Absolute monocyte counts could predict disease activity and secondary loss of response of patients with Crohn's disease treated with anti-TNF-α drug.

BACKGROUND: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. METHODS: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. RESULTS: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. CONCLUSION: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD.

The impact of hypertension follow-up management on the choices of signing up family doctor contract services: does socioeconomic status matter?

BACKGROUND: This study aimed to explore the association between hypertension follow-up management and family doctor contract services, as well as to examine whether socioeconomic status (SES) had an interaction effect on this relationship among older adults in China. METHODS: We used data from the sixth National Health Service Survey of Shandong Province, China, including 3,112 older adults (age ≥ 60 years) with hypertension in 2018. Logistic regression models and a margins plot were used to analyze the role of SES in the relationship between hypertension follow-up management and family doctor contract services. RESULTS: The regular hypertension follow-up management rate and family doctor contracting rate were 81.8% and 70.9%, respectively, among older adults with hypertension. We found that participants with regular hypertension follow-up management were more likely to sign family doctor contract services (OR=1.28, 95%CI: 1.04, 1.58, P=0.018). The interaction effect occurred in the groups who lived in rural areas (OR=1.55, 95%CI: 1.02, 2.35), with high education level (OR=0.53, 95%CI: 0.32, 0.88) and had high incomes (OR=0.53, 95%CI: 0.35, 0.81). CONCLUSIONS: Our findings suggested that regular hypertension follow-up management was associated with family doctor contract services and SES influenced this relationship. Primary health care should improve the contracting rate of family doctors by strengthening follow-up management of chronic diseases. Family doctors should focus on improving services quality and enriching the content of service packages especially for older adults with higher income and education level.

Catastrophic health expenditure and health-related quality of life among older adults in Shandong, China: the moderation effect of daily care by adult children.

BACKGROUND: Catastrophic health expenditure (CHE) has a considerable impact on older people in later life, but little is known about the relationship between catastrophic health expenditure and health-related quality of life (HRQOL). The aim of this study was to examine the relationship between catastrophic health expenditure and health-related quality of life in older people, and to explore whether the daily care provided by adult children is a moderator in this relationship. METHODS: Data from the sixth National Health Services Survey in Shandong Province, China. The sample consisted of 8599 elderly people (age ≥ 60 years; 51.7% of female). Health-related quality of life was measured by the health utility value of EQ-5D-3 L. Interaction effects were analyzed using Tobit regression models and marginal effects analysis. RESULTS: The catastrophic health expenditure prevalence was 60.5% among older people in Shandong, China. catastrophic health expenditure was significantly associated with lower health-related quality of life (ß= - 0.142, P < 0.001). We found that adult children providing daily care services to their parents mitigated the effect of catastrophic health expenditure on health-related quality of life among older people (ß = 0.027, P = 0.040). CONCLUSIONS: Our findings suggested that catastrophic health expenditure was associated with health-related quality of life and the caring role of older adult children moderated this relationship. Reducing the damage caused by catastrophic health expenditure helps to improve health-related quality of life in older people. Adult children should increase intergenerational contact, provide timely financial and emotional support to reduce the negative impact of catastrophic health expenditure on health-related quality of life.

Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2.

Acute liver injury is the basis of the pathogenesis of diverse liver diseases. However, the mechanism underlying liver injury is complex and not completely understood. In our study, we revealed that CERK, which phosphorylates ceramide to produce ceramide-1-phosphate (C1P), was the sphingolipid pathway-related protein that had the most significantly upregulated expression during acute liver injury. A functional study confirmed that CERK and C1P attenuate hepatic injury both in vitro and in vivo through antioxidant effects. Mechanistic studies have shown that CERK and C1P positively regulate the protein expression of NRF2, which is a crucial protein that helps maintain redox homeostasis. Furthermore, our results indicated that C1P disrupted the interaction between NRF2 and KEAP1 by competitively binding to KEAP1, which allowed for the nuclear translocation of NRF2. In addition, pull-down assays and molecular docking analyses revealed that C1P binds to the DGR domain of KEAP1, which allows it to maintain its interaction with NRF2. Importantly, these findings were verified in human primary hepatocytes and a mouse model of hepatic ischemia‒reperfusion injury. Taken together, our findings demonstrated that CERK-mediated C1P metabolism attenuates acute liver injury via the binding of C1P to the DGR domain of KEAP1 and subsequently the release and nuclear translocation of NRF2, which activates the transcription of cytoprotective and antioxidant genes. Our study suggested that the upregulation of CERK and C1P expression may serve as a potential antioxidant strategy to alleviate acute liver injury.

Effects of tidal hydrology on soil phosphorus forms in the Yellow River estuary wetland: A field study of soil core translocation.

Phosphorus (P) forms in soil are related to the P cycle and play an important role in maintaining the productivity and function of wetlands. Tidal hydrology is a key factor controlling soil P forms in estuary wetlands; however, the response of soil P forms to tidal hydrological changes remains unclear. A translocation experiment in the Yellow River Estuary wetland was conducted to study the effect of hydrological changes on P forms in the soil, in which freshwater marsh soils in the supratidal zone were translocated to salt marshes in different intertidal zones (up-high-tidal zone, high-tidal zone, and middle-tidal zone). Over a 23-month experiment, soil properties showed varying changes under different tidal hydrology conditions, with an increase in pH, salinity, Ca2+ and salt ions and a decrease in iron oxide and nutrients. Compared with the control, the content of different forms of phosphorus (total phosphorus, inorganic phosphorus, organic phosphorus, and calcium-bound phosphorus) in the cultured soil cores decreased from 3.3 % to 67.0 % in the intertidal zones, whereas the content of ferrum­aluminum-bound phosphorus increased from 58.9 % to 65.1 % at the end of the experiment. According to the partial least squares structural equation model, P forms are influenced by tidal hydrology mainly through the mediation of salt ions and nutrient levels. These results suggest that seawater intrusion promotes the release of P in the supratidal zone soil of estuary wetlands.

Analyzing the structure-activity relationship of raspberry polysaccharides using interpretable artificial neural network model.

The structure-activity relationship has been a hot topic in the field of polysaccharide research. Six polysaccharides and three polysaccharide fragments were obtained from raspberry pulp. Based on their structural information and immune-enhancing activity data, an artificial neural network (ANN) model was used for prediction, and Gradient-weighted class activation mapping (Grad-CAM) algorithm was exploited for explanation structure-activity relationship of these raspberry polysaccharides in the present study. The structural information and immune activity data of raspberry polysaccharides were respectively used as input and output in the ANN model. The training and testing losses of ANN model was no longer decreased after trained for 200 epochs. The mean-square error (MSE) of training set and test set stabilized around 0.003 and 0.013, and the mean absolute percentage error (MAPE) of training set and test set were 0.21 % and 0.98 %, indicating the trained ANN model converged well and exhibited strong robustness. The interpretability analysis showed that molecular weight, content of arabinose, galactose or galacturonic acid, and glycosyl linkage patterns of →3)-Arap-(1→, Araf-(1→, →4)-Galp-(1 â†’ were the main structural factors greatly affecting the immune-enhancing activity of raspberry polysaccharides. This work may provide a new perspective for the study of structure-activity relationship of polysaccharides.

Novel noninvasive indices for the assessment of liver fibrosis in primary biliary cholangitis.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Activities of daily living limitations and the use of physical examination among older adults with informal care in China: do gender and residence make differences?

BACKGROUND: This study investigated the relationship between activities of daily living (ADL) limitations and the use of physical examination among older adults receiving informal care, and to further examine whether this relationship varies by gender and urban-rural areas. METHODS: The data in this study were obtained from the sixth Health Service of Shandong province, China. In total, 8,358 older adults aged 60 years or older who received informal care were included in the analysis. Binary logistic regression models were conducted to explore the association between ADL limitations and the use of physical examination and examine the differences between gender and urban-rural areas. RESULTS: The prevalence of limitations in ADL and physical examination utilization rate among older adults receiving informal care in Shandong Province were 14.12% and 72.31%, respectively. After adjusting for confounders, ADL limitations were negatively correlated with the utilization of physical examination services among older adults receiving informal care (OR = 0.74, 95% CI: 0.64, 0.87, P < 0.001), and there were gender and rural-urban differences. The association between ADL limitations and the use of physical examination was statistically significant in older women receiving informal care (OR = 0.65, 95% CI: 0.53, 0.80, P < 0.001). And only among urban older adults receiving informal care, those with ADL limitations had lower utilization of physical examination services than participants without ADL limitations (OR = 0.59, 95% CI: 0.47, 0.74, P < 0.001). CONCLUSIONS: Our study suggested that the relationship between ADL limitations and the use of physical examination among older adults receiving informal care differed by gender and urban-rural areas in Shandong, China. These findings implied that the government should provide more health resources and personalized physical examination service programs, especially to meet the differential needs of women and urban old adults receiving informal care, to contribute to the implementation of healthy aging strategies.

Personalizing age of gastric cancer screening based on comorbidity in China: Model estimates of benefits, affordability and cost-effectiveness optimization.

The benefits of gastric cancer screening are related to age and comorbidity status, but reliable estimates are lacking in China. This study aimed to estimate the benefits and affordability of the gastric cancer screening strategy by level of comorbidity to inform decisions to screening age. We assessed six current gastric cancer screening strategies in China using a microsimulation model with different starting and stopping ages and comorbidity profiles, for a total of 378 strategies. 1,000,000 individuals were simulated in the model and followed the alternative strategies. Primary outcomes included gastric cancer incidence, the number of endoscopy and complications, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs are discounted by 5% per year. Sensitivity analyses were used to evaluate model uncertainty. Strategies with longer screening durations were associated with higher benefits of life-year gained and gastric cancer deaths averted, but were also accompanied by a large number of endoscopy screening, and complication events. Using the threshold of US$18,575 per QALY gained, at the no, moderate, and severe comorbidity level, the leading cost-effectiveness strategies were the new gastric cancer screening scoring system strategy (NGCS) screening from age 40 years to 60 years (40-60), 40-55-NGCS, and 40-55-NGCS strategy, respectively. The results are robust in sensitivity analyses. Our study illustrates the importance of considering comorbidity conditions and age when determining the starting and stopping screening age for gastric cancer and informs the discussion on personalizing decisions. The trade-off between benefits and harms can also be referenced when necessary.

The relationship between handgrip strength and cognitive function among older adults in China: Functional limitation plays a mediating role.

BACKGROUND: The deterioration of cognitive function with age has become a major public health issue. To date, the underlying mechanisms of the association between handgrip strength and cognitive function were poorly understood. This study aimed to examine the mediating effect of functional limitation in the longitudinal relationship between handgrip strength and subsequent cognitive function. METHODS: This research recruited 4416 participants aged 60 and above from wave 2015 and 2018 of the China Longitudinal Study of Health and Retirement (CHARLS). We conducted the linear regression model and bootstrap analyses to test the mediating role of functional limitation in the relationship between handgrip strength and cognitive function. RESULTS: After adjusting the confounders, handgrip strength was positively associated with subsequent cognitive function (ß = 0.12, P < 0.001) and was negatively associated with functional limitation (ß = -0.14, P < 0.001). The mediation effect of functional limitation accounted for 23.33 % of the total effect regarding the handgrip strength with cognitive function, and the magnitude of mediation effect was a*b = 0.021 (95%CI: 0.017-0.027). LIMITATIONS: The variable of functional limitations was self-reported. And this study did not analyse the severity and duration of handgrip strength loss and functional limitations, which may lose some information. CONCLUSIONS: Our findings revealed that handgrip strength not only directly influenced cognitive function among older individuals but also indirectly via functional limitation over 3-year follow-up. Physical exercise targeting handgrip strength and functional limitation may be an effective approach to prevent and delay cognitive decline.

Effect of electron acceptor addition on the temperature sensitivity of soil anaerobic carbon mineralization in the Yellow River Estuary wetland, China.

The temperature sensitivity of soil carbon mineralization (Q10) is an important index to evaluate the responses of ecosystem carbon cycling to climate change. We examined the effects of three electron acceptors [SO42-, NO3- and Fe(Ⅲ)] addition on the Q10 value of anaerobic carbon mineralization of Phragmites australis community soil (0-10 cm) in the Yellow River Estuary wetland with the closed culture-gas chromatography method. The results showed that the three electron acceptors addition inhibited the production of CO2 and CH4 during the 48-day culture period, with a decrease of 17.3%-20.8% for CO2 and 29.2%-36.2% for CH4. Generally, the CO2 production differed with the concentrations of electron acceptors, while CH4 production differed with the type of electron acceptors. The CO2:CH4 ratios were significantly different with temperature, indicating an obvious temperature dependence for the anaerobic carbon mineralization pathway. The Q10 values of CO2 and CH4 production under three electron acceptor additions ranged from 1.08 to 1.11 and from 1.19 to 1.37, respectively, showing an increasing trend compared with the control. The type and concentration of electron acceptors affected the temperature dependence of CO2 production, while electron acceptors affected that of CH4 production. It is suggested that the input of reducing salts would retard the mineralization loss of organic carbon in estuary freshwater wetlands under the background of climate change, but enhance the sensitivity of carbon mineralization to increasing temperature.

Activities of daily living limitations and family doctor contract services among overweight and obese older adults: is there a rural-urban difference?

BACKGROUND: The purpose of this study was to evaluate the relationship between activities of daily living (ADL) limitations and family doctor contract services among overweight and obese older adults, as well as to examine whether this association varies by urban-rural residence. METHODS: Data for the present study were obtained from the sixth Health Service of Shandong province, China. A total of 4,249 overweight and obese older adults were included in this study. Binary logistic regression models were used to evaluate the relationship between ADL limitations and family doctor contract services, to examine the potential differences between urban and rural areas. RESULTS: Of 4,249 overweight and obese older adults, the prevalence of limitations in ADL and family doctor service contracting rate in Shandong province were 12.47% and 66.46%, respectively. The results of the regression analyses revealed that overweight and obese older adults with ADL limitations were more likely to sign up for family doctor services than those without ADL limitations (OR = 1.27, 95%CI: 1.02-1.58, P = 0.033). Only among rural overweight and obese older adults, the relationship between ADL limitations and family doctor contract services was statistically significant (OR = 1.50, 95%CI: 1.13-1.99, P = 0.005). CONCLUSIONS: Our study found a significant association between ADL limitations and family doctor contract services among overweight and obese older adults in Shandong, China. This relationship differed by urban-rural residence. To promote the positive development of the family doctor contract service system, the government should increase publicity, provide personalized contracted services, and prioritize the healthcare needs of overweight and obese older adults with ADL limitations, with special attention to rural areas.

The Effect of Polymer Blends on the In Vitro Release/Degradation and Pharmacokinetics of Moxidectin-Loaded PLGA Microspheres.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0-t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

[Expression of Cyclooxygenase-2 in Patients With Snow-White Sign of Advanced Colorectal Adenomas].

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age (P=0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P>0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas (P=0.004),large adenomas (P=0.006),adenomas in distal colon (P=0.015),protruding polyps (P=0.044),and late-stage pathology (P=0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification (P=0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign (P<0.001,P=0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign (P=0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign (P=0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.

Chronic Diarrhea with Villous Blunting of the Small Intestine Under Capsule Endoscopy in Common Variable Immunodeficiency and X-Linked Agammaglobulinemia: A Case Series.

Introduction: Primary immunodeficiencies (PIDs) are a heterogeneous group of disorders, common variable immunodeficiency disorder (CVID) and X-linked agammaglobulinemia (XLA) are PIDs related to B-cell defect, characterized by reduced levels of immunoglobulins and immune dysregulation. Infections are the most common clinical manifestations, while underlying autoimmune and inflammatory conditions are present in some patients with CVID and XLA, leading to clinical misdiagnosis and diagnostic delay. Chronic diarrhea in patients with CVID and XLA, particularly complicated malabsorption and protein-energy malnutrition, is responsible for poor prognostic outcomes. Methods: In this study, we described three PID adult patients (two with CVID and one with XLA) who presented with varying degrees of chronic diarrhea, weight loss, and protein-energy malnutrition. We suggest that villous blunting of the small intestine under capsule endoscopy may be an endoscopic feature of PID-related enteropathy, thus highlighting the application of capsule endoscopy in patients with CVID and XLA presenting with chronic diarrhea. Conclusion: We also summarize regular Ig supplementation is the basic treatment for CVID and XLA patients, proper enteral nutrition and probiotic therapy can be explored to use to alter gut microbiota and modulate intestinal immune response. However, vedolizumab is not helpful to PID-related enteropathy therapy, as it exacerbates the inflammatory response in extra-intestinal organs and ultimately causes poor clinical outcomes.

Diversity of soil seed bank and influencing factors in the nascent wetland of the Yellow River Delta.

Soil seed bank is the growth and reproduction source of vegetation community, playing an important role in vegetation establishment, succession and renewal, biodiversity maintenance. This study has selected the nascent wetland in the Yellow River Delta (YRD) formed in 1996 as study area and investigated the diversity and key influencing factors of soil seed bank diversity. The study results show that: (1) The soil seed bank in the study area has a simple structure, containing relatively few species. A total of five plant species, which belong to four families and five genera, were found in this bank, with Phragmites australis and Suaeda salsa being the dominant plants. (2) All species are herbs without woody species. One herb is annual herb and the others are perennial herbs. (3) From the sea to the river, the changes rules of the overall density and diversity of the seed bank are not obvious. (4) The dispersal distance from salt and freshwater has a significant influence on the density of the soil seed bank but has no significant influence on the diversity. Meanwhile, the soil salt content has a significant negative influence on the diversity of seed banks. (5) Aboveground vegetation did not closely relationship with diversity of soil seed bank. All above results can provide basic data and scientific evidence for the conservation of vegetation communities in the nascent wetlands and vegetation restoration in the degraded wetlands in the YRD.

N-doped carbon sheets supported P-Fe3O4-MoO2 for freshwater and seawater electrolysis.

Electric-driven freshwater/seawater splitting is an attractive and sustainable route to realize the generation of H2 and O2. Molybdenum-based oxides exhibit poor activity toward freshwater/seawater electrolysis. Herein, we adjusted the electronic structure of MoO2 by constructing N-doped carbon sheets supported P-Fe3O4-MoO2 nanosheets (P-Fe3O4-MoO2/NC). P-Fe3O4-MoO2/N-doped carbon sheets were precisely prepared by pyrolysis of Schiff base Fe complex and MoO3 nanosheets through phosphorization. Benefiting from the unique structures of the samples, it required 119/145 mV to drive freshwater/seawater reduction reaction at 10 mA/cm2. P-Fe3O4-MoO2/NC catalysts exhibited superior freshwater/seawater oxidation reactivity with 180/189 mV at 10 mA/cm2 compared with commercial RuO2. The low cell voltages for P-Fe3O4-MoO2/NC were 1.47 and 1.59 V towards freshwater and seawater electrolysis, respectively. Our work might shed light on the structural modulation of Mo-based oxides for enhancing freshwater and seawater electrolysis activity.

CIRC_0085323 SILENCING INHIBITS TNF-Α-INDUCED NORMAL HUMAN COLONIC EPITHELIAL CELL INFLAMMATION AND APOPTOSIS THROUGH THE MIR-495-3P/TRAF3 AXIS.

ABSTRACT: Background: Previous data have suggested the involvement of circular RNA (circRNA) in ulcerative colitis (UC) development. However, the role and mechanism of circ_0085323 in UC occurrence have not been reported. Methods: Normal human colonic epithelial cells (NCM460) were treated with TNF-α to simulate UC-like cell inflammation and injury in vitro. The expression of circ_0085323, microRNA-495-3p (miR-495-3p), and TNF receptor-associated factor 3 (TRAF3) was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blotting analysis. Cell viability, cell proliferation, and cell apoptosis were investigated by cell counting kit-8 assay, 5-ethynyl-29-deoxyuridine assay, and flow cytometry analysis, respectively. IL-1ß, IL-6, and IL-8 production were analyzed by enzyme-linked immunosorbent assays. Lactate dehydrogenase activity was assessed by a lactate dehydrogenase activity detection assay. The interactions among circ_0085323, miR-495-3p, and TRAF3 were identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0085323 was overexpressed in the colonic mucosal tissues of UC patients and TNF-α-stimulated NCM460 cells. Circ_0085323 knockdown relieved TNF-α-induced inhibitory effect on the proliferation of NCM460 cells and promoting effects on cell apoptosis and inflammation. Circ_0085323 acted as a miR-495-3p sponge, and the effects of circ_0085323 silencing on TNF-α-induced NCM460 cell injury were attenuated by decreasing miR-495-3p expression. TRAF3 was targeted by miR-495-3p, and circ_0085323 combined with miR-495-3p to regulate TRAF3. TRAF3 depletion not only alleviated TNF-α-induced NCM460 cell damage but also partially revoked the effect of circ_0085323 silencing combined with miR-495-3p depletion on TNF-α-induced NCM460 cell injury. Conclusions: Circ_0085323 knockdown ameliorated TNF-α-induced NCM460 cell injury by regulating the miR-495-3p/TRAF3 axis, which suggested that circ_0085323 might be a therapeutic target for UC.

Diagnostic and Prognostic Value of Aspartate Transaminase-to-platelet Ratio Index, Gamma-glutamyl Transpeptidase-to-platelet Ratio, and Fibrosis-4 for Compensated Hepatitis B-related Liver Cirrhosis.

The aim of this study was to investigate a serodiagnostic model as a substitute for liver stiffness measurement (LSM) for diagnosing compensated liver cirrhosis (LC). This retrospective study included 150 patients with compensated hepatitis B-related LC and 153 with chronic Hepatitis B virus (HBV) infection. It was conducted from May 2017 to June 2022 at Qinghai University Affiliated Hospital, China. The values of LSM, aspartate transaminase-to-platelet ratio index (APRI), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), and fibrosis-4 (FIB-4) were evaluated in all admitted patients. The diagnostic value of APRI, GPR, FIB-4, and LSM was assessed using the receiver operating characteristic (ROC) curve. FIB-4 score (AUC=0.842; specificity=77.8%; sensitivity=80.7%; cut-off=2.824) was the best substitute for LSM from the three serum scoring models. The Cox regression model indicated that a FIB-4 score ≥2.824 was an independent predictor of prognosis for compensated hepatitis B-related LC (HR=1.15, 95%CI: 1.07-1.23, p<0.001). This study's findings suggested that FIB-4 could be the best substitute for LSM and may help to assess LC prognosis. Key Words: APRI, GPR, FIB-4, LSM, Diagnosis, Liver cirrhosis.

The emergence of multi-drug resistant and virulence gene carrying Escherichia coli strains in the dairy environment: a rising threat to the environment, animal, and public health.

Escherichia coli is a common inhabitant of the intestinal microbiota and is responsible for udder infection in dairy cattle and gastro-urinary tract infections in humans. We isolated E. coli strains from a dairy farm environment in Xinjiang, China, and investigated their epidemiological characteristics, phenotypic and genotypic resistance to antimicrobials, virulence-associated genes, and phylogenetic relationship. A total of 209 samples were collected from different sources (feces, slurry, water, milk, soil) and cultured on differential and selective agar media (MAC and EMB). The presumptive identification was done by the VITEK2 system and confirmed by 16S rRNA gene amplification by PCR. Antimicrobial susceptibility testing was done by micro-dilution assay, and genomic characterization was done by simple and multiplex polymerase chain reaction (PCR). A total of 338 E. coli strains were identified from 141/209 (67.5%) of the samples. Most of the E. coli strains were resistant to sulfamethoxazole/trimethoprim (62.43%), followed by cefotaxime (44.08%), ampicillin (33.73%), ciprofloxacin (31.36%), tetracycline (28.99%), and a lesser extent to florfenicol (7.99%), gentamicin (4.44%), amikacin (1.77%), and fosfomycin (1.18%). All of the strains were susceptible to meropenem, tigecycline, and colistin sulfate. Among the resistant strains, 44.4% were identified as multi-drug resistant (MDR) showing resistance to at least one antibiotic from ≥3 classes of antibiotics. Eighteen out of 20 antibiotic-resistance genes (ARGs) were detected with sul2 (67.3%), blaTEM (56.3%), gyrA (73.6%), tet(B) (70.4%), aph(3)-I (85.7%), floR (44.4%), and fosA3 (100%, 1/1) being the predominant genes among different classes of antibiotics. Among the virulence-associated genes (VAGs), ompA was the most prevalent (86.69%) followed by ibeB (85.0%), traT (84.91%), ompT (73.96%), fyuA (23.1%), iroN (23.1%), and irp2 gene (21.9%). Most of the E. coli strains were classified under phylogenetic group B1 (75.45%), followed by A (18.34%), C (2.96%), D (1.18%), E (1.18%), and F (0.30%). The present study identified MDR E. coli strains carrying widely distributed ARGs and VAGs from the dairy environment. The findings suggested that the dairy farm environment may serve as a source of mastitis-causing pathogens in animals and horizontal transfer of antibiotic resistance and virulence genes carrying bacterial strains to humans via contaminated milk and meat, surface water and agricultural crops.