Genetic susceptibility modifies the association of long-term air pollution exposure on Parkinson's disease.

Inconsistent findings exist regarding the potential association between polluted air and Parkinson's disease (PD), with unclear insights into the role of inherited sensitivity. This study sought to explore the potential link between various air pollutants and PD risk, investigating whether genetic susceptibility modulates these associations. The population-based study involved 312,009 initially PD-free participants with complete genotyping data. Annual mean concentrations of PM2.5, PM10, NO2, and NOx were estimated, and a polygenic risk score (PRS) was computed to assess individual genetic risks for PD. Cox proportional risk models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between ambient air pollutants, genetic risk, and incident PD. Over a median 12.07-year follow-up, 2356 PD cases (0.76%) were observed. Compared to the lowest quartile of air pollution, the highest quartiles of NO2 and PM10 pollution showed HRs and 95% CIs of 1.247 (1.089-1.427) and 1.201 (1.052-1.373) for PD incidence, respectively. Each 10 µg/m3 increase in NO2 and PM10 yielded elevated HRs and 95% CIs for PD of 1.089 (1.026-1.155) and 1.363 (1.043-1.782), respectively. Individuals with significant genetic and PM10 exposure risks had the highest PD development risk (HR: 2.748, 95% CI: 2.145-3.520). Similarly, those with substantial genetic and NO2 exposure risks were over twice as likely to develop PD compared to minimal-risk counterparts (HR: 2.414, 95% CI: 1.912-3.048). Findings suggest that exposure to air contaminants heightens PD risk, particularly in individuals genetically predisposed to high susceptibility.

Tissue and serum miR-149-3p/5p in hospitalized patients with inflammatory bowel disease: Correlation with disease severity and inflammatory markers.

This study aimed to investigate the expression levels of tissue and serum miR-149-3p and miR-149-5p in hospitalized patients with inflammatory bowel disease (IBD). A total of 35 ulcerative colitis (UC) patients, 12 Crohn's disease (CD) patients, and 25 healthy controls were included in the study. The miRNAs expressions were measured in tissue and serum samples using quantitative real-time polymerase chain reaction (qRT-PCR). Inflammatory biomarkers were measured, including serum albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), and fecal calprotectin. MiR-149-3p and miR-149-5p were significantly decreased in the inflamed areas of both CD and UC patients compared to tissue controls, which was consistent with decreased serum levels in IBD patients compared to healthy controls. When distinguishing UC patients from healthy controls, serum miR-149-3p showed 74% sensitivity and 96% specificity, while serum miR-149-5p exhibited 63% sensitivity and 96% specificity. In the CD versus healthy control comparison, miR-149-3p achieved 100% sensitivity and 96% specificity, while miR-149-5p demonstrated 92% sensitivity and 96% specificity. In the UC versus CD comparison, miR-149-5p showed 75% sensitivity and 77% specificity, while miR-149-3p displayed 67% sensitivity and 80% specificity. Significant correlations were identified between the tissue and serum expression of miR-149-3p/5p and disease activity scores, as well as inflammatory biomarkers in both CD and UC patients. Decreased expression of miR-149-3p and miR-149-5p is associated with disease activity in IBD patients. These miRNAs demonstrate diagnostic potential and may serve as biomarkers for monitoring disease activity in IBD.

Peripheral neural mechanism of visceral pain and acupoint sensitization in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis model mice. / ç»“è‚ ç‚Žæ¨¡åž‹å°é¼ å† è„ç—›åŠç©´ä½æ•åŒ–çš„å¤–å‘¨ç¥žç»æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To explore the neural mechanism of visceral pain and related somatic (acupoints) sensitization by using in vivo calcium imaging of dorsal root ganglia (DRG) neurons. METHODS: Eight BALB/c mice were randomly divided into control and model groups, with 4 mice in each group. The colitis model was induced by colorectal perfusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) once daily for 7 days. Mice of the control group received colorectal perfusion of normal saline once daily for 7 days. The location and area of the somatic neurogenic inflammation (cutaneous exudation of Evans blue ï¼»EBï¼½) of the 2 groups of mice were observed after intravenous injection of EB. For pain behavioral tests, sixteen C57BL/6J mice were randomly divided into control and model groups, with 8 mice in each group, and a Von Frey filament was used to stimulate the referred somatic reactive regions in colitis mice, and the number of avoidance and paw withdraw reaction within 10 tests was recorded. For in vivo DRG calcium imaging tests, 24 Pirt-GCaMP6s transgenic mice were randomly and equally divided into control group and colitis model group. The responses of the neurons in L6 or L4 DRG to colorectal distension (CRD), lower back brushing, or mechanical stimulation at the hindpaw were observed using confocal fluorescence microscope. RESULTS: Compared with the control group, the area of EB exudation spot in the hindpaw and lower back regions was increased in the colitis model group (P<0.05), and the avoidance or paw withdraw numbers induced by Von Frey stimulation at the lower back and hindpaw were increased (P<0.01, P<0.05), indicating that colitis induced regional skin (acupoints) sensitization in the lower back and hindpaw regions. Compared with the control group, the percentage of L6 DRG neurons activated by 60 mm Hg CRD in the colitis model mice were apparently increased (P<0.01), the activated neurons mainly involved the medium-sized DRG neurons (P<0.01). In Pirt-GCaMP6s transgenic mice, following brushing the skin of the receptive field (lower back) of L6 DRG neurons, the fluorescence intensity of the brushing-activated DRG neurons and small, medium and large-sized neurons were significantly higher in the colitis model group than those in the control group (P<0.001, P<0.01, P<0.05). After brushing and clamping the skin of the right hindpaw (receptive field of L4 DRG neurons), the percentages of the activated L4 DRG neurons were obviously higher in the colitis model group than those in the control group (P<0.01, P<0.05), while there were no significant changes in the proportion of small, medium and large-sized neurons between the control and colitis model groups. CONCLUSIONS: Colitis may lead to body surface sensitization at the same and adjacent neuro-segments as well as to an increase of the number and activity of the responsive lumbar DRG neurons, among which the L6 DRG neurons at the same neuro-segment as the rectum colon showed an increase in the number of responders and intensity of calcium fluorescence signal while L4 DRG neurons at the level adjacent to the rectum colon showed an increase in the number of responders, suggesting that there may be different mechanisms of peripheral neural sensitization.

Tackling global health security by building an academic community for One Health action.

BACKGROUND: One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet. MAIN TEXT: The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation. CONCLUSIONS: The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.

The Cellular Underpinnings of the Human Cortical Connectome.

The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cortex. The cortical sheet can be broadly divided into distinct networks, which are further embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here, using transcriptional data from the Allen Human Brain Atlas, we demonstrate that imputed cell type distributions are spatially coupled to the functional organization of cortex, as estimated through fMRI. Cortical cellular profiles follow the macro-scale organization of the functional gradients as well as the associated large-scale networks. Distinct cellular fingerprints were evident across networks, and a classifier trained on post-mortem cell-type distributions was able to predict the functional network allegiance of cortical tissue samples. These data indicate that the in vivo organization of the cortical sheet is reflected in the spatial variability of its cellular composition.

Glucose 6 phosphatase dehydrogenase (G6PD): a novel diagnosis marker related to gastrointestinal cancers.

BACKGROUND: Glucose 6 phosphatase dehydrogenase (G6PD) is a key regulator of the pentose phosphate pathway (PPP). However, the exact role of G6PD in gastrointestinal cancers remains unclear. The purpose of this study is to explore the correlation of G6PD with clinical features, pathological stages, diagnosis and prognosis of gastrointestinal cancers, as well as uncover possible mechanisms of G6PD on mutations, immunity and signaling pathways. METHODS: G6PD mRNA expression data were downloaded from TCGA and GEO databases. Protein expression was examined by the HPA database. The correlation of G6PD expression with clinical and pathological characteristics was explored. The pROC package in R language was used to evaluate the diagnostic value of G6PD expression in gastrointestinal cancers. We accessed the correlation of disease-free survival (DFS) with G6PD online by Kaplan-Meier plotter. Univariate Cox regression and stepwise multiple Cox regression analysis were performed to determine the association between G6PD and patient's overall survival. In addition, genomic alterations, mutation profiles, immune infiltration, drug sensitivity and enrichment analysis related with G6PD were visualized. RESULTS: After a pan-cancerous genomic analysis, we found that G6PD expression was the highest in African American esophageal carcinoma (ESCA) patients (P<0.05). G6PD was correlated with age, weight, disease stage, lymph node metastasis and pathological grade. Notably, G6PD showed an excellent predictive diagnosis ability for liver hepatocellular carcinoma (LIHC) (AUC=0.949, 95% CI=0.925-0.973, P<0.001). G6PD can improve the DFS of esophageal adenocarcinoma (EAC) and pancreatic adenocarcinoma (PAAD) patients (P<0.05). Both Univariate Cox regression and stepwise multiple Cox regression analysis in R language determined that G6PD expression was closely related with LIHC (P<0.001). G6PD was found to have a high mutation rate in colon adenocarcinoma and ESCA and gene amplification in ESCA, Cholangiocarcinoma, PAAD and LIHC. Copy number of G6PD was missing in LIHC. G6PD was also related to mutation of TP53 (P<0.05). Particularly, it was positively correlated with CD276 in all gastrointestinal cancers and negatively with HERV-H LTR-associating 2 in ESCA and stomach adenocarcinoma. The abnormal expression of G6PD was related to the increase of CD4+ Th2 subsets and the decrease of CD4+ (non-regulatory) of T cells. G6PD was sensitive to FK866, Phenformin, AICAR etc., while resistant to RO-3306, CGP-082996, TGX221 etc. G6PD was found to closely interact with TALDO1, GAPDH and TP53. G6PD related biological processes included aging, nutritional response and daunorubicin metabolism, and related pathways included PPP, cytochrome P450 metabolism of exogenous substances and glutathione metabolism. CONCLUSION: G6PD is highly expressed in gastrointestinal cancers. It is a carcinogenic indicator related to prognosis and can be used as a potential diagnostic marker of gastrointestinal cancers, so as to provide new strategy for cancer treatment.

High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer

Purpose The poor prognosis of ovarian cancer is largely due to platinum resistance. It has been demonstrated that nucleotide excision repair (NER) involving centrin-2(CETN2) is connected to platinum resistance in ovarian cancer. The molecular mechanism of CETN2 in ovarian cancer and the mechanism affecting the outcome of chemotherapy are unknown. Methods The protein–protein interaction (PPI) network was mapped after obtaining the interacting proteins of CETN2, and the interacting genes were subjected to enrichment analysis. To examine the relationship between CETN2 and platinum resistance, gene microarray data and clinical data related to platinum resistance in ovarian cancer were downloaded. The possible signaling pathway of CETN2 was investigated by Gene set enrichment analysis (GSEA). Immune infiltration analysis was performed. Immunohistochemistry (IHC) and quantitative real-time PCR (QRT-PCR) were used to examine the expression of CETN2 in clinical samples in relation to the effectiveness of chemotherapy. The capacity of CETN2 to predict chemotherapy results was proven by receiver operating characteristic (ROC) curves after the construction of two prediction models, the logistic regression model and the decision tree model. The impact of CETN2 on prognosis was examined using the Kaplan–Meier technique. Result CETN2 was associated with NER, oxidative phosphorylation (OXPHOS) and cell cycle pathways in ovarian cancer drug-resistant samples. In clinical samples, CETN2 showed its possible correlation with immune infiltration. The protein expression level of CETN2 was significantly higher in platinum-resistant patients than that in platinum-sensitive patients, and the expression level had some predictive value for chemotherapy outcome, and high CETN2 protein expression was associated with poorer progression-free survival (AU)

Brain-Based Predictions of Psychiatric Illness-Linked Behaviors Across the Sexes.

BACKGROUND: Individual differences in functional brain connectivity can be used to predict both the presence of psychiatric illness and variability in associated behaviors. However, despite evidence for sex differences in functional network connectivity and in the prevalence, presentation, and trajectory of psychiatric illnesses, the extent to which disorder-relevant aspects of network connectivity are shared or unique across the sexes remains to be determined. METHODS: In this work, we used predictive modeling approaches to evaluate whether shared or unique functional connectivity correlates underlie the expression of psychiatric illness-linked behaviors in males and females in data from the Adolescent Brain Cognitive Development Study (N = 5260; 2571 females). RESULTS: We demonstrate that functional connectivity profiles predict individual differences in externalizing behaviors in males and females but predict internalizing behaviors only in females. Furthermore, models trained to predict externalizing behaviors in males generalize to predict internalizing behaviors in females, and models trained to predict internalizing behaviors in females generalize to predict externalizing behaviors in males. Finally, the neurobiological correlates of many behaviors are largely shared within and across sexes: functional connections within and between heteromodal association networks, including default, limbic, control, and dorsal attention networks, are associated with internalizing and externalizing behaviors. CONCLUSIONS: Taken together, these findings suggest that shared neurobiological patterns may manifest as distinct behaviors across the sexes. Based on these results, we recommend that both clinicians and researchers carefully consider how sex may influence the presentation of psychiatric illnesses, especially those along the internalizing-externalizing spectrum.

Wave-like properties of functional dynamics across the cortical sheet.

The human cortex is organized in a hierarchical manner. Pines et al.1 show that wave-like hemodynamic activity flows along this architecture, from unimodal through association cortices, providing fertile ground for researchers seeking to map links across behavioral and cognitive states.

A high-quality reference genome for the fission yeast Schizosaccharomyces osmophilus.

Fission yeasts are an ancient group of fungal species that diverged from each other from tens to hundreds of million years ago. Among them is the preeminent model organism Schizosaccharomyces pombe, which has significantly contributed to our understandings of molecular mechanisms underlying fundamental cellular processes. The availability of the genomes of S. pombe and 3 other fission yeast species S. japonicus, S. octosporus, and S. cryophilus has enabled cross-species comparisons that provide insights into the evolution of genes, pathways, and genomes. Here, we performed genome sequencing on the type strain of the recently identified fission yeast species S. osmophilus and obtained a complete mitochondrial genome and a nuclear genome assembly with gaps only at rRNA gene arrays. A total of 5,098 protein-coding nuclear genes were annotated and orthologs for more than 95% of them were identified. Genome-based phylogenetic analysis showed that S. osmophilus is most closely related to S. octosporus and these 2 species diverged around 16 million years ago. To demonstrate the utility of this S. osmophilus reference genome, we conducted cross-species comparative analyses of centromeres, telomeres, transposons, the mating-type region, Cbp1 family proteins, and mitochondrial genomes. These analyses revealed conservation of repeat arrangements and sequence motifs in centromere cores, identified telomeric sequences composed of 2 types of repeats, delineated relationships among Tf1/sushi group retrotransposons, characterized the evolutionary origins and trajectories of Cbp1 family domesticated transposases, and discovered signs of interspecific transfer of 2 types of mitochondrial selfish elements.

High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer.

PURPOSE: The poor prognosis of ovarian cancer is largely due to platinum resistance. It has been demonstrated that nucleotide excision repair (NER) involving centrin-2(CETN2) is connected to platinum resistance in ovarian cancer. The molecular mechanism of CETN2 in ovarian cancer and the mechanism affecting the outcome of chemotherapy are unknown. METHODS: The protein-protein interaction (PPI) network was mapped after obtaining the interacting proteins of CETN2, and the interacting genes were subjected to enrichment analysis. To examine the relationship between CETN2 and platinum resistance, gene microarray data and clinical data related to platinum resistance in ovarian cancer were downloaded. The possible signaling pathway of CETN2 was investigated by Gene set enrichment analysis (GSEA). Immune infiltration analysis was performed. Immunohistochemistry (IHC) and quantitative real-time PCR (QRT-PCR) were used to examine the expression of CETN2 in clinical samples in relation to the effectiveness of chemotherapy. The capacity of CETN2 to predict chemotherapy results was proven by receiver operating characteristic (ROC) curves after the construction of two prediction models, the logistic regression model and the decision tree model. The impact of CETN2 on prognosis was examined using the Kaplan-Meier technique. RESULTS: CETN2 was associated with NER, oxidative phosphorylation (OXPHOS) and cell cycle pathways in ovarian cancer drug-resistant samples. In clinical samples, CETN2 showed its possible correlation with immune infiltration. The protein expression level of CETN2 was significantly higher in platinum-resistant patients than that in platinum-sensitive patients, and the expression level had some predictive value for chemotherapy outcome, and high CETN2 protein expression was associated with poorer progression-free survival. CONCLUSIONS: CETN2 protein had a significant effect on ovarian cancer platinum sensitivity and prognosis, which may be related to the activation of NER, OXPHOS and cell cycle pathways upon CETN2 upregulation. Further research is necessary to determine the therapeutic application value of CETN2, which may be a new biomarker of chemoresponsiveness.

Characteristics of changes in volatile organic compounds and microbial communities during the storage of pickles.

The variations of volatile organic compounds (VOCs) and microbial communities of three pickles during storage at 4°C for one week were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), high-throughput sequencing, and Spearman correlation analysis. A total of 50 VOCs were identified from three pickles. During storage, most alcohols, aldehydes, ketones, and esters decreased, while acids increased, and sulfides, alkenes, and phenols were relatively equal. Firmicutes, Cyanobacteria, and Proteobacteria were the predominant bacterial phyla, and Weissella, Streptophyta, Leuconostoc, Bacillariophyta, and Lactobacillus were the predominant bacterial genera in three pickles. The bacterial diversity level significantly decreased during storage (P < 0.05). Spearman correlation coefficient indicated that Leuconostoc, Lactobacillus, and Weissella were highly correlated with the flavor of pickles, while Bacillariophyta and Streptophyta were highly correlated with the flavor formation of pickles during storage. These results could contribute to a better understanding of the impact of bacteria in flavor formation during pickle storage.

Analysis of work stress and its influencing factors among nursing staff in Tianjin City / 中华劳动卫生职业病杂志

Objective: To explore the current situation of work stress among nursing staff in Tianjin City and analyze its influencing factors. Methods: From August to October 2020, 26002 nursing staff from tertiary hospitals, secondary public hospitals, secondary private hospitals, primary hospitals, and other medical institutions in Tianjin City were selected as objects, and their general situation and working stress situation were surveyed by the general information questionnaire and the Nurse's Work Stressor Scale. Single factor analysis and multiple linear regression analysis were used to explore the influencing factors of work stress among nursing staff. Results: The average age of 26002 nursing staff was (33.86±8.28) years old, and the average working years were (11.84±9.12) years. There were 24874 women (95.66%) and 1128 men (4.34%). The total score of work stress was (79.82±21.69), and the average score of workload and time allocation dimension was the highest (2.55±0.79). The results of multiple linear regression analysis showed that marital status (β=-0.015, P=0.014), employment form as contract system (β=0.022, P=0.001), post as clinical nursing (β=0.048, P<0.001), education level (β=0.024, P<0.001), age (β=0.050, P<0.001), working years (β=0.075, P<0.001), and professional title (β=0.036, P<0.001) were the influencing factors of work stress, which explained 22.8% of the total variation in work stress of nursing staff (F=24.25, P<0.001) . Conclusion: The work stress among nursing staff in Tianjin City is high, the corresponding departments and nursing managers should adopt scientific management methods to reduce the workload of nursing staff according to the influencing factors of work stress, so as to create a good atmosphere for further promoting the healthy development of nursing career and nursing industry in the new era.

Population Pharmacokinetics and Pharmacodynamics of Isoniazid and its Metabolite Acetylisoniazid in Chinese Population.

Objective: We aimed to establish a population pharmacokinetic (PPK) model for isoniazid (INH) and its major metabolite Acetylisoniazid (AcINH) in healthy Chinese participants and tuberculosis patients and assess the role of the NAT2 genotype on the transformation of INH to AcINH. We also sought to estimate the INH exposure that would achieve a 90% effective concentration (EC90) efficiency for patients with various NAT2 genotypes. Method: A total of 45 healthy participants and 157 tuberculosis patients were recruited. For healthy subjects, blood samples were collected 0-14 h after administration of 300 mg or 320 mg of the oral dose of INH; for tuberculosis patients who received at least seven days therapy with INH, blood samples were collected two and/or six hours after administration. The plasma concentration of INH and AcINH was determined by the reverse-phase HPLC method. NAT2 genotypes were determined by allele-specific amplification. The integrated PPK model of INH and AcINH was established through nonlinear mixed-effect modeling (NONMEM). The effect of NAT2 genotype and other covariates on INH and AcINH disposition was evaluated. Monte Carlo simulation was performed for estimating EC90 of INH in patients with various NAT2 genotypes. Results: The estimated absorption rate constant (Ka), oral clearance (CL/F), and apparent volume of distribution (V2/F) for INH were 3.94 ± 0.44 h-1, 18.2 ± 2.45 L⋅h-1, and 56.8 ± 5.53 L, respectively. The constant of clearance (K30) and the volume of distribution (V3/F) of AcINH were 0.33 ± 0.11 h-1 and 25.7 ± 1.30 L, respectively. The fraction of AcINH formation (FM) was 0.81 ± 0.076. NAT2 genotypes had different effects on the CL/F and FM. In subjects with only one copy of NAT2 *5, *6, and *7 alleles, the CL/F values were approximately 46.3%, 54.9%, and 74.8% of *4/*4 subjects, respectively. The FM values were approximately 48.7%, 63.8%, and 86.9% of *4/*4 subjects, respectively. The probability of target attainment of INH EC90 in patients with various NAT2 genotypes was different. Conclusion: The integrated parent-metabolite PPK model accurately characterized the disposition of INH and AcINH in the Chinese population sampled, which may be useful in the individualized therapy of INH.

The regulatory effect of total flavonoids of Sedum aizoon L. on oxidative stress in type 1 diabetic mice.

In this study, the optimal extraction conditions for the total flavonoids of Sedum aizoon L. (STF) were optimized by response surface methodology. Evaluation of the antioxidant in vitro of STF, and modulatory effects of glucolipid metabolism, and oxidative stress in mice with type 1 diabetes mellitus (T1DM). STF showed good antioxidant capacity in vitro. STF could improve glucolipid metabolism, organ coefficients, and antioxidant stress enzymes in T1DM mice effectively, reduce the damage to liver tissue, and regulate redox imbalance in the organism by modulating the Nrf2/Keap1/ARE signaling pathway. The results of this study could provide a theoretical reference for the application of Sedum aizoon L. in the development of auxiliary hypoglycemic functional foods and improvement of diabetes.

Identification of Senescence-Related Subtypes, the Development of a Prognosis Model, and Characterization of Immune Infiltration and Gut Microbiota in Colorectal Cancer.

Cellular senescence is associated with tumorigenesis, and the subtype and prognostic signatures of senescence-related genes (SRGs) in the tumor microenvironment (TME) and gut microbiota have not been fully determined. Analysis of 91 SRGs obtained from the GSEA and MSigDB, and mRNA sequencing of genes in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases enabled the identification of two distinct molecular types of colorectal cancer (CRC). Patient samples were clustered into two subtypes, with Kaplan-Meier survival analyses showing significant differences in patient survival between the two subtypes. Cluster C2 was associated with patient clinicopathological features, high immune score, high abundance of immune infiltrating cells and somewhat high abundance of bacteria. A risk model based on eight SRGs showed that a low risk score was characterized by inhibition of immune activity and was indicative of better prognosis in patients with CRC. In combination with clinical characteristics, risk score was found to be an independent prognostic predictor of survival in patients with CRC. In conclusion, the present study showed that senescence-related subtypes and a signature consisting of eight SRGs were associated with CRC patient prognosis, as well as with immune cell infiltration and gut microbiota. These findings may enable better prediction of CRC patient prognosis and facilitate individualized treatments.

The pharmacokinetics of tacrolimus in peripheral blood mononuclear cells and limited sampling strategy for estimation of exposure in renal transplant recipients.

PURPOSE: Intracellular exposure of tacrolimus (TAC) may be a better marker of therapeutic effect than whole blood exposure. We aimed to evaluate the influence of genetic polymorphism on the pharmacokinetics of TAC in peripheral blood mononuclear cells (PBMCs) and develop limited sampling strategy (LSS) models to estimate the area under the curve (AUC0-12h) in the PBMC of Chinese renal transplant patients. METHODS: Ten blood samples of each of the 23 renal transplant patients were collected 0-12h after 14 (10-18) days of TAC administration. PBMCs were separated and quantified. The TAC level in PBMCs was determined, and pharmacokinetic parameters were estimated by noncompartmental study. The AUC0-12h of TAC in whole blood was estimated by Bayesian approach based on a population pharmacokinetic model established in 65 renal transplant patients. The influence of CYP3A5 and ABCB1 genotypes on exposure was estimated. By applying multiple stepwise linear regression analysis, LSS equations for TAC AUC0-12h in the PMBC of renal transplant patients were established, and the bias and precision of various equations were identified and compared. RESULTS: We found a modest correlation between TAC exposure in whole blood and PBMC (r2 = 0.5260). Patients with the CYP3A5 6986GG genotype had a higher AUC0-12h in PBMCs than those with the 6986 AA or GA genotype (P = 0.026). Conversely, patients with the ABCB1 3435TT genotype had a higher AUC0-12h in PBMC than those with the 3435 CC and CT genotypes (P = 0.046). LSS models with 1-4 blood time points were established (r2 = 0.570-0.989). The best model for predicting TAC AUC0-12h was C2-C4-C6-C10 (r2 = 0.989). The model with C0.5-C6 (r2 = 0.849) can be used for outpatients who need monitoring to be performed in a short period. CONCLUSIONS: The CYP3A5 and ABCB1 genotypes impact TAC exposure in PBMCs, which may further alter the effects of TAC. The LSS model consisting of 2-4 time points is an effective approach for estimating full TAC AUC0-12h in Chinese renal transplant patients. This approach may provide convenience and the possibility for clinical monitoring of TAC intracellular exposure.

[Clinical therapeutic effect on bronchial asthma by the observation of skin reaction after acupoint application based on chronic disease management platform of asthma].

OBJECTIVE: To compare the therapeutic effect on bronchial asthma between presence of skin reaction and the absence of skin reaction after acupoint application. METHODS: Sixty-one patients with bronchial asthma were treated with acupoint application during the hottest periods of summer ("dog days"). The acupoints included Dingchuan (EX-B 1), Feishu (BL 13), Xinshu (BL 15), Pishu (BL 20) and Shenshu (BL 23). The treatment was given once every 7 days, with the herbal plaster remained for 6 h each time, and 4 treatments were required totally. According to the local skin reaction after acupoint application, a skin reaction group (30 cases, 2 cases dropped off) and a non-skin reaction group (31 cases) were divided. Separately, before treatment and 1 year after treatment, using chronic disease management platform of asthma, the number of asthma attacks, the score of asthma control test (ACT) and the score of asthma quality of life questionnaire (AQLQ) were recorded online. Besides, the therapeutic effect was observed in the two groups 1 year after treatment. RESULTS: One year after treatment, the number of asthma attacks was reduced as compared with that before treatment in the patients of either group (P<0.001), the score of ACT and each domain in AQLQ, i.e. activity limitation, asthma symptoms, psychological state, reactions to stimuli and self-health care as well as the total scores of AQLQ were all increased as compared with those before treatment (P<0.001). The number of asthma attacks in the skin reaction group was less than the non-skin reaction group (P<0.05), the score of ACT and each domain of AQLQ and the total scores of AQLQ were all higher than the non-skin reaction group successively (P<0.05, P<0.01). The total effective rate was 82.1% (23/28) in the skin reaction group, better than 67.7% (21/31) in the non-skin reaction group (P<0.05). CONCLUSION: In treatment of acupoint application for bronchial asthma, the clinical therapeutic effect is better in the patients with local skin reaction after acupoint application. The chronic disease management platform of asthma is convenient for online evaluation.

Effect of Acupuncture on Cognitive Function of Insomnia Patients Compared with Drugs: A Protocol for Meta-analysis and Systematic Review.

Insomnia, one of the most common sleep disorders, is thought to have an adverse effect on cognitive function. At the same time, people with cognitive dysfunction are more prone to insomnia. At present, pharmacotherapy is the main treatment for insomnia, but there are some shortcomings such as poor long-term efficacy and potential dependence. There is some evidence that acupuncture has some advantages in alleviating insomnia and improving cognitive function. This study is aimed at investigating the effects of acupuncture and drugs on cognitive function in patients with insomnia and evaluating the efficacy and safety of these two interventions, providing strong evidence for clinical decision-making. The study will retrieve eight major databases: China National Knowledge Infrastructure, Wanfang Database, VIP Database for Chinese Technical Periodicals, SinoMed, PubMed, Web of Science, Embase, and Cochrane Library. Dissertations, conference papers, and ongoing experiments will also be retrieved for supplement. Literature screening and data extraction will be completed by two authors independently (JJ and X-QW). If there were any disagreements, they would be discussed or referred to a third person for adjudication (W-ZW). Authors will use Cochrane risk of bias tool to assess the included studies. The Review Manager Statistical (RevMan) software is used to conduct the statistical process of meta-analysis, and funnel plot is used to evaluate reporting biases. The Grading of Recommendations Assessment Development and Evaluation (GRADE) Profiler can be used to be aware of the quality of evidence.

The efficacy of acupuncture on the sleep structure of patients with insomnia: A systematic review and meta-analysis.

This study aims to evaluate the efficacy of acupuncture on the sleep structure of patients with insomnia, so as to provide a valuable basis for the effectiveness of acupuncture in the treatment of insomnia. We conducted searches based on MeSH terms and free words in Cochrane Library, PubMed, Web of science, CKNI (China Knowledge Resource Integrated Database), WanFang Database, and Chongqing VIP Information from the inception of these database until 10 July 2020 for randomized controlled trials (RCTs) that investigated acupuncture treatment in patients with insomnia, and pertinent details of the results were saved. Comprehensive analysis showed that: (1) compared with the Western medicine groups, the acupuncture groups showed significant advantages in reducing the percentage of N1 sleep stage and N2 sleep stage, as well as increasing that of N3 sleep stage and REM sleep stage. However, no significant difference was found in increasing the effective rate, reducing total PSQI score, improving the total sleep time, reducing sleep latency, and improving sleep efficiency between the Western medicine groups and the acupuncture groups. (2) Compared with the sham acupuncture groups, the acupuncture treatment showed advantages in increasing the effective rate, reducing Pittsburgh Sleep Quality Index (PSQI) score, increasing the total sleep time, and improving sleep efficiency. However, no significant difference was observed between the sham acupuncture groups and the acupuncture groups with regard to reducing sleep latency, the percentage of N1 sleep stage and N2 sleep stage, as well as increasing that of N3 sleep stage and REM sleep stage.