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BackgroundChemoresistance is a common problem for cancer treatment worldwide. Circulating exosomal microRNAs (miRNAs) have been considered as promising biomarkers of cancers. However, few studies have assessed the relationship between serum/plasma exosomal microRNAs and chemoresistance in colorectal cancer (CRC).MethodsBased on previous microarray analysis, we selected 30 miRNAs which are aberrantly expressed during CRC progression and then detected their expression levels in three pairs of oxaliplatin/5-fluorouracil-resistant CRC cell lines and the corresponding secreted exosomes. Six candidate exosomal miRNAs were identified for further evaluating potential value in predicting chemotherapeutic effect in advanced CRC patients. Finally, the molecular mechanisms of these miRNAs in drug resistance were explored by bioinformatics preliminarily.ResultsWe observed that the expression of 14 miRNAs was significantly higher in three drug-resistant CRC cells comparing with their parental cells. Among these miRNAs, miR-21-5p, miR-1246, miR-1229-5p, miR-135b, miR-425 and miR-96-5p are also up-regulated in exosomes from culture media of resistant cells. Clinical sample analysis confirmed that the expression levels of miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p in serum exosomes were significantly higher in chemoresistant patients in contrast with chemosensitive controls. ROC curve showed that the combination of the four miRNAs had an area of under the curve (AUC) of 0.804 (P < 0.05). In addition, GO analysis and KEGG pathway analysis revealed that these miRNAs were enriched in PI3K-Akt signaling pathway, FoxO signaling pathway and autophagy pathway.ConclusionsOur study demonstrates that a panel of serum exosomal miRNAs containing miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p could significantly distinguish the chemotherapy-resistant group from advanced colorectal cancer patients. Targeting these miRNAs may promote chemosensitivity to oxaliplatin and 5-fluorouracil, and might be promising strategy for CRC treatment.

Tumor‐associated macrophages (TAMs) are one of the most abundant cell types in colorectal cancer (CRC) tumor microenvironment (TME). Recent studies observed complicated “cross‐talks” between cancer cells and macrophages in TME. However, the underlying mechanisms are still poorly elucidated. Here, PD‐L1 levels are very low in CRC cells but highly abundant in TAMs, and a specific PD‐L1+CD206+ macrophage subpopulation are identified, which is induced by tumor cells and associated with a poor prognosis. Mechanistic investigations reveal that CRC cells can secrete small extracellular vesicles (sEVs) taken up by macrophages that induce M2 like polarization and PD‐L1 expression, resulting in increased PD‐L1+CD206+ macrophage abundance and decreased T cell activity in CRC TME. sEV‐derived miR‐21‐5p and miR‐200a are identified as key signaling molecules mediating the regulatory effects of CRC on macrophages. Further studies reveal that CRC‐derived miR‐21‐5p and miR‐200a synergistically induces macrophage M2 like polarization and PD‐L1 expression by regulating the PTEN/AKT and SCOS1/STAT1 pathways, resulting in decreased CD8+ T cell activity and increased tumor growth. This study suggests that inhibiting the secretion of specific sEV‐miRNAs from CRC and targeting PD‐L1 in TAMs may serve as novel methods for CRC treatment as well as a sensitization method for anti‐PD‐L1 therapy in CRC. A specific PD‐L1+CD206+ macrophage risk subgroup is identified in colorectal cancer, which is induced by tumor‐derived sEV‐miRNAs. This subgroup promotes tumor growth by inducing an immunosuppressive tumor microenvironment. Hence, targeting specific tumor sEV‐miRNAs that regulate PD‐L1 in tumor‐associated macrophages may serve as a novel treatment strategy and a sensitization method for anti‐PD‐L1 therapy in colorectal cancer.

Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index’s prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P  < 0.01) and a 79% higher risk of ICU mortality (HR 1.79 [95% CI 1.28 to 2.51], P  < 0.001). Model 3 showed that ICU mortality risks for Q4, Q3, and Q2 were 240%, 75%, and 33% higher, respectively (HR 3.40 [95% CI 2.24 to 5.16], P  < 0.001; HR 1.75 [95% CI 1.16 to 2.63], P  = 0.007; HR 1.33 [95% CI 1.20 to 1.53], P  < 0.001). RCS regression analysis identified a nonlinear association between the TyG index and mortality (overall P  < 0.001; P for nonlinearity < 0.001, with an inflection point at 8.9). Subgroup analysis showed that the effect size and direction were consistent across different subgroups, suggesting the stability of the results. This study demonstrates that a higher TyG index is significantly associated with increased in-hospital and ICU mortality risk in critically ill sepsis patients, with evidence of non-linear correlation. Therefore, the TyG index helps identify the mortality prognosis of sepsis patients in the ICU.

The present study used publicly available genome-wide association study (GWAS) summary data to perform three two-sample Mendelian randomization (MR) studies, aiming to examine the causal links between gut microbiome and BCC, melanoma skin cancer, ease of skin tanning. SNPs associated with exposures to basal cell carcinoma, melanoma skin cancer and ease of skin tanning from the genome-wide association study data of UK Biobank and MRC-IEU (MRC Integrative Epidemiology Unit), and the meta-analysis data from Biobank and MRC-IEU were used as instrumental variables (IVs). The casual estimates were assessed with a two-sample Mendelian randomisation test using the inverse-variance-weighted (IVW) method, Wald ratio, MR-Egger method, maximum likelihood, weighted median, simple mode, and weighted mode. After the application of MR analysis, diffirent effects of multiple groups of gut microbiota was observed for BCC, melanoma skin cancer and ease of skin tanning. The relationships between the gut microbiome and BCC, melanoma skin cancer, ease of skin tanning were supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between between the gut microbiome and BCC, melanoma skin cancer, ease of skin tanning. Our study initially identified potential causal roles between the gut microbiome and BCC, melanoma skin cancer, ease of skin tanning, and highlighted the role of gut microbiome in the progression of basal cell carcinoma, melanoma skin cancer, ease of skin tanning.

Hypertrophic scars (HS), classified as abnormal scarring, result from an overactive tissue response during wound healing following dermal trauma. Nonetheless, the precise mechanistic pathway underlying its occurrence remains elusive. The principal aim of this study is to elucidate the causal relationship among gut microbiota (GM), immune cell function, and hypertrophic scarring in a European demographic. Leveraging the genome-wide association analysis (GWAS) database, we conducted a two-sample Mendelian randomization (MR) study on gut microbiota (GM), immune cells, and HS. To ascertain the causality between GM, immune cells, and HS, we utilized the inverse variance weighted (IVW) method while employing multiple approaches to negate the effects of pleiotropy and heterogeneity. Furthermore, we quantitatively evaluated the influences of immune cells-mediated GM on hypertrophic scar through a two-step MR analysis. The two-sample MR analysis demonstrated a potential causality between 5 genera of gut microbiotas and 23 immune cell traits with respect to hypertrophic scarring. Further, our results showed that the causal pathway from the genus Subdoligranulum to hypertrophic scar (HS) was mediated by B cell-activating factor receptor (BAFF-R) on CD20- CD38- B cell, with a beta value of 0.034 (95% CI [0.002, 0.066]; P  = 0.004), contributing to 7.60% of the total effect of Subdoligranulum on HS. Similarly, CD24 on IgD + CD38 + B cell exhibited a causal impact in the pathway from genus Coprococcus 1 to HS, with a beta value of -0.015 (95% CI [-0.029, -0.001]; P  = 0.023), constituting 6.70% of the total effect of Coprococcus 1 on HS. Additionally, the CD8 + T cell %T cell mediated the causal pathway from the genus Adlercreutzia to HS with a beta value of 0.075 (95% CI [0.017, 0.133]; P  = 0.024), contributing to 10.10% of the total effect of Adlercreutzia on HS. Our study indicates that the development of hypertrophic scars might be influenced by specific gut microbiota and immune cells. We highlight the possible role of two distinct immune cell genotypes as mediators in this relationship. However, most statistical significance of these findings was not maintained after FDR correction, suggesting our results should be viewed as preliminary and interpreted with caution. Further research is needed to confirm these associations.

Background Nano‐sized extracellular vesicles secreted by cells play key roles in intercellular crosstalk, and appear to be an excellent biocompatible material as therapeutic cargoes in vivo. Previously, we have demonstrated that miR‐204‐5p is a key tumor suppressor that could inhibit tumor growth, metastasis and chemoresistance. Methods A HEK293T cell line stably expressing miR‐204‐5p (293T‐miR‐204) was constructed by lentivirus transduction. Fluorescence real‐time quantitative PCR (qPCR) was applied to measure the expression of miR‐204‐5p. CCK‐8 and colony formation assays were used to evaluate the in vitro anticancer effects, and the flow cytometry was used to detect apoptosis. The in vivo therapeutic effects of exosomal miR‐204‐5p were evaluated using a xenograft mouse model. Western blots were used to detect the protein levels of CD63, Flotillin‐2, RAB22A and Bcl2. The protein levels of RAB22A and Bcl2 in tumor tissues were measured by immunohistochemistry staining. Results MiR‐204‐5p was clearly upregulated in CRC cells after coculturing with 293T‐miR‐204 cell‐derived conditioned medium (CM) or exosomes. CCK‐8 and colony formation assays showed that the cell proliferation ability of CRC cells was clearly inhibited by 293T‐miR‐204 cell‐derived CM or exosomes. The inhibitory effects of exosomal miR‐204‐5p on cell proliferation were further confirmed in other types of cancers. Exosomal miR‐204‐5p could induce apoptosis and increase the sensitivity of cancer cells to the chemotherapeutic drug—5‐fluorourcil. In addition, exosomal miR‐204‐5p inhibited the tumor growth in mice. Western blot assay and IHC staining showed that the protein levels of miR‐204‐5p targets were clearly decreased in cancer cells or xenograft tissues treated with exosomal miR‐204‐5p. Conclusions In this study, we confirmed that exosomal miR‐204‐5p could efficiently inhibit cancer cell proliferation, induce apoptosis and increase chemosensitivity by specifically suppressing the target genes of miR‐204‐5p in human cancer cells. In this study, we confirmed that exosomal miR‐204‐5p could efficiently inhibit cancer cell proliferation, induce apoptosis, and increase chemosensitivity by specifically suppressing the target genes of miR‐204‐5p in human cancer cells.

Background Although the effective application of negative pressure wound therapy (NPWT) has been exemplified in diverse clinical studies, its potential and safety, specifically regarding paediatric burns, are yet to be fully confirmed. Our most recent systematic review and meta-analysis strive to investigate the impact of NPWT within the realm of paediatric burns. Methods We sourced relevant articles from databases including PubMed, Embase, the Cochrane Database, Web of Science, the International Clinical Trials Registry Platform, China National Knowledge Infrastructureris, the VIP Database for Chinese Technical Periodicals, and the Wanfang database. We defined the primary outcome measure as the healing time, while healing rate, numbers of dressing changes, detection rate of positive bacteria, incidence rate of adverse reactions, scar scale scores, and treatment costs were considered as secondary outcome measures. Pooling of data was conducted and the results were articulated as relative risk (RR), mean difference (MD), and standardized mean difference (SMD), all with a 95% confidence interval (CI). Results In this systematic review and meta-analysis, a total of 12 studies involving 1033 individuals were examined, including 559 paediatric burn patients who underwent NPWT (referred to as the treatment group) and 543 patients who received treatments other than NPWT (referred to as the control group). The amalgamated data from these studies exhibited that the treatment group experienced significant reductions in healing time (SMD = -1.60; 95% CI: -2.26 - -0.95; p  < 0.001, I 2  = 92.8%), the number of required dressing changes (SMD = -4.6; 95% CI: -5.84 - -3.36; p  < 0.001, I 2  = 92.4%), positive bacteria detection rate (RR = 0.61; 95% CI: 0.26–1.46; p  = 0.004, I 2  = 81.8%), incidence of adverse reactions (RR = 0.61; 95% CI: 0.33–1.12; p  = 0.005, I 2  = 68%), scar scale scores (SMD = -1.66; 95% CI: -2.54 - -0.79; p  < 0.001, I 2  = 89.4%), as well as in treatment costs (SMD = 0.92; 95% CI: -1.66–3.49; p  < 0.001, I 2  = 98.4%). Additionally, these individuals showed an increased rate of healing (RR = 1.17; 95% CI: 0.99–1.39; p  < 0.001, I 2  = 78%). Subgroup analysis did not find that the degree of burn was one of the sources of high heterogeneity. Conclusion Our meta-analysis points to the effectiveness of NPWT in treating paediatric burns. Notably, it significantly mitigates healing duration, frequency of dressing alterations, positive bacterial detection rate, adverse reactions incidence, scar scale scores and treatment costs, all while propelling the acceleration of wound healing.

Background Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This latest systematic review and meta‐analysis aim to examine the effects of autologous epidermal cell suspensions in re‐epithelialization of skin lesions. Methods Relevant articles were retrieved from PubMed, Embase, Cochrane Database, Web of Science, International Clinical Trials Registry Platform, China National Knowledge Infrastructureris, VIP Database for Chinese Technical Periodicals and Wanfang database. The primary output measure was the healing time, and the secondary outputs were effective rate, size of donor site for treatment, size of study treatment area, operation time, pain scores, repigmentation, complications, scar scale scores and satisfaction scores. Data were pooled and expressed as relative risk (RR), mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval (CI). Results Thirty‐one studies were included in this systematic review and meta‐analysis, with 914 patients who received autologous epidermal cell suspensions (treatment group) and 883 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced healing time (SMD = −0.86; 95% CI: −1.59–0.14; p = 0.02, I2 = 95%), size of donar site for treatment (MD = −115.41; 95% CI: −128.74–102.09; p<0.001, I2 = 89%), operation time (MD = 25.35; 95% CI: 23.42–27.29; p<0.001, I2 = 100%), pain scores (SMD = −1.88; 95% CI: −2.86–0.90; p = 0.0002, I2 = 89%) and complications (RR = 0.59; 95% CI: 0.36–0.96; p = 0.03, I2 = 66%), as well as significantly increased effective rate (RR = 1.20; 95% CI: 1.01–1.42; p = 0.04, I2 = 77%). There were no significant differences in the size of study treatment area, repigmentation, scar scale scores and satisfaction scores between the two groups. Conclusion Our meta‐analysis showed that autologous epidermal cell suspensions is beneficial for re‐epithelialization of skin lesions as they significantly reduce the healing time, size of donar site for treatment, operation time, pain scores and complications, as well as increased effective rate. However, this intervention has minimal impact on size of treatment area, repigmentation, scar scale scores and satisfaction scores.

Background Severe burn injuries induce hypermetabolism, leading to protein catabolism, impaired wound healing, and increased infection risk. Burn patients often experience androgen depletion, exacerbating these issues. Oxandrolone, a synthetic anabolic steroid, has shown promise in counteracting these metabolic disturbances. This updated meta-analysis evaluates the efficacy and safety of oxandrolone in burn patients, incorporating recent studies, pediatric populations, long-term outcomes, and combination therapies. Methods This PRISMA 2020-compliant systematic review searched 9 databases (PubMed, Embase, Cochrane, WOS, WHO-ICTRP, CNKI, VIP, Wanfang, CBMdisc) for RCTs published between 2005 and 2025 using validated strategies combining controlled vocabulary (MeSH/Emtree) and free-text terms for burn/trauma AND androgen analogs (e.g., oxandrolone, nandrolone). Included trials compared androgen analogs vs. controls (placebo/standard care) in burn patients, reporting ≥ 1 predefined outcome: (1) Lean body mass (recovery phase, ≥ 14 days post-burn); (2) Mild side effects (hepatic dysfunction [ALT/AST ≥ 2 × ULN] or edema); (3) Infections; (4) Mortality; (5) Surgical procedures; (6) LOS/TBSA; (7) Absolute LOS. Dual-independent screening, data extraction, and risk-of-bias assessment (Cochrane RoB 2.0 per outcome) were performed. Random-effects meta-analyses generated standardized mean differences (SMD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% CIs. Results Fourteen RCTs (2005–2025; n = 2822 patients: 1203 intervention vs. 1619 controls) demonstrated significant reductions in surgical procedures (SMD = − 1.25; 95% CI − 2.45 to − 0.04; p  = 0.04; I 2  = 97.2%) and length of stay normalized to TBSA (LOS/TBSA) (SMD = − 1.07; 95% CI − 2.43 to 0.29; p  = 0.007; I 2  = 98.1%), alongside enhanced anabolic recovery evidenced by increased weight gain (SMD = 0.58; 95% CI − 1.21 to 2.38; p  < 0.001) and lean mass (SMD = 1.30; 95% CI − 0.47 to 3.24; p  < 0.001; I 2  ≥ 95.0%). However, no mortality benefit was observed (RR = 1.04; 95% CI 0.47–2.32; p  = 0.913; I 2  = 66.5%), with unchanged infection rates (RR = 0.83; 95% CI 0.67–1.02; p  = 0.639) and no improvement in donor site healing (SMD = − 1.48; 95% CI − 2.18 to 0.77; p  = 0.116). Safety analysis revealed a non-significant increase in treatment-related side effects (hepatic dysfunction/edema; RR = 1.82; 95% CI 0.52–6.42; p  = 0.34), notably higher transaminase elevations in adults (19% vs. 5% placebo; p  = 0.002). Conclusion Oxandrolone demonstrates clinical utility in burn management by significantly reducing surgical burden (SMD = − 1.25; p  = 0.04), shortening hospitalization (LOS/TBSA SMD = − 1.07; p  = 0.007), and enhancing anabolic recovery (weight gain SMD = 0.58; lean mass SMD = 1.30; both p  < 0.001). However, extreme heterogeneity (I 2  ≥ 95.0%) and temporal limitations necessitate cautious interpretation. Critically, it confers no mortality benefit (RR = 1.04; p  = 0.913), fails to reduce infections (RR = 0.83; p  = 0.639), and elevates hepatotoxicity risk in adults (19% vs. 5%; p  = 0.002). These findings support its adjunctive role in metabolic rehabilitation but mandate risk-stratified implementation.

Background Alginate-based dressings are widely used in burn care for their absorptive and healing properties; however, inconsistencies in clinical outcomes remain. Methods This study followed the PRISMA guidelines, we systematically searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials (RCTs) comparing alginate dressings to other treatments in burn patients and their donor sites. Inclusion criteria focused on prospective trials with measured outcomes such as healing time, pain scores, dressing change frequency, and adverse events. Data extraction and quality assessment adhered to standardized methods, and meta-analyses were performed using R 4.4.2 and Stata 15.0 with the GRADE approach to evaluate evidence certainty. Data were aggregated and reported as relative risk (RR), mean difference (MD) and standardized mean difference (SMD), with a 95% confidence interval (CI). Results Fifteen studies met the inclusion criteria. The meta-analysis revealed a significantly shorter healing time with alginate dressings versus controls, showing a MD of -1.09 days (95% CI: -1.67 to -0.31, p  < 0.001, I 2  = 94.6%). Pain scores also favored alginate dressings, with a SMD of -1.37 (95% CI: -2.53 to -0.21, p  = 0.000, I 2  = 90.9%). There was no significant difference in dressing change frequency, with an SMD of 2.18 (95% CI: -4.29 to -0.07, p  = 0.000, I 2  = 94.0%). Adverse events showed a RR of 0.81 (95% CI: 0.50 to 1.30, p  = 0.021, I 2  = 51.1%), indicating similar safety profiles in both groups. Conclusion Our findings indicate that alginate dressings not only significantly reduce healing time but also offer clinically relevant benefits, including reduced pain and fewer dressing changes, making them a valuable option in burn wound management. However, their effect on dressing change frequency and adverse events remains comparable to control treatments. Despite the methodological limitations such as high heterogeneity and potential biases, alginate dressings maintain advantages in clinical settings. Standardization of evaluation criteria and long-term studies are necessary to enhance the understanding and application of alginate dressings in diverse burn wound and donor site wound care settings.