Genome-wide identification, molecular evolution and gene expression of P450 gene family in Cyrtotrachelus buqueti.

BACKGROUND: Insect Cytochrome P450 monooxygenase (CYPs or P450s) plays an important role in detoxifying insecticides, causing insect populations to develop resistance. However, the molecular functions of P450 gene family in Cyrtotrachelus buqueti genome are still lacking. RESULTS: In this study, 71 CbuP450 genes have been identified. The amino acids length of CbuP450 proteins was between 183 aa ~ 1041 aa. They are proteins with transmembrane domains. The main component of their secondary structure is α-helix and random coils. Phylogenetic analysis showed that C. buqueti and Rhynchophorus ferrugineus were the most closely related. This gene family has 29 high-frequency codons, which tend to use A/T bases and A/T ending codons. Gene expression analysis showed that CbuP450_23 in the female adult may play an important role on high temperature resistance, and CbuP450_17 in the larval may play an important role on low temperature tolerance. CbuP450_10, CbuP450_17, CbuP450_23, CbuP450_10, CbuP450_16, CbuP450_20, CbuP450_23 and CbuP450_ 29 may be related to the regulation of bamboo fiber degradation genes in C. buqueti. Protein interaction analysis indicates that most CbuP450 proteins are mainly divided into three aspects: encoding the biosynthesis of ecdysteroids, participating in the decomposition of synthetic insecticides, metabolizing insect hormones, and participating in the detoxification of compounds. CONCLUSIONS: We systematically analyzed the gene and protein characteristics, gene expression, and protein interactions of CbuP450 gene family, revealing the key genes involved in the stress response of CbuP450 gene family in the resistance of C. buqueti to high or low temperature stress, and identified the key CbuP450 proteins involved in important life activity metabolism. These results provided a reference for further research on the function of P450 gene family in C. buqueti.

Accuracy of dynamic navigation compared to static surgical guides and the freehand approach in implant placement: a prospective clinical study.

BACKGROUND: Computer-guided implant surgery has improved the quality of implant treatment by facilitating the placement of implants in a more accurate manner. This study aimed to assess the accuracy of implant placement in a clinical setting using three techniques: dynamic navigation, static surgical guides, and freehand placement. We also investigated potential factors influencing accuracy to provide a comprehensive evaluation of each technique's advantages and disadvantages. MATERIALS AND METHODS: Ninety-four implants in 65 patients were included in this prospective study. Patients were randomly assigned to one of three groups: dynamic navigation, static surgical guides, or freehand placement. Implants were placed using a prosthetically oriented digital implant planning approach, and postoperative CBCT scans were superimposed on preoperative plans to measure accuracy. Seven deviation values were calculated, including angular, platform, and apical deviations. Demographic and consistency analyses were performed, along with one-way ANOVA and post-hoc tests for deviation values. RESULTS: The mean global platform, global apical, and angular deviations were 0.99 mm (SD 0.52), 1.14 mm (SD 0.56), and 3.66° (SD 1.64°) for the dynamic navigation group; 0.92 mm (SD 0.36), 1.06 mm (SD 0.47), and 2.52° (SD 1.18°) for the surgical guide group; and 1.36 mm (SD 0.62), 1.73 mm (SD 0.66), and 5.82° (SD 2.79°) for the freehand group. Both the dynamic navigation and surgical guide groups exhibited statistically significant differences in all values except depth deviations compared to the freehand group (p < 0.05), whereas only the angular deviation showed a significant difference between the dynamic navigation and surgical guide groups (p = 0.002). CONCLUSION: Our findings highlight the superior accuracy and consistency of dynamic navigation and static surgical guides compared to freehand placement in implant surgery. Dynamic navigation offers precision and flexibility. However, it comes with cost and convenience considerations. Future research should focus on improving its practicality. TRIAL REGISTRATION: This study was retrospectively registered at the Thai Clinical Trials Register-Medical Research Foundation of Thailand (MRF) with the TCTR identification number TCTR20230804001 on 04/08/2023. It was also conducted in accordance with the Declaration of Helsinki and approved by the institutional ethics committee at the Xian Jiaotong University Hospital of Stomatology, Xian, China (xjkqII[2021] No: 043). Written informed consent was obtained from all participants.

Prediction of vascular complications in free flap reconstruction with machine learning.

OBJECTIVE: This study aims to explore the risk factors of vascular complications following free flap reconstruction and to develop a clinical auxiliary assessment tool for predicting vascular complications in patients undergoing free flap reconstruction leveraging machine learning methods. METHODS: We reviewed the medical data of patients who underwent free flap reconstruction at the Affiliated Hospital of Zunyi Medical University retrospectively from January 1, 2019, to December 31, 2021. Statistical analysis was used to screen risk factors. A training data set was generated and augmented using the synthetic minority oversampling technique. Logistic regression, random forest and neural network, models were trained, using this dataset. The performance of these three predictive models was then evaluated and compared using a test set, with four metrics, area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 570 patients who underwent free flap reconstruction were included in this study, 46 of whom developed postoperative vascular complications. Among the models tested, the neural network model exhibited superior performance on the test set, achieving an AUC of 0.828. Multivariate logistic regression analysis identified that preoperative hemoglobin levels, preoperative fibrinogen levels, operation duration, smoking history, the number of anastomoses, and peripheral vascular injury as statistically significant independent risk factors for vascular complications post-free flap reconstruction. The top five predictive factors in the neural network were fibrinogen content, operation duration, donor site, body mass index (BMI), and platelet count. CONCLUSION: Hemoglobin levels, fibrinogen levels, operation duration, smoking history, and anastomotic veins are independent risk factors for vascular complications following free flap reconstruction. These risk factors enhance the ability of machine learning models to predict the occurrence of vascular complications and identify high-risk patients. The neural network model outperformed the logistic regression and random forest models, suggesting its potential to aid clinicians in early identification of high-risk patients thereby mitigating patient suffering and improving prognosis.

A cost-effectiveness analysis of fluoride varnish application in preventing Root caries in elderly persons: a Markov simulation study.

BACKGROUND: Root caries are prevalent issues that affect dental health, particularly among elderly individuals with exposed root surfaces. Fluoride therapy has shown effectiveness in preventing root caries, but limited studies have addressed its cost-effectiveness in elderly persons population. This study aimed to evaluate the cost-effectiveness of a fluoride treatment program for preventing root caries in elderly persons within the context of Chinese public healthcare. METHODS: A Markov simulation model was adopted for the cost-effectiveness analysis in a hypothetical scenario from a healthcare system perspective. A 60-year-old subject with 23 teeth was simulated for 20 years. A 5% sodium fluoride varnish treatment was compared with no preventive intervention in terms of effectiveness and cost. Tooth years free of root caries were set as the effect. Transition probabilities were estimated from the data of a community-based cohort and published studies, and costs were based on documents published by the government. The incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Univariate and probabilistic sensitivity analyses were performed to evaluate the influence of data uncertainty. RESULTS: Fluoride treatment was more effective (with a difference of 10.20 root caries-free tooth years) but also more costly (with a difference of ¥1636.22). The ICER was ¥160.35 per root caries-free tooth year gained. One-way sensitivity analysis showed that the risk ratio of root caries in the fluoride treatment group influenced the result most. In the probabilistic sensitivity analysis, fluoride treatment was cost-effective in 70.5% of the simulated cases. CONCLUSIONS: Regular 5% sodium fluoride varnish application was cost-effective for preventing root caries in the elderly persons in most scenarios with the consideration of data uncertainty, but to a limited extent. Improved public dental health awareness may reduce the incremental cost and make the intervention more cost-effective. Overall, the study shed light on the economic viability and impact of such preventive interventions, providing a scientific basis for dental care policies and healthcare resource allocation.

Effects of dietary citrus pulp level on the growth and intestinal health of largemouth bass (Micropterus salmoides).

BACKGROUND: Citrus pulp (CP) is rich in pectin, and studies have shown that pectin possesses antioxidant, anti-inflammatory, and gut microbiota-regulating properties. However, the application of CP in aquafeed is limited. In this study, the effect of dietary inclusion of CP on the intestinal health of largemouth bass (Micropterus salmoides) was investigated. Juveniles of similar size (6.95 ± 0.07 g) were fed isonitrogenous and isoenergetic diets containing different levels of CP (0%, 3%, 6%, 9%, 12%, or 15%) for 58 days. RESULTS: As the level of CP in the feed for largemouth bass increased, the fish's growth performance and intestinal health initially improved and then declined. Adding low doses of CP (≤9%) to the feed had no significant impact on the growth performance of large-mouth black bass, whereas high doses of CP (>9%) significantly reduced their growth performance. Adding 6%, 9%, or 12% of CP to that feed enhanced the expression of genes related to tight junctions, anti-inflammatory activity, anti-apoptotic activity, and antioxidant activity in the intestines of largemouth bass. It reduced intestinal inflammation and improved intestinal nutrient absorption, intestinal mucosal barrier function, and intestinal antioxidant capacity. Moreover, it improved the α-diversity, structure, and function of the intestinal flora. The addition of 6% CP had the most beneficial effect on the intestinal health of largemouth bass. On the other hand, the addition of 15% CP had adverse effects on the intestinal antioxidant capacity and intestinal mucosal barrier function of largemouth bass. CONCLUSION: Adding 6-9% CP to the feed for largemouth bass can improve their intestinal health without having a significant impact on their growth performance. CP could serve as a novel prebiotic and immunostimulant ingredient in aquafeed. © 2023 Society of Chemical Industry.

[Construction of clinical efficacy evaluation system based on optimal clinical experience].

Evidence-based medicine plays an important role in promoting the scientific nature of clinical decision-making. Howe-ver, there is a problem where evidence derived from clinical research may not necessarily be applicable to individual patients. Evidence-based medicine has been introduced into the field of traditional Chinese medicine(TCM) for over 20 years, and although certain achievements have been made, the overall level of clinical research evidence based on the principles of evidence-based medicine in TCM is not high. The acceptance of TCM diagnosis and treatment guidelines developed based on evidence-based medicine methods is generally low. As revealed by the analysis of the problems in the application of evidence-based medicine in the field of TCM, it is found that there is a structural contradiction between clinical randomized controlled trial(RCT) of TCM and the characteristics of TCM clinical practice. They cannot comprehensively, objectively, and truthfully reflect the clinical efficacy and safety of TCM. Conducting clinical RCTs of TCM in pursuit of "evidence" actually means giving up the advantages of TCM in clinical treatment based on syndrome differentiation, prescription changes along with syndromes, and treatment in accordance with three categories of disease cause, which leads to sacrificing some clinical effectiveness of TCM. Based on the concept of evidence-based medicine, this article proposed the construction of "clinical syndrome-based medicine" based on the optimal clinical experience, which was suitable for the characteristics of TCM clinical practice. The key to clinical syndrome-based medicine is the optimal clinical experience, and the core elements of the optimal clinical experience are regularity and reproducibility. Real-world research methods are recommended as a reference for obtaining the optimal clinical experience. Clinical syndrome-based medicine, combining the characteristics of TCM clinical practice and incorporating the concept of evidence-based medicine, is the product of integrating TCM into evidence-based medicine. It is dedicated to improving the clinical efficacy of TCM along with evidence-based medicine.

[Research progress on the construction and applications of metal-organic frameworks in chromatographic stationary phases].

Metal-organic frameworks (MOFs) are a class of porous crystalline materials composed of metal centers or clusters assembled with organic ligands. These materials possess excellent properties, such as large surface areas, high porosities, uniform pore sizes, and diverse structures. Thus, MOFs have been widely applied in various fields, including catalysis, adsorption, sensing, sample pretreatment, and chromatographic separation. The applications of MOFs as stationary phases for chromatographic separation and analysis have attracted considerable attention from the research community in recent years. Compared with traditional chromatographic stationary phases, such as mesoporous silica, nanoparticles, and porous layers, MOFs possess flexible and tunable pore sizes and structures, thereby enabling precise control over their intermolecular interactions. Furthermore, the wide range of functional ligands and topologies of MOFs could potentially facilitate the separation and analysis of complex samples. These unique advantages render MOFs highly suitable for constructing novel chromatographic stationary phases.This article focuses primarily on the construction methods of MOFs as chromatographic stationary phases, and provides an overview of the latest research advancements in their applications in several chromatographic separation techniques such as high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrochromatography (CEC). The existing methods for the preparation and construction of MOFs-based chromatographic stationary phases are classified and evaluated. The construction methods for MOFs as stationary phases for HPLC mainly include filling, precursor-doped polymerization, and post-modification. The construction methods for MOFs as stationary phases for GC predominantly include in situ growth, static coating, and dynamic coating. The stationary phases for CEC can be categorized into packed columns, monolithic columns, and open-tubular columns. Compared with monolithic and packed columns, open-tubular CEC (OT-CEC) offers numerous advantages, including a more flexible and convenient preparation method, enhanced compatibility with various separation media, and higher separation efficiency. Consequently, OT-CEC has emerged as an important method for investigating the preparation of stationary phases for CEC. Several methods such as physical adsorption, covalent attachment, and electrostatic interactions have been developed for the preparation and modification of MOFs-based CEC stationary phases, and extensive studies have been conducted to optimize the performance and applications of MOFs in OT-CEC. However, the existing methods for constructing MOFs-based chromatographic stationary phases present certain limitations. Therefore, the selection of the appropriate MOFs, optimization of their preparation methods, and examination of their performance in different separation modes have become the focus of intensive research.This review also summarizes the different analytical targets (e. g., chiral small molecules, biomacromolecules, and nonchiral molecules) and corresponding separation effects achieved using various MOFs-based chromatographic stationary phases. Finally, future studies focusing on the development of MOFs as chromatographic separation media are discussed. Overall, this review provides a valuable reference for the rational construction and practical applications of advanced MOFs-based chromatographic stationary phases.

Association of carbohydrate intake from different sources with all-cause and cardiovascular mortality among chronic kidney disease populations: assessment of 1999-2018 National Health and Nutrition Examination Survey participation.

This study analysed the data from the NHANES (1999-2018) to examine how different sources of carbohydrate intake affected the all-cause and cardiovascular mortality of 11,302 chronic kidney disease (CKD) patients. The data were adjusted for other factors using various methods. The results showed that CKD patients (stages 1-2 and 3-5) who consumed more carbohydrates from whole grains, fruits, vegetables and less carbohydrates from fruit juice or sauces had lower mortality rates. Replacing fat intake with carbohydrates from whole grains (HR = 0.86[0.78-0.95]), fruits (raw) (HR = 0.79[0.70-0.88]) and non-starchy vegetables (HR = 0.82[0.70-0.96]), but not protein intake, was linked to lower all-cause mortality. The fibre content in carbohydrates might partly account for the benefits of selected carbohydrate intake. This study provided practical recommendations for optimising the carbohydrate sources in CKD patients.

MicroRNA-125a-3p Modulate Amyloid ß-Protein through the MAPK Pathway in Alzheimer's Disease.

BACKGROUND: MicroRNA (miR)-125a-3p is reported to play an important role in some central nervous system diseases, such as Alzheimer's disease (AD). However, a study has not been conducted on the mechanism of miR-125a-3p in the pathological process of AD. METHODS: First, we assessed the expression of miR-125a-3p in AD cohort. Subsequently, we altered the expressions of miR-125a-3p to assess its role in cell viability, cell apoptosis, amyloid-ß (Aß) metabolism, and synaptic activity. Finally, we identified its potential mechanism underlying AD pathology. RESULTS: This study unveiled the potential function of miR-125a-3p through modulating amyloid precursor protein processing. Additionally, miR-125a-3p influenced cell survival and activated synaptic expression through the modulation of Aß metabolism in the mitogen-activated protein kinase (MAPK) pathway via fibroblast growth factor receptor 2. CONCLUSION: Our study indicates that targeting miR-125a-3p may be an applicable therapy for AD in the future. However, more in vitro and in vivo studies with more samples are needed to confirm these results.

Amino-carboxyl cellulose for adsorption of Cd2+ and Pb2.

An amino-carboxyl cellulose was synthesized using the grafting of glycine on the aldehyde cellulose through a Schiff base reaction for the adsorption of heavy metals with Cd2+ and Pb2+ as the representative. Higher affinity of the amino-carboxyl cellulose was found at pH 4.5-5.0 for Cd2+ and 4.0-5.5 for Pb2+. The equilibrium was achieved within 30 min. The adsorption capacities of amino-carboxyl cellulose (Cd2+: 85.7 mg g-1, Pb2+: 115.1 mg g-1, Cu2+: 68.2 mg g-1, Co2+: 60.1 mg g-1, Ni2+ 48.5 mg g-1 and Zn2+: 52.8 mg g-1) at 30 °C were observed. A mild increase in the adsorption capacities of Cd2+ and Pb2+ from 15 to 45 °C was observed. Adsorption data correlated well with the Langmuir and pseudo-second order equations, illustrating chemisorption of Cd2+ and Pb2+ by the amino-carboxyl cellulose. The adsorption of the amino-carboxyl cellulose for Cd2+ and Pb2+ was a spontaneous and endothermic. The amino-carboxyl cellulose owned a high reusability after 4 cycles.

Impact of inflammation and anti-inflammatory modalities on diabetic cardiomyopathy healing: From fundamental research to therapy.

Diabetic cardiomyopathy (DCM) is a prevalent cardiovascular complication of diabetes mellitus, characterized by high morbidity and mortality rates worldwide. However, treatment options for DCM remain limited. For decades, a substantial body of evidence has suggested that the inflammatory response plays a pivotal role in the development and progression of DCM. Notably, DCM is closely associated with alterations in inflammatory cells, exerting direct effects on major resident cells such as cardiomyocytes, vascular endothelial cells, and fibroblasts. These cellular changes subsequently contribute to the development of DCM. This article comprehensively analyzes cellular, animal, and human studies to summarize the latest insights into the impact of inflammation on DCM. Furthermore, the potential therapeutic effects of current anti-inflammatory drugs in the management of DCM are also taken into consideration. The ultimate goal of this work is to consolidate the existing literature on the inflammatory processes underlying DCM, providing clinicians with the necessary knowledge and tools to adopt a more efficient and evidence-based approach to managing this condition.

[Study on the relationship between severe knee osteoarthritis and bone marrow edema].

OBJECTIVE: To investigate the relationship between bone marrow edema and pathological changes, symptoms and signs of severe knee osteoarthritis. METHODS: From January 2020 to March 2021, 160 patients with severe knee osteoarthritis who underwrent MRI of the knee at the Department of Bone and Joint, Wangjing Hospital, China Academy of Chinese Medical Sciences were included. Eighty patients with bone marrow edema were selected as the case group, including 12 males and 68 females, aged from 51 to 80 years old with an average of (66.58±8.10) years old, the duration of disease 5 to 40 months with an average of (15.61±9.25) months. Eighty patients without bone marrow edema were selected as the control group, including 15 males and 65 females, aged from 50 to 80 years old with an average of (67.82±8.05) years old, the duration of disease 6 to 37 months with an average of (15.75±8.18) months, BMI was (28.26±3.13) kg·m-2 ranged from 21.39 to 34.46 kg·m-2. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score (WORMS). The degree of knee osteoarthritis was evaluated by Kellgren- Lawrence(K-L) grade and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The degree of joint pain was evaluated by visual analogue scale(VAS) and WOMAC pain score, the joint signs were evaluated by tenderness, percussion pain, joint swelling and joint range of motion. To explore the relationship between bone marrow edema and knee osteoarthritis, the prevalence of bone marrow edema and K-L grade were compared between the two groups. Furthermore the WORMS score and WOMAC index, pain-related score, and sign-related score correlation coefficient were analyzed to further explore the relationship between bone marrow edema and knee osteoarthritis index, joint pain symptoms and signs. RESULTS: There was 68.75% (55/80) of the patients in the case group were in K-L grade Ⅳ, and 52.5% (42/80) in the control group, indicating a higher proportion of patients with grade Ⅳ in the case group than the control group (χ2=4.425, P<0.05). In the case group, there was a strong correlation between bone marrow edema WORMS score and knee osteoarthritis WOMAC index. (r=0.873>0.8, P<0.001), a moderate correlation between WORMS score and VAS score and WOMAC pain score(r=0.752, 0.650>0.5, P<0.001), a moderate correlation between WORMS score and percussion pain score (r=0.784>0.5, P<0.001), and a weak correlation between WORMS score and VAS and tenderness score, joint swelling score and joint range of motion score (r=0.194, 0.259, 0.296<0.3, P<0.001). CONCLUSION: Our study suggests that severe knee osteoarthritis is associated with an increased risk of bone marrow edema. Bone marrow edema can also lead to knee osteoarthritis joint pain, with percussion pain being a positive sign, but tenderness, joint swelling and limitation of activity are not significantly related to bone marrow edema.

[Study on correlation between bone marrow edema and osteoporosis in patients with severe knee osteoarthritis].

OBJECTIVE: To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis. METHODS: Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group. RESULTS: The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001). CONCLUSION: Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.

Efficacy and mortality of ceftazidime/avibactam-based regimens in carbapenem-resistant Gram-negative bacteria infections: A retrospective multicenter observational study.

OBJECTIVES: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. METHODS: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. RESULTS: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality. CONCLUSION: CAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients' different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter.

Lobetyolin Alleviates Ferroptosis of Skeletal Muscle in 5/6 Nephrectomized Mice via Activation of Hedgehog-GLI1 Signaling.

BACKGROUND: Muscle wasting increases morbidity and mortality and is related to chronic kidney disease (CKD) and dialysis. It is still unclear whether ferroptosis occurs during this progression and whether it is a potential intervention target for the treatment of CKD-related muscle injury. PURPOSE: The objective is to identify potential compounds for treating ferroptosis and muscle wasting and explore the potential mechanisms in vivo/in vitro. METHODS: Initially, we explored whether ferroptosis is present in the skeletal muscle of 5/6 nephrectomized (NPM) mice via RNA-Seq analysis, TUNEL staining, Oil red O staining, MDA/GSH/GSSG level detection and real-time quantitative PCR (qPCR). Subsequently, utilizing our established molecular phenotyping strategy, we screened potential traditional Chinese herb-derived compounds for alleviation of muscle wasting and ferroptosis. HE staining, Oil red O staining, TUNEL staining, immunofluorescence staining, MDA/GSH/GSSG level detection, Fe level detection, western blotting and qPCR were applied to assess the effects of the identified compound on muscle wasting and ferroptosis and explore the potential mechanism. Furthermore, RNA-Seq analysis, ChIP-Seq analysis and further experiments in vitro were performed to determine the role of Hedgehog signaling in the effect of Lobetyolin (LBT) on ferroptosis. RESULTS: In NPM mice, skeletal muscle dysfunction, lipogenesis, reduced GSH/GSSG ratio, decreased GSH content, increased MDA production and and higher levels of ferroptosis markers were observed. LBT treatment (30 mg/kg or 50 mg/kg) significantly alleviates skeletal muscle injury by inhibiting ferroptosis. Additionally, in an in vitro investigation, C2C12 cells exposed to Indolyl sulfate (IS) induced ferroptosis and LBT treatment (20 µM and 50 µM) protected C2C12 from such injury, consistent with the results from the in vivo analysis. Furthermore, it was found LBT increased the levels of protein involving Hedgehog signaling pathway (SMO and GLI1), and rescue analysis revealed that this pathway played a crucial role in the regulation of ferroptosis. Further experiments demonstrated that LBT upregulated a series of suppressors of ferroptosis by activating Gli1 transcription. CONCLUSION: LBT alleviates CKD-induced muscle injury by inhibiting ferroptosis through activation of the Hedgehog signaling pathway.

LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR.

OBJECTIVE: Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. METHODS: The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/ß-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and ß-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. RESULTS: Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/ß-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. CONCLUSION: LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

A user-friendly nomogram for predicting radioiodine refractory differentiated thyroid cancer.

Background: The diagnosis of radioiodine refractory differentiated thyroid cancer (RAIR-DTC) is primarily based on clinical evolution and iodine uptake over the lesions, which is still time-consuming, thus urging a predictive model for timely RAIR-DTC informing. The aim of this study was to develop a nomogram model for RAIR prediction among DTC patients with distant metastases (DM). Methods: Data were extracted from the treatment and follow-up databases of Peking Union Medical College Hospital between 2010 and 2021. A total of 124 patients were included and divided into RAIR (n=71) and non-RAIR (n=53) according to 2015 ATA guidelines. All patients underwent total thyroidectomy followed by at least two courses of RAI treatment. Serological markers and various clinical, pathological, genetic status, and imaging factors were integrated into this study. The pre-treatment stimulated Tg and pre- and post-treatment suppressed Tg at the first and second course RAI treatment were defined as s-Tg1, s-Tg2, sup-Tg1, and sup-Tg2, respectively. Δs-Tg denoted s-Tg1/s-Tg2, and Δs-TSH denoted s-TSH1/s-TSH2. Multivariate logistic regression and correlation analysis were utilized to determine the independent predictors of RAIR. The performance of the nomogram was assessed by internal validation and receiver operating characteristic (ROC) curve, and benefit in clinical decision-making was assessed using decision curve. Results: In univariate logistic regression, nine possible risk factors were related to RAIR. Correlation analysis showed four of the above factors associated with RAIR. Through multivariate logistic regression, Δs-Tg/Δs-TSH<1.50 and age upon diagnosis were obtained to develop a convenient nomogram model for predicting RAIR. The model was internally validated and had good predictive efficacy with an AUC of 0.830, specificity of 0.830, and sensitivity of 0.755. The decision curve also showed that if the model is used for clinical decision-making when the probability threshold is between 0.23 and 0.97, the net benefit of patients is markedly higher than that of the TreatAll and TreatNone control groups.By using 1.50 as a cut-off ofΔs-Tg/Δs-TSH, differing biochemical progression among the generally so-called RAIR can be further stratified as meaningfully rapidly or slowly progressive patients (P=0.012). Conclusions: A convenient user-friendly nomogram model was developed with good predictive efficacy for RAIR. The progression of RAIR can be further stratified as rapidly or slowly progressive by using 1.50 as a cut-off value of Δs-Tg/Δs-TSH.

One-year Efficacy of the Defocus Incorporated Multiple Segment Lens in Chinese Myopic Children.

SIGNIFICANCE: These data demonstrate that defocus incorporated multiple segment (DIMS) lens reduces myopia progression in children during the first year of use. PURPOSE: This study aimed to investigate the efficacy of DIMS myopia control spectacle lens in Chinese myopic children aged 6 to 15 years. METHODS: This is a retrospective study of 1-year longitudinal data. A total of 180 Chinese myopic children were selected from patients at Zhongshan Ophthalmic Center, Sun Yat-sen University, from February 2018 to January 2021. One group consisted of 90 children aged 6 to 15 years, with spherical equivalent refraction -0.50 to -7.75 D (-3.82 ± 1.57 D) and fitted with the DIMS lens. The other group consisted of 90 children fitted with single-vision spectacle lenses and matched with the DIMS group for age, sex, refraction, and progression of myopia in the previous year. One-year myopia progression was measured retrospectively in two groups. Unpaired t test was used to compare the myopia progression between the DIMS group and the control group. Pearson correlation was used to explore the relationship between myopia progression, age, and baseline refraction. RESULTS: After 1 year of DIMS lens wear, myopia progression was significantly lower in the DIMS group (-0.51 ± 0.50 vs. -0.85 ± 0.51 D, P < .001). Myopia progression was positively correlated with age in both groups. The difference between the DIMS and control groups was more pronounced for children aged 10 to 15 years than for children aged 6 to 9 years. CONCLUSIONS: This study confirms that the DIMS lens reduces myopia progression during the first year of use. Efficacy seems to increase with age.

18F-FDG PET-Based Combined Baseline and End-Of-Treatment Radiomics Model Improves the Prognosis Prediction in Diffuse Large B Cell Lymphoma After First-Line Therapy.

RATIONALE AND OBJECTIVES: To develop a combined model incorporating the clinical and PET features for identifying patients with diffuse large B-cell lymphoma (DLBCL) at high risk of progression or relapse after first-line therapy, compared to International Prognostic Index (IPI) and Deauville score (DS) assessment. MATERIALS AND METHODS: 271 18F-FDG PET images with DLBCL were retrospectively collected and randomly divided into the training (n=190) and test dataset (n=81). All visible lesions were annotated. Baseline, end-of-treatment (EoT), and delta PET radiomics features were extracted. IPI model, the baseline clinical model group (MG), DS model, the combined clinical MG, the PET-based radiomics MG, and the combined MG were constructed to predict 2-year time to progression (2Y-TTP). For each MG, the cross-combination method was performed to generate 1680 candidate models based on three normalization methods, 20 features, 4 feature-selection methods, and 7 classifiers. The model achieving the highest AUC was selected as the best for each MG. Cox regression analysis was further performed. RESULTS: In the test set, the best combined model showed better discriminative power compared to IPI model, the best baseline clinical model, DS model, the best combined clinical model, and the best PET-based radiomics model (AUC 0.898 vs. 0.584, 0.695, 0.756, 0.824, 0.832; p < 0.001, 0.014, 0.018, 0.152, 0.042, respectively). The combined model was superior to other models for progression-free-survival prediction (C-index: 0.853 vs. 0.568, 0.666, 0.753, 0.808, 0.814, respectively). CONCLUSION: A combined model for identifying patients at high risk of progression or relapse after first-line therapy was constructed, superior to IPI and DS assessment.

A velocity-guided Harris hawks optimizer for function optimization and fault diagnosis of wind turbine.

Harris hawks optimizer (HHO) is a relatively novel meta-heuristic approach that mimics the behavior of Harris hawk over the process of predating the rabbits. The simplicity and easy implementation of HHO have attracted extensive attention of many researchers. However, owing to its capability to balance between exploration and exploitation is weak, HHO suffers from low precision and premature convergence. To tackle these disadvantages, an improved HHO called VGHHO is proposed by embedding three modifications. Firstly, a novel modified position search equation in exploitation phase is designed by introducing velocity operator and inertia weight to guide the search process. Then, a nonlinear escaping energy parameter E based on cosine function is presented to achieve a good transition from exploration phase to exploitation phase. Thereafter, a refraction-opposition-based learning mechanism is introduced to generate the promising solutions and helps the swarm to flee from the local optimal solution. The performance of VGHHO is evaluated on 18 classic benchmarks, 30 latest benchmark tests from CEC2017, 21 benchmark feature selection problems, fault diagnosis problem of wind turbine and PV model parameter estimation problem, respectively. The simulation results indicate that VHHO has higher solution quality and faster convergence speed than basic HHO and some well-known algorithms in the literature on most of the benchmark and real-world problems.