R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

M2 Macrophage-Derived Small Extracellular Vesicles Ameliorate Pyroptosis and Intervertebral Disc Degeneration.

Intervertebral discs (IVDs) have a limited self-regenerative capacity and current strategies for IVD regeneration are unsatisfactory. Recent studies showed that small extracellular vesicles derived from M2 macrophage cells (M2-sEVs) inhibited inflammation by delivery of various bioactive molecules to recipient cells, which indicated that M2-sEVs may offer a therapeutic strategy for the repair of IVDs. Herein, we investigated the roles and mechanisms of M2-sEVs on IVD regeneration. The in vitro results demonstrated that M2-sEVs inhibited pyroptosis, preserved cellular viability, and promoted migration of nucleus pulposus cells (NPCs). Bioinformatics analysis and verification experiments of microRNA (miR) expression showed that miR-221-3p was highly expressed in M2-sEVs. The mechanism of action was explored and indicated that M2-sEVs inhibited pyroptosis of NPCs through transfer of miR-221-3p, which suppressed the expression levels of phosphatase and tensin homolog and NOD-, LRR-, and pyrin domain-containing protein 3. Moreover, we fabricated decellularized ECM-hydrogel (dECM) for sustained release of M2-sEVs, which exhibited biocompatibility and controlled release properties. The in vivo results revealed that dECM-hydrogel containing M2-sEVs (dECM/M2-sEVs) delayed the degeneration of intervertebral disc degeneration (IDD) models. In addition to demonstrating a promising therapeutic for IDD, this study provided valuable data for furthering the understanding of the roles and mechanisms of M2-sEVs in IVD regeneration.

Causal associations between the gut microbiota and multiple myeloma: a two-sample Mendelian randomization study.

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Adsorption performance and mechanism of pectin modified with ß-cyclodextrin for Zn2+ and Cu2.

Removing heavy metals from aqueous solutions has drawn more and more attentions these years because of their serious global health challenge to human society. To develop an adsorbent with green, stable and high-efficiency for adsorption of heavy metals, pectin ß-cyclodextrin composite was successfully prepared and used for Zn2+ and Cu2+ adsorption for the first time. Various variables that influence the adsorption performance were explored, and the optimal adsorption conditions were determined. According to the pseudo-second-order kinetic model, the adsorption process of Zn2+ and Cu2+ by the adsorbent was mainly chemical adsorption. The adsorbent adsorption process was an exothermic and non-spontaneous process. According to the Langmuir isotherm model, the maximum adsorption capacity was 12.51 ± 0.33 and 24.98 ± 0.23 mg/g for Zn2+ and Cu2+, respectively. The FTIR, EDX and XPS results revealed that the main mechanisms of removing pollutants by adsorbent were ion exchange and coordination. In addition, electrostatic attraction and chelation were present in the adsorption process. After five adsorption desorption cycles, the pectin ß-cyclodextrin composite adsorbent still exhibited adsorption and regeneration capabilities. This study provides a low-cost, effective and simple method for preparation of modified pectin, which has excellent application potential in the removal of heavy metal ions from wastewater.

Association of ambient PM2.5 and its components with in vitro fertilization outcomes: The modifying role of maternal dietary patterns.

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the "Fruits-Vegetables-Dairy" pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the "Puffed food-Bakery-Candy" pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the "Grains-Tubers-Legumes". Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

Microsyringe-assisted visual volume detection based on phase separation: the case of chymosin milk-clotting activity study.

The constantly diverse demand scenarios for rapid on-site analysis have put forward high requirements for developing low-cost and user-friendly visual detection methods. Therefore, developing a visual detection method with simple operation and intuitive results has important practical value in the field of analysis and detection, but it is also challenging. In this work, we propose a microsyringe-assisted visual volume detection method based on phase separation, and apply it to analyze the milk-clotting activity of chymosin. Chymosin can cause phase separation of milk with whey in the mobile phase and curd in the gel state. The network structures of casein in curd can trap water molecules, resulting in separation of whey from curd gradually. Therefore, the analysis of chymosin milk-clotting activity can be realized according to the volume of whey measured using a portable microsyringe. This method shows a good linear correlation when the concentration of chymosin ranges from 1.02 U L-1 to 1020 U L-1 and the limit of detection of this method for chymosin is calculated to be 0.03 U mL-1. This work successfully realizes the visual analysis of chymosin milk-clotting activity based on the enzyme-triggered phase separation. It also shows great promise to be applied in other phase separation-based detection systems with the advantages of high accuracy, great portability and user-friendliness.

Pentavalent Rotavirus Vaccine Coverage and Trends in Rotavirus Detection Before and After This Vaccination in Chengdu, China.

Pentavalent rotavirus vaccine (RV5) coverage and changes in rotavirus detection in the prevaccine and postvaccine era in Chengdu were investigated. The results showed that the coverage of RV5 had been increasing but still relatively low. Nevertheless, the dramatical decline in the rotavirus detection was observed after the introduction of RV5. Efforts to improve the coverage of rotavirus vaccination should continue to maximize the public health benefits.

Systematic review and meta-analysis of repetitive transcranial magnetic stimulation (rTMS) for activities of daily living in Alzheimer's disease.

OBJECTIVE: This systematic review of randomised controlled trials (RCTs) was conducted to assess the effect of repetitive transcranial magnetic stimulation (rTMS) on activities of daily living (ADLs) in Alzheimer's disease (AD) patients. DATA SOURCES: Ten databases were retrieved for pertinent Chinese and English literatures published up until January 2024. REVIEW METHODS: All RCTs of rTMS for ADLs in AD were included in this meta-analysis. Two researchers independently selected the literatures, retrieved the data of included literatures, accessed risk-of-bias of literatures with the Cochrane Collaboration's quality criteria and then cross-checked. Meta-analysis was carried out with Cochrane's Review Manager (RevMan, version 5.4). The PRISMA guidelines were followed in this systematic review. RESULTS: The 37 literatures involving 2461 patients with AD were included in this study. Compared with the control groups received the interventions such as routine pharmacotherapy, cognitive training, ect., with/without sham-rTMS, the experiment groups received the interventions of the control groups and rTMS. The findings were as follows: ADL scale [mean difference (MD) = -3.92, 95%CI (-4.93, -2.91), P < 0.00001]; Barthel Index (BI) [MD = 9.75, 95% CI (6.66, 12.85), P < 0.00001]; Modified Barthel Index (MBI) [MD = 5.43, 95% CI (3.13, 7.73), P < 0.00001]. The differences were statistically significant for all indicators. In 29 studies, rTMS stimulation sites were located in the dorsolateral prefrontal cortex (DLPFC). CONCLUSION: The rTMS could improve the ADLs in AD patients, and the DLPFC was a frequently used stimulation site of the rTMS for AD treatment.

NALA: a Nesterov accelerated look-ahead optimizer for deep learning.

Adaptive gradient algorithms have been successfully used in deep learning. Previous work reveals that adaptive gradient algorithms mainly borrow the moving average idea of heavy ball acceleration to estimate the first- and second-order moments of the gradient for accelerating convergence. However, Nesterov acceleration which uses the gradient at extrapolation point can achieve a faster convergence speed than heavy ball acceleration in theory. In this article, a new optimization algorithm which combines adaptive gradient algorithm with Nesterov acceleration by using a look-ahead scheme, called NALA, is proposed for deep learning. NALA iteratively updates two sets of weights, i.e., the 'fast weights' in its inner loop and the 'slow weights' in its outer loop. Concretely, NALA first updates the fast weights k times using Adam optimizer in the inner loop, and then updates the slow weights once in the direction of Nesterov's Accelerated Gradient (NAG) in the outer loop. We compare NALA with several popular optimization algorithms on a range of image classification tasks on public datasets. The experimental results show that NALA can achieve faster convergence and higher accuracy than other popular optimization algorithms.

Alzheimer's Disease Knowledge Graph Enhances Knowledge Discovery and Disease Prediction.

Background: Alzheimer's disease (AD), a progressive neurodegenerative disorder, continues to increase in prevalence without any effective treatments to date. In this context, knowledge graphs (KGs) have emerged as a pivotal tool in biomedical research, offering new perspectives on drug repurposing and biomarker discovery by analyzing intricate network structures. Our study seeks to build an AD-specific knowledge graph, highlighting interactions among AD, genes, variants, chemicals, drugs, and other diseases. The goal is to shed light on existing treatments, potential targets, and diagnostic methods for AD, thereby aiding in drug repurposing and the identification of biomarkers. Results: We annotated 800 PubMed abstracts and leveraged GPT-4 for text augmentation to enrich our training data for named entity recognition (NER) and relation classification. A comprehensive data mining model, integrating NER and relationship classification, was trained on the annotated corpus. This model was subsequently applied to extract relation triplets from unannotated abstracts. To enhance entity linking, we utilized a suite of reference biomedical databases and refine the linking accuracy through abbreviation resolution. As a result, we successfully identified 3,199,276 entity mentions and 633,733 triplets, elucidating connections between 5,000 unique entities. These connections were pivotal in constructing a comprehensive Alzheimer's Disease Knowledge Graph (ADKG). We also integrated the ADKG constructed after entity linking with other biomedical databases. The ADKG served as a training ground for Knowledge Graph Embedding models with the high-ranking predicted triplets supported by evidence, underscoring the utility of ADKG in generating testable scientific hypotheses. Further application of ADKG in predictive modeling using the UK Biobank data revealed models based on ADKG outperforming others, as evidenced by higher values in the areas under the receiver operating characteristic (ROC) curves. Conclusion: The ADKG is a valuable resource for generating hypotheses and enhancing predictive models, highlighting its potential to advance AD's disease research and treatment strategies.

[Vertical Distribution Characteristics and Driving Factors of Bacterioplankton and Nitrogen Phosphorus Cycle Genes in Danjiangkou Reservoir].

Danjiangkou Reservoir is a critical water source for the South-to-North Water Diversion Project, which harbors a diverse bacterioplankton community with varying depths, and the understanding of its nitrogen and phosphorus cycle and associated driving factors remains limited. In this study, we selected five ecological sites within Danjiangkou Reservoir and conducted metagenomics analysis to investigate the vertical distribution of bacterioplankton communities in the surface, middle, and bottom layers. Furthermore, we analyzed and predicted the function of nitrogen and phosphorus cycles, along with their driving factors. Our findings revealed the dominance of Proteobacteria, Actinobacteria, and Planctomycetes in the Danjiangkou Reservoir. Significant differences were observed in the structure of bacterioplankton communities across different depths, with temperature （T）, oxidation-reduction potential （ORP）, dissolved oxygen （DO）, and Chla identified as primary factors influencing the bacterioplankton composition. Analysis of nitrogen cycle functional genes identified 39 genes, including gltB, glnA, gltD, gdhA, NRT, etc., which were involved in seven main pathways, encompassing nitrogen fixation, nitrification, denitrification, and dissimilatory nitrate reduction. Phosphorus cycle function gene analysis identified 54 genes, including pstS, ppx-gppA, glpQ, ppk1, etc., primarily participating in six main pathways, including organic P mineralization, inorganic P solubilization, and regulatory. Cluster analysis indicated that different depths were significant factors influencing the composition and abundance of nitrogen and phosphorus cycle functional genes. The composition and abundance of nitrogen and phosphorus cycle functional genes in the surface and bottom layers differed and were generally higher than those in the middle layer. Deinococcus, Hydrogenophaga, Limnohabitans, Clavibacter, and others were identified as key species involved in the nitrogen and phosphorus cycle. Additionally, we found significant correlations between nitrogen and phosphorus cycle functional genes and environmental factors such as DO, pH, T, total dissolved solids （TDS）, electrical conductivity （EC）, and Chla. Furthermore, the content of these environmental factors exhibited depth-related changes in the Danjiangkou Reservoir, resulting in a distinct vertical distribution pattern of bacterioplankton nitrogen and phosphorus cycle functional genes. Overall, this study sheds light on the composition, function, and influencing factors of bacterioplankton communities across different layers of Danjiangkou Reservoir, offering valuable insights for the ecological function and diversity protection of bacterioplankton in this crucial reservoir ecosystem.

Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology.

Background: Multiple myeloma (MM) is a heterogeneous plasma-derived hematopoietic malignancy with complex genetic mutation contributing to the pathogenesis. Though gene sequencing has been applied in MM, genetic features from Chinese MM patients are reported less. We investigated the genetic mutation of newly diagnosed multiple myeloma (NDMM) patients and explore its correlation with cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH). Methods: A total of 206 patients with NDMM were enrolled. After enriching plasma cells with CD138 magnetic beads, 92 MM-related target gene mutations were detected by the Illumina sequencing platform, and six common genetic abnormalities were detected by FISH. Results: 162 cases (78.6%) had at least one gene mutation detected by NDMM. The top 5 mutated genes were KRAS, NRAS, TRAF3, BRAF, and TP53. Cytogenetic abnormalities detected by FISH have a certain correlation with gene mutations, t(11;14) translocations are often accompanied by CCND1 and TP53 mutations, KLHL6 in t(4;14), SP140, CDKN1B and PRKD2 in t(14;16) and t(14;20) translocations. The mutation ratio was higher for EGR1, while lower of CCND1 in patients with gain 1q21. The TP53 mutation was more likely in patients with 17p deletion. The gene mutation affects the pathway of the RNA process is more frequently occurring in males and age less than 70 years patients. The International Staging System (ISS) Stage III correlated with gene mutations in the NK-κB pathway while Revised ISS (R-ISS) Stage III correlated with the DNA damage repair pathway. Conclusions: There are various gene mutations in NDMM patients, mainly RAS/MAPK and NF-κB pathway gene pathways.

ISIS 449884 Injection Add-On to Metformin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase II Clinical Study.

INTRODUCTION: ISIS 449884, a 2'-O-methoxyethyl antisense oligonucleotide that targets the glucagon receptor (GCGR), has demonstrated an ability to reduce hepatic glucose output and lower the blood glucose level. The primary objective of this study was to investigate the safety and efficacy of ISIS 449884 as an add-on to metformin in a population of Chinese patients with type 2 diabetes mellitus (T2DM). METHOD: This was a multicenter, placebo-controlled (2:1), randomized, double-blind, parallel-enrollment, multiple-dose phase II study in Chinese patients with T2DM. A total of 90 patients who were uncontrolled by stable metformin monotherapy were randomized into three cohorts. Thirty subjects were enrolled in each cohort and received injections of ISIS 449884 (50 mg or 60 mg weekly or 100 mg every other week) or a corresponding volume of placebo (0.25 mL and 0.3 mL weekly or 0.5 mL every other week) subcutaneously in a 2:1 ratio for 16 weeks. RESULTS: The primary efficacy endpoint was analyzed in 88 subjects (ISIS 449884, n = 59; placebo, n = 29). The corrected LS mean change from baseline in glycated hemoglobin (HbA1c) at week 17 in the pooled ISIS 449884 treatment group was - 1.31% (95% CI - 1.66%, - 0.96%), and that in the pooled placebo group was 0.15% (95% CI - 0.37%, 0.66%). The LS mean difference between the two groups was - 1.46% (95% CI - 1.92%, - 1.00%, P < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 53/60 subjects (88.3%) and 25/30 subjects (83.3%) in the pooled ISIS 449884 treatment group and the pooled placebo group, respectively, with similar incidences. Drug-related TEAEs occurred in 41/60 subjects (68.3%) and 9/30 subjects (30.0%), respectively. TEAEs of grade 3 or higher occurred in 5/60 (8.3%) subjects and 2/30 (6.7%) subjects, respectively, and none of them were drug related. CONCLUSIONS: The ISIS 449884 injection add-on to metformin significantly reduced HbA1c in patients with T2DM uncontrolled by stable metformin monotherapy and showed an acceptable benefit/risk profile. CLINICAL TRIAL REGISTRATION: www.chinadrugtrials.org.cn , CTR20191096.

Folate supplementation as a beneficial add-on treatment in relieving depressive symptoms: A meta-analysis of meta-analyses.

The results of meta-analyses investigating the role of folate on depression are conflicting. The aim of this umbrella meta-analysis was to obtain an overall effect and give a concise and resolving conclusion. International scientific databases including PubMed, Scopus, and Web of Science were searched up to Oct 2023. All observational and interventional meta-analyses investigating the role of folate in depression were included in the study. Random-effects model was employed to obtain pooled results. I 2 statistics and Cochrane Q test were used to assess the between-study heterogeneity. The quality of included meta-analyses was evaluated using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR2) questionnaire. Overall 11 studies were included, of which 8 studies went under quantitative evaluation. The results indicated that folate supplementation significantly relieved depression symptoms [(SMD: -0.42; 95% CI: -0.57, -0.27, p < .001; I 2 = 0.0%, p-heterogeneity = 0.554) (WMD: -3.20; 95% CI: -4.00, -2.41, p < .001, I 2 = 14.8%, p-heterogeneity = 0.318)] with low levels of heterogeneity. Also, based on observational studies, folate insufficiency significantly increased the odds ratio of depression by 35% (OR:1.35; 95% CI: 1.27, 1.42, p < .001, I 2 = 8.7%, p-heterogeneity = 0.350). The findings support the fact that folate supplementation could be suggested as an efficacious and adjuvant agent in the alleviation of depression symptoms along with routine medications.

Ischemic cardio-cerebrovascular disease and all-cause mortality in Chinese elderly patients: a propensity-score matching study.

BACKGROUND: Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. METHODS: This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. RESULTS: Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5-86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P < 0.001) individuals with a higher burden of comorbidities. Over a median follow-up of 10.4 years, 398 (38.8%) all-cause deaths were identified. Compared with the MICCD group, the CICCD group exhibited a higher adjusted hazard ratio (HR) (95% confidential interval, CI) of 1.71 (1.32-2.39) for long-term mortality after adjusting for potential confounders. The sensitivity analysis results remained robust. After inverse probability of treatment weighting (IPTW) modeling, the CICCD group displayed an even worse mortality risk (IPTW-adjusted HR: 2.07; 95% CI 1.47-2.90). In addition, anemia (adjusted HR: 1.48; 95% CI 1.16-1.89) and malnutrition (adjusted HR: 1.43; 95% CI 1.15-1.78) are also independent risk factors for all-cause mortality among elderly and very elderly patients. CONCLUSIONS: Our results thus suggest that elderly patients with ischemic cardio-cerebrovascular disease and anemia or malnutrition may have higher mortality, which may be predicted upon admission. These findings, however, warrant further investigation.

Efficacy and safety of anlotinib in combination with immune checkpoint inhibitors or not as advanced non-small cell lung cancer treatment: a systematic review and network meta-analysis.

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Combined anlotinib and immune checkpoint inhibitors (ICIs) therapy may have synergistic antitumor effects in NSCLC. This study aimed to comparing the efficacy and safety of anlotinib and ICIs treatment, monotherapy and combination in NSCLC. Methods: We performed a systematic review and network meta-analysis of 14 studies involving 4,308 NSCLC patients across four regimens: anlotinib, ICIs, anlotinib plus ICIs, and placebo. Efficacy outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety outcomes included treatment-related adverse events (TRAEs), TRAE grade three or higher (TRAE ≥3). Analyses were performed in RevMan 5.3 and R 3.5.1 (gemtc package). P<0.05 or effect estimate with 95% confidence interval (CI) that did not include 1 indicated statistical significance. Results: Fourteen publications involving 4,308 patients across four treatment regimens (anlotinib, ICIs, anlotinib plus ICIs, placebo) were included. For PFS, network meta-analysis showed all three interventions significantly improved PFS versus placebo. Anlotinib plus ICIs demonstrated the greatest PFS improvement [hazard ratio (HR) =0.24; 95% CI: 0.14, 0.36], followed by anlotinib (HR =0.37; 95% CI: 0.23, 0.58), and ICIs (HR =0.43; 95% CI: 0.27, 0.67). For OS, compared to placebo, anlotinib plus ICIs showed the greatest OS improvement (HR =0.52; 95% CI: 0.33, 0.74), followed by anlotinib (HR =0.66; 95% CI: 0.47, 0.95), and ICIs (HR =0.72; 95% CI: 0.54, 0.97). For ORR, anlotinib plus ICIs demonstrated the greatest improvement versus placebo [odds ratio (OR) =5.29; 95% CI: 3.32, 8.58], followed by anlotinib (OR =4.38; 95% CI: 2.42, 8.19), and ICIs (OR =2.17; 95% CI: 1.65, 2.89). For DCR, anlotinib plus ICIs showed the greatest improvement versus placebo (OR =13.32; 95% CI: 4.99, 45.09), followed by anlotinib (OR =5.56; 95% CI: 2.17, 14.38), and ICIs (OR =3.46; 95% CI: 1.29, 10.85). Compared to placebo, anlotinib was associated with the highest risk of TRAEs (OR =3.67, 95% CI: 1.12, 15.77), followed by ICIs (OR =1.83; 95% CI: 1.26, 2.69). Due to lack of data on anlotinib plus ICIs, no comparison was conducted. For grade ≥3 TRAEs, compared to placebo, anlotinib increased the risk (OR =3.67; 95% CI: 1.12, 15.77), while anlotinib plus ICIs (OR =2.45; 95% CI: 0.51, 11.6) and ICIs (OR =1.29; 95% CI: 0.33, 4.38) did not increase the risk. Conclusions: Anlotinib combined with ICIs demonstrates improved efficacy over monotherapy for NSCLC treatment, without increased adverse events.

Effects of Exercise on Frailty in Older People Based on ACSM Recommendations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: The objective of the study was to carry out an analysis of the methodological quality of clinical trials (effects of exercise on frailty in older people) based on ACSM recommendations. Methods: The search scope included PubMed, Embase, Web of Science, Cochrane, and literature that cannot be retrieved from the database. The topic was the impact of exercise on frailty in elderly people. Changes in five outcome measures (FP, BI, SPPB, GS, and BMI) were assessed using mean differences (MD) and 95% confidence intervals (95% CI). A random effects model (RE) was used to conduct a meta-analysis and compare the results between subgroups. Results: The intervention effects of exercise on the five outcome indicators of frailty in elderly people were all significant (p < 0.05). The effect of a high-consistency subgroup on outcome indicators FP and GS was more significant than that of the low- or uncertain-consistency subgroup (MD: -1.09 < -0.11, MD: 2.39 >1.1). There was no significant difference in the intervention effect as reflected in the outcome measures SPPB and BMI in the high-consistency subgroup (p = 0.07, p = 0.34). There was no significant difference in the impact of the intervention on the outcome measure BI between the two subgroups (p = 0.06, p = 0.14). Conclusions: Exercise prescriptions with high consistency with ACSM recommendations may be more effective in both FP and GS interventions than those with uncertain or low consistency. However, it is essential to note that the data derived from the meta-analysis is still subject to the small number of studies, the unknown degree of consistency of participants in individual studies, and the different mix of cases in the studies.

Axial Compressive Behaviours of Coal Gangue Concrete-Filled Circular Steel Tubular Stub Columns after Chloride Salt Corrosion.

The axial compressive behaviours of coal gangue concrete-filled steel tube (GCFST) columns after chloride salt corrosion were investigated numerically. Numerical modelling was conducted through the static analysis method by finite element (FE) analysis. The failure mechanism, residual strength, and axial load-displacement curves were validated against tests of the coal gangue aggregate concrete-filled steel tube (GCFST) columns at room and natural aggregate concrete-filled steel tube (NCFST) columns after salt corrosion circumstance. According to the analysis on the stress distribution of the steel tube, the stress value of the steel tube decreased as the corrosion rate increased at the same characteristic point. A parametric analysis was carried out to determine the effect of crucial variation on residual strength. It indicated that material strength, the steel ratio, and the corrosion rate made a profound impact on the residual strength from the FE. The residual strength of the columns exposed to chloride salt was in negative correlation with the corrosion rate. The impact on the residual strength of the column was little, obvious by the replacement rate of the coal gangue. A simplified design formula for predicting the ultimate strength of GCFST columns after chloride salt corrosion exposure was proposed.