Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.

Genetic diversity and differentiation analysis reveals geographical structure characteristics of Dermatophagoides farinae (Acari: Pyroglyphidae).

Dermatophagoides farinae (Acari: Pyroglyphidae) has been reported as one of the major sources of indoor allergens that trigger allergic disease in humans. In this study, the genetic diversity and differentiation of nine geographic populations of D. farinae were investigated by analyzing mitochondrial and nuclear genes (COI, Cytb, COI+Cytb, and ITS). The results showed high genetic diversity across the D. farinae populations. The BX (Benxi) population showed the lowest genetic diversity, possibly due to climatic causes. Significant genetic differentiation was observed among D. farinae populations based on mitochondrial genes. The analysis of molecular variance (AMOVA) results elucidated that the contribution to the rate of variation was primarily from among populations. Phylogenetic analysis and haplotype network based on mitochondrial genes both indicated significant geographic structure among D. farinae populations. The nine geographic populations of D. farinae were divided into two groups with the Qinling Mountains-Huai River Line serving as the boundary for spatial analysis of molecular variance analysis (SAMOVA). However, the Mantel test analysis showed no association between genetic differentiation and geographic distance because of the high level of gene flow among some populations through the transportation of stored food. Overall, these results indicate both significant genetic differentiation among D. farinae populations, but also significant gene exchange between them. Results from the analysis of the nuclear gene ITS differed from the mitochondrial genes due to differences in molecular markers between mitochondrial genes and nuclear genes. These observations improve our understanding of the genetic diversity and structure of D. farinae populations.

Re-exploration of tetrahydro-ß-carboline scaffold: Discovery of selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting and neuroprotective activities.

Histone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-ß-carboline (THßC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bidentate chelating manner. In vitro, 11d induced neurite outgrowth of PC12 cells without producing toxic effects and showed obvious neuroprotective activity in a model of H2O2-induced oxidative stress.

Parkinson's disease patients with absence of normal dipping status were more vulnerable to cognitive impairment from the early stages.

INTRODUCTION: The objective of this study was to determine the characteristics of cognitive function in Parkinson's disease (PD) patients with different dipping statuses. METHODS: Consecutive PD patients were recruited for this study. All participants underwent 24-h ambulatory blood pressure monitor (ABPM). Corresponding scales were employed to evaluate both motor and non-motor symptoms. The subjects were categorized into reverse, reduced, normal, and extreme dipping groups based on dipping patterns. Additionally, they were divided into early and non-early stage groups according to the disease duration being more than 5 years. RESULTS: The proportions of the four dipping groups in the early and non-early stage groups exhibited no significant differences. The Montreal Cognitive Assessment (MoCA) scores in the reverse group were significantly lower than those in the normal dipping group (16.2 ± 5.8 vs 21.1 ± 6.1,P = 0.003). The attention as well as delayed recall scores in the reverse dipping group were significant lower than those in the normal dipping group (P = 0.042; P < 0.001). The multivariate linear regression analysis revealed that absence of normal dipping was an independent risk factor (OR = -2.252; P = 0.027) for MoCA scores for PD patients. CONCLUSIONS: PD patients with absence of normal dipping status were more vulnerable to cognitive impairment from the early stages of the disease. The 24-h ABPM is recommended for early detection of abnormal dipping status and identification of individuals at risk for cognitive decline.

Body composition changes in patients with differentiated thyroid cancer after iodine-131 treatment and short-term levothyroxine replacement and suppression therapy.

PURPOSE: The purposes of this study were to assess the changes in body composition in patients who underwent thyroidectomy due to differentiated thyroid cancer (DTC) after radioactive iodine therapy (RAI) and short-term levothyroxine (LT4) supplementation and to explore the correlations between body composition distribution and corresponding blood indices. METHODS: Fifty-seven thyroidectomized DTC patients were included. Serum was tested for several biochemical indices of thyroid function, lipids, and bone metabolism, and body composition parameters were measured via dual-energy X-ray absorptiometry before and 4-6 weeks after RAI and LT4 supplementation. RESULTS: The body composition of DTC patients changed after RAI. Fat mass in all parts of the body decreased (range of relative change (RRC) -12.97--2.80%). Bone mineral content (BMC) increased throughout the body (relative change (RC) 12.12%), head (RC 36.23%), pelvis (RC 9.00%), and legs (RC 3.15%). Similarly, bone mineral density (BMD) increased in different regions (RRC 3.60-26.43%), except for the arms. Notably, lean mass in the arms (RC 4.30%) and legs (RC 3.67%) increased, while that in the head decreased (RC -2.75%), while total lean mass did not change at 4-6 weeks after LT4 supplementation. Furthermore, changes in fat distribution in the android region were related to the changes in total cholesterol (r = -0.390) and low-density lipoprotein cholesterol (r = -0.354), and changes in the BMC and BMD of the lumbar spine were positively associated with the changes in calcitonin (r = 0.302 and 0.325, respectively). CONCLUSIONS: After RAI and short-term LT4 supplementation in DTC patients, body composition rapidly and positively changed and was characterized by decreased fat mass and increased BMC and BMD.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients.

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice.

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

Integrated microbiome and metabolome analysis reveals a distinct microbial and metabolic signature in Graves' disease and hypothyroidism.

Recent studies reveal that imbalanced microbiota is related to thyroid diseases. However, studies on the alterations in fecal metabolites in Graves' disease and clinical hypothyroidism patients are insufficient. Here, we identified 21 genera and 53 metabolites that were statistically significant among Graves' disease patients, hypothyroidism patients, and controls integrating microbiome and untargeted metabolome analysis. Disease groups revealed a decreased abundance in butyrate-producing microbiota and an increased abundance in potentially pathogenic microbiota. Lipids molecules were the major differential metabolites identified in all fecal samples. Network analysis recognized that microbiota may affect thyroid function by targeting specific metabolites. We further identified specific microbiota and metabolites that could distinguish Graves' disease patients, hypothyroidism patients, and controls. Our study reveals a distinct microbial and metabolic signature in hypothyroidism patients and Graves' disease patients and further validates the potential role of microbiota in thyroid diseases, providing new ideas for future research into the etiology and clinical intervention of thyroid diseases.

Association of gastrointestinal symptoms and skipping breakfast with anxiety and depressive symptoms in quarantined Chinese college students during the Shanghai 2022 lockdown: a cross sectional survey.

BACKGROUND: This study aimed to evaluate the prevalence of anxiety and depressive symptoms among quarantined college students at school in Shanghai 2022 lockdown during the COVID-19 pandemic and investigate the association of gastrointestinal discomfort related-factors and skipping breakfast with anxiety and depressive symptoms. METHODS: 384 quarantined college students in Shanghai China were recruited in this cross-sectional study from April 5th to May 29th, 2022. Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) were used to assess anxiety and depressive symptoms, respectively. RESULTS: The prevalence of anxiety and depressive symptoms were 56.8% and 62.8%, respectively. Longer quarantine duration, higher education level, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were significantly associated with anxiety symptoms. Moreover, longer quarantine duration, being woman, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were markedly related to depressive symptoms. Notably, regularly physical exercising and taking positive attitude towards COVID-19 were negatively correlated with anxiety and depressive symptoms. CONCLUSIONS: More attention should be paid to anxiety and depressive symptoms of quarantined college students and universities should provide timely psychological monitoring and intervention services to mitigate the impact of negative emotions on students. Effectively relieving gastrointestinal symptoms, insisting on eat breakfast, regularly exercising, and taking a positive attitude towards to COVID-19 might contribute to preventing the anxiety and depressive symptoms for those college students experiencing a long-term quarantine.

Soft error mitigation and recovery of SRAM-based FPGAs using brain-inspired hybrid-grained scrubbing mechanism.

Soft error has increasingly become a critical concern for SRAM-based field programmable gate arrays (FPGAs), which could corrupt the configuration memory that stores configuration data describing the custom-designed circuit architecture. To mitigate this kind of error, this study proposes a brain-inspired hybrid-grained scrubbing mechanism consisting of fine-grained and coarse-grained scrubbing to mitigate and repair the errors as quickly as possible after an SEU occurrence. Inspired by the human brain's ability to filter out redundant and irrelevant information, we propose a mechanism that can mask invalid position information when errors occur. Compared with the scrubbing of full configuration memory, this mechanism can achieve precise error location and recovery utilizing targeted scrubbing of specific frames or modules. The effectiveness is evaluated by executing fault injection campaigns on the International Symposium on Circuits and Systems 1989 (ISCAS89) benchmark circuits and fault tolerant fast Fourier transform (FT-FFT) circuit. If upsets are detected, they will be repaired with fine-grained or coarse-grained scrubbing depending on their location. The experiment results show that this mechanism can effectively mitigate and repair single-bit upsets (SBUs) and double-bit upsets (DBUs). In addition, the mechanism is proven to be superior in error recovery time and hardware overhead compared to counterpart approaches.

Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

Objective: To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. Methods: A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. Results: The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Conclusions: Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

Employment intentions among rural order-oriented medical students in inner mongolia autonomous region, China.

BACKGROUND: The program of the "Free Training of Chinese Rural Order-Oriented Medical Students" is a plan to train general practitioners who can work at rural medical institutions. However, many students have been unwilling to fulfill their commitments and actually work in their assigned locations. OBJECTIVE: This study aimed to provide some explanation by exploring factors influencing the employment intentions of rural order-oriented medical students in Inner Mongolia Autonomous Region of China to provide a basis for formulating relevant supporting policies to help increase the fulfillment rate of medical students. METHODS: We conducted a cross-sectional study with a stratified cluster sampling method at four medical universities in Inner Mongolia using a survey questionnaire. Multivariate logistic regression was used to identify factors that were significantly associated with employment intentions. RESULTS: Approximately 67% of students were willing to work in rural areas, whereas 33% were not. Order-oriented medical students who were dissatisfied with, or indifferent to, training, were unclear about policy, were of Han ethnicity, or came from an urban area, had lower intentions to accept employment in rural areas. The training satisfaction in particular had the greatest predictive effect. CONCLUSION: The implementation of the program "Free Training of Chinese Rural Order-Oriented Medical Students" has been affected by the low actual employment intentions. This study may provide a useful basis on which medical educators and health policy makers can formulate relevant supporting policies and develop strategies to increase the number of order-oriented medical students who working in rural areas where they are most needed.

Association between Different Types of Plant-Based Diets and Dyslipidemia in Middle-Aged and Elderly Chinese Participants.

Plant-based dietary patterns may reduce the risk of dyslipidemia. However, not all plant-based foods are beneficial, and limited data exist for the Chinese population. We investigated the association between different plant-based dietary indices and the risk of dyslipidemia in a Chinese middle-aged and elderly population. The study participants (n = 4096) consisted of adults between 35 and 74 years of age from Xinjiang, China. Dietary consumption of the study participants was evaluated using a semi-quantitative food-frequency questionnaire (FFQ). Three different plant-based dietary indices were calculated using data from dietary surveys, including overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Based on these indices, we created an adjusted plant-based diet index (aPDI) based on the Xinjiang population actual dietary behavior and health effects of food. We measured the levels of total cholesterol, triglyceride, LDL-C, and HDL-C in the blood of the study participants. We used multivariable logistic regression and restricted cubic spline to analyze the relationship between plant-based diets and dyslipidemia. The findings showed that 36.6% of the participants had dyslipidemia. Higher PDI adherence was related to lower odds of dyslipidemia (Q3 vs. Q1, OR: 0.780, 95% CI: 0.641-0.949; Q4 vs. Q1, OR: 0.799, 95% CI: 0.659-0.970). High aPDI was related to lower odds of dyslipidemia (Q4 vs. Q1, OR: 0.770, 95% CI: 0.628-0.945; Q5 vs. Q1, OR: 0.748, 95% CI: 0.607-0.921). High scores for PDI, hPDI, and aPDI were all related to a reduced risk of low HDL-C (OR: 0.638, 95% CI: 0.491-0.823; OR: 0.661, 95% CI: 0.502-0.870; OR: 0.580, 95% CI: 0.443-0.758). Conversely, a high uPDI score was associated with an increased risk of low HDL-C (OR: 1.349, 95% CI: 1.046-1.740). There was no non-linear relationship between PDI, hPDI, uPDI, and aPDI and the risk of different types of dyslipidemia. Plant-based dietary indices are related to specific types of dyslipidemia risk. Appropriately increasing the consumption of plant-based foods while improving the quality of plant-based dietary patterns is critical for the prevention of dyslipidemia, especially low HDL-C, in the population.

Social support and vicarious posttraumatic growth among psychological hotline counselors during COVID-19: the role of resilience and cognitive reappraisal.

Background: The COVID-19 pandemic is a serious threat to people's lives and mental health. As a key worker providing psychological assistance services, the purpose of this study was to explore the relationship between social support and vicarious posttraumatic growth of psychological hotline counselors during COVID-19 and its mechanism. Methods: A questionnaire survey was conducted among 241 psychological hotline counselors. Path analysis was conducted through structural equation modeling. Results: The direct path from social support to vicarious posttraumatic growth of psychological hotline counselors was not significant, but the indirect path between them was significant. Social support can influence vicarious posttraumatic growth of psychological hotline counselors through the mediating effects of resilience and cognitive reappraisal as well as the chain mediating effects of these two factors. Conclusions: Social support does not directly stimulate vicarious posttraumatic growth in psychological hotline counselors, but social support can influence counselors' vicarious posttraumatic growth through the role of resilience, cognitive reappraisal, and the chain-mediated effects of psychological resilience and cognitive reappraisal. This encourages hotline counselors to be intentional about applying resources to balance the effects of trauma work on them as they face their clinical work.

CCL22 and CCL26 are potential biomarkers for predicting distant metastasis in thyroid carcinoma.

OBJECTIVES: Chemokines have been suggested to play significant roles in the progression of malignant cancers. This study aimed to identify the chemokines related to malignant progression in thyroid carcinoma. METHODS: The mRNA expression levels of 52 chemokines were compared between differentiated thyroid cancer (DTC) samples and normal thyroid tissues from The Cancer Genome Atlas database; survival analysis was then performed on the basis of differentially expressed chemokines. A retrospective study was conducted on the level of differentially expressed chemokines in 76 DTC patients. Functional pathway analysis was performed to explore chemokine-related regulatory mechanisms. RESULTS: We identified 20 chemokines with differentially expressed mRNA levels through publicly available data. High levels of CCL22 and CCL26 were found to be related with metastasis in clinical DTC samples. High levels of CCL22 were found to be significantly related to poor prognosis in DTC patients. Pathway analyses revealed that cytokines might affect cancer progression through cytokine-cytokine receptor and cytokine-interleukin interactions. CONCLUSIONS: CCL22 and CCL26 could serve as prognostic biomarkers in thyroid carcinoma.

Anxiety and depression status prior to radioactive iodine therapy among differentiated thyroid cancer patients during the COVID­19 pandemic.

OBJECTION: The psychological health of thyroid cancer patients cannot be ignored; however, few studies have been conducted on the psychological status and influencing factors of thyroid cancer patients before radioactive iodine (RAI) therapy. The aim of this study was to investigate the incidence and risk factors for anxiety and depression in thyroid cancer patients prior to RAI therapy. METHODS: Clinical data were collected from patients with differentiated thyroid cancer (DTC) patients preparing for RAI therapy. Anxiety and depression were measured before RAI therapy using the Generalized Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-9). We used the chi-square test and logistic regression analysis to identify independent risk factors for anxiety and depression. RESULTS: A total of 112 patients with thyroid cancer were included. Of these, 72.32% (n = 81) were female, with a mean age of 41.50 years. Anxiety and depression were reported by 46 (41.08%) and 38 (33.93%) patients, respectively. Based on the chi-square test and univariate logistic regression analysis, being female and having ever-experienced RAI therapy were significant risk factors for anxiety and depression among DTCs prior to RAI therapy. On multivariable analysis, the results of model 2 which included age, sex, education level, and ever suffering radioactive iodine therapy showed that being female was markedly associated with anxiety and depression in these patients, while having ever undergone RAI therapy was significantly related to anxiety but not depression. CONCLUSIONS: The incidence of anxiety and depression among patients with DTC prior to RAI therapy were 41.08% and 33.93%, respectively. Being female and having ever experienced RAI therapy significantly influenced anxiety and depression. Based on these findings, anxiety and depression assessment should be an important part of pre-RAI therapy in patients with DTC, and appropriate psychological nursing intervention can be carried out for key patients.

Association between abdominal obesity indices and risk of cardiovascular events in Chinese populations with type 2 diabetes: a prospective cohort study.

BACKGROUND: Waist circumference (WC), visceral adiposity index (VAI), lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) are considered surrogate indicators of abdominal fat deposition, but the longitudinal association of these indices with cardiovascular (CV) events in adults with type 2 diabetes (T2D) remains unclear. Our study aimed to examine the associations between abdominal obesity indices and incident CV events among people with T2D and to compare their predictive performance in risk assessment. METHODS: The present study included 2328 individuals with T2D from the Xinjiang Multi-Ethnic Cohort. Multivariable Cox regression analyses were applied to assess the associations between abdominal obesity indices and CV events. Harrell's concordance statistic (C-statistic), net reclassification improvement (NRI) index, and integrated discrimination improvement (IDI) index were utilized to evaluate the predictive performance of each abdominal obesity index. RESULTS: At a median follow-up period of 59 months, 289 participants experienced CV events. After multivariable adjustment, each 1-SD increase in WC, VAI, LAP, and CVAI was associated with a higher risk of CV events in people with T2D, with adjusted hazard ratios (HRs) being 1.57 [95% CI (confidence interval): 1.39-1.78], 1.11 (95% CI 1.06-1.16), 1.46 (95% CI 1.36-1.57), and 1.78 (95% CI 1.57-2.01), respectively. In subgroup analyses, these positive associations appeared to be stronger among participants with body mass index (BMI) < 25 kg/m2 compared to overweight/obese participants. As for the predictive performance, CVAI had the largest C-statistic (0.700, 95% CI 0.672-0.728) compared to VAI, LAP, WC, and BMI (C-statistic: 0.535 to 0.670, all P for comparison < 0.05). When the abdominal obesity index was added to the basic risk model, the CVAI index also showed the greatest incremental risk stratification (C-statistic: 0.751 vs. 0.701, P < 0.001; IDI: 4.3%, P < 0.001; NRI: 26.6%, P < 0.001). CONCLUSIONS: This study provided additional evidence that all abdominal obesity indices were associated with the risk of CV events and highlighted that CVAI might be a valuable abdominal obesity indicator for identifying the high risk of CV events in Chinese populations with T2D. These results suggest that proactive assessment of abdominal obesity could be helpful for the effective clinical management of the diabetic population.

The regulation role and diagnostic value of fibrinogen-like protein 1 revealed by pan-cancer analysis.

Although the role of fibrinogen-like protein 1 (FGL1) in tumorigenesis is well known, a pan-cancer analysis of FGL1 lacks. We used bioinformatics techniques to analyze cancer data from publicly available datasets from The Cancer Genome Atlas, UALCAN, TIMER, Gene Expression Profiling Interactive Analysis, cBioPortal, Search Tool for the Retrieval of Interacting Genes, and DAVID. FGL1 expression was significantly regulated in various common tumors than in normal tissues; it was increased in lung adenocarcinoma and decreased in colon adenocarcinoma. Cox regression analysis demonstrated that the upregulation of FGL1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS) in stomach adenocarcinoma, brain low-grade glioma, cervical squamous cell carcinoma, and endocervical adenocarcinoma. Decreased FGL1 methylation levels were observed in majority of tumor types. FGL1 expression was significantly associated with the levels of immune cell subtypes and immune checkpoint genes. Deep deletion was the most common genetic mutation in FGL1 that led to frame-shift mutations, which was closely associated with poor progression-free interval, disease-specific survival, and OS in patients with FGL1 mutations. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that FGL1-related genes participate in diverse pathways. Ubiquitin-mediated proteolysis is significantly correlated to the function of FGL1, which was identified for the first time in the present study. This pan-cancer study provides a deep understanding of the functions of FGL1 in progression of many tumors and demonstrates that FGL1 may be a potential biomarker for the diagnosis, prognosis, and immune infiltration in cancer.

Network pharmacology analysis of the mechanism of Huisheng oral liquid in the treatment of lung cancer.

Background: To study the active ingredient and possible mechanism of Huisheng oral liquid in the treatment of lung cancer by network pharmacology. Methods: The active ingredient and drug targets of Huisheng oral liquid were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and lung cancer targets were screened using the Gene Expression Omnibus (GEO) database. The drug targets of the effective components of Huisheng oral liquid were matched with disease targets and the obtained intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to construct a protein-protein interaction (PPI) network. R software and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for Gene Ontology (GO) and KEGG enrichment analyses, and Cytoscape software was used to construct a Huisheng oral liquid component target-lung cancer target network. The function and pathway of the therapeutic target of Huisheng oral liquid for lung cancer were analyzed. Results: A total of 1,376 differentially expressed genes (DEGs) of lung cancer were obtained, and 185 potential effective components of Huisheng oral liquid in the treatment of lung cancer were obtained, including quercetin, luteolin, kaempferol, and baicalein. There were 36 intersecting targets between Huisheng oral liquid and lung cancer, and the key targets for lung cancer treatment were CDKN1A, CCNB1, MDM2, CDK1, ErbB2, E2F1, EGFR, etc. Huisheng oral liquid mainly regulates the p53 signaling pathway. Conclusions: The mechanism of Huisheng oral liquid in the treatment of lung cancer is mainly reflected in regulating tumor cell apoptosis, inhibiting angiogenesis, and improving immunity.