Lipoprotein(a) in atherosclerotic cardiovascular disease and proprotein convertase subtilisin/kexin-type 9 inhibitors.

High plasma lipoprotein(a) (Lp(a)) levels increase the cardiovascular risk in populations with atherosclerotic cardiovascular disease (ASCVD). Apolipoprotein (a) [apo(a)], a unique protein component of Lp(a), plays an important role in the pathogenesis of atherosclerosis. Statins, the primary medication in managing ASCVD, lower low-density lipoprotein cholesterol (LDL-C) but concurrently elevate plasma Lp(a) levels, contributing to an increased residual cardiovascular risk. In turn, proprotein convertase subtilisin/kexin-type 9 (PCSK9) inhibitors, a novel class of LDL-C lowering drugs, effectively reduce plasma Lp(a) levels, which is believed to decrease residual cardiovascular risk. However, the mechanism by which PCSK9 inhibitors reduce Lp(a) levels remains unknown. In addition, there are some clinical limitations of PCSK9 inhibitors. Here, we systematically review the past, present, and prospects of studies pertaining to Lp(a), PCSK9 inhibitors, and ASCVD.

PREVALENCE OF DEPRESSION AMONG UNIVERSITY STUDENTS IN CHINA: A PROTOCOL FOR A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Depression is a mental disorder characterized by a persistent and long-lasting depressive mood. OBJECTIVE: The aim of this study was to analyze the prevalence of depression among university students in China and to provide guidance for psychological intervention and improvement of depression among this specific population. METHODS: A systematic search was conducted on PubMed, CNKI, Wang-fang database, and Web of Science to identify relevant articles. The articles were cross-sectional studies focusing on the prevalence of depression among university students in China, with clearly defined criteria for diagnosing depression included. Excel was used independently and in duplicate to perform the screening process that involved title, abstract screening, full-text screening, data extraction and assessment of risk of bias. The standards recommended by the Agency for Healthcare Research and Quality (AHRQ) was used to evaluate the quality of observational studies. RESULTS: STATA 11.0 was used to pool the outcomes and perform meta-analysis, including the prevalence of depression among university students and influential factors such as sex, major, region, and the impact of COVID-19. CONCLUSION: Practical psychological interventions are needed in universities in China. Continuously attention is suggested to be paid to Chinese university students' mental health, especially after public health event such as COVID-19.

Influence of perinatal factors on full-term low-birth-weight infants and construction of a predictive model.

BACKGROUND: Being too light at birth can increase the risk of various diseases during infancy. AIM: To explore the effect of perinatal factors on term low-birth-weight (LBW) infants and build a predictive model. This model aims to guide the clinical management of pregnant women's healthcare during pregnancy and support the healthy growth of newborns. METHODS: A retrospective analysis was conducted on data from 1794 single full-term pregnant women who gave birth. Newborns were grouped based on birth weight: Those with birth weight < 2.5 kg were classified as the low-weight group, and those with birth weight between 2.5 kg and 4 kg were included in the normal group. Multiple logistic regression analysis was used to identify the factors influencing the occurrence of full-term LBW. A risk prediction model was established based on the analysis results. The effectiveness of the model was analyzed using the Hosmer-Leme show test and receiver operating characteristic (ROC) curve to verify the accuracy of the predictions. RESULTS: Among the 1794 pregnant women, there were 62 cases of neonatal weight < 2.5 kg, resulting in an LBW incidence rate of 3.46%. The factors influencing full-term LBW included low maternal education level [odds ratio (OR) = 1.416], fewer prenatal examinations (OR = 2.907), insufficient weight gain during pregnancy (OR = 3.695), irregular calcium supplementation during pregnancy (OR = 1.756), and pregnancy hypertension syndrome (OR = 2.192). The prediction model equation was obtained as follows: Logit (P) = 0.348 × maternal education level + 1.067 × number of prenatal examinations + 1.307 × insufficient weight gain during pregnancy + 0.563 × irregular calcium supplementation during pregnancy + 0.785 × pregnancy hypertension syndrome - 29.164. The area under the ROC curve for this model was 0.853, with a sensitivity of 0.852 and a specificity of 0.821. The Hosmer-Leme show test yielded χ 2 = 2.185, P = 0.449, indicating a good fit. The overall accuracy of the clinical validation model was 81.67%. CONCLUSION: The occurrence of full-term LBW is related to maternal education, the number of prenatal examinations, weight gain during pregnancy, calcium supplementation during pregnancy, and pregnancy-induced hypertension. The constructed predictive model can effectively predict the risk of full-term LBW.

The Regulatory Effect of Vitamin D on Pancreatic Beta Cell Secretion in Patients with Type 2 Diabetes.

Increasing evidence suggests that vitamin D is one of the causes of accelerated development of Insulin Resistance (IR) and islet cell secret dysfunction. Numerous studies have shown that vitamin D can reduce inflammation, activate the transcription of the insulin receptors and related genes, and increase insulin-mediated glucose transport, thereby reducing IR. This article reviews the molecular mechanisms related to vitamin D deficiency and pancreatic ß-cell dysfunction in patients with Type 2 Diabetes (T2D).

Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia.

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

Life Satisfaction and Its Relationship With Personality Traits Among Medical College Students in China.

BACKGROUND: Life satisfaction is a comprehensive psychological index to measure a person's life quality. Previous studies have found that population sociological factors, physiological factors, psychological factors, and social factors all affect life satisfaction, but few studies have looked at the role of stable psychological factors, such as personality, in life satisfaction. Thus, this study combined previous research results and theories to study the current situation of college students' life satisfaction and its correlation with personality. OBJECTIVE: This study aims to comprehensively assess the life satisfaction levels among university students enrolled in a medical college in China, explore their correlation with various demographic factors and personality traits, identify potential areas for intervention, and provide recommendations for improving students' overall well-being and fostering the development of a positive and healthy personality. METHODS: A stratified cluster sampling method was used to select college students from a university. The questionnaire consists of general characteristics, a life satisfaction scale, and the Big Five Inventory. Descriptive statistical methods were conducted to describe the college students' life satisfaction status; an analysis of variance was performed to compare the score of life satisfaction among different demographic features; and the correlation between the score of life satisfaction and the Big Five Inventory was also analyzed. RESULTS: A total of 3116 subjects were included in this survey. The life satisfaction of females was higher than that of males in the dimensions of family, friends, school, and overall satisfaction (p<0.05). The life satisfaction of males in the self dimension was higher than that of females (p<0.05). The life satisfaction of different weight types had statistical significance in the life dimension (p<0.05). The life satisfaction of family, school, and overall well-being among smoking college students was lower than that of non-smoking college students (p<0.05). The life satisfaction of non-drinking college students in family, friends, life, school, and overall life satisfaction scores was higher than those of drinking college students (p<0.05). College students who get plenty of sleep a day (more than eight hours) scored higher life satisfaction scores in the self dimension than sleep-deprived college students (p<0.05). In addition to the family dimension, students taking long physical exercise breaks every day had higher life satisfaction scores in every dimension than students lacking physical exercise (p<0.05). The mean score of personality in the agreeableness and openness dimensions is the highest. Correlation analysis showed that the personality score in each dimension was positively correlated with the life satisfaction score in each dimension except for the neuroticism dimension of personality (p<0.05). CONCLUSION: The life satisfaction of college students is different for different lifestyles. The student management department should pay attention to the physical and mental health of college students with low life satisfaction and further find out the reasons for the difference in life satisfaction. Meanwhile, education should be strengthened for college students and encourage them to give up smoking and alcohol; strengthen physical training; and university education should strengthen the personality cultivation of college students.

METAVISION: a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy.

PURPOSE: To develop a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy (MTM) and to explore the metamorphopsia pattern of MTM. DESIGN: Observational, cross-sectional study. METHODS: We designed a new system. RESULTS: Of the 445 eyes tested, 188 (42.25%) were deemed by patients to have metamorphopsia impacting their daily lives while 257 (57.75%) were considered to have no metamorphopsia symptoms. The Amsler grid, M-CHARTS and METAVISION tests displayed sensitivities for metamorphopsia of 95.74%, 89.89% and 100%, respectively. The specificities of the Amsler grid, M-CHARTS and METAVISION tests are 100%. The metamorphopsia questionnaire and METAVISION scores were highly consistent (average intraclass correlation coefficient=0.951, p<0.001) and strongly correlated (R=0.879, p<0.001). The METAVISION score was highly correlated with the stages of MTM (R=0.837, p<0.001), whereas there was a moderate correlation between the M-CHARTS M-score and the stages of MTM (R=0.679, p<0.001). CONCLUSIONS: Quantification of metamorphopsia is important and useful for MTM management. The METAVISION is a clinically applicable and comprehensive approach for quantifying metamorphopsia, which can be used in clinical settings.

Risk factors and patterns for progression of fellow-eye myopic traction maculopathy: a 3-year retrospective cohort study.

AIMS: To investigate the effect of preretinal tractional structures (PTS) and posterior scleral structures (PSS) on myopic traction maculopathy (MTM) progression. METHODS: This retrospective cohort study included 185 fellow highly myopic eyes of 185 participants who underwent surgery for MTM. PTS included epiretinal membrane, incomplete posterior vitreous detachment and their combination. PSS included posterior staphyloma and dome-shaped macula (DSM). The MTM stage was graded according to the Myopic Traction Maculopathy Staging System. Optical coherence tomography was used to identify MTM progression, defined as an upgrade of MTM. The Kaplan-Meier method with log-rank test was used to assess MTM progression over the 3-year follow-up period. Risk factors for progression were identified using Cox regression analysis. RESULTS: MTM progression was observed in 48 (25.9%) eyes. Three-year progression-free survival (PFS) rates for eyes with PTS, staphyloma and DSM were 53.7%, 58.2% and 90.7%, respectively. Eyes with PTS and staphyloma exhibited lower 3-year PFS rates than those without PTS or staphyloma (P log-rank test =0.002 and <0.001), while eyes with DSM had a higher 3-year PFS rate than eyes without DSM (P log-rank test=0.01). Multivariate Cox regression analysis showed that PTS (HR, 3.23; p<0.001) and staphyloma (HR, 7.91; p<0.001) were associated with MTM progression, whereas DSM (HR, 0.23; p=0.046) was a protective factor. CONCLUSION: Both PTS and PSS play a critical role in the progression of MTM. Addressing these factors can aid in the management of MTM.

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Serum brain-derived neurotrophic factor levels in type 2 diabetes mellitus patients and its association with cognitive impairment: A meta-analysis.

OBJECTIVE: To compare the serum levels of brain-derived neurotrophic factor (BDNF) in type 2 diabetes mellitus (T2DM) patients with healthy controls (HC) and evaluate the BDNF levels in T2DM patients with/without cognitive impairment. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for the published English literature on BDNF in T2DM patients from inception to December 2022. The BDNF data in the T2DM and HC groups were extracted, and the study quality was evaluated using the Agency for Healthcare Research and Quality. A meta-analysis of the pooled data was conducted using Review Manager 5.3 and Stata 12.0 software. RESULTS: A total of 18 English articles fulfilled with inclusion criteria. The standard mean difference of the serum BDNF level was significantly lower in T2DM than that in the HC group (SMD: -2.04, z = 11.19, P <0.001). Besides, T2DM cognitive impairment group had a slightly lower serum BDNF level compared to the non-cognitive impairment group (SMD: -2.59, z = 1.87, P = 0.06). CONCLUSION: BDNF might be involved in the neuropathophysiology of cerebral damage in T2DM, especially cognitive impairment in T2DM.

MyD88 exacerbates inflammation-induced bone loss by modulating dynamic equilibrium between Th17/Treg cells and subgingival microbiota dysbiosis.

BACKGROUND: This study aimed to investigate the contribution of myeloid differentiation primary-response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis-induced experimental periodontitis. METHODS: Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate-resistant acid phosphatase (TRAP), the receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age- and sex-matched homozygous littermates (wild-type [WT, Myd88+/+] and Myd88-/- on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed. RESULTS: P. gingivalis-infected Myd88-/- mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88-/- CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL-10 and IL-17a expressions in gingival tissue at D14-D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88-/- mice. The Myd88-/- mice exhibited characteristic increases in gram-positive species and species having probiotic properties, while gram-negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88-/- mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection. CONCLUSIONS: MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis-induced experimental periodontitis.

Research Progress of Risk Factors Associated with Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM) is a common endocrine condition associated with adverse pregnancy outcomes. In recent years, a growing number of risk factors associated with gestational diabetes mellitus have been defined. GDM poses a serious threat to maternal health. The etiology is complex and multifactorial and can be divided into inherent and modifiable factors. The inherent factors have been described in other literature, while the modifiable factors are mainly the risk of lifestyle habits. In this study, we performed a narrative review of the progress of risk factors associated with gestational diabetes mellitus.

Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Vitamin D May Play a Vital Role in Alleviating Type 2 Diabetes Mellitus by Modulating the Ferroptosis Signaling Pathway.

Ferroptosis is an iron-dependent death mode mediated by the aggregation of lipid peroxides and lipid-reactive oxygen species. It is characterized by iron-dependent lipid peroxide accumulation accompanied by oxidoreductase deficiency. Pancreatic beta cell dysfunction and insulin resistance are two major causes of type 2 diabetes mellitus (T2DM). Iron accumulation and metabolism may play a role in the development of T2DM. The molecular mechanism of ß cell apoptosis and iron death in T2DM were reviewed. In addition, we discuss recent insights on the relationship between the trace element iron and apoptosis of ß cells in T2DM.

"Adjacent Bed Effect" of Total Knee Arthroplasty Patients During the Perioperative Period.

BACKGROUND: Knee osteoarthropathy is one of the most common degenerative joint diseases in the elderly, total knee arthroplasty (TKA) is the most commonly used treatment for end-stage knee osteoarthropathy. Negative emotions such as anxiety have been extensively documented in knee osteoarthropathy patients. AIM: This study aimed to investigate the Emotional Contagion during hospitalization in patients undergoing TKA. METHODS: Eligible subjects were divided into three case groups according to their anxiety states and bed arrangement. All subjects underwent a unilateral, cemented TKA under general anesthesia. Post-operative recovery outcomes including pain, pain behavior and physical function were recorded pre-operation, 1-day, 1 week, 2-weeks, 1-month and 3-months post-operation. RESULTS: A total of 38 subjects were included in the final analysis. Subjects with anxiety had higher Visual Analogue Scale pain scores, PROMIS-Pain Behavior scores than subjects without anxiety in the Contagion Group preoperation (p ≤ .05). Non-anxiety subjects hospitalized in beds physically adjacent to anxiety subjects experienced more severe pain and poorer function (p ≤ .05). After discharge, all clinical outcomes gradually became lower than anxiety subjects in the Contagion Group, reaching levels similar to non-anxiety subjects in the No Contagion Group within 1 month (p>.05). CONCLUSIONS: This study showed that patients with anxiety may have an "Adjacent Bed Effect" on patients with TKA in the adjacent bed, which may be associated with poorer postoperative recovery, including pain and physical function. We speculate this phenomenon can be effectively avoided by the nursing team through accurately assessing psychological status and reasonable bed arrangements in the inpatient assessment phase.

DIFFERENCES IN THE PROGRESSION BETWEEN MYOPIC MACULOSCHISIS EYES WITH AND WITHOUT MACULAR DETACHMENT IN THE NATURAL COURSE OF THE DISEASE: A Retrospective Longitudinal Study Based on the New Myopic Traction Maculopathy Staging System.

PURPOSE: To investigate the pace of visual acuity loss in myopic maculoschisis eyes with or without macular detachment and identify associated risk factors. METHODS: One thousand three hundred and thirty-four eyes of 991 patients with high myopia were reviewed. A new myopic traction maculopathy staging system classified four retinal stages and three foveal stages. To the myopic traction maculopathy eyes with normal fovea, maculoschisis with and without macular detachment was defined as Stage 3a and Stages 1a, 2a respectively. RESULTS: One hundred and ten (8.25%) eyes with maculoschisis were included, with a follow-up of 24.00 ± 17.47 months. Of them, 84 (76.36%) were Stages 1a, 2a, and 26 (23.64%) were Stage 3a. The visual acuity loss per year during the follow-up period was similar between eyes with Stages 1a, 2a and Stage 3a (3.13 ± 12.21 vs. 3.41 ± 18.42 letters, P = 0.930). Multivariate analyses revealed that vitreomacular interface factors were significantly associated with visual acuity loss during the follow-up, no matter in Stages 1a, 2a or Stage 3a ( P = 0.039 and P = 0.038, respectively). In the Stages 1a, 2a group, the percentage of eyes that lost at least 10 letters at the final visit compared with the baseline visual acuity was higher in eyes with vitreomacular interface factors than in those without vitreomacular interface factors (13 eyes, 50.00% vs. 14 eyes, 24.14%, P = 0.019). CONCLUSION: No differences were found in visual acuity loss pace between Stages 1a, 2a and Stage 3a. Surgical intervention or at least more intensive follow-up should be considered for Stages 1a, 2a eyes with vitreomacular interface factors, to promote a more favorable visual outcome.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance.

INTRODUCTION: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. METHODS: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. RESULTS: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I-IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I-V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. CONCLUSIONS: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

TCM syndrome differentiation in colorectal cancer patients assisted by differences in gut microbiota: An exploratory study.

Objective: To explore the difference in gut microbiota between different traditional Chinese Medicine (TCM) syndromes in patients with colorectal cancer (CRC) and its internal relationship. Methods: From June 2020 to August 2021, 109 colorectal cancer patients with a clear pathological diagnosis who had not yet undergone surgery or chemotherapy were classified according to the TCM syndrome classification, and the feces samples of 109 patients with preoperative colorectal cancer were collected. 16s rRNA gene sequencing was used to determine gut microbiota diversity and abundance in CRC patients with different TCM syndrome, and LEfSe analysis was made to screen different TCM syndrome for differential representative microbiota. Results: 109 patients were divided into 5 syndromes by TCM syndrome classification, which were Liver and Kidney Yin Deficiency Syndrome (LKYDS, n = 19), Spleen Deficient Qi Stagnation Syndrome (SDQSS, n = 30), Stasis and Poison Obstruction Syndrome (SPOS, n = 17), Damp-Heat Syndrome (DHS, n = 30), Qi and Blood Deficiency Syndrome (QBDS, n = 13). Alpha diversity index showed significant differences among the five groups of TCM syndromes, with Shannon index being highest in the SDQSS group and lowest in the LKYDS (p = 0.003). ACE index being highest in the SDQSS group and lowest in the SPOS (p = 0.010). PD whole tree index being highest in the SDQSS group and lowest in the SPOS (p = 0.017). Similarly, beta diversity showed significant differences among the five groups of TCM syndromes, with principal coordinate analysis (PCo1 = 31.86 %, PCo2 = 5.62 %) showing separation and coincidence between the groups, and Adonis group differences showing coincidence between the QBDS-LKYDS (p = 0.702), QBDS-DHS (p = 0.133), and SDQSS-DHS (p = 0.260) groups. LEfSe analysis revealed that the representative microbiota of DHS patients was Dialister sp Marseille P5638 (LDA = 3.05, p＜0.001), the representative microbiota of SPOS patients was Oscillospirales (LDA = 4.78, p = 0.029), the representative microbiota of SDQSS patients was Selenomonadaceae (LDA = 3.94, p = 0.003), the representative microbiota of LKYDS patients was Dialister (LDA = 4.19, p = 0.001), and the representative microbiota of QBDS patients was Akkermansia muciniphila (LDA = 4.23, p = 0.006). Conclusions: There are significant differences in gut microbiota between different TCM syndromes in CRC patients. The five microbiota, Dialister sp Marseille P5638, Oscillospirales, Selenomonadaceae, Dialister, and Akkermansia muciniphila, may be differential markers of TCM syndrome in CRC and are expected to be one of the bases for accurate TCM syndrome differentiation of CRC.

[Astragalus polysaccharide inhibits IDO1 expression in colon tumor microenvironment to increase intratumoral CD8~+ T cell infiltration].

This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.