Impact of PD-L1 gene polymorphisms and interactions with cooking with solid fuel exposure on tuberculosis.

Introduction Given that PD-L1 is a crucial immune checkpoint in regulating T cell responses, the aim of this study was to explore the impact of PD-L1 gene polymorphism and its interaction with cooking with solid fuel on susceptibility to tuberculosis (TB) in Chinese Han populations. Methods A total of 503 TB patients and 494 healthy controls were enrolled in this case-control study. Mass spectrometry (MS) technology was applied to genotype rs2297136 and rs4143815 of PD-L1 genes. The associations between SNPs and TB were assessed using unconditional logistic regression analysis. Marginal structural linear odds models were used to estimate the gene-environment interactions. Results Compared with genotype CC, genotypes GG and CG + GG at rs4143815 locus were significantly associated with susceptibility to TB (OR: 3.074 and 1.506, respectively, P<0.05). However, no statistical association was found between rs2297136 SNP and TB risk. Moreover, the relative excess risk of interaction (RERI) between rs4143815 of the PD-L1 gene and cooking with solid fuel was 2.365 (95% CI 1.922,2.809), suggesting positive interactions with TB susceptibility. Conclusion The rs4143815 polymorphism of the PD-L1 gene was associated with susceptibility to TB in Chinese Han populations. There were significantly positive interactions between rs4143815 and cooking with solid fuel.

Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

PLK4 reflects extrathyroidal invasion, high tumor stage and poor prognosis in papillary thyroid carcinoma patients.

Objective: This study aimed to assess the value of PLK4 as a biomarker in papillary thyroid carcinoma (PTC). Methods: This study reviewed 230 PTC patients receiving surgical resections. PLK4 was detected in tumor tissues and samples of normal thyroid gland tissues by immunohistochemistry. Results: PLK4 was elevated in tumor tissues versus normal thyroid gland tissues (p < 0.001). Tumor PLK4 was linked with extrathyroidal invasion (p = 0.036), higher pathological tumor stage (p = 0.030), node stage (p = 0.045) and tumor/node/metastasis stage (p = 0.022) in PTC patients. Tumor PLK4 immunohistochemistry score >3 was linked with shortened disease-free survival (p = 0.026) and overall survival (p = 0.028) and independently predicted poorer disease-free survival (hazard ratio: 2.797; p = 0.040). Conclusion: Tumor PLK4 reflects extrathyroidal invasion, higher tumor stage and shortened survival in PTC.

Association of Antihypertensive Drug-Related Gene Polymorphisms with Stroke in the Chinese Hypertensive Population.

Background: Antihypertensive therapy is crucial for preventing stroke in hypertensive patients. However, the efficacy of antihypertensive therapy varies across individuals, partially due to therapy-related genetic variations among individuals. We investigated the association of antihypertensive drug-related gene polymorphism with stroke in patients with hypertension. Methods: Demographic information, medication, and outcome data were obtained from a hypertensive patient management system, and a PCR fluorescence probe technique was used to detect 7 gene polymorphic loci (CYP2D6∗10, ADRB1, CYP2C9∗3, AGTR1, ACE, CYP3A5∗3, and NPPA), and these loci were compared between patients with and without stroke. Logistic regression was performed to analyze the association of these genetic variations with stroke risk in hypertensive patients while controlling for potential factors. Results: The prevalence of stroke in the hypertensive population in Changsha County of Hunan Province was 2.75%. The mutation frequencies of ADRB1 (1165G > C), CYP2D6∗10, CYP2C9∗3, AGTR1 (1166A > C), ACE (I/D), NPPA (2238T > C), and CYP3A5∗3 were 74.43%, 57.23%, 4.26%, 5.71%, 31.62%, 1.17%, and 69.58%, respectively. Univariate analysis revealed that ADRB1 polymorphism was associated with stroke (χ2 = 8.659, P < 0.05), with a higher stroke risk in the CC group than in the GC and GG groups (GC + GG). Multivariate unconditional logistic regression analysis showed that the CC genotype in ADRB1 (vs. the GC + GG genotype) was associated with an increased risk of stroke [odds ratio (OR) = 1.184, P<0.05] in hypertensive patients. No association was observed between CYP2D6∗10, CYP2C9∗3, AGTR1 (1166A > C), ACE (I/D), CYP3A5∗3, and NPPA (2238T > C) polymorphisms and stroke. Conclusions: ADRB1 (1165G > C) gene polymorphism is associated with the risk of stroke in Chinese hypertensive patients. The CC genotype is correlated with a higher risk of stroke than the GC + GG genotype.

Association between living arrangements and health risk behaviors among the Hakka older adults in Fujian, China.

BACKGROUND: Behavioral lifestyles are important social determinants of health. The impact of changes in living arrangements on behavioral lifestyles is currently under-explored. This study aims to examine the association between living arrangements and health risk behaviors among the Hakka older adults. METHODS: Data were extracted from China's Health-Related Quality of Life Survey for Older Adults 2018. Living arrangements were divided into five categories: living alone, living with spouse only, living with child, mixed habitation, and others. Five health risk behaviors, including unhealthy dietary patterns, drinking, smoking, irregular sleep practices, and physical inactivity were measured. Logistic regression analysis was used to assess the association between living arrangements and specific health risk behaviors, and generalized linear models were established to test the association between living arrangements and the number of health risk behaviors. RESULTS: A total of 1,262 Hakka older adults were included in this study. Compared to those living alone, those living with spouse only were less likely to have unhealthy dietary patterns (OR = 0.45, P < 0.05) and drinking (OR = 0.50, P < 0.05), those living with the child were less likely to experience unhealthy dietary patterns (OR = 0.35, P < 0.001), drinking (OR = 0.32, P < 0.001), smoking (OR = 0.49, P < 0.05), and physical inactivity (OR = 0.13, P < 0.01). Moreover, those who were living with child (ß = -0.78, P < 0.001) or mixed habitation (ß = -0.33, P < 0.05) tended to engage in fewer health risk behaviors than those living alone. CONCLUSIONS: This study suggests significant differences in health risk behaviors among the Hakka older adults with different living arrangements. Living with the child could reduce the occurrence of health risk behaviors in the Hakka older adults and thus maintain their health status.

Polymorphisms in PI3K/AKT genes and gene­smoking interaction are associated with susceptibility to tuberculosis.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages. AIM: This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB. METHODS: This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction. RESULTS: Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction. CONCLUSION: We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB.

Insights on enhancing piezocatalytic performance of Bi2WO6@PDA homojunction from phase coexistence and electron transfer mediators.

Piezocatalytic technology with controllable generation of reactive oxygen species (ROS) is emerging in wastewater treatment. This study employed the synergetic regulation of functional surface and phase interface modification to effectively accelerate redox reaction in piezocatalytic process. We anchored the conductive polydopamine (PDA) onto Bi2WO6 (BWO) using template method, in which a small amount of Bi precipitation to induce partial phase transition of BWO from tetragonal to orthorhombic (t/o) in virtue of simple calcination. ROS traceability studies have identified the synergistic relationship between charge separation and transfer. Polarization in two-phase coexistence is intimately modulated by the orthorhombic relative central cation displacement. The orthorhombic phase with large electric dipole moment significantly promotes the generation of piezoresistive effect of intrinsic tetragonal BWO and optimizes the charge distribution. PDA further overcomes the obstruction of carrier migration at the phases interface to accelerate the generation rate of free radicals. Consequently, the superior rhodamine B (RhB) piezocatalytic degradation rate of 0.10 and 0.32 min-1 were delivered by t/o-BWO and t/o-BWO@PDA, respectively. This work reveals a feasible polarization enhancement strategy for the phase coexistence, and flexibly introduces the in-situ synthesized economical polymer conductive unit into the piezocatalysts.

Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

Objective: To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). Methods: In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. Results: Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. Conclusion: Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Utility of video-assisted method for identifying and preserving the external branch of the superior laryngeal nerve during thyroidectomy.

Background: The EBSLN is vulnerable to damage during thyroidectomy, results in voice related complications, negatively affect patient quality of life, routine identification of the EBSLN prior to surgical manipulation is necessary for a complication-free thyroidectomy. We aimed to validate a video-assisted procedure for identifying and preserving the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy and analyze the EBSLN Cernea classification and the localization of the nerve entry point (NEP) from the insertion of the sternothyroid muscle. Methods: A prospective descriptive study was performed; 134 patients, who scheduled for lobectomy with an intraglandular tumor max diameter ≤ 4 cm and without extrathyroidal extension, were randomly divided into the video-assisted surgery (VAS) and conventional open surgery (COS) groups. We used the video-assisted surgical procedure for visually identifying the EBSLN directly, and compared the differences in the visual identification rate and total identification rate of the two groups. We also measured the localization of the NEP using the insertion of the sternothyroid muscle as a reference. Results: There was no statistically significant difference in clinical characteristics between the two groups. The visual identification rate and total identification rate were significantly higher in the VAS group than the COS group (91.04% vs. 77.61%, 100% vs. 89.6%). The EBSLN injury rate was 0 in both groups. The mean vertical distance (VD) of the NEP from the sternal thyroid insertion was 1.18 mm (SD 1.12 mm, range, 0-5 mm), with approximately 88.97% of the results occurring within the 0-2 mm range. The mean horizontal distance (HD) was 9.33 mm (SD 5.03 mm, range, 0-30 mm), with over 92.13% of the results occurring within the 5-15 mm range. Conclusion: Both the visual and total identification rates of the EBSLN were significantly higher in the VAS group. This method provided a good visual exposure rate of the EBSLN, aiding in identifying and protecting the EBSLN during thyroidectomy.

Subchronic Microcystin-LR Aggravates Colorectal Inflammatory Response and Barrier Disruption via Raf/ERK Signaling Pathway in Obese Mice.

Microcystin-LR (MC-LR) is an extremely poisonous cyanotoxin that poses a threat to ecosystems and human health. MC-LR has been reported as an enterotoxin. The objective of this study was to determine the effect and the mechanism of subchronic MC-LR toxicity on preexisting diet-induced colorectal damage. C57BL/6J mice were given either a regular diet or a high-fat diet (HFD) for 8 weeks. After 8 weeks of feeding, animals were supplied with vehicle or 120 µg/L MC-LR via drinking water for another 8 weeks, and their colorectal were stained with H&E to detect microstructural alterations. Compared with the CT group, the HFD and MC-LR + HFD-treatment group induced a significant weight gain in the mice. Histopathological findings showed that the HFD- and MC-LR + HFD-treatment groups caused epithelial barrier disruption and infiltration of inflammatory cells. The HFD- and MC-LR + HFD-treatment groups raised the levels of inflammation mediator factors and decreased the expression of tight junction-related factors compared to the CT group. The expression levels of p-Raf/Raf and p-ERK/ERK in the HFD- and MC-LR + HFD-treatment groups were significantly increased compared with the CT group. Additionally, treated with MC-LR + HFD, the colorectal injury was further aggravated compared with the HFD-treatment group. These findings suggest that by stimulating the Raf/ERK signaling pathway, MC-LR may cause colorectal inflammation and barrier disruption. This study suggests that MC-LR treatment may exacerbate the colorectal toxicity caused by an HFD. These findings offer unique insights into the consequences and harmful mechanisms of MC-LR and provide strategies for preventing and treating intestinal disorders.

Environmental noise exposure and health outcomes: an umbrella review of systematic reviews and meta-analysis.

BACKGROUND: Environmental noise is becoming increasingly recognized as an urgent public health problem, but the quality of current studies needs to be assessed. To evaluate the significance, validity and potential biases of the associations between environmental noise exposure and health outcomes. METHODS: We conducted an umbrella review of the evidence across meta-analyses of environmental noise exposure and any health outcomes. A systematic search was done until November 2021. PubMed, Cochrane, Scopus, Web of Science, Embase and references of eligible studies were searched. Quality was assessed by AMSTAR and Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Of the 31 unique health outcomes identified in 23 systematic reviews and meta-analyses, environmental noise exposure was more likely to result in a series of adverse outcomes. Five percent were moderate in methodology quality, the rest were low to very low and the majority of GRADE evidence was graded as low or even lower. The group with occupational noise exposure had the largest risk increment of speech frequency [relative risk (RR): 6.68; 95% confidence interval (CI): 3.41-13.07] and high-frequency (RR: 4.46; 95% CI: 2.80-7.11) noise-induced hearing loss. High noise exposure from different sources was associated with an increased risk of cardiovascular disease (34%) and its mortality (12%), elevated blood pressure (58-72%), diabetes (23%) and adverse reproductive outcomes (22-43%). In addition, the dose-response relationship revealed that the risk of diabetes, ischemic heart disease (IHD), cardiovascular (CV) mortality, stroke, anxiety and depression increases with increasing noise exposure. CONCLUSIONS: Adverse associations were found for CV disease and mortality, diabetes, hearing impairment, neurological disorders and adverse reproductive outcomes with environmental noise exposure in humans, especially occupational noise. The studies mostly showed low quality and more high-quality longitudinal study designs are needed for further validation in the future.

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. OBJECTIVE: The aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. METHODS: We used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. RESULTS: The cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. CONCLUSIONS: Existing targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

Disease burden and attributable risk factors of neonatal disorders and their specific causes in China from 1990 to 2019 and its prediction to 2024.

BACKGROUND: Neonatal health is a cornerstone for the healthy development of the next generation and a driving force for the progress of population and society in the future. Updated information on the burden of neonatal disorders (NDs) are of great importance for evidence-based health care planning in China, whereas such an estimate has been lacking at national level. This study aims to estimate the temporal trends and the attributable burdens of selected risk factors of NDs and their specific causes in China from 1990 to 2019, and to predict the possible trends between 2020 and 2024. METHODS: Data was explored from the Global Burden of Disease study (GBD) 2019. Six measures were used: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute numbers and age-standardized rates (with 95% uncertainty intervals) were calculated. The specific causes of NDs mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). An autoregressive integrated moving average (ARIMA) model was used to forecast disease burden from 2020 to 2024. RESULTS: There were notable decreasing trends in the number of deaths (84.3%), incidence (30.3%), DALYs (73.5%) and YLLs (84.3%), while increasing trends in the number of prevalence (102.3%) and YLDs (172.7%) from 1990 to 2019, respectively. The corresponding age-standardized rates changed by -74.9%, 0.1%, -65.8%, -74.9%, 86.8% and 155.1%, respectively. Four specific causes of NDs followed some similar and different patterns. The prediction results of the ARIMA model shown that all measures still maintained the original trends in the next five years. Low birth weight, short gestation, ambient particulate matter pollution and household air pollution from solid fuels were the four leading risk factors. CONCLUSION: The health burden due to NDs is declining and is likely to continue to decline in the future in China. Delaying the increasing burden of disability may be the next target of concern. Targeted prevention and control strategies for specific causes of NDs are urgently needed to reduce the disease burden.

Bibliometric analysis of the 100 most-cited papers about the role of gut microbiota in irritable bowel syndrome from 2000 to 2021.

AIM: Over the last few decades, gut microbiota research has been the focus of intense research and this field has become particularly important. This research aimed to provide a quantitative evaluation of the 100 most-cited articles on gut microbiota and IBS and highlight the most important advances in this field. METHODS: The database Web of Science Core Collection was used to download the bibliometric information the top 100 most-cited papers. Microsoft Excel 2021, CiteSpace, VOSviewer, R software, and an online analytical platform ( https://bibliometric.com/ ) were was applied to perform bibliometric analysis of these papers. RESULTS: The total citation frequency in the top 100 article ranged from 274 to 2324, with an average citation of 556.57. A total of 24 countries/regions made contributions to the top 100 cited papers, and USA, Ireland, and China were the most top three productive countries. Cryan JF was the most frequently nominated author, and of the top 100 articles, 20 listed his name. Top-cited papers mainly came from the Gastroenterology (n = 13, citations = 6373) and Gut (n = 9, citations = 3903). There was a significant citation path, indicating publications in molecular/biology/immunology primarily cited journals in molecular/biology/genetics fields. Keywords analysis suggested that the main topics on gut microbiota and IBS were mechanisms of microbiome in brain-gut axis." Behavior" was the keyword with the strongest burst strength (2.36), followed by "anxiety like behavior" (2.24), "intestinal microbiota" (2.19), and "chain fatty acid" (1.99), and "maternal separation" (1.95). CONCLUSION: This study identified and provided the bibliometric information of the top 100 cited publications related to gut microbiota and IBS. The results provided a general overview of this topic and might help researchers to better understand the evolution, Influential findings and hotspots in researching gut microbiota and IBS, thus providing new perspectives and novel research ideas in this specific area.

The association of iron status, supplement iron in the first-trimester pregnancy with gestational diabetes mellitus: A nested case-control study.

AIMS: The objective of this study was to examine whether the level of iron and iron supplements in the first-trimester pregnancy is associated with gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study using data from an established cohort in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. Iron status indicators were tested in early pregnancy. Information on iron supplements use was collected by questionnaires. Binary logistic regression was used to obtain odds ratio (OR). The relative excess risk of interaction (RERI) was applied to evaluate the interaction. RESULTS: We observed that pregnant women with normal ferritin levels (≥30 ng/ml) and iron supplements were associated with a 3.701-fold increased risk of GDM (OR: 3.701, 95% CI: 1.689-8.112) compared with the ferritin <30 ng/ml and without iron supplements group. Similarly, pregnant women with normal serum iron (SI) levels (≥9 µmol/L) and iron supplements were associated with a 5.447-fold increased risk of GDM (OR: 5.447, 95% CI: 2.246-13.209) compared with the SI < 9 µmol/L and without iron supplement group. We found an additive interaction between ferritin and iron supplements on the presence of GDM (RERI: 1.164, 95%CI: 0.333-1.994) and SI and iron supplements on the risk of GDM (RERI: 6.375, 95%CI: 4.494-8.256). CONCLUSION: Pregnant women with normal ferritin or SI levels and iron supplements could significantly increase the risks for GDM.

Evaluation of Combined use of Fecal Multigene Mutation Test and Fecal Immunochemical Test for Colorectal Cancer Screening.

BACKGROUND: The aim was to investigate the value of concomitant use of fecal KRAS-APC-p53-BRAF mutation test and a fecal immunochemical test (FIT) for colorectal cancer (CRC) screening. METHODS: Stool samples of 279 subjects were collected from the Fujian provincial hospital and divided into five groups: CRC (n = 82); advanced adenoma (AA, n = 76); non-advanced adenoma (NAA, n = 24); healthy control (n = 85); and interference group (n = 12). All stool samples were tested using a fecal multigene mutation (KRAS-APC-p53-BRAF) Kit and FIT. RESULTS: The sensitivity of combined use of fecal multigene mutation test and FIT for detecting CRC [84.15% (69/ 82)] was significantly higher than that of fecal multigene mutation test [47.56% (39/82), p < 0.001] or FIT [71.95% (59/82), p < 0.001] alone. The sensitivity of combined use for detection of AA [48.68% (37/76)] was also significantly higher than that of multigene mutation test [26.32% (20/76), p < 0.001] or FIT [28.95% (22/76), p < 0.001] alone. The specificity of combined use for detection of NAA and healthy control was 87.16%. CONCLUSIONS: The combination of fecal multigene (KRAS-APC-p53-BRAF) mutation test and FIT has greater sensitivity than alone and may be a useful noninvasive method for CRC screening.

Case report: Balloon compression for cervical chyle leakage post neck dissection.

Postoperative chyle leakage (CL) is a rare but severe complication after neck dissection, and most patients with this complication can be treated conservatively. However, in patients with high-flow leakage, efficient and well-tolerated conservative treatment options are still lacking, and the treatments can be complicated. In this study, we report a case with CL of 1100 ml/day after neck dissection that was successfully treated by balloon compression.

AST-to-ALT ratio in the first trimester and the risk of gestational diabetes mellitus.

Background: Aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) has been reported affect the risk of type 2 diabetes (T2DM), but it is uncertain if it has relationship with gestational diabetes mellitus (GDM). Objectives: Our study aimed to investigate the association between AST/ALT ratio in the first trimester and the risk of subsequent development of GDM. Method: This prospective cohort study enrolling 870 pregnant women, 204 pregnant women with missing data or liver diseases were excluded, 666 pregnant women were included in this study containing 94 GDM women. Blood samples were collected in the first trimester. Univariate analysis and multivariate logistic regression were used to evaluate the association between AST/ALT and GDM. Nomogram was established based on the results of multivariate logistic analysis. Receiver Operating Characteristic (ROC) curves and calibration curves were used to evaluate the predictive ability of this nomogram model for GDM. Decision curve analysis (DCA) was used to examine the clinical net benefit of predictive model. Results: AST/ALT ratio (RR:0.228; 95% CI:0.107-0.488) was associated with lower risk of GDM after adjusting for confounding factors. Indicators used in nomogram including AST/ALT, maternal age, preBMI, waist circumference, glucose, triglycerides, high density lipoprotein cholesterol and parity. The area under the ROC curve (AUC) value of this predictive model was 0.778, 95% CI (0.724, 0.832). Calibration curves for GDM probabilities showed acceptable agreement between nomogram predictions and observations. The DCA curve demonstrated a good positive net benefit in the predictive model. Conclusions: The early AST/ALT level of pregnant women negatively correlated with the risk of GDM. The nomogram including AST/ALT at early pregnancy shows good predictive ability for the occurrence of GDM.

Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway.

Microcystin-LR (MC-LR) is a very common toxic cyanotoxins threating ecosystems and the public health. This study aims to explore the long-term effects and potential toxicity mechanisms of MC-LR exposure at environmental levels on colorectal injury. We performed histopathological, biochemical indicator and multi-omics analyses in mice with low-dose MC-LR exposure for 12 months. Long-term environmental levels of MC-LR exposure caused epithelial barrier disruption, inflammatory cell infiltration and an increase of collagen fibers in mouse colorectum. Integrated proteotranscriptomics revealed differential expression of genes/proteins, including CSF1R, which were mainly involved in oxidative stress-induced premature senescence and inflammatory response. MC-LR induced chronic inflammation and fibrosis through oxidative stress and CSF1R/Rap1b signaling pathway were confirmed in cell models. We found for the first time that long-term environmental levels of MC-LR exposure caused colorectal chronic inflammation, fibrosis and barrier disruption via a novel CSF1R/Rap1b signaling pathway. Moreover, MC-LR changed the gut microbiota and microbial-related metabolites in a vicious cycle aggravating colorectal injury. These findings provide novel insights into the effects and toxic mechanisms of MC-LR and suggest strategies for the prevention and treatment of MC-caused intestinal diseases.