Stability and Controller Research of Double-Wing FMAV System Based on Controllable Tail.

This study aimed to enhance the stability and response speed of a passive stabilized double-wing flapping micro air vehicle (FMAV) by implementing a feedback-controlled biomimetic tail. A model for flapping wings accurately calculated the lift force with only a 2.4% error compared to the experimental data. Experimental tests established the relationship between control torque and tail area, swing angle, and wing-tail spacing. A stability model for the double-wing FMAV was developed, incorporating stabilizing sails. Linearization of the hovering state facilitated the design of a simulation controller to improve response speed. By adjusting the feedback loops of velocity, angle, and angular velocity, the tail controller reduced the angle simulation response time from 4 s to 0.1 s and the velocity response time from 5.64 s to 0.1 s. In take-off experiments, a passive stabilized prototype with an adjustable tail angle exhibited enhanced flight stability compared to fixed tails, reducing standard deviation by 72.96% at a 0° take-off angle and 56.85% at a 5° take-off angle. The control axis standard deviation decreased by 38.06% compared to the passive stability axis, confirming the effectiveness of the designed tail angle controller in reducing angular deflection and improving flight stability.

Phosphodiesterase type 5 inhibitor tadalafil reduces prostatic fibrosis via MiR-3126-3p/FGF9 axis in benign prostatic hyperplasia.

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFß1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFß1 suppression. Overall, TGFß1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.

Study on stability evaluation of goaf based on AHP and EWM-taking the northern new district of Liaoyuan city as an example.

Throughout the history of coal mining in all countries of the world, large areas of goaf have been left behind, and sudden collapses and surface subsidence of large areas of goaf may occur, especially for mining areas with long mining cycles. The northern new district of the Liaoyuan mining area has been subjected to nearly half a century of mining activities, accompanied by a gradual accumulation of disasters, which have occurred frequently in recent years. In order to assess the stability of the goaf in the study area, this paper proposes a hybrid decision-making multi-factor integrated evaluation method. The distribution of underground goafs was determined using geophysical exploration techniques (seismic survey and transient electromagnetic method) and geological drilling exploration. First, an evaluation index system was established based on the specifications of the goaf, the ecological and geological environment, and the mining conditions; the system included 14 indicators. Two weight calculation methods, AHP-EWM, were employed to determine the comprehensive weight of each indicator by combining subjective and objective weights on the basis of improved game theory. Subsequently, the fuzzy comprehensive evaluation method was utilised to complete the stability rating of each block in the study area, and MapGIS and ArcGIS were employed to complete the drawing of the stability zoning map of the northern new district goaf. The study area was divided into three zones of stability, basic stability and instability, according to the critical value. These zones accounted for 23.03%, 36.45% and 40.52% of the total area of the study area, respectively. The comprehensive on-site investigation revealed a decrease in the size and number of collapse pits and the rate of damage to the houses from the unstable zone to the stable zone. This indicates that the results of the division are consistent with the actual situation. The classification results are consistent with the actual ground disaster situation, thus verifying the rationality and validity of the evaluation method. The results indicate that the stability of the study area is generally at the lower middle level.

Study on the ecological environment quality and its driving factors of the spatial transformation of production-living-ecological space in Baishan City.

In order to strengthen the overall planning and coordination of urban construction and ecological space in Baishan City, we should formulate a scientific land type planning of Production-Living-Ecological Space (PLES). In this paper, land use dynamic attitude model, land use transfer matrix, land use function center of gravity transfer model, eco-environmental quality index(EEQI) and geographic detector model are used to discuss the spatio-temporal evolution of PLES in Baishan City from 2000 to 2020. Spatio-temporal evolution of EEQI and its influencing factors. The results show that: (1) During the study period, Baishan City showed the characteristics that the production space first increased and then decreased, the ecological space decreased, and the living space continued to increase. Among them, the ecological space is the dominant space of Baishan City, covering an area of more than 80%. From the perspective of the transformation of PLES, from 2000 to 2020, Baishan City is mainly characterized by the transformation of ecological space into production space and living space. In the second type of space, green ecological space, forestry ecological space and other ecological space have decreased, while other types of space have increased in varying degrees. (2) During the study period, the overall EEQI of Baishan City remained in good condition, and the ecological environment quality(EEQ) of the three periods were 0.6571, 0.6412 and 0.6562 respectively. The higher EEQI is distributed in Changbai County and Linjiang City, while the areas with lower EEQI are concentrated in the north-central part of Hunjiang City, the middle part of Jiangyuan District and the northwest of Fusong County. (3) According to the analysis of the influencing factors of EEQ, the influence of the factors of spatial differentiation of EEQI in Baishan City changed significantly from 2000 to 2020, and the average annual rainfall was the core factor affecting the spatial differentiation of EEQ in Baishan City, the second is the urbanization rate and the distance from the county government, and the interaction between the average annual rainfall and the distance from the county government has a strong influence on the spatial differentiation of EEQ in Baishan City. This study reveals the evolution of spatial types and EEQ of PLES in Baishan City, and provides a scientific reference for the effective management and utilization of land resources in Baishan City.

Trends in utilization patterns of newer glucose-lowering drugs in US adults with type 2 diabetes and a history of coronary heart disease or heart failure: 2005-2019.

BACKGROUND: The newer glucose-lowering drugs (GLDs), including Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), have demonstrated superior cardio- and renal protective benefits compared to older GLDs in individuals with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). OBJECTIVE: This study examined the trends of the newer GLDs use in people with T2D who had a history of coronary heart disease or heart failure in the United States. METHOD: We used 2005-2019 data from the Medical Expenditure Panel Survey (MEPS). Individuals with self-reported diabetes and CVD history were identified. RESULTS: There was a steady increase in the use of GLP-1RA only from 2008 (3 %) to 2019 (21 %) and SGLT2i only from 2014 (5 %) to 2019 (12 %). Individuals with dual use of both newer GLD classes increased from 0.62 % in 2015 to 6 % in 2019. The overall uptake of these two newer drugs in 2019 was less than 40 %. In other words, 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments. CONCLUSION: The use of GLP-1RA and SGLT2i among individuals with T2D and a history of CVD was low and varied by insurance type. Policy-level interventions are needed to improve the use of these newer treatments further. SUMMARY: We examined how newer glucose-lowering drugs are used among individuals with type 2 diabetes and at high risk for coronary heart disease or heart failure in the US. We found that 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments due to the variation of insurance type.

Weakened connection between spring leaf-out and autumn senescence in the Northern Hemisphere.

Vegetation autumn phenology is critical in regulating the ecosystem carbon cycle and regional climate. However, the dominant drivers of autumn senescence and their temporal shifts under climate change remain poorly understood. Here, we conducted a multi-factor analysis considering both direct climatic controls and biological carryover effects from start-of-season (SOS) and seasonal peak vegetation activities on the end-of-season (EOS) to fill these knowledge gaps. Combining satellite and ground observations across the northern hemisphere, we found that carryover effects from early-to-peak vegetation activities exerted greater influence on EOS than the direct climatic controls on nearly half of the vegetated land. Unexpectedly, the carryover effects from SOS on EOS have significantly weakened over recent decades, accompanied by strengthened climatic controls. Such results indicate the weakened constraint of leaf longevity on senescence due to prolonged growing season in response to climate change. These findings underscore the important role of biological carryover effects in regulating vegetation autumn senescence under climate change, which should be incorporated into the formulation and enhancement of phenology modules utilized in land surface models.

Alfentanil versus fentanyl for emergency department rapid sequence induction with ketamine: A-FAKT, a pilot randomized trial.

BACKGROUND: Fentanyl is often administered during rapid sequence induction of anesthesia (RSI) in the emergency department (ED) to ameliorate the hypertensive response that may occur. Due to its more rapid onset, the use of alfentanil may be more consistent with both the onset time of the sedative and the commencement of laryngoscopy. As such, we compared the effect of alfentanil and fentanyl on post-induction hemodynamic changes when administered as part of a standardized induction regimen including ketamine and rocuronium in ED RSI. METHODS: This was a double-blind pilot randomized controlled trial of adult patients requiring RSI in the ED of three urban Australian hospitals. Patients were randomized to receive either alfentanil or fentanyl in addition to ketamine and rocuronium for RSI. Non-invasive blood pressure and heart rate were measured immediately before and at two, four, and six minutes after induction. The primary outcome was the occurrence of at least one post-induction systolic blood pressure outside the pre-specified range of 100-160mmHg (with adjustment for patients with baseline hypertension). Secondary outcomes included hypertension, hypotension, hypoxia, first-pass intubation success, 30-day mortality, and the pattern of hemodynamic changes. RESULTS: A total of 61 patients were included in the final analysis (31 in the alfentanil group and 30 in the fentanyl group). The primary outcome was met in 58% of the alfentanil group and 50% of the fentanyl group (difference 8%, 95% confidence interval: -17% to 33%). The 30-day mortality rate, first-pass success rate, and incidences of hypertension, hypotension, and hypoxia were similar between the groups. There were no significant differences in systolic blood pressure or heart rate between the groups at any of the measured time-points. CONCLUSION: Alfentanil and fentanyl produced comparable post-induction hemodynamic changes when used as adjuncts to ketamine in ED RSI. Future studies could consider comparing different dosages of these opioids.

Tamm-cavity terahertz detector.

Efficiently fabricating a cavity that can achieve strong interactions between terahertz waves and matter would allow researchers to exploit the intrinsic properties due to the long wavelength in the terahertz waveband. Here we show a terahertz detector embedded in a Tamm cavity with a record Q value of 1017 and a bandwidth of only 469 MHz for direct detection. The Tamm-cavity detector is formed by embedding a substrate with an Nb5N6 microbolometer detector between an Si/air distributed Bragg reflector (DBR) and a metal reflector. The resonant frequency can be controlled by adjusting the thickness of the substrate layer. The detector and DBR are fabricated separately, and a large pixel-array detector can be realized by a very simple assembly process. This versatile cavity structure can be used as a platform for preparing high-performance terahertz devices and opening up the study of the strong interactions between terahertz waves and matter.

Application of New Polymer Soil Amendment in Ecological Restoration of High-Steep Rocky Slope in Seasonally Frozen Soil Areas.

In seasonally frozen soil areas, high-steep rocky slopes resulting from open-pit mining and slope cutting during road construction undergo slow natural restoration, making ecological restoration generally challenging. In order to improve the problems of external soil attachment and long-term vegetation growth in the ecological restoration of high-steep rocky slopes in seasonally frozen areas, this study conducted a series of experiments through the combined application of polyacrylamide (PAM) and carboxymethyl cellulose (CMC) to assess the effects of soil amendments on soil shear strength, water stability, freeze-thaw resistance, erosion resistance, and vegetation growth. This study showed that the addition of PAM-CMC significantly increased the shear resistance and cohesion of the soil, as well as improving the water stability, freeze-thaw resistance, and erosion resistance, but the internal friction angle of the soil was not significantly increased after reaching a certain content. Moderate amounts of PAM-CMC can extend the survival of vegetation, but overuse may cause soil hardening and inhibit vegetation growth by limiting air permeability. It was observed by a scanning electron microscope (SEM) that the gel membrane formed by PAM-CMC helped to "bridge" and bind the soil particles. After discussion and analysis, the optimum application rate of PAM-CMC was 3%, which not only improved the soil structure but also ensured the growth of vegetation in the later stage under the optimum application rate. Field application studies have shown that 3% PAM-CMC-amended soil stably attaches to high-steep rocky slopes, with stable vegetation growth, and continues to grow after five months of freeze-thaw action, with no need for manual maintenance after one year.

Terahertz Sensing of L-Valine and L-Phenylalanine Solutions.

To detect and differentiate two essential amino acids (L-Valine and L-Phenylalanine) in the human body, a novel asymmetrically folded dual-aperture metal ring terahertz metasurface sensor was designed. A solvent mixture of water and glycerol with a volume ratio of 2:8 was proposed to reduce the absorption of terahertz waves by reducing the water content. A sample chamber with a controlled liquid thickness of 15 µm was fabricated. And a terahertz time-domain spectroscopy (THz-TDS) system, which is capable of horizontally positioning the samples, was assembled. The results of the sensing test revealed that as the concentration of valine solution varied from 0 to 20 mmol/L, the sensing resonance peak shifted from 1.39 THz to 1.58 THz with a concentration sensitivity of 9.98 GHz/mmol∗L-1. The resonance peak shift phenomenon in phenylalanine solution was less apparent. It is assumed that the coupling enhancement between the absorption peak position of solutes in the solution and the sensing peak position amplified the terahertz localized electric field resonance, which resulted in the increase in frequency shift. Therefore, it could be shown that the sensor has capabilities in performing the marker sensing detection of L-Valine.

[Effects of different exercise modes on neuromuscular junction and metabolism of skeletal muscle-related proteins in aging rats].

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.

An adaptive discretized RNN algorithm for posture collaboration motion control of constrained dual-arm robots.

Although there are many studies on repetitive motion control of robots, few schemes and algorithms involve posture collaboration motion control of constrained dual-arm robots in three-dimensional scenes, which can meet more complex work requirements. Therefore, this study establishes the minimum displacement repetitive motion control scheme for the left and right robotic arms separately. On the basis of this, the design mentality of the proposed dual-arm posture collaboration motion control (DAPCMC) scheme, which is combined with a new joint-limit conversion strategy, is described, and the scheme is transformed into a time-variant equation system (TVES) problem form subsequently. To address the TVES problem, a novel adaptive Taylor-type discretized recurrent neural network (ATT-DRNN) algorithm is devised, which fundamentally solves the problem of calculation accuracy which cannot be balanced well with the fast convergence speed. Then, stringent theoretical analysis confirms the dependability of the ATT-DRNN algorithm in terms of calculation precision and convergence rate. Finally, the effectiveness of the DAPCMC scheme and the excellent convergence competence of the ATT-DRNN algorithm is verified by a numerical simulation analysis and two control cases of dual-arm robots.

Emerging Role of Sorting Nexin 17 in Human Health and Disease.

The distortion of the cellular membrane transport pathway has a profound impact on cell dynamics and can drive serious physiological consequences during the process of cell sorting. SNX17 is a member of the Sorting Nexin (SNX) family and plays a crucial role in protein sorting and transport in the endocytic pathway. SNX17, SNX27, and SNX31 belong to the SNX-FERM subfamily and possess the FERM domain, which can assist in endocytic transport and lysosomal degradation. The binding partners of SNX27 have been discovered to number over 100, and SNX27 has been linked to the development of Alzheimer's disease progression, tumorigenesis, cancer progression, and metastasis. However, the role and potential mechanisms of SNX17 in human health and disease remain poorly understood, and the function of SNX17 has not been fully elucidated. In this review, we summarize the structure and basic functions of SNX protein, focusing on providing current evidence of the role and possible mechanism of SNX17 in human neurodegenerative diseases and cardiovascular diseases.

Edible bird's nest regulates glucose and lipid metabolic disorders via the gut-liver axis in obese mice.

Edible bird's nest (EBN) is a traditional food known for its nourishing and functional properties and is found to be involved in anti-oxidation, anti-aging, and anti-influenza mechanisms, immune regulation, and improving cardiovascular diseases, among others. However, the potential of EBN to improve glycolipid metabolism disorders in high-fat-diet induced obesity and the underlying mechanisms remain unexplored. We examined the effects of EBN on glycolipid metabolism in obese mice fed a high-fat diet. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. The obese mice were selected and divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac and low-, medium-, and high-dose EBN], with 12 mice in each group. After 10 weeks of continuous gavage intervention, only mice in the high-dose EBN intervention group had lower body weight and total fat content, especially visceral fat. Meanwhile, intervention with three doses of EBN reduced serum FBG, TC, LDL, Ox-LDL, IL-1ß, IL-6, and TNF-α levels and increased serum HDL levels and energy expenditure. Using the high dosage as a paradigm, EBN intervention increased the sialic acid content in LDL, decreased TMAO in the liver, and increased GLP-1 levels in sera. EBN increased the colonic abundances of Akkermansia, Lactobacillus, and Desulfovibrio and reduced those of Lysinibacillus and Bacillus. The changes in the microbial community contribute to increasing colonic bile acids, reducing lipopolysaccharide synthesis to protect the intestinal barrier, and lowering inflammation levels. Changes were also observed in colonic transcripts and metabolites and liver gene transcripts and metabolites, which were mainly enriched in pathways of glycolipid metabolism, immune function amelioration, inflammatory signal mitigation, circadian rhythm, bile acid metabolism and insulin resistance. Therefore, EBN may enhance the gut microbiota and intestinal immunity, relieve chronic inflammation levels in serum, improve antioxidant capacity and circadian rhythm in the liver, promote bile acid metabolism, and decrease lipid absorption and lipid synthesis via the gut-liver axis. Consequently, this may reduce blood lipid and fat accumulation as well as improve islet function and reduce blood glucose levels.

Decoding chromosome organization using CheC-PLS: chromosome conformation by proximity labeling and long-read sequencing.

Genomic approaches have provided detailed insight into chromosome architecture. However, commonly deployed techniques do not preserve connectivity-based information, leaving large-scale genome organization poorly characterized. Here, we developed CheC-PLS: a proximity-labeling technique that indelibly marks, and then decodes, protein-associated sites. CheC-PLS tethers dam methyltransferase to a protein of interest, followed by Nanopore sequencing to identify methylated bases - indicative of in vivo proximity - along reads >100kb. As proof-of-concept we analyzed, in budding yeast, a cohesin-based meiotic backbone that organizes chromatin into an array of loops. Our data recapitulates previously obtained association patterns, and, importantly, exposes variability between cells. Single read data reveals cohesin translocation on DNA and, by anchoring reads onto unique regions, we define the internal organization of the ribosomal DNA locus. Our versatile technique, which we also deployed on isolated nuclei with nanobodies, promises to illuminate diverse chromosomal processes by describing the in vivo conformations of single chromosomes.

A detailed overview of quercetin: implications for cell death and liver fibrosis mechanisms.

Background: Quercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential. Purpose: This review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis. Methods: A comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employed were "quercetin", "natural sources of quercetin", "quercetin extraction methods", "bioavailability of quercetin", "pharmacokinetics of quercetin", "cell death pathways", "apoptosis", "autophagy", "pyroptosis", "necroptosis", "ferroptosis", "cuproptosis", "liver fibrosis", and "hepatic stellate cells". These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis. Results: This review details quercetin's involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin's effects on liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin's structure and its potential for specific actions in the liver. Conclusion: The paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential.

Association between low cognitive performance and diabetes-related health indicators across racial and ethnic groups in adults with diabetes.

AIM: To examine the associations between low cognitive performance (LCP) and diabetes-related health indicators (including body mass index [BMI], HbA1c, systolic blood pressure [SBP], low-density lipoprotein [LDL] and self-reported poor physical health) and whether these associations vary across racial/ethnic subgroups. METHODS: We identified adults aged 60 years or older with self-reported diabetes from the 2011-2014 National Health and Nutrition Examination Survey. Individuals with cognitive test scores in the lowest quartile were defined as having LCP. We used regression models to measure the associations of LCP with diabetes-related biometrics (BMI, HbA1c, SBP and LDL); and self-reported poor physical health. Moreover, we explored potential variations in these associations across racial/ethnic subgroups. RESULTS: Of 873 (261 with LCP) adults with diabetes, LCP was associated with higher HbA1c, SBP and LDL (adjusted difference: 0.41%, 5.01 mmHg and 5.08 mg/dL, respectively; P < .05), and greater odds of reporting poor physical health (adjusted odds ratio: 1.59, P < .05). The association between LCP and HbA1c was consistent across racial/ethnic groups, and notably pronounced in Hispanic and Other. BMI worsened with LCP, except for non-Hispanic Black. Excluding the Other group, elevated SBP was observed in people with LCP, with Hispanic showing the most significant association. LDL levels were elevated with LCP for Hispanic and Other. Physical health worsened with LCP for both non-Hispanic Black and Hispanic. CONCLUSIONS: We quantified the association between LCP and diabetes-related health indicators. These associations were more pronounced in Hispanic and Other racial/ethnic groups.

Overall survival benefits of cancer drugs initially approved by the US Food and Drug Administration on the basis of immature survival data: a retrospective analysis.

BACKGROUND: New cancer drugs can be approved by the US Food and Drug Administration (FDA) on the basis of surrogate endpoints while data on overall survival are still incomplete or immature, with too few deaths for meaningful analysis. We aimed to evaluate whether clinical trials with immature survival data generated evidence of overall survival benefit during the period after marketing authorisation, and where that evidence was reported. METHODS: In this retrospective analysis, we searched Drugs@FDA to identify cancer drug indications approved between Jan 1, 2001, and Dec 31, 2018, on the basis of immature survival data. We systematically collected publicly available data on postapproval overall survival results in labelling (Drugs@FDA), journal publications (MEDLINE via PubMed), and clinical trial registries (ClinicalTrials.gov). The primary outcome was availability of statistically significant overall survival benefits during the period after marketing authorisation (until March 31, 2023). Additionally, we evaluated the availability and timing of overall survival findings in labelling, journal publications, and ClinicalTrials.gov records. FINDINGS: During the study period, the FDA granted marketing authorisation to 223 cancer drug indications, 95 of which had overall survival as an endpoint. 39 (41%) of these 95 indications had immature survival data. After a minimum of 4·3 years of follow-up during the period after marketing authorisation (and median 8·2 years [IQR 5·3-12·0] since FDA approval), additional survival data from the pivotal trials became available in either revised labelling or publications, or both, for 38 (97%) of 39 indications. Additional data on overall survival showed a statistically significant benefit in 12 (32%) of 38 indications, whereas mature data yielded statistically non-significant overall survival findings for 24 (63%) indications. Statistically significant evidence of overall survival benefit was reported in either labelling or publications a median of 1·5 years (IQR 0·8-2·3) after initial approval. The median time to availability of statistically non-significant overall survival results was 3·3 years (2·2-4·5). The availability of overall survival results on ClinicalTrials.gov varied considerably. INTERPRETATION: Fewer than a third of indications approved with immature survival data showed a statistically significant overall survival benefit after approval. Notable inconsistencies in timing and availability of information after approval across different sources emphasise the need for better reporting standards. FUNDING: None.

Improvements in the health-related quality-of-life benefit of cancer drugs approved in China, 2005-2020: an observational study.

Background: Health-related quality of life (HRQoL), along with overall survival (OS), is a critical study endpoint for measuring the clinical benefits of cancer drugs. Previous studies have examined the OS benefit of new cancer drugs approved in China. However, their HRQoL benefits have not been systematically evaluated. We aimed to characterise the measurement and improvement of HRQoL associated with cancer drugs approved in China. Methods: This mixed-methods study comprises of a literature review and a cross-sectional study, including all antineoplastic agents approved in China between January 1, 2005 and December 31, 2020. A systematic search was conducted on December 31, 2023 to extract HRQoL information of identified drugs. We extracted information on the characteristics of HRQoL assessment and statistically significant HRQoL gains compared with the control treatment. Findings: A total of 64 novel cancer drugs, corresponding to 115 cancer indications, supported by randomised clinical trials were approved in China between 2005 and 2020. Among the indications, 78 (67.8%) used HRQoL as an endpoint in the pivotal trial. By December 31, 2023, after a median follow-up of 5.3 (range, 3.0-18.8) years from approval, HRQoL information was available for more than half of the indications (75, 65.2%). Thirty-three indications (28.7%) reported statistically significant improvement in HRQoL, with 22 (19.1%) also having documented OS benefit. Approximately one-third of the indications (39, 33.9%) showed no difference in HRQoL, with 21 (18.3%) having documented OS gains. Three indications (2.6%) reported worsening HRQoL. The most commonly used HRQoL measurements were individual disease-specific instruments (62 of 75, 82.7%) while the most frequently employed analysis metric was the mean change scores from baseline (56 of 75, 74.7%). Interpretation: Fewer than one-third of cancer indications approved in China had shown HRQoL improvements. There was considerable heterogeneity in the analysis and reporting of HRQoL benefits associated with new cancer drugs approved in China. These findings emphasise the important role of HRQoL evaluation and analysis in clinical research and the necessity of improving the standardization of HRQoL assessment. Funding: National Natural Science Foundation of China (72274004).