Response Surface Optimization for Water-Assisted Extraction of Two Saponins from Paris polyphylla var. yunnanensis Leaves.

The process of extracting polyphyllin II and polyphyllin VII by water-assisted extraction was established and optimized in this study. Response surface methodology was used to establish a prediction model to optimize the extraction conditions. Based on the one-way test, the Box-Behnken design with three factors and three levels was used for the experimental program, and the composition analysis was carried out by high-performance liquid chromatography (HPLC). The optimal extraction conditions for polyphyllin II and polyphyllin VII were as follows: extraction time of 57 and 21 min, extraction temperature of 36 and 32 °C, solid-to-liquid ratio of 1:10 and 1:5 g/mL, respectively, and the yields of polyphyllin II and polyphyllin VII were 1.895 and 5.010%, which was similar to the predicted value of 1.835 and 4.979%. The results of the ANOVA showed that the model fit was good, and the Box-Behnken response surface method could optimize the water-assisted extraction of saponins from the leaves of Paris polyphylla var. yunnanensis. This study provides a theoretical basis for the application of polyphyllin II and polyphyllin VII in pharmaceutical production.

PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway.

Acute lung injury (ALI) is a common clinical syndrome, which often results in pulmonary edema and respiratory distress. It has been recently reported that phosphatidylethanolamine binding protein 4 (PEBP4), a basic cytoplasmic protein, has anti-inflammatory and hepatoprotective effects, but its relationship with ALI remains undefined so far. In this study, we generated PEBP4 knockout (KO) mice to investigate the potential function of PEBP4, as well as to evaluate the capacity of alveolar fluid clearance (AFC) and the activity of phosphatidylinositide 3-kinases (PI3K)/serine-theronine protein kinase B (PKB, also known as AKT) signaling pathway in lipopolysaccharide (LPS)-induced ALI mice models. We found that PEBP4 deficiency exacerbated lung pathological damage and edema, and increased the wet/dry weight ratio and total protein concentration of bronchoalveolar lavage fluid (BALF) in LPS-treated mice. Meanwhile, PEBP4 KO promoted an LPS-induced rise in the pulmonary myeloperoxidase (MPO) activity, serum interleuin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, and pulmonary cyclooxygenase-2 (COX-2) expression. Mechanically, PEBP4 deletion further reduced the protein expression of Na+ transport markers, including epithelial sodium channel (ENaC)-α, ENaC-γ, Na,K-ATPase α1, and Na,K-ATPase ß1, and strengthened the inhibition of PI3K/AKT signaling in LPS-challenged mice. Furthermore, we demonstrated that selective activation of PI3K/AKT with 740YP or SC79 partially reversed all of the above effects caused by PEBP4 KO in LPS-treated mice. Altogether, our results indicated the PEBP4 deletion has a deterioration effect on LPS-induced ALI by impairing the capacity of AFC, which may be achieved through modulating the PI3K/AKT pathway.

Efficacy of different doses of corticosteroids in treating severe COVID-19 pneumonia.

BACKGROUND: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. RESULTS: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8-16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. CONCLUSION: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.

MIIP downregulation drives colorectal cancer progression through inducing peri-cancerous adipose tissue browning.

BACKGROUND: The enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC. RESULTS: MIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1's glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of ß-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression. CONCLUSIONS: Our data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of ß-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.

Stable Aluminum Metal Anode Enabled by Dual-Functional Molybdenum Nanoparticles.

Constructing robust anode with strong aluminophilicity and rapid desolvation kinetics is essential for achieving high utilization, long-term durability, and superior rate performance in Al metal-based energy storage, yet remains largely unexplored. Herein, molybdenum nanoparticles embedded onto nitrogen-doped graphene (Mo@NG) are designed and prepared as Al host to regulate the deposition behavior and achieve homogeneous Al plating/stripping. The monodispersed Mo nanoparticles reduce the desolvation energy barrier and promote the deposition kinetics of Al. Additionally, Mo nanoparticles act as aluminophilic nucleation sites to minimize the Al nucleation overpotential, further guiding uniform and dense Al deposition. As a result, the dual-functional Mo@NG endows Al anodes with low voltage hysteresis, reversible Al plating/stripping with high coulombic efficiency, and excellent high-rate capability under 5 mA cm-2 . Moreover, the as-designed Al metal full batteries deliver a high capacity retention of 92.8% after 3000 cycles at 1 A g-1 . This work provides an effective solution to optimize the electrochemical properties of Al metal anode from the perspective of desolvation and deposition reactions, towards the development of high-safety and long-cycling aluminum-ion batteries.

Association of PD-L1 Expression with Clinicopathologic Characters in Gastric Cancer: A Comprehensive Meta-analysis.

PURPOSE: The expression level of programmed death ligand-1(PD-L1) in patients with gastric cancer is the key to determining the use of immune drugs. The relationship between PD-L1 expression level and clinical characteristics is worth exploring. METHODS: By setting the search terms correlated to PD-L1 and gastric cancer, a nearly comprehensive search was carried out in four major databases, and the deadline for searching was September 1, 2022. The retrieved documents were further screened by strict inclusion and exclusion criteria after removing the duplication. Next, the quality of the included studies was evaluated with the Newcastle-Ottawa Scale (NOS) scale. Finally, the STATA15.1 software was used to process data and draw plots, and the odds ratios (ORs) were adopted to assess the pooled effect size. RESULTS: A total of 85 works of literature were included in this study through screening strictly, and detailed data were extracted after evaluating the quality of the literature. The process of analysis was conducted in the whole population, Asia-Africa population, European and American population, and Asian population with CPS≥1, amd all found that the expression of PD-L1 in gastric cancer was correlated with age, tumor size, EBV infection, Her-2 expression and microsatellite status. However, the subgroup of the region also found some differences in Asian and Western regions, which was interesting and worth studying further. The included research of this study did not have significant publish bias. CONCLUSION: After careful analysis, this study found that age (>60 years), tumor size (>5cm), EBV infection (+), Her-2 expression (+), microsatellite status (MSI), and mismatch repair status (dMMR) were risk factors for positive expression of PD-L1 in gastric cancer.

Transcrocetin Meglumine Salt Inhibits Spinal Glial Cell-Mediated Proinflammatory Cytokines and Attenuates Complete Freund's Adjuvant-Induced Inflammatory Pain.

INTRODUCTION: Inflammatory pain is a significant global clinical challenge that involves both unpleasant sensory and emotional experiences. The treatment of pain is imminent, and we are committed to seeking new analgesics for pain relief. Transcrocetin meglumine salt (TCMS), a saffron metabolite derived from the crocin apocarotenoids, has exhibited the ability to cross the blood-brain barrier and exert neuroprotective effects. In this study, we aimed to investigate whether TCMS could ameliorate complete Freund's adjuvant (CFA)-induced inflammatory pain in mice and elucidate its underlying mechanisms. METHODS: Here, we established an inflammatory pain model in mice by injecting CFA into the left hind paw. Three days later, we administered intraperitoneal injections of TCMS (10 mg/kg) or saline to the animals. We examined mechanical allodynia, thermal hypersensitivity, and anxiety behavior. Furthermore, the activation of glial cells and proinflammatory cytokines in the spinal cord were detected. RESULTS: Our results showed that TCMS significantly reversed the mechanical allodynia and thermal hypersensitivity in the CFA-injected mice. Furthermore, TCMS administration effectively inhibited the activation of microglia and astrocytes in the spinal cord induced by CFA. Additionally, TCMS suppressed the production and release of spinal proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, in CFA-injected mice. CONCLUSION: Taken together, our findings demonstrate that TCMS holds promise as an innovative analgesic due to its ability to ameliorate inflammatory reactions.

The clinical burden of newly diagnosed Heart failure among patients with Reduced, mildly Reduced, and preserved ejection fraction.

Background: Contemporary analyses of the distribution of heart failure (HF) patients by groups of ejection fraction are not available or are limited to hospitalized patients. Our objective was to quantify the per-person and system level clinical burden of a broad population of HF patients. Methods: We studied 16,516 patients with a new HF diagnosis recorded in the electronic medical record of a U.S. integrated delivery system between 2005 and 2017. We used the diagnosis date as the index date and the nearest echocardiogram result to classify patients as HFrEF (n = 2,430), HFmrEF (n = 1,646), HFpEF (n = 12,440) and followed them through 2019 for major clinical outcomes (all-cause mortality, HF hospitalizations [HHF], all-cause hospitalizations, incident chronic kidney disease [CKD], progression of eGFR category, progression of CKD, incident type 2 diabetes [T2D], and progression to insulin use). We compared age and sex adjusted incidence rates and rate ratios of the outcomes between the HF types. Results: Incidence rates for most outcomes were significantly higher among patients with HFrEF compared with HFpEF. HHF was 59 % greater, mortality 31 % greater, and CKD incidence 55 % greater, (p < 0.001 for all comparisons). However, the larger size of the HFpEF group generated 4.7-6.7 times as many total outcomes. Conclusions: Regardless of subtype, the presence of HF was associated with poor clinical outcomes. Incidence rates were higher for HFrEF than HFpEF, but as the latter represented 75% of the study population, HFpEF caused a greater overall burden on the health care system, reflecting the high unmet need of target therapies for HFpEF.

Cytoplasmic SIRT1 promotes paclitaxel resistance in ovarian carcinoma through increased formation and survival of polyploid giant cancer cells.

Therapeutic resistance is a notable cause of death in patients with ovarian carcinoma. Polyploid giant cancer cells (PGCCs), commonly arising in tumor tissues following chemotherapy, have recently been considered to contribute to drug resistance. As a type III deacetylase, Sirtuin1 (SIRT1) plays essential roles in the cell cycle, cellular senescence, and drug resistance. Accumulating evidence has suggested that alteration in its subcellular localization via nucleocytoplasmic shuttling is a critical process influencing the functions of SIRT1. However, the roles of SIRT1 subcellular localization in PGCC formation and subsequent senescence escape remain unclear. In this study, we compared the differences in the polyploid cell population and senescence state of PGCCs following paclitaxel treatment between tumor cells overexpressing wild-type SIRT1 (WT SIRT1) and those expressing nuclear localization sequence (NLS)-mutated SIRT1 (SIRT1NLSmt ). We investigated the involvement of cytoplasmic SIRT1 in biological processes and signaling pathways, including the cell cycle and cellular senescence, in ovarian carcinoma cells' response to paclitaxel treatment. We found that the SIRT1NLSmt tumor cell population contained more polyploid cells and fewer senescent PGCCs than the SIRT1-overexpressing tumor cell population. Comparative proteomic analyses using co-immunoprecipitation (Co-IP) combined with liquid chromatography-mass spectrometry (LC-MS)/MS showed the differences in the differentially expressed proteins related to PGCC formation, cell growth, and death, including CDK1 and CDK2, between SIRT1NLSmt and SIRT1 cells or PGCCs. Our results suggested that ovarian carcinoma cells utilize polyploidy formation as a survival mechanism during exposure to paclitaxel-based treatment via the effect of cytoplasmic SIRT1 on PGCC formation and survival, thereby boosting paclitaxel resistance. © 2023 The Pathological Society of Great Britain and Ireland.

[Characteristics of Antibiotic Contamination of Soil in China in Past Fifteen Years and the Bioremediation Technology: A Review].

In recent years, the contamination of antibiotics and their resistance genes (ARGs) has attracted the extensive attention of researchers at home and abroad. Soil is an important sink for the migration and transformation of antibiotics and ARGs, which pose a threat to soil organisms and human health. According to the relevant investigations in the past 15 years, the soil has been polluted by antibiotics to varying degrees in China. Bioremediation is a green and environment-friendly remediation technology, which has great potential in the remediation of antibiotic-contaminated soil. This review summarized the spatial and temporal characteristics of antibiotic pollution of soils in China in the past 15 years and the application of plants, animals, and microorganisms in the remediation of antibiotic-contaminated soil. In particular, the recent research advances of microbial electrochemical systems in removing antibiotics and ARGs in soil were reviewed, and the unaddressed issues of relevant research and the direction of future development were proposed, in order to provide a scientific basis for soil pollution remediation.

Expression of aquaporin 1, 3 and 5 in colorectal carcinoma: correlation with clinicopathological characteristics and prognosis.

Background: Prognostic biomarkers in colorectal carcinoma (CRC) have an important role in therapeutic strategy. Studies have shown that high expression of Aquaporin (AQP) is associated with poor prognosis in a variety of human tumors. AQP is involved in the initiation and development of CRC. The present study aimed to investigate the correlation between the expression of AQP1, 3 and 5 and clinicopathological features or prognosis in CRC. Methods: The AQP1, 3 and 5 expressions were analyzed based on the immunohistochemical staining of tissue microarray specimens including 112 patients with CRC between June 2006 and November 2008. The expression score of AQP (Allred_score and H_score) was digitally obtained with Qupath software. Patients were divided into high or low expression subgroups based on the optimal cut-off values. The relationship between expression of AQP and clinicopathological characteristics were evaluated using chi-square test, t-test, or one-way ANOVA, when appropriate. Survival analysis of 5-year progression free survival (PFS) and overall survival (OS) was performed with time-dependent ROC, Kaplan-Meier curves, univariate and multivariate COX analysis. Results: The AQP1, 3 and 5 expressions were associated with regional lymph node metastasis, histological grading, and tumor location in CRC, respectively (p < 0.05). Kaplan-Meier curves showed that patients with high AQP1 expression had worse 5-year PFS than those with low AQP1 expression (Allred_score: 47% vs. 72%, p = 0.015; H_score: 52% vs. 78% p = 0.006), as well as 5-year OS (Allred_score: 51% vs. 75%, p = 0.005; H_score: 56% vs. 80%, p = 0.002). Multivariate Cox regression analysis indicated that AQP1 expression was an independent risk prognostic factor (p = 0.033, HR = 2.274, HR95% CI: 1.069-4.836). There was no significant correlation between the expression of AQP3 and 5 and the prognosis. Conclusion: The AQP1, 3 and 5 expressions correlate with different clinicopathological characteristics and the AQP1 expression may be a potential biomarker of prognosis in CRC.

Medical Costs of Chronic Kidney Disease and Type 2 Diabetes Among Newly Diagnosed Heart Failure Patients With Reduced, Mildly Reduced, and Preserved Ejection Fraction.

The economic burden of heart failure (HF) is enormous, but studies of HF costs typically consider the disease to be a single entity. We sought to distinguish the medical costs for patients with HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). We identified 16,516 adult patients with an incident HF diagnosis and an echocardiogram from 2005 to 2017 in the electronic medical record of Kaiser Permanente Northwest. Using the echocardiogram nearest to the first diagnosis date, we classified patients with HFrEF (ejection fraction [EF] ≤40%), HFmrEF (EF 41% to 49%), or HFpEF (EF ≥50%). We calculated annualized inpatient, outpatient, emergency, pharmaceutical medical utilization and costs and total costs in $2,020, adjusted for age and gender using generalized linear models, with further analysis of the effects of co-morbid chronic kidney disease (CKD) and type 2 diabetes (T2D). For all HF types, 1 in 5 patients were affected by both CKD and T2D, and costs were significantly higher when both co-morbidities were present. Total per-person costs were significantly higher for HFpEF ($33,740, 95% confidence interval $32,944 to $34,536) than HFrEF ($27,669, $25,649 to $29,689) or HFmrEF ($29,484, $27,166 to $31,800), driven by in- and outpatient visits. Across HF types, visits approximately doubled with the presence of both co-morbidities. Due to greater prevalence, HFpEF accounted for the majority of total and resource-specific treatment costs of HF, regardless of the presence of CKD and/or T2D. In summary, the economic burden was greater per HFpEF patient and was further amplified by co-morbid CKD and T2D. HFpEF accounted for the large majority of total HF costs, underscoring the need to implement effective treatments.

Trends in heart failure prevalence in Japan 2014-2019: a report from healthcare administration databases.

AIMS: Contemporary estimates of heart failure (HF) prevalence in Japan are scarce. We aimed to estimate HF prevalence and trends in Japan using nationally representative, large administrative claims databases. METHODS AND RESULTS: This retrospective analysis used data from the Japan Medical Data Center (JMDC) (age ≤74 years) and the Medical Data Vision (MDV) (all ages) databases (study period: 1 January 2014-31 December 31 2019). We calculated HF prevalence using crude and sex-/age-standardized models (weighting based on Japanese census data, 2014-2019). Among 8 954 313 individuals aged ≤74 years from JMDC, and 27 920 174 of all ages from MDV, the cumulative 6 year (2014-2019) crude and sex-/age-standardized prevalence of HF per 1000 persons (95% confidence intervals) in Japan was 21.80 [21.70, 21.89] and 41.79 [30.25, 56.11] using JMDC and 65.09 [65.00, 65.18] and 60.95 [46.94, 77.62], respectively, using MDV. We observed an increasing yearly trend in crude HF prevalence per 1000 persons: 11.12 in 2014 and 14.69 in 2019 for JMDC; 58.09 and 77.18, respectively, for MDV. There was an overall increasing trend of comorbidities over time (2014-2019) among HF patients, especially in type 2 diabetes, malignant cancer, chronic kidney disease, and atrial fibrillation. From 2014 to 2019, the percentage of patients in JMDC with type 2 diabetes increased from 15.4% to 20.8% and 23.4% to 31.5% in MDV; malignant cancer frequency increased from 16.5% to 20.1% in JMDC and 18.8% to 23.9% in MDV; frequency of chronic kidney disease increased from 14.8% to 17.7% in JMDC and 18.2% to 22.7% in MDV; and frequency of atrial fibrillation increased from 13.6% to 15.6% in JMDC and 23.8% to 29.0% in MDV. CONCLUSIONS: We estimated that the prevalence of HF in Japan was 2.2-3.7% for patients aged ≤74 during the period 2014-2019 using the JMDC database, while the prevalence for patients of all ages was 6.5% using the MDV database.

Construction and Enhanced Efficiency of Bi2MoO6/ZnO Compo-Sites for Visible-Light-Driven Photocatalytic Performance.

Bi2MoO6 was one of the important bismuth-based semiconductors with a narrow bandgap, and has been widely used in selective oxidation catalysts, supercapacitors, and energy-storage devices. A series of Bi2MoO6/ZnO composite photocatalysts with different mass ratios were synthesized by the hydrothermal method. The synthesized samples were characterized by XRD, PL, UV-Vis, SEM, TEM, XPS, and BET analysis techniques. Under visible light conditions, Methylene blue (MB) was used as the target degradation product to evaluate its photocatalytic performance. The results showed that the degradation rate constant of Bi2MoO6/ZnO (0.4-BZO) was about twice that of the traditional photocatalysis of ZnO. The Bi2MoO6/ZnO composite catalyst maintained stable performance after four consecutive runs. The high photocatalytic activity of Bi2MoO6/ZnO was attributed to the efficient electron transport of the heterojunction, which accelerates the separation of electron-hole pairs and reduces the probability of carrier recombination near the Bi2MoO6/ZnO heterojunction. Bi2MoO6/ZnO nanocomposites have potential applications in the field of photodegradation.

Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease.

OBJECTIVES: To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. METHODS: The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. RESULTS: A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). CONCLUSION: A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. KEY POINTS: • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.

Risk Factors for Glycemic Control in Hospitalized Patients with Type 2 Diabetes Receiving Continuous Subcutaneous Insulin Infusion Therapy.

INTRODUCTION: Patients with diabetes are confronted with numerous obstacles to achieve adequate glycemic control during hospitalization. The aim of this study was to explore the risk factors associated with glycemic control in hospitalized patients with type 2 diabetes mellitus (T2DM) treated with continuous subcutaneous insulin infusion (CSII). METHODS: This cross-sectional study included 5223 patients hospitalized with T2DM in a tertiary hospital in Xiamen (China) between January 2017 and December 2019. All patients were managed according to established protocols for glycemic monitoring and insulin pump treatment regimens. Demographic information and clinical profiles were collected from electronic health records. Multiple linear regression analysis was used to identify the risk factors associated with glycemic control. RESULTS: Among the 5223 hospitalized patients with T2DM receiving CSII therapy, 55.2% achieved their ideal blood glucose level (3.9-10.0 mmol/L), 44.5% experienced hyperglycemia (> 10.0 mmol/L), and 0.3% experienced hypoglycemia (< 3.9 mmol/L) during their hospitalization. Multivariate analyses showed that among inpatients with T2DM, older age, male gender, higher low-density lipoprotein-cholesterol (LDL-C) level, lower C-peptide (C-P) level, lower body mass index (BMI), longer duration of diabetes, previous insulin prescriptions, nephropathy, and retinopathy were factors more likely to be associated with a blood glucose level in the hyperglycemic range (P < 0.05). We also observed that among hospitalized patients with T2DM, those with lower BMI, lower C-P, lower LDL-C, longer disease duration, and previous insulin prescriptions were more likely to correlate with a higher proportion of hypoglycemia range (all P < 0.05). CONCLUSION: Older age, male gender, lower BMI, lower C-P, higher LDL-C, previous insulin prescriptions, longer duration of diabetes, nephropathy, and retinopathy may be risk factors for a higher proportion of hyperglycemic events in hospitalized patients with T2DM under CSII therapy. Furthermore, lower BMI, lower C-P, lower LDL-C, longer duration of diabetes, and previous insulin prescriptions were found to be important factors for a higher proportion of hypoglycemic events. Evaluating the clinical features, comorbidities, and complications of hospitalized patients is essential to achieve reasonable glycemic control.

Targeted Metabolomics Study of Human Plasma Revealed Activation of the Cytochrome P450 Epoxygenase/Epoxide Hydrolase Axis in Patients with IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of chronic kidney disease. The pathogenic mechanism of IgAN remains largely unknown and thus a specific therapeutic target is lacking. Here, we reported that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis was activated in the patients and is likely a therapeutic target for IgAN. Specifically, quantitative profiling of the plasma from IgAN patients and healthy controls revealed significant changes in plasma levels of CYP/EH-mediated lipid epoxides and diols. Subsequently, CYP2C8, CYP2C18, CYP2J2, EPHX1, and EPHX2 were found to be significantly increased in whole blood cells at mRNA levels from the IgAN patients when compared with those of healthy controls. Immunohistochemical analysis showed that all five CYPs and two EHs were upregulated in the kidney tissue from IgAN patients when compared with normative renal tissue, but the expression locations of the proteins were different with most of them. Treatment of HK-2 cells with IgA1 increased cell viability, compressed cell apoptosis, and increased the protein levels of CYP2C9, EPHX1, and EPHX2. All the results agreed that CYPs/EHs axis is likely the prophylactic and therapeutic target for IgAN, providing IgAN patients with a new intervention strategy.

Functional Characterization of Two RNA Methyltransferase Genes METTL3 and METTL14 Uncovers the Roles of m6A in Mediating Adaptation of Plutella xylostella to Host Plants.

N6-methyladenosine (m6A) is one of the major epigenetic modifications in eukaryotes. Although increasing functions of m6A have been identified in insects, its role in Plutella xylostella L. for host plant adaptation remains unclear. In the current study, we show that the m6A content of P. xylostella was relatively low in different developmental stages and tissues, with no significant differences. Two RNA methyltransferase genes, PxMETTL3 (methyltransferase-like 3) and PxMETTL14 (methyltransferase-like 14), were identified and characterized. PxMETTL3 could be transcribed into two transcripts, and PxMETTL14 had only one transcript; both of these genes were highly expressed in egg and adult stages and reproductive tissues. The CRISPR/Cas9-mediated knockout of PxMETTL3 (ΔPxMETTL3-2) or PxMETTL14 (ΔPxMETTL14-14) confirmed their function in m6A installation into RNA. Furthermore, upon transfer from an artificial diet to the host plant, the mutant strains were affected in terms of larval and pupal weight or adult emergence rate, while the wildtype (WT) strain did not exhibit any difference. In addition, the fecundity and egg hatching rate of the WT strain decreased significantly, whereas only the ΔPxMETTL14-14 mutant strain displayed significantly decreased fecundity. There seemed to be a tradeoff between the stress adaptation and reproduction in P. xylostella mediated by m6A modification. During host transfer, the expression of PxMETTL14 was consistent with the change in m6A content, which implied that PxMETTL14 could respond to host plant defense effectively, and may regulate m6A content. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially expressed transcripts with changes in m6A levels revealed that the potential functions of m6A-related genes may be involved in steroid biosynthesis for larval performance and metabolic pathways for adult reproduction. Overall, our work reveals an epigenetic regulation mechanism for the rapid adaptation of P. xylostella to variations in the host environment.

Bundle branch block and nonspecific intraventricular conduction delay prevalence using Chinese nationwide survey data.

OBJECTIVE: We aimed to determine the prevalence of and the factors associated with intraventricular conduction disturbance in the Chinese population. METHODS: Electrocardiographic data from 42,031 people were retrospectively analysed. The weighted prevalences of left bundle branch block (LBBB), right bundle branch block (RBBB), bifascicular block and nonspecific intraventricular conduction delay (NS-IVCD) were calculated. The independently associated factors were determined using logistic regression analysis. RESULTS: The weighted prevalence for Chinese people older than 45 years was 0.17% for LBBB, 2.16% for RBBB and 0.44% for NS-IVCD. The weighted prevalence for RBBB combined with left anterior fascicular block was 0.17%, and 0.05% for RBBB combined with left posterior fascicular block. There were significant differences in the weighted prevalences of RBBB and NS-IVCD between men and women. The weighted prevalence of LBBB and RBBB increased markedly with increasing age. Age and diabetes were independent factors associated with LBBB, compared with age and sex for RBBB and sex and coronary artery disease for NS-IVCD. CONCLUSIONS: This study provided reliable data for the weighted prevalence of and factors associated with LBBB, RBBB and NS-IVCD in Chinese adults.

Hepatocyte-Conditional Knockout of Phosphatidylethanolamine Binding Protein 4 Aggravated LPS/D-GalN-Induced Acute Liver Injury via the TLR4/NF-κB Pathway.

Acute liver injury (ALI) is a disease that seriously threatens human health and life, and a dysregulated inflammation response is one of the main mechanisms of ALI induced by various factors. Phosphatidylethanolamine binding protein 4 (PEBP4) is a secreted protein with multiple biological functions. At present, studies on PEBP4 exist mainly in the field of tumors and rarely in inflammation. This study aimed to explore the potential roles and mechanisms of PEBP4 on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALI. PEBP4 was downregulated after treatment with LPS/D-GalN in wild-type mice. PEBP4 hepatocyte-conditional knockout (CKO) aggravated liver damage and repressed liver functions, including hepatocellular edema, red blood cell infiltration, and increased aspartate aminotransferase (AST)/alanine aminotrans-ferase (ALT) activities. The inflammatory response was promoted through increased neutrophil infiltration, myeloperoxidase (MPO) activities, and cytokine secretions (interleukin-1ß, IL-1ß; tumor necrosis factor alpha, TNF-α; and cyclooxygenase-2, COX-2) in PEBP4 CKO mice. PEBP4 CKO also induced an apoptotic effect, including increasing the degree of apoptotic hepatocytes, the expressions and activities of caspases, and pro-apoptotic factor Bax while decreasing anti-apoptotic factor Bcl-2. Furthermore, the data demonstrated the levels of Toll-like receptor 4 (TLR4), phosphorylation-inhibitor of nuclear factor kappaB Alpha (p-IκB-α), and nuclear factor kappaB (NF-κB) p65 were upregulated, while the expressions of cytoplasmic IκB-α and NF-κB p65 were downregulated after PEBP4 CKO. More importantly, both the NF-κB inhibitor (Ammonium pyrrolidinedithiocarbamate, PDTC) and a small-molecule inhibitor of TLR4 (TAK-242) could inhibit TLR4/NF-κB signaling activation and reverse the effects of PEBP4 CKO. In summary, the data suggested that hepatocyte-conditional knockout of PEBP4 aggravated LPS/D-GalN-induced ALI, and the effect is partly mediated by activation of the TLR4/NF-κB signaling pathway.