Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity.

Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.

Lifestyle factors on the long-term survival of gastric cancer patients after radical resection: A cohort study.

Background: This retrospective cohort study aimed to evaluate the effect of lifestyle factors (e.g., smoking, drinking, physical exercise, and sleep duration) on the long-term survival of gastric cancer (GC) patients after radical resection. Materials and Methods: GC patients after radical resection were enrolled from January 2016 to December 2017. Their baseline clinical data, lifestyle factors, and prognosis were collected. The primary endpoint was all-cause death. The relationship between the variables and survival was examined using the Cox proportional hazards model. Results: A total of 309 patients were enrolled and 296 patients were followed up for a median of 54.0 months, with 130 confirmed deaths. Older age (>60 years) (hazard ratio [HR]: 1.307, 95% confidence interval [CI]: 1.056-2.161, P = 0.006), advanced tumor, node, and metastasis stage (P < 0.05), poorly pathological differentiation (HR: 1.765, 95% CI: 1.080-2.884, P = 0.023), history of smoking (P < 0.001), never physical exercise (HR: 2.057, 95% CI: 1.170-3.617, P = 0.012), long sleep duration (≥8 h) (HR: 4.160, 95% CI: 1.501-11.533, P = 0.006), and short sleep duration (<6 h) (HR: 3.417, 95% CI: 1.312-8.900, P = 0.012) were independent indicators of a poor overall survival in GC patients after radical resection. Conclusion: Smoking cessation, proper sleep duration, and regular physical exercise habits can improve the long-term survival of GC patients after radical resection.

A tracking work on how Sm4CL2 re-directed the biosynthesis of salvianolic acids and tanshinones in Salvia miltiorrhiza hairy roots.

KEY MESSAGE: Overexpression and antisense expression of Sm4CL2 re-directed the biosynthesis of salvianolic acids and tanshinones in Salvia miltiorrhiza hairy roots. Danshen (Salvia miltiorrhiza Bunge) is a widely used traditional Chinese medicine and its main active ingredients are water-soluble phenolic acids and lipophilic diterpenoids which are produced through the phenylpropanoid pathway and terpenoid pathway, respectively. 4-Coumaric acid: Coenzyme A ligase (4CL) is a key enzyme in the phenylpropanoid metabolism. We had obtained Sm4CL2-overexpressing (Sm4CL2-OE) and antisense Sm4CL2-expressing (anti-Sm4CL2) danshen hairy roots over ten years ago. In the follow-up study, we found that total salvianolic acids in Sm4CL2-OE-4 hairy roots increased to 1.35 times of the control-3, and that in anti-Sm4CL2-1 hairy roots decreased to 37.32% of the control-3, but tanshinones in anti-Sm4CL2-1 was accumulated to 1.77 ± 0.16 mg/g of dry weight, compared to undetectable in Sm4CL2-OE-4 and the control-3 hairy roots. Interestingly, Sm4CL2-OE-4 hairy roots contained more lignin, 1.36 times of the control-3, and enhanced cell wall and xylem lignification. Transcriptomic analysis revealed that overexpression of Sm4CL2 caused the upregulation of other phenylpropanoid pathway genes and antisense Sm4CL2 expression resulted in the downregulation of other phenylpropanoid pathway genes but activated the expression of terpenoid pathway genes like SmCYP76AK5, SmGPPS.SSUII.1 and SmDXS2. Protein-protein interaction analysis suggested that Sm4CL2 might interact with PAL, PAL4, CSE, CCoAOMT and SmCYP84A60, and appeared to play a key role in the interaction network. The tracking work in this study proved that Sm4CL2 could redirect both salvianolic acids and tanshinones biosynthesis possibly through synergistically regulating other pathway genes. It also indicated that genetic modification of plant secondary metabolism with biosynthetic gene might cause other responses through protein-protein interactions.

Dual effects of endogenous formaldehyde on the organism and drugs for its removal.

Endogenous formaldehyde (FA) is produced in the human body via various mechanisms to preserve healthy energy metabolism and safeguard the organism. However, endogenous FA can have several negative effects on the body through epigenetic alterations, including cancer growth promotion; neuronal, hippocampal and endothelial damages; atherosclerosis acceleration; haemopoietic stem cell destruction and haemopoietic cell production reduction. Certain medications with antioxidant effects, such as glutathione, vitamin E, resveratrol, alpha lipoic acid and polyphenols, lessen the detrimental effects of endogenous FA by reducing oxidative stress, directly scavenging endogenous FA or promoting its degradation. This study offers fresh perspectives for managing illnesses associated with endogenous FA exposure.

Comparative metabolomic and transcriptomic analysis of Saccharomyces cerevisiae W303a and CEN.PK2-1C.

Saccharomyces cerevisiae is a health microorganism closely related to human life, especially in food and pharmaceutical industries. S. cerevisiae W303a and CEN.PK2-1C are two commonly used strains for synthetic biology-based natural product production. Yet, the metabolomic and transcriptomic differences between these two strains have not been compared. In this study, metabolomics and transcriptomics were applied to analyze the differential metabolites and differential expression genes (DEGs) between W303a and CEN.PK2-1C cultured in YPD and SD media. The growth rate of W303a in YPD medium was the lowest compared with other groups. When cultured in YPD medium, CEN.PK2-1C produced more phenylalanine than W303a; when cultured in SD medium, W303a produced more phospholipids than CEN.PK2-1C. Transcriptomic analysis revealed that 19 out of 22 genes in glycolysis pathway were expressed at higher levels in CEN.PK2-1C than that in W303a no matter which media were used, and three key genes related to phenylalanine biosynthesis including ARO9, ARO7 and PHA2 were up-regulated in CEN.PK2-1C compared with W303a when cultured in YPD medium, whereas seven DEGs associated with phospholipid biosynthesis were up-regulated in W303a compared with CEN.PK2-1C when cultured in SD medium. The high phenylalanine produced by CEN.PK2-1C and high phospholipids produced by W303a indicated that CEN.PK2-1C may be more suitable for synthesis of natural products with phenylalanine as precursor, whereas W303a may be more appropriate for synthesis of phospholipid metabolites. This finding provides primary information for strain selection between W303a and CEN.PK2-1C for synthetic biology-based natural product production.

[Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor].

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Sleep duration and risk of hyperlipidemia: a systematic review and meta-analysis of prospective studies.

PURPOSE: Current studies indicate that the association between sleep duration and risk of hyperlipidemia is uncertain. This systematic review aimed to evaluate relevant prospective studies and make a definite conclusion. METHODS: Three databases were searched for prospective studies on the relationship between sleep duration and hyperlipidemia risk from their inception to October 2020. RESULTS: We identified twelve studies involving 114,439 participants. Follow-up for incident hyperlipidemia ranged from 200 days to 10 years. Neither long (RR:1.00, 95%CI:0.90-1.11, P > 0.05) nor short (RR:0.99, 95%CI:0.94-1.05, P > 0.05) sleep duration had a significant association with increased hyperlipidemia risk in adults. However, long sleep duration was decidedly associated with low HDL-C (RR:0.19, 95%CI: - 0.03-0.40, P < 0.05) and high triglycerides (RR: - 0.20, 95%CI: - 0.43-0.03, P < 0.05) in children and adolescents. CONCLUSION: Long sleep duration has strong associations with risks of low HDL-C and high triglycerides in children and adolescents. The mechanisms underlying this association deserves to be explored in future studies.

Toothbrushing frequency and gastric and upper aerodigestive tract cancer risk: A meta-analysis.

OBJECTIVE: Results of epidemiological studies evaluating the association between toothbrushing and gastric and upper aerodigestive tract (UADT) cancer risk showed inconsistent results. The purpose of this study was to evaluate the association between toothbrushing and gastric and UADT cancer risk and quantify the dose-response association between them. METHODS: We searched the PubMed, EMBASE and Cochrane Library databases to identify relevant studies on toothbrushing and gastric and UADT cancer risk. Statistical analyses were performed using STATA 12.0 software. RESULTS: A total of 30 studies of involving 1 194 017 participants met eligibility criteria and were included in the meta-analysis. Meta-analysis using a random-effect model showed that the high frequency of toothbrushing was associated with significantly reduced risk of gastric and UADT cancers (OR: 0.55, 95% CI 0.46-0.64, P < .05). Our dose-response analysis presented that every increased toothbrushing per day might reduce oral cavity cancer risk by 6%, pharyngeal cancer risk by 11%, laryngeal cancer risk by 3%, oesophageal cancer risk by 6% and gastric cancer risk by 4%. CONCLUSIONS: This meta-analysis suggested the negative relationship between frequency of toothbrushing and risk of gastric and UADT cancers. Toothbrushing may be a protective factor for gastric and UADT cancers. However, this association must be further validated through large prospective studies.

Influencing factors for mental health of general practitioners in Hebei Province under the outbreak of COVID-19: A cross-sectional study.

OBJECTIVE: This study aimed to understand the mental health status of general practitioners (GPs) in Hebei Province during the outbreak of coronavirus disease 2019, analyse influencing factors, and establish and evaluate the risk prediction model. METHODS: During February 25-29, 2020, a self-designed questionnaire was used to conduct an online survey of GPs in Hebei Province. The survey included a questionnaire on GPs' basic information, a questionnaire on GPs' working hardware and software facilities, and a questionnaire on GPs' mental health condition. A total of 1040 participants returned the completely filled valid questionnaire, and the answers were analyzed using the χ2 test, Wilcoxon rank-sum test and logistic regression with SPSS 20.0 software. Based on the results of binary logistic regression analysis, a risk prediction model was established, and the receiver operating characteristic curve was used to evaluate the model. RESULTS: The results showed that 44.2% (460/1040) of GPs expressed anxiety after the outbreak. Absence of prescreening clinics, fever clinics or isolated observation rooms in primary medical institutions; persons in the administrative area required to be isolated; low sleep quality of GPs and less than 6 hours of sleep per day of GPs were risk factors affecting the mental health status of GPs. Also, epidemic-related training and adequate protective equipment were the protective factors for the mental health status of GPs. CONCLUSION: The government should strengthen the infrastructure construction of community institutions, equip them with sufficient epidemic protection equipment, ensure the rest time of GPs and strengthen mental health training to ensure the mental and physical health of GPs.

smi-miR396b targeted SmGRFs, SmHDT1, and SmMYB37/4 synergistically regulates cell growth and active ingredient accumulation in Salvia miltiorrhiza hairy roots.

KEY MESSAGE: MIR396b had been cloned and overexpressed in Salvia miltiorrhiza hairy roots. MiR396b targets SmGRFs, SmHDT1, and SmMYB37/4 to regulate cell growth and secondary metabolism in S. miltiorrhiza hairy roots. Danshen (Salvia miltiorrhiza Bunge) is a valuable medicinal herb with two kinds of clinically used natural products, salvianolic acids and tanshinones. miR396 is a conserved microRNA and plays extensive roles in plants. However, it is still unclear how miR396 works in S. miltiorrhiza. In this study, an smi-MIR396b has been cloned from S. miltiorrhiza. Overexpression of miR396b in danshen hairy roots inhibited hairy root growth, reduced salvianolic acid concentration, but enhanced tanshinone accumulation, resulting in the biomass and total salvianolic acids respectively reduced to 55.5 and 72.1% of the control and total tanshinones increased up to 1.91-fold of the control. Applied degradome sequencing, 5'RLM-RACE, and qRT-PCR, 13 targets for miR396b were identified including seven conserved SmGRF1-7 and six novel ones. Comparative transcriptomics and microRNomics analysis together with qRT-PCR results confirmed that miR396b targets SmGRFs, SmHDT1, and SmMYB37/4 to mediate the phytohormone, especially gibberellin signaling pathways and consequentially resulted in the phenotype variation of miR396b-OE hairy roots. Furthermore, miR396b could be activated by methyl jasmonate, abscisic acid, gibberellin, salt, and drought stresses. The findings in this study indicated that smi-miR396b acts as an upstream and central regulator in cell growth and the biosynthesis of tanshinones and salvianolic acids, shedding light on the coordinated regulation of plant growth and biosynthesis of active ingredients in S. miltiorrhiza.

Causation Analysis of Risk Coupling of Gas Explosion Accident in Chinese Underground Coal Mines.

The coal mine production industry is a complex sociotechnical system with interactive relationships among several risk factors. Currently, causation analysis of gas explosion accidents is mainly focused on the aspects of human error and equipment fault, while neglecting the interactive relationships among risk factors. A new method is proposed through risk coupling. First, the meaning of risk coupling of a gas explosion is defined, and types of risk coupling are classified. Next, the coupled relationship and coupled effects among risk factors are explored through combining the interpretative structural modeling (ISM) and the NK model. Twenty-eight representative risk factors and 16 coupled types of risk factors are obtained through analysis of 332 gas explosion accidents in coal mines in China. Through the application of the combined ISM-NK model, an eight-level hierarchical model of risk coupling of a gas explosion accident is established, and the coupled degrees of different types of risk coupling are assessed. The hierarchical model reveals that two of the 28 risk factors, such as state policies, laws, and regulations, are the root risk factors for gas explosions; nine of the 28 risk factors, such as flame from blasting, electric spark, and local gas accumulation, are direct causes of gas explosions; whereas 17 of the risk factors, such as three-violation actions, ventilation system, and safety management, are indirect ones. A quantitative analysis of the NK model shows that the probability of gas explosion increases with the increasing number of risk factors. Compared with subjective risk factors, objective risk factors have a higher probability of causing gas explosion because of risk coupling.

Overexpression of SmMYB9b enhances tanshinone concentration in Salvia miltiorrhiza hairy roots.

KEY MESSAGE: A Salvia miltiorrhiza R2R3-MYB gene, SmMYB9b , has been cloned and characterized. Overexpression of SmMYB9b resulted in a significant improvement of tanshinones, the lipophilic active ingredients in danshen hairy roots. Plant R2R3-MYB transcription factors play important roles in various physiological and biochemical processes. Danshen (Salvia miltiorrhiza bunge) is a valuable medicinal herb with tanshinones and salvianolic acids as the principal bioactive ingredients. A number of putative R2R3-MYB transcription factors have been identified in the plant, but their function remains to be studied. Here, we report the cloning of SmMYB9b, an S20 R2R3-MYB member and its regulatory properties. SmMYB9b contains an open reading frame of 792 bp in length and encodes a 264-amino acid protein. Its transcripts were most abundant in blooming flowers (except for calyces) and increased with flower development. Exogenous abscisic acid strongly activated its transcription. Gibberellins and methyl jasmonate also showed a time-dependent activation effect on its transcription, but to a weaker degree. Overexpression of SmMYB9b in danshen hairy roots enhanced tanshinone concentration to 2.16 ± 0.39 mg/g DW, a 2.2-fold improvement over the control. In addition to increased tanshinone concentration, the hairy root growth and lateral hairy root formation were also suppressed. KEGG pathway enrichment analysis with de novo RNAseq data indicated that stress-response-related metabolic pathways, such as the terpenoid and plant hormone signal transduction pathways, were significantly enriched, implying possible implication of SmMYB9b in such processes. Quantitative RT-PCR analysis showed that the transcription of terpenoid biosynthetic genes SmDXS2, SmDXR, SmGGPPS, and SmKSL1 was significantly up-regulated in danshen hairy roots over expressing SmMYB9b. These data suggest that overexpression of SmMYB9b results in enhanced tanshinone concentration through stimulation of the MEP pathway. The present findings shed new light on elucidating the roles of R2R3-MYB in the biosynthesis of diterpenoids in S. miltiorrhiza.

Enhancing diterpenoid concentration in Salvia miltiorrhiza hairy roots through pathway engineering with maize C1 transcription factor.

Tanshinones are valuable natural diterpenoids from danshen (Salvia miltiorrhiza Bunge). Here, it was demonstrated that maize transcription factor C1 improved the accumulation of tanshinones by comprehensively upregulating the pathway genes, especially SmMDC and SmPMK in danshen hairy roots, yielding total tanshinones up to 3.59mg g(-1) of dry weight in line C1-6, a 3.4-fold increase compared with the control. Investigation of 2024bp of the SmMDC promoter fragment revealed that C1-mediated upregulation of terpenoid genes was possibly due to the direct interaction of C1 with its recognition sequences. The increase of tanshinones was accompanied by a decrease of salvianolic acid production, the other bioactive ingredient in danshen, by up to 37% compared with the control. This was the result of the downregulation of SmTAT, the entry-point gene of the tyrosine pathway, which promoted metabolic flow to anthocyanins rather than to salvianolic acids. Based on the findings of the present study, it was concluded that cis-acting elements shared by terpenoid and phenylpropanoid biosynthetic genes are partially responsible for the C1-stimulated variation of tanshinone and salvianolic acid concentrations.

[Optimization of induction and culture conditions for hairy roots of Salvia miltiorrhiza].

To establish induction and liquid culture system for hairy roots of Danshen (Salvia miltiorrhiza), Agrobacterium rhizogenes A4, LBA9402, 15834 as test bacterium were used to infect aseptic leaves of Danshen. The hairy roots were induced and positive transgenic hairy roots were selected with PCR using rolB and rolC as the target gene. Then hairy roots of S. miltiorrhiza were harvested and salvianolic acids were extracted with 70% methanol containing 1% formic acid. The content of salvianolic acid B (SalB) and rosmarinic acid (RA) were determined by HPLC. According to the above research results, the Danshen hairy roots induced by A. rhizogenes LBA9402 were inoculated into the following group of culture media: MSOH, MS, B5, and 6,7-V liquid media. Then the same methods of extraction and determination for the content of Danshen hairy roots were adopted. Last, the hairy roots of S. miltiorrhiza induced by A. rhizogenes LBA9402 were inoculated into the MSOH liquid media with different pH values. The content of salvianolic acid were extracted with 70% methanol containing 1% formic acid and determined by HPLC. As a result, three kinds of A. rhizogenes A4, LBA9402, 15834 could induce hairy roots and Ri plasmids were integrated into the genome of S. miltiorrhiza by PCR. Danshen hairy roots induced by A. rhizogenes LBA9402 and A4 produced much more salvianolic acid, which were (3.27 ± 0.37)% [including (1.04 ±0.36)% of RA and (2.22 ± 0.29)% of SalB] and (3.17 ± 0.20)% [including (0.92 ± 0.31)% of RA and (2.25 ± 0.26)% of SalB], respectively. Hairy roots induced by A. rhizogenes LBA9402 when they were cultured in MSOH liquid media produced much more salvianolic acid, which was (4.56 ± 0.36)%, including (1.12 ± 0.26)% of RA and (3.44 ± 0.23)% of SalB. Hairy roots induced by A. rhizogenes LBA9402 produced the most salvianolic acid when they were cultured in MSOH liquid media with the pH value 4.81, which was 4.85%, including 1.16% of RA and 3.69% of SalB. So Danshen hairy roots induced by A. rhizogenes LBA9402 and A4 produced much more salvianolic acid when they were cultured in MSOH liquid media with the pH value 4.81. The research had established the foundation on genetic engineering to improve the quality of S. miltiorrhiza.

Influencing factors of knowledge proficiency of general practitioners in rural China for esophageal cancer prevention and treatment: a cross-sectional study.

BACKGROUND: This study aims to investigate the knowledge of rural general practitioners (GPs) in esophageal cancer (EC) prevention and treatment in China and analyze relevant influencing factors, so as to improve the ability of rural GPs in EC prevention and treatment. METHODS: This cross-sectional study was conducted from November 5, 2021, to November 20, 2021. A self-designed questionnaire was used to conduct an online survey. Multivariable logistic regression models were used to identify the influencing factors of knowledge proficiency of GPs in rural China for EC prevention and treatment. RESULTS: This study included 348 participants from 12 rural areas in Hebei Province. The mean accuracy rate on all question items was 42.3% ± 10.67%. Sex (OR = 2.870, 95% CI: 1.519-5.423), educational level (OR = 3.256, 95% CI: 1.135-9.339), and comprehension of clinical practice guidelines for EC (OR = 4.305, 95% CI: 2.023-9.161) were significant predictors for GPs' knowledge proficiency of EC prevention and treatment (P < 0.05). CONCLUSIONS: The study indicated that knowledge proficiency of rural GPs of EC prevention and control still awaits to be improved. Sex, educational level, and comprehension of clinical practice guidelines for EC were significant predictors for their proficiency.

Environmental stimulus-responsive mesoporous silica nanoparticles as anticancer drug delivery platforms.

Currently, cancer poses a significant health challenge in the medical community. Traditional chemotherapeutic agents are often accompanied by toxic side effects and limited therapeutic efficacy, restricting their application and advancement in cancer treatment. Therefore, there is an urgent need for developing intelligent drug release systems. Mesoporous silica nanoparticles (MSNs) have many advantages, such as a large specific surface area, substantial pore volume and size, adjustable mesoporous material pore size, excellent biocompatibility, and thermodynamic stability, making them ideal carriers for drug delivery and release. Additionally, they have been widely used to develop novel anticancer drug carriers. Recently, MSNs have been employed to design responsive systems that react to the tumor microenvironment and external stimuli for controlled release of anticancer drugs. This includes factors within the intratumor environment, such as pH, temperature, enzymes, and glutathione as well as external tumor stimuli, such as light, magnetic field, and ultrasound, among others. In this review, we discuss the research progress on environmental stimulus-responsive MSNs in anticancer drug delivery systems, including internal and external environment single stimulus-responsive release and combined stimulus-responsive release. We also summarize the current challenges associated with environmental stimulus-responsive MSNs and elucidate future directions, providing a reference for the functionalization modification and practical application of these MSNs.

Dynamic changes in the gut microbiota during three consecutive trimesters of pregnancy and their correlation with abnormal glucose and lipid metabolism.

INTRODUCTION: During normal pregnancy, changes in the gut microbiota (GM) in response to physiological alterations in hormonal secretion, immune functions and homeostasis have received extensive attention. However, the dynamic changes in the GM during three consecutive trimesters of pregnancy and their relationship with glucose and lipid metabolism have not been reported. In this study, we aimed to investigate the dynamic changes in the diversity and species of the GM during three consecutive trimesters in women who naturally conceived, and their relationships with abnormal fasting blood glucose (FBG) and serum lipid levels. METHODS: A total of 30 pregnant women without any known chronic or autoimmune inflammatory disease history before pregnancy were enrolled during the first trimester. Serum and stool samples were collected during the first trimester, the second trimester, and the third trimester. Serum samples were tested for FBG and blood lipid levels, and stool specimens were analyzed by 16S rDNA sequencing. RESULTS: The abundance ratio of bacteroidetes/firmicutes showed an increasing tendency in most of the subjects (19/30, 63.3%) from the first to the third trimester. LEfSe analysis showed that the abundance of Bilophila was significantly increased from the first to the third trimester. In addition, at the genus level, the increased relative abundance of Mitsuokella, Clostridium sensu stricto and Weissella were potentially involved in the development of high FBG during pregnancy. The raised relative abundance of Corynebacterium, Rothia and Granulicatella potentially contributed to the occurrence of dyslipidemia during pregnancy. CONCLUSIONS: There are dynamic changes in the GM during the three trimesters, and the alterations in some bacterium abundance may contribute to the development of high FBG and dyslipidemia during pregnancy. Monitoring enterotypes and correcting dysbiosis in the first trimester may become new strategies for predicting and preventing glucolipid metabolism disorders during pregnancy.

Preoperative monocyte to high-density lipoprotein ratio as a predictor of survival outcome of gastric cancer patients after radical resection.

Aim: This study aimed to verify the prognostic value of monocyte to high-density lipoprotein ratio (MHR) in gastric cancer patients after radical resection. Methods: The Cox proportional hazards model was used to determine the risk variables for survival. Results: Older age (>60 years) (hazard ratio [HR]: 1.832; 95% CI: 1.167-2.725; p = 0.009), advanced tumor node metastasis stage (p < 0.05), lymphatic invasion (HR: 1.639; 95% CI: 1.114-3.032; p < 0.05), vascular invasion (HR: 2.002; 95% CI: 1.246-5.453; p = 0.028) and high MHR (HR: 1.154; 95% CI: 1.062-2.315; p = 0.021) were independent poor prognostic factors for gastric cancer patients after radical resection. Conclusion: Older age, advanced tumor node metastasis stage, lymphatic invasion, vascular invasion and high MHR were independent poor prognostic factors for gastric cancer patients after radical resection.

Analysis of the Interaction Mechanism of the Risk Factors of Gas Explosions in Chinese Underground Coal Mines.

Gas explosion accidents easily cause severe casualties in Chinese underground coal mines. Systematic analysis of accident causation is crucial for the prevention of gas explosions. This study identifies the representative risk factors of gas explosions and determines the interrelationship among these risk factors to highlight weak links and develop countermeasures. A total of 21 representative risk factors of gas explosions were identified through 128 case studies and front-line investigations. On this basis, a five-level hierarchical structure model of gas explosions was established to explore the complex interrelationships among the representative risk factors based on a combination of the Decision-Making Trial and Evaluation Laboratory (DEMATEL) and Interpretive Structural Modeling (ISM) methods. Moreover, the Matrix of Cross Impact Multiplications Applied to Classification (MICMAC) method was applied to achieve risk factor classification into four clusters, namely, driving factors, linkage factors, dependent factors and autonomous factors. The results indicated that the interrelationships and emergence properties among the risk factors may cause gas explosions, which should give more attention to the interrelationships among multiple factors and multiple subsystems for coal enterprises. Meanwhile, the complex geological conditions, poor safety supervision, inadequate safety education and training, incomplete execution safety regulations and poor safety technology and input are the long-term focus of risk management for coal enterprises. Finally, 10 countermeasures were proposed to control these representative risk factors and interrelationships. The results are helpful to the development of gas explosion risk management policies and to the preferential allocation of limited resources to resolve these issues.