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Benefiting from the good electromechanical performance, ionic conductive hydrogel can easily convert the deformation into electrical signals, showing great potential in wearable electronic devices. However, due to the high water content, icing and water evaporation problems seriously limit their development. Although additives can ease these disadvantages, the accompanying performance degradation and complex preparation processes couldn't meet application needs. In this work, a convenient method was provided to prepare ionic conductive hydrogels with sensitive electromechanical performance, harsh environmental tolerance, and long-term stability without additives. Based on the hydratability between metal ions and water molecules resulting in spatial condensation of the hydrogel framework, the hydrogel exhibits good flexibility and ionic conductivity (70.3 mS/cm). Furthermore, the metal salt can bind with water molecules to reduce the vapor pressure, thus endowing the hydrogel with good freezing resistance (-40 °C) and long-term stability over a wide temperature range (-20 °C-50 °C). Based on these unique advantages, the hydrogel shows good sensitivity. Even in a harsh environment, it still maintained excellent stability (-20 °C-50 °C, GF = 2.2, R2 > 0.99). Assembled with a Wi-Fi device, the hydrogel sensor demonstrates good health activity and physiological state detection performance, demonstrating great potential for wearable medical devices.
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The oxidation state (OS) holds significant importance in the field of chemistry and serves as a crucial parameter for tracking electrons. Lanthanide (Ln) elements predominately exhibit a +III oxidation state, with a few elements such as Ce, Pr, Nd, Tb, and Dy able to achieve a +IV oxidation state. Over the past century, numerous attempts to synthesize Pr(V) have been made without success until recent reports on Pr(V) oxides and nitride-oxide in the gas phase expanded our understanding of Ln elements. However, the formation of Pr(V) in the condensed phase remains an open question. In this work, based on advanced quantum chemical investigations, we predict that formation of the solid-state CsPrVF6 from Pr(III) and Pr(IV) complexes is exothermic, indicating that CsPrVF6 is stable. The crystal structure comprises [PrF6]- octahedral clusters occupying the interstitial spaces of Cs cations. Electronic structure analysis reveals that the CsPrF6 crystal has a closed-shell structure and that Pr reaches its highest oxidation state of +V. The results indicate that the existence of Pr(V) in solid-state Ln fluorides is not impossible, which enriches our understanding of high-valence Ln compounds.
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The potential of high entropy oxides (HEOs) as high-performance energy storage materials and catalysts has been mainly understood through their bulk structures. However, the importance of their surfaces, which may play an even more critical role, remains largely unknown. In this study, we employed advanced scanning transmission electron microscopy to investigate the atomic-scale structural and chemical responses of CeYLaHfTiZrOx HEOs to high-temperature redox environments. Our observations reveal dynamic elemental and structural reconstructions in the surface of HEOs under different gas environments, contrasting with the high stability of the bulk structure. Notably, the surfaces of HEO particles consistently exhibit abundant oxygen vacancies, regardless of the redox environment. These findings indicate that HEOs offer distinct advantages in facilitating chemical and electrochemical reactions, relying on oxygen vacancies. Our results also suggest that the exceptional performance of HEOs in energy storage applications arises from surface structural and chemical adaptability.
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BACKGROUND: Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis. METHODS: Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023. RESULTS: Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve. CONCLUSIONS: Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.
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Metal halide perovskites have emerged as promising materials for X-ray detection due to their high X-ray attenuation coefficients, defect tolerance, and suitability for large-area, low-temperature fabrication. However, the intrinsic high ion conductivity of these materials presents challenges, such as high dark current density and current drift, which impair the stability and sensitivity of perovskite X-ray detectors. This study introduces an approach to mitigating these issues by incorporating 2,2,3,3,3-pentafluoropropylamine hydrochloride (PFH) into polycrystalline MAPbI3-xClx films using a one-step blade-coating method. PFH aggregates at grain boundaries, raising local vacuum energy levels and passivating surface defects, thereby reducing ion conductivity without affecting electron conductivity. As a result, this approach significantly reduces the dark current and enhances sensitivity, achieving a low detection limit of 14.7 nGyair/s. Additionally, it improves signal stability, consistency, and response speed of the detector. These findings suggest that PFH is a promising additive for advancing the performance and practical application of polycrystalline metal halide perovskite-based X-ray detectors.
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Combining the hydrogen (H2) extraction process and organic oxidation synthesis in photooxidation-reduction reactions mediated by semiconductors is a desirable strategy because rich chemicals are evolved as byproducts along with hydrogen in trifling conditions upon irradiation, which is the only effort. The bifunctional photocatalytic strategy facilitates the feasible formation of a CâO/CâC bond from a large number of compounds containing a X-H (X = C, O) bond; therefore, the production of H2 can be easily realized without support from third agents like chemical substances, thus providing an eco-friendly and appealing organic synthesis strategy. Among the widely studied semiconductor nanomaterials, ZnxCd1-xS has been continuously studied and explored by researchers over the years, and it has attracted much consideration owing to its unique advantages such as adjustable band edge position, rich elemental composition, excellent photoelectric properties, and ability to respond to visible light. Therefore, nanostructures based on ZnxCd1-xS have been widely studied as a feasible way to efficiently prepare hydrogen energy and selectively oxidize it into high-value fine chemicals. In this Review, first, the crystal and energy band structures of ZnxCd1-xS, the model of twin nanocrystals, the photogenerated charge separation mechanism of the ZB-WZ-ZB homojunction with crisscross bands, and the Volmer-Weber growth mechanism of ZnxCd1-xS are described. Second, the morphology, structure, modification, synthesis, and vacancy engineering of ZnxCd1-xS are surveyed, summarized, and discussed. Then, the research progress in ZnxCd1-xS-based photocatalysis in photocatalytic hydrogen extraction (PHE) technology, the mechanism of PHE, organic substance (benzyl alcohol, methanol, etc.) dehydrogenation, the factors affecting the efficiency of photocatalytic discerning oxidation of organic derivatives, and selective C-H activation and C-C coupling for synergistic efficient dehydrogenation of photocatalysts are described. Conclusively, the challenges in the applicability of ZnxCd1-xS-based photocatalysts are addressed for further research development along this line.
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BACKGROUND: Bariatric surgery induces significant weight loss, increases insulin sensitivity and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement. METHODS: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using non-targeted metabolic liquid chromatography-mass spectrometry (LC-MS) method. RESULTS: During the 1, 3, and 6 months postoperative follow-up, the BMI, HOMA-IR, liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement and liver fat content reduction. CONCLUSIONS: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.
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Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , China/epidemiología , Estudios Retrospectivos , Hospitalización/estadística & datos numéricos , Teorema de Bayes , Política de Salud , PandemiasRESUMEN
Reconstruction for large-scale temporomandibular joint (TMJ) defects can be challenging. Previously, we utilized the medial femoral condyle (MFC) flap for TMJ reconstruction. However, the optimal fixation method remains uncertain. In this study, ï¬nite element analysis was used to study the effects of three different fixation types of bone graft: overlap type, bevel type, and flush type. Models of different fixation types of MFC flap were reconstructed from CT images. A standard internal fixation model for extracapsular condylar fracture was also included as a control. Displacement of bone graft, deformation of plates and screws, and stress distribution of plates, screws, and cortical and cancellous of the bone graft were analyzed by ï¬nite element analysis to investigate their biomechanical features. The displacement of the bone graft and deformation of plates and screws in three different fixation types showed no significant difference. The overlap type and flush type of fixation displayed the lowest and highest stress respectively. All three fixation types could satisfy the mechanical requirement and face no risk of breakage and the major displacement of the MFC bone graft. These results provide insights into the optimal fixation approach for MFC bone grafts, offering valuable guidance and reference for clinical application.
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Solution chemistry of actinide ions is critical to understanding the solvation behaviors and hydrolysis process. Using tetravalent thorium ion Th4+ as a representative example, we investigate the local structures and dynamic behaviors of hydrated Th4+ ions by ab initio molecular dynamics (AIMD) simulations using the recently developed norm-conserving pseudopotentials and basis sets optimized for actinides (J.-B. Lu et al., J. Chem. Theory Comput. 2021, 17, 3360-3371). AIMD simulations reveal two distinct solvation shells, with the first shell comprising 9 water molecules at approximately rTh-O = 2.50 Å and exhibiting a tricapped trigonal prism geometry. These conclusions are confirmed through metadynamics simulations and further structural analysis. AIMD simulations also show the slight effect of temperature and counterions on the structure of the solution. The structured solvation shells of the highly charged Th4+ ion with the specific geometry, distinct from the structure of liquid water, lead to corresponding structural changes in the hydrogen bond network in water. Additionally, beyond the solvent-shared ion pair (SIP) state observed in the unbiased AIMD simulations, the metadynamics simulations reconstruct a two-dimensional free energy surface that clearly indicates the potential stability of the contact ion pair (CIP) state in the system with Cl- as a counterion. The findings in this work provide insights into the solution chemistry of actinides and serve as a reference for studying other actinide solution systems.
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Here, we report the synthesis of a series of oxyacanthine derivatives and evaluation for their anti-SARS-CoV-2 activity in Vero E6 cells. In order to eliminate the potential metabolic activation caused by para-methylene phenol moiety in oxyacanthine, totally 29 derivatives were designed and synthesized, resulting in 23 compounds with antivirus IC50 below 5.00 µM and 9 compounds with antivirus IC50 below 1.00 µM. Among them, amides compound 4a and 4d exhibited potent anti-SARS-CoV-2 activity and the most favorable selectivity index (SI) in vitro with the SI values of 115 and 70, respectively. The pharmacokinetic properties of 4a and 4d were also assessed. Much more improved exposure in mice, longer half-life (T1/2), and increased oral bioavailability were observed for both compounds 4a and 4d compared with oxyacanthine.
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BACKGROUND: Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma. METHODS: In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing. FINDINGS: Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred. INTERPRETATION: Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy. FUNDING: National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Raw potato fries are a type of potato by-product (PBP), and they have great potential as a partial replacement of grain in animal feeds to improve the environmental sustainability of food production. This study aimed to investigate the effects of replacing corn with different levels of PBP (0%, 12.84%, 25.65%, and 38.44%) in the total mixed ration (TMR) of Angus bull. Sixty 16-month-old Angus bulls (548.5 ± 15.0 kg, mean ± SD) were randomly assigned to four treatments. The results indicated that with the increase in the substitution amount of PBP, the body weight decreased significantly. The dry matter apparent digestibility and starch apparent digestibility linearly decreased as PBP replacement increased. The feed ingredient composition in the TMR varied, leading to a corresponding change in the rumen microbiota, especially in cellulolytic bacteria and amylolytic bacteria. The abundance of Succiniclasticum in the 12.84% PBP and 38.44% PBP diets was significantly higher than that in the 0% PBP and 25.65% PBP diets. The abundance of Ruminococcus linearly increased. In conclusion, using PBP to replace corn for beef cattle had no negative impact on rumen fermentation, and the decrease in apparent digestibility explained the change in growth performance. Its application in practical production is highly cost-effective and a strategy to reduce food waste.
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The inevitable UV aging of microplastics (MPs) is one of the key factors affecting their interaction with antibiotics. In this study, polyethylene (PE) and polystyrene (PS) MPs were aged with UV irradiation. The adsorption isotherms and kinetics of ciprofloxacin (CIP) to virgin and aged MPs were investigated through various models, and the effects of pH on the adsorption amount were explored. Characterization revealed that the surfaces of aged MPs became rougher, and the hydrophilicity increased. These aged MPs were still in the early stage of aging on the basis of their carbonyl index (CI) (<0.2) and O/C (<0.04) values. The adsorption isotherms indicated that the adsorption mechanism of aged PE was different from that of virgin PE. Compared with virgin PE, the adsorption amount of aged PE increased by 87.80-95.45%, and the adsorption rate decreased by 65.52-80.74%. However, aging did not significantly affect the equilibrium adsorption amount or adsorption rate of aged PS. The external diffusion rate (Kext) (about 2.29-0.36â h-1) was almost 30 times greater than the internal diffusion rate (Kint) in the film-pore mass transfer (FPMT) model, indicating that CIP adsorption rate was dominated by external diffusion. A hydrated functional zone is thought to form around aged MPs, thus changing the adsorption mechanism and adsorption amount of aged PE. Therefore, more attention should be given to alterations in the hydrated functional zone in the early stage of MPs aging.
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Craniomaxillofacial (CMF) and nasal landmark detection are fundamental components in computer-assisted surgery. Medical landmark detection method includes regression-based and heatmap-based methods, and heatmap-based methods are among the main methodology branches. The method relies on high-resolution (HR) features containing more location information to reduce the network error caused by sub-pixel location. Previous studies extracted HR patches around each landmark from downsampling images via object detection and subsequently input them into the network to obtain HR features. Complex multistage tasks affect accuracy. The network error caused by downsampling and upsampling operations during training, which interpolates low-resolution features to generate HR features or predicted heatmap, is still significant. We propose standard super-resolution landmark detection networks (SRLD-Net) and super-resolution UNet (SR-UNet) to reduce network error effectively. SRLD-Net used Pyramid pooling block, Pyramid fusion block and super-resolution fusion block to combine global prior knowledge and multi-scale local features, similarly, SR-UNet adopts Pyramid pooling block and super-resolution block. They can obviously improve representation learning ability of our proposed methods. Then the super-resolution upsampling layer is utilized to generate detail predicted heatmap. Our proposed networks were compared to state-of-the-art methods using the craniomaxillofacial, nasal, and mandibular molar datasets, demonstrating better performance. The mean errors of 18 CMF, 6 nasal and 14 mandibular landmarks are 1.39 ± 1.04, 1.31 ± 1.09, 2.01 ± 4.33 mm. These results indicate that the super-resolution methods have great potential in medical landmark detection tasks. This paper provides two effective heatmap-based landmark detection networks and the code is released in https://github.com/Runshi-Zhang/SRLD-Net.
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Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBBPenk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBBPenk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.
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BACKGROUND: Post-acute sequelae of COVID-19 (PASC) is incurring a huge health and economic burden worldwide. There is currently no effective treatment or recommended drug for PASC. METHODS: This prospective randomized controlled study was conducted in a hospital in China. The effect of intermittent hypoxia exposure (IHE; 5-min hypoxia alternating with 5-min normal air, repeated five times) on dyspnea and fatigue was investigated in patients meeting the NICE definition of PASC. Patients were computationally randomized to receive normoxia exposure (NE) and routine therapy or IHE and routine therapy. Six-minute walk distance (6MWD) and spirometry were tested before and after the interventions; the Borg Dyspnea Scale (Borg) and the modified Medical Research Council Dyspnea Scale (mMRC) were used to assess dyspnea; and the Fatigue Assessment Scale (FAS) and the Chalder Fatigue Scale-11 (CFQ-11) were used to assess fatigue. The study was registered in the Chinese Clinical Trial Registry (ChiCTR2300070565). FINDINGS: Ninety-five participants (33 males and 62 females) were recruited between March 1, 2023 and December 30, 2023. Forty-seven patients in the IHE group received 10.0 (9.0, 15.0) days of IHE, and 48 patients in NE group received 10.0 (8.0, 12.0) days of NE. 6MWD, forced vital capacity (FVC), FVC %pred, forced expiratory volume in 1 s (FEV1), FEV1 %pred, tidal volume (VT), and dyspnea and fatigue scales markedly improved after IHE (p < 0.05), and improvements were greater than in the NE group (all p < 0.05). Furthermore, participants in IHE group had better subjective improvements in dyspnea and fatigue than those in the NE group (p < 0.05). Compared with <10 days of IHE, ≥10 days of IHE had a greater impact on 6MWD, FVC, FEV1, FEV1 %pred, VT, FAS, and CFQ-11. No severe adverse events were reported. INTERPRETATION: IHE improved spirometry and 6MWD and relieved dyspnea and fatigue in PASC patients. Larger prospective studies are now needed to verify these findings.
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COVID-19 , Disnea , Fatiga , Hipoxia , Síndrome Post Agudo de COVID-19 , Humanos , Disnea/fisiopatología , Disnea/etiología , Masculino , Femenino , COVID-19/complicaciones , COVID-19/fisiopatología , Fatiga/etiología , Fatiga/fisiopatología , Persona de Mediana Edad , Estudios Prospectivos , Hipoxia/fisiopatología , Adulto , Prueba de Paso/métodos , Anciano , Espirometría/métodos , ChinaRESUMEN
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently been linked to be associated with acute pancreatitis (AP), but the clinical characteristics are unclear. This study investigated the clinical characteristics of SGLT-2i and AP and provided reference for the prevention and treatment of AP. RESEARCH DESIGN AND METHODS: Case reports, case series, and clinical studies of SGLT2i induced AP were collected by retrieving Chinese and English data from the database until 31 December 2023. RESULTS: Twenty-one patients were included, with a median age of 50.5 years (range 26,73). SGLT-2i were mainly involved in empagliflozin (13 cases, 61.9%), canagliflozin (4 cases, 19%) and dapagliflozin (4 cases, 19%). The median time from initial administration to the onset of AP was 21 days (range 1, 120). Abdominal pain (21 cases, 100%) was the most commonly complained symptom. The median lipase value was 388 U/L (range 36, 10000), and the median amylase value was 535 U/L (range 26, 3765). Twenty-one patients recovered completely after stopping the drug and receiving conservative treatment. CONCLUSIONS: SGLT-2i are associated with AP. Given the rising prescription of SGLT-2i, physicians should consider these agents as a potential cause of pancreatitis after excluding other etiologies.
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The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.
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Nutrición Enteral , Recien Nacido Prematuro , Nutrición Parenteral , Guías de Práctica Clínica como Asunto , Humanos , Nutrición Parenteral/normas , Nutrición Parenteral/métodos , Recién Nacido , Nutrición Enteral/normas , Nutrición Enteral/métodos , Sociedades MédicasRESUMEN
Monoacylglycerol lipase (MAGL) is a key enzyme responsible for the metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG), and has attracted great interest due to its involvement in various physiological and pathological processes, such as cancer progression. In the past, a number of covalent irreversible inhibitors have been reported for MAGL, however, experimental evidence highlighted some drawbacks associated with the use of these irreversible agents. Therefore, efforts were mainly focused on the development of reversible MAGL inhibitor in recent years. Here, we designed and synthesized a series of naphthyl amide derivatives (12-39) as another type of reversible MAGL inhibitors, exemplified by ± 34, which displayed good MAGL inhibition with a pIC50 of 7.1, and the potency and selectivity against endogenous MAGL were further demonstrated by competitive ABPP. Moreover, the compound showed appreciable antiproliferative activities against several cancer cells, including H460, HT29, CT-26, Huh7 and HCCLM-3. The investigations culminated in the discovery of the naphthyl amide derivative ± 34, and it may represent as a new scaffold for MAGL inhibitor development, particularly for the reversible ones.