Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice.

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-ß-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.

A synergistic study of policy and literature on rumor governance.

Rumor governance is an important guarantee for social stability and public safety. Based on the life cycle and crisis cycle model, this paper conducts a synergistic analysis of China's rumor governance policies and regulations and the core scientific research literature on rumor governance in WOS and CNKI. In this paper, we use the TF-IDF algorithm to count the word frequencies of 326 policy and regulation texts, the Jieba-RoBERTa-Kmeans model to cluster high-frequency keywords, and CiteSpace software and the LLR clustering algorithm are utilized to extract and cluster keywords from 391 documents in the WOS database and from 703 documents in the CNKI database. Based on the synergistic analysis of the life cycle model, it is found that the research on policies and regulations precedes the research on literature, and both are in the period of refinement.Based on the synergistic analysis using the co-occurrence comparison of subject terms in the crisis cycle model, it is found that there is a lack of research in the stages of prevention, monitoring, and governance, and this paper proposes the systematic governance mechanism and strategy for crisis resolution that conforms to the trend of life cycle evolution and is synergistic with policy and literature. This study has only selected Chinese policies and regulations, and the proposed governance strategies have not yet been verified in practice; future research can expand the scope and depth of the study and conduct empirical research and pilot projects.

[Carbapenemase Genes, Virulence Genes, and Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Derived From Bloodstream Infections]. / è¡€æµæ„ŸæŸ“ç¢³é’éœ‰çƒ¯è€è¯è‚ºç‚Žå ‹é›·ä¼¯èŒçš„è€è¯åŸºå› å’Œæ¯’åŠ›åŸºå› åŠåˆ†å­æµè¡Œç— å­¦ç ”ç©¶.

Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China. Methods: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentration (MIC) was determined by microbroth dilution method. The common carbapenemase resistant genes and virulence factors were identified by PCR. Homology analysis was performed by multilocus sequencing typing. Whole genome sequencing was performed to analyze the genomic characteristics of CRKP without carbapenemase. Results: The 131 strains of CRKP showed resistance to common antibiotics, except for polymyxin B (1.6% resistance rate) and tigacycline (8.0% resistance rate). A total of 105 (80.2%) CRKP strains carried the Klebsiella pneumoniae carbapenemase (KPC) resistance gene, 15 (11.4%) strains carried the New Delhi Metallo-ß-lactamase (NDM) gene, and 4 (3.1%) isolates carried both KPC and NDM genes. Sequence typing (ST) 11 (74.0%) was the dominant sequence type. High detection rates for mrkD (96.2%), fimH (98.5%), entB (100%), and other virulence genes were reported. One hypervirulent CRKP strain was detected. The seven strains of CRKP that did not produce carbapenemase were shown to carry ESBL or AmpC genes and had anomalies in membrane porins OMPK35 and OMPK36, according to whole genome sequencing. Conclusion: In a large-scale tertiary-care general hospital, CRKP mainly carries the KPC gene, has a high drug resistance rate to a variety of antibiotics, and possesses multiple virulence genes. Attention should be paid to CRKP strains with high virulence.

Whole-genome sequencing analysis of widely disseminated infection caused by ST2631 methicillin-sensitive Staphylococcusaureus.

Existing studies revealed high clonal diversity among Staphylococcus aureus bacteremia isolates, especially for methicillin-sensitive S. aureus (MSSA) strains. A 66-year-old male patient presenting with a widespread methicillin-sensitive Staphylococcus aureus (MSSA) infection, accompanied by concurrent carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection.To evaluate the evolution of the present isolate, whole genome sequencing and bioinformatics analysis were performed for all available MSSA isolates. This patient recovered eventually through drainage and antibiotics combination. Therefore, the virulence factors of MSSA, as the primary pathogenicity, led to widely disseminated infection. The appropriate initial treatment is a major concern after culture identification.

Clinical manifestations, antimicrobial resistance and genomic feature analysis of multidrug-resistant Elizabethkingia strains.

BACKGROUND: Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. METHODS: Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. RESULTS: The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five ß-lactamase genes (blaGOB, blaBlaB, blaCME, blaOXA, and blaTEM) responsible for ß-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that "metabolism" constituted the largest category within the core genome, while "information storage and processing" was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (ß-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. CONCLUSION: The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

Optimal parameter selection for the THz-CCS system based on an incoherent light source.

Terahertz cross correlation spectroscopy (THz-CCS) systems using broadband incoherent light as the pumping source have received increasing attention from researchers in recent years. However, a comprehensive and in-depth understanding of THz-CCS is still needed to obtain a detailed optimization scheme. Here we systematically investigate the influences of the detection parameters, light propagation process, and pump source on the CCS signals. The impacts of the filter slopes and time constants in lock-in detection are revealed for optimizing the signal-to-noise ratio and bandwidth of the THz signal. By varying the optical fiber length and dispersion coefficient, the dispersion insensitivity of THz-CCS was experimentally demonstrated. The comparison of different pump sources (SLD and ASE) shows that the over-wide and non-flat pump spectrum may attenuate the CCS signal because of the energy waste brought by the photomixing process under the limited bandwidth of the photomixer. Our research may lead to a deeper understanding and further optimization of the THz-CCS system, which will promote the development and widespread application of what is to the best of our knowledge a new technique.

Rational Lithium Salt Molecule Tuning for Fast Charging/Discharging Lithium Metal Battery.

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

Sentiment analysis of video danmakus based on MIBE-RoBERTa-FF-BiLSTM.

Danmakus are user-generated comments that overlay on videos, enabling real-time interactions between viewers and video content. The emotional orientation of danmakus can reflect the attitudes and opinions of viewers on video segments, which can help video platforms optimize video content recommendation and evaluate users' abnormal emotion levels. Aiming at the problems of low transferability of traditional sentiment analysis methods in the danmaku domain, low accuracy of danmaku text segmentation, poor consistency of sentiment annotation, and insufficient semantic feature extraction, this paper proposes a video danmaku sentiment analysis method based on MIBE-RoBERTa-FF-BiLSTM. This paper constructs a "Bilibili Must-Watch List and Top Video Danmaku Sentiment Dataset" by ourselves, covering 10,000 positive and negative sentiment danmaku texts of 18 themes. A new word recognition algorithm based on mutual information (MI) and branch entropy (BE) is used to discover 2610 irregular network popular new words from trigrams to heptagrams in the dataset, forming a domain lexicon. The Maslow's hierarchy of needs theory is applied to guide the consistent sentiment annotation. The domain lexicon is integrated into the feature fusion layer of the RoBERTa-FF-BiLSTM model to fully learn the semantic features of word information, character information, and context information of danmaku texts and perform sentiment classification. Comparative experiments on the dataset show that the model proposed in this paper has the best comprehensive performance among the mainstream models for video danmaku text sentiment classification, with an F1 value of 94.06%, and its accuracy and robustness are also better than other models. The limitations of this paper are that the construction of the domain lexicon still requires manual participation and review, the semantic information of danmaku video content and the positive case preference are ignored.

Trends and driving forces of agricultural carbon emissions: A case study of Anhui, China.

To facilitate accurate prediction and empirical research on regional agricultural carbon emissions, this paper uses the LLE-PSO-XGBoost carbon emission model, which combines the Local Linear Embedding (LLE), Particle Swarm Algorithm (PSO) and Extreme Gradient Boosting Algorithm (XGBoost), to forecast regional agricultural carbon emissions in Anhui Province under different scenarios. The results show that the regional agricultural carbon emissions in Anhui Province generally show an upward and then downward trend during 2000-2021, and the regional agricultural carbon emissions in Anhui Province in 2030 are expected to fluctuate between 11,342,100 tones and 14,445,700 tones under five different set scenarios. The projections of regional agricultural carbon emissions can play an important role in supporting the development of local regional agriculture, helping to guide the input and policy guidance of local rural low-carbon agriculture and promoting the development of rural areas towards a resource-saving and environment-friendly society.

Hemin/G-quadruplex and AuNPs-MoS2 based novel dual signal amplification strategy for ultrasensitively sandwich-type electrochemical thrombin aptasensor.

In this work, a novel sandwich-type electrochemical aptasensor based on the dual signal amplification strategy of hemin/G-quadruplex and AuNPs-MoS2 was designed and constructed, which realized the highly sensitive and specific detection of thrombin (TB). In this aptasensor, the 15-mer TB-binding aptamer (TBA-1) modified with thiol group was immobilized on the surface of AuNPs modified glassy carbon electrode (AuNPs/GCE) as capturing elements. Another thiol-modified 29-mer TB-binding aptamer (TBA-2) sequence containing G-quadruplex structure for hemin immobilization was designed. The formed hemin/G-quadruplex/TBA-2 sequence was further combined to the AuNPs decorated flower-like molybdenum disulfide (AuNPs-MoS2) composite surface via Au-S bonds, acting the role of reporter probe. In presence of the target TB, the sandwich-type electrochemical aptamer detection system could be formed properly. With the assistance of the dual signal amplification of AuNPs-MoS2 and hemin/G-quadruplex toward H2O2 reduction, the sandwich-type electrochemical aptasensor was successfully constructed for sensitive detection of TB. The results demonstrate that the fabricated aptasensor displays a wide linear range of 1.0 × 10-6 âˆ¼ 10.0 nM with a low detection limit of 0.34 fM. This proposed aptasensor shows potential application in the detection of TB content in real biological samples with high sensitivity, selectivity, and reliability.

The metabolic slowdown caused by the deletion of pspA accelerates protein aggregation during stationary phase facilitating antibiotic persistence.

Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A (pspA) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA. Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA. This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase.

Vitamin C, vitamin E, ß-carotene and risk of Parkinson's disease: a systematic review and dose-response meta-analysis of observational studies.

OBJECTIVE: This study aimed to explore the relationship between the intake of vitamin C, vitamin E and ß-carotene, and the risk of Parkinson's disease (PD). METHODS: Web of Science, Embase, PubMed, Cochrane library, CNKI, and WanFang databases were searched from inception to 29 August 2022 for observational studies reporting the odds ratios (ORs) or relative risks (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) of PD by Vitamin C/Vitamin E/ß-carotene intake. Random-effects models, publication bias assessment, subgroup, sensitivity and dose-response analyses were performed, using.Stata version 12.0. RESULTS: A total of 13 studies were included. There was no significant association between high-dose vitamin C intake and the risk of PD compared with low-dose vitamin C intake (RR = 0.98, 95%CI:0.89,1.08). Compared with low-dose intake, high-dose intake of vitamin E can prevent the risk of PD (RR = 0.87, 95%CI:0.77,0.99). Compared with lower ß-carotene intake, there was a borderline non-significant correlation between higher intake and PD risk (RR = 0.91, 95%CI:0.82,1.01), and high dose ß-carotene intake was found to be associated with a lower risk of PD in women (RR = 0.78, 95%CI:0.64,0.96). CONCLUSION: This study shows that vitamin E intake can reduce the risk of PD and play a preventive role.

Breaking barriers: Stereotactic ablative proton and photon radiation therapy for renal cell carcinoma with extensive metastases: A case report.

Patients with advanced renal cancer (RCC) often have limited success with systemic therapy due to tumor heterogeneity. However, stereotactic ablative radiotherapy (SABR) has been shown to have a beneficial therapeutic effect for oligometastatic disease when used early. Despite this, current guidelines recommend the use of tyrosine kinase inhibitors (TKIs) as the first-line therapeutic agent for patients with recurrent or metastatic kidney cancer. Additionally, there is limited data on the combination of systemic treatment and SABR for extensive metastatic RCC due to concerns about high toxicity. Proton therapy offers a promising treatment option as it emits energy at a specific depth, generating high target doses while minimizing damage to normal tissue. This allows for precise treatment of various tumor lesions. In this case report, we describe a high-risk 65-year-old male with extensive pleural and thoracic lymph node metastases and 2 bone metastases of clear cell renal cancer. While the targeted therapy and immunotherapy effectively treated the bone metastases, it was not effective in treating the chest metastases, including the pleural and lymph node metastases. Thus, the patient received full-coverage radiotherapy with photon for primary renal tumor and intensity-modulated proton therapy (IMPT) for thoracic metastases. The patient showed no evidence of disease for 1 year after the initial radiotherapy, and no severe SABR-related adverse effects were observed until now. The combination of targeted therapy and immunotherapy with full-coverage radiotherapy may be a promising treatment option for selected patients with extensive metastatic renal cancer, especially as proton therapy allows for more precise control of the beam and minimal damage to normal tissue. This case has motivated us to investigate the potential advantages of administering proton therapy concurrently with systemic therapy in the management of metastatic renal cell carcinoma patients.

A positive feedback circuit driven by m6A-modified circular RNA facilitates colorectal cancer liver metastasis.

BACKGROUND: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. METHODS: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. RESULTS: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. CONCLUSIONS: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Terahertz Metasurfaces Exploiting the Phase Transition of Vanadium Dioxide.

Artificially designed modulators that enable a wealth of freedom in manipulating the terahertz (THz) waves at will are an essential component in THz sources and their widespread applications. Dynamically controlled metasurfaces, being multifunctional, ultrafast, integrable, broadband, high contrasting, and scalable on the operating wavelength, are critical in developing state-of-the-art THz modulators. Recently, external stimuli-triggered THz metasurfaces integrated with functional media have been extensively explored. The vanadium dioxide (VO2)-based hybrid metasurfaces, as a unique path toward active meta-devices, feature an insulator-metal phase transition under the excitation of heat, electricity, and light, etc. During the phase transition, the optical and electrical properties of the VO2 film undergo a massive modification with either a boosted or dropped conductivity by more than four orders of magnitude. Being benefited from the phase transition effect, the electromagnetic response of the VO2-based metasufaces can be actively controlled by applying external excitation. In this review, we present recent advances in dynamically controlled THz metasurfaces exploiting the VO2 phase transition categorized according to the external stimuli. THz time-domain spectroscopy is introduced as an indispensable platform in the studies of functional VO2 films. In each type of external excitation, four design strategies are employed to realize external stimuli-triggered VO2-based THz metasurfaces, including switching the transreflective operation mode, controlling the dielectric environment of metallic microstructures, tailoring the equivalent resonant microstructures, and modifying the electromagnetic properties of the VO2 unit cells. The microstructures' design and electromagnetic responses of the resulting active metasurfaces have been systematically demonstrated, with a particular focus on the critical role of the VO2 films in the dynamic modulation processes.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

A neutrophil extracellular traps-related classification predicts prognosis and response to immunotherapy in colon cancer.

Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.

Intensive blood pressure control on arterial stiffness among older patients with hypertension.

BACKGROUND: Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. METHODS: The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60-80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes. RESULTS: The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8-73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7-110.1 cm/s) in the standard treatment group (P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s-1·year-1vs. 36.7 cm·s-1·year-1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70-80 years or with SBP <140 mmHg. CONCLUSION: Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; No. NCT03015311.

Manual compass measurement and trigonometric determination of proptosis.

PURPOSE: To determine the accuracy of manual compass measurement and trigonometric determination of proptosis (MCMATDP). METHODS: This agreement study included 120 eyes without eye diseases or injury of 60 patients who visited the ophthalmic clinic of Peking University Shenzhen Hospital from February 2020 to June 2020. The absolute values of proptosis were measured by MCMATDP and computed tomography (CT). The differences between the two methods were shown by Bland-Altman plot. RESULTS: The cohort comprised 25 males and 35 females (average age 38.3 years). The absolute value of proptosis measured by CT was correlated with the MCMATDP. Further analysis showed that a 95% limit of agreement (LoA) was - 0.53 to 0.60 mm in the right eye and - 0.46 to 0.55 mm in the left eye between CT and MCMATDP. In addition, the 95% LoA was - 0.49 to 0.60 mm in both eyes between the two methods. All points were < 5% in Bland-Altman plots. CONCLUSIONS: Compared to CT, MCMATDP is rather consistent in proptosis measurement. The new method is feasible in clinical practice when measuring proptosis. With the development of non-contact intelligent measurement software and the continuous improvement in measurement accuracy, a non-invasive, simple, and inexpensive measurement mode is true based on the theory of MCMATDP.