Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Food impaction on three-dimensional printed models with periodontal ligament simulation.

OBJECTIVE: This study aims to evaluate food impaction on three-dimensional (3D) printed models with periodontal ligament simulation. MATERIALS AND METHODS: Based on a commercial typodont pair, 3D maxillary and mandibular models were created with no teeth and with tooth sockets that were 1 mm wider than the original ones from 24 to 27 or 34 to 37 for periodontal ligament simulation with vinyl polysiloxane impression material. In total, 35 pairs of 7 combinations, including maxillary/mandibular typodonts in occlusion with maxillary/mandibular 3D models with/without a distal gap of canines on 3D models (tooth 23 or 33) were mounted on hinge articulators and divided into seven groups (n = 5). Each sample experienced the same manual chewing simulation on a customized device. The proximal surfaces were photographed to measure the percentage of food impaction area using ImageJ software. RESULTS: Group with fixed maxillary and mandibular teeth showed more food impaction than other groups with significant differences in the average of maxilla and the average of all proximal areas. CONCLUSION: The flexibility of the periodontal ligament and the degree of freedom of the teeth in their sockets may contribute to the extent of food impaction in proximal spaces.

DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma.

BACKGROUND: The faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear. METHODS: The shRNA-specific DNMT1 knockdown was employed to target DNMT1 on oral cancer cells in vitro, as was the use of DNMT1 inhibitors. A xenografted OSCC mouse model was established to determine the effect on tumor suppression. High-throughput microarrays of DNA methylation, bulk and single-cell RNA sequencing analysis, multiplex immunohistochemistry, functional sphere formation and protein immunoblotting were utilized to explore the molecular mechanism involved. Analysis of human samples revealed associations between DNMT1 expression, global DNA methylation and collaborative molecular signaling with oral malignant transformation. RESULTS: We investigated DNMT1 expression boosted steadily during oral malignant transformation in human samples, and its inhibition considerably minimized the tumorigenicity in vitro and in a xenografted OSCC model. DNMT1 overexpression was accompanied by the accumulation of cancer-specific DNA hypomethylation during oral carcinogenesis; conversely, DNMT1 knockdown caused atypically extensive genome-wide DNA hypomethylation in cancer cells and xenografted tumors. This novel DNMT1-remodeled DNA hypomethylation pattern hampered the dual activation of PI3K-AKT and CDK2-Rb and inactivated GSK3ß collaboratively. When treating OSCC mice, targeting DNMT1 achieved greater anticancer efficacy than the PI3K inhibitor, and reduced the toxicity of blood glucose changes caused by the PI3K inhibitor or combination of PI3K and CDK inhibitors as well as adverse insulin feedback. CONCLUSIONS: Targeting DNMT1 remodels a novel global DNA hypomethylation pattern to facilitate anticancer efficacy and minimize potential toxic effects via balanced signaling synergia. Our study suggests DNMT1 is a crucial gatekeeper regarding OSCC destiny and treatment outcome.

Mixed response to the first-line treatment of KRAS G12C inhibitor, sotorasib, in non-small cell lung cancer: A brief report.

Key Clinical Message: One Kirsten Ras (KRAS) G12C mutated non-small cell lung cancer (NSCLC) patient had improved poor performance status and obtained mixed response with the first-line KRAS-targeted treatment of sotorasib. After disease progression, partial response was achieved with chemotherapy plus immunotherapy. KRAS G12C mutated immunoenvironment in NSCLC may favor the immunotherapy. Abstract: KRAS is one of the most commonly mutated genes, which used to be untargetable. The phase II CodeBreak 100 trial revealed 6.8-month median progress-free survival (PFS) and 12.5-month overall survival (OS) in previously treated KRAS G12C-mutant NSCLC patients treated with KRAS inhibitor, sotorasib. The specimens of the brain, lymph node (LN), and blood from the patient were analyzed by next-generation sequencing. Hematoxylin and eosin staining and immunohistochemistry were performed for pathological characterization. Computed tomography (CT) and magnetic resonance imaging (MRI) scan were used for treatment response evaluation. The patient was diagnosed in a bad Eastern Cooperative Oncology Group performance status (ECOG-PS) with metastatic KRAS G12C-mutated lung adenocarcinoma who had achieved mixed response to sotorasib as the first-line treatment. Although 5-month PFS of the treatment with sotorasib was not surprising, the patient achieved significantly improved ECOG-PS score from 4 to 1. Subsequently, partial response (PR) was achieved with the treatment of pemetrexed plus pembrolizumab. This case highlights superior efficacy of first-line treatment with sotorasib for the advance untreated KRAS G12C-mutant patients. The high efficacy of the treatment with chemotherapy plus immunotherapy revealed that immunoenvironment of KRAS G12C-mutated patient may favor the immunotherapy.

Screening approach by a combination of computational and in vitro experiments: identification of fluvastatin sodium as a potential SIRT2 inhibitor.

BACKGROUND: Sirtuins (SIRTs) are NAD+-dependent deacetylases that play various roles in numerous pathophysiological processes, holding promise as therapeutic targets worthy of further investigation. Among them, the SIRT2 subtype is closely associated with tumorigenesis and malignancies. Dysregulation of SIRT2 activation can regulate the expression levels of related genes in cancer cells, leading to tumor occurrence and metastasis. METHODS: In this study, we used computer simulations to screen for novel SIRT2 inhibitors from the FDA database, based on which 10 compounds with high docking scores and good interactions were selected for in vitro anti-pancreatic cancer metastasis testing and enzyme binding inhibition experiments. The results showed that fluvastatin sodium may possess inhibitory activity against SIRT2. Subsequently, fluvastatin sodium was subjected to molecular docking experiments with various SIRT isoforms, and the combined results from Western blotting experiments indicated its potential as a SIRT2 inhibitor. Next, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations were performed, revealing the binding mode of fluvastatin sodium at the SIRT2 active site, further validating the stability and interaction of the ligand-protein complex under physiological conditions. RESULTS: Overall, this study provides a systematic virtual screening workflow for the discovery of SIRT2 activity inhibitors, identifies the potential inhibitory effect of fluvastatin sodium as a lead compound on SIRT2, and opens up a new direction for developing highly active and selectively targeted SIRT2 inhibitors.

Disadvantaged social status contributed to sleep disorders: An observational and genome-wide gene-environment interaction analysis.

BACKGROUND: Sleep is a natural and essential physiological need for individuals. Our study aimed to research the associations between accumulated social risks and sleep disorders. METHODS: In this study, we came up with a polysocial risk score (PsRS), which is a cumulative social risk index composed of 13 social determinants of health. This research includes 239,165 individuals with sleep disorders and social determinants of health data from the UK Biobank cohort. First, logistic regression models were performed to examine the associations of social determinants of health and sleep disorders, including chronotype, narcolepsy, insomnia, snoring, short and long sleep duration. Then, PsRS was calculated based on statistically significant social determinants of health for each sleep disorder. Third, a genome-wide gene-environment interaction study was conducted to explore the interactions between single-nucleotide polymorphisms and PsRS in relation to sleep disorders. RESULTS: Higher PsRS scores were associated with worse sleep status, with the adjusted odds ratio (OR) ranging from 1.10 (95% Confidence interval [CI]: 1.09-1.11) to 1.29 (95% CI: 1.27-1.30) for sleep disorders. Emotional stress (OR = 1.36, 95% CI: 1.28-1.43) and not in paid employment (OR = 2.62, 95% CI: 2.51-2.74) were found to have significant contributions for sleep disorders. Moreover, multiple single-nucleotide polymorphisms were discovered to have interactions with PsRS, such as FRAS1 (P = 2.57 × 10-14) and CACNA1A (P = 8.62 × 10-14) for narcolepsy, and ACKR3 (P = 1.24 × 10-8) for long sleep. CONCLUSIONS: Our findings suggested that cumulative social risks was associated with sleep disorders, while the interactions between genetic susceptibility and disadvantaged social status are risk factors for the development of sleep disorders.

Investigation of Levan-Derived Nanoparticles of Dolutegravir: A Promising Approach for the Delivery of Anti-HIV Drug as Milk Admixture.

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV.

Stabilizing Zn/electrolyte Interphasial Chemistry by a Sustained-release Drug Inspired Indium-chelated Resin Protective Layer for High-areal-capacity Zn//V2O5 Batteries.

For zinc-metal batteries, the instable chemistry at Zn/electrolyte interphasial region results in severe hydrogen evolution reaction (HER) and dendrite growth, significantly impairing Zn anode reversibility. Moreover, an often-overlooked aspect is this instability can be further exacerbated by the interaction with dissolved cathode species in full batteries. Here, inspired by sustained-release drug technology, an indium-chelated resin protective layer (Chelex-In), incorporating a sustained-release mechanism for indium, is developed on Zn surface, stabilizing the anode/electrolyte interphase to ensure reversible Zn plating/stripping performance throughout the entire lifespan of Zn//V2O5 batteries. The sustained-release indium onto Zn electrode promotes a persistent anticatalytic effect against HER and fosters uniform heterogeneous Zn nucleation. Meanwhile, on the electrolyte side, the residual resin matrix with immobilized iminodiacetates anions can also repel H2O and detrimental anions (SO42- and polyoxovanadate ions dissolved from V2O5 cathode) outside the electric double layer. This dual synergetic regulation on both electrode and electrolyte sides culminates a more stable interphasial environment, effectively enhancing Zn anode reversibility in practical high-areal-capacity full battery systems. Consequently, the bio-inspired Chelex-In protective layer enables an ultralong lifespan of Zn anode over 2800 h, which is also successfully demonstrated in ultrahigh areal capacity Zn//V2O5 full batteries (4.89 mAh cm-2).

The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.

Predicting influenza-like illness trends based on sentinel surveillance data in China from 2011 to 2019: A modelling and comparative study1.

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

Outcomes of carotid endarterectomy in octogenarians compared to their younger counterparts: a retrospective observational study.

Purpose: This study was performed to analyze the association between age and outcomes of carotid endarterectomy (CEA) by comparing postoperative outcomes between octogenarians and younger patients. Methods: From November 1994 to December 2022, 1,585 internal carotid arteries of 1,434 patients were enrolled. Patients were stratified into 2 groups: octogenarians (≥80 years old) and non-octogenarians (<80 years old). Primary endpoints were early (≤30 days) outcomes of ipsilateral stroke, any stroke, myocardial infarction, death, and major adverse cardiovascular events (MACE). We also compared overall any stroke and death between the 2 groups. Results: One of 132 octogenarians (0.8%) and 17 of 1,453 non-octogenarians (1.1%) experienced ipsilateral stroke within 30 days. Thirty-day MACE occurred in 4 of 132 octogenarians (3%) and 44 of 1,453 non-octogenarians (3%). There were no significant differences in any early (≤30 days) outcomes. Symptomatic status was associated with increased 30-day MACE (odds ratio [OR], 2.610; 95% confidence interval [CI], 1.450-4.696; P = 0.003) and 30-day any stroke (OR, 3.999; 95% CI, 1.627-9.828; P = 0.003). Symptomatic status was also associated with overall any stroke (hazard ratio [HR], 2.885; 95% CI, 1.865-4.463; P < 0.001), but age of ≥80 years was not associated with 30-day MACE, 30-day any stroke, or overall stroke. Age of ≥80 years was only associated with overall survival (HR, 2.644; 95% CI, 1.967-3.555; P < 0.001). Conclusion: CEA would be a safe and effective treatment for octogenarians with low 30-day complications and long-term stroke rates, comparable with that of younger counterparts. Advanced age is not a contraindication for CEA.

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

BACKGROUND AND AIM: The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. METHODS: This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. RESULTS: A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. CONCLUSION: MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

Association Between Pornography Use, Sexism, and Sexual Violence Myth Acceptance in Chinese Men: The Moderating Effect of Perceived Realism.

Pornography is spreading more and more widely due to websites, applications, and social media. It has attracted the attention of a large number of researchers who are sometimes divided on the impact of pornography. However, the relationship between pornography and sexual violence myths has received little scholarly attention in China. Based on the 3AM model and previous research, the study examined hostile sexism (HS) as a mediator and perceived realism as a moderator in the links between pornography use frequency and sexual violence myths in a sample of Chinese men (N = 376). The results showed that although pornography use and sexual violence myths did not directly correlate with one another, there was an indirect correlation through HS. Further, perceived realism moderated the relationship between pornography use frequency and HS. When participants' perceived realism was high (i.e. +1 SD), the indirect effect of HS was strong; when participants' perceived realism was low (i.e. -1 SD), the indirect effect of HS was not significant. Taken together, the findings reveal the cross-cultural consistency of the 3AM theory in China, and the findings provide new insight into the potential impact of pornography on sexism. At the same time, the results suggest an increase in appropriate education and interventions to reduce the incidence of sexual violence.

Pragmatic strategies to address health disparities along the continuum of care in chronic liver disease.

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

SEEI: spherical evolution with feedback mechanism for identifying epistatic interactions.

BACKGROUND: Detecting epistatic interactions (EIs) involves the exploration of associations among single nucleotide polymorphisms (SNPs) and complex diseases, which is an important task in genome-wide association studies. The EI detection problem is dependent on epistasis models and corresponding optimization methods. Although various models and methods have been proposed to detect EIs, identifying EIs efficiently and accurately is still a challenge. RESULTS: Here, we propose a linear mixed statistical epistasis model (LMSE) and a spherical evolution approach with a feedback mechanism (named SEEI). The LMSE model expands the existing single epistasis models such as LR-Score, K2-Score, Mutual information, and Gini index. The SEEI includes an adaptive spherical search strategy and population updating strategy, which ensures that the algorithm is not easily trapped in local optima. We analyzed the performances of 8 random disease models, 12 disease models with marginal effects, 30 disease models without marginal effects, and 10 high-order disease models. The 60 simulated disease models and a real breast cancer dataset were used to evaluate eight algorithms (SEEI, EACO, EpiACO, FDHEIW, MP-HS-DHSI, NHSA-DHSC, SNPHarvester, CSE). Three evaluation criteria (pow1, pow2, pow3), a T-test, and a Friedman test were used to compare the performances of these algorithms. The results show that the SEEI algorithm (order 1, averages ranks = 13.125) outperformed the other algorithms in detecting EIs. CONCLUSIONS: Here, we propose an LMSE model and an evolutionary computing method (SEEI) to solve the optimization problem of the LMSE model. The proposed method performed better than the other seven algorithms tested in its ability to identify EIs in genome-wide association datasets. We identified new SNP-SNP combinations in the real breast cancer dataset and verified the results. Our findings provide new insights for the diagnosis and treatment of breast cancer. AVAILABILITY AND IMPLEMENTATION: https://github.com/scutdy/SSO/blob/master/SEEI.zip .

Construction of Hydrogels with Highly Salt-Resistant Honeycomb Porous Structures for Solar Desalination and Steam Generation.

Interfacial solar desalination is a method for desalinating seawater using solar energy, and the long-term use of this technology requires a stable evaporation rate and some ability to prevent salt crystallization. To address these issues, carbonized polydopamine-coated bentonite (C@PBT), poly(vinyl alcohol), and cellulose nanofibers were used to construct a three-dimensional oriented hydrogel evaporator with a multilayered honeycomb porous structure for long-term desalination. Carbon nanoparticles transferred between the layers of the bentonite, which increases the spacing of the layers and confers a more effective solar light trapping ability. The evaporation rate was 2.26 kg m-2 h-1 in 20 wt % NaCl solution, and no salt crystals were precipitated from the surface of the evaporator in 12 h of continuous operation. This phenomenon occurs due to the wide distribution of pore sizes and the large size of the pores within the evaporator, which create ample space for salt ions to move freely. Furthermore, after undergoing 300 cycles of compression, its internal pore structure remains intact, and the rate of evaporation remains stable. It ensures the evaporator stability during outdoor cycles. The research work provides an effective method to solve the salt accumulation problem and shows its great potential for application.

Expert consensus on the clinical application of immunotherapy in breast cancer: 2024.

Background: Significant progress has been made in immunotherapy of breast cancer (BC) with the approval of multiple immune checkpoint inhibitors (ICIs), particularly in early and metastatic triple-negative breast cancer (TNBC) settings. Most guidelines have recommended immune therapy as the important approach in BC, yet several critical aspects still require further clarification, including proper patient selection, treatment duration, optimized chemotherapy partner, predictive biomarkers, and specific considerations for Chinese patients. Methods: (I) Establishment of expert group: the expert group consists of 32 experts from departments such as medical oncology, breast surgery, and pathology; (II) literature search: mainly conducted in English databases (such as PubMed, Embase, and Cochrane Library) and Chinese databases (such as China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Database), with a search cutoff date of April 23, 2024; (III) assessment of evidence quality and recommendation strength: evidence quality and recommendation opinions are graded based on the evidence category and recommendation level of the Chinese Society of Clinical Oncology (CSCO) guidelines; (IV) consensus formulation: on the March 2, 2024, through online consensus meeting, the consensus content is thoroughly discussed, and opinions from all experts are solicited. Results: The consensus meeting has resulted in 15 detailed recommendations, providing clearer guidance on the clinical application of immunotherapy in BC management. The core suggestions are as follows: for early-stage II-III TNBC and metastatic TNBC (mTNBC) in the first-line setting, programmed cell death protein 1 (PD-1) inhibitors can be considered. However, for hormone receptor-positive/human epidermal growth factor receptor 2-negative BC (HR+/HER2- BC), HER2+ BC, and mTNBC in later lines of therapy, evidence is lacking to support the use of immunotherapy. Conclusions: This consensus provides a comprehensive overview of BC immunotherapy, including immunotherapy for early-stage BC and late-stage BC, immune related adverse event (irAE) management, biomarkers of immunotherapy, and future directions. The consensus consolidates these deliberations into 15 evidence-based recommendations, serving as a practical guide for clinicians to more scientifically and systematically manage the clinical application of immunotherapy.

Associations of the Serum KL-6 with Severity and Prognosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: As a biomarker of alveolar-capillary basement membrane injury, Krebs von den Lungen-6 (KL-6) is involved in the occurrence and development of pulmonary diseases. However, the role of the KL-6 in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has yet to be elucidated. This prospective study was designed to clarify the associations of the serum KL-6 with the severity and prognosis in patients with AECOPD. METHODS: This study enrolled 199 eligible AECOPD patients. Demographic data and clinical characteristics were recorded. Follow-up was tracked to evaluate acute exacerbation and death. The serum KL-6 concentration was measured via an enzyme-linked immunosorbent assay. RESULTS: Serum KL-6 level at admission was higher in AECOPD patients than in control subjects. The serum KL-6 concentration gradually elevated with increasing severity of AECOPD. Pearson and Spearman analyses revealed that the serum KL-6 concentration was positively correlated with the severity score, monocyte count and concentrations of C-reactive protein, interleukin-6, uric acid, and lactate dehydrogenase in AECOPD patients during hospitalization. A statistical analysis of long-term follow-up data showed that elevated KL-6 level at admission was associated with longer hospital stays, an increased risk of future frequent acute exacerbations, and increased severity of exacerbation in COPD patients. CONCLUSION: Serum KL-6 level at admission is positively correlated with increased disease severity, prolonged hospital stay and increased risk of future acute exacerbations in COPD patients. There are positive dose-response associations of elevated serum KL-6 with severity and poor prognosis in COPD patients. The serum KL-6 concentration could be a novel diagnostic and prognostic biomarker in AECOPD patients.