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Background: Team-based learning (TBL) is a widely recognised pedagogical strategy used in diverse fields and courses. Despite the success of TBL, certain concerns have arisen regarding social loafing within group collaboration contexts; this loafing can reduce the overall effectiveness of learning. Objectives: This study addressed the aforementioned concerns by integrating group awareness (GA) information into each stage of TBL, resulting in a TBL + GA system designed to enhance TBL instruction. During online collaborative learning, GA information provides insights into the activities completed by peers and thus the peers' preparedness and achievement; this knowledge fosters motivation, participation, and reflection. Methods: A quasiexperiment was performed with students from two freshman classes (40 and 41 students, respectively) in a Taiwanese university; the control and experimental classes used the TBL only and TBL + GA systems, respectively. Student learning effort was evaluated in terms of preclass preparation, including the use of learning materials and online test scores. Learning achievement was evaluated by assessing the quality of students' assignments. Student feedback, including peer evaluations and students' perceptions of their TBL experience, was collected and compared for the two classes. Results and Conclusions: The TBL + GA system significantly enhanced the preclass preparation efforts of the participants, mitigating social loafing. This improvement manifested as higher practice engagement and better online assessment scores. The TBL + GA system also improved assignment quality and elicited more constructive and positive peer feedback. Implications: Integrating GA information into each stage of TBL may positively affect the effectiveness of instruction. The proposed TBL + GA system can serve as a practical model for instructors seeking to enhance TBL implementation and foster a more engaging and constructive learning environment.

Kidney is a major metabolic organ of human body. Amino acids are not only the basic components of protein， but also important metabolites in human body. Recent researches have demonstrated that amino acids play an important role in the pathophysiological development of various renal diseases. Through detecting the changes of amino acid spectrum in patients with different renal diseases， amino acid metabonomics may help to make early screening and diagnosis of the disease， guide later treatment and predict clinical outcomes. This review summarized the applications of amino acid metabonomics and discussed the clinical value of amino acid metabonomics in renal diseases.

Team-Based Learning (TBL) has been widely applied in different fields (courses) and has been indicated to be efficient. Meanwhile, many studies have asserted that Group awareness (GA) information, which visually displays peers' learning context and activities, can increase peer participation within an online collaborative learning environment. As the level of preparation by students before class affects their subsequent learning performance in the TBL process, this study incorporates GA information into the preparation stage of TBL process and further develops the online TBL + GA system in order to raise peer preparation level. Furthermore, self-regulated learning (SRL) levels of a student and online learning environment interactively influence learning effectiveness. Accordingly, this study further investigates how the TBL + GA environment influences students with different SRL levels. Two freshman classes were randomly chosen, with one as the control class (using the traditional TBL) and the other as the experimental class using the TBL + GA. Analytical results indicate that although the two classes do not reach significance overall on preparation level, TBL + GA can significantly enhance preparation levels for high-SRL students, but not low-SRL students.

Contribution: This study used a guided reflective thinking mechanism to improve students' acceptance of flipped classrooms while promoting the development of students' will and self-regulated learning strategies to enhance their preclass preparation and participation in classroom activities. Background: Previous research has provided evidence of the impact of flipped classrooms on student learning, but an understanding of the relationship between flipped classrooms, learning strategies, and learning outcomes is limited. Intended Outcome: The learning strategies used by students in the flipped classroom were examined, and the effectiveness of incorporating a guided reflective thinking mechanism into the flipped classroom teaching design of a digital logic (DL) course was evaluated. Application Design: Referring to the strategic learning model, this study integrated the mechanism of guided reflective thinking into the instructional design of a flipped classroom for first-year students in the Department of Electrical Engineering of a junior college in Taiwan. Findings: The results show that the flipped classroom teaching design that guides the reflective thinking mechanism can promote the development of students' strategies to enhance their attitude, motivation, time management, concentration, self-testing, and solving learning difficulties, thereby improving their performance in DL courses. Furthermore, self-testing strategies are the most important predictor of students' performance in DL courses.

Abstract The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

Abstract Background This retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China. Methods A retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected. Results Patients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0–1, 2–3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0–1 (20.0%) than those with score 2–3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0–1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2–3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0–1 and 2–3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy. Conclusion Compared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0–1.

Abstract Objective To determine the performance of intravoxel incoherent motion (IVIM) parameters and the extracellular volume fraction (ECV) in distinguishing between different subtypes of lung cancer and predicting lymph node metastasis (LNM) status in patients with non-small-cell lung cancer (NSCLC). Methods One hundred sixteen patients with lung cancer were prospectively recruited. IVIM, native, and postcontrast T1 mapping examinations were performed, and the T1 values were measured to calculate the ECV. The differences in IVIM parameters and ECV were compared between NSCLC and small-cell lung cancer (SCLC), adenocarcinoma (Adeno-Ca) and squamous cell carcinoma (SCC), and NSCLC without and with LNM. The assessment of each parameter’s diagnostic performance was based on the area under the receiver operating characteristic curve (AUC). Results The apparent diffusion coefficient (ADC), true diffusion coefficient (D), and ECV values in SCLC were considerably lower compared with NSCLC (all p 0.887). The D value in SCC was substantially lower compared with Adeno-Ca (p 0.708). Conclusion IVIM parameters and ECV can serve as non-invasive biomarkers for assisting in the pathological classification and LNM status assessment of lung cancer patients. Critical relevance statement IVIM parameters and ECV demonstrated remarkable potential in distinguishing pulmonary carcinoma subtypes and predicting LNM status in NSCLC. Key Points Lung cancer is prevalent and differentiating subtype and invasiveness determine the treatment course. True diffusion coefficient and ECV showed promise for subtyping and determining lymph node status. These parameters could serve as non-invasive biomarkers to help determine personalized treatment strategies. Graphical Abstract

Introduction: Atopic dermatitis (AD) is a common chronic, recurrent, and non-infectious inflammatory skin disease. Dupilumab is a human monoclonal antibody with clinical efficacy in severe AD and has a good safety profile. Case Presentation: We hereby describe a previously unreported case of multisystem Langerhans cell histiocytosis (MS-LCH) that is associated with a history of AD treatment using dupilumab. Conclusion: A single case of MS-LCH with a history of dupilumab treatment for AD was described for the first time. This case highlights that given its susceptibility to skin involvement, LCH needs to be considered as a differential diagnosis for skin lesions that are not improved by established therapies.

BackgroundTicks are widely distributed throughout China and are the second most prevalent pathogen vectors in the world, following only mosquitoes. Tick bites can lead to Lyme disease, forest encephalitis, and other illnesses that may result in death under severe circumstances. Materials and methods: Ticks collected from March 2021 to May 2023 were pooled and used in metatranscriptomic analyses to gain insight into the diversity and distribution of tick-borne viruses in Inner Mongolia. Next-generation sequencing (NGS) outcomes were validated, and viral prevalence across distinct tick species was determined through the application of polymerase chain reaction (PCR) paired with Sanger sequencing.ResultsA total of 20 RNA viruses belonging to at least 8 families, including Chuviridae, Flaviviridae, Solemoviridae, Nairoviridae, Partitiviridae, Phenuiviridae, Rhabdoviridae, and Totiviridae, and to unclassified families were identified by NGS. Five of the identified RNA viruses (Nuomin virus, Yezo virus, tick-borne encephalitis virus, Alongshan virus, and Beiji nairovirus) are considered human pathogens. A potential human pathogen, Mukawa virus, was also among the identified viruses. Ixodes persulcatus carried a significantly greater number of viral species than did Dermacentor nuttalli, Hyalomma marginatum, and Haemaphysalis concinna. The prevalence of coinfection with multiple viruses differed in I. persulcatus from Hinggan League and Hulun Buir, and Beiji nairovirus was the codominant virus species.ConclusionsThere is a remarkable diversity of RNA viruses harboured by ticks in Inner Mongolia, with variations observed in the distribution of these tick-borne viruses across different regions and tick hosts.

ObjectivesThis review aimed to assess the safety and efficacy of SARS-CoV-2 vaccines in patients with chronic liver disease (CLD).MethodsCochrane Central Register of Controlled Trials, PubMed, Embase, and Web of Science were searched from 2020 to 2024. Data was extracted following Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. The random-effects model (when I2 ≥ 50%) or fixed effect model (I2 < 50%) was used.Results29 studies were included in this review. Compared to healthy controls (HCs), patients with CLD had a higher incidence of mild adverse events (RR = 1.60, p < 0.001), while the incidence of severe adverse events was similar (RR = 1.08, p = 0.92). Seropositivity rates of three antibodies in patients were lower than in HCs [neutralizing antibody (RR = 0.86, p = 0.002), anti-spike antibody (RR = 0.97, p = 0.06) and anti-receptor binding domain antibody (RR = 0.95, p = 0.04)]. Compared to unvaccinated patients, vaccinated patients had lower rates of SARS-CoV-2 infection, hospitalization and death (p ≤ 0.05).ConclusionSARS-CoV-2 vaccines showed good safety and efficacy in CLD patients, but antibody response appeared to be decreased. Therefore, SARS-CoV-2 vaccines and booster doses should be given priority in this vulnerable population.

ObjectivesThis work aims to establish a dataset of ratios between tissue free water tritium (TFWT) and organically bound tritium (OBT) (containing both exchangeable and non-exchangeable OBT) in different types of seafood from Zhejiang province, China, thus to provide references for rapid screening of potential contamination of tritium in biological samples.MethodsFive types of seafood (fish, prawn, mussel, crab and kelp) were collected from Jiaxing, Ningbo, Zhoushan, Taizhou and Wenzhou city in Zhejiang Province in 2022, and measured for TFWT and OBT using tube furnace combustion system and liquid scintillation counting.ResultsThe observed activity concentrations of TFWT and OBT in this study were within the range of 1.01-10.09 Bq/L and 0.51-7.61 Bq/L, respectively. No significant difference in OBT/TFWT ratio was observed among different types of seafood (p > 0.05), among the geographic distribution of the five cities (p > 0.05), nor among the area of coastline, fishing ground and island (p > 0.05). Additionally, there was no significant difference in the OBT/TFWT ratio between seafood from area with and without nuclear power plant operation (p > 0.05). The mean OBT/TFWT ratio of fish, prawn, mussel, crab and kelp was 0.37 ± 0.19, 0.48 ± 0.27, 0.63 ± 0.33, 0.82 ± 0.50, and 0.64 ± 0.37, respectively. The mean and range of OBT/TFWT ratios were 0.59 ± 0.37 and 0.15-2.09 in all seafood collected from the five cities in Zhejiang Province, respectively.ConclusionsOur results indicate that tritium in seafood from coastal cities in Zhejiang Province is at the background level, and the operation of nuclear power plants in the province has no notable impact on the radioactivity levels of tritium in local marine biota. This study filled the gap in OBT/TFWT ratios in seafood, which provides new dataset for rapid detection of tritium contamination in nuclear emergencies.

The interactions between corn amylose (CA) and Moringa oleifera seed salt-soluble protein (MOSP) were explored to improve the gel properties of MOSP. With increasing CA content, the MOSP-CA gel network structure was improved but the size of the gel porosity decreased firstly and then increased; the water holding retention (WHR) of MOSP-CA was decreased from approximately 94 % to 85.43 ± 2.54 %. The MOSP-CA-2.5 gel exhibited the best water holding stability (WHS), with a value of 37.1 ± 0.33 %. The MOSP-CA gel hardness increased with CA concentration, and MOSP-CA-2.5 showed relatively optimal cohesiveness, elasticity, adhesiveness, and chewiness. Meanwhile, MOSP-CA-2.5 exhibited gel strength. Incorporation of CA significantly increased the exposure of hydrophobic residues and the concentration-dependent increase in disulfide bonds in MOSP-CA gel. Thus, hydrophobic interactions, hydrogen bonds, and disulfide bonds collectively stabilized the structure of MOSP-CA gel. The findings would broaden the application of MOSP and improve the utilization value of MOSP in various industries.

Abstract Background According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti‐tumor activity associated with Qi‐supplementing herbs, specifically the paired use of Huangqi and Danggui. Methods Analysis of compatibility regularity was conducted to screen the combination of Qi‐supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti‐tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti‐tumor activity and the mechanism of the active ingredients were verified by molecular experiments. Results There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti‐tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti‐tumor effects of the extract. Conclusions The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

Abstract In this study, we experimentally identify the effect of liquid dielectrophoresis (LDEP) force on a superhydrophobic surface in directing the trajectory of moving water droplets across designed interdigitated electrodes and show that this method is capable of rapidly selecting droplets at a high speed (200 mm/s). As the droplets traverse down the surface by the electric field, their deflection on the edge of these electrodes is achieved successively, allowing for the selective manipulation of discrete droplets. A series of experiments were conducted to validate the relationships among droplet deflections, applied electric fields, and dynamic contact angles. Our findings reveal that the principal driving force behind the droplet deflections is the LDEP force, which can provide instant manipulation of moving droplets rather than a variation in contact angles brought about by electrowetting. This study presents a proof-of-concept experiment utilizing LDEP for high-throughput droplet selection and also highlights the potential applications of this mechanism in high-speed digital microfluidics (DMF) and biological separation methodologies.

Abstract Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. HFD-induced obese mice exhibited depression-like behaviors and a reduction in hippocampus volume, which were reversed by treatment with an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes in IDO levels were observed post-1-MT treatment, suggesting that other mechanisms may be involved in the anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis to clarify the potential underlying mechanism of the anti-depressive effect of 1-MT in HFD-induced depressive mice and found a significant enrichment of shared differential genes in the extracellular matrix (ECM) organization pathway between the 1-MT-treated and untreated HFD-induced depressive mice. Therefore, we hypothesized that changes in ECM play a crucial role in the anti-depressive effect of 1-MT. To this end, we investigated perineuronal nets (PNNs), which are ECM assemblies that preferentially ensheath parvalbumin (PV)-positive interneurons and are involved in many abnormalities. We found that HFD is associated with excessive accumulation of PV-positive neurons and upregulation of PNNs, affecting synaptic transmission in PV-positive neurons and leading to glutamate-gamma-aminobutyric acid imbalances in the hippocampus. The 1-MT effectively reversed these changes, highlighting a PNN-related mechanism by which 1-MT exerts its anti-depressive effect.

Abstract Background Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. Materials and methods AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. Results Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1β, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1β, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. Conclusion These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.

Abstract Objective To investigate the risk factors and maternal and fetal outcomes of preeclampsia after pregnancy in patients with primary chronic hypertension. Methods A total of 500 singleton pregnant women with a history of hypertension who were admitted for delivery at our Hospital from March 2015 to May 2022 were retrospectively collected by random sampling and divided into the non-occurrence group (n = 200) and the occurrence group (n = 300) according to whether they were complicated by preeclampsia. Afterward, the general data and the pregnancy-related data of patients were collected for comparison. Results The univariate analysis showed significant differences between the non-occurrence group and the occurrence group in terms of the proportion of preeclampsia history (4.00% VS 24.67%, χ2 = 37.383, P 3 years (18.00% VS 31.67%, χ2 = 11.592, P 3 years (OR = 3.456, 95% CI: 2.157 ∼ 5.161, χ2 = 9.348, P

Abstract FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.

Abstract Background To explore the safety and effectiveness of personalized exercise intervention during chemotherapy for lung cancer patients who were relatively weak and with compromised cardiopulmonary function. Methods Thirty‐eight lung cancer patients treated with chemotherapy at Peking University Third Hospital were enrolled in this prospective study. The exercise group (N = 21) received individualized exercise guidance based on personal test results and exercised regularly, while the control group (N = 17) only received exercise education and planed exercise methods according to their own preferences. Both groups underwent three fitness tests and clinical indicator assessments at 0, 6, and 12 weeks after starting the exercise, and the differences in trends of various indicators between the two groups were compared. Results No exercise‐related adverse events occurred during the 12‐week exercise period. After 12 weeks of exercise training, in terms of fitness, the exercise group showed significant improvements in 6‐min walk test (6MWT) (p

Objective: Physical activity (PA) and sedentary behavior (SB) include several domains, whether the association of PA and SB with perceived stress is domain-specific is not clear. This study aims to identify associations of physical activity (exercise and housework) and leisure-time sedentary behavior (LTSB) with perceived stress among Chinese adults. Methods: The data were collected from the 2015 China Health and Nutrition Survey (CHNS). Respondents completed multiple questionnaires developed by the CHNS team, from which we extracted and sorted PA and LTSB data. Perceived stress was measured using the 14-item Perceived Stress Scale. PA was measured using a questionnaire covering 7 types of commonly practiced exercises and 4 types of housework activities among Chinese individuals. Consecutive questions were used to inquire about the time spent on each type of PA. The measurement of LTSB was conducted in the same manner. Data analysis involved Chi-square test and logistic regression. Results: 11,471 adults were included, with an average age of 52.3 years, and 48.3 % were male. 69.9 % (8,019) of respondents reported high perceived stress. Following adjustment for age, gender and other factors, perceived stress was lower for adults reporting medium exercise time (1–2 h) compared with excessively (≥2 h) (OR=1.314 [95 %CI 1.071, 1.612], P

IntroductionHypoxia due to reduced partial pressure of oxygen from high-altitude exposure affects the cognitive function of high-altitude migrants. Executive function is an important component of human cognitive function, characterized by high oxygen consumption during activity, and its level can be measured using cognitive control capacity (CCC). In addition, there is evidence for the potential value of hyperbaric oxygen (HBO) interventions in improving cognitive decline on the plateau. Therefore, the objective of this study was to investigate the effect of long-term high-altitude exposure on CCC in high-altitude newcomers and whether hyperbaric oxygen intervention has an ameliorative effect.MethodsThis study measured the magnitude of participants’ CCC using a Backward Masking Majority Function Task (MFT-M). Study 1 was a controlled study of different altitude conditions, with 64 participants in the high-altitude newcomer group and 64 participants in the low-altitude resident group, each completing the MFT-M task once. Study 2 was a controlled HBO intervention study in which newcomers who had lived at a high altitude for 2 years were randomly divided into the HBO group (n = 28) and control group (n = 28). 15 times hyperbaric oxygen interventions were performed in the HBO group. Subjects in both groups completed the MFT-M task once before and once after the intervention.ResultsStudy 1 showed that CCC was significantly higher in the low-altitude resident group than in the high-altitude newcomer group (p = 0.031). Study 2 showed that the CCC in the HBO group was significantly higher after 15 hyperbaric interventions than before (p = 0.005), while there was no significant difference in the control group (p = 0.972). The HBO group had significantly higher correct task rates than the control group after the intervention (p = 0.001).ConclusionThis study confirms that long-term high-altitude exposure leads to impairment of CCC in high-altitude newcomers and that hyperbaric oxygen intervention is effective in improving CCC.

Abstract In the treatment of uveal melanoma (UVM), histone deacetylase inhibitors (HDACi) have emerged as a promising epigenetic therapy. However, their clinical efficacy is hindered by the suboptimal pharmacokinetics and the strong self‐rescue of tumor cells. To overcome these limitations, reactive oxygen species (ROS)‐responsive nanoparticles (NPs) are designed that encapsulate HDACi MS‐275 and the glutamine metabolism inhibitor V‐9302. Upon reaching the tumor microenvironment, these NPs can disintegrate, thereby releasing MS‐275 to increase the level of ROS and V‐9302 to reduce the production of glutathione (GSH) related to self‐rescue. These synergistic effects lead to a lethal ROS storm and induce cell pyroptosis. When combined with programmed cell death protein 1 monoclonal antibodies (α‐PD‐1), these NPs facilitate immune cell infiltration, improving anti‐tumor immunity, converting “immune‐cold” tumors into “immune‐hot” tumors, and enhancing immune memory in mice. The findings present a nano‐delivery strategy for the co‐delivery of epigenetic therapeutics and metabolic inhibitors, which induces pyroptosis in tumors cells and improves the effectiveness of chemotherapy and immunotherapy.

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on Primary Membranous Nephropathy. However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥ 4 g/24 h, serum albumin < 30 g/L, and eGFR ≥ 30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/d and intravenous CTX 500 mg/m2 per month until the total dose reached 6–8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint(P=0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, P=0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, P=0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, P=0.03) among patients with massive proteinuria (urine protein ≥ 8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, P=0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.