CircCOL1A1 promotes proliferation, migration, and invasion of colorectal cancer (CRC) cells and glutamine metabolism through GLS1 up-regulation by sponging miR-214-3p.

BACKGROUND: Circular ribose nucleic acids (circRNAs), an abundant type of noncoding RNAs, are widely expressed in eukaryotic cells and exert a significant impact on the initiation and progression of various disorders, including different types of cancer. However, the specific role of various circRNAs in colorectal cancer (CRC) pathology is still not fully understood. METHODS: The initial step involved the use of quantitative reverse transcription polymerase chain reaction (RT-qPCR) to assess the expression levels of circRNAs and messenger RNA (mRNA) in CRC cell lines and tissues. Subsequently, functional analyses of circCOL1A1 knockdown were conducted in vitro and in vivo through cell counting kit (CCK)-8, colony formation and transwell assays, as well as xenograft mouse model of tumor formation. Molecular expression and interactions were investigated using luciferase reporter assays, Western blot analysis, RNA immunoprecipitation (RIP), and immunohistochemical staining. RESULTS: The RT-qPCR results revealed elevated levels of circCOL1A1 expressions in CRC tissues and cell lines as compared to the normal counterparts. In addition, circCOL1A1 expression level was found to be correlated with TNM stage, lymph node metastases, distant metastases, and invasion. Knockdown of circCOL1A1 resulted in impaired invasion, migration, and proliferation of CRC cells, and suppressed tumor generation in the animal model. We further demonstrated that circCOL1A1 could act as a sponge for miR-214-3p, suppressing miR-214-3p activity and leading to the upregulation of GLS1 protein to promote glutamine metabolism. CONCLUSION: These findings suggest that circCOL1A1 functions as an oncogenic molecule to promote CRC progression via miR-214-3p/GLS1 axis, hinting on the potential of circCOL1A1 as a therapeutic target for CRC.

Effects of Nutrient Solution Application Rates on Yield, Quality, and Water-Fertilizer Use Efficiency on Greenhouse Tomatoes Using Grown-in Coir.

The yield, quality, and water-fertilizer use efficiency of crops are important parameters for assessing rational water and fertilizer management. For an optimal water and fertilizer system with respect to the nutrient solution irrigation of greenhouse tomatoes using cultivation substrates, a two-year greenhouse cultivation experiment was conducted from 2022 to 2023. Three drip fertigation treatments (T1, T2, and T3) were implemented in the experiment, where nutrient solutions were supplied when the substrate's water content reached 60%, 70%, and 80%. The frequency of nutrient solution applications is based on weighing coconut coir strips in the morning and evening at 7:00 to determine the daily water consumption of plants. Nutrient solutions were supplied when the substrate's water content reached the lower limit, and the upper limit for nutrient supply was set at 100% of the substrate water content. The nutrient solution application was carried out multiple times throughout the day, avoiding the midday heat. The nutrient solution formula used was the soilless tomato cultivation formula from South China Agricultural University. The results show that plant height and the leaf area index rapidly increased in the early and middle stages, and later growth tended to stabilize; the daily transpiration of tomatoes increased with an increase in nutrient solution supply, and it was the greatest in the T3 treatment. Between the amount of nutrient solution application and the number of years, the yield increased with the increase of the amount of nutrient solution, showing T3 > T2 > T1. Although the average yield of the T2 treatment was slightly lower than that of the T3 treatment by 3.65%, the average irrigation water use efficiency, water use efficiency, and partial fertilizer productivity of the T2 treatment were significantly higher than those of the T3 treatment by 29.10%, 19.99%, and 28.89%, respectively (p < 0.05). Additionally, soluble solid, vitamin C, and soluble sugar contents and the sugar-acid ratio of tomatoes in the T2 treatment were greater than those in the other two treatments (p < 0.05). Using the TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) method, it was concluded that the nutrient solution application rate of 70% can significantly increase water and fertilizer use efficiency and markedly improve the nutritional and flavor quality of the fruit without a significant reduction in yield. This finding provides significant guidance for the high-yield, high-quality, and efficient production of coconut coir-based cultivated tomatoes in greenhouses.

Comprehensive analysis of ADGRE5 gene in human tumors: Clinical relevance, prognostic implications, and potential for personalized immunotherapy.

Purpose: The Adhesion G protein receptor E5 (ADGRE5) gene is involved in a wide range of biological functions in human tumors; however, its specific molecular mechanism and significance in the analysis of human tumors have not yet been determined. Here, we provide a comprehensive genomic architecture of ADGRE5 in the tumor immune microenvironment and its clinical relevance across a broad range of solid tumors. Methods: In this study, we used publicly available bioinformatics databases, with a primary focus on The Cancer Genome Atlas (TCGA) database and GTEx data, to conduct a comprehensive analysis of the impact on patient prognosis associated with ADGRE5. Results: Statistics of more than 30 solid tumors from TCGA and Cancer Cell Line Encyclopedia (CCLE) were examined. ADGRE5 was differentially expressed in several cancers and was significantly associated with survival outcomes. Higher ADGRE5 levels were associated with worse prognosis in adrenocortical carcinoma, low grade glioma of the brain (LGG), lung squamous cell carcinoma, liver hepatocellular carcinoma, and uveal melanoma (UVM). Additionally, ADGRE5 was found to be an independent risk factor for LGG and UVM. The clinical relevance of ADGRE5 in tumor immunogenicity was further investigated. The expression level of ADGRE5 was not only strongly associated with tumor infiltration, such as tumor-infiltrating immune cells and immune subtypes, but also with tumor mutation burden, pyroptosis, and epithelial-mesenchymal transition in various types of cancer (P < 0.05). Furthermore, we noted that ADGRE5 exhibited a positive association with targeted drug sensitivity and conversely, a negative association with traditional chemotherapeutic drug sensitivity. Thus, ADGRE5 is expected to be a guiding marker gene for clinical prognosis and personalized tumor immunotherapy.

An EM-Tracked Approach for Calibrating the 3D Pose of Flexible Endoscopes.

Flexible endoscopes are ideal instruments for visualizing and diagnosing the inner surfaces of organs via a minimally invasive incision. Calibrating a flexible endoscope is a troublesome yet inevitable process in image-based tools tracking. Aiming to simplify the calibration process, we propose an electromagnetic (EM)-tracked calibration approach that does not require any predefined poses of the EM sensor. A three-stage calibration protocol was presented in an extensor. First, the orientation of the endoscope tube was derived by conducting a circular rotation of the endoscope around its axis utilizing a pair of tightly bearing stands. Second, the 3D position of the endoscope tip was acquired by having the tip come into contact with a flat plane. Third, the pose model of the bending section was derived and transformed into the local coordinate system of the EM sensor attached to the endoscope handle. To assess the accuracy of the proposed calibration approach, two experiments were designed and performed. Experimental results indicate accuracies of 0.09 ± 0.06 deg and 0.03 ± 0.19 deg in the estimation of the endoscope tube orientation and 0.52 ± 0.29, 0.33 ± 0.11, and 0.29 ± 0.17 mm in the x, y, and z estimations of the endoscope tip position, respectively. The proposed approach is accurate and easy to operate, does not require the employment of custom calibration markers, and can be used not only in surgical training systems but also in the endoscopic-based tools tracking.

A New "Mix and Measure" Method for Rapid Quantitative Determination of Alkalinity Based on Proton Equilibrium and Definite Integral of Buffer Capacity.

Alkalinity is crucial in environmental control of ecosystems, wastewater and drinking water treatment, and industrial process control. In this work, we reported a new equation for calculating alkalinity based on the definition of buffer capacity in acid-base buffer solutions and the quantitative relationship between the buffer capacity and pH changes. A "mix and measure" method was developed using this new equation, involving mixing a solution with unknown alkalinity and a standard solution in a specific volume ratio, followed by measuring the pH after mixing. The alkalinity of the solution can be calculated using the newly developed equation. The "mix and measure" method is much more efficient than traditional titration methods for determination of alkalinity because it is restricted by the titration stoichiometric point. Additionally, we demonstrated the rapid determination of the alkalinity for a series of solutions using a portable detection system. This system exhibited precision and accuracy comparable to those of traditional titration methods. The portable system offers great potential for the on-site and real-time determination of alkalinity for industrial control and environmental monitoring purposes.

Association of the L3MBTL3 rs1125970 and rs4897367 Gene Polymorphisms With Coronary Heart Disease Susceptibility in the Chinese Population: A Case-Control Study.

ABSTRACT: Coronary heart disease (CHD) is a prevalent heart disease with high incidence and mortality rates worldwide, and its pathogenesis is related to genetic factors. L3MBTL3 has been reported to be potentially linked to CHD susceptibility. This study aims to explore the correlation between L3MBTL3 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese population. Three SNPs (rs1125970 A/T, rs4897367 T/C, and rs2068957 A/G) in L3MBTL3 from 649 patients with CHD and 649 healthy controls were genotyped using the Agena MassARRAY platform. The relationship between SNPs and CHD risk was evaluated by logistic regression analysis. Our study indicated that rs1125970 (TT: odds ratio [OR] = 0.76, P = 0.014) and rs4897367 (TT: OR = 0.74, P = 0.021) were related to a decreased susceptibility to CHD. Stratified analyses showed that rs1125970 could reduce the risk of CHD in males, subjects aged <60 years, with a body mass index <24 kg/m 2 , and nonhypertensive patients. rs4897367 exerted a risk-decreasing influence on CHD in nondiabetic patients. In the haplotype analysis, individuals with the T rs4897367 A rs2068957 haplotype were less likely to develop CHD (OR = 0.74, P = 0.024). In summary, L3MBTL3 rs1125970 and rs4897367 were significantly correlated with a decreased susceptibility to CHD in the Chinese population.

Inorganic phosphate regulated high luminescence NaYF4:Yb3+, Er3+ as an iron ion fluorescent nanoprobe.

The iron ion in industrial circulating cooling water is an important indicator for early warning of equipment corrosion and control level. It is interesting to construct an upconversion luminescence iron ion nanoprobe with a common inorganic phosphate water treatment agent. Herein, inorganic phosphate sodium hexametaphosphate (SHMP) was used to regulate the morphology and functionalization of NaYF4:Yb3+, Er3+ upconversion luminescent nanoprobe (UCNPs) and applied to fluorometric detection of trace Fe(III) in water based on the fluorescence quenching which is caused by the selective coordination between hexametaphosphate on the surface of UCNPs and Fe(III). The structure, morphology, and luminous intensity of UCNPs were regulated by disodium hydrogen phosphate (ADSP), sodium tripolyphosphate (STPP) and sodium hexametaphosphate(SHMP). The UCNPs functionalized with SHMP has high sensitivity and selectivity for Fe(III) detection. The linear range and detection limit are 1.0-50 µM and 0.2 µM, respectively. The method has satisfactory results for the detection of trace Fe(III) in industrial circulating cooling water.

Efficacy of unblinded and blinded intermittently scanned continuous glucose monitoring for glycemic control in adults with type 1 diabetes.

Objective: Intermittently scanned continuous glucose monitoring (isCGM) is used for unblinded or blinded monitoring of interstitial glucose. We aimed to compare the efficacy of blinded and unblinded isCGM with the FreeStyle Libre system for glycemic control in adults with type 1 diabetes (T1D). Research design and methods: This randomized clinical trial conducted between October 2018 and September 2019 across four endocrinology practices in China included 273 adults aged ≥18 years with T1D, who were randomly divided in a 2:1 ratio into the unblinded (n = 199) or blinded isCGM group (n = 78). In the blinded group, the clinician used FreeStyle Libre Pro system for monitoring, but self-monitoring was also performed by the patients. Results: Two hundred sixteen (78%) participants completed the study (152 [75%] in the unblinded and 64 [82%] in the blinded group). At 12 weeks, a significant increase in TIR (3.9-10.0 mmol/L) was only observed in the unblinded group, along with a significant decrease in hyperglycemia (>13.9 mmol/L), hypoglycemia (<3.0 mmol/L), glycemic variability. Further, the mean HbA1c reduction from baseline to 12 weeks was 0.5% in the unblinded isCGM group and 0.4% in the blinded isCGM group respectively (P < 0.001), but the significance did not remain after adjustment for between-group differences. Finally, 99.5% of the blinded isCGM values and 93.8% the of unblinded isCGM values were obtained at the final visit. Conclusions: The unblinded isCGM system was associated with benefits for glucose management, but nearly 100% of the attempted profiles were obtained successfully with the blinded isCGM system. Thus, combining real-time and retrospective data with isCGM might be the most impactful way to utilize flash glycemic monitoring devices.

microRNA regulation of skin pigmentation in golden-back mutant of crucian carp from a rice-fish integrated farming system.

BACKGROUND: MicroRNAs (miRNAs) are endogenous small non-coding RNAs (21-25 nucleotides) that act as essential components of several biological processes. Golden-back crucian carp (GBCrC, Carassius auratus) is a naturally mutant species of carp that has two distinct body skin color types (golden and greenish-grey), making it an excellent model for research on the genetic basis of pigmentation. Here, we performed small RNA (sRNA) analysis on the two different skin colors via Illumina sequencing. RESULTS: A total of 679 known miRNAs and 254 novel miRNAs were identified, of which 32 were detected as miRNAs with significant differential expression (DEMs). 23,577 genes were projected to be the targets of 32 DEMs, primarily those involved in melanogenesis, adrenergic signaling in cardiomyocytes, MAPK signaling pathway and wnt signaling pathway by functional enrichment. Furthermore, we built an interaction module of mRNAs, proteins and miRNAs based on 10 up-regulated and 13 down-regulated miRNAs in golden skin. In addition to transcriptional destabilization and translational suppression, we discovered that miRNAs and their target genes were expressed in the same trend at both the transcriptional and translational levels. Finally, we discovered that miR-196d could be indirectly implicated in regulating melanocyte synthesis and motility in the skin by targeting to myh7 (myosin-7) gene through the luciferase reporter assay, antagomir silencing in vivo and qRT-PCR techniques. CONCLUSIONS: Our study gives a systematic examination of the miRNA profiles expressed in the skin of GBCrC, assisting in the comprehension of the intricate molecular regulation of body color polymorphism and providing insights for C. auratus breeding research.

Effect of resistance vs. aerobic exercise in pre-diabetes: an RCT.

BACKGROUND: This study aimed to assess the different impacts of aerobic and resistance exercise intervention on pre-diabetes and its possible influencing factor (obesity) to identify which exercise intervention mode was better for pre-diabetes to control their blood glucose levels. METHODS: Single-blind randomized controlled trial. Participants were recruited from Southwest Hospital between February 2016 and May 2017 and randomly divided into three groups using stratified randomization: aerobic exercise (A), resistance exercise (R), and control (C). The effects of each group were analyzed, and the relationship with obesity was investigated following a 12-week intervention. RESULTS: Eighty participants were enrolled (9 were lost, and 1 was excluded). Finally, 26 participants were included in group A, 23 in group R, and 21 in group C. In groups A and R, FPG, OGTT 2-h PG, and HOMA2-IR decreased by 6.17% (P = 0.001) and 4.81% (P = 0.019), 20.39% (P < 0.001) and 16.50% (P < 0.001), and 8.34% (P = 0.026) and 18.31% (P = 0.001, superior to that in group A), respectively (all P < 0.001 compared with group C, with no significant differences between groups A and R). The ratio of reversal to euglycemia was 69.2% (P = 0.003 compared with group C) in group A and 43.5% (P = 0.213 compared with group C) in group R. The decreased ratio of GSP in group R was greater (65.2%, P = 0.008 compared with group C) compared with group A (38.5%, P = 0.355 compared with group C). Decreases in the parameters BMI (3.1 ± 3.2% P < 0.001, moderately positive correlation with the decreased FPG level, r = 0.498, P = 0.010, two-tailed) and waist circumference (3.1 ± 2.7% P < 0.001) were noted in group A, but no significant correlations were noted between other indicators in group R. CONCLUSIONS: Both resistance and aerobic exercise can control and reverse IGR. Compared with aerobic exercise, resistance exercise may be superior in terms of GSP and IR improvement. Aerobic exercise decreases blood glucose levels through weight loss. However, the effect of resistance exercise might not be mediated via weight loss and obesity control. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038304. Registered on September 17, 2020.

Effects of liraglutide or lifestyle interventions combined with other antidiabetic drugs on abdominal fat distribution in people with obesity and type 2 diabetes mellitus evaluated by the energy spectrum ct: A prospective randomized controlled study.

Objective: To study the effects of liraglutide or lifestyle interventions combined with other antidiabetic drugs on glucose metabolism and abdominal fat distribution in patients with obesity and type 2 diabetes mellitus (T2DM). Methods: From April 30, 2020, to April 30, 2022, a prospective randomized controlled study was carried out at the Endocrinology Department of Beijing Hospital, the National Center of Gerontology. According to the in- and exclusion criteria and by the random table method, revisited T2DM patients were selected as the research subjects and were allocated into a Study group (taking liraglutide) and a Control group (underwent lifestyle interventions). All patients received continuous 12-weeks interventions to the endpoint, and the changes of value [Δ=(endpoint)-(baseline)] of physical measurements, blood tests, the energy spectrum CT examination results, and body composition analysis results were analyzed and compared. Results: A total of 85 people completed this study, and among them, 47 were in the Study group and 38 were in the Control group. Compared with the Control group, the changes of hemoglobin A1c (HbA1c) level (-0.78 ± 1.03% vs. -1.57 ± 2.00%, P=0.025), visceral fat area (0.91 ± 16.59 cm2 vs. -7.1 ± 10.17 cm2, P=0.011), and subcutaneous fat area of abdomen [0 (-18.75, 15.5) cm2 vs. -16.5 (-41.75, -2.25) cm2, P=0.014] were all greater in the Study group. The adverse events caused by liraglutide were mainly concentrated in the gastrointestinal system and all of them were minor adverse events. Conclusion: Liraglutide can be the drug of choice for weight management and reduction of abdominal fat distribution in patients with obesity and T2DM.

Case report: Prompt response to radiotherapy and chemotherapy combined with crizotinib in gingival sarcomatoid squamous cell carcinoma with MET 14 mutation.

Background: As a kind of squamous cell carcinoma of head and neck (HNSCC), gingival sarcomatoid squamous cell carcinoma (GSSCC) is a rare biphasic malignant neoplasm. To date, surgical resection was often utilized for gingival squamous cell carcinoma (GSCC), while for patients with advanced gingival carcinoma who cannot tolerate surgery, radiotherapy and chemotherapy can be regarded as a treatment strategy. Many molecular-targeted drugs were investigated and approved for the treatment of malignant diseases, including hematologic diseases and solid tumors. Although targeted therapies such as EGFR inhibitors have shown therapeutic efficacy in HNSCC, there are still some patients who cannot benefit from it. New therapeutic targets and strategies should be further explored. Case presentation: An 83-year-old woman was referred to our hospital with left lower gingival mass for more than 1 month in June 2021. Pathologic diagnosis is sarcomatoid squamous cell carcinoma. Due to the large tumor at the time of diagnosis and poor quality of life, the patient was intolerant to surgery, so she was given radiotherapy (RT) combined with concurrent chemotherapy (CT) with albumin bound paclitaxel. According to next-generation sequencing (NGS) results (MET exon 14 skipping mutation-positive), she was treated with crizotinib, a tyrosine kinase inhibitor that targets MET. Through the comprehensive treatment, the patient's condition promptly improved, clinical complete remission (CR) was achieved in 2 months, and 9-month progression-free survival (PFS) was obtained. She finally died from non-cancer-related diseases. Conclusion: Here we report the treatment of a GSSCC patient with MET mutation, who responded to crizotinib promptly and positively. It provides a new reference for understanding MET abnormalities in GSSCC and offers a new idea for the targeted treatment of gingival carcinoma.

Prevalence of obstructive sleep apnea syndrome in hospitalized patients with type 2 diabetes in Beijing, China.

AIMS/INTRODUCTION: To estimate the prevalence, and patient clinical and demographic profile, as well as risk factors associated with obstructive sleep apnea syndrome (OSAS) in hospitalized patients with type 2 diabetes mellitus in Beijing, China. MATERIALS AND METHODS: Hospitalized adult patients with type 2 diabetes mellitus were consecutively screened and invited for an overnight polysomnography from four hospitals in Beijing, China, from May 2016 to February 2017. We used the American Academy of Sleep Medicine 2012 polysomnography recording techniques and scoring criteria to identify the type of apnea and the severity of OSAS. The χ2 -test was used to evaluate differences between groups regarding the prevalence, and demographic and other clinical parameters. RESULTS: A total of 735 patients were found eligible for the study, of whom 309 patients completed the overnight polysomnography. The mean age of the patients was 58.2 ± 10.9 years, and most (67.3%) were men. The prevalence of overall (apnea hypopnea index ≥5/h), moderate-to-severe (apnea hypopnea index ≥15/h) and severe (apnea hypopnea index ≥30/h) OSAS was 66.3% (95% confidence interval 60.8-71.6%), 35.6% (95% confidence interval 30.3-41.2%) and 16.5% (95% confidence interval 12.5-21.1%), respectively. Central and mixed apnea contributed 12% to all sleep-disordered breathing. With the aggravation of OSAS, the combined prevalence for central, mixed and obstructive apnea increased from 57% to 70%. We found OSAS to be associated with older age, obesity, self-reported snoring and apnea, and diabetes complications. CONCLUSIONS: Guidelines on screening and treatment of OSAS among hospitalized patients with diabetes are needed to direct the routine practice for diabetes endocrinologists for optimal clinical care of such patients.

Comparing the effects of twice-daily exenatide and insulin on renal function in patients with type 2 diabetes mellitus: secondary analysis of a randomized controlled trial.

This is a secondary analysis of a randomized controlled trial (RCT) on the effects of the glucagon-like peptide-1 receptor agonists exenatide and insulin aspartate 30 injection on carotid intima-media thickness. Here, we report the renal outcomes of the intervention in patients with type 2 diabetes mellitus (T2DM). Data from the RCT study was used to evaluate the effect of exenatide or insulin given for 52 weeks on estimated glomerular filtration rate (eGFR) in patients with T2DM. The primary end point was the change in the eGFR from baseline between the exenatide and insulin groups in normal versus overweight patients and patients with obesity. The secondary end point was the correlation between change in eGFR and oxidative stress, glycemic control, and dyslipidemia. There was a significant difference in eGFR between the insulin and exenatide groups at 52 weeks (p=0.0135). Within the insulin group, the eGFR remained below baseline at 52 weeks in all patients, and there was an increase in body weight in the normal group compared with the overweight patients and patients with obesity. The opposite was observed in the exenatide group. A decrease in body weight was prominent in the exenatide group at 52 weeks (p<0.05), the eGFR was below baseline in overweight patients and patients with obesity and significantly above baseline in the normal group (p<0.05). The eGFR was positively correlated to 8-oxo-7,8-dihydroguanosine in the insulin group (p<0.05) but not the exenatide group. It can be concluded that compared with insulin, exenatide may improve renal function in overweight patients and patients with obesity more than in normal-weight patients with T2DM, but a further RCT is needed to confirm this effect.

The older, the less potential benefit for type 2 diabetes from weight control.

BACKGROUND: Although moderate weight loss improves outcomes of type 2 diabetes mellitus (T2DM) in young and middle-aged adults, there is a lack of high-quality evidence to support the strong relationship between obesity and T2DM in older people. This study aims to investigate whether the association of obesity with T2DM changes with aging. METHODS: In this cross-sectional study, we recruited 63,180 Chinses and US subjects from 3 datasets. Subjects were divided into young & middle-aged (≤59 years), young-old (60-75 years), and old-old (≥75 years). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for the association between obesity and T2DM, stratified by common confounders. A sliding-window based algorithm and restricted cubic splines were used to smoothly estimate the changes with aging. RESULTS: The OR (95% CI) for the associations between general obesity and T2DM were decreased from the young & middle-aged group (OR, 5.91; 95% CI, 5.33-6.56) to the young-old group (OR, 3.98; 95% CI, 3.56-4.45) and then to the old-old group (OR, 3.06; 95% CI, 2.57-3.66). The trend for this reduced association with aging persisted after stratification by obesity type, region, gender, recruiting time, hypertension, and hyperlipidemia in both Chinese and Americans. We also identified a weakened gender disparity for this association between the young & middle-aged subjects (P for disparity < 0.001) and the old-old group (P for disparity = ~ 0.36). CONCLUSIONS: The obesity-T2DM association is clearly reduced with aging, which indicates that the elderly may gain fewer potential benefits in weight lose than the younger patients. Considering this attenuated association, as well as the increased incidence of geriatric syndrome in the elderly, clinicians should comprehensively balance the benefits and side effects of weight loss in geriatric T2DM interventions.

The association study between CYP20A1, CYP4F2, CYP2D6 gene polymorphisms and coronary heart disease risk in the Han population in southern China.

BACKGROUND: Coronary heart disease (CHD) is a disease that seriously harms human health. Genetic factors seriously affect the CHD susceptibility. The CYP20A1, CYP4F2 and CYP2D6 are important drug metabolism enzymes in the human body. OBJECTIVE: We aimed to explore the association between CYP20A1, CYP4F2, CYP2D6 single nucleotide polymorphisms (SNPs) and CHD risk in the Chinese Southern Han population. METHODS: Based on the 'case-control' experimental design (505 cases and 508 controls), we conducted an association study between 5 candidate SNPs selected from CYP20A1 (rs2043449), CYP4F2 (rs2108622, rs3093106, rs309310), CYP2D6 (rs1065852) and CHD risk. Logistic regression was used to analyze the CHD susceptibility under different genetic models. Multi-factor dimensionality reduction (MDR) was used to analyze the interaction of 'SNP-SNP' in CHD risk. RESULTS: Our results showed that under multiple genetic models, CYP2D6 rs1065852 significantly increased the CHD risk in these participants who are ≤ 60 years old (OR 1.40, CI 1.07-1.82, p = 0.013), smokers (OR 1.40, CI 1.02-1.93, p = 0.039), or have family history (OR 1.24, CI 1.02-1.51, p = 0.035). CYP4F2 SNPs rs2108622 (OR 0.63, CI 0.43-0.93, p = 0.020), rs3093106 (OR 0.52, CI 0.29-0.92, p = 0.023), and rs309310 (OR 0.55, CI 0.31-0.96, p = 0.033) were potentially associated with the course of CHD patients. CONCLUSION: Our study found that CY2D6 rs1065852 has an outstanding and significant association with increased CHD risk. Our study provided data supplements for CHD genetic susceptibility loci, and also provided a new and valuable reference for CHD drug treatment.

Stress responses of the intestinal digestion, antioxidant status, microbiota and non-specific immunity in Songpu mirror carp (Cyprinus carpio L.) under starvation.

Songpu mirror carp, Cyprinus carpio L., is a new variety of common carp that has become an economically important freshwater fish in China. However, it remains unknown how its metabolism is regulated under starvation. Here, we investigated how intestinal digestion, antioxidant status, microbiota and immune activities were affected under starvation stress. The feeding regimes were designed as follows: ST0 comprised fish allowed to feed continuously; ST1 comprised fish starved for 1 week; ST2 comprised fish starved for 2 weeks; ST3 comprised fish starved for 3 weeks; ST4 comprised fish starved for 4 weeks. Our results showed a significant decrease in the level of intestinal amylase, lipase, and protease activities in the group ST4 (P < 0.05). Compared with the control group, intestinal antioxidant enzyme activities were significantly increased during short-term starvation. The gene expression levels of interleukin 1ß (IL-1ß), interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-α) were elevated in the groups ST3 and ST4. We also detected the reduction in the expression levels of interleukin 10 (IL-10) and transforming growth factor ß (TGF-ß2) compared with those of the group ST0. Notably, the gut microbial composition was dominated by Proteobacteria, Acidobacteria, Actinobacteria, Bacteroidetes, and Firmicutes. The relative abundance of the dominant microbial phyla changed significantly under starvation stress. Taken together, our results suggest that starvation can induce the change of intestinal digestion, non-specific immunity and microbiota in Songpu mirror carp, and provide new insights into its habitat selection and adaptation to environmental changes.

Efficacy of Exenatide Administered Twice Daily in Body Mass Index Reduction in Patients with Type 2 Diabetes Mellitus.

Background: Exenatide is a glucagon-like peptide-1 receptor agonist that can reduce body weight. This study aimed to determine the efficacy of exenatide on body mass index (BMI) reduction in patients with type 2 diabetes mellitus (T2DM) with differing baseline body weight, blood glucose, and atherosclerotic status and to determine if there is a correlation between BMI reduction and cardiometabolic indices in these patients. Methods: This retrospective cohort study used data from our randomized controlled trial. A total of 27 T2DM patients treated with combination therapy of exenatide twice daily and metformin for 52 weeks were included. The primary endpoint was a change in the BMI from the baseline to week 52. The secondary endpoint was a correlation between BMI reduction and cardiometabolic indices. Findings. The BMIs of overweight and obesity patients and those with glycated hemoglobin (HbA1c) ≥ 9% significantly decreased -1.42 ± 1.48 kg/m2(P=0.015) and -0.87 ± 0.93 kg/m2(P=0.003), respectively, at the baseline after 52 weeks of treatment. There was no reduction in BMI in patients with normal weight, HbA1c <9%, the nonatherosclerosis group, and the atherosclerosis group. The decrease in BMI was positively correlated with changes in blood glucose, high-sensitivity C-reactive protein (hsCRP), and systolic blood pressure (SBP). Conclusion: BMI scores improved after exenatide treatment for 52 weeks in T2DM patients. Weight loss was affected by baseline body weight and blood glucose level. In addition, BMI reduction from the baseline to 52 weeks was positively correlated with baseline HbA1c, hsCRP, and SBP. Trial Registration. Chinese Clinical Trial Registry (ChiCTR-1800015658).

The effect of CYP7B1 polymorphisms on the risk of coronary heart disease in Hainan Han population.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of human death worldwide. Genetic factors play an important role in the occurrence of CHD. Our study is designed to investigate the influence of CYP7B1 polymorphisms on CHD risk. METHODS: In this case-control study, 508 CHD patients and 510 healthy individuals were recruited to determine the correlation between CYP7B1 polymorphisms (rs7836768, rs6472155, and rs2980003) and CHD risk. The associations were evaluated by computing odds ratios (OR) and 95% confidence intervals (CI) with logistic regression analysis. The association between SNP-SNP interaction and CHD susceptibility was carried out by multifactor dimensionality reduction analyses. RESULTS: Our study found that rs6472155 is significantly associated with an increased risk of CHD in age > 60 years (OR 2.20, 95% CI = 1.07-4.49, p = 0.031), women (OR 3.17, 95% CI = 1.19-8.44, p = 0.021), and non-smokers (3.43, 95% CI = 1.16-10.09, p = 0.025). Rs2980003 polymorphism has a lower risk of CHD in drinkers (OR 0.47, 95% CI = 0.24-0.91, p = 0.025). Further analyses based on false-positive report probability validated these significant results. Besides, it was found that rs6472155 polymorphism was associated with uric acid level (p = 0.034). CONCLUSION: Our study indicated that CYP7B1 polymorphisms are related to the risk of CHD, which provides a new perspective for prevent of CHD.

Blocking circ_0014130 suppressed drug resistance and malignant behaviors of docetaxel resistance-acquired NSCLC cells via regulating miR-545-3p-YAP1 axis.

Recent evidences have claimed that circular RNAs are deregulated in docetaxel (DTX) resistance in malignant tumors, including non-small-cell lung cancer (NSCLC). Hsa_circ_0014130 (circ_0014130) is a new biomarker in NSCLC. However, its role in DTX-resistant NSCLC remained to be annotated. In this study, real-time PCR was used to measure expression of circ_0014130, and circ_0014130 was upregulated in NSCLC tumors and DTX-resistant NSCLC cells (NCI-H1299/DTX and A549/DTX). MTT assay analyzed the half inhibitory concentration (IC50) of DTX, and it was lowered by circ_0014130 interference in DTX-resistant NSCLC cells. Moreover, colony formation assay, flow cytometry, transwell assays, and xenograft tumor model revealed that silencing circ_0014130 facilitated apoptosis rate of DTX-resistant NSCLC cells, suppressed the colony formation, migration and invasion, and retarded xenograft tumor growth in nude mice. Dual-luciferase reporter assay and RNA immunoprecipitation confirmed that circ_0014130 was one competing endogenous RNA (ceRNA) for miRNA (miR)-545-3p, and circ_0014130 modulated expression of yes-associated protein 1 (YAP1), a target gene for miR-545-3p. YAP1 upregulation and miR-545-3p downregulation were allied with circ_0014130 upregulation in NSCLC tumors and DTX-resistant NSCLC cells. Functionally, downregulating miR-545-3p could abate the effects of circ_0014130 knockdown in DTX-resistant NSCLC cells in vitro, whereas its overexpression exerted similar effects of circ_0014130 knockdown. Either, restoring YAP1 partially reversed miR-545-3p effects in DTX-resistant NSCLC cells. Collectively, there might be a novel circ_0014130-miR-545-3p-YAP1 ceRNA pathway in regulation of chemoresistance and malignant behaviors of DTX-resistant NSCLC cells, suggesting a potential therapeutic approach for DTX resistance.