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Abstract Background This study aimed at investigating the relationship between the weekend catch-up outdoor duration (WCOD) and prevalence of myopia among students in China. Methods This cross-sectional study recruited participants in 107 schools (six cities, 30 districts) from China from May to June 2021. Demographic characteristics (age, grade, sex, ethnicity, BMI, resident, and parents’ myopia), optically habits (bad writing habits, working/studying time per day, continuous working/studying time per day, and screen time per day) and outdoor duration (weekday and weekend) were obtained from questionnaire. WCOD was defined as outdoor time 1 h longer on weekends than on weekdays. Spherical equivalent (SE) of refractive error were measured with non-cycloplegic refraction. Adjusted multivariate logistic regression analysis was performed to evaluate the relationship between WCOD and prevalence of myopia. Results Students with myopia had shorter WCOD compared with those without myopia (P

Abstract Increasing the molecular weight while maintaining mono-dispersity has been proved crucial in innovating high-performance photovoltaic materials in giant oligomeric acceptors. However, developing efficient giant oligomeric donors to replace the batch-varied polymers remains challenging due to a lack of design principles. Here, by designing two unique isomeric rhodanine-based linkers, we successfully regulate the assembly behaviors of giant dimeric donors (G-Dimer-Ds) and fabricate the first all-giant-oligomer OSCs pairing with giant dimeric acceptor DY. Multiple characterizations demonstrate the small homo-molecular interaction with strong thermal-driven assembly capability in G-Dimer-D2 simultaneously facilitates reducing energetic disorder, improving charge transport and obtaining stable morphology, resulting in a satisfactory efficiency of 15.70% and long-term photostability with an extrapolated T 80 of ca.10,000 hours, and further enhancing thermal-driven assembly promotes efficiency of 16.05%. Our results provide construction approaches on efficient giant donors, and propose a promising type of OSC with completely definite structures, high efficiency and superior stability.

[Introduction] With the development of photovoltaics, energy storage, new building materials and prefabricated construction industry, Building Integrated Photovoltaic (BIPV) technology which features the integrated design and manufacturing of photovoltaic modules with components such as roofs, walls and sunshades is evolving as Building Integrated Photovoltaic and Energy Storage (BIPVES) technology. [Method] The article proposed the world's first rechargeable cement-based battery, promoting the integration of building walls with photovoltaic power generation and storage and discharging devices. Cross-disciplinary innovation was applied to equipment and materials, where high-definition, high transmittance patterned designs were printed on glass surfaces to manufacture high-efficiency photovoltaic building materials. Prefabricated energy storage walls were developed and integrated with various steel-structure prefabricated building systems to achieve customized production and prefabricated construction, leading to a transformative trend of integrating building components with photovoltaics and energy storage. [Result] Cement-based batteries allow building walls to have multiple functions, including photovoltaic power generation, energy storage and power supply; The new generation of photovoltaic building materials helps save costs on building facade decoration materials and reduce building carbon emissions; The integration of photovoltaics, energy storage and renewable energy technologies in buildings can achieve maximum benefits. [Conclusion] The new photovoltaic building materials and new energy storage technologies such as cement-based batteries show promising prospects. Combining and integrating rechargeable battery components, photovoltaic exterior panels, prefabricated building walls and embedded parts for widespread application is feasible.

Abstract The ternary strategy proves effective for breakthroughs in organic photovoltaics (OPVs). Elevating three photovoltaic parameters synergistically, especially the proportion‐insensitive third component, is crucial for efficient ternary devices. This work introduces a molecular design strategy by comprehensively analyzing asymmetric end groups, side‐chain engineering, and halogenation to explore the outstanding optoelectronic properties of the proportion‐insensitive third component in efficient ternary systems. Three asymmetric non‐fullerene acceptors (BTP‐SA1, BTP‐SA2, and BTP‐SA3) are synthesized based on the Y6 framework and incorporated as the third component into the D18:Y6 binary system. BTP‐SA3, featuring asymmetric terminal (difluoro‐indone and dichloride‐cyanoindone terminal), with branched alkyl side chains, exhibited high open‐circuit voltage (VOC), balanced crystallinity and compatibility, achieving synergistic enhancements in VOC (0.862 V), short circuit‐current density (JSC, 27.52 mA cm−2), fill fact (FF, 81.01%), and power convert efficiency (PCE, 19.19%). Device based on D18/Y6:BTP‐SA3 (layer‐by‐layer processed) reached a high efficiency of 19.36%, demonstrating a high tolerance for BTP‐SA3 (10–50%). This work provides novel insights into optimizing OPVs performances in multi‐component systems and designing components with enhanced tolerance.

Abstract The overactivated immune cells in the infectious lesion may lead to irreversible organ damages under severe infections. However, clinically used immunosuppressive anti‐inflammatory drugs will usually disturb immune homeostasis and conversely increase the risk of infections. Regulating the balance between anti‐inflammation and anti‐infection is thus critical in treating certain infectious diseases. Herein, considering that hydrogen peroxide (H2O2), myeloperoxidase (MPO), and neutrophils are upregulated in the inflammatory microenvironment and closely related to the severity of appendectomy patients, an inflammatory‐microenvironment‐responsive nanomedicine is designed by using poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles to load chlorine E6 (Ce6), a photosensitizer, and luminal (Lum), a chemiluminescent agent. The obtained Lum/Ce6@PLGA nanoparticles, being non‐toxic within normal physiological environment, can generate cytotoxic single oxygen via bioluminescence resonance energy transfer (BRET) in the inflammatory microenvironment with upregulated H2O2 and MPO, simultaneously killing pathogens and excessive inflammatory immune cells in the lesion, without disturbing immune homeostasis. As evidenced in various clinically relevant bacterial infection models and virus‐induced pneumonia, Lum/Ce6@PLGA nanoparticles appeared to be rather effective in controlling both infection and inflammation, resulting in significantly improved animal survival. Therefore, the BRET‐based nanoparticles by simultaneously controlling infections and inflammation may be promising nano‐therapeutics for treatment of severe infectious diseases.

Skin photoaging, caused by prolonged exposure to ultraviolet (UV) radiation, manifests as intricate biological transformations, encompassing oxidative damage and structural alterations. Despite a growing need for effective interventions, the existing therapeutic repertoire for treating skin photoaging remains constrained. Recent investigations have shifted focus towards the application of hydrogels as a novel avenue for addressing this concern. Various active substances can be combined with hydrogels for transdermal delivery, including compounds from the ocean, plants, cell active substances, which can promote skin UV damage repair mainly through antioxidant, anti-inflammatory and promote collagen production. This review seeks to offer a thorough summary of recent progress in employing hydrogels for addressing skin photoaging. Topics covered include the mechanism of skin photoaging, and emerging trends in hydrogel-based therapies for skin rejuvenation. The discussion also explores challenges and outlines potential future directions in leveraging hydrogels as therapeutic agents to address skin photoaging.

IntroductionsIdentifying patients with non-small cell lung cancer (NSCLC) who are optimal candidates for immunotherapy is a cornerstone in clinical decision-making. The tumor immune microenvironment (TIME) is intricately linked with both the prognosis of the malignancy and the efficacy of immunotherapeutic interventions. CD8+ T cells, and more specifically, tissue-resident memory CD8+ T cells [CD8+ tissue-resident memory T (TRM) cells] are postulated to be pivotal in orchestrating the immune system's assault on tumor cells. Nevertheless, the accurate quantification of immune cell infiltration—and by extension, the prediction of immunotherapeutic efficacy—remains a significant scientific frontier.MethodsIn this study, we introduce a cutting-edge non-invasive radiomic model, grounded in TIME markers (CD3+ T, CD8+ T, and CD8+ TRM cells), to infer the levels of immune cell infiltration in NSCLC patients receiving immune checkpoint inhibitors and ultimately predict their response to immunotherapy. Data from patients who had surgical resections (cohort 1) were employed to construct a radiomic model capable of predicting the TIME. This model was then applied to forecast the TIME for patients under immunotherapy (cohort 2). Conclusively, the study delved into the association between the predicted TIME from the radiomic model and the immunotherapeutic outcomes of the patients.ResultFor the immune cell infiltration radiomic prediction models in cohort 1, the AUC values achieved 0.765, 0.763, and 0.675 in the test set of CD3+ T, CD8+ T, and CD8+ TRM, respectively. While the AUC values for the TIME-immunotherapy predictive value were 0.651, 0.763, and 0.829 in the CD3-immunotherapy response model, CD8-immunotherapy response model, and CD8+ TRM-immunotherapy response model in cohort 2, respectively. The CD8+ TRM-immunotherapy model exhibited the highest predictive value and was significantly better than the CD3-immunotherapy model in predicting the immunotherapy response. The progression-free survival (PFS) analysis based on the predicted levels of CD3+ T, CD8+ T, and CD8+ TRM immune cell infiltration showed that the CD8+ T cell infiltration level was an independent factor (P=0.014, HR=0.218) with an AUC value of 0.938.DiscussionOur empirical evidence reveals that patients with substantial CD8+ T cell infiltration experience a markedly improved PFS compared with those with minimal infiltration, asserting the status of the CD8+ T cell as an independent prognosticator of PFS in the context of immunotherapy. Although CD8+ TRM cells demonstrated the greatest predictive accuracy for immunotherapy response, their predictive strength for PFS was marginally surpassed by that of CD8+ T cells. These insights advocate for the application of the proposed non-invasive radiomic model, which utilizes TIME analysis, as a reliable predictor for immunotherapy outcomes and PFS in NSCLC patients.

Abstract Background Neuroblastoma (NB), a type of solid tumor in children, has a poor prognosis. Few blood biomarkers can accurately predict the prognosis, including recurrence and survival, in children with NB. In this study, we found that the serum total cholesterol (Tchol) level was associated with the prognosis of patients through a retrospective study. Methods Multivariate Cox regression model was used to identify the independent risk factors in the children with NB. Kaplan–Meier method was used to analyze the correlation between the common biomarkers, including the serum Tchol level, and the prognosis of the patients. ROC curves were used to predict the accuracy of the International Neuroblastoma Staging System (INSS) stage and Children’s Oncology Group (COG) risk stratification after adding the serum Tchol level. Results Compared with the other patients, serum Tchol level was significantly increased in the relapsed and died patients (P

Background The primary objective was to examine the association between the lactate/albumin ratio (LAR) and the prognosis of patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT).Methods Utilizing the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0) database, we categorized 703 adult AKI patients undergoing CRRT into survival and non-survival groups based on 28-day mortality. Patients were further grouped by LAR tertiles: low (< 0.692), moderate (0.692-1.641), and high (> 1.641). Restricted cubic splines (RCS), Least Absolute Shrinkage and Selection Operator (LASSO) regression, inverse probability treatment weighting (IPTW), and Kaplan-Meier curves were employed.Results In our study, the patients had a mortality rate of 50.07% within 28 days and 62.87% within 360 days. RCS analysis revealed a non-linear correlation between LAR and the risk of mortality at both 28 and 360 days. Cox regression analysis, which was adjusted for nine variables identified by LASSO, confirmed that a high LAR (>1.641) served as an independent predictor of mortality at these specific time points (p 1.641) was found to be an autonomous predictor of mortality at both 28 and 360 days in critically ill patients with AKI undergoing CRRT.

Abstract The multi‐component strategy has proven effective in advancing the performance of organic photovoltaics (OPVs), enhancing photocurrent and fill factor through spectral complementarity and morphology optimization. However, the open‐circuit voltage (VOC) mechanism in multi‐component systems lacks systematic investigation. In this study, we explore the influence of alloy‐like phases on energy level distribution and energy loss mechanisms in multi‐component OPVs. Appropriate modulation of donor alloy‐like phases maintains the original intermolecular stacking, enhances component compatibility, reduces acceptor aggregation, and improves acceptor phase purity, mitigating non‐radiative recombination losses. Additionally, suitable alloy‐like phase modulation elevates charge transfer (CT) states, reducing the gap between CT and local exciton state, lowering reorganization energy, and alleviating radiative recombination loss below the bandgap. Through synergistic optimization (layer‐by‐layer method with solid additive), ternary devices based on Y6 acceptor achieve a notable 19.41% power conversion efficiency, offering new insights for the analysis of the energy loss of the multi‐component OPVs.

Summary: Continuous renal replacement therapy (CRRT) is a commonly utilized treatment modality for individuals experiencing severe acute kidney injury (AKI). The objective of this research was to construct and assess prognostic models for the timely discontinuation of CRRT in critically ill AKI patients receiving this intervention. Data were collected retrospectively from the MIMIC-IV database (n = 758) for model development and from the intensive care unit (ICU) of Huzhou Central Hospital (n = 320) for model validation. Nine machine learning models were developed by utilizing LASSO regression to select features. In the training set, all models demonstrated an AUROC exceeding 0.75. In the validation set, the XGBoost model exhibited the highest AUROC of 0.798, leading to its selection as the optimal model for the development of an online calculator for clinical applications. The XGBoost model demonstrates significant predictive capabilities in determining the discontinuation of CRRT.

Abstract Polymerization degree plays a vital role in material properties. Previous methodologies of molecular weight control generally cannot suppress or alleviate batch-to-batch variations in device performance, especially in polymer solar cells. Herein, we develop an in-situ photoluminescence system in tandem with a set of analysis and processing procedures to track and estimate the polymerization degree of organic photovoltaic materials. To support the development of this protocol, we introduce polymer acceptor PYT constructed by near-infrared Y-series small molecule acceptors via Stille polymerization, and shed light on the correlations between molecular weight, spectral parameters, and device efficiencies that enable the design of the optical setup and confirm its feasibility. The universality is verified in PYT derivatives with stereoregularity and fluoro-substitution as well as benzo[1,2-b:4,5-b’]dithiophene-based polymers. Overall, our result provides a tool to tailor suitable conjugated oligomers applied to polymer solar cells and other organic electronics for industrial scalability and desired cost reduction.

Abstract Background Patients admitted to the surgical intensive care unit (SICU) often suffer from multi-organ dysfunction and have a high mortality rate. Therefore, finding a simple but effective clinical indicator to predict the prognosis of patients is essential to improve their survival. The aim of this study was to investigate the relationship between blood urea nitrogen to serum albumin ratio (B/A) and short-term mortality among patients from the SICU. Methods All eligible adult patients admitted to the SICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were recruited for this study. Participants were divided into a death group (n = 638) and a survival group (n = 2,048) based on the 90-day prognosis, and then grouped by B/A quartiles. We used restricted cubic splines (RCS) to visually analyze the correlation of B/A with 30- and 90-day risk of death. Cumulative survival rates were estimated using Kaplan–Meier survival curves according to B/A quartiles and evaluated using the log-rank test. Cox proportional risk models were developed and sensitivity analyses were performed to explore whether B/A was independently associated with short-term outcomes in SICU patients. Receiver operating characteristic (ROC) curves were analyzed to ascertain the value of B/A for prognosticating 90-day outcome. Results A total of 2686 participants were included in the final study, and their 30-day and 90-day all-cause mortality rates were 17.61% and 23.75%, respectively. The differences in 30-day and 90-day mortality rates were statistically significant among the four groups of patients (all p 9.69) was an independent risk factor for 30-day and 90-day all-cause mortality in SICU patients. The analysis of ROC curves demonstrated that B/A exhibited a significant predictive ability for 90-day mortality, with an optimal threshold of 6.587, a sensitivity of 56.9%, and a specificity of 64.8%. Conclusions Elevated B/A (> 9.69) on admission was an independent risk factor for short-term mortality in SICU patients, and clinicians should pay more attention to this group of patients and intervene clinically at an early stage to reduce mortality.

BackgroundExploring factors associated with the outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) has become a hot focus in research. We sought to investigate the associations of inflammatory markers and blood cell count in cerebrospinal fluid with the outcome of aSAH patients.MethodsWe carried a retrospective study including 200 patients with aSAH and surgeries. The associations of neutrophil, lymphocyte, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII), system inflammation response index (SIRI), and blood cell count in cerebrospinal fluid on the 1st and 7th postoperative days with the outcome of aSAH patients were investigated by univariate analysis and multivariate logistic regression model.ResultsAccording to the modified Rankin scale (mRS) score, there were 147 patients with good outcome and 53 patients with poor outcome. The neutrophil, NLR, SIRI, and SII levels on the seventh postoperative day in patients with poor outcome were all significantly higher than patients with good outcome, P < 0.05. The multivariate logistic regression model including inflammatory markers and blood cell counts in cerebrospinal fluid on the 1st postoperative day confirmed that red blood cell count in cerebrospinal fluid (≥177 × 109/L; OR: 7.227, 95% CI: 1.160–45.050, P = 0.034) was possibly associated with poor outcome of aSAH patients, surgical duration (≥169 min), Fisher grade (III–IV), hypertension, and infections were also possibly associated with the poor outcome. The model including inflammatory markers and blood cell counts in cerebrospinal fluid on the 7th postoperative day confirmed that red blood cell count in cerebrospinal fluid (≥54 × 109/L; OR: 39.787, 95% CI: 6.799–232.836, P < 0.001) and neutrophil-lymphocyte ratio (≥8.16; OR: 6.362, 95% CI: 1.424–28.428, P = 0.015) were all possibly associated with poor outcome of aSAH patients. The NLR (r = 0.297, P = 0.007) and SIRI (r = 0.325, P = 0.003) levels were all correlated with the count of red blood cells in cerebrospinal fluid.DiscussionHigher neutrophil-lymphocyte ratio and higher red blood cell count in cerebrospinal fluid were all possibly associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage. However, we need a larger sample study.

BackgroundImproving health care in cities with a diverse, international population is crucial for ensuring health equity, particularly for foreigners facing challenges due to cultural and language barriers. This situation is especially relevant in China, a major destination for expatriates and travelers, where optimizing health care services and incorporating international standards in the public sector are vital. Achieving this involves understanding the operational details, cultural and linguistic nuances, and advancing medical digitalization. A strategic approach focusing on cultural competence and awareness of health care systems is essential for effectively navigating health care for foreigners and expatriates in China. ObjectiveThe aim of this study was to perform an in-depth analysis of the subjective and objective experiences of local and international patients in public hospitals in China to provide a basis for enhancing the medical experience of all patients. MethodsA structured questionnaire was provided to patients at an international outpatient service of a top-tier university hospital in China. Qualitative analysis of the survey responses was performed to methodically categorize and analyze medical treatment, focusing on patient demand and satisfaction across four main category elements (“high demand, high satisfaction”; “high demand, low satisfaction”; “low demand, high satisfaction”; and “low demand, low satisfaction”), enabling a detailed cross-sectional analysis to identify areas for improvement. ResultsElements falling under “high demand, high satisfaction” for both Chinese and international patients were primarily in the realms of medical quality and treatment processes. In contrast, elements identified as “high demand, low satisfaction” were significantly different between the two patient groups. ConclusionsThe findings highlight the importance of systematic, objective research in advancing the quality of international health care services within China’s leading academic medical centers. Key to this improvement is rigorous quality control involving both patients and providers. This study highlights the necessity of certifying such centers and emphasizes the role of digital platforms in disseminating information about medical services. This strategy is expected to cater to diverse patient needs, enhancing the overall patient experience. Furthermore, by developing comprehensive diagnosis and treatment services and highlighting the superior quality and costs associated with international health care, these efforts aim to foster a sense of belonging among international patients and increase the attractiveness of China’s medical services for this demographic.

Stem cell-based therapies exhibit considerable promise in the treatment of diabetes and its complications. Extensive research has been dedicated to elucidate the characteristics and potential applications of adipose-derived stromal/stem cells (ASCs). Three-dimensional (3D) culture, characterized by rapid advancements, holds promise for efficacious treatment of diabetes and its complications. Notably, 3D cultured ASCs manifest enhanced cellular properties and functions compared to traditional monolayer-culture. In this review, the factors influencing the biological functions of ASCs during culture are summarized. Additionally, the effects of 3D cultured techniques on cellular properties compared to two-dimensional culture is described. Furthermore, the therapeutic potential of 3D cultured ASCs in diabetes and its complications are discussed to provide insights for future research.

Background: Sepsis is a prevalent and severe medical condition which is frequently observed in the intensive care unit (ICU). Although numerous biomarkers have been identified to predict the prognosis of sepsis, the lactate dehydrogenase to albumin ratio (LDH/ALB ratio) has not been extensively investigated. The principal objective of this study is to assess the relationship between LDH/ALB ratio and all-cause mortality in patients with sepsis. Methods: This study included all adult critically ill patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.0) database. Propensity score matching (PSM) analysis was conducted to mitigate bias, and Kaplan-Meier curves were performed to evaluate the cumulative survival across different groups. The association between the LDH/ALB ratio and mortality was examined through restricted cubic spline (RCS) analysis and Cox regression analysis. The robustness of the findings was confirmed through subgroup analyses. Additionally, the prognostic capability of the LDH/ALB ratio was further evaluated using receiver operating characteristic (ROC) curve analysis. Results: There were 6059 adult patients with sepsis enrolled in the final analysis. RCS revealed a non-linear relationship between the LDH/ALB ratio and an increased risk of ICU all-cause mortality (χ2 = 46.900, P

Objective To compare the efficacy and safety of different anti-vascular endothelial growth factor (VEGF) agents combined with different delivery methods for neovascular glaucoma (NVG).Design Systematic review and Bayesian network meta-analysis (NMA).Data sources PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, ISRCTN and Chinese databases including the China National Knowledge Infrastructure, China Science Periodical Database (Wanfang Database), VIP Journal Integration Platform and China Biology Medicine Database were searched from inception to 5 September 2022.Eligibility criteria We included randomised controlled trials (RCTs) that investigated the treatment of NVG using different anti-VEGF agents combined with various methods of drug administration, without any language limitations. All patients included underwent panretinal laser photocoagulation and there were no restrictions on prior glaucoma surgery.Data extraction and synthesis Two independent reviewers extracted data and assessed the risk of bias. Random-effect Bayesian NMA was conducted to compare the efficacy and safety and rank priority of anti-VEGF regimens. The source of heterogeneity and the related factors affecting the stability of the results were also explored. CINeMA (Confidence in Network Meta-Analysis) was used to assess the certainty of evidence.Results Our analysis included 17 RCTs involving a total of 1311 eyes from 1228 patients. We examined five different treatment regimens, which used three different anti-VEGF drugs. The following treatments showed a significant decrease in intraocular pressure (IOP) compared with the control group at 1 month after glaucoma surgery: simultaneous intravitreal and intracameral injection of conbercept (ICCIVC) (mean difference (MD)=−11.56, 95% credible interval (CrI) −20.8 to −2.24), intravitreal injection of conbercept (MD=−8.88, 95% CrI −13.93 to −3.78), intravitreal injection of ranibizumab (MD=−7.62, 95% CrI −10.91 to −4.33) and intravitreal injection of bevacizumab IVB) (MD=−5.51, 95% CrI −10.79 to −0.35). The surface under the cumulative ranking curve (SUCRA) analysis indicated that ICCIVC (82.0%) may be the most effective regimen in reducing IOP. In terms of safety, there were no statistically significant differences among the interventions. According to the SUCRA analysis, ICCIVC (68.0%) was considered the safest choice with the fewest complications. Subgroup and meta-regression analyses showed that mean age was the main source of heterogeneity. Sensitivity analysis demonstrated the robustness of the study results.Conclusion ICCIVC was more effective and safer than other anti-VEGF regimens for NVG. Simultaneous intravitreal and intracameral injection was found to be the best route of administration, and conbercept was found to be the superior drug selection when compared with ranibizumab and bevacizumab.PROSPERO registration number CRD42022309676.

Abstract Introduction A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p

Assessing the spatio-temporal variability and driving forces of soil erosion on the Loess Plateau is critical for ecological and environmental management. In this paper, the Revised Universal Soil Loss Equation (RUSLE) model, the patch-generating land use simulation, and the Geographical Detector are used to investigate the spatio-temporal variations of the Loess Plateau’s soil erosion from 2000 to 2050. The results showed that: (1) The primary categories of soil erosion from 2000 to 2020 were moderate, mild, and slight, and the average level of soil erosion exhibited a decreasing and then an increasing tendency during the last 20 years. (2) Soil erosion was directly impacted by changes in land use, with cropland and forest being the primary land use and land cover changes in the study region. Cropland and construction land being turned into woodland between 2000 and 2020 resulted in a significant decrease in the severity of soil erosion. Projected soil erosion is expected to increase significantly between 2020 and 2050 due to arable land being converted into construction land. (3) The key variables impacting the spatial distribution of soil erosion were LUCC (Land-Use and Land-Cover Change), NDVI (Normalized Difference Vegetation Index), and slope, and the interplay of these variables may increase their ability to explain soil erosion. Grasslands with an NDVI ranging from 0.9 to 1, rain ranging from 0.805 to 0.854 m, a slope above 35°, and a terrain elevation ranging from 1595 to 2559 m were identified as having a high risk of soil erosion. Soil erosion prevention and management efforts should focus on the ecological restoration of upland areas in the future.

Background: Cardiogenic shock (CS) is a critical illness with a high mortality rate in clinical practice. Although some biomarkers have been found to be associated with mortality in patients suffering from CS in previous studies. The albumin-corrected anion gap (ACAG) has not been studied in depth. Our study aimed to explore the relationship between ACAG and mortality in patients with CS. Methods: All baseline data was extracted from Medical Information Mart for Intensive Care-IV version: 2.0 (MIMIC-IV). According to the prognosis at 30 days of follow-up, they were divided into survivors and non-survivors groups. The survival curves between the two groups were drawn using the Kaplan-Meier method and the log-rank test. Valid factors were selected using the least absolute shrinkage and selection operator (LASSO) logistic analysis model. Analysis was performed to investigate the relationship between mortality and all enrolled patients using restricted cubic spline (RCS) and Cox proportional hazards models. Receiver operating characteristic (ROC) curves were used to assess the predictive ability of ACAG. Evaluation of final result stability using sensitivity analysis. Results: 839 cases were selected to meet the inclusion criteria and categorized into survivors and non-survivors groups in the final analysis. The ACAG value measured for the first time at the time of admission was selected as the research object. Kaplan-Meier (K-M) survival curves showed that cumulative 30- and 90-day survival decreased progressively with elevated ACAG (p < 0.001), and multifactorial Cox regression analyses showed ACAG to be an independent risk factor for increased 30- and 90-day mortality in patients suffering from CS (p < 0.05). RCS curves revealed that all-cause mortality in this group of patients increased with increasing ACAG (χ2 = 5.830, p = 0.120). The ROC curve showed that the best cutoff value for ACAG for predicting 30-day mortality in patients with CS was 22.625, with a sensitivity of 44.0% and a specificity of 74.7%. The relationship between ACAG and CS short-term mortality remained stable in all sensitivity analyses (All p < 0.05). Conclusions: The ACAG is an independent risk factor for 30- and 90-day mortality in CS patients and predicts poor clinical outcomes in CS patients. According to our study, elevated ACAG at admission, especially when ACAG >20 mmol/L, was an independent predictor of all-cause mortality in CS.

Abstract Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5–6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64–30.36) and 11.60 (95% CI: 8.28–13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34–0.64, p

With the rapid development of synthetic biology, recombinant human collagen has emerged as a cutting-edge biological material globally. Its innovative applications in the fields of material science and medicine have opened new horizons in biomedical research. Recombinant human collagen stands out as a highly promising biomaterial, playing a pivotal role in crucial areas such as wound healing, stroma regeneration, and orthopedics. However, realizing its full potential by efficiently delivering it for optimal therapeutic outcomes remains a formidable challenge. This review provides a comprehensive overview of the applications of recombinant human collagen in biomedical systems, focusing on resolving this crucial issue. Additionally, it encompasses the exploration of 3D printing technologies incorporating recombinant collagen to address some urgent clinical challenges in regenerative repair in the future. The primary aim of this review also is to spotlight the advancements in the realm of biomaterials utilizing recombinant collagen, with the intention of fostering additional innovation and making significant contributions to the enhancement of regenerative biomaterials, therapeutic methodologies, and overall patient outcomes.

ObjectiveInsulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the “common soil” of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings.MethodsWe analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models.ResultsThe LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc.ConclusionThe ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

Summary: Influenza B circulates annually and causes substantial disease burden in humans. However, little is known about the infection mechanisms of influenza B virus (IBV). Here, we find that the host factor cyclophilin A (CypA) facilitates IBV replication by targeting IBV non-structural protein 1 (BNS1) and nucleoprotein (BNP). CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination to stabilize BNS1 by upregulating OTUD4 expression. Meanwhile, CypA and the E3 ligase MIB1 competitively interact with BNP to inhibit its proteasomal degradation. Moreover, cyclosporine A treatment or CypA R55A mutation results in an impaired function of CypA in IBV replication. Notably, BNP hijacks CypA into the nucleus to enhance the activity of viral ribonucleoprotein complexes by enhancing the interaction between BNP and IBV polymerase basic protein 1. Taken together, this study unveils the critical role of CypA in facilitating IBV replication, suggesting that CypA is a promising target for anti-IBV drug.

Müller cells play an integral role in the development, maintenance, and photopic signal transmission of the retina. While lower vertebrate Müller cells can differentiate into various types of retinal neurons to support retinal repair following damage, there is limited neurogenic potential of mammalian Müller cells. Therefore, it is of great interest to harness the neurogenic potential of mammalian Müller cells to achieve self-repair of the retina. While multiple studies have endeavored to induce neuronal differentiation and proliferation of mammalian Müller cells under defined conditions, the efficiency and feasibility of these methods often fall short, rendering them inadequate for the requisites of retinal repair. As the mechanisms and methodologies of Müller cell reprogramming have been extensively explored, a summary of the reprogramming process of unlocking the neurogenic potential of Müller cells can provide insight into Müller cell fate development and facilitate their therapeutic use in retinal repair. In this review, we comprehensively summarize the progress in reprogramming mammalian Müller cells and discuss strategies for optimizing methods and enhancing efficiency based on the mechanisms of fate regulation.

Background The early identification of patients at high risk for acute kidney injury (AKI) with a poor prognosis is crucial to prevent complications and minimize mortality. This study sought to investigate the association between albumin-corrected anion gap (ACAG) and all-cause mortality among critically ill patients with AKI.Methods All eligible AKI patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV version 2.0) database were considered for participation in this study. We employed Kaplan–Meier curves to assess the 30-d and 360-d cumulative survival rates among various groups. Flexibly visualizing the connection between ACAG and mortality, we utilize restricted cubic splines (RCS) and multivariate Cox regression models. Result robustness underwent assessment through subgroup analyses and sensitivity analyses. Receiver-operating characteristic (ROC) curves were generated to evaluate the predictive performance of ACAG.Results The study included 9625 AKI participants, of whom 58.60% were male, and the 360-d all-cause mortality rate was 39.89%. According to Kaplan–Meier analysis, the 30-d and 360-d cumulative survival rates for AKI patients were significantly lower in the high ACAG group than in the normal ACAG group. RCS analysis indicated that ACAG levels had a non-linear correlation with the risk of 30-d and 360-d mortality for AKI patients. Cox regression analysis demonstrated that ACAG is an independent risk indicator for 30-d and 360-d prognosis in AKI patients in the ICU.Conclusions Elevated ACAG levels (> 20 mmol/L) at ICU admission were associated with 30-d and 360-d all-cause mortality in critically ill patients with AKI.

The inferior short-circuit current density (JSC) of the conjugated block copolymers (CBCs) based single component organic solar cells (SCOSCs), compared with that of binary all-polymer systems, is the main reason for their limited power conversion efficiency (PCE). To improve the JSC of SCOSCs by enhancing the light-harvesting ability, we designed and synthesized three narrower bandgap acceptor monomers with different chlorine-substituted terminals, and incorporated them into the CBCs. As the position of chlorine substitution altered, the blend morphology, the device performance, and the physical mechanism changed accordingly. It is worth noting that the PB-b-PYCl-2-based SCOSCs exhibited a significantly improved JSC, accompanied by the best PCE of 13.42 %, and good thermal stability. This study illustrated the terminal chlorination strategy is a promising way to modify the device performance of the SCOSCs.

AbstractObjective To compare the efficacy and safety of hyperthermic intrathoracic/intraperitoneal chemotherapy versus conventional intrapleural/intraperitoneal chemotherapy in the treatment of malignant pleural or peritoneal effusion.Methods A randomized clinical trial was carried out in 8 cancer centers across China. Patients with malignant pleural or peritoneal effusion were randomly assigned to the study group or control group. Patients in the study group were treated with cisplatin-based hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC), while the control group was treated with conventional intrapleural or intraperitoneal chemotherapy using same chemotherapeutic regime as the study group. The objective response rate (ORR) was analyzed as primary outcome. Quality-of-life (QOL) score was recorded as secondary outcome using the questionnaire 30 (QLQ-C30) of the European Organization for Research and Treatment of Cancer (EORTC). The efficacy and safety of the two treatments were compared.Results Total 135 patients were recruited and randomized in this study, with 67 patients in the study group and 68 patients in the control group. The ORR in the study group (80.70%) was significantly higher than that in the control group (31.03%, p

Abstract Objectives Cancer metastasis to the kidney is a rare event. We retrospectively analyzed clinicopathologic characteristics in 6 cases of diagnosed renal metastases from primary lung cancer. We also provide clinical follow-up data and brief review of the literature. Methods Immunohistochemistry was used to evaluate the expression of TTF-1, NapsinA, CK7, CK(AE1/AE3), P63, P40, CgA, PAX-8, GATA3 and Ki-67 in primary tumor and metastases. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed. Results With the help of immunohistochemistry and combined clinical history, we found four cases were lung adenocarcinomas, one case was lung squamous cell carcinoma, and the other case was lung small cell carcinoma metastases to the kidney.The patients were all male by gender and had a mean age of 62 years, and metastasis to the left kidney were more universal. Most of the tumors histological grade originating from the lung were poorly-moderately differentiated, and the time to metastasis to the kidney was relatively short for squamous lung cancer and small cell lung cancer, while the time to metastasis for lung adenocarcinoma was related to its degree of differentiation. Overall, we found the prognosis of lung cancer patients with renal metastases were poor especially with multi-site metastases. Conclusions Distinguishing primary and secondary tumors of the kidney is essential to guide treatment and prevent unnecessary surgery, so clinical information, radiology, histological correlation of the primary tumor, and immunohistochemical findings help the pathologist determine correct diagnosis.

Abstract Introduction Primary breast lymphoma (PBL) is a rare disease, treatment of which excerpts does not reach a consensus. This retrospective study was conducted to analyze clinical features and survival outcomes of different therapeutic methods. Materials and methods Records of 67 patients with stage IE/IIE primary breast lymphoma were reviewed from the medical record system. Survival information was gathered by searching the outpatient system. Clinicopathological characteristics were compared by chi-squared or Fisher’s exact tests. A comparison of survival curves was performed by log-rank tests. The Cox proportional hazard model was applied for multivariate analysis. Results At the median follow-up time of 65.23 months (range, 9–150 months), there were 27 (40.3%) relapses, 28 (41.8%) distant metastases, and 21 (31.3%) deaths. The 5-year progression-free survival (PFS) and overall survival (OS) were 52.1% and 72.4%. Pathological types (DLBCL vs. non-DLBCL, p = 0.001) and rituximab use (p

IntroductionObservational studies have reported the association between gut microbiota and the risk of lower respiratory tract infections (LRTIs). However, whether the association reflects a causal relationship remains obscure.MethodsA bidirectional twosample Mendelian randomization (MR) analysis was conducted by assessing genome-wide association study (GWAS) summary statistics for gut microbiota taxa and five common LRTIs. MR methods including inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode were used to analyze the causality. Gene pleiotropy was tested using MR-Egger regression and MR-PRESSO methods. Cochran’s Q test was used to check for heterogeneity. Leave-one-out analysis was used to assess the stability of effect sizes. Detected significant associations were validated by using an independent LRTI GWAS summary statistics dataset. An optional MR method of causal analysis using summary effect estimates (CAUSE) was further performed as a validation to avoid potential false-positive results.ResultsAccording to the MR-Egger estimates in forward MR analysis, a causal effect of gut Blautia on increased odds of bronchiectasis and pneumonia was suggested. MR-Egger regression pleiotropy intercept methods detected no significant horizontal pleiotropy between the instrumental variables of these associations. MR-PRESSO global test examined no potential horizontal pleiotropy. Cochran’s Q test showed that no heterogeneity biased the results. The leave-one-out sensitivity analyses suggested robust causality results. These associations with consistent effect direction were successfully replicated in IVW analysis by using the validation GWAS dataset. However, these evidence of causality did not survive after applying strict Bonferroni correction or CAUSE analysis. The reverse MR analysis failed to achieve consistent results in the effect of LRTIs on gut microbiota through comprehensive discovery and validation processes.DiscussionThis study established no strong causality between genetically predicted gut microbiome and the risk of lower respiratory tract infections. However, specific subtypes of microbial genera, such as Blautia, were identified as potential influencers and require further investigation, particularly at the species or strain levels.

Objectives: With the characteristics of mindfulness and breathing techniques, Tai Chi has been recommended with therapeutic values in chronic obstructive pulmonary disease (COPD). However, its strengths as a complementary exercise for conventional pulmonary rehabilitation (PR) remain unclear. Design and setting: This single-blinded randomised controlled trial recruited patients with mild to severe stable COPD. Eligible participants were randomly assigned to the group with usual care (control), total body recumbent stepper (TBRS) exercise, Tai Chi (TC), or combined TBRS exercise and Tai Chi (TBRS-TC). Patients received a two-month hospital-based supervised exercise, followed by a ten-month community- or home-based rehabilitation program. Results: A total of 120 participants were recruited, and 102 were included in the per-protocol analysis. The mean changes in St George’s Respiratory Questionnaire (SGRQ) total score from baseline to the post-hospital exercise in the control group, TBRS group, TC group, and TBRS-TC group was 2.62 (95 % CI −8.99 to 8.99), −9.28 (95 % CI −13.96 to −4.60), −10.19 (95 % CI −13.72 to −6.67), and −16.75 (95 % CI −20.25 to −13.24), respectively, with a statistically significant difference between groups in favor of the TBRS-TC exercise (P

BackgroundPatients with rheumatic diseases have an increased likelihood of being admitted to the intensive care unit (ICU), highlighting the importance of promptly identifying high-risk individuals to enhance prognosis. This study aimed to assess the correlation of red blood cell distribution width to albumin ratio (RAR) with the 90-days and 360-days survival rates among critically ill rheumatic patients.MethodsAdult rheumatic patients admitted to the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included. The participants were categorized into two groups, survivors (n = 436) and non-survivors (n = 192), based on their 90-days survival outcome. The population was further classified into tertiles using RAR values, with RAR 6.07 (n = 209). Kaplan–Meier curves were utilized to evaluate the cumulative survival rates at 90-days and 360-days. The association between RAR and mortality was assessed using restricted cubic splines (RCS) and multivariate Cox regression analysis. Additional subgroup analyses and sensitivity analyses were conducted to further explore the findings. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive performance of RAR.ResultsThis study involved 628 critically ill patients with rheumatic diseases, and they had an all-cause mortality of 30.57% at 90-days and 38.69% at 360-days. Kaplan–Meier analysis showed a gradual decrease in both 90-days and 360-days cumulative survival with increasing RAR (χ2 = 24.400, p 6.07) was significantly correlated with mortality. The ROC curves demonstrated that an optimal cut-off value of RAR for predicting 90-days mortality was determined to be 5.453, yielding a sensitivity of 61.5% and specificity of 60.3%.ConclusionElevated RAR (> 6.07) was associated with all-cause mortality at 90-days and 360-days among critically ill patients with rheumatic diseases, serving as an independent risk factor for unfavorable prognosis.

Background Pancreatic cancer (PAC) is one of the most malignant cancer types and immunotherapy has emerged as a promising treatment option. PAC cells undergo metabolic reprogramming, which is thought to modulate the tumor microenvironment (TME) and affect immunotherapy outcomes. However, the metabolic landscape of PAC and its association with the TME remains largely unexplored.Methods We characterized the metabolic landscape of PAC based on 112 metabolic pathways and constructed a novel metabolism-related signature (MBS) using data from 1,188 patients with PAC. We evaluated the predictive performance of MBS for immunotherapy outcomes in 11 immunotherapy cohorts from both bulk-RNA and single-cell perspectives. We validated our results using immunohistochemistry, western blotting, colony-formation assays, and an in-house cohort.Results MBS was found to be negatively associated with antitumor immunity, while positively correlated with cancer stemness, intratumoral heterogeneity, and immune resistant pathways. Notably, MBS outperformed other acknowledged signatures for predicting immunotherapy response in multiple immunotherapy cohorts. Additionally, MBS was a powerful and robust biomarker for predicting prognosis compared with 66 published signatures. Further, we identified dasatinib and epothilone B as potential therapeutic options for MBS-high patients, which were validated through experiments.Conclusions Our study provides insights into the mechanisms of immunotherapy resistance in PAC and introduces MBS as a robust metabolism-based indicator for predicting response to immunotherapy and prognosis in patients with PAC. These findings have significant implications for the development of personalized treatment strategies in patients with PAC and highlight the importance of considering metabolic pathways and immune infiltration in TME regulation.

Background: Binafuxi granules are a traditional Uighur medicine (TUM) for treating the common cold with fever. However, high-quality clinical studies supporting its efficacy and safety are lacking. Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial, patients with common cold and fever were randomly assigned to a high-dose group, low-dose group, and placebo group in a 1:1:1 ratio. Outcomes were time to fever relief, time to fever clearance, proportion of afebrile patients, time to symptom disappearance, rate of symptom disappearance, effective rate, emergency drug usage and safety assessment. Results: A total of 235 patients were recruited. Of these, 234 were included in the full analysis set (FAS), and 217 were included in the per-protocol set (PPS). In the FAS analysis, the median time to fever relief was 6.00 h, 5.54 h and 10.65 h (P = 0.31) in the high-dose group, low-dose group and placebo group, respectively. The median time to fever clearance was 18.29 h, 20.08 h and 25.00 h (P = 0.0018), respectively, and the proportion of afebrile patients was 92.4%, 89.7% and 71.4% (P = 0.0002), respectively. There was a significant difference in the disappearance time and disappearance rate of all symptoms and of individual symptoms. No serious adverse events were found. Conclusions: Binafuxi granules can dose-dependently shorten the fever course and improve clinical symptoms in patients suffering from the common cold with fever. Trial Registration: This trial was registered at Chinese Clinical Trial Registry (ChiCTR-IIR-17013379).

Simultaneous localization and mapping (SLAM) is a fundamental function of intelligent robots. To reduce the influence of dynamic objects on SLAM in dynamic environments, this study pro-poses a visual SLAM based on sequential image segmentation, referred to as SIIS-SLAM. Based on ORB-SLAM3, SIIS-SLAM integrates the sequential image instance segmentation and optical flow dynamic detection module. The sequential image segmentation module is designed to eliminate the effectiveness of dynamic objects in the estimation of relative pose between sequential frames. Specifically, based on the coarse relative pose estimated by ORB-SLAM3 and the box coordinates of instances detected by Mask R-CNN, the sequential image segmentation module effectively improves the speed and accuracy of instance segmentation. Dynamic objects can be effectively detected by combining the instance segmentation results and optical flow module. Filtering the feature points in dynamic objects can improve the accuracy and robustness of SLAM. Experimental results demonstrate that SIIS-SLAM achieves the better accuracy in dynamic environments compared to ORB SLAM3 and other advanced methods.

Abstract Introduction Older adults are among the most vulnerable groups during the COVID-19 epidemic, contributing to a large proportion of COVID-19-related death. Medication review and reconciliation by pharmacist can help reduce the number of potentially inappropriate medications but these services were halted during COVID-19. Aim To assess the prevalence and factors associated with inappropriate medicine use among older populations with COVID-19. Methods This was a cross-sectional, retrospective analysis of medications among hospitalized older adults with COVID-19. Potentially inappropriate medication use was categorized using the Beer’s and STOPP criteria. Results Combining both criteria, 181 (32.7%) of the 553 patients were identified to have used at least one or more potentially inappropriate medication. A marginally higher number of inappropriate medications was documented using the Beers 2019 criteria (151 PIM in 124 patients) compared to STOPP criteria (133 PIMS in 104 patients). The long-term use of proton pump inhibitors (n = 68; 12.3%) and drugs which increases the risk of postural hypotension were the most commonly reported PIM (n = 41; 7.4%). Potentially inappropriate medication use was associated with previous history of hospital admission in the past 12 months (Odds ratio [OR]: 2.27; 95% CI 1.29–3.99) and higher number of discharge medications. Conclusions Nearly, one in three older adults with COVID-19 had been prescribed a PIM, and the proportion of older adults with polypharmacy increased after discharge. This highlights the importance of having clinical pharmacist conducting medication reviews to identify PIMs and ensure medication appropriateness.

Abstract Background Sepsis is a common critical illness in intensive care unit (ICU) and seriously threatens the life of patients. Therefore, to identify a simple and effective clinical indicator to determine prognosis is essential for the management of sepsis patients. This study was mainly based on blood urea nitrogen to albumin ratio (B/A), a comprehensive index, to explore its correlation with the prognosis of sepsis patients during hospitalization. Methods Totally, adult patients in ICU who were diagnosed with sepsis in Medical Information Mart for Intensive Care IV(MIMIC-IV) database from 2008 to 2019 were involved in this study. The study population were divided into survivors group and non-survivors group based on the prognosis during hospitalization. Restricted cubic spline (RCS) was utilized to analyze the association between B/A level and the risk of ICU all-cause mortality in patients with sepsis and determine the optimal cut-off value of B/A. The study population was divided into low B/A group and high B/A group based on the optimal cut-off value. The survival curve of ICU cumulative survival rate was draw through Kaplan–Meier method. The correlation between B/A and the prognosis of patients was conducted by multivariate Cox regression analysis. Furthermore, we performed sensitivity analyses to assess the robustness of the results. Results A total of 10,578 patients with sepsis were enrolled, and the ICU all-cause mortality was 15.89%. The patients in the non-survivors group had higher B/A values and more comorbidities than those in the survivors group. RCS showed that the risk of ICU all-cause mortality increased with the B/A level, showing a non-linear trend (χ2 = 66.82, p

Objective To investigate the efficacy and safety of a novel method of hyperthermic intraperitoneal chemotherapy (HIPEC) as adjuvant therapy for stage-III gastric cancer. Methods Patients with stage-III gastric cancer who underwent D2 radical gastrectomy were randomly assigned to the HIPEC or control group four weeks after surgery. The HIPEC group was treated with cisplatin (60 mg/m2) administered with a HIPEC device on days 1 and 3 (30 mg/m2 each time), along with oral S-1, 40–60 mg, twice daily, for 14 days. The control group was treated with cisplatin (60 mg/m2) administered intravenously plus oral S-1 (40–60 mg, 2/d for 14 days). The primary outcome of the study was disease-free survival (DFS). Results Total 114 patients were included in the study, with 57 patients in each group. The median DFS was 29.0 months in the HIPEC group, which was significantly longer than that in the control group (15.0 months, p = 0.006). The two-year DFS rate in the HIPEC group was higher than that in the control group (50.4% vs. 25.5%). Median OS was 42.0 month in the HIPEC group and 31.0 month in the control (p = 0.042). Peritoneal metastasis occurred in six patients in the HIPEC group (10.5%) and 12 patients in the control (21.1%, p = 0.198). No significant difference in the incidence of adverse event except for thrombocytopenia. Conclusion HIPEC with cisplatin plus oral S-1 is a safe and effective adjuvant therapy for patients with advanced gastric cancer following D2 radical gastrectomy. Trial registration: This study was registered at ClinicalTrials.gov with the identifier (NCT number): NCT02396498

Abstract Background Developing adequate regional anaesthesia for knee surgeries without affecting lower limb mobilization is crucial to perioperative analgesia. However, reports in this regard are limited. We proposed a technique for ultrasound-guided peripatellar plexus (PP) block. Compared with the femoral nerve (FN) block, we hypothesized that this technique would provide a noninferior block duration and a complete cutaneous sensory block in the peripatellar region without affecting lower limb mobilization. An investigation was conducted to verify our hypothesis in cadavers and volunteers. Methods The study was designed in two parts. First, eight cadaveric lower limbs were dissected to verify the feasibility of PP block after methylene blue injection under ultrasound. Second, using a noninferiority study design, 50 healthy volunteers were randomized to receive either a PP block (PP group) or an FN block (FN group). The primary outcome was the duration of peripatellar cutaneous sensory block, with the prespecified noninferiority margin of -3.08 h; the secondary outcome was the area of peripatellar cutaneous sensory block; in addition, the number of complete anaesthesias of the incision line for total knee arthroplasty and the Bromage score 30 min after block were recorded. Results The PP was successfully dyed, whereas the FN and saphenous nerve were unstained in all cadaveric limbs. The mean difference of the block duration between the two groups was − 1.24 (95% CI, -2.81 − 0.33) h, and the lower boundary of the two-sided 95% CI was higher than the prespecified noninferiority margin (Pnoninferiority = 0.023), confirming the noninferiority of our technique over FN block. The cutaneous sensory loss covered the entire peripatellar region in the PP group. PP block achieved complete anaesthesia of the incision line used for total knee arthroplasty and a Bromage score of 0 in 25 volunteers, which differed significantly from that of volunteers who underwent FN block. Conclusion Ultrasound-guided PP block is a feasible technique. Compared with FN block, PP block provides noninferior block duration and complete blocking of the peripatellar region without affecting lower limb mobilization. Trial registration This study was registered in the Chinese Clinical Trial Register (registration no. ChiCTR2000041547, registration date 28/12/2020).

Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3. Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo. We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection.

Transfer printing of small-molecular organic semiconductors often faces challenges due to surface adhesion mismatch. Here, we developed a sacrificing-layer-assisted transfer printing technique for the deposition of small-molecular thin films. High-boiling-point ethylene glycol (EG) was doped in aqueous solution poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as the sacrificing layer to manipulate residual water in film, which allowed chlorobenzene solution to spontaneously spread and form uniform film. The residual water guaranteed film delamination from the stamp, allowing for its transfer onto various substrates and seeding layers. As a proof of concept, laterally conductive organic photodetectors using recyclable EG-PEDOT:PSS electrodes and a small-molecular active layer were consecutively fabricated via transfer printing in ambient air. The resulting device exhibited a high on/off ratio of 711 and a fast rise time of 0.5 ms. Notably, the polymer electrode and the bulk heterojunction demonstrated unique repairability and recyclability.

Background: Although previous studies have reported that many biomarkers can determine the prognosis of patients with acute myocardial infarction (AMI), serum anion gap (AG) has not been well studied. We aimed to investigate the association between serum AG and mortality in patients with AMI. Methods: Adult patients first admitted to the ICU and diagnosed with AMI from 2008 to 2019 in the MIMIC-IV database were included. Patients were divided into the survival and non-survival groups based on 30-day and 90-day outcomes. According to the AG value (15.12 mmol/L) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low AG groups. The Kaplan-Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test. Multivariate Cox regression analysis and RCS analysis were constructed to assess the relationship between AG and recent all-cause mortality in patients with AMI. Results: 4446 patients were enrolled. The 30-day and 90-day mortality rates in the high AG group (25.53%, 31.75%) were higher than that in the low AG group (9.73%, 14.01%, P

When acid phosphogypsum (APG) is recycled as aggregate of cemented backfill in mines, pretreatment is usually needed to reduce its adverse impact on the backfill. In this study, a new approach of using a neutral salt (CaCO3) to pretreat APG has been proposed to enhance the strength development of the cemented PG backfill. The role of CaCO3 in cemented PG backfill acting as a reactant is explored. In the pretreatment stage, CaCO3 reacted with the residual acid in PG, and the generated calcium ions could solidify the impurities, such as soluble phosphate and fluoride, with solidification rates reaching 90% and 99%, respectively. This neutral modifier buffered pH values of PG aggregate from 1.8 to about 5.0, and excess dosage of CaCO3 did not adjust the pH value of aggregate to an excessively high level. Hence, there was no interference with the hydration reaction of the binder (cement). Using PG pretreated with CaCO3 as aggregate for cemented backfill effectively accelerated the setting process of backfill and increased the unconfined compressive strength (UCS) of the backfill matrix from 0.14 MPa to 2.27 MPa at 28-day age. The present results suggest that CaCO3 pretreatment is an effective way to improve the accessibility of PG as aggregate, thus significantly increasing the utilization rate of PG and enhancing the backfill performance.

Techniques of 3D modeling have earned increasing popularity in scientific studies as they offered unprecedented traits in representing objects. As with all mathematical models, the 3D model will be useful once its accuracy has been validated with direct measurements and the robustness of its predictive capability tested. Although measures of body mass and volume are essential to comprehend the life history of animals, such morphometrics, especially total volume, are challenging to obtain from marine mammals due to their elusive nature, aquatic lifestyle, and large size. In this study, accurate measurements of body volume were directly detected from fresh carcasses of eleven finless porpoises (Neophocaena asiaeorientalis sunameri) and used to validate 3D models recreated from the same animals using Blender 3D graphics. Published models using truncated cones or elliptical shapes, based on 3, 5, 8, or 19 measurements of girths or heights & widths along the body, were also applied to porpoises to verify their accuracy. The Blender-generated 3D model produced the most accurate estimates of body volume compared to conventional truncated models, with a mean error of only 2.5% to the direct volume measurements. When photogrammetric images are available, the model can predict the body volumes based on total length alone. Similar accuracy was possible with the elliptical model using 19 height & width measurements (5% increments in total length). However, significant (p < 0.001) inaccuracy resulted from truncated models with 3, 5, or 8 girth measurements and elliptical models with 3 or 5 height & width measurements, and the accuracy of these models also decreased significantly as the number of measurement sites was reduced. Moreover, Blender 3D models can be extrapolated to animals with images absent, and such predicted volumes were tested to be trustworthy (overall skill = 0.998, r = 0.998, p < 0.01). Therefore, we recommend that researchers use either digital 3D models or elliptical models with 5% increments sectioning the torso to obtain accurate estimates of the body volumes of free-ranging marine mammals.

Background: Cardiac arrest (CA) is a common event in the intensive care unit (ICU), which seriously threatens the prognosis of patients. Therefore, it is crucial to determine a simple and effective clinical indicator to judge the prognosis of patients after a CA for later treatments. The purpose of this study was to investigate the relationship between the lactate dehydrogenase to albumin ratio (LAR) and the prognosis of patients after a CA. Methods: The clinical data of participants was obtained from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0; 2008 to 2019). According to the 30-day prognosis, patients were divided into a survivors group (n = 216) and a non-survivors group (n = 304). The optimal LAR threshold was determined using restricted cubic spline (RCS), which divided patients into a high LAR group (≥15.50, n = 257) and a low LAR group (

Multiple myeloma (MM) is still an incurable hematologic malignancy, which is eagerly to the discovery of novel therapeutic targets and methods. N-acetyltransferase 10 (NAT10) is the first reported regulator of mRNA acetylation that is activated in many cancers. However, the function of NAT10 in MM remains unclear. We found significant upregulation of NAT10 in MM patients compared to normal plasma cells, which was also highly correlated with MM poor outcome. Further enforced NAT10 expression promoted MM growth in vitro and in vivo, while knockdown of NAT10 reversed those effects. The correlation analysis of acetylated RNA immunoprecipitation sequencing (acRIP-seq) and ribosome profiling sequencing (Ribo-seq) combined with RIP-PCR tests identified centrosomal protein 170 (CEP170) as an important downstream target of NAT10. Interfering CEP170 expression in NAT10-OE cells attenuated the acceleration of cellular growth caused by elevated NAT10. Moreover, CEP170 overexpression promoted cellular proliferation and chromosomal instability (CIN) in MM. Intriguingly, remodelin, a selective NAT10 inhibitor, suppressed MM cellular growth, induced cellular apoptosis in vitro and prolonged the survival of 5TMM3VT mice in vivo. Collectively, our data indicate that NAT10 acetylates CEP170 mRNA to enhance CEP170 translation efficiency, which suggests that NAT10 may serve as a promising therapeutic target in MM.

Abstract Background The need for the left ureter to pass through the subsigmoid during ileal conduit diversion surgery has not been investigated in any studies. A modified technique is simply used in the ileal conduit with the left ureter straight over the sigmoid colon due to the possible damage and lack of scientifically validated advantages of this procedure. Our study aimed to investigate the feasibility of the suggested surgical technique, as well as to evaluate perioperative outcomes and postoperative complications with a focus on the prevalence of small bowel obstruction (SBO) and ureteroileal anastomotic stricture (UAS). Methods A prospective single-center cohort of 84 consecutive patients undergoing laparoscopic radical cystectomy (LRC) and ileal conduit urinary diversion was conducted between January 2018 and April 2020. The incidence of SBO and UAS, perioperative outcomes, and postoperative complications were compared between a trial group of 30 patients receiving the modified procedure and a control group of 54 patients receiving the conventional Bricker ileal conduit. Results The two groups were comparable concerning patient characteristics and clinicopathologic features. No differences were observed in terms of the operation time, perioperative outcomes, and short-term (