Pancreatic agenesis and altered m6A methylation in the pancreas of PDX1-mutant cynomolgus macaques.

As an essential transcriptional activator, PDX1 plays a crucial role in pancreatic development and ß-cell function. Mutations in the PDX1 gene may lead to type 4 maturity-onset diabetes of the young (MODY4) and neonatal diabetes mellitus. However, the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models. In this study, three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology, all of which succumbed shortly postpartum, exhibiting pancreatic agenesis. Notably, one tri-allelic PDX1-mutant cynomolgus macaque (designated as M4) developed a pancreas, whereas the two mono-allelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation. RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions, indicating developmental delay and PDX1 haploinsufficiency. A marked change in m6A methylation was identified in the M4 pancreas, confirmed through cultured PDX1-mutant islet organoids. Notably, overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids. This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.

Influence of Financial Toxicity on the Quality of Life in Lung Cancer Patients Undergoing Immunotherapy: The Mediating Effect of Self-Perceived Burden.

Purpose: The purpose of this study is to understand the level of quality of life (QOL) of lung cancer patients receiving immunotherapy and to clarify the potential mediating role of self-perceived burden (SPB) in the relationship between financial toxicity (FT) and QOL. Patients and Methods: A convenience sample of 342 lung cancer patients receiving immunotherapy was recruited from a cancer hospital from October 2022 to April 2023 for this cross-sectional study. The participants were requested to complete the following structured questionnaires: a sociodemographic and clinical questionnaire, the Functional Assessment of Cancer Therapy-Lung (FACT-L), the Self-Perceived Burden Scale (SPBS) and the COmprehensive Score for Financial Toxicity (COST). The data were subjected to Pearson correlation analysis and bootstrapping analysis in structural equation modelling. Results: The total FACT-L score was 79.90±15.84 points in 322 lung cancer patients receiving immunotherapy. FT (ß = 0.37, P < 0.01) and SPB (ß = -0.27, P < 0.01) had a direct effect on QOL. In addition, SPB partly mediated the association between FT and QOL, and the standardized indirect effect was 0.19, accounting for 33.9% of the total effect. Conclusion: The present study revealed that there is still much room for improvement in the QOL of lung cancer patients during immunotherapy. A greater financial burden resulted in a greater self-perceived burden and was thus associated with inferior QOL. It is imperative for oncology nurses to routinely assess QOL, FT or risk and SPB for lung cancer patients undergoing immunotherapy as well as to assist those patients in understanding the potential financial risk of each choice and help them take more active roles in their routine clinical care.

Selection strategy for endoscopic necrosectomy approaches of infected walled-off pancreatic necrosis: Analysis of 101 patients from a single center with long-term follow-up.

OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.

Pattern and extent of intrahepatic infiltration of perihilar cholangiocarcinoma - A case-control study based on liver panoramic digital pathology.

BACKGROUND: The extent of intrahepatic infiltration of perihilar cholangiocarcinoma (PHCC) remains unclear. This research aimed to explore the pattern and extent of intrahepatic infiltration of PHCC to guide surgical treatment and pathological research. MATERIALS AND METHODS: This study included 62 patients diagnosed with PHCC who underwent major hepatectomy. A whole-mount digital liver pathology system (WDLPS) for hepatectomy specimens greater than 10 × 10 cm was used to panoramically assess the intrahepatic infiltration extent of PHCC. RESULTS: The distal intrahepatic infiltration (DIHI) and radial liver invasion (RLI) were important parts of intrahepatic infiltration for PHCC explored by WDLPS. The study confirmed that 75.8% of PHCCs had RLI and the infiltration distance in all patients were within 15,000 µm, 62.9% of PHCCs had DIHI greater than 1 cm away from the main tumor in liver parenchyma. The recurrence-free survival rates and overall survival rates of patients with DIHI were poorer than the patients without DIHI (P＜0.0001, P=0.0038). Arterial invasion on the resected side could be an excellent predictor. A total of 105 liver lobes were resected from 62 PHCC patients. The invasion rates of the left lateral, left medial, right anterior, and right posterior lobe of PHCC were 79%, 100, 100%, and 69% respectively. CONCLUSION: The presence of DIHI in most PHCCs was a significant predictor of poor postoperative recurrence and survival. Based on the extent of intrahepatic infiltration, minor hepatectomy was not suitable as the curative surgery for PHCC. Major hepatectomy and liver transplantation were the ideal radical treatment.

Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to Helicobacter pylori in an acidic environment.

Helicobacter pylori (H. pylori) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and H. pylori does not readily develop drug resistance. Through in vivo experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. After treatment with desoxyshikonin, colonization of H. pylori in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in H. pylori, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.

Omicron variant infection worsen the prognosis of haemodialysis (HD) patients.

BACKGROUND: Haemodialysis (HD) patients are predisposed to physical ailments, and their occurrence of coronavirus disease 2019 (COVID-19) could potentially lead to a more unfavourable prognosis. However, the impact of SARS-CoV-2 (Omicron variant) infection on the prognosis of HD patients remains unclear. This study aimed to explore the impact of Omicron variant infection on the prognosis of HD patients. METHODS: Eligible participants were patients undergoing maintenance HD treatment during a large-scale outbreak of COVID-19 (Omicron variant) in Shanghai, China, from April 7 to May 30, 2022. According to SARS-CoV-2 infection status of participants, the HD patients were divided into two groups: a COVID-19 group and a non-COVID-19 group. The primary outcome assessed was in-hospital mortality, and secondary outcomes encompassed the incidence of severe cases, admission to intensive care, length of hospital stay, and blood indices. Statistical analysis was conducted by comparative analysis and multiple logistic regression. RESULTS: This study recruited 588 HD patients, including 199 cases in the COVID-19 group and 389 in the non-COVID-19 group. In the COVID-19 group, the mortality rate was 8.45% (17/199), whereas in the non-COVID-19 group, the rate was 3.34% (13/389) (p < 0.05). Compared with the non-COVID-19 group, the COVID-19 group had a risk ratio (RR) with 95% confidence interval (CI) of 2.56 (1.27-5.15) for mortality, and the absolute risk difference (ARD) with 95% CI of 5.20% (1.34%-9.06%). Multiple logistic regression confirmed Omicron variant as a risk factor for mortality among HD patients. Additionally, the COVID-19 group had a higher proportion of severe cases, intensive care admission, hypocalcaemia and hyperphosphatemia and longer hospitalization duration, compared to the non-COVID-19 group (p < 0.05). CONCLUSIONS: Omicron variant infection was associated with increased mortality risk in HD patients, and Omicron infection worsen the prognosis of HD patients. Enhancing immune protection against SARS-CoV-2 is crucial for HD patients during the ongoing COVID-19 pandemic.

Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy.

AIM: To analyze the distribution of fibrovascular proliferative membranes (FVPMs) in proliferative diabetic retinopathy (PDR) patients that treated with pars plana vitrectomy (PPV), and to evaluate the outcomes separately. METHODS: This was a retrospective and cross-sectional study. Consecutive 25-gauge (25-G) PPV cases operated for PDR from May 2018 to April 2020. According to the FVPMs images outlined after operations, subjects were assigned into three groups: arcade type group, juxtapapillary type group, and central type group. All patients were followed up for over one year. General characteristics, operation-related variables, postoperative parameters and complications were recorded. RESULTS: Among 103 eyes recruited, the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different (both P<0.01), with 95 (92.23%) FVPMs located in the nasal quadrants, and 74 (71.84%) in the inferior. The eyes with a central FVPM required the longest operation time, with silicon oil used in most patients, generally combined with tractional retinal detachment (RD) and rhegmatogenous RD, the worst postoperative best-corrected visual acuity (BCVA) and the highest rates of recurrent RD (all P<0.05). FVPM type, age of onset diabetes mellitus, preoperative BCVA, and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement (all P<0.05). Compared with the central type group, the arcade type group had higher rates of BCVA improvement. CONCLUSION: FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade vessels. Performing 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

A novel scoring system based on sIL-2R for predicting IVIG resistance in Chinese children with KD.

OBJECTIVE: This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. METHODS: A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. RESULTS: In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. CONCLUSION: Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Prediction of clear cell renal cell carcinoma ≤ 4cm: visual assessment of ultrasound characteristics versus ultrasonographic radiomics analysis.

Objective: To investigate the diagnostic efficacy of the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model based on ultrasonographic radiomics for the differentiation of small clear cell Renal Cell Carcinoma (ccRCC) and Renal Angiomyolipoma (RAML). Methods: The clinical, ultrasound, and contrast-enhanced CT(CECT) imaging data of 302 small renal tumors (maximum diameter ≤ 4cm) patients in Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2022 were retrospectively analyzed, with 182 patients of ccRCC and 120 patients of RAML. The ultrasound images of the largest diameter of renal tumors were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from ROI segmented images. The patients were randomly divided into training and internal validation cohorts in the ratio of 7:3. The Random Forest algorithm of the Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model. The efficacy of the prediction models was verified in an independent external validation cohort consisting of 69 patients, from 230 small renal tumor patients in two different institutions. The Delong test compared the predictive ability of three models and CECT. Calibration Curve and clinical Decision Curve Analysis were applied to evaluate the model and determine the net benefit to patients. Results: 491 ultrasonographic radiomics features were extracted from 302 small renal tumor patients, and 9 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. In the internal validation cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy of the clinical ultrasound imaging model, ultrasonographic radiomics model, comprehensive model, and CECT were 0.75, 76.7%, 60.0%, 70.0%; 0.80, 85.6%, 61.7%, 76.0%; 0.88, 90.6%, 76.7%, 85.0% and 0.90, 92.6%, 88.9%, 91.1%, respectively. In the external validation cohort, AUC, sensitivity, specificity, and accuracy of the three models and CECT were 0.73, 67.5%, 69.1%, 68.3%; 0.89, 86.7%, 80.0%, 83.5%; 0.90, 85.0%, 85.5%, 85.2% and 0.91, 94.6%, 88.3%, 91.3%, respectively. The DeLong test showed no significant difference between the clinical ultrasound imaging model and the ultrasonographic radiomics model (Z=-1.287, P=0.198). The comprehensive model showed superior diagnostic performance than the ultrasonographic radiomics model (Z=4. 394, P<0.001) and the clinical ultrasound imaging model (Z=4. 732, P<0.001). Moreover, there was no significant difference in AUC between the comprehensive model and CECT (Z=-0.252, P=0.801). Both in the internal and external validation cohort, the Calibration Curve and Decision Curve Analysis showed a better performance of the comprehensive model. Conclusion: It is feasible to construct an ultrasonographic radiomics model for distinguishing small ccRCC and RAML based on ultrasound images, and the diagnostic performance of the comprehensive model is superior to the clinical ultrasound imaging model and ultrasonographic radiomics model, similar to that of CECT.

High efficiency of biosurfactants in stabilizing oil micro-droplets within the aging time scale of milliseconds: a microfluidic study.

Rapid adsorption of surfactants onto a freshly formed interface is vital for emulsification because emulsification is a competitive process occurring between the very short time span of interface formation and surfactant mass transport. The biosurfactant surfactin has been previously reported to reach adsorption equilibrium at the hydrophobic/hydrophilic interface within hundreds of milliseconds and rapidly reduce the interfacial tension compared to chemically synthesized surfactants. According to a prior study, surfactin is expected to exhibit good performance in stabilizing micro-droplets of oil within the aging time scale of milliseconds. Herein, the stabilities of micro-droplets of n-hexadecane in the presence of a biosurfactant, surfactin (C15-SFT), and a chemically synthesized surfactant, sodium cetyl benzene sulfonate (8-SCBS), were investigated using a microfluidic method. The coalescence frequency of micro-droplets, the evolution of micro-droplet size, and the coalescence time of micro-droplets were evaluated. The results indicated that C15-SFT exhibited superiority over 8-SCBS in stabilizing the micro-droplets of n-hexadecane. Biosurfactant C15-SFT effectively reduced the fusion probability between oil droplets and elongated the coalescence time compared to 8-SCBS, and these phenomena were obvious at a shorter aging time (150 ms) and lower surfactant concentration (0.1 × critical micelle concentration). The stabilities of micro-droplets increased with aging time and the bulk concentration of surfactants. Stable micro-droplets of n-hexadecane were formed in 1 × 10-4 mol L-1 C15-SFT solution at 600 ms aging time, and the bulk concentration was 1 × 10-3 mol L-1 in the case of 8-SCBS. The micro-droplets rarely coalesced in the presence of 1 × 10-4 mol L-1 C15-SFT after 600 ms aging time, but the micro-droplets in 1 × 10-4 mol L-1 8-SCBS coalesced frequently in the midstream and downstream of the coalescence chamber, and big droplets were dominant in the emulsion. The coalescence time of micro-droplets stabilized by C15-SFT was obviously longer than that of those stabilized by 8-SCBS under the same condition, indicating that the interfacial film formed by C15-SFT has much strength to resist coalescence during collisions. This work is helpful for understanding the activity of lipopeptides in the very short early stage of the emulsification process, laying the foundation for biosurfactant research in the fields of enhanced oil recovery, bioremediation of contaminated water or soil, etc.

CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.

Retinal vascular leakage is a major event in several retinal diseases, including diabetic retinopathy (DR). In a previous study, we demonstrated that the aqueous humor concentration of Cystatin C (CST3), a physiological inhibitor of cysteine protease, is negatively correlated with the severity of diabetic macular edema. However, its function in the retina has not been clearly elucidated. In this study, we found a significant decrease in the aqueous humor concentration of CST3 with DR progression. Furthermore, we found that CST3 was expressed in retinal endothelial cells and that its expression was significantly downregulated in high glucose-treated human retinal microvascular endothelial cells (HRMECs) and the retinal vessels of oxygen-induced retinopathy (OIR) mice. Silencing CST3 expression resulted in decreased HRMEC migration and tubule formation ability. Exogenous addition of the CST3 protein significantly improved HRMEC migration and tubular formation. In-vivo experiments demonstrated that CST3 silencing induced retinal vascular leakage in WT mice, while its intravitreal injection significantly reduced retinal leakage in OIR mice. Mechanistically, CST3 promoted the expression of the downstream adhesion molecules, claudin5, VE-cadherin, and ZO-1, in retinal vascular cells by regulating the Rap1 signaling pathway. Therefore, this study revealed a novel mechanism by which CST3 improves retinal vascular function and provided evidence that it is a potential therapeutic target for retinal vascular leakage.

Microfluidic fabrication of monodisperse microcapsules with gas cores.

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.

Fluorescent probe for imaging intercellular tension: molecular force approach.

Cellular mechanical force plays a crucial role in numerous biological processes, including wound healing, cell development, and metastasis. To enable imaging of intercellular tension, molecular tension probes were designed, which offer a simple and efficient method for preparing Au-DNA intercellular tension probes with universal applicability. The proposed approach utilizes gold nanoparticles linked to DNA hairpins, enabling sensitive visualization of cellular force in vitro. Specifically, the designed Au-DNA intercellular tension probe includes a molecular spring flanked by a fluorophore-quencher pair, which is anchored between cells. As intercellular forces open the hairpin, the fluorophore is de-quenched, allowing for visualization of cellular force. The effectiveness of this approach was demonstrated by imaging the cellular force in living cells using the designed Au-DNA intercellular tension probe.

Triazine-structured covalent organic framework nanosheets with inherent hydrophilicity for the highly efficient and selective enrichment of glycosylated peptides.

Protein glycosylation plays a crucial role in various biological processes and is related to various diseases. Highly specific enrichment of glycopeptides before mass spectrometry detection is crucial for comprehensive glycoproteomic analysis. However, it still remains a great challenge due to the absence of affinity materials with excellent enrichment efficiency. In this work, a triazine structure linked by a -NH- bond of two-dimensional (2-D) covalent organic framework (COF) nanosheets was synthesized as an affinity adsorbent for the selective capture of glycopeptides. In particular, by introducing hydrophilic monomers via a bottom-up approach, the 2-D COF (denoted as NENP-1) nanosheets were provided with abundant amino groups and inherent hydrophilicity. Owing to the specific surface area and excessive accessible sites for hydrophilicity, the resulting NENP-1 nanosheets exhibited an outstanding glycopeptide enrichment efficiency from standard samples with a superior detection sensitivity (1 × 10-10 M), good enrichment selectivity (1 : 800, HRP tryptic digest to BSA protein), excellent binding capacity (100 mg g-1), great reusability, and recovery (60.2%). Furthermore, using the NENP-1 nanosheet adsorbent, twenty-four endogenous glycopeptides in the serum of patients with gastric cancer were successfully identified by LC-MS/MS technology, which illustrates a promising prospective of hydrophilic COF nanosheets in glycoproteomics research.

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Efficacy and safety of remimazolam versus propofol for intraoperative sedation during regional anesthesia: A phase II, multicenter, randomized, active-controlled, single-blind clinical trial.

This study aimed to evaluate the efficacy and safety of remimazolam for intraoperative sedation during regional anesthesia. It was a phase II-multicenter, randomized, single-blind, parallel-group, active-controlled clinical trial (No. ChiCTR2100054956). From May 6, 2021 to July 4, 2021, patients were randomly enrolled from 17 hospitals in China. A total of 105 patients aged 18-65 years who underwent selective surgery under regional anesthesia were included. Patients received different sedatives with different dosages: 0.1 mg/kg remimazolam (HR), 0.05 mg/kg remimazolam (LR), or 1.0 mg/kg propofol (P) group, followed by a maintenance infusion. Main outcome measures included the efficacy of sedation measured by Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) levels (1-4, 1-3, 2-3, 3, and 2-4) during the sedation procedure (the duration percentage) and incidence of adverse reactions. It showed that the duration percentage of MOAA/S levels 1-4 was 100.0 [8.1]% (median [interquartile range]), 89.9 [20.2]%, 100.0 [7.7]% in the HR, LR, and P groups, respectively. The percentage of patients in the HR, LR, and P groups who achieved MOAA/S levels 1-4 within 3 min after administration was 85.7%, 58.8%, and 82.9%, respectively. However, the time to recovery from anesthesia after withdrawal of sedatives (7.9 ± 5.7 min), incidence of anterograde amnesia (75%), and adverse effects were not statistically significant among the three groups. These findings suggest that a loading dose of remimazolam 0.1 mg/kg followed by a maintenance infusion of 0-3 mg/kg/h provides adequate sedation for patients under regional anesthesia without increasing adverse reactions.

Carbon peaking prediction scenarios based on different neural network models: A case study of Guizhou Province.

Global warming, caused by greenhouse gas emissions, is a major challenge for all human societies. To ensure that ambitious carbon neutrality and sustainable economic development goals are met, regional human activities and their impacts on carbon emissions must be studied. Guizhou Province is a typical karst area in China that predominantly uses fossil fuels. In this study, a backpropagation (BP) neural network and extreme learning machine (ELM) model, which is advantageous due to its nonlinear processing, were used to predict carbon emissions from 2020 to 2040 in Guizhou Province. The carbon emissions were calculated using conversion and inventory compilation methods with energy consumption data and the results showed an "S" growth trend. Twelve influencing factors were selected, however, five with larger correlations were screened out using a grey correlation analysis method. A prediction model for carbon emissions from Guizhou Province was established. The prediction performance of a whale optimization algorithm (WOA)-ELM model was found to be higher than the BP neural network and ELM models. Baseline, high-speed, and low-carbon scenarios were analyzed and the size and time of peak carbon emissions in Liaoning Province from 2020 to 2040 were predicted using the WOA-ELM model.

Global, regional, and national trends in metabolic risk factor-associated mortality among the working-age population from 1990-2019: An age-period-cohort analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.