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Abstract Background Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC. Methods We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024. Results Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively. Conclusion ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population.

Abstract Aims As a potential surrogate of carotid‐femoral pulse wave velocity, estimated pulse wave velocity (ePWV) has been confirmed to independently predict the cardiovascular events, but the association between ePWV and heart failure has not been well confirmed. Therefore, we performed this cohort study to evaluate the association between ePWV and risk of new‐onset heart failure. Methods and results A total of 98 269 employees (mean age: 51.77 ± 12.56 years, male accounted for 79.9%) without prior heart failure who participated in the 2006–2007 health examination were selected as the observation cohort, with an average follow‐up of 13.85 ± 1.40 years. Area under the receiver operator characteristic curve (AUC) of ePWV was calculated in prediction of heart failure. The adjusted Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. The category‐free net reclassification index (NRI) was calculated to evaluate the reclassification performance of cardiovascular risk models after adding ePWV. The AUC of ePWV was 0.74 in prediction of heart failure. After adjusting for the traditional cardiovascular risk factors except for age and blood pressure, the risk of new‐onset heart failure increased by 35% [hazard ratio (HR): 1.35, 95% confidence interval (CI): 1.33–1.37] for each 1 m/s increase in ePWV. Subgroup analysis showed that ePWV was significantly associated with incident heart failure regardless of THE presence (HR: 1.33, 95% CI: 1.31–1.36, P

Abstract Background Drug shortage is a worldwide problem that seriously threatens public health. China released the most comprehensive list of key drug shortage monitoring varieties ever in 2022. We aim to analyze the attributes and characteristics of the medicines within the list to provide a reference for improving China’s supply security of shortage drugs. Methods We used public data to extract information on drug types, dosage forms, indications, classification of clinical uses, whether they were included in medical catalogs such as the National Essential Drugs, and the number of drug and active pharmaceutical ingredient (API) manufacturers. A descriptive statistical analysis was used. Results Of the 980 drugs on the list, 99.59% were chemicals and 92.65% were injectables. Drugs for blood and hematopoietic organs, the cardiovascular system, and the digestive tract and metabolism ranked among the top three shortages. Verification of the medical catalogs showed that 90.41% of the drugs belonged to the national essential drugs, 95.10% were medicare drugs, 2.55% were volume-based procurement drugs, and 14.70% were for rare diseases, and 42.04% were for children. In terms of drug supply capacity, 21.33% of drug approvals are less than 10, and there were even 26 drugs for exclusive production, close to 90% of manufacturers need to purchase APIs from outside. Among the 256 APIs included in the list, 152 APIs had less than 10 manufacturers, and there were even 5 APIs produced by only one enterprise nationwide. Conclusions The situation of drug shortages in China was severe and complex, with serious shortages of medicines adapted to basic medical and healthcare needs and clinically necessary medicines, and a need to improve the production capacity of drugs and the ability to supply APIs. We recommend strengthening drug monitoring and stockpiling and accelerating the approval of shortage drugs to improve drug supply security.

Objective: To evaluate the quality of dying and death among deceased patients with cancer in Shanghai from the perspective of healthcare providers. Methods: This cross-sectional study was conducted in Shanghai from April to July 2023. A convenience sample of 261 healthcare providers working at eight healthcare institutions participated. Each participant was asked to evaluate the quality of dying and death of one deceased patient who had been cared for recently using the Good Death Scale for patients in China (GDS-PCN). The scale included family companionship (eight items), dying with peace (six items), professional care (six items), preparation & no regrets (five items), maintaining dignity (four items), keeping autonomy (four items), and physical wellbeing (three items) seven dimensions, 36 items. Results: The total GDS-PCN score was 144.11 ± 17.86. The professional care dimension scored the highest (4.21 ± 0.58), whereas the preparation and no regret dimension scored the lowest (3.75 ± 0.70). Significant differences in the GDS-PCN scores were based on the healthcare institution grade, ward type, hospitalization duration, communication about the condition, treatment, and death-related topics with the healthcare provider, and decision-making style (P

Migrasomes are recently identified organelles that form at the ends or forks of retraction fibers (RFs) behind migrating cells and are expelled from the cell through cell migration. Migrasomes contain signaling molecules which are captured by surrounding cells along with migrasomes or released into the extracellular environment following the rupture of the migrasomes. Finally, through the action of these signaling molecules, migrasomes facilitate the entire process of information conveyance. In addition, migrasomes also serves as a “scavenger” by removing damaged mitochondria from the cell to ensure cellular viability. Thus, migrasomes play a pivotal role in the integration of temporal, spatial, specific chemical information and the clearance of cellular harmful substances, critical for grasping migrasomes’ functions. This review delves into the latest advancements in migrasomes research, covering aspects such as migrasomes’ discovery, distribution, structure and characteristics, genesis and regulation mechanisms, and their correlation with diseases. Additionally, we scrutinize the present investigational findings on migrasomes within the cancer domain, examining their potential impact on cancer and prospective research avenues.

Abstract Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device’s soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Abstract Long noncoding RNA MYLK antisense RNA 1 (MYLK‐AS1) is the crux in multiple diseases. Therefore, the purpose of this study was to investigate the possible mechanism of MYLK‐AS1. A total of 62 colon cancer (CC) specimens and paired adjacent normal tissues were collected, and the expression of MYLK‐AS1, microRNA (miR)‐101‐5p/cell division cycle 42 (CDC42) was detected. CC cell lines were transfected with MYLK‐AS1, miR‐101‐5p, CDC42‐related plasmids, and the biological functions and markers of epithelial‐mesenchymal transition (EMT) were analyzed. The binding relationship between MYLK‐AS1, miR‐101‐5p, and CDC42 was evaluated. In CC tissues and cell lines, MYLK‐AS1 and CDC42 were highly expressed, and miR‐101‐5p was lowly expressed. Inhibition of MYLK‐AS1 or upregulation of miR‐101‐5p can inhibit CC cell growth and EMT. miR‐101‐5p inhibited CDC42/N‐wasp axis activation in CC cells by targeting CDC42. Knockdown of CDC42 or upregulation of miR‐101‐5p partially reversed the effects caused by upregulation of MYLK‐AS1. MYLK‐AS1, which is significantly upregulated in CC, may be a molecular sponge for miR‐101‐5p, and MYLK‐AS1 promotes the activation of the CDC42/N‐wasp axis in CC cells by targeting CDC42 through miR‐101‐5p, which in turn promotes tumor development. MYLK‐AS1 may be a potential biomarker and target for CC therapy.

Abstract Metabolic dysfunction‐associated steatohepatitis (MASH) is the severe form of non‐alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin‐derived peptide ALY688 (ALY688‐SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell‐derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High‐fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688‐SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688‐SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin‐like signaling, including the AMP‐activated protein kinase and p38 mitogen‐activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688‐SR in mice did not influence body weight but significantly ameliorated CDAHF‐induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688‐SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro‐inflammatory and pro‐fibrotic genes as demonstrated by transcriptomic analysis. ALY688‐SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin‐mediated signaling.

Since 2019, the Ministry of Natural Resources has comprehensively promoted the research and development of universal equipment and the automatic monitoring and forewarning of geological hazard. As of June 2023, it has been applied to 55 000 potential points of geological hazard in 17 key geological hazard prevention provinces, and the national geological hazard monitoring and forewarning system has entered a rapid development stage. At present, the system receives more than 10 million monitoring data every day, and has made positive progress in massive data storage management, parallel processing of time series data, intelligent analysis of big data and multi-parameter risk early warning. However, there are many challenges in data security of the system, especially in data consistency, data tamper resistance and system reliability. On the basis of systematic research on the characteristics of the blockchain technology and its typical application in related fields, this paper proposes a “trusted data flow” technology based on distributed ledger and consensus mechanism, according to which the overall framework of “blockchain + NRWSL” is formed, and a prototype system is established. The test data show that the improved system can solve the problem of data inconsistency between provinces and Ministry of Natural Resources, identify and prevent illegal data tampering, ensure the stable operation of the system under multi-node failure conditions, and the overall performance loss of the system is less than 20%. The research results provide technical methods for the application of blockchain technology to geological hazard risk early warning systems at all levels in China, and also provide top-level design ideas for improving the security of geological hazard monitoring data and the early warning system.

Abstract The electrochemical reduction of carbon dioxide to formic acid is a promising pathway to improve CO2 utilization and has potential applications as a hydrogen storage medium. In this work, a zero-gap membrane electrode assembly architecture is developed for the direct electrochemical synthesis of formic acid from carbon dioxide. The key technological advancement is a perforated cation exchange membrane, which, when utilized in a forward bias bipolar membrane configuration, allows formic acid generated at the membrane interface to exit through the anode flow field at concentrations up to 0.25 M. Having no additional interlayer components between the anode and cathode this concept is positioned to leverage currently available materials and stack designs ubiquitous in fuel cell and H2 electrolysis, enabling a more rapid transition to scale and commercialization. The perforated cation exchange membrane configuration can achieve >75% Faradaic efficiency to formic acid at

Abstract Background The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM). Method A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed. Results First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD. Conclusions NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.

Rainfall, especially local concentrated heavy rainfall, is one of the major factors triggering sudden geological hazards such as landslides and debris flow. According to historical disaster statistics in China, locally short-term concentrated heavy rainfall is the primary triggering factor for debris flows, accounting for approximately 70% of the total number of landslides. Recent alterations in seasonal rainfall patterns, with accelerated spring floods and plum rain in southern China, as well as delayed autumn rain in the northern regions, have led to an increase in geological disasters, expanded risk-prone areas, and prolonged risk management periods. Therefore, conducting rainfall monitoring is of great significance for landslides and debris flow early warning and prediction. To ensure precise early warnings and predictions, the accuracy, sensitivity, stability, and scientifically grounded installation of rainfall monitoring equipment are prerequisites. This study, comparing two types of rain gauges-- tipping bucket and piezoelectric—in terms of measurement principles, technical specifications, installation methods, and operational maintenance, conducted both indoor simulated rainfall experiments and field tests within complex scenes. The results reveal that the piezoelectric rain gauge maintains an error range within 4%. These findings highlight that in the context of complex geological hazard monitoring scenarios, the piezoelectric rain gauge proves more suitable than the tipping bucket rain gauge, regardless of measurement range, accuracy, installation, or post-installation maintenance considerations

Abstract The use of multiple cost-effectiveness thresholds in pharmacoeconomic evaluation is a hotly debated topic in the international academic community. This study analyzed and discussed thresholds in the context of pharmacoeconomic evaluation and reimbursement decision-making. We suggest that the thresholds inferred from reimbursement decisions should be distinguished from cost-effectiveness threshold in pharmacoeconomic evaluation. Pharmacoeconomic evaluations should adopt a fixed threshold, which should not vary with the subjects evaluated. This would help avoid the invitation of numerous cost-effectiveness thresholds for a specific drug, an exceptional disease, a type of innovation, or a certain level of malignancy, which misleads economic evaluation adopting restless changing standards and making pharmacoeconomic evaluation and decision-making more complex and contradictory.

Freeze–thaw damage significantly contributes to the degradation of concrete structures. A critical precondition for concrete to experience frost damage is reaching its critical saturation level. This study conducted freeze–thaw experiments on concrete specimens under both open and sealed moisture conditions to elucidate the mechanisms of freeze–thaw damage and the pivotal role of moisture. The research assessed concrete’s water absorption, ultrasonic pulse velocity, and compressive strength under restricted water conditions to study damage accumulation patterns. The findings indicate that implementing water limitation measures during freeze–thaw cycles can regulate concrete’s water absorption rate, reduce the loss of ultrasonic pulse velocity, and minimize strength degradation, with an observed strength increase of up to 36.22%. Consequently, these measures protect concrete materials from severe frost damage. Furthermore, a predictive model for concrete freeze–thaw deterioration was established based on regression analysis and relative dynamic modulus theory, confirming the critical role of water limitation in extending the service life of concrete structures in cold regions.

The superpixel usually serves as a region-level feature in various image processing tasks, and is known for segmentation accuracy, spatial compactness and running efficiency. However, since these properties are intrinsically incompatible, there is still a compromise within the overall performance of existing superpixel algorithms. In this work, the property constraint in superpixels is relaxed by in-depth understanding of the image content, and a novel two-stage superpixel generation framework is proposed to produce content-aware superpixels. In the global processing stage, a diffusion-based online average clustering framework is introduced to efficiently aggregate image pixels into multiple superpixel candidates according to color and spatial information. During this process, a centroid relocation strategy is established to dynamically guide the region updating. According to the area feature in manifold space, several superpixel centroids are then split or merged to optimize the regional representation of image content. Subsequently, local updating is adopted on pixels in those superpixel regions to further improve the performance. As a result, the dynamic centroid relocating strategy offers online averaging clustering the property of content awareness through coarse-to-fine label updating. Extensive experiments verify that the produced superpixels achieve desirable and comprehensive performance on boundary adherence, visual satisfactory and time consumption. The quantitative results are on par with existing state-of-the-art algorithms in terms with several common property metrics.

Objective:Since 2016, China has successively implemented Accelerated Drug Marketing Registration Procedures (ADMRPs) for drugs, including Breakthrough Therapy Drug (BTD), Conditional Approval (CA), and Priority Review and Approval (PRA), which have played an important role in promoting the development and review of clinically urgently needed drugs. In this study, we focused on the antineoplastic and immunomodulating agents approved for marketing through ADMRPs, to provide a reference for promoting the formation of a stable and mature regulatory system for the review and approval of antineoplastic drugs and immunomodulating agents in China.Methods:Reviewed the National Medical Products Administration (NMPA) drug review reports for the years 2016–2022 and screened the antineoplastic and immunomodulating agents approved through ADMRPs. Then, with the help of the NMPA website and the Yaozhi Database, two researchers independently queried and entered the detailed information of the selected drugs, and checked with each other. The attribute classification and main characteristics of the drugs were then analyzed with descriptive statistics to obtain the trend of drug types, drug review and approval status, and timeliness.Results:A total of 206 antineoplastic and immunomodulating agents were approved for marketing through five accelerated marketing registration procedures (or procedure combinations), with the average review time shortened by about 81 days. Among them, imported drugs accounted for a larger proportion, the most drugs for treating non-small cell lung cancer and lymphoma, and the largest number of PD-1/PDL-1 inhibitors, but pediatric drugs and rare disease drugs accounted for a smaller proportion.Conclusion:ADMRPs can promote the accessibility of antineoplastic and immunomodulating agents in China and safeguard the life and health rights of more patients. Nevertheless, it is necessary to pay attention to the expansion of the types of indications for medicines and to increase the development of drugs that are urgently needed by a small number of patients.

BackgroundIn November 2015, China launched a pilot program for its Drug Marketing Authorization Holder (MAH) system, aiming to integrate production and research and development resources to spur drug innovation. While many scholars have examined the theoretical relationship between the MAH system and pharmaceutical manufacturing innovation, empirical studies have been scarce.MethodsThis study uses inter-provincial panel data on China's pharmaceutical manufacturing industry from 2009 to 2019, along with synthetic control methods, to offer a robust analysis of the impact of the MAH paradigm on innovation quality in pilot provinces. We treat the 2015 MAH system implementation in ten provinces as a natural experiment and account for the mediating effects of R&D investments, allowing us to discern the underlying mechanisms.ResultsOur findings demonstrate a significant positive effect of China's MAH system on innovation quality in the pharmaceutical manufacturing industry. Specifically, the system is most effective in Jiangsu, Guangdong, and Shandong provinces. We also identify R&D investments as playing a mediating role in facilitating the favorable impact of the MAH system on innovation quality.ConclusionOur study highlights the crucial importance of the MAH system in promoting innovation quality in China's pharmaceutical manufacturing industry, providing vital empirical support for its adoption and further enhancement. This research also offers practical insights for policymakers and R&D decision-makers in the pharmaceutical sector.

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor β (TGF-β) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Abstract In the setting of the increasing density of exploration wells, and the decreasing scale and increasing difficulty of discovering Jurassic paleogeomorphology reservoirs, it is urgent to deepen the fine depiction of pre-Jurassic paleogeomorphology features and to analyze their controlling effect on reservoirs. Based on abundant logging data combined with indoor microscopic observation and experimental testing, the paper applies the theory of reservoir configuration analysis for the first time to the single-channel period division of the pre-Jurassic Meng-Shaan paleochannel which deposited with the braided channel sand bodies. Meanwhile, it reveals the controlling effect of hydrocarbon accumulation and the distribution characteristics of the Yan 101 reservoir as ' paleogeomorphology and sedimentary facies combination' to determine the type, 'migration channel' to determine the distributing range, and 'low-amplitude structure' to determine the trap in the study area, and also the reservoir accumulation modes in different channel ranges have established. In conclusion, the single-channel boundary of the Meng-Shaan paleochannel in different periods controls the path of oil and gas migration, thus controlling the distribution range and reservoir type of the Yan 10 reservoir. Moreover, depending on the production data we derived that it should prefer the composite trap reservoir of the Fuxian period and the Yan 102 period, as well as the structural reservoir on the periphery of the Yan 102 period single-channel for the further exploration of the Yan 10 paleogeomorphology reservoirs within the development range of the Meng-Shaan ancient river. In particular, the lithologic trap reservoirs within the Fuxian period channel and the Meng-Shaan main channel, such as the reservoirs of the 'Source' of the secondary channel type and the paleochannel type, which could as a replacement accumulation model for increasing reserves and production.

Abstract A representative class of kagome materials, AV3Sb5 (A = K, Rb, Cs), hosts several unconventional phases such as superconductivity, $${{\mathbb{Z}}}_{2}$$ Z 2 non-trivial topological states, and electronic nematic states. These can often coexist with intertwined charge-density wave states. Recently, the discovery of the isostructural titanium-based single-crystals, ATi3Bi5 (A = K, Rb, Cs), which exhibit similar multiple exotic states but without the concomitant charge-density wave, has opened an opportunity to disentangle these complex states in kagome lattices. Here, we combine high-resolution angle-resolved photoemission spectroscopy and first-principles calculations to investigate the low-lying electronic structure of RbTi3Bi5. We demonstrate the coexistence of flat bands and several non-trivial states, including type-II Dirac nodal lines and $${{\mathbb{Z}}}_{2}$$ Z 2 non-trivial topological surface states. Our findings also provide evidence for rotational symmetry breaking in RbTi3Bi5, suggesting a directionality to the electronic structure and the possible emergence of pure electronic nematicity in this family of kagome compounds.

Abstract Background Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed to replace non-alcoholic fatty liver disease (NAFLD) to emphasize the pathogenic association between fatty liver disease and metabolic dysfunction. Studies have found that MAFLD independently increases the risk of myocardial infarction and stroke. But the relationship between MAFLD and heart failure (HF) is not fully understood. Objectives This study aimed to explore the association between MAFLD and the risk of HF. Methods The study included 98,685 participants without HF selected from the Kailuan cohort in 2006. All participants were divided into non-MAFLD group and MAFLD group according to MAFLD diagnostic criteria. After follow-up until December 31, 2020, the Cox regression analysis model was used to calculate the effect of MAFLD on the risk of HF. Results During the median follow-up of 14.01 years,3260 cases of HF were defined, the HF incidence density of non-MAFLD group and MAFLD group was 2.19/1000pys and 3.29/1000pys, respectively. Compared with the non-MAFLD group, participants with MAFLD had an increased risk of HF (HR: 1.40, 95% CI: 1.30–1.50); in addition, an exacerbation of fatty liver disease was associated with an increased risk of HF in people with MAFLD. We also observed a higher risk of HF among the different metabolic dysfunction of MAFLD in people with both fatty liver disease and type 2 diabetes (HR, 1.95; 95% CI, 1.73–2.20). Conclusions Our findings suggest that the risk of HF was significantly increased in participants with MAFLD, and an exacerbation of fatty liver disease was associated with an increased risk of HF in people with MAFLD. In addition, we should pay more attention to people with MAFLD with type 2 diabetes.

Abstract. Background:. Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. Methods:. Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy (n = 102) or chemotherapy (n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. Results:. Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs. 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs. 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs. 7.0 months, P

Abstract Background Immune checkpoint inhibitors (ICI)-based combination strategies have improved the survival outcomes in advanced non-small cell lung cancers; however, data regarding their efficacy remains limited for uncommon histological types, including large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC). Methods We retrospectively analyzed a total of 60 patients with advanced LCC and LCNEC – 37 treatment-naïve and 23 pre-treated – who received pembrolizumab with or without chemotherapy. Treatment and survival outcomes were analyzed. Results Of the 37 treatment-naïve patients who received first-line pembrolizumab combined with chemotherapy, the 27 patients with LCC had an overall response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 88.9% (24/27); whereas 10 patients with LCNEC had an ORR of 70% (7/10) and DCR of 90% (9/10). The median progression-free survival (mPFS) was 7.0 months (95% confidence intervals [CI]: 2.2–11.8) and median overall survival (mOS) was 24.0 months (95%CI: 0.0–50.1) for first-line pembrolizumab plus chemotherapy of LCC (n = 27), whereas mPFS was 5.5 months (95%CI: 2.3–8.7) and mOS was 13.0 months (95%CI: 11.0–15.0) for first-line pembrolizumab plus chemotherapy of LCNEC (n = 10). Of the 23 pre-treated patients who received subsequent-line pembrolizumab with or without chemotherapy, mPFS was 2.0 months (95% CI: 0.6–3.4) and mOS was 4.5 months (95% CI: 0.0–9.0) for LCC and mPFS was 3.8 months (95% CI: 0.0–7.6) and mOS was not reached for LCNEC. Conclusion Our study provides real-world clinical evidence of the anti-tumor activity of pembrolizumab plus chemotherapy in advanced LCC and LCNEC, indicating that this regimen could serve as a treatment option, particularly as first-line therapy, for improving the survival outcomes of patients with these rare histological subtypes of lung cancer. Trial registration NCT05023837(ESPORTA, 27/08/2021).

Aiming at the problem that it is difficult to achieve the real-time and accurate measurement of the bolter miner’s position and orientation during the excavation process in coal mines, which leads to the difficulty in achieving directional excavation, a guidance method for bolter miner based on dual-screen visual target is proposed. Using two vertically installed light-sensitive imaging screens to form the dual-screen visual target surfaces and the indication laser emitted by the laser instrument presents light spots on the front and rear target surfaces. Combining with the visual measurement, high-precision raster calibration and other technology are applied to establish the mapping relationship of the spot centroid between 2D-3D coordinates, which is used to form the point cloud data of the coordinates. Based on the principle of grid indexing, coordinate transformation and Euler angle solving, combining with the biaxial inclinometer at the bottom of target to obtain the bolter miner body’s real-time position and orientation, the key points’ horizontal/vertical deviations relative to the roadway axis are calculated, which can provide data support for deviation correction during the excavation process. The off-target problem of the system is analyzed by constructing a mathematical model. Meanwhile, the effectiveness of the guidance method is verified by building an experimental platform. The experimental results indicate that this method can achieve a precision measurement of six-degrees-of-freedom spatial pose for the machine body. When the measurement distance is 9 m, the repeatability measurement precision of the yaw angle is better than 0.01º and the error of absolute measurement is less than 0.05º. Within the measurement range of 15−40 m, which uses the total station and mining laser to set the planning line, the measurement errors of key points’ horizontal/vertical deviations are less than 5 mm and 15 mm, respectively. The guiding system developed based on this method has also been successfully applied to the underground roadway excavation in coal mine, which fully meets the requirements of underground roadway excavation and the positioning of the machine body’s key points. The error characteristic of the guiding method is independent of the test distance. Also, all optical measurement functions involved in the method are realized inside the target, which can effectively shield the influence of the underground complex environment for the measurement function, and greatly improve the capacity of anti-dust interference in field application.

IntroductionIn March 2016, the Chinese government officially launched a nationwide consistency evaluation of the quality and efficacy of generic drugs.MethodsThis paper conducted an empirical study using the Difference-in-Differences method to explore the effect of this policy on the innovation quality of China’s pharmaceutical manufacturing industry and further analyzed the underlying mechanism of action.ResultsThe results of the study show that the generic consistency evaluation policy has a significant promotion effect on the innovation quality of China’s pharmaceutical manufacturing industry, and the promotion effect is the largest for non-state-owned enterprises and enterprises in the central region; in addition, the intensity of R&D capital investment and R&D personnel investment which play a mediating role.DiscussionTherefore, we should fully recognize the positive effect of generic drug consistency evaluation policy on improving the innovation quality of the pharmaceutical manufacturing industry and pay attention to the necessity of regional coordination and unification in policy implementation and the formulation of supporting policy tools. This study provides empirical evidence for the implementation effect of the generic drug consistency evaluation policy, which can provide an essential reference for the further improvement of the procedure and the R&D decision-making of pharmaceutical enterprises.

Background: Clinical trials have been widely recognized as an effective treatment approach by physicians and cancer patients alike. Physicians’ evaluations suggest that many patients are likely to continue experiencing benefits from extended dosing of investigational new drugs even after withdrawing from clinical trials.Objective: Given the uncertainty surrounding the efficacy and safety of investigational new drugs, it is essential to continually assess the benefits of extended dosing for patients.Methods: The trial group for this study comprised patients who requested extended dosing after withdrawing from clinical trials at Hunan Cancer Hospital between 2016 and 2020. The control group consisted of patients who received conventional treatment and were enrolled in a 1:1 ratio. Follow-up assessments were conducted every 3 months for both groups, and included monitoring of patients’ health status, survival time, disease control or remission, treatment modalities received, and medical costs.Results: A total of twenty-three patient pairs were successfully matched for this study. The Ethics Committee approved extended dosing for all patients in the trial group, with an average gap period of 16.48 days between their withdrawal from clinical trials and continuous access to the investigational drugs. The median overall survival for patients after withdrawal from clinical trials was 17.3 months in the extended dosing group and 12.9 months in the control group, with no significant difference observed between the two groups (p > 0.250). The median total cost of treatment after the previous clinical trial was 38,006.76 RMB, of which the median cost of therapeutic drugs for conventional treatment was 15,720 RMB, while extended dosing was provided free of charge.Conclusion: Extended dosing can indeed provide benefits, including survival benefits and economic benefits, to cancer patients after their withdrawal from clinical trials and will clinically present an additional treatment option for patients.

A novel type of underwater pier reinforcement technology was proposed. A non-dispersive mortar (NDM) and stainless steel tube (SS) were adopted to strengthen an underwater concrete column. The strengthened column takes advantage of the good adhesion of NDM and the corrosion resistance of SS. The NDM pouring and curing processes were both conducted in an underwater environment, which simulated the environment of underwater bridge pier reinforcement. An axial compression test was carried out on 16 strengthened columns and 3 unconfined concrete columns to explore the reinforcement effect of SS thickness and NDM type, including the 2–6 mm thickness of SS, the epoxy-based NDM, and the cement-based NDM. The test results indicated that all the specimens showed extrusion expansion failure. The increase in the thickness of SS resulted in a significant improvement in the load capacity of the specimens, and the stress-strain curves showed the strengthening stage and softening stage according to the confinement factor of the SS thickness. After adding cement-based NDM and epoxy-based NDM, the strength of the specimens increased by 6.2–21.4 % and 8.8–31.5 %, respectively. In the case of the same thickness of SS, cement-based NDM showed a better reinforcement effect. The stress-strain curves for the strengthened columns can be divided into three stages. Calculation models were proposed to predict the full stress-strain curves, including the calculation method of the capacity. The calculated results are in good agreement with the experimental data.

Summary: Major histocompatibility complex (MHC) class II-reactive CD8+ T cells are found in humans and animals, but little is known about their identity, development, and function. In this study, we discover a group of CD8+ T cells reactive to both MHC class I and II molecules in MHC class II-deficient mice. We clone their T cell receptors (TCRs) and analyze their development and function. In wild-type animals, thymocytes bearing those TCRs are purged by negative selection. In the absence of MHC class II, they develop into mature CD8+ T cells. When encountering MHC class II in the periphery, they undergo robust activation and proliferation, attack self-tissues, and cause lethal autoimmune diseases. In adoptive T cell therapy, those CD8+ T cells are able to efficiently control MHC class II-expressing tumors. This study opens the door to investigation of dual-reactive CD8+ T cells, their development and selection in the thymus, and the perils and promises when their normal development and selection are compromised.

Abstract Background In addition to high vaccination levels, COVID-19 control requires uptake and continued adherence to personal hygiene and social distancing behaviors. It is unclear whether residents of a city with successive experience in worldwide pandemics such as SARS, would quickly adopt and maintain preventive behaviors. Methods A population-based, longitudinal telephone survey was conducted between in first local wave of the COVID-19 pandemic (April 2020) and third local wave (December 2020) (n = 403). The study examined factors associated with personal hygiene and social distancing behavior fatigue, as measured by reduced adherence. Results Over 9 months, face mask use increased (96.5–100%, p

Abstract Purpose This study evaluated the performance of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) in patients without LI-RADS-defined hepatocellular carcinoma (HCC) risk factors (RF−). Methods Patients with LI-RADS-defined HCC risk factors (RF+) and RF− were enrolled in a retrospective study. Additionally, a prospective evaluation in the same centre was performed as a validation set. The diagnostic performances of the CEUS LI-RADS criteria in RF+ and RF− patients were compared. Results Overall, we included 873 patients in the analyses. In the retrospective study, the LI-RADS category (LR)-5 specificities for diagnosing HCC did not differ between the RF+ and RF− groups (77.5% [158/204] vs 91.6% [196/214], P = 0.369, respectively). However, the positive predictive value (PPV) of CEUS LR-5 was 95.9% (162/169) and 89.8% (158/176) in the RF+ and RF− groups, respectively (P = 0.029). In the prospective study, the PPV of LR-5 for HCC lesions was significantly higher in the RF+ group than in the RF− group (P = 0.030). The sensitivity and specificity did not differ between the RF+ and RF− groups (P = 0.845 and P = 0.577, respectively). Conclusions The CEUS LR-5 criteria shows clinical value for diagnosis of HCC in patients with and without risks.

Abstract Small cell lung cancer (SCLC) is an aggressive malignancy associated with poor prognosis. Metastasis to sites outside the chest at the time of initial diagnosis, such as bone, brain, and liver metastasis have been found in most SCLC patients. Iris metastases from SCLC have rarely been previously reported, and often cause eye pain and blindness in patients. Here, we report a patient with SCLC who presented with iris metastasis in the right eye and metastasis in the left adrenal gland due to disease progression on first‐line therapy, which subsequently caused pain and blindness in the right eye. The patient was treated with second‐line irinotecan combined with anlotinib and atezolizumab and did not receive any local treatment in the right eye. After only one cycle of treatment, the iris metastases in the right eye were smaller than before, and the visual acuity in the right eye recovered. At the same time, her left adrenal metastases were also significantly smaller than before. Our case suggests that systemic therapy with effective treatment options can similarly improve iris metastases in patients.

Abstract Background Physical activity (PA) can be affected by extreme temperatures, however fewer studies have identified factors impacting this relationship. This study sought to identify factors associated with changes of outdoor PA during extreme cold/heat events in a sub-tropical Chinese urban population, including factors of sociodemographic, health conditions, temperature-related awareness and attitude, and protective behaviours. Methods Two telephone surveys were conducted a week after extreme cold/heat events in 2016 and 2017 among a cohort of Hong Kong residents over age 15. Data was collected on self-reported changes in outdoor PA level during the periods of extreme temperatures, health status, comorbidities, sociodemographic, and temperature-related awareness, and behavioural variables. We conducted multivariable logistic regression analyses to assess predictors of change in outdoor PA over the two extreme temperature events. Results and Conclusion: Among 435 participants (42.8% response rate), over a third of the participants reported decreased outdoor PA level in extreme temperature events, while 10% reported an increase in extreme heat. Self-reported cardiovascular diseases were associated with decreased PA level in extreme cold, while hypertension was associated with unchanged/increased PA level in extreme heat. These results suggest physical activity to be an important consideration in the understanding of climate change-and-health pathways and meriting further research.

Green investment (GI) has great potential to reach China's 'double carbon' target. However, it is still unknown what factors will govern the impact of GI on carbon emissions. This research relaxes the homogeneity and linearity assumed in traditional empirical models and adopts a newly developed partially linear functional-coefficient model to estimate the specific response function of GI on carbon emissions under regional heterogeneity. The results indicate that the role of GI plays a relatively greater role in the western and central regions than in the eastern regions. This highlights the latecomer advantage of the central and western regions under the 'double carbon' target. The beneficial effect of GI on carbon emission intensity is only apparent once the province's economic development level exceeds a certain threshold. For provinces with low GDP per capita, it is recommended to prioritize economic development. When the logarithm of the province's GDP per capita is higher than 9.70, we encourage strong GI. As the industrial structure continues to upgrade, the marginal effect of GI on carbon emissions will continue to increase after a key inflection point.

Abstract Background Ki-67 is widely used as a proliferative and prognostic factor in HCC. This study aimed to analyze the relationship between dynamic contrast-enhanced ultrasonography (DCE-US) parameters and Ki-67 expression. Methods One hundred and twenty patients with histopathologically confirmed HCC who underwent DCE-US were included in this prospective study. Patients were classified according to the Ki-67 marker index into low Ki-67 (

Abstract Background Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associated mouse prone 10 (SAMP10) model, with a special focus on the role of growth differentiation factor 11 (GDF‐11). Methods Nine‐week‐old male SAMP10 mice were randomly assigned to a non‐YBMT group (n = 6) and a YBMT group (n = 7) that received the bone marrow of 8‐week‐old C57BL/6 mice. Results Compared to the non‐YBMT mice, the YBMT mice showed the following significant increases (all P < 0.05 in 6–7 mice): endurance capacity (>61.3%); grip strength (>37.9%), percentage of slow myosin heavy chain fibres (>14.9–15.9%). The YBMT also increased the amounts of proteins or mRNAs for insulin receptor substrate 1, p‐Akt, p‐extracellular signal‐regulated protein kinase1/2, p‐mammalian target of rapamycin, Bcl‐2, peroxisom proliferator‐activated receptor‐γ coactivator (PGC‐1α), plus cytochrome c oxidase IV and the numbers of proliferating cells (n = 5–7, P < 0.05) and CD34+/integrin‐α7+ muscle stem cells (n = 5–6, P < 0.05). The YMBT significantly decreased the levels of gp91phox, caspase‐9 proteins and apoptotic cells (n = 5–7, P < 0.05) in both muscles; these beneficial changes were diminished by the blocking of GDF‐11 (n = 5–6, P < 0.05). An administration of mouse recombinant GDF‐11 improved the YBMT‐mediated muscle benefits (n = 5–6, P < 0.05). Cell therapy with young bone marrow from green fluorescent protein (GFP) transgenic mice exhibited GFP+ myofibres in aged muscle tissues. Conclusions These findings suggest that YBMT can prevent muscle wasting and dysfunction by mitigating apoptosis and proliferation via a modulation of GDF‐11 signalling and mitochondrial dysfunction in SAMP10 mice.

Abstract Background This study aims to investigate the potential association of peripheral inflammatory blood cell parameters with the incidence and progression of chronic kidney disease (CKD) in patients with diabetes. Methods The cross‐sectional study included 1192 subjects with diabetes derived from one center. The cohort study included 2060 subjects with diabetes derived from another two centers followed up for 4 years. Logistic regression and Cox proportional hazards models were used to evaluate the association of peripheral inflammatory blood cell with CKD. Results In the cross‐sectional study, neutrophil count performed best as an independent risk factor for CKD (odds ratio 2.556 [95% confidence interval 1.111, 5.879]) even after 1:1 case–control matching for age, gender, history of high blood pressure and duration of diabetes. Spline regression revealed a significant linear association of CKD incidence with continuous neutrophil count in excess of 3.6 × 109/L. In the cohort study, subjects were grouped based on tertile of neutrophil count and neutrophil‐to‐lymphocyte ratio. Cox regression analysis results showed that only neutrophil count was independently associated with CKD progression (the highest group vs. the lowest group, hazard ratio 2.293 [95% confidence interval 1.260, 4.171]) after fully adjusting for potential confounders. The cumulative incidence of CKD progression in patients with diabetes gradually increased with increasing neutrophil count (53 (7.7%) subjects in the lowest group vs. 60 (8.2%) in the middle group vs. 78 (12.2%) in the highest group). Conclusions This study suggested that neutrophil count is an independent risk factor for progression of CKD in patients with diabetes.

The semantic segmentation of drone LiDAR data is important in intelligent industrial operation and maintenance. However, current methods are not effective in directly processing airborne true-color point clouds that contain geometric and color noise. To overcome this challenge, we propose a novel hybrid learning framework, named SSGAM-Net, which combines supervised and semi-supervised modules for segmenting objects from airborne noisy point clouds. To the best of our knowledge, we are the first to build a true-color industrial point cloud dataset, which is obtained by drones and covers 90,000 m2. Secondly, we propose a plug-and-play module, named the Global Adjacency Matrix (GAM), which utilizes only few labeled data to generate the pseudo-labels and guide the network to learn spatial relationships between objects in semi-supervised settings. Finally, we build our point cloud semantic segmentation network, SSGAM-Net, which combines a semi-supervised GAM module and a supervised Encoder–Decoder module. To evaluate the performance of our proposed method, we conduct experiments to compare our SSGAM-Net with existing advanced methods on our expert-labeled dataset. The experimental results show that our SSGAM-Net outperforms the current advanced methods, reaching 85.3% in mIoU, which ranges from 4.2 to 58.0% higher than other methods, achieving a competitive level.

Abstract Background Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in aging-related degenerative disease. Methods and results We investigated the efficacy of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on sarcopenia-related skeletal muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice. We randomly assigned 24-week-old male SAMP10 mice to a UC-MSC treatment group and control group. At 12 weeks post-injection, the UC-MSC treatment had ameliorated sarcopenia-related muscle changes in performance, morphological structures, and mitochondria biogenesis, and it enhanced the amounts of proteins or mRNAs for myosin heavy chain, phospho-AMP-activated protein kinase, phospho-mammalian target of rapamycin, phospho-extracellular signal-regulated kinase1/2, peroxisome proliferator-activated receptor-γ coactivator, GLUT-4, COX-IV, and hepatocyte growth factor in both gastrocnemius and soleus muscles, and it reduced the levels of proteins or mRNAs for cathepsin K, cleaved caspase-3/-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and gp91phox mRNAs. The UC-MSC treatment retarded mitochondria damage, cell apoptosis, and macrophage infiltrations, and it enhanced desmin/laminin expression and proliferating and CD34+/Integrin α7 + cells in both types of skeletal muscle of the SAMP10 mice. In vitro, we observed increased levels of HGF, PAX-7, and MoyD mRNAs at the 4th passage of UC-MSCs. Conclusions Our results suggest that UC-MSCs can improve sarcopenia-related skeletal muscle atrophy and dysfunction via anti-apoptosis, anti-inflammatory, and mitochondrial biogenesis mechanisms that might be mediated by an AMPK-PGC1-α axis, indicating that UC-MSCs may provide a promising treatment for sarcopenia/muscle diseases.

BackgroundAs health systems across the world respond to the coronavirus disease 2019 (COVID-19), there is rising concern that patients without COVID-19 are not receiving timely emergency care, resulting in avoidable deaths. This study examined patterns of self-reported health service utilization, their socio-demographic determinants and association with avoidable deaths during the COVID-19 outbreak. MethodsA cross-sectional telephone survey was conducted between March 22 and April 1, 2020, during the peak rise in confirmed COVID-19 cases in Hong Kong. Cantonese-speaking Hong Kong residents over 18-years-old were recruited using a computerised random digital dialling (RDD) system. The RDD method used stratified random sampling to ensure a representative sample of the target population by age, gender, and residential district. A structured self-reported questionnaire was used. ResultsOut of 1738 placed calls, 765 subjects responded to the questionnaire (44.0% response rate). The factors associated with avoiding medical consultation included being female (37.2% vs. 22.5%, P < .001), married (32.8% vs. 27%, P = .044), completing tertiary education (35.3% vs. 27.7% (secondary) vs. 14.8% (primary), P = .005), and those who reported a “large/very large” impact of COVID-19 on their mental health (36.1% vs 30.5% (neutral) vs. 19.7% (very small/small), P = .047) using logistic regression analysis. ConclusionMarried females with both higher educational attainment and concern about COVID-19 were associated with avoiding healthcare services. Timely public communication to encourage and promote early health seeking treatment even during extreme events such as pandemics are needed.

Abstract Background Atherosclerotic cardiovascular diseases (CVD) is the leading cause of death in diabetes, but the full range of biomarkers reflecting atherosclerotic burden and CVD risk in people with diabetes is unknown. Metabolomics may help identify novel biomarkers potentially involved in development of atherosclerosis. We investigated the serum metabolomic profile of subclinical atherosclerosis, measured using ankle brachial index (ABI), in people with type 2 diabetes, compared with the profile for symptomatic CVD in the same population. Methods The Edinburgh Type 2 Diabetes Study is a cohort of 1,066 individuals with type 2 diabetes. ABI was measured at baseline, years 4 and 10, with cardiovascular events assessed at baseline and during 10 years of follow-up. A panel of 228 metabolites was measured at baseline using nuclear magnetic resonance spectrometry, and their association with both ABI and prevalent CVD was explored using univariate regression models and least absolute shrinkage and selection operator (LASSO). Metabolites associated with baseline ABI were further explored for association with follow-up ABI and incident CVD. Results Mean (standard deviation, SD) ABI at baseline was 0.97 (0.18, N = 1025), and prevalence of CVD was 35.0%. During 10-year follow-up, mean (SD) change in ABI was + 0.006 (0.178, n = 436), and 257 CVD events occurred. Lactate, glycerol, creatinine and glycoprotein acetyls levels were associated with baseline ABI in both univariate regression [βs (95% confidence interval, CI) ranged from − 0.025 (− 0.036, − 0.015) to − 0.023 (− 0.034, − 0.013), all p

Objective: To standardize the distress management of gastric cancer patients receiving chemotherapy, the adapted Cancer-related Distress Management Guidelines were implemented in nursing practice among gastric cancer patients receiving chemotherapy based on A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT). Methods: Based on the theoretical framework of CAN-IMPLEMENT, A multidisciplinary team was established, barriers and facilitators obstacles of guidelines implementation in medical oncology units were assessed, corresponding solutions were formulated, the guidelines implementation process was monitored, and implementation results were evaluated. Results: The multidisciplinary team developed review criteria, standardized work paths, assessment tools, training manuals for healthcare professionals, education manuals for patients and their caregivers. After guidelines implementation, the completion rate of the distress management record came up to 97.9% (189/193). From September 2017 to December 2018, the compliance of medical staff on most items in the audit checklist was improved, ranging from 57.1% (100/175) to 100.0% (193/193). The positive distress rate of gastric cancer patients receiving chemotherapy was decreased from 22.7% (32/141) to 9.3% (18/193) (P

Abstract Background Cachexia is a complicated metabolic disorder that is characterize by progressive atrophy of skeletal muscle. Cathepsin K (CTSK) is a widely expressed cysteine protease that has garnered attention because of its enzymatic and non‐enzymatic functions in signalling in various pathological conditions. Here, we examined whether CTSK participates in cancer‐induced skeletal muscle loss and dysfunction, focusing on protein metabolic imbalance. Methods Male 9‐week‐old wild‐type (CTSK+/+, n = 10) and CTSK‐knockout (CTSK−/−, n = 10) mice were injected subcutaneously with Lewis lung carcinoma cells (LLC; 5 × 105) or saline, respectively. The mice were then subjected to muscle mass and muscle function measurements. HE staining, immunostaining, quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and western blotting were used to explore the CTSK expression and IRS1/Akt pathway in the gastrocnemius muscle at various time points. In vitro measurements included CTSK expression, IRS1/Akt pathway‐related target molecule expressions, and the diameter of C2C12 myotubes with or without LLC‐conditioned medium (LCM). An IRS1 ubiquitin assay, and truncation, co‐immunoprecipitation, and co‐localization experiments were also performed. Results CTSK+/+ cachectic animals exhibited loss of skeletal muscle mass (muscle weight loss of 15%, n = 10, P 15%, n = 10, P 30%, n = 5, P

Heavy rainfall causes large volumes of freshwater and nutrient salts to flow from rivers into the sea. This leads to major changes in the ecological environment of estuarine waters in a short period of time. The responses of the estuarine hydro-environment become more complex with the concentrated construction of artificial structures, which is a major cause of marine ecological disasters. This paper considers the Tang Estuary in Qinhuangdao, where artificial structures (e.g., ports, artificial islands, and bridges) are concentrated, as a prototype with the weak tidal dynamic environment. A nested prototype of hydrodynamics and water quality was established using a Delft3D model, with coupled waves and flows. The model was used to simulate the spatial and ephemeral characteristics of the short-term responses of ecological environmental factors, such as dissolved inorganic nitrogen (DIN), nitrate-nitrogen (i.e., NO3-N), ammonium-nitrogen (NH4-N), and orthophosphate (i.e., PO4-P), to an episode of heavy rainfall in August 2022. The results showed that concentrations of DIN and NO3-N in the source areas remain high after the flooding process. The concentration recovered to normal values approximately 5.5 days after the flooding process. In contrast, NH4-N and PO4-P showed a response with ephemeral correspondence with the flooding process, and concentration recovery took only approximately 1 day. This paper proposes two short-term response modes of pollutant diffusion, which provide help in exploring the role of hydro-environmental changes in offshore algal hazards and the effect of permeable buildings on pollutant dispersion. This additionally provides possibilities with the forecasting of red tide and green tide, and for their prevention in the future.

Summary: The precise sequence control of polymer chain is an important research topic of polymer chemistry. Although some methods such as iterative synthesis and supramolecular polymerization have been developed to fabricate sequence-controllable polymer, it is still a great challenge to consecutively prepare multiple supramolecular polymers with different sequence structures. In this work, through the reasonable utilization of assembly motifs, we integrated multiple host-guest recognitions and metal coordination interactions to prepare different sequence-controlled supramolecular polymers by a multistep assembly strategy. This research provides inspiration for the design and preparation of supramolecular polymers with different sequence structures.

Importance: Brain–computer interface (BCI) decodes and converts brain signals into machine instructions to interoperate with the external world. However, limited by the implantation risks of invasive BCIs and the operational complexity of conventional noninvasive BCIs, applications of BCIs are mainly used in laboratory or clinical environments, which are not conducive to the daily use of BCI devices. With the increasing demand for intelligent medical care, the development of wearable BCI systems is necessary. Highlights: Based on the scalp-electroencephalogram (EEG), forehead-EEG, and ear-EEG, the state-of-the-art wearable BCI devices for disease management and patient assistance are reviewed. This paper focuses on the EEG acquisition equipment of the novel wearable BCI devices and summarizes the development direction of wearable EEG-based BCI devices. Conclusions: BCI devices play an essential role in the medical field. This review briefly summarizes novel wearable EEG-based BCIs applied in the medical field and the latest progress in related technologies, emphasizing its potential to help doctors, patients, and caregivers better understand and utilize BCI devices.

BackgroundThe unmet needs in treating acute myeloid leukemia(AML) promote us to look for more effective and less toxic therapies. In this study, we discovered that Yinzhihuang injection(YZHI), a traditional Chinese patent medicine for hepatitis treatment, suppressed the growth of AML cells.MethodAnti-proliferative activities of YZHI were measured by CCK-8 assay. Cell cycle arrest was evaluated by PI staining, and apoptosis was evaluated by annexin V/PI staining. To explore the cell cycle arrest and cell death mechanism induced by YZHI, we assessed a series of assays, including measurements of the protein expression and cellular ATP. The anti-tumor activity was further demonstrated in nude mice.ResultsFlow cytometric and biochemical analysis revealed that YZHI caused cell cycle arrest and induced apoptosis in the AML HL-60 cells. Mechanistically, YZHI activated AMPK by promoting phosphorylation of the kinase. The active AMPK negatively regulated the downstream target mTORC1, leading to the inhibition of cell proliferation and induction of apoptosis. Pretreatment with the AMPK inhibitor compound C rescued YZHI induced apoptosis and partially restored cell proliferation of HL-60. Consistent with the data in vitro, YZHI obviously suppressed subcutaneous xenograft growth in nude mice.ConclusionsIn a word, our data suggest that YZHI can be repurposed for the treatment of AML, which is worthy of further clinical evaluation.

Online reviews of consumers after purchasing drugs online reflect the factors affecting their satisfaction. How to understand customer satisfaction through online reviews and tapping their needs to improve satisfaction has become an urgent issue facing pharmaceutical e-commerce companies. Based on the online reviews of Alibaba Health Pharmacy, six representative OTC online medicines were selected for this study, including the following categories: tonics, anti-cold drugs, rheumatism and orthopaedic drugs, skin drugs, gastrointestinal drugs, vitamins, and calcium. By training and testing the LDA topic model, five potential topics are extracted as factors affecting customer satisfaction, including drug efficacy, drug cost performance, online customer service, logistics and transportation, and packaging. In this paper, Sentiment Analysis is used to process the review text to quantify the sentiment tendency of the review, and determine the evaluation scale value. Then, the random dominance among various drug factors is determined based on the Stochastic Dominance Rules. Finally, the PROMETHEE–Ⅱ method is used to determine the ranking value of the importance of each factor. The results suggest that the factors in different types of OTC drugs rank differently, which is also rationalized in this paper. This study provides a significant reference for improving customer satisfaction with pharmaceutical e-commerce.

The research on the recycling of discarded drugs has become an important direction of the green supply chain in China. Faced with the great challenge of recycling discarded drugs in China, it is necessary to make clear the behavior choice of each recycling subject. This paper constructs an evolutionary game model among government, drugs recycling companies and consumers, describes the evolutionary game process, and analyzes the influence of the gain of government, drug recycling enterprises and consumers on the evolutionary stable strategy trend. By using Matlab simulation software to simulate the evolution of tripartite behavior, the final result is obtained: The government's choice of a strong regulatory strategy has an important positive role in guiding the entire discarded drug recovery market. Consumer's choice of active participation strategy and enterprise's choice of active participation strategy are most beneficial to the healthy development of the discarded drug recovery market. This study provides some valuable theoretical support and reference for the national decision-making of discarded drug recovery, helps to solve the problem of discarded drug recovery, and provides theoretical support and policy-making recommendations for the ultimate achievement of sustainable development goals.