[Research progress on C_(20)-diterpenoid alkaloids and their bioactivities in Ranunculaceae].

C_(20)-diterpenoid alkaloids are mainly distributed in plants of genus Aconitum, Delphinium, and Consolida in the Ranunculaceae. Their chemical structures are mainly categorized into nine types such as atisines, denudatines, hetidines, and hetisines. Bioactivity studies have shown that C_(20)-diterpenoid alkaloids have exhibited superior anti-tumor, analgesic, antiarrhythmic, and anti-inflammatory effects. In this review, the chemical structures and biological activities of 190 C_(20)-diterpenoid alkaloids reported in the Ranunculaceae from 2002 to the present were summarized, so as to provide a reference for the subsequent research on C_(20)-diterpenoid alkaloids in plants of Ranunculaceae.

[Guidelines for traditional dietary care in autumn and winter].

The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.

Puerarin inhibits macrophage M1 polarization by combining STAT1 to reduce myocardial damage in EAM model mice.

Myocarditis is an inflammatory lesion of the myocardium that is caused by a variety of factors. At present, treatment of symptoms remains the main clinical intervention, but it cannot reduce the myocarditis damage caused by inflammation. M1 macrophages are thought to contribute significantly to the occurrence and development of inflammation by secreting a large number of proinflammatory factors. Puerarin is an isoflavone derivative isolated from pueraria that can be used as a dietary supplement and exerts wide range of anti-inflammatory and antioxidant effects. However, the mechanism underlying its anti-inflammatory effects needs to be further studied. The objective of this study was to investigate whether puerarin inhibited M1 polarization by affecting the JAK-STAT signaling pathway in a mouse model of autoimmune myocarditis, thus inhibiting the occurrence of inflammation in experimental autoimmune myocarditis (EAM) model mice. The results showed that EAM model mice treated with puerarin showed milder clinical symptoms and inflammatory infiltration than EAM model mice. Puerarin suppressed the in vivo and in vitro JAK1/2-STAT1 signal transduction in macrophages, thus inhibiting M1 polarization, reducing the secretion of proinflammatory factors, and ultimately decreasing IFN-γ and TNF-α levels in vivo, which led to myocardial apoptosis. Thus, puerarin could alleviate myocardial damage caused by inflammation. The conclusion of this study was that puerarin reduced myocardial damage in EAM model mice by regulating the polarization of macrophages toward M1, and this inhibitory effect may be achieved by inhibiting JAK1/2-STAT1 signaling.

Predictive ability of rule of 3's in parathyroid cancer - outcomes from a South Asia cohort.

Background Preoperative diagnosis of parathyroid cancer (PTTC) where possible allows for en-bloc resection of the tumour, which is associated with excellent prognosis. The rule of > 3 (size of tumour larger than 3cm; corrected calcium more 3mmol/L) as proposed by Schulte and Talat, has a specificity of 95% in predicting malignancy in parathyroid neoplasms. We looked at the impact of rule of 3's in predicting malignancy and outcomes on intervention in a South Asia cohort. Methods Patients who underwent parathyroid surgery between 2010 - 2023 at two tertiary referral centres were assessed. Patients with PTTC were selected and their clinicopathological parameters, treatment modalities, and outcomes were analyzed. Results 13 of 336 (3.8%) patients with a mean age of 61.8 (+/-17.5) years was diagnosed with PC during the study period. The highest mean preoperative values were: PTH (92.4+/-66.27 pmol/L), highest corrected calcium (3.21+/- 0.28 mmol/L) and alkaline phosphatase (419 IU/ml). Nine patients underwent en bloc excision while the other had focussed parathyroidectomy. Recurrences were recorded in 2 (28.5%) patients over a mean follow up period of 69 (+/-48.6) months. One patient with lung metastasis underwent video assisted thoracic surgery (VATS). There was no disease specific mortality in this cohort during the study period. Conclusions In our experience, the predictive rule of 3's has low sensitivity to suspect parathyroid cancer preoperatively, resulting in limited usefulness in clinical practice. Outcomes appear to be less favourable with higher recurrence rates in cases where less than enbloc resection is performed.

Maduraflavacins A-E, Unusual Phenyl Polyene Metabolites Produced by a Rare Marine-Derived Actinomadura sp.

Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E (1-5), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C (1-3) possessed a 1-N-ß-d-glucosamine-(3 → 1)-O-ß-d-glucopyranosyl-(3 → 1)-O-ß-d-glucopyranosyl-(6 → 1)-O-ß-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus, respectively.

Effect of miR-184 on Multiple Myeloma by Targeting Notch1.

OBJECTIVE: Multiple myeloma (MM) is caused by abnormal cloning of plasma cells. miR-184 is abnormally expressed in several types of tumors, but its expression and role in MM have not been reported. METHODS: The bone marrow samples of healthy controls and MM patients were collected, and plasma cells were sorted. The multiple myeloma cell line OPM-2 was cultured and assigned into miR-NC+siRNA-NC group, miR-184 inhibitor+siRNA-NC group, and miR-184 inhibitor+siRNA-Notch1 group. Cell proliferation was assessed by MTT assay. Clone formation was evaluated by colony formation assay. Cell apoptosis activity was tested with flow cytometry. Notch1 and cleaved caspase3 protein expressions were detected. RESULTS: MiR-184 expression was increased in myeloma plasma cells (P<0.05). Transfection of miR-184 inhibitor can downregulate miR-184 expression, increase the levels of Notch1 and cleaved caspase3, inhibit OPM-2 cell proliferation, restrain colony formation, enhance caspase3 activity, and suppress tumor cell invasion (P<0.05). However, administration of siRNA-Notch1 retarded the effect of miR-184 inhibitor by decreasing the expressions of Notch1 and cleaved caspase3, enhancing colony formation and tumor cell invasion, as well as inhibiting caspase3 activity and cell proliferation. CONCLUSION: Our data indicated that miR-184 expression is increased in myeloma plasma cells. Down-regulation of miR-184 promotes MM cell apoptosis and inhibits proliferation and colony formation by regulating Notch1 expression.

The influencing factors of nurses' job engagement in tertiary, A grade hospitals in East China: A cross-sectional study.

AIM: To explore the effects of demographic characteristics, mental workload, and Adversity quotient (AQ) on the job engagement of nurses in East China. DESIGN: A quantitative and cross-sectional study. METHOD: The survey collected questionnaire data on mental workload, adversity quotient, and job engagement from 473 nurses selected working in 12 Grade-A tertiary hospitals based on informed consent in East China between July 2020 and March 2021. RESULTS: The total score of mental workload was 78.24 ± 11.65, the adversity quotient score was 128.26 ± 15.84, job engagement score was 42.32 ± 7.79. Job engagement has a remarkable positive correlation with adversity quotient (r = 0.613, p<0.001), and a negative correlation with mental workload (r = -0.499, p<0.001). Mental workload has an apparent negative correlation with adversity quotient (r = -0.291, p<0.001). Labor-management relationship with current organization, department, study to get a degree or diploma in spare time, attitude towards a career in Nursing, attitude towards the current career position, satisfaction with marriage, social support, load feelings, self-assessment, control, and endurance could predict 70.9% of job engagement of nurses. CONCLUSIONS: The mental workload of nurses was higher, the AQ was at a medium level, and the job engagement of nurses was also slightly higher. Labor-management relationship with current organization, department, study to get a degree or diploma in spare time, attitude towards a career in Nursing, attitude towards the current career position, satisfaction with marriage, social support, load feelings, self-assessment, control, and endurance had predictive effects on nurses' job engagement. It is necessary to take a variety of measures according to the social-demographic characteristics, improve the adversity quotient, and evaluate the mental workload correctly, to improve the job engagement of nurses. IMPACT: The epidemic situation and other emergencies make the work pressure of nurses in Grade-A tertiary hospitals increase suddenly. It should pay attention to the influence of different demographic factors, and pay attention to the correct guidance of work demand-mental workload, as well as the cultivation, and improvement of job resource-AQ, which can improve the job engagement of nurses to some extent. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Characterization and comparison of metabolites in colostrum from yaks, buffaloes, and cows based on UPLC-QTRAP-MS metabolomics.

Colostrum from yaks and buffaloes possesses substantial nutritional value, yet the complete array of metabolites within remains insufficiently elucidated. This study scrutinizes the metabolite profiles of yak, buffalo, and cow colostrum utilizing targeted metabolomics paired with ultra-performance liquid chromatography-tandem triple quadrupole linear ion trap mass spectrometry (UPLC-QTRAP-MS). The analysis detected 362 metabolites across all samples. Furthermore, 63, 77, and 46 differential metabolites were selected between yak and buffalo colostrum, yak and cow colostrum, and buffalo and cow colostrum, respectively. Yak colostrum notably contained higher concentrations of inositol, glycine, and carnitine, whereas buffalo colostrum was distinguished by a substantial presence of primary bile acids, which facilitate fat digestion. These findings offer profound insights into yak and buffalo colostrum, providing critical data to propel advancements in the dairy industry.

Effects of integrated traditional Chinese and Western medicine for acute pancreatitis: A real-world study in a tertiary teaching hospital.

AIM: This study aimed to evaluate whether integrated traditional Chinese medicine (TCM) and Western medicine (WM) is more effective than WM for acute pancreatitis (AP). METHODS: Patients with AP were enrolled and divided into the TCM and WM (TCM&WM) and WM groups according to the therapeutic protocol in real clinical settings. We applied 1:3 propensity score matching, which was to adjust confounding factors. The primary outcome was mortality, whereas the secondary outcomes were organ failure, organ supportive therapies, local complications, hospitalization cost, and length of hospital stay. Sensitivity and subgroup analyses were also performed. RESULTS: Of 5442 patients with AP, 4691 and 751 were included in the TCM&WM and WM groups, respectively. After PSM, patient baseline characteristics were well balanced. Compared with the WM group (n = 734), the TCM&WM group (n = 2096) had lower overall mortality rate (1.7% vs. 3.4%; risk ratio, 0.482; 95% confidence interval, 0.286-0.810; p = 0.005). The TCM&WM group was associated with lower risk of persistent renal failure, multiple organ failure, and infection, lower utilization of organ supportive therapies, shortened lengths of hospital and intensive care unit stay, and lower hospital costs. Sensitivity analyses showed similar results. Subgroup analysis favored TCM&WM treatment for patients aged < 60 years, with hypertriglyceridic etiology, and with admission interval between 24 and 48 h. CONCLUSION: TCM&WM treatment can achieve lower risks of mortality and organ failure and better economic effectiveness in patients with AP than WM treatment. This study provides a promising alternative of TCM&WM treatment for AP in the real-world setting.

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis.

BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

CRISPR/Cas9-based editing of NF-YC4 promoters yields high-protein rice and soybean.

Genome editing is a revolution in biotechnology for crop improvement with the final product lacking transgenes. However, most derived traits have been generated through edits that create gene knockouts. Our study pioneers a novel approach, utilizing gene editing to enhance gene expression by eliminating transcriptional repressor binding motifs. Building upon our prior research demonstrating the protein-boosting effects of the transcription factor NF-YC4, we identified conserved motifs targeted by RAV and WRKY repressors in the NF-YC4 promoters from rice (Oryza sativa) and soybean (Glycine max). Leveraging CRISPR/Cas9 technology, we deleted these motifs, resulting in reduced repressor binding and increased NF-YC4 expression. This strategy led to increased protein content and reduced carbohydrate levels in the edited rice and soybean plants, with rice exhibiting up to a 68% increase in leaf protein and a 17% increase in seed protein, and soybean showing up to a 25% increase in leaf protein and an 11% increase in seed protein. Our findings provide a blueprint for enhancing gene expression through precise genomic deletions in noncoding sequences, promising improved agricultural productivity and nutritional quality.

Development of Integrin-Facilitated Bispecific Aptamer Chimeras for Membrane Protein Degradation.

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3ß1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins. ITGBACs consist of two aptamers, one targeting ITGA3B1 and another binding to the membrane-associated protein of interest (POI), effectively transporting the POI into lysosomes for degradation. Our findings demonstrate that ITGBACs effectively eliminate pathological membrane proteins, such as CD71 and PTK7, inducing significant cell-cycle arrest and apoptosis and markedly inhibiting tumor growth in tumor-bearing mice models. Therefore, this work provides a novel and versatile membrane protein degradation platform, offering a promising targeted therapy based on tumor-specific LTRs.

The Association Between Triglyceride Glucose-Body Mass Index and Kidney Impairment in Patients with Type 2 Diabetes Mellitus.

Purpose: Insulin resistance is associated with kidney impairment in patients with type 2 diabetes mellitus (T2DM). The triglyceride glucose-body mass index (TyG-BMI), which combines the TyG index with body mass index (BMI), has received significant attention as a tool for evaluating insulin resistance. Thus, the aim of this study was to explore the association between TyG-BMI and kidney impairment in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: The cross-sectional analysis included 1080 patients with T2DM, and data were collected retrospectively. TyG-BMI was calculated by fasting blood glucose, triglyceride, and body mass index. Results: TyG-BMI was significantly higher in T2DM patients with albuminuria than those without albuminuria (232.16 [206.52-268.02] vs 229.83 [206.11-255.64], p =0.023). T2DM patients with chronic kidney disease (CKD) showed a significantly higher value of TyG-BMI compared with those without CKD (232.23 [206.46-268.28] vs 229.73 [206.11-255.49], p=0.014). Correlation analysis showed a significantly positive association between TyG-BMI and metabolic parameters including BMI (r = 0.866, p < 0.001), TG (r = 0.630, p < 0.001), TC (r = 0.119, p < 0.001), HDL-C (r = -0.374, p < 0.001), FBG (r = 0.297, p < 0.001), and HbA1c (r = 0.116, p < 0.001) in patients with T2DM. The binary logistic regression analysis found that TyG-BMI was an independent factor for albuminuria (OR = 1.004, 95% CI: 1.001-1.008, p = 0.010) and CKD (OR = 1.005, 95% CI: 1.001-1.008, p = 0.005) in patients with T2DM respectively. Conclusion: The study suggests that TyG-BMI is associated with kidney impairment in patients with T2DM. Given that TyG-BMI is a novel parameter of insulin resistance, the study results indicates that clinicians should pay close attention to screening for kidney impairment in T2DM patients with insulin resistance.

Geometric consistency among atherosclerotic plaques in carotid arteries evaluated by multidimensional parameters.

The three-dimensional (3D) geometry of carotid atherosclerotic plaques is associated with multiple cardiovascular diseases. However, it is unknown if carotid plaques of different sizes are consistent in 3D geometry, with a lack of quantitative observation. We aim to evaluate the geometric consistency of carotid plaques using the correlations between multidimensional parameters. 42 cases with asymptomatic stenosis caused by atherosclerotic plaque in the carotid artery were included. Carotid plaques and calcifications were identified on computed tomography angiography images and 3D reconstructed. Multidimensional geometric parameters (length, surface area, volume, etc.) were measured on the reconstructed 3D structures. Linear and non-linear (power function) fittings were used to investigate the relationships between multidimensional parameters. The analysis was performed based on cases and plaques, respectively. Spearman rank correlation analysis, R-squared, and p-values were used to evaluate the significance of the relationship. Significant relationship was defined as R-squared >0.25 and p < 0.05. In total, 112 atherosclerotic plaques and 74 calcifications were extracted. In plaque-based analysis, significant correlations were widely observed between paired multidimensional parameters of carotid plaques, where non-linear fitting showed higher R-squared values. Plaque volume and surface area were significantly correlated with total volume and total surface area of intra-plaque calcifications. In subject-based analysis, triglycerides and total cholesterol were significantly correlated with carotid plaque size. There is a consistency in geometry among carotid atherosclerotic plaques of different sizes. The size of a carotid plaque is associated with the patient's lipid profile.

The global burden of maternal disorders attributable to iron deficiency related sub-disorders in 204 countries and territories: an analysis for the Global Burden of Disease study.

Background: Pregnancy-related anemia presents a significant health concern for approximately 500 million women of reproductive age worldwide. To better prevent maternal disorders, it is essential to understand the impact of iron deficiency across different maternal disorders, regions, age groups, and subcategories. Methods: Based on the comprehensive maternal disorders data sourced from the 2019 Global Burden of Disease study, an investigation was carried out focusing on Disability-Adjusted Life Years (DALYs) associated with iron deficiency spanning the period from 1990 to 2019. In addition, Estimated Annual Percentage Changes (EAPCs) were computed for the duration of the study. Results: Our study indicates decreasing mortality rates and years of life lost due to maternal conditions related to iron deficiency, such as maternal hemorrhage, miscarriage, abortion, hypertensive disorders, and infections. However, mortality rates and years of life lost due to indirect and late maternal deaths, as well as deaths aggravated by HIV/AIDS, have increased in high socio-demographic index (SDI) regions, especially in North America. Moreover, the proportion of maternal deaths aggravated by HIV/AIDS due to iron deficiency is rising globally, especially in Southern Sub-Saharan Africa, Oceania, and Georgia. In addition, in the Maldives, the age-standardized DALYs for maternal disorders attributable to iron deficiency exhibited a notable decreasing trend, encompassing a range of conditions. Furthermore, there was a significant decrease in Disability-Adjusted Life Years rate for miscarriages and preterm births among women aged 15-49, with hypertensive disorders posing the highest burden among women aged 15-39. Conclusion: The burden of maternal disorders caused by iron deficiency is decreasing in most regions and subtypes, except for deaths aggravated by HIV/AIDS. By thoroughly understanding the details of how iron deficiency impacts the health of pregnant women, health policymakers, healthcare professionals, and researchers can more effectively pinpoint and address the root causes of inequalities in maternal health.

Loss of TREM2 diminishes CAA despite an overall increase of amyloid load in Tg-SwDI mice.

INTRODUCTION: The microglial receptor triggering receptor expressed on myeloid cells 2 (TREM2) is a major risk factor for Alzheimer's disease (AD). Experimentally, Trem2 deficiency affects parenchymal amyloid beta (Aß) deposition. However, the role of TREM2 in cerebrovascular amyloidosis, especially cerebral amyloid angiopathy (CAA), remains unexplored. METHODS: Tg-SwDI (SwDI) mice, a CAA-prone model of AD, and Trem2 knockout mice were crossed to generate SwDI/TWT, SwDI/THet, and SwDI/TKO mice, followed by pathological and biochemical analyses at 16 months of age. RESULTS: Loss of Trem2 led to a dramatic decrease in CAA and microglial association, despite a marked increase in overall brain Aß load. Single nucleus RNA sequencing analysis revealed that in the absence of Trem2, microglia were activated but trapped in transition to the fully reactive state, with distinct responses of vascular cells. DISCUSSION: Our study provides the first evidence that TREM2 differentially modulates parenchymal and vascular Aß pathologies, offering significant implications for both TREM2- and Aß-targeting therapies for AD. HIGHLIGHTS: Triggering receptor expressed on myeloid cells 2 (TREM2) differentially modulates brain parenchymal and vascular amyloidosis. Loss of Trem2 markedly reduces cerebral amyloid angiopathy despite an overall increase of amyloid beta load in Tg-SwDI mice. Microglia are trapped in transition to the fully reactive state without Trem2. Perivascular macrophages and other vascular cells have distinct responses to Trem2 deficiency. Balanced TREM2-targeting therapies may be required for optimal outcomes.

Cofrogliptin once every 2 weeks as add-on therapy to metformin versus daily linagliptin in patients with type 2 diabetes in China: A randomized, double-blind, non-inferiority trial.

AIM: We evaluated the efficacy and safety of cofrogliptin, a novel dipeptidyl peptidase-4 inhibitor taken once every 2 weeks (Q2W), compared with linagliptin (taken daily) in patients with type 2 diabetes inadequately controlled on metformin in China. MATERIALS AND METHODS: In this phase 3 randomized, double-blind, active-controlled, multicentre study, patients were randomly assigned 1:1:1 to receive cofrogliptin 10 mg Q2W, cofrogliptin 25 mg Q2W, or linagliptin 5 mg daily, all as an add-on treatment to metformin, for 24 weeks. Eligible patients could enter an open-label extension period and receive cofrogliptin 25 mg Q2W for an additional 28 weeks. The primary endpoint was change in glycated haemoglobin from baseline to 24 weeks, with a non-inferiority margin of 0.4% for cofrogliptin versus linagliptin treatment. RESULTS: Overall, 465 patients entered the 24-week treatment period (median age: 57.0 years). The least-squares mean (standard error) change in glycated haemoglobin from baseline to week 24 was -0.96 (0.063), -0.99 (0.064) and -1.07 (0.065) for the cofrogliptin 10 mg, cofrogliptin 25 mg and linagliptin 5 mg groups, respectively. The between-group difference met the predefined margin for non-inferiority of cofrogliptin (10 and 25 mg) versus linagliptin treatment. The incidence of common adverse events (≥5% patients) during the 24-week treatment period was similar between treatment groups. There were no serious hypoglycaemic events. CONCLUSION: In Chinese patients with type 2 diabetes inadequately controlled on metformin, the glucose-lowering effect of cofrogliptin (Q2W) was non-inferior to linagliptin (daily), with a similar safety profile maintained over 52 weeks of treatment.

Energy dissipation damage constitutive relation of CFRP passively confined coal sample.

In view of the stability problem of coal pillars left over during coal resource mining, (Carbon Fiber Reinforced Polymer) CFRP sheet is applied in coal pillar reinforcement. Uniaxial compression tests of CFRP passively confined coal samples are carried out to explore the mechanical response mechanism of passively confined coal samples under different layers, and the energy dissipation damage constitutive relationship of CFRP passively confined coal samples is established based on the energy dissipation principle. The conclusions are: As CFRP layers increased, the local damage of coal samples before the peak evolved from a 'cliff-like jagged' to a 'capillary jagged', with post-peak instability marked by a shift to more 'cliff-like' characteristics. The tests revealed improvements in peak strength and elastic modulus, with a defined functional relationship between these properties and CFRP layers. The energy storage capacity of passively confined coal samples improved with CFRP layers, requiring less axial deformation to achieve equivalent energy levels. The energy dissipation rate showed an initial decrease followed by an increase, with a minimum inflection point, the elastic energy consumption ratio tends to decrease slowly and then rapidly during post-peak instability. A damage constitutive relationship and evolution equation were developed, highlighting that the CFRP sheet significantly inhibits damage, with diminishing effectiveness beyond two layers. The study concludes that three-layer CFRP sheets provide optimal confinement, offering a novel strategy for the reinforcement of coal pillars and the prevention and control of rock burst, without considering the actual coal pillar dimensions and shape. To sum up, the use of CFRP sheet to strengthen coal pillar has considerable potential research value in strengthening coal pillar and improving the recovery rate of coal resources.

Longitudinal study of the manifestations and mechanisms of technology-related prescribing errors in pediatrics.

OBJECTIVES: To examine changes in technology-related errors (TREs), their manifestations and underlying mechanisms at 3 time points after the implementation of computerized provider order entry (CPOE) in an electronic health record; and evaluate the clinical decision support (CDS) available to mitigate the TREs at 5-years post-CPOE. MATERIALS AND METHODS: Prescribing errors (n = 1315) of moderate, major, or serious potential harm identified through review of 35 322 orders at 3 time points (immediately, 1-year, and 4-years post-CPOE) were assessed to identify TREs at a tertiary pediatric hospital. TREs were coded using the Technology-Related Error Mechanism classification. TRE rates, percentage of prescribing errors that were TREs, and mechanism rates were compared over time. Each TRE was tested in the CPOE 5-years post-implementation to assess the availability of CDS to mitigate the error. RESULTS: TREs accounted for 32.5% (n = 428) of prescribing errors; an adjusted rate of 1.49 TREs/100 orders (95% confidence interval [CI]: 1.06, 1.92). At 1-year post-CPOE, the rate of TREs was 40% lower than immediately post (incident rate ratio [IRR]: 0.60; 95% CI: 0.41, 0.89). However, at 4-years post, the TRE rate was not significantly different to baseline (IRR: 0.80; 95% CI: 0.59, 1.08). "New workflows required by the CPOE" was the most frequent TRE mechanism at all time points. CDS was available to mitigate 32.7% of TREs. DISCUSSION: In a pediatric setting, TREs persisted 4-years post-CPOE with no difference in the rate compared to immediately post-CPOE. CONCLUSION: Greater attention is required to address TREs to enhance the safety benefits of systems.

High efficiency removal of antibiotic resistance gene with designer zinc-finger protein.

The use of agricultural biomass-based fertilizers, and the release of feces into the environment leads to last-lasting pollution of antibiotic resistance genes that cannot be removed from waters via traditional methods, resulting in significant health threats. To solve this issue, an antibiotic resistance gene removal method was proposed and tested that used sequence-specific DNA-binding designer zinc finger proteins, which target an 18-bp DNA sequence for specific antibiotic resistance gene binding and removal. Targeting the sulfonamide-resistant sul1 gene, sul1-binding zinc-finger protein was designed, overexpressed, and purified. This protein showed specific binding with sul1 over tetA that do not have the targeted sequence. This protein was further immobilized on agarose-based resins to prepare a sul1-removal column. When loaded with 10 mg protein, this column can remove over 99 % sul1 in water, suggesting high efficiency. This work presents a new method attempting to eliminate environmental and health threats posed by antibiotic resistance genes.