V-first ligation sequences are viable and safe options in laparoscopic rectal cancer surgery. The V-first approach may be more effective in reducing levels of CTCs in peripheral blood. Further randomized studies are warranted to explore these findings comprehensively.

Abstract Background Increasing studies focused on the efficacy of acupuncture on pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization-embryo transfer (IVF-ET). However, debatable conclusions have been drawn from different randomized controlled trials (RCTs), which might be related to different doses of acupuncture. Objective To evaluate whether acupuncture has a dose-dependent effect on pregnancy outcomes in patients with PCOS undergoing IVF-ET in systematically reviewing. Methods Seven electronic databases were searched from inception to October 10th, 2024. The Cochrane Collaboration’s tool ROB 2.0 (ROB 2.0) provided an assessment for the risk of bias. The acupuncture dose was extracted, then categorized into high, medium, and low dose according to the scoring system results, the evidence was assessed by Slavin’s qualitative best-evidence synthesis approach in a rigours methodological way. Clinical pregnancy rate (CPR) was regarded as the primary outcome. Results A total of 953 subjects met the eligibility criteria in 12 RCTs were included, among which two studies were low dose, four were medium dose, and six were high dose. The overall quality of included studies was low, 50.00% (6/12) studies were low risk, 16.67% (2/12) studies were some concerns, and 33.33% (4/12) studies were high risk. Comparing the results, the consistent high-dose result among high-quality trials provides strong evidence for a positive correlation between high-dose acupuncture and pregnancy outcomes. Conclusion A trend indicates that higher acupuncture doses yield better outcomes for PCOS patients undergoing IVF-ET. Further confirmation through direct comparisons of different doses was needed. Trial registration The systematic review has been registered on PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), and the registration number is CRD42023400187.

Abstract Comprehensive characterizations of genetic diversity and demographic models of ethnolinguistically diverse Chinese populations are essential for elucidating their forensic characteristics and evolutionary past. We developed a 114-plex NGS InDel panel to genotype 114 genome-wide markers and investigated the genetic structures of Zhuang, Hui, Miao, Li, Tibetan, Yi, and Mongolian populations, encompassing five language families. This panel demonstrated robust performance, with exceptional potential for forensic individual identification and paternity testing, evidenced by the combined power of discrimination for 77 autosomal InDels (ranged from 1-3.6400 × 10–30 to 1-3.5713 × 10–32) and the combined power of exclusion (ranged from 1-2.1863 × 10–6 to 1-2.1261 × 10–7). The cumulative mean exclusion chance for 32 X-chromosomal InDels varied between 0.99996 and 0.99999 for trios and 0.99760 to 0.99898 for duos. We also analyzed genetic similarities and differences between these populations and 27 global populations, revealing distinct clusters among African, South Asian, East Asian, and European groups, with a close genetic affinity to East Asians. Notably, we identified geography-related genetic substructures: Inner Mongolia Mongolians and Gansu Huis formed a northern branch, Tibetans and Yis from Sichuan constituted a highland branch, and Guangxi Zhuangs exhibited close ties with Hainan Lis and Guangxi Miaos in the southern branch. Additionally, many InDels proved to be ancestry-informative markers for biogeographic ancestry inference. Collectively, these findings underscore the utility of the 114-plex NGS InDel panel as a complementary tool for forensic investigations and as a source of insights into the genetic architecture of ethnolinguistically distinct Chinese populations.

Abstract Background Machine learning (ML) has been widely applied to predict the outcomes of numerous diseases. The current study aimed to develop a prognostic prediction model using machine learning algorithms and identify risk factors associated with residual back pain in patients with osteoporotic vertebrae compression fracture (OVCF) following percutaneous vertebroplasty (PVP). Methods A total of 863 OVCF patients who underwent PVP surgery were enrolled and analyzed. One month following surgery, a Visual Analog Scale (VAS) score of ≥ 4 was deemed to signify residual low back pain following the operation and patients were grouped into a residual pain group and pain-free group. The optimal feature set for both machine learning and statistical models was adjusted based on a 2000-resample bootstrap-based internal validation via an exhaustive search. The area under the curve (AUC), classification accuracy, sensitivity, and specificity of each model were then calculated to evaluate the predictive performance of each model. Results In our current study, two main findings were observed: (1) Compared with statistical models, ML models exhibited superior predictive performance, with SVM demonstrating the highest prediction accuracy; (2) several variables were identified as the most predictive factors by both the machine learning and statistical models, including bone cement volume, number of fractured vertebrae, facet joint violation, paraspinal muscle degeneration, and intravertebral vacuum cleft. Conclusion Overall, the study demonstrated that machine learning classifiers such as SVM can effectively predict residual back pain for patients with OVCF following PVP while identifying associated predictors in a multivariate manner.

Abstract Background This study aims to develop and validate an integrated predictive model combining CT radiomics and clinical parameters for early assessment of acute pancreatitis severity. Methods A retrospective cohort of 246 patients with acute pancreatitis was analyzed, with a 70%-30% split for training and validation groups. CT image segmentation was performed using ITK-SNAP, followed by the extraction of radiomics features. The stability of the radiomics features was assessed through inter-observer Intraclass Correlation Coefficient analysis. Feature selection was carried out using univariate analysis and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. A radiomics model was constructed through logistic regression to compute the radiomics score. Concurrently, univariate and multivariate logistic regression were employed to identify independent clinical risk factors for the clinical model. The radiomics score and clinical variables were integrated into a combined model, which was visualized with a nomogram. Model performance and net clinical benefit were evaluated through the area under the receiver operating characteristic curve (AUC), the DeLong test, and decision curve analysis. Results A total of 913 radiomics features demonstrated satisfactory consistency. Eight features were selected for the radiomics model. Serum calcium, C-reactive protein, and white blood cell count were identified as independent clinical predictors. The AUC of the radiomics model was 0.871 (95% CI, 0.793–0.949) in the training cohort and 0.859 (95% CI, 0.751–0.967) in the validation cohort. The clinical model achieved AUCs of 0.833 (95% CI, 0.756–0.910) and 0.810 (95% CI, 0.692–0.929) for the training and validation cohorts, respectively. The combined model outperformed both the radiomics and clinical models, with an AUC of 0.905 (95% CI, 0.837–0.973) in the training cohort and 0.908 (95% CI, 0.824–0.992) in the validation cohort. The DeLong test confirmed superior predictive performance of the combined model over both the radiomics and clinical models in the training cohort, and over the clinical model in the validation cohort. Decision curve analysis further demonstrated that the combined model provided greater net clinical benefit than the radiomics or clinical models alone. Conclusion The clinical-radiomics model offers a novel tool for the early prediction of acute pancreatitis severity, providing valuable support for clinical decision-making.

Abstract Background Circulating tumour DNA (ctDNA) has emerged as a valuable liquid biopsy biomarker in the field of oncology, including head and neck squamous cell carcinomas (HNSCCs), offering potential insights into cancer diagnosis, progression, and prognosis. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in HNSCC. Methods PubMed and Ovid were searched as part of our review. Studies that investigated the relationship between ctDNA and prognosis in HNSCC patients were included. Outcomes extracted included basic characteristics, ctDNA details and survival data. Meta-analysis was performed on eligible studies to determine pooled progression-free/recurrence-free survival (RFS/PFS) and overall survival (OS). Results Twenty-two studies were included, involving 5062 HNSCC patients from 11 countries. The meta-analysis demonstrated that the positive ctDNA/methylation detection was associated with worse OS (HR = 2.00, 95% CI 1.35–2.96) and worse PFS/RFS (HR = 3.54, 95% CI 1.05–11.85). Positive ctEBV DNA was associated with poorer OS (HR = 2.86, 95% CI 1.84–4.45) and poorer PFS/RFS (HR = 1.93, 95% CI 1.74–2.13). Positive ctHPV DNA was associated with poorer OS (HR = 1.38, 95% CI 1.07–1.38) but not PFS/PFS (HR = 1.33, 95% CI 0.96–1.85). Conclusion Meta-analysis indicates that the status of ctDNA is significantly associated with the prognosis of HNSCC patients, with ctDNA/methylation-negative patients demonstrating better PFS/RFS and OS.

Abstract Background The incidence of androgenetic alopecia in males is on the rise annually, with hair transplantation using follicular unit extraction (FUE) gaining increasing acceptance as an appropriate treatment for these individuals. Methods A retrospective study was undertaken, involving 158 male patients diagnosed with androgenetic alopecia, who underwent treatment between January 2016 and December 2020 at the Medical Cosmetology Department of the First Affiliated Hospital of Xi’an Medical University. Demographic data and treatment characteristics were documented and analyzed. Clinical efficacy, operation-related complications, patient satisfaction rates, and quality of life scores were assessed and analyzed. Results Following FUE hair transplantation, over 90% of the hair follicles survived in 158 patients, with more than 85% of patients achieving a hair follicle survival rate exceeding 95% at 12 months post-operation. Patient satisfaction rates exceeded 98%, while the complication rate was below 6%. Conclusion Our findings demonstrate that FUE is a minimally invasive hair transplant technique associated with a high hair follicle survival rate and optimal hair density. This approach proves effective in treating male androgenetic alopecia and merits further clinical application.

Abstract Background Although mesenchymal stem cells (MSCs) have been proven to be appropriate candidates for the treatment of AKI-CKD, their efficacy is limited and variable. Astilbin (AST) had a protective effect on MSCs from oxidative stress via ROS-scavenging, however, whether it can improve MSCs’ renoprotection and the underlying mechanism need to be elucidated. Methods AST-pretreated MSCs were administered intravenously into the ischemia–reperfusion injury mice models and the renal function, pathological changes and inflammation. Were evaluated. In addition, DARTS, molecular docking, surface plasma resonance(SPR), dual-luciferase reporter gene assay and the ChIP-PCR were utilized to explore the potential signaling pathways through which AST exert renal protective effects on MSCs. Results AST-pretreated MSCs markedly improved kidney function, reduced kidney pathological injury and inflammation in AKI and AKI-CKD mice. RNA-seq results showed that PTGS2 related pathway was significantly up-regulated in MSCs after AST pretreatment. DARTS assay, molecular docking and SPR assay revealed that AST could bind with the transcriptional factor of Kruppel-Like Factor 4(KLF4) protein. The promoter of PTGS2 had the binding and transcriptional activation by KLF4. Furthermore, AST pretreatment promoted the secretion of PGE2 in MSCs. And then the westren blot results showed that the protein levels of CD163 and CD206 were upregulated after coculture in AST-pretreated MSCs, indicating that the polarization of RAW264.7 cells towards M2-like macrophages was induced. Knockdown of PTGS2 reversed the ability of AST-pretreated MSCs in converting macrophages to M2 phenotype and reducing their therapeutic effects on AKI-CKD mice. Conclusion AST pretreatment enhances the efficacy of MSCs on AKI and AKI-CKD mice by inducing of M2-like phenotype polarization in macrophages through the PTGS2-mediated pathway. This approach not only provides a novel strategy to strengthen the capability of MSCs but also helps elucidate the beneficial effects of the Chinese herbal medicine AST.

Abstract Background No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure. Methods This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.3 mmol/L) admitted within 72 h from the onset of symptoms. Patients were dichotomised on study day 3 into either target reaching (plasma triglyceride ≤ 5.65 mmol/L) or not. The primary outcome was organ failure-free days (OFFD) to 14 days of enrolment. The association between target-reaching and OFFD was modelled. Additionally, the slope in plasma triglyceride over the first three days in response to treatment was calculated, and its association with OFFD was assessed as a sensitivity analysis. Results Among the 300 enrolled patients, 211 underwent exclusive medical treatment, and 89 underwent various blood purification therapies. Triglyceride levels were available in 230 patients on study day 3, among whom 122 (53.0%) had triglyceride levels of ≤ 5.65 mmol/l. The OFFD was not different between these patients and those in whom plasma triglyceride remained > 5.65 mmol/L [median (IQR): 13 (10–14) vs. 14 (10–14), p = 0.46], even after adjustment for potential confounders. For the decline slopes, there was no significant change in OFFD with a steeper decline slope [risk difference, − 0.088, 95% CI, − 0.334 to 0.158, p = 0.48]. Conclusions Triglyceride-lowering therapies vary greatly across centres. More rapid triglyceride decline was not associated with improving incidence and duration of organ failure.

Abstract Background Ischemic stroke (IS) is a commonly seen cerebrovascular disease which seriously endangers the health of middle age and old people. However, its etiology and pathogenesis have not yet fully comprehended. miR-30 gene is a novel gene which may be involved in IS. However, no studies have investigated the relationship between IS and the single-nucleotide polymorphisms (SNPs) of miR-30. Therefore, this study examined the relationship between miR-30 polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) and the risk of IS. Methods Totally 248 IS patients and 230 age-, sex- and race-matched controls were involved in this study. Based on SNPscan technique, four polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) were genotyped. Results There exists a significant association between rs2222722 polymorphism and the risk of IS according to analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 1.616, 95% CI: 0.943–2.768, P = 0. 081); (AA vs. GG: adjusted OR = 2.447, 95% CI: 1.233–4.858, P = 0.011); dominant model: adjusted (OR = 1.806, 95% CI, 1.082–3.016, P = 0.024); (G vs. A: adjusted OR = 1.492, 95% CI: 1.148–1.939, P = 0.003). Besides, miR-30a expression was significantly higher in patients undergoing IS relative to that in controls (P

Abstract Background This study aims to evaluate the efficacy and clinical outcomes of Nice knot-assisted fixation in the management of comminuted and displaced clavicle fractures. Methods A systematic search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, China Biology Medicine (CBM) database, CNKI, Wanfang, and VIP database, to identify studies comparing Nice knot-assisted fixation with traditional surgical treatment for displaced midshaft clavicle fractures. The primary outcomes assessed included fracture healing times, hospitalization days, complications, and functional outcomes. Secondary outcomes such as intraoperative blood loss, operative time, incision length, and fluoroscopy time were also evaluated. Data were analyzed using random-effects models, and summary statistics including Mean Difference (MD), risk ratios (RRs) and theirs’ 95% confidence intervals (CIs) were calculated. Results Screening of the literature yielded a total of 11 studies meeting the inclusion criteria, involving 754 patients. Meta-analysis of the pooled data demonstrated a significant advantage of Nice knot-assisted fixation over traditional surgical treatment in terms of operative time (MD = -11.53, 95% CI: -18.16 to -4.91, p = 0.0006) and blood loss (MD = -14.19, 95% CI: -20.93 to -7.45, p = 0.00001). Additionally, Nice knot-assisted fixation was associated with reduced fracture healing time (MD = -0.63, 95% CI: -1.12 to -0.14, p = 0.01) rather than hospitalization days (MD = -0.47, 95% CI: -1.14 to 0.21, p = 0.18) and complications (RR = 0.48, 95% CI: 0.23 to 1.01, p = 0.05) compared to traditional surgical treatment. Moreover, nice knot-assisted fixation was associated with increased constant-murley score and Neer score, and reduced visual analogue scale (VAS) score compared to traditional surgical treatment. Conclusion This study highlights that Nice knot assistance offers advantages in reducing intraoperative blood loss, shortening operation time, and achieving favorable postoperative outcomes.

Abstract Background The zoonotic infectious diseases of poverty (zIDPs) are a group of diseases contributing to global poverty, with significant impacts on a substantial population. This study aims to describe the global, regional, and national burden of zIDPs—schistosomiasis, cystic echinococcosis, cysticercosis, and food-borne trematodiases (FBTs)—to support policy making and resource allocation for their control and elimination. Methods Data of zIDPs from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were retrieved from 1990 to 2021. The age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rate were described and the estimated annual percentage changes (EAPCs) were calculated to quantify their burden and temporal trends. Spearman correlation analysis was conducted to examine the relationship between age-standardized rates and Socio-demographic Index (SDI). Results In 2021, these zIDPs exhibited a certain level of ASPRs and age-standardized DALY rates, while maintaining relatively low ASMRs. Noticeably, schistosomiasis presented the highest ASPR of 1914.299 (95% UI: 1378.920, 2510.853 per 100,000 population) and an age-standardized DALY rate of 21.895 (95% UI: 12.937, 37.278 per 100,000 population) among the zIDPs. The tapestry of burden—woven predominantly through low and lower-middle SDI regions—stretched across Africa, Latin America, and parts of Asia. From 1990 to 2021, a kaleidoscopic shift was observed globally as ASPRs, ASMRs, and age-standardized DALY rates declined significantly, as reflected by the EAPC values. Negative correlations were observed between the ASPRs, ASMRs, age-standardized DALY rates of schistosomiasis (r value = − 0.610, − 0.622 and − 0.610), cystic echinococcosis (− 0.676 of ASMR, − 0.550 of age-standardized DALYs), cysticercosis (− 0.420, − 0.797 and − 0.591) and the SDI. In contrast, a slight positive correlation was noted between the ASPR, age-standardized DALY rates of FBTs and SDI with r value of 0.221 and 0.213, respectively. Conclusion The burden of zIDPs declined across almost all endemic regions from 1990 to 2021, yet still predominated in low and low-middle SDI regions. Substantial challenges exist to achieve the goal of control and elimination of zIDPs, and integrated approaches based on One Health need to be strengthened to improve health outcomes. Graphical Abstract

Abstract Background In supporting primary healthcare in delivering high-quality care for individuals with type 2 diabetes mellitus (T2DM), previous research emphasized strategies to facilitate communication and collaboration between primary healthcare providers and hospitals. This study aims to evaluate the effectiveness of case discussion conferences between specialists from hospitals and primary healthcare providers in China on the optimization of diabetes management and the improvement of patient health outcomes. Methods This study will be a parallel cluster randomized controlled trial in which primary healthcare institutions in Shouguang city and Shangsi County will be randomly allocated to the intervention and control groups. The intervention will involve regular case discussion conferences where attendants will meet to discuss complex cases with patients diagnosed with type 2 diabetes mellitus, exchange experiences, and seek and provide expert advice. Family doctor teams from primary healthcare institutions and specialists from secondary or tertiary hospitals will engage in these conferences. Data will be collected at baseline and at the 6- and 12-month follow-ups. The primary clinical outcome measures will focus on the changes in the HbA1c and FBG levels of patients under management. The secondary outcomes will include other physiological indicators, such as blood pressure, BMI, and cholesterol. The evaluation will extend to changes in the capabilities and behaviors of primary healthcare providers. Furthermore, the feasibility and adherence of this intervention will be thoroughly assessed. Discussion This study is designed to generate robust evidence on the effectiveness of case discussion conferences, an interprofessional collaboration strategy, in enhancing diabetes care delivery in primary healthcare, with the ultimate goal of improving patient health outcomes. Trial registration Chinese Clinical Trial Registry ChiCTR2300078829. Registered on December 19, 2023. https://www.chictr.org.cn/showproj.html?proj=210293

Abstract Background Age-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin–angiotensin system (RAS) in human ovary and it plays a key role. Methods After collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells. Results First, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r 0.05). Conclusions Together, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline.

Abstract Aims The present study aims to develop a nano-delivery system that encapsulates berberine (BBR) into PLGA-based nanoparticles (BPL-NPs), to treat ulcerative colitis (UC). Furthermore, the therapeutic efficacy and molecular targeting mechanisms of BPL-NPs in the management of UC are thoroughly examined. Methods Emulsion solvent-driven methods were used to self-assemble BBR and PLGA into nanoparticles, resulting in the development of the nano-delivery system (BPL-NPs). The therapeutic effectiveness of BPL-NPs was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice and a lipopolysaccharide (LPS)-induced model of inflammation in THP-1 macrophages. The interaction between Mφs and NCM-460 cells was investigated using a co-culture system. The molecular targeting ability of BPL-NPs in the treatment of UC was validated through in vitro as well as in vivo experiments. Results The BPL-NPs demonstrated a particle size of 184 ± 22.4 nm, enhanced dispersibility in deionized water, and a notable encapsulation efficiency of 31.1 ± 0.2%. The use of BPL-NPs clearly improved the clinical symptoms and pathological changes associated with UC in mice while also ensuring minimal toxicity. In addition, BPL-NPs improved intestinal epithelial cell apoptosis and enhanced the function of the intestinal barrier by inhibiting M1 Mφs infiltration and IL-6 signaling pathway in mice with UC. Furthermore, the BPL-NPs were found to selectively target the IL-6/IL-6R axis during the M1 Mφs-induced apoptosis of NCM460 cells. Conclusion The BPL-NPs were confirmed to harbor anti-inflammatory effects both in vitro and in vivo, along with enhanced water solubility and bioactivity. In addition, the precise targeting of the IL-6/IL-6R axis was confirmed as the mechanism by which the BPL-NPs exerted therapeutic effects in UC, as demonstrated in both in vitro as well as in vivo studies. Graphical Abstract

Abstract Background Older patients with coronary artery disease (CAD) are particularly vulnerable to the efficacy and adverse drug reactions, and may therefore particularly benefit from personalized medication. Drug–gene interactions (DGIs) occur when an individual’s genotype affects the pharmacokinetics and/or pharmacodynamics of a victim drug. Objectives This study aimed to investigate the impact of cardiovascular-related DGIs on the clinical efficacy and safety outcomes in older patients with CAD. Methods Hospitalized older patients (≥ 65 years old) with CAD were consecutively recruited from August 2018 to May 2022. Eligible patients were genotyped for the actionable pharmacogenetic variants of CYP2C9, CYP2C19, CYP2D6, CYP3A5, and SLCO1B1, which had clinical annotations or implementation guidelines for cardiovascular drugs. Allele frequencies and DGIs were determined in the cohort for the 5 actionable PGx genes and the prescribed cardiovascular drugs. All patients were followed up for at least 1 year. The influence of DGIs on the cardiovascular drug-related efficacy outcomes (all-cause mortality and/or major cardiovascular events, MACEs) and drug response phenotypes of “drug-stop” and “dose-decrease” were evaluated. Results A total of 1,017 eligible older patients with CAD were included, among whom 63.2% were male, with an average age of 80.8 years old, and 87.6% were administrated with polypharmacy (≥ 5 medications). After genotyping, we found that 96.0% of the older patients with CAD patients had at least one allele of the 5 pharmacogenes associated with a therapeutic change, indicating a need for a therapeutic change in a mean of 1.32 drugs of the 19 cardiovascular-related drugs. We also identified that 79.5% of the patients had at least one DGI (range 0–6). The median follow-up interval was 39 months. Independent of age, negative association could be found between the number of DGIs and all-cause mortality (adjusted HR: 0.84, 95% CI: 0.73–0.96, P = 0.008), and MACEs (adjusted HR: 0.84, 95% CI: 0.72–0.98, P = 0.023), but positive association could be found between the number of DGIs and drug response phenotypes (adjusted OR: 1.24, 95% CI: 1.05–1.45, P = 0.011) in the elderly patients with CAD. Conclusions The association between cardiovascular DGIs and the clinical outcomes emphasized the necessity for the integration of genetic and clinical data to enhance the optimization of cardiovascular polypharmacy in older patients with CAD. The causal relationship between DGIs and the clinical outcomes should be established in the large scale prospectively designed cohort study.

Abstract Background The family Lauraceae is subdivided into six main lineages: Caryodaphnopsideae, Cassytheae, Cryptocaryeae, Hypodaphnideae, Laureae, and Neocinnamomeae. However, phylogenetic relationships among these lineages have been debatable due to incongruence between trees constructed using nuclear ribosomal DNA (nrDNA) sequences and chloroplast (cp) genomes. As with cp DNA, the mitochondrial (mt) DNA of most flowering plants is maternally inherited, so the phylogenetic relationships recovered with mt genomes are expected to be consistent with that from cp genomes, rather than nrDNA sequences. Results The mitogenome of Machilus yunnanensis, with a length of 735,392 bp, has a very different genome size and gene linear order from previously published magnoliid mitogenomes. Phylogenomic reconstructions based on 41 mt genes from 92 Lauraceae mitogenomes resulted in highly supported relationships: sisterhood of the Laureae and a group containing Neocinnamomeae and Caryodaphnopsideae, with Cassytheae being the next sister group, followed by Cryptocaryeae. However, we found significant incongruence among the mitochondrial, chloroplast, and nuclear phylogenies, especially for the species within the Caryodaphnopsideae and Neocinnamomeae lineages. Time-calibrated phylogenetic analyses showed that the split between Caryodaphnopsideae and Neocinnamomeae dated to the later Eocene, around 38.5 Ma, Laureae originated in the Late Cretaceous, around 84.9 Ma, Cassytheae originated in the mid-Cretaceous around 102 Ma, and Cryptocaryeae originated in the Early Cretaceous around 116 Ma. From the Late Cretaceous to the Paleocene, net diversification rates significantly increased across extant clades of major lineages, and both speciation rates and net diversification rates continued steady growth towards the present. Conclusions The topology obtained here for the first time shows that mt genes can be used to support relationships among lineages of Lauraceae. Our results highlight that both Caryodaphnopsideae and Neocinnamomeae lineages are younger than previously thought, likely first diversifying in the Eocene, and species in the other extant lineages of Lauraceae dates in a long-time span from the Early Cretaceous to the Eocene, and the climate of a period of about 90 million years was relatively warm, while the extant species of Lauraceae then continuously diversified with global cooling from the Eocene to the present day.

Abstract Background Short-term exposure to ozone (O3) has been associated with higher stroke mortality, but it is unclear whether this association differs between urban and rural areas. The study aimed to compare the association between short-term exposure to O3 and ischaemic and haemorrhagic stroke mortality across rural and urban areas and further investigate the potential impacts of modifiers, such as greenness, on this association. Methods A multi-county time-series analysis was carried out in 19 counties of Shandong Province from 2013 to 2019. First, we employed generalized additive models (GAMs) to assess the effects of O3 on stroke mortality in each county. We performed random-effects meta-analyses to pool estimates to counties and compare differences in rural and urban areas. Furthermore, a meta-regression model was utilized to assess the moderating effects of county-level features. Results Short-term O3 exposure was found to be associated with increased mortality for both stroke subtypes. For each 10-µg/m3 (lag0-3) rise in O3, ischaemic stroke mortality rose by 1.472% in rural areas and 1.279% in urban areas. For each 0.1-unit increase in the Enhanced Vegetation Index (EVI) per county, the ischaemic stroke mortality caused by a 10-µg/m3 rise in O3 decreased by 0.60% overall and 1.50% in urban areas. Conclusions Our findings add to the evidence that short-term O3 exposure increases ischaemic and haemorrhagic stroke mortality and has adverse effects in urban and rural areas. However, improving greenness levels may contribute to mitigating the detrimental effects of O3 on ischaemic stroke mortality.

Abstract Eradicating Helicobacter pylori (H. pylori) can cause an imbalance in the microbiota. Dysbiosis of the gut microbiome may produce multiple diseases and bacterial infections. The objective of this study was to investigate the influence of Helicobacter pylori (H. pylori) infection and its eradication on the composition of the oral tongue coating microbiota. A cohort of 35 participants was recruited and categorized into two groups: the H. pylori negative group (N group) consisting of 12 individuals and the H. pylori positive group (23 individuals). Within the H. pylori positive group, subjects were further stratified into the H. pylori pre-eradicated group (HPQ group) and the H. pylori eradicated group (HPH group). H. pylori positive individuals were treated with a quadruple regimen containing bismuth, and tongue coating samples were collected both prior to and following treatment. Concurrently, tongue coating samples were collected from H. pylori negative individuals. High-throughput 16S rRNA sequencing technology was employed to assess the microbial composition of the tongue coating in the N group, HPQ group, and HPH group. Pertinent clinical data were documented. Microbial diversity was found to significantly differ among the N group, HPQ group, and HPH group, as evidenced by variations in Chao1 index, Shannon index, and Partial Least Squares Discriminant Analysis (PLS-DA). The dominant bacterial phyla identified across all groups included Bacteroidetes, Proteobacteria, Firmicutes, Fusobacteria, Actinobacteria, and Saccharibacteria. At the phylum level, Firmicutes exhibited higher relative abundance in the HPQ group in comparison to both the N group and HPH group. Conversely, Bacteroidetes displayed greater prevalence in the N group and HPH group. Linear Discriminant Analysis Effect Size (LEfSe) analysis indicated a higher abundance of Romboutsia, Rothia, and Turiciactor in the HPQ group. Our study revealed significant disparities in microbial diversity and richness among the three groups. Furthermore, our findings suggest a potential association between the presence of Streptococcus, Rothia and H. pylori positive individuals.

Abstract Background In the context of spinal cord injury (SCI), infiltrating macrophages assume prominence as the primary inflammatory cells within the lesion core, where the fibrotic scar is predominantly orchestrated by platelet-derived growth factor receptor beta (PDGFRβ+) fibroblasts. Galectin-3, a carbohydrate-binding protein of the lectin family, is notably expressed by infiltrating hematogenous macrophages and mediates cell-cell interactions. Although Galectin-3 has been shown to contribute to the endocytic internalization of PDGFRβ in vitro, its specific role in driving fibrotic scar formation after SCI has not been determined. Methods We employed a crush mid-thoracic (T10) SCI mouse model. Galectin-3 inhibition after SCI was achieved through intrathecal injection of the Galectin-3 inhibitor TD139 or in situ injection of lentivirus carrying Galectin-3-shRNA (Lv-shLgals3). A fibrosis-induced mice model was established by in situ injection of platelet-derived growth factor D (PDGFD) or recombinant Galectin-3 (rGalectin-3) into the uninjured spinal cord. Galectin-3 internalization experiments were conducted in PDGFRβ+ fibroblasts cocultured in conditioned medium in vitro. Results We identified the spatial and temporal correlation between macrophage-derived Galectin-3 and PDGFRβ in fibroblasts from 3 to 56 days post-injury (dpi). Administration of TD139 via intrathecal injection or in situ injection of Lv-shLgals3 effectively mitigated fibrotic scar formation and extracellular matrix deposition within the injured spinal cord, leading to better neurological outcomes and function recovery after SCI. Furthermore, the fibrosis-inducing effects of exogenous PDGFD in the uninjured spinal cord could be blocked by TD139. In vitro experiments further demonstrated the ability of PDGFRβ+ fibroblasts to internalize Galectin-3, with Galectin-3 inhibition resulting in reduced PDGFRβ expression. Conclusions Our finding underscores the pivotal role of macrophage-derived Galectin-3 in modulating the sustained internalized activation of PDGFRβ within fibroblasts, providing a novel mechanistic insight into fibrotic scarring post-SCI.

Abstract Background Methylation of histone 3 lysine 36 (H3K36me) has emerged as an essential epigenetic component for the faithful regulation of gene expression. Despite its importance in development and disease, how the molecular agents collectively shape the H3K36me landscape is unclear. Results We use mouse mesenchymal stem cells to perturb the H3K36me methyltransferases (K36MTs) and infer the activities of the five most prominent enzymes: SETD2, NSD1, NSD2, NSD3, and ASH1L. We find that H3K36me2 is the most abundant of the three methylation states and is predominantly deposited at intergenic regions by NSD1, and partly by NSD2. In contrast, H3K36me1/3 are most abundant within exons and are positively correlated with gene expression. We demonstrate that while SETD2 deposits most H3K36me3, it may also deposit H3K36me2 within transcribed genes. Additionally, loss of SETD2 results in an increase of exonic H3K36me1, suggesting other (K36MTs) prime gene bodies with lower methylation states ahead of transcription. While NSD1/2 establish broad intergenic H3K36me2 domains, NSD3 deposits H3K36me2 peaks on active promoters and enhancers. Meanwhile, the activity of ASH1L is restricted to the regulatory elements of developmentally relevant genes, and our analyses implicate PBX2 as a potential recruitment factor. Conclusions Within genes, SETD2 primarily deposits H3K36me3, while the other K36MTs deposit H3K36me1/2 independently of SETD2 activity. For the deposition of H3K36me1/2, we find a hierarchy of K36MT activities where NSD1 > NSD2 > NSD3 > ASH1L. While NSD1 and NSD2 are responsible for most genome-wide propagation of H3K36me2, the activities of NSD3 and ASH1L are confined to active regulatory elements.

Abstract Background Chronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers. Methods We obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy. Results After the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10−4 ≤ P

Abstract Objectives Preterm delivery rates have increased obviously worldwide over the past decade, yet reliable epidemiological studies on the incidence of preterm birth and temporal trends are not available in Hainan, The Free Trade Port in China. We aimed to describe the rate of preterm birth and trends between 2010 and 2021 and to primarily explore risk factors associated with preterm birth in Hainan, China. Methods This was an observational study was based on data from the Hainan Provincial Birth Certificate System (HPBCS) for live births between 1 January 2010 and 31 December 2021. We included pregnancies resulting in at least one live birth, with newborns born at a gestational age of 28 weeks or greater, or with a birth weight of 1000 g or more. The outcome were preterm birth rates and their trends over time. Potential risk factors were collected, including infant gender, maternal age, paternal age, maternal ethnicity, paternal ethnicity, home address, and single or multiple pregnancies. The logistic regression model was used to assess the relationship between preterm birth and potential risk factors. Results A total of 1,537,239 live births and 86,328 preterm births were investigated, giving a total preterm birth rate of 5.62%. The overall preterm birth rate increased from 4.47% in 2010 to 7.12% in 2021 (compound annual growth rate [CAGR] 4.32). The CAGR of late preterm birth is consistent with the overall preterm birth rate (4.32%). The fastest growth is observed in the rate of very preterm births (5.53%), while the rate of moderate preterm births exhibits the slowest growth (3.87%). Infant gender, multiple pregnancy, home address, parental age, and ethnicity had significant effects on preterm birth. Conclusion The preterm birth rate was increasing year by year from 2010 to 2021 in Hainan, The Free Trade Port in China. Incidence of preterm births in Hainan Province in relation to multiple pregnancies, infant sex, parental age, parental race and residential address.

Abstract Background The surgical clinical practice skill training is an important part of medical undergraduate education. Surgical skills are complex and difficult to master. However, the traditional teaching method has some disadvantages, for example, low student participation, weak learning atmosphere, inadequate mastery of the subject matter. We innovatively put forward the segmented teaching method in the field of clinical practice skills training. The segmented teaching method refers to dividing a specific teaching content into several relatively independent parts and providing segmented practice for each part. This approach enhances students’ learning outcomes.The aim of this controlled study is to investigate the effects of the segmented teaching methods on clinical practice skills training in medical students. Methods 31 medical students participating in clinical practice skill training at The First Affiliated Hospital of University of South China from March to April 2024 were randomly assigned to either the experimental group (n = 16) receiving segmented teaching method or the control group (n = 15) receiving traditional teaching method. After completion of practical exercises, both groups underwent operational assessments, theoretical assessments, Mini-Clinical Evaluation Exercise (Mini-CEX), and Student Evaluation of Educational Quality (SEEQ) for teaching quality evaluation. A comparative analysis of the results between the two groups was conducted. Results After implementing the program, there were no statistically significant differences (P > 0.05) between the experimental and control groups in theoretical assessment scores, Mini-CEX clinical judgment scores, and SEEQ teaching quality evaluation scores. However, compared to the control group, the experimental group demonstrated better operational assessment scores, higher Mini-CEX scores in history taking, physical examination, professionalism, doctor-patient communication, organizational efficiency, and comprehensive abilities, with statistically significant differences (P

Abstract Background Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. Results The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. Conclusions This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

Abstract Aim To construct evidence-based sensitive quality indicators for patients’ rapid rehabilitation care after combined pancreaticoduodenectomy (PD) and to provide a reference for clinical nursing professionals to scientifically evaluate the quality of patients’ rehabilitation post-PD. Background Since PD is associated with higher surgical risk and anastomotic complications, it leads to higher complication rates and longer postoperative recovery cycles. This reiterates the need for rapid recovery of patients after PD; however, the evaluation of sensitive nursing care indicators regarding rapid recovery post-PD has not yet been established to date. Methods Based on the Donabedian structure-process-result theory model, we used available literature, semi-structured interviews, the Delphi method, and hierarchical analysis to establish a sensitive indicator system for patients’ rapid rehabilitation after PD and evaluate the importance of such indicators. Results There were two rounds of expert correspondence, and the effective recovery rate of the questionnaires of these rounds was 100%. The expert authority coefficients, as well as the Kendall coordination coefficients of the expert opinions, were 0.859 and 0.872 as well as 0.423 and 0.431, with statistically significant differences (p

Abstract Background Although electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients. Methods PubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected. Results Six studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97–1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = − 0.21, 95% CI = − 1.60–1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90–1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05–1.25, P = 0.002; RR = 1.21, 95% CI = 1.01–1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups. Conclusions Electronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

Abstract Podocalyxin-like protein (PODXL) is known to originate from tumor cells in several cancers; however, which cell type it is expressed in, whether and how it may contribute to tumor progression after radiotherapy or chemoradiotherapy in cervical cancer (CC) remain unknown. In this study, we investigated these issues using a cohort of 180 immune stain data, single-cell RNA sequencing (scRNA-seq) data of 29,453 cells, and bulk RNA sequencing data from 187 cervical cancer samples treated with radiotherapy or chemoradiotherapy. ScRNA-seq analysis revealed that PODXL was predominantly expressed in tumor endothelial cells (TECs) of CC, which was corroborated by tumor section staining. Moreover, the PODXL expression level was negatively associated with progression-free survival and overall survival of 180 CC patients receiving radiotherapy or chemoradiotherapy (both p

Abstract Objective We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients.

Abstract Background Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. Methods Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12 months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12 months, mean changes in lipid levels from baseline to 12 months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. Discussion The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. Trial registration ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Abstract Purpose To minimize radiation exposure to the small bowel (SB) in patients undergoing treatment for gynecological tumors by adopting a comfortable positioning method. Methods and patients All 76 women undergoing Intensity-Modulated Radiation Therapy (IMRT) were included in this study. Patients were immobilized in a supine position using a vacuum bag and thermoplastic cast formation. In the trial group (n = 36), patients raised their buttocks and a solid foam pad was placed under the sacral tail before immobilization. The control group (n = 40) received treatment in the standard supine position. The SB was delineated from the pubic symphysis to the total iliac bifurcation in computed tomography (CT) scans. Result In the trial group, a significant reduction in SB volume within the pelvic cavity was observed (mean 399.17 ± 158.7 cc) compared to the control group (mean 547.48 ± 166.9 cc), with a p-value less than 0.001. The trial group showed a statistically significant reduction in the absolute volume of irradiated SB at each dose, ranging from the low dose (10 Gy) to the high dose (45 Gy). In the control group, a negative correlation was found between SB and bladder volumes (R = -0.411, P = 0.008), whereas in the trial group, this correlation was weaker (R = -0.286, P = 0.091), with no significant relationship observed between bladder volume and SB. Conclusion The high buttocks supine position effectively reduces SB radiation exposure without the need for bladder distension. This positioning method holds promise for reducing SB irradiation in various pelvic tumors.

Abstract Background Spinal cord injury (SCI) often leads to a loss of motor and sensory function. Axon regeneration and outgrowth are key events for functional recovery after spinal cord injury. Endogenous growth of axons is associated with a variety of factors. Inspired by the relationship between developing nerves and blood vessels, we believe spinal cord-derived microvascular endothelial cells (SCMECs) play an important role in axon growth. Results We found SCMECs could promote axon growth when co-cultured with neurons in direct and indirect co-culture systems via downregulating the miR-323-5p expression of neurons. In rats with spinal cord injury, neuron-targeting nanoparticles were employed to regulate miR-323-5p expression in residual neurons and promote function recovery. Conclusions Our study suggests that SCMEC can promote axon outgrowth by downregulating miR-323-5p expression within neurons, and miR-323-5p could be selected as a potential target for spinal cord injury repair. Graphical Abstract

Abstract Colorectal cancer (CRC) is a common malignant tumor with the third and second highest incidence and mortality rates among various malignant tumors. Despite significant advancements in the present therapy for CRC, the majority of CRC cases feature proficient mismatch repair/microsatellite stability and have no response to immunotherapy. Therefore, the search for new treatment options holds immense importance in the diagnosis and treatment of CRC. In recent years, clinical research on immunotherapy combined with epigenetic therapy has gradually increased, which may bring hope for these patients. This review explores the role of epigenetic regulation in exerting antitumor effects through its action on immune cell function and highlights the potential of certain epigenetic genes that can be used as markers of immunotherapy to predict therapeutic efficacy. We also discuss the application of epigenetic drug sensitization immunotherapy to develop new treatment options combining epigenetic therapy and immunotherapy.

Abstract Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer. Graphical abstract

Abstract Background With the advancement of world population aging, age-related sarcopenia (SP) imposes enormous clinical burden on hospital. Clinical research of SP in non-geriatric wards has not been appreciated, necessitating further investigation. However, observational studies are susceptible to confounders. Mendelian randomization (MR) can effectively mitigate bias to assess causality. Objective To investigate the correlation between SP and comorbidities in orthopedic wards, and subsequently infer the causality, providing a theoretical basis for developing strategies in SP prevention and treatment. Methods Logistic regression models were employed to assess the correlation between SP and comorbidities. The MR analysis was mainly conducted with inverse variance weighted, utilizing data extracted from the UK and FinnGen biobank (Round 9). Results In the cross-sectional analysis, SP exhibited significant associations with malnutrition (P = 0.013) and some comorbidities, including osteoporosis (P = 0.014), body mass index (BMI) (P = 0.021), Charlson Comorbidity Index (CCI) (P = 0.006). The MR result also provided supporting evidence for the causality between SP and hypertension, osteoporosis and BMI. These results also withstood multiple sensitivity analyses assessing the validity of MR assumptions. Conclusion The result indicated a significant association between SP and BMI, CCI, malnutrition, and osteoporosis. We highlighted that SP and comorbidities deserved more attention in non-geriatric wards, urging further comprehensive investigation.

Abstract Background Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy. Methods Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI. Results By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections. Conclusions Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts. Graphical Abstract

Abstract Background Chemotherapy remains the standard first-line treatment for pancreatic adenocarcinoma, but with limited efficacy. We aimed to explore the feasibility of adding the PARP inhibitor fuzuloparib to mFOLFIRINOX in the locally advanced/metastatic (LA/M) setting. Methods This was the dose-escalation and -expansion, phase 1b portion of a phase 1b/2 study. Patients were given oral fuzuloparib at escalating doses starting at 30 mg twice daily (BID) plus intravenous mFOLFIRINOX q2w for 8–12 cycles, followed by maintenance fuzuloparib at 150 mg BID. Cohorts at the maximal tolerated dose (MTD) and lower dose of fuzuloparib were expanded. Primary endpoints were dose-limiting toxicity (DLT), MTD, and recommended phase 2 dose (RP2D). Results As of data cutoff on Jan 15, 2023, 39 patients were recruited. 12 patients were enrolled during dose escalation (30 mg [n = 4]; 60 mg [n = 6]; 100 mg [n = 2]). DLT occurred in 1 patient in 60 mg cohort and 1 patient in 100 mg cohort. 60 mg BID was determined to be the MTD, and then 60 and 30 mg cohorts were expanded to 22 and 15 patients, respectively. The most common grade ≥ 3 treatment-related adverse events were hematologic toxicities. Efficacy in 60 mg cohort seemed to be most favorable, with an objective response rate of 50.0% (95% CI, 26.0–74.0) and disease control rate of 94.4% (95% CI, 72.7–99.9). Conclusions First-line fuzuloparib plus mFOLFIRINOX followed by maintenance fuzuloparib was generally safe and showed encouraging anti-tumor activity in patients with LA/M pancreatic adenocarcinoma. The RP2D of fuzuloparib combination was 60 mg BID. Trial registration ClinicalTrials.gov, NCT04228601.

Abstract Background Machine learning (ML) is extensively employed for forecasting the outcome of various illnesses. The objective of the study was to develop ML based classifiers using a stacking ensemble strategy to predict the Japanese Orthopedic Association (JOA) recovery rate for patients with degenerative cervical myelopathy (DCM). Methods A total of 672 patients with DCM were included in the study and labeled with JOA recovery rate by 1-year follow-up. All data were collected during 2012–2023 and were randomly divided into training and testing (8:2) sub-datasets. A total of 91 initial ML classifiers were developed, and the top 3 initial classifiers with the best performance were further stacked into an ensemble classifier with a supported vector machine (SVM) classifier. The area under the curve (AUC) was the main indicator to assess the prediction performance of all classifiers. The primary predicted outcome was the JOA recovery rate. Results By applying an ensemble learning strategy (e.g., stacking), the accuracy of the ML classifier improved following combining three widely used ML models (e.g., RFE-SVM, EmbeddingLR-LR, and RFE-AdaBoost). Decision curve analysis showed the merits of the ensemble classifiers, as the curves of the top 3 initial classifiers varied a lot in predicting JOA recovery rate in DCM patients. Conclusions The ensemble classifiers successfully predict the JOA recovery rate in DCM patients, which showed a high potential for assisting physicians in managing DCM patients and making full use of medical resources.

Abstract Background Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion. Case presentation The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem. Conclusions This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion.

Abstract Background This study was to explore the relationship between cardiovascular health (CVH) and the risk of all-cause mortality in patients with osteoarthritis (OA). Methods This cohort study retrieved the data of 3642 patients with OA aged ≥ 20 years from the 2007—2018 National Health and Nutrition Examination Survey (NHANES). CVH was evaluated based on Life’s Essential 8 (LE8) includes diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The outcome of all-cause mortality was assessed using the death certificate records of participants from the National Death Index. Variables that might affect all-cause mortality were used as covariates. The weighted univariate COX proportional hazards model was used to explore the association between each covariate and all-cause mortality. The weighted univariate and multivariate COX proportional hazards models were used to explore the association between different CVH levels and all-cause mortality. A restricted cubic spline (RCS) curve was plotted to show the association between different CVH levels and all-cause mortality in OA patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results Findings show that people with moderate CVH (HR = 0.67, 95% CI = 0.45—0.98) and high CVH (HR = 0.47, 95% CI = 0.26—0.87) were associated with reduced risk of all-cause mortality in patients with OA. The HR of all-cause mortality in patients with OA decreased by 0.12 as per 10 points increase of LE8 score (HR = 0.81, 95% CI = 0.73—0.90). The RCS curve revealed that the HR of all-cause mortality decreased with the increase in LE8 score. The survival probability of patients in the high CVH group was higher than the moderate CVH group and low CVH group (p = 0.002). Conclusion Moderate-to-high CVH is associated with a decreased risk of all-cause mortality in patients with OA. These findings might provide a reference for the formulation of prognosis improvement strategies for the management of patients with OA.

Abstract Background Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human ADSCs and SDSCs will have a synergistic effect that will increase the chondrogenic potential of osteoarthritis (OA) chondrocytes in vitro and attenuate the cartilage degeneration of early and advanced OA in vitro. Methods ADSCs, SDSCs, and chondrocytes were isolated from OA patients who underwent total knee arthroplasty. The ADSCs–SDSCs mixed cell ratios were 1:0 (ADSCs only), 8:2, 5:5 (5A5S), 2:8, and 0:1 (SDSCs only). The chondrogenic potential of the OA chondrocytes was evaluated in vitro with a transwell assay or pellet culture with various mixed cell groups. The mixed cell group with the highest chondrogenic potential was then selected and injected into the knee joints of nude rats of early and advanced OA stages in vivo. The animals were then evaluated 12 and 20 weeks after surgery through gait analysis, von frey test, microcomputed tomography, MRI, and immunohistochemical and histological analyses. Finally, the mechanisms underlying these findings were investigated through the RNA sequencing of tissue samples in vivo and Western blot of the OA chondrocyte autophagy pathway. Results Among the MSCs treatment groups, 5A5S had the greatest synergistic effect that increased the chondrogenic potential of OA chondrocytes in vitro and inhibited early and advanced OA in vivo. The 5A5S group significantly reduced cartilage degeneration, synovial inflammation, pain sensation, and nerve invasion in subchondral nude rat OA, outperforming both single-cell treatments. The underlying mechanism was the activation of chondrocyte autophagy via the FoxO1 signaling pathway. Conclusion A combination of human ADSCs and SDSCs demonstrated higher potential than a single type of stem cell, demonstrating potential as a novel treatment for OA.

Abstract Purpose To identify the key risk factors for venous thromboembolism (VTE) in urological inpatients based on the Caprini scale using an interpretable machine learning method. Methods VTE risk data of urological inpatients were obtained based on the Caprini scale in the case hospital. Based on the data, the Boruta method was used to further select the key variables from the 37 variables in the Caprini scale. Furthermore, decision rules corresponding to each risk level were generated using the rough set (RS) method. Finally, random forest (RF), support vector machine (SVM), and backpropagation artificial neural network (BPANN) were used to verify the data accuracy and were compared with the RS method. Results Following the screening, the key risk factors for VTE in urology were “(C 1) Age,” “(C 2) Minor Surgery planned,” “(C 3) Obesity (BMI > 25),” “(C 8) Varicose veins,” “(C 9) Sepsis ( 45 min),” “(C 19) Laparoscopic surgery (> 45 min),” “(C 20) Patient confined to bed (> 72 h),” “(C18) Malignancy (present or previous),” “(C 23) Central venous access,” “(C 31) History of DVT/PE,” “(C 32) Other congenital or acquired thrombophilia,” and “(C 34) Stroke ( 45 minutes),” and “(C 21) Malignancy (present or previous)” were the main factors influencing mid- and high-risk levels, and some suggestions on VTE prevention were indicated based on these three factors. The average accuracies of the RS, RF, SVM, and BPANN models were 79.5%, 87.9%, 92.6%, and 97.2%, respectively. In addition, BPANN had the highest accuracy, recall, F1-score, and precision. Conclusions The RS model achieved poorer accuracy than the other three common machine learning models. However, the RS model provides strong interpretability and allows for the identification of high-risk factors and decision rules influencing high-risk assessments of VTE in urology. This transparency is very important for clinicians in the risk assessment process.

Abstract Background Savolitinib, a small molecule inhibitor, has gained approval as the inaugural medication in China that specifically targets MET kinase. Patients with advanced non-small cell lung cancer (NSCLC) who show MET exon 14 skipping now have a new and innovative treatment option available. Case report In this case report, we describe a patient who experienced drug-induced liver injury (DILI) due to the administration of savolitinib. After being prescribed with savolitinib (400 mg per day, oral), a 73-year-old male diagnosed with stage IV NSCLC with MET exon 14 skipping mutation experienced an increase in liver enzymes and bilirubin levels according to his laboratory tests conducted one month later. Following a 14-day course of hepatoprotective medication, the liver function reverted back to its normal state. After receiving savolitinib (200 mg per day, oral) for one week, the patient was once again diagnosed with severe liver impairment. Then savolitinib was discontinued and received treatment with hepatoprotective drugs for one week. Following the restoration of normal liver function, another attempt was made to administer a small amount of savolitinib (100 mg per day, oral). Thus far, the patient has been followed up and there has been no recurrence of liver damage. Additionally, the lung CT scan revealed ongoing tumor shrinkage with no apparent indications of spreading or metastasis. The Roussel Uclaf Causality Assessment Method (RUCAM) determined that savolitinib was “highly probable” cause of DILI. Moderate-severe was determined to be the extent of DILI severity. Conclusion To the best of our understanding, this is the initial instance of DILI resulting from the use of savolitinib as a standalone treatment in a real-world setting. During the administration of savolitinib, healthcare professionals should carefully consider the potential occurrence of DILI. Administering the patient with a small amount of savolitinib resulted in a remarkable response against the tumor, leading us to speculate that the effectiveness of savolitinib might be associated with its plasma concentration. Studying the pharmacokinetics and pharmacodynamics (PK/PD) of savolitinib is beneficial for tailoring and accurately prescribing the medication to each individual.

Abstract Background Estimated glucose disposal rate (eGDR) is a novel, clinically available, and cost-effective surrogate of insulin resistance. The current study aimed to assess the association between eGDR and prevalent heart failure (HF), and further evaluate the value of eGDR in detecting prevalent HF in a general population. Methods 25,450 subjects from the National Health and Nutrition Examination Survey 1999–2018 were included. HF was recorded according to the subjects’ reports. Logistic regression was employed to analyze the association between eGDR and HF, the results were summarized as Per standard deviation (SD) change. Then, subgroup analysis tested whether the main result from logistic regression was robust in several conventional subpopulations. Finally, receiver-operating characteristic curve (ROC) and reclassification analysis were utilized to evaluate the potential value of eGDR in improving the detection of prevalent HF. Results The prevalence of reported HF was 2.96% (753 subjects). After adjusting demographic, laboratory, anthropometric, and medical history data, each SD increment of eGDR could result in a 43.3% (P 0.05). Additionally, ROC analysis displayed a significant improvement in the detection of prevalent HF (0.869 vs. 0.873, P = 0.008); reclassification analysis also confirmed the improvement from eGDR (All P

Abstract Background Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. Methods This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. Results The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P

Abstract Background Peutz–Jeghers syndrome (PJS), a rare dominantly inherited disease, is primarily characterized by hamartomatous polyps and melanotic macules as well as by an increased risk of cancer. The current study aimed to identify the pathogenic gene and pathogenic mechanism of a proband with PJS, thereby offering precise prevention and treatment strategies for PJS. Methods A detailed clinical examination was performed of the proband diagnosed with PJS and her family members. In addition, peripheral venous blood was collected from the family members to extract genomic DNA. The pathogenic genes of the proband were identified using whole-exome sequencing, and the candidate pathogenic variants were verified via Sanger sequencing. Meanwhile, co-segregation tests were performed among six family members. Finally, reverse transcription-polymerase chain reaction (RT-PCR) was performed to assess transcript variants in the peripheral blood cells of patients and non-related healthy controls. Results Genetic testing revealed a rare splicing variant c.921-1G > C in STK11 in the proband and in her sister and nephew, and the variant co-segregated among the affected family members and nonrelated healthy controls. The proband phenotypically presented with a rare gastric-type adenocarcinoma of the cervix. RT-PCR revealed that the STK11 c.921-1G > C variant could produce two transcripts. Of note, 40 base pairs were deleted in the aberrant transcript between exons 3 and 4, resulting in a frameshift variant and premature termination of the amino acid in exon 6 and ultimately leading to the loss of its functional domain in the STK11 protein. Finally, RT-PCR showed that compared with healthy controls, STK11 mRNA expression level was C in intron 7 of STK11 may be a pathogenic variant in patients with PJS. However, this variant (in intron 7) may not produce abnormal transcripts (deletion of 40 base pairs between exons 3 and 4), and PJS may be attributed to the decrease in STK11 expression. Therefore, this study emphasized the importance of genetic counseling, pre-symptomatic monitoring, and early complication management in PJS.

Abstract Tumor-associated macrophages (TAMs) are pivotal in cancer progression, influencing tumor growth, angiogenesis, and immune evasion. This review explores the spatial and temporal heterogeneity of TAMs within the tumor microenvironment (TME), highlighting their diverse subtypes, origins, and functions. Advanced technologies such as single-cell sequencing and spatial multi-omics have elucidated the intricate interactions between TAMs and other TME components, revealing the mechanisms behind their recruitment, polarization, and distribution. Key findings demonstrate that TAMs support tumor vascularization, promote epithelial-mesenchymal transition (EMT), and modulate extracellular matrix (ECM) remodeling, etc., thereby enhancing tumor invasiveness and metastasis. Understanding these complex dynamics offers new therapeutic targets for disrupting TAM-mediated pathways and overcoming drug resistance. This review underscores the potential of targeting TAMs to develop innovative cancer therapies, emphasizing the need for further research into their spatial characteristics and functional roles within the TME.