Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, highlighting the urgent need for novel preventive and therapeutic strategies. Emerging research highlights the crucial role of the gut microbiota, including bacteria, fungi, viruses, and their metabolites, in the pathogenesis of CRC. Dysbiosis, characterized by an imbalance in microbial composition, contributes to tumorigenesis through immune modulation, metabolic reprogramming, and genotoxicity. Specific bacterial species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis , along with fungal agents like Candida species, have been implicated in CRC progression. Moreover, viral factors, including Epstein-Barr virus and human cytomegalovirus, are increasingly recognized for their roles in promoting inflammation and immune evasion. This review synthesizes the latest evidence on host-microbiome interactions in CRC, emphasizing microbial metabolites, such as short-chain fatty acids and bile acids, which may act as both risk factors and therapeutic agents. We further discuss the latest advances in microbiota-targeted clinical applications, including biomarker-assisted diagnosis, next-generation probiotics, and microbiome-based interventions. A deeper understanding of the role of gut microbiome in CRC pathogenesis could pave the way for diagnostic, preventive, and personalized therapeutic strategies.
Humans ; Dysbiosis/microbiology* ; Colorectal Neoplasms/metabolism* ; Gastrointestinal Microbiome/physiology* ; Animals

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Objective: To systematically evaluate the detection rate of prenatal depression in Chinese women, so as to provide the reference for mental health care during pregnancy among women. Methods: Publications pertaining to the detection rate of prenatal depression in Chinese women were retrieved from international and national databases from inception to July 30, 2023, including CNKI, Wanfang Data, VIP, PubMed and other databases. The Stata 17.0 software was used for meta analysis, sensitivity analysis was performed using the leave-one-out method, and the publication bias was evaluated using funnel plot and Egger's test. Results: A total of 5 687 publications were retrieved, and 60 studies were finally included, with 58 in Chinese and 2 in English, 51 of medium quality and 9 of high quality, and 114 168 participants. The results of meta-analysis showed that the overall detection rate of prenatal depression in Chinese women was 23.7% (95%CI: 20.0%-27.5%). The detection rates of prenatal depression in the first, second and third trimesters were 22.1% (95%CI: 15.5%-28.6%), 16.3% (95%CI: 12.0%-20.6%) and 19.9% (95%CI: 16.0%-23.7%), in Eastern and Midwestern China were 19.7% and 27.5%, and in women with an education level of junior high school or below and high school or above were 27.2% and 17.9%, respectively, with statistically significant differences (all P<0.05). Sensitivity analysis showed that the study results were stable. There were publication bias in the results of overall detection rate of prenatal depression, and detection rates in the second and third trimester. Conclusions The overall detection rate of prenatal depression in Chinese women ranges from 20.0% to 27.5%. There are differences in the detection rate of prenatal depression in different pregnancies, with the highest detection rate in the first trimester.

Objective: To investigate the association between frailty and type 2 diabetes mellitus (T2DM) using a bidirectional two-sample Mendelian randomization (MR) analysis, so as to provide the evidence for the prevention and control of frailty and T2DM. Methods: Frailty status was assessed using the Fried Frailty Score (FFS), with aggregated data sourced from 386 565 European samples in the UK Biobank. The T2DM data were obtained from the summary results of genome-wide analysis published by the Diabetes Genetics Replication and Meta-analysis Consortium, excluding the UK Biobank data, including 455 313 European samples. Eligible single nucleotide polymorphism site were selected from the FFS and T2DM summary data as instrumental variables. The bidirectional MR analysis was performed using the inverse-variance weighted method. The heterogeneity was assessed using the modified Cochran Q test. The horizontal pleiotropy of instrumental variables was examined using MR-Egger regression. The robustness of the results was evaluated using the leave-one-out method. The bias was tested using funnel plot. Results: The forward MR analysis revealed a statistically significant association between increased FFS and an increased risk of T2DM (OR=2.280, 95%CI: 1.169-4.447). The reverse MR analysis showed a statistically significant association between T2DM and increased FFS (β=0.026, 95%CI: 0.012-0.041). Both bidirectional MR results were robust, with no horizontal pleiotropy of the instrumental variables was found (all P>0.5); and the funnel plots did not show significant basis. Conclusion The study found a bidirectional causal association between frailty and T2DM.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective To explore the phenotypic conversion of regulatory T cells (Tregs) in the lungs of mice with bronchopulmonary dysplasia (BPD)-affected mice. Methods A total of 20 newborn C57BL/6 mice were divided into air group and hyperoxia group, with 10 mice in each group. The BPD model was established by exposing the newborn mice to hyperoxia. Lung tissues from five mice in each group were collected on postnatal days 7 and 14, respectively. Histopathological changes of the lung tissues was detected by HE staining. The expression level of surfactant protein C (SP-C) in the lung tissues was examined by Western blot analysis. Flow cytometry was performed to assess the proportion of FOXP3⁺ Tregs and RORγt⁺FOXP3⁺ Tregs in CD4⁺ lymphocytes. The concentrations of interleukin-17A (IL-17A) and IL-6 in lung homogenate were measured by using ELISA. Spearman correlation analysis was used to analyze the correlation between FOXP3⁺Treg and the expression of SP-C and the correlation between RORγt⁺FOXP3⁺ Tregs and the content of IL-17A and IL-6. Results The hyperoxia group exhibited significantly decreased levels of SP-C and radical alveolar counts in comparison to the control group. The proportion of FOXP3⁺Tregs was reduced and that of RORγt⁺FOXP3⁺Tregs was increased. IL-17A and IL-6 concentrations were significantly increased. SP-C was positively correlated with the expression level of RORγt⁺FOXP3⁺ Tregs. RORγt⁺FOXP3⁺ Tregs and IL-17A and IL-6 concentrations were also positively correlated. Conclusion The number of FOXP3⁺ Tregs in lung tissue of BPD mice is decreased and converted to RORγt⁺ FOXP3⁺ Tregs, which may be involved in hyperoxy-induced lung injury.
Animals ; Mice ; Mice, Inbred C57BL ; Bronchopulmonary Dysplasia ; T-Lymphocytes, Regulatory ; Interleukin-17 ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Hyperoxia ; Interleukin-6 ; Forkhead Transcription Factors ; Lung

Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P＜0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P＜0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P＜0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children.Methods:A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People′s Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors.Results:Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference ( χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference ( χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS ( HR=1.97, 95% CI 1.11-3.49), PFS ( HR=2.95, 95% CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions:ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.