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Flos Carthami (FC) has a good therapeutic effect on chronic alcoholic liver injury (CALI) in clinical practice, but the treatment mechanism is not very clear. Therefore, elucidating the molecular mechanism of action of FC in treating CALI is of great significance for the further development and application of drugs. Male Wistar rats were as the research object. The model group rats were orally administered with 8 mL/kg alcohol for 28 days to establish a CALI model, while the treatment group rats were orally administered with high (4.2903 g/kg), medium (1.4301 g/kg), and low (0.4767 g/kg) doses of FC extract. Potential biomarkers related to CALI were identified using rat serum metabonomics analysis methods combined with ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS) technology, and the regulatory mechanisms of FC on these biomarkers were investigated. The BP neural network model was established by MATLAB software to deal with the classification problem of omics data. The H&E staining experiment found that after gavage, high-dose FC extract can reduce the degree of liver cell damage. Compared with the model group, the expression levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the high-dose FC group decrease, indicating that the high-dose FC extract has liver protective effect. The classification accuracy of the BP neural network model is 95.8%, and the classification effect is good. Through volcanic map analysis, a total of twenty biomarkers related to CALI are identified, and FC can have a callback effect on these biomarkers. The results indicated that FC may exert therapeutic effect on CALI by regulating the metabolism of triglycerides, fatty acids, phospholipids, bile acids, amino acids and Vitamin E. This study provides a theoretical foundation for the promotion and clinical application.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2–3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC. Methods In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo. Results Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967–0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033–6.605, P

Abstract The pink stem borer, Sesamia inferens Walker (Lepidoptera: Noctuidae), is one of the most notorious pest insects of rice and maize crops in the world. Here, we generated a high-quality chromosome-level genome assembly of S. inferens, using a combination of Illumina, PacBio HiFi and Hi-C technologies. The total assembly size was 973.18 Mb with a contig N50 of 33.39 Mb, anchored to 31 chromosomes, revealing a karyotype of 30 + Z. The BUSCO analysis indicated a high completeness of 98.90% (n = 5286), including 5172 (97.8%) single-copy BUSCOs and 58 (1.1%) duplicated BUSCOs. The genome contains 58.59% (564.58 Mb) repeat elements and 26628 predicted protein-coding genes. The chromosome-level genome assembly of S. inferens provides in-depth knowledge and will be a helpful resource for the Lepidoptera and pest control research communities.

The chemoselective probe technique combines the benefits of chemical derivatization and solid-phase extraction, allowing for simultaneous enhancement of analyte ionization efficiency, reduction of matrix interference, and improvement in chromatographic separation. This innovative technique holds great promise for applications in metabolomics research, metabolic tracking, and natural product isolation and purification. This review provides a comprehensive overview of the advancements in chemoselective probes from 2007 to 2024, focusing on the progress in probe design, particularly cleavable linkers. Additionally, it discusses the application of chemoselective probes in LC-MS analysis of small-molecular-weight compounds.

Abstract Background In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. Methods A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants’ levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. Results Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47–0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44–0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28–0.59), stroke (OR, 0.44; 95% CI, 0.26–0.74), hypertension (OR, 0.27; 95% CI, 0.14–0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21–0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. Conclusions In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

Sugarcane aphid, Melanaphis sacchari Zehntner, is an important piercing-sucking pest on sorghum, sugarcane, and other graminaceous crops, not only damaging host plants by direct feeding, but also transmitting plant viruses that is detrimental to crop production. To evaluate the performance of two native parasitoid species, Aphelinus varipes (Förster) and Lysiphlebia japonica (Ashmead), on M. sacchari, the age stage, two-sex life table analysis was conducted to evaluate the demographic parameters of the two species. The results showed that the two parasitoids parasitized M. sacchari and completed their whole life history. The number of eggs laid by A. varipes (F: 209.49 offspring/female) and the number of oviposition days (Od: 14.18 d) were significantly higher than those of L. japonica (F: 87.47 offspring/female, Od: 3.36 d). Moreover, the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) of A. varipes (r: 0.3746 d-1, λ: 1.4160 d-1, R0: 113.125 offspring/individual) were significantly higher for A. varipes than those of L. japonica (r: 0.3386 d-1, λ: 1.4030 d-1, R0: 48.092 offspring/individual). In addition, the net killing rate (C0) of A. varipes was 119.57 (eggs/female), which was significantly higher than that of L. japonica (53.34 eggs/female). These findings suggested that A. varipes had higher performance with promising potential as biological control agent for sugarcane aphid.

We propose a broadband noise test method (10 Hz–1 MHz) using a direct power method to measure the excess noise of InGaAs/InP avalanche photodiodes (APDs) with a separate absorption, grading, charge, and multiplication structure. By this means, the impact ionization coefficient ratio (the k value) can be accurately determined. Compared with previous studies, this method can distinguish between low-frequency noise and excess noise, so for an appropriate high frequency spectral range, the excess noise can be analyzed without mixing in other noise information. Three different APDs fabricated in-house with different diameters (12, 25, and 60 µm) were investigated using the above-mentioned method under temperatures varying from −10 to −40 °C. Our findings showed that the k value of the APDs decreased as the temperature decreased. When the temperature decreased to −40 °C, the k value of the 12, 25, and 60 µm diameter diodes was as low as 0.1, 0.3, and 0.2, respectively. The measurement results are consistent with our device design and not only provide useful information for the future selection of device materials and structures but also demonstrate the feasibility of the broadband noise measurement method in the accurate determination of the k value. It indicates that low excess noise can be achieved by utilizing the temperature dependence of k.

IntroductionClonal fragmentation helps to assess clonal plants' growth resilience to human and environmental disturbance. Although clonal integration in epiphytes in tropical rubber plantations is important to understand their role in enhancing biodiversity and ecosystem services, research on this subject is limited. These plantations are typically monospecific economic forests that face increased anthropogenic disturbances.MethodsIn this study, we selected the clonal fern Pyrrosia nuda to study its survival status, biomass, maximum quantum yield of photosystem II (Fv/Fm), and frond length in response to the level of clonal fragmentation in a tropical rubber plantation.Results and discussionThe results showed that (1) clonal fragmentation significantly negatively affected the survival rate, biomass, and frond length of clonal plants, but with minimal effects on Fv/Fm at different growth stages; (2) the performance of a ramet (e.g., biomass or frond length) increased with ramet developmental ages and decreased with the number of ramets in a clonal fragment. The age-dependent impacts of clonal fragmentation provide insights into the biodiversity conservation of epiphytes and forest management in man-made plantations. Therefore, to better conserve the biodiversity in tropical forests, especially in environment-friendly rubber plantations, there is a need to reduce anthropogenic disturbances and alleviate the level of fragmentation.

Abstract With the rapid development of multimedia technology and the massive accumulation of user data, a huge amount of data is rapidly generated and shared over the network, while the problems of inappropriate data access and abuse persist. Reversible data hiding in encrypted images (RDHEI) is a privacy-preserving method that embeds protected data in an encrypted domain and accurately extracts the embedded data without affecting the original content. However, the amount of embedded data has been one of the major limitations in the performance and application of RDHEI. Currently, the main approaches to improve the capacity of RDHEI are either to increase the overall capacity or to reduce the length of the auxiliary information. In this paper, we propose a novel RDHEI scheme based on multi-prediction and adaptive Huffman encoding. To increase the overall capacity, we propose a multi-prediction, called MED+GAP predictor, to generate the label map data of non-reference pixels prior to image encryption. Then, an adaptive Huffman coding is designed to compress the generated labels in order to reduce the embedding length of the auxiliary information used for the extraction and recovery. Experiments show that the proposed method with MED+GAP predictor and adaptive Huffman coding improves 0.052 bpp, 0.023 bpp, and 0.047 bpp on average over the other state-of-the-art methods on the BOSSBase, BOWS-2, and UCID datasets, respectively, while maintaining security and reversibility.

Abstract Background Adolescent depression has grown to be a major social concern in China. During the coronavirus pandemic, the incidence of depression among Chinese adolescents increased substantially. More research is required to inform the prevention and intervention of adolescent depression in China. Depression is associated with Early Maladaptive Schemas (EMSs). Childhood abuse and neglect are distal antecedents of adolescent depression. It is not known how depression and EMSs interact in adolescence and how childhood abuse and neglect contribute to this relationship. This study aimed to examine the reciprocal relationships between depression and EMSs, as well as the long-term effects of childhood abuse and neglect on depression and EMSs during adolescence. The work also investigates gender differences in these mechanisms. Methods Using a two-wave longitudinal design, we recruited 3,485 Chinese adolescents (M age = 13.2; 43.2% females) from three Shanxi Province, China middle schools. All participants completed self-report questionnaires addressing childhood abuse and neglect, depression, and EMSs. Structural equation models examined reciprocal relationships between depression and EMS, as well as the effect of childhood abuse and neglect on depression and EMSs. Multi-group analysis addressed gender differences. Results Results indicated that greater depression predicted more EMSs measured later, but EMSs did not predict subsequent depression. Childhood abuse and neglect had different effects on depression and EMSs during adolescence. Specifically, exposure to childhood abuse related to more severe depression and EMSs in adolescence and contributed to the perpetuation of EMSs by increasing depression. Exposure to childhood neglect showed a direct effect on depression and indirectly reinforced subsequent EMSs through depression. There were no gender differences. Conclusion These findings contribute to a better understanding of the emergence and course of depression in early adolescence, suggesting that childhood abuse and neglect are critical early risk factors. Additionally, depression plays a key role in promoting schema perpetuation among adolescents exposed to childhood maltreatment, providing important implications for relevant prevention and intervention in early adolescence.

Abstract Background We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. Methods This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline’s clinical efficacy and safety were performed to control confounding factors. Results For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. Conclusions Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient’s age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Abstract Introduction Proton pump inhibitor (PPI) abuse poses an overwhelming threat to the allocation of medical resources and places a heavy burden on global medical expenses. In this study, we put forward our prospective prescription review system and evaluated the effects of this system on clinical outcomes, rational medication use and costs related to PPIs. Methods A retrospective cohort study was conducted in which the included patients were divided into a preintervention group (2019.10–2020.09) and a postintervention group (2020.10–2021.09). To reduce the bias of patients’ baseline characteristics, the propensity score matching (PSM) method was employed. The primary endpoints were the incidence of stress ulcers (SUs), the improvement and cure rates of gastrointestinal haemorrhage, the defined daily dose (DDD), the drug utilization index (DUI) and the DDD/100 patient-days. The secondary endpoints included the types of unreasonable medication orders for PPIs, the PPI utilization rate and PPI costs. Results A total of 53,870 patients were included to evaluate the secondary endpoints, and 46,922 patients were paired by PSM and assessed to evaluate the primary endpoints. The number of PPIs used and PPI costs were significantly lower in the postintervention group than in the preintervention group (P

In order to enhance the operational efficiency of the healthcare industry, this paper investigates a medical information diagnostic platform through the application of swarm and evolutionary algorithms. This paper begins with an analysis of the current development status of medical information diagnostic platforms based on Chat Generative Pre-trained Transformer (ChatGPT) and Internet of Things (IoT) technology. Subsequently, a comprehensive exploration of the advantages and disadvantages of swarm and evolutionary algorithms within the medical information diagnostic platform is presented. Further, the optimization of the swarm algorithm is achieved through reverse learning and Gaussian functions. The rationality and effectiveness of the proposed optimization algorithm are validated through horizontal comparative experiments. Experimental results demonstrate that the optimized model achieves favorable performance at the levels of minimum, average, and maximum algorithm fitness values. Additionally, preprocessing data in a 10 * 10 server configuration enhances the algorithm’s fitness values. The minimum fitness value obtained by the optimized algorithm is 3.56, representing a 3 % improvement compared to the minimum value without sorting. In comparative experiments on algorithm stability, the optimized algorithm exhibits the best stability, with further enhancement observed when using sorting algorithms. Therefore, this paper not only provides a new perspective for the field of medical information diagnostics but also offers effective technical support for practical applications in medical information processing.

Background: Ibrutinib, a potent Bruton’s tyrosine kinase inhibitor with marked efficacy against hematological malignancies, is associated with the heightened risk of atrial fibrillation (AF). Although ibrutinib-induced AF is linked to enhanced oxidative stress, the underlying mechanisms remain unclear. Objective: This research aimed to explore the molecular mechanism and regulatory target in ibrutinib-induced AF. Methods: We performed in vivo electrophysiology studies using ibrutinib-treated mice, and then employed proteomic and single-cell transcriptomic analyses to identify the underlying targets and mechanisms. The effects of A-kinase anchoring protein 1 (AKAP1) depletion on mitochondrial quality surveillance (MQS) were evaluated using both in vivo and ex vivo AKAP1 overexpression models. Results: Atrial AKAP1 expression was significantly reduced in ibrutinib-treated mice, leading to inducible AF, atrial fibrosis, and mitochondrial fragmentation. These pathological changes were effectively mitigated in an overexpression model of ibrutinib-treated mice injected with an adeno-associated virus carrying Akap1. In ibrutinib-treated atrial myocytes, AKAP1 down-regulation promoted dynamin-related protein 1 (DRP1) translocation into mitochondria by facilitating DRP1 dephosphorylation at Ser637, thereby mediating excessive mitochondrial fission. Impaired MQS was also suggested by defective mitochondrial respiration, mitochondrial metabolic reprogramming, and suppressed mitochondrial biogenesis, accompanied by excessive oxidative stress and inflammatory activation. The ibrutinib-mediated MQS disturbance can be markedly improved with the inducible expression of the AKAP1 lentiviral system. Conclusions: Our findings emphasize the key role of AKAP1-mediated MQS disruption in ibrutinib-induced AF, which explains the previously observed reactive oxygen species overproduction. Hence, AKAP1 activation can be employed to prevent and treat ibrutinib-induced AF.

IntroductionCanopy species need to shift their ecological adaptation to improve light and water resources utilization, and the study of intraspecific variations in plant leaf functional traits based at individual scale is of great significance for evaluating plant adaptability to climate change.MethodsIn this study, we evaluate how leaf functional traits of giant trees relate to spatial niche specialization along a vertical gradient. We sampled the tropical flagship species of Parashorea chinensis around 60 meters tall and divided their crowns into three vertical layers. Fourteen key leaf functional traits including leaf morphology, photosynthetic, hydraulic and chemical physiology were measured at each canopy layer to investigate the intraspecific variation of leaf traits and the interrelationships between different functional traits. Additionally, due to the potential impact of different measurement methods (in-situ and ex-situ branch) on photosynthetic physiological parameters, we also compared the effects of these two gas exchange measurements.Results and discussionIn-situ measurements revealed that most leaf functional traits of individual-to-individual P. chinensis varied significantly at different canopy heights. Leaf hydraulic traits such as midday leaf water potential (MWP) and leaf osmotic potential (OP) were insignificantly correlated with leaf photosynthetic physiological traits such as maximal net assimilation rate per mass (Amass). In addition, great discrepancies were found between in-situ and ex-situ measurements of photosynthetic parameters. The ex-situ measurements caused a decrease by 53.63%, 27.86%, and 38.05% in Amass, and a decrease of 50.00%, 19.21%, and 27.90% in light saturation point compared to the in-situ measurements. These findings provided insights into our understanding of the response mechanisms of P. chinensis to micro-habitat in Xishuangbanna tropical seasonal rainforests and the fine scale adaption of different resultant of decoupled traits, which have implications for understanding ecological adaption strategies of P. chinensis under environmental changes.

Abstract Background & aims The individual effect of working schedule on survival in the hypertensive population has not been adequately studied. Shiftworkers are also prone to unhealthy lifestyles like pro-inflammatory diet. Therefore, we assessed the effect of shift work and its joint association with dietary inflammatory potential on mortality risk among the large US nationally representative sample of adult hypertensive population. Methods Data were from a nationally representative prospective cohort among US hypertensive population (n = 3680; weighted population, 54,192,988). The participants were linked to the 2019 public-access linked mortality archives. The working schedule were self-reported using the Occupation Questionnaire Section. Dietary inflammatory index (DII) scores were equally calculated using the 24-hour dietary recall (24 h) interviews. Multivariable Cox proportional hazards regression models were used to estimate hazard ratio and 95% confidence intervals (95%CI) for survival of hypertension individuals by work schedule and dietary inflammatory potential. The joint effect of work schedule and dietary inflammatory potential was then examined. Results Among the 3680 hypertension individuals (39.89% female [n = 1479] and 71.42% white [n = 1707]; weighted mean [SE] age, 47.35 [0.32] years), 592 individuals reported shift work status. 474 (10.76%) reported shift work status with pro-inflammatory dietary pattern (DII scores > 0). 118 (3.06%) reported shift work status with anti-inflammatory dietary pattern (DII scores

Abstract Background Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. Methods The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. Results Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40–5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54–3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. Conclusion GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

AIM: To investigate the effect of nasolacrimal duct packing combined with sodium hyaluronate gel injection in locating the nasal broken end in lacrimal canaliculus anastomosis which is difficult to find the broken end.METHODS:A total of 13 patients(13 eyes)with traumatic single lacrimal canaliculus rupture were treated in our hospital. RS lacrimal duct drainage tube was inserted into the lacrimal duct from intact lacrimal canaliculus to fill the nasolacrimal duct, then sodium hyaluronate gel was injected to make sodium hyaluronate gel overflow from the nasal broken end of fractured lacrimal canaliculus, which was used to locate the nasal broken end which was difficult to find and completed the lacrimal anastomosis operation.RESULTS: Among the patients with 13 eyes who were difficult to find the broken end, the nasolacrimal duct was filled with RS lacrimal duct drainage tube. After injection of sodium hyaluronate gel, the gel overflowed from the nasal broken end under direct vision of the microscope, and the lacrimal duct drainage tube was successfully inserted, and the success rate of finding the broken end was 100%. Thirteen eyes were extubated after being placed for 3mo, and then were followed up for 6mo. Among them, 9 eyes were cured, 3 eyes were markedly effective and 1 eye was ineffective. The cure rate was 69%, and the total effective rate was 92%.CONCLUSION: A new technique for rapid location of nasal broken end is proposed for patients in which are difficult to find the broken end. This method is simple to operate and requires a relatively low clinical experience. It is suitable for patients with different degrees of single lacrimal canaliculus rupture and can complete complex lacrimal canaliculus rupture anastomosis in a short time.

The eastern Sichuan Basin in China holds vast potential for oil and gas exploration in the Lower-Middle Jurassic strata. However, the geological characteristics and hydrocarbon accumulation patterns of this region remain largely unclear. During the deposition period of the Lower-Middle Jurassic strata, the eastern Sichuan is characterized by the formation of multiple sets of source, reservoir, and caprock assemblages through depositing lake-delta-fluvial deposits, which have great exploration potential. The Jurassic source rocks in eastern Sichuan are mainly developed in the Dongyuemiao Member, Da’anzhai Member, and Liangshan Formation. These source rocks have a total organic carbon (TOC) content greater than 1 and a varying range of organic matter maturity, with a Ro value of 0.8–2.0. The kerogen in these source rocks is primarily type II, with a smaller proportion being type III. A range of reservoir rocks can be found in the Jurassic strata of eastern Sichuan, with sandstone reservoirs being predominantly found in the Liangshan Formation, Shaximiao Formation, and Zhenzhuchong Member. Shale reservoirs are mostly present in the Dongyuemiao, Da’anzhai, Liangshan, and Maanshan Members, and there is a limited distribution of limestone reservoirs in the Da’anzhai Member and Dongyuemiao Formation. The arrangement of source rocks and reservoir rocks in eastern Sichuan has led to the formation of three types of reservoir-forming combinations, including lower generation and upper storage, self-generation and self-storage, and composite. Sandstone reservoirs are typically of lower generation and upper storage, shale reservoirs are primarily of self-generation and self-storage, and limestone reservoirs are mostly composite. The exploration of Jurassic oil and gas in eastern Sichuan should prioritize “layer and area selections.” The Da’anzhai, Dongyuemiao, and Liangshan shale reservoirs should be the primary exploration targets, with the semi-deep lake deposits in the syncline area being the most favorable. The degree of fracture development in the exploration area also has a significant impact on the shale oil and gas content. The Liangshan Formation and Shaximiao Formation sandstone reservoirs can serve as secondary exploration targets, with anticline areas that have better sealing conditions being more favorable. Limestone reservoirs have limited distribution, and exploration areas with high and steep fractures are relatively more advantageous.

Abstract We report for the first time the use of experimental electron density (ED) as training data for the generation of drug-like three-dimensional molecules based on the structure of a target protein pocket. Similar to a structural biologist building molecules based on their ED, our model functions with two main components: a generative adversarial network (GAN) to generate the ligand ED in the input pocket and an ED interpretation module for molecule generation. The model was tested on three targets: a kinase (hematopoietic progenitor kinase 1), protease (SARS‐CoV‐2 main protease), and nuclear receptor (vitamin D receptor), and evaluated with a reference dataset composed of over 8000 compounds that have their activities reported in the literature. The evaluation considered the chemical validity, chemical space distribution-based diversity, and similarity with reference active compounds concerning the molecular structure and pocket-binding mode. Our model can generate molecules with similar structures to classical active compounds and novel compounds sharing similar binding modes with active compounds, making it a promising tool for library generation supporting high-throughput virtual screening. The ligand ED generated can also be used to support fragment-based drug design. Our model is available as an online service to academic users via https://edmg.stonewise.cn/#/create .

Abstract Spermatogenesis is a complex biological process that produces haploid spermatozoa and requires precise regulation by many tissue-specific factors. In this study, we explored the role and mechanism of Fork head box J2 (FOXJ2, which is highly expressed in spermatocytes) in the regulation of spermatogenesis using a germline-specific conditional Foxj2 knock-in mouse model (Stra8-Cre; Foxj2 tg/tg mouse). Foxj2 overexpression in mouse testes led to spermatogenesis failure, which started at the initiation of meiosis, and resulted in male infertility. Lysosomes and autophagy-related genes were upregulated in Stra8-cre; Foxj2 tg/tg mouse testes and the number of autolysosomes in the spermatocytes in Stra8-cre; Foxj2 tg/tg mice was increased. Chromatin immunoprecipitation-PCR and Dual-luciferase reporter assays showed that Lamp2 (encoding lysosome‐associated membrane protein‐2) was a target of FOXJ2. Foxj2 overexpression increased the expression levels of Lamp2a and Hsc70 (70-kDa cytoplasmic heat shock protein) in the Stra8-cre; Foxj2 tg/tg mouse testes. Our results suggested that Foxj2 overexpression in the germ cells of mouse testes affects chaperone-mediated autophagy by upregulating LAMP2A, leading to spermatogenesis failure at the initiation of meiosis, thus resulting in male infertility. Our findings provide a new insight into the function of FOXJ2 in spermatogenesis and the significance of autophagy regulation in spermatogenesis.

Background: Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The Jagged1 (JAG1) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in JAG1 with isolated BA risk in the Chinese Han population.Methods: We genotyped 31 tag single nucleotide polymorphisms covering the JAG1 gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of JAG1 homologs were investigated in zebrafish embryos, and the roles of jag1a and jag1b in biliary development were examined by morpholino knockdown in zebrafish.Results: Single nucleotide polymorphisms rs6077861 [PAllelic = 1.74 × 10−4, odds ratio = 1.78, 95% confidence interval: 1.31–2.40] and rs3748478 (PAllelic = 5.77 × 10−4, odds ratio = 1.39, 95% confidence interval: 1.15–1.67) located in the intron region of JAG1 showed significant associations with BA susceptibility. The JAG1 homologs, jag1a and jag1b genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96 h postfertilization. Knockdown of both jag1a and jag1b led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model.Conclusion: Common genetic variants of JAG1 were associated with BA susceptibility. Knockdown of JAG1 homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that JAG1 might be implicated in the etiology of BA.

Directional axon regeneration and remyelination are crucial for repair of spinal cord injury (SCI), but existing treatments do not effectively promote those processes. Here, we propose a strategy for construction of niche-specific spinal white matter-like tissue (WMLT) using decellularized optic nerve (DON) loaded with neurotrophin-3 (NT-3)-overexpressing oligodendrocyte precursor cells. A rat model with a white matter defect in the dorsal spinal cord of the T10 segment was used. The WMLT transplantation group showed significant improvement in coordinated motor functions compared with the control groups. WMLT transplants integrated well with host spinal cord white matter, effectively addressing several barriers to directional axonal regeneration and myelination during SCI repair. In WMLT, laminin was found to promote development of oligodendroglial lineage (OL) cells by binding to laminin receptors. Interestingly, laminin could also guide linear axon regeneration via interactions with specific integrins on the axon surface. The WMLT developed here utilizes the unique microstructure and bioactive matrix of DON to create a niche rich in laminin, NT-3 and OL cells to achieve significant structural repair of SCI. Our protocol can help to promote research on repair of nerve injury and construction of neural tissues and organoids that form specific cell niches.

Abstract Background Alveolar recruitment maneuvers (ARMs) is an important part of lung-protective ventilation strategies (LPVSs), but the optimal duration and interval Remain unclear. Methods Patients:252 patients who underwent holmium laser lithotripsy surgery and meet inclusion criteria were included and randomized into three groups based on the duration and frequency of ARMs (Regular, one 30 s ARM (RARMs); Improved and intermittent, three 10s ARMs (IARMs); and Control (C), no ARMs).Interventions: Groups R and I received ARMs at 20 cmH2O pressures every 30 min. All patients received the same anesthesia and mechanical ventilation. Measurements:Outcomes included heart rate and mean arterial pressure changes during ARMs and postoperative pulmonary complications (PPCs) within the first 7 postoperative days. Main results Incidences of PPCs in groups R(7.1%) and I (5.0%)were slightly lower than those in group C (8.9%).This indicated the potential to reduce lung injury. Heart rate and mean arterial pressure fluctuations during ARMs were significantly higher in groups R and I than in group C (P

Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught extensive attention due to its antioxidant properties. Herein, we investigated the effect of dietary silybin supplementation on growth performance and determined its protective effect on paraquat (PQ)-induced intestinal oxidative damage and microflora dysbiosis in weaned piglets. In trial 1, a total of one hundred twenty healthy weaned piglets were randomly assigned into five treatments with six replicate pens per treatment and four piglets per pen, where they were fed basal diets supplemented with silybin at 0, 50, 100, 200, or 400 mg/kg for 42 days. In trial 2, a total of 24 piglets were randomly allocated to two dietary treatments with 12 replicates per treatment and 1 piglet per pen: a basal diet or adding 400 mg/kg silybin to a basal diet. One-half piglets in each treatment were given an intraperitoneal injection of paraquat (4 mg/kg of body weight) or sterile saline on day 18. All piglets were euthanized on day 21 for sample collection. The results showed that dietary supplementation with 400 mg/kg silybin resulted in a lower feed conversion ratio, diarrhea incidence, and greater antioxidant capacity in weaned piglets. Dietary silybin enhanced intestinal antioxidant capacity and mitochondrial function in oxidative stress piglets induced by PQ. Silybin inhibited mitochondria-associated endogenous apoptotic procedures and then improved the intestinal barrier function and morphology of PQ-challenged piglets. Moreover, silybin improved intestinal microbiota dysbiosis induced by the PQ challenge by enriching short-chain fatty-acid-producing bacteria, which augmented the production of acetate and propionate. Collectively, these findings indicated that dietary silybin supplementation linearly decreased feed conversion ratio and reduced diarrhea incidence in normal conditions, and effectively alleviated oxidative stress-induced mitochondrial dysfunction, intestinal damage, and microflora dysbiosis in weaned piglets.

Tyrosine kinase inhibitors (TKIs) are a novel category of antitumor agents with remarkable efficacy in extending patient survival. However, clinical use of TKIs has been hindered by the major adverse effect of atrial fibrillation (AF). Recent studies have revealed that TKIs induce metabolic alterations and remodeling in cardiomyocytes, thus perturbing energy metabolism. Specifically, mitochondrial dysfunction and shifts in cardiac substrate utilization have been implicated in the mechanisms underlying TKI-induced AF. In light of these findings, this article reviews the energy metabolism-associated pathways involved in TKI-induced AF, identifies precise therapeutic targets for managing this condition, and discusses evidence that may contribute to the development of novel TKIs without cardiac adverse effects.

Sand bodies in the Jurassic lacustrine-fluvial sedimentary system in the Sichuan Basin are realistic objects of shallow tight oil and gas exploration and development. Due to the influence of sedimentary microfacies, sand bodies have geological characteristics such as type diverse, variable lithology, significant thickness variation, and strong heterogeneity. Therefore, the fine description and prediction of different types of sand bodies is the current bottleneck for exploration and development. Based on the classification of various sand group types of the 1st member of Jurassic Shaximiao Formation, reservoir analysis was carried out, logging and geophysical response characteristics were concluded, and fine identification and spatial prediction were made by time-sharing window. Results show that: (1) The 1st member of Shaximiao Formation can be divided into 5 sand groups, among which the 1st sand group is mainly littoral-shallow lacustrine sheet sand and beach bar sand, and the 2nd to 5th sand groups are delta front facies channel-plain channel; (2) The average porosity of channel sand is 4.68%, which is significantly higher than that of bottom sheet sand (3.1%). The physical properties of the Ⅰ channel are the best, followed by the Ⅳ, Ⅱ, and Ⅲ channels. (3) The prediction standard of channel sand is: natural gamma < 65 API, and the prediction standard of sheet sand locates between 65 and 75 API. In sand body prediction, for sheet sands (beach bars), the study time window is extracted to be within 0-20 ms, and for river channels, the study time window is in the range of 20-100 ms upwards from the bottom of the Shaximiao Formation. Finally, a set of methods suitable for fine description and prediction of different types of sand bodies in the lacustrine-fluvial sedimentary system was established.

BackgroundTai Chi is good for improving the physical fitness of older adults. But few studies have reported the effects of Tai Chi on the postural balance and quality of life of older adults with gait disorders.ObjectiveThis review aimed to assess the influence of tai chi on postural stability and quality of life in older adults with abnormal gait.MethodAccording to the literature retrieval principles, the works published from the inception date to May 2023 were retrieved, including the following databases: PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, EBSCOhost, and Google Scholar. Subsequently, literature screening and quality assessment were performed.ResultsA total of 16 randomized controlled trials were included in this study, Tai Chi intervention can affect populations with Parkinson's disease (PD), no exercise, mild cognitive impairment (MCI), chronic stroke, sedentary, fear of falling, or history of falling. Postural instability is associated with balance, gait, the Unified Parkinson's Disease Rating Scale Motor Subscale 3 (UPDRS III), mobility, lower body strength, and falls. Only two articles looked at quality of life. The Yang style is the most commonly used in the intervention. Nonetheless, most studies were performed on female participants, hence, more research on older male populations is needed.ConclusionTai Chi intervention benefits postural balance in patients with gait disorders. 12 weeks is the most common intervention period for patients with gait disorders. The frequency of intervention is seven articles twice a week, and the intervention time is about 60 minutes. The Tai Chi intervention methods in this study involve Yang Style, Sun Style, Taoist Tai Chi, and Health Qigong Tai Chi, but the Yang Style Tai Chi intervention is the most widely used.

The Jurassic Da’anzhai Member in Sichuan Basin is an important target for shale oil exploration. Whole rock X-ray diffraction analysis, thin section, SEM and TOC testing, as well as major and trace element analysis are used to analyze the relationship of lithofacies and pore types with the sedimentary environment of the Da’anzhai Member in the Central Sichuan Basin. The results show the Da’anzhai Member in the Well Ren’an 1 (RA1) is divided into six types of lithofacies, based on a three-level division method of mineral composition-TOC-mineral structure— namely, massive mud-bearing shell limestone lithofacies (F), thick argillaceous shell limestone lithofacies (E), laminated clay silt shale lithofacies (D), thin shell calcareous shale lithofacies (C), laminated shell-bearing shale lithofacies (B), and thick clay shale lithofacies (A). The pore spaces include intergranular pores, intergranular dissolution pores, authigenic calcite intergranular pores, authigenic quartz intercrystalline pores, intergranular pores of clay minerals or pyrite nodules, as well as organic pores. The Da’anzhai Member was deposited in a semi-deep to shallow lake sedimentary environment, with relatively low salinity. This strata experienced moderate-to-strong chemical weathering as a result of the semi-arid, warm and humid paleoclimate environmental conditions that persisted during its deposition; low weathering and dry paleoclimate conditions occurred periodically. Paleoenvironment is an important influence on the lithofacies and pore types of the Da’anzhai Member. The persistence of arid climate conditions contributed to a decline in water depth, relatively high salinity, low organic productivity, and the deposition of carbonate rocks that characterize lithofacies E and F; mostly intercrystalline pores formed in these lithofacies in response to the prevailing arid climate conditions. Conversely, warm, and humid climate conditions increased the inflow of fresh water, terrigenous debris, and nutrients into the lacustrine basin that led to the deposition of fine-grained sedimentary rocks of lithofacies A, B, and C. These lithofacies are characterized by abundant nano pores, such as clay intercrystalline pores and organic pores.

Abstract. Background:. Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients. Methods:. From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA2DS2-VA score (excluding female sex from the CHA2DS2-VASc score). Results:. Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%–1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65–0.73), higher than that of CHA2DS2-VA score (0.66, 95% CI: 0.62–0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA2DS2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%–15.7%). Conclusion:. In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA2DS2-VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration:. www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Abstract Background Perioperative patients are at risk of developing stress ulcers (SU), which can cause clinically important bleeding. Stress ulcer prophylaxis (SUP) is widely applied to the patients in Intensive care unit (ICU) as well as the general ward, so it may lead to overmedication. However, there have been no surveys regarding SUP knowledge or prescribing habits. Objective Our study assessed the knowledge, attitudes, and prescribing behavior of the surgeons toward perioperative patients regarding SUP and determined factors associated with low knowledge and high level of prescribing behaviors. Methods We performed a cross-sectional survey using questionnaires, randomly sampling 1266 surgeons on their current SUP practices. Results Proton pump inhibitors for SUP were used the most (94%); 43% used lansoprazole. Guideline awareness was inconsistent; the most familiar guideline was the National Medical Journal of China, and 46% were unaware of any guidelines. The predictors of low knowledge score regarding SUP in multivariable analysis were the hospital grade (p = 0.000), the type of hospital (p = 0.044), attendance at continuing education programs (p = 0.037), the awareness of clinical practice guidelines (CPGs) for SUP (p = 0.000). Twenty-one percent of physicians were high prescribers. High prescribing behavior was associated with hospital grade(p = 0.000), education level(p = 0.010) and attendance at continuing education programs (p = 0.000). Conclusion We found that most surgeons used SUP, primarily proton pump inhibitors. However, surgeons knew little about the SUP guidelines, which may lead to insufficient SUP knowledge and overmedication. In addition, hospital grade, the type of hospital and attendance at continuing education programs may also affect the low knowledge of SUP. Hospital grade, education level and attendance at continuing education programs may affect high prescribing behavior.

The objective of this study was to investigate the effects of dietary supplementation with different types of potassium and magnesium on the reproductive performance, antioxidant capacity, and immunity of sows. Forty-five Landrace × Yorkshire sows at the late gestation stage (85 d) were randomly assigned to three groups (n = 15). Sows in the control group (CON), potassium chloride and magnesium sulfate group (PM), and potassium-magnesium sulfate group (PMS) were fed with a basal diet, a basal diet supplemented with magnesium sulfate (0.20%) and potassium chloride (0.15%), or a basal diet supplemented with potassium-magnesium sulfate (0.45%), respectively. The results showed that dietary supplementation with PMS did not yield significant effects on the reproductive performance compared with the CON group (p > 0.05). However, it significantly elevated the level of insulin-like growth factor 1 (IGF-1) in plasma and immunoglobulin A (IgA) in colostrum (p < 0.05). Furthermore, PMS significantly augmented the activities of catalase (CAT) and superoxide dismutase (SOD) while reducing the levels of malondialdehyde (MDA) in comparison to the CON group (p < 0.05). Compared with the PM group, the PMS group significantly reduced the incidence rate of intrauterine growth restriction (IUGR) (p < 0.05) and significantly decreased the concentration of the proinflammatory cytokine (TNF-α) level in plasma (p < 0.05). These results indicated that dietary supplementation with PMS during late gestation could enhance sows’ antioxidant capacity and the IgA level in colostrum. These findings will provide a theoretical reference for the use of magnesium and potassium in sow production to improve sows’ health.

Abstract Background Green tea has been one of the most popular beverages in China since ancient times. Mixed results concerning the effect of green tea consumption on the incidence of hypertension have been published over the past decades. However, no previous studies have focused on longevous individuals in China and the sex differences in the association between habitual green tea intake and hypertension. Methods The data extracted from the database of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2018 were used for a secondary analysis. Logistic regression models were employed to examine the odds ratio (OR) of daily green tea consumption on the incidence of hypertension by sex. Results A total of 9277 individuals were included in the analysis (39.8% were men). The included individuals had a mean age of 80.9 and 84.8 years for those who drank green tea daily and those who had never, respectively (p

Objective We aimed to determine the prevalence of and the factors associated with intraventricular conduction disturbance in the Chinese population. Methods Electrocardiographic data from 42,031 people were retrospectively analysed. The weighted prevalences of left bundle branch block (LBBB), right bundle branch block (RBBB), bifascicular block and nonspecific intraventricular conduction delay (NS-IVCD) were calculated. The independently associated factors were determined using logistic regression analysis. Results The weighted prevalence for Chinese people older than 45 years was 0.17% for LBBB, 2.16% for RBBB and 0.44% for NS-IVCD. The weighted prevalence for RBBB combined with left anterior fascicular block was 0.17%, and 0.05% for RBBB combined with left posterior fascicular block. There were significant differences in the weighted prevalences of RBBB and NS-IVCD between men and women. The weighted prevalence of LBBB and RBBB increased markedly with increasing age. Age and diabetes were independent factors associated with LBBB, compared with age and sex for RBBB and sex and coronary artery disease for NS-IVCD. Conclusions This study provided reliable data for the weighted prevalence of and factors associated with LBBB, RBBB and NS-IVCD in Chinese adults.

Abstract Aims This study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing. Methods and results This study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in‐hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra‐hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65–80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61–79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of β‐blockers and angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10–3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02–2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63–3.52, P = 0.368). Conclusions Worse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served.

Abstract Background Patients with atrial fibrillation (AF) underwent a high risk of hospitalization, which has not been paid much attention to in practice. Therefore, we aimed to assess the incidence, causes and predictors of hospitalization in AF patients. Methods From August 2011 to December 2017, a total number of 20,172 AF patients from the Chinese Atrial Fibrillation Registry (China-AF) Study were prospectively selected for this study. We described the incidence, causes of hospitalization by age groups and sex. The Fine-Gray competing risk model was employed to identify predictors of first all-cause and first cause-specific hospitalization. Results After a mean follow-up of 37.3 ± 20.4 months, 7,512 (37.2%) AF patients experienced one or more hospitalizations. The overall incidence of all-cause hospitalization was 24.0 per 100 patient-years. Patients aged < 65 years were predominantly hospitalized for AF (42.1% of the total hospitalizations); while patients aged 65–74 and ≥ 75 years were mainly hospitalized for non-cardiovascular diseases (43.6% and 49.3%, respectively). We found patients complicated with heart failure (HF)[hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.02–1.18], established coronary artery disease (CAD) (HR 1.24, 95%CI 1.17–1.33), ischemic stroke/transient ischemic attack (TIA) (HR 1.22, 95%CI 1.15–1.30), diabetes (HR 1.14, 95%CI 1.08–1.20), chronic obstructive pulmonary disease (COPD) (HR 1.28, 95%CI 1.02–1.62), gastrointestinal disorder (HR 1.37, 95%CI 1.21–1.55), and renal dysfunction (HR 1.24, 95%CI 1.09–1.42) had higher risks of hospitalization. Conclusions More than one-third of AF patients included in this study were hospitalized at least once during over 3-year follow-up. The main cause for hospitalization among the elderly patients (≥ 65 years) is non-cardiovascular diseases rather than AF. Multidisciplinary management of comorbidities should be advocated to reduce hospitalization in AF patients older than 65 years old. Clinical Registry http://www.chictr.org.cn/showproj.aspx?proj=5831 . Unique identifier: ChiCTR-OCH-13003729. The registration date is October 22, 2013.

Abstract Background Myocardial strain assessed with cardiovascular magnetic resonance (CMR) feature tracking can detect early left ventricular (LV) myocardial deformation quantitatively in patients with a variety of cardiovascular diseases, but this method has not yet been applied to quantify myocardial strain in patients with atrial fibrillation (AF) and no coexistent cardiovascular disease, i.e., the early stage of AF. This study sought to compare LV myocardial strain and T1 mapping indices in AF patients and healthy subjects, and to investigate the associations of a portfolio of inflammation, cardiac remodeling and fibrosis biomarkers with LV myocardial strain and T1 mapping indices in AF patients with no coexistent cardiovascular disease. Methods The study consisted of 80 patients with paroxysmal AF patients and no coexistent cardiovascular disease and 20 age- and sex-matched healthy controls. Left atrial volume (LAV), LV myocardial strain and native T1 were assessed with CMR, and compared between the AF patients and healthy subjects. Biomarkers of C-reactive protein (CRP), transforming growth factor beta-1 (TGF-β1), collagen III N-terminal propeptide (PIIINP), and soluble suppression of tumorigenicity 2 (sST2) were obtained with blood tests, and compared between the AF patients and healthy controls. Associations of these biomarkers with those CMR-measured parameters were analyzed for the AF patients. Results For the CMR-measured parameters, the AF patients showed significantly larger LAV and LV end-systolic volume, and higher native T1 than the healthy controls (max P = 0.027). The absolute values of the LV peak systolic circumferential strain and its rate as well as the LV diastolic circumferential strain rate were all significantly reduced in the AF patients (all P

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury. However, achieving good outcome remains difficult. Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites. However, it has not been reported whether this material promotes axonal regeneration in vivo. In the present study, a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells. This functional scaffold promoted the directional growth and remyelination of regenerating axons. In vitro, the porcine decellularized optic nerve contained many straight, longitudinal channels with a uniform distribution, and microscopic pores were present in the channel wall. The spatial micro topological structure and extracellular matrix were conducive to the adhesion, survival and migration of neural stem cells. The scaffold promoted the directional growth of dorsal root ganglion neurites, and showed strong potential for myelin regeneration. Furthermore, we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo. Four weeks later, the regenerating axons grew straight, the myelin sheath in the injured/transplanted area recovered its structure, and simultaneously, the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced. Together, these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration. All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2019-B034) on February 28, 2019.

Chinese clinical pharmacists consider improving the quantity and quality of consultations to be an important task in providing better pharmaceutical care. To achieve this goal, we developed a clinical pharmacist consultation method using multidisciplinary individualized medication recommendations (MIMRs) and studied the effects of its implementation. A retrospective study of 812 clinical pharmacist-led consultations was conducted. In the pre-intervention group, medication advice was given based on the purpose of the consultation. In the post-intervention group, a consultation method using MIMRs was implemented, in which clinical pharmacists with specialties in anticoagulation, gastroenterology, and nutrition were asked to give individualized medication recommendations. Outcomes, including the effectiveness rate of consultations (ERC) and acceptance rate of consultations (ARC), were compared between the two groups using propensity score matching method. Patterns and numbers of consultations and individualized medication recommendations were also compared. The results showed that the ERC in the post-intervention group compared with the ERC in the pre-intervention group was 83.3% vs 74.0%, respectively (P < .05). Significant difference was also shown between the two groups in ARC (98.4% vs 92.2%, P < .05). The total number of consultations increased, as did the number of general consultations, multidisciplinary/difficult consultations, anti-infection consultations, and non–anti-infection consultations specifically. As a result, we proposed that the implementation of MIMRs can improve the effects of treatment and increase the number of consultations by pharmacists, which is worthy of further promotion to better serve physicians and patients.

Abstract Background Novel coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and precise fatality data by age group is needed urgently. This study to delineate the clinical characteristics and outcome of COVID-19 patients aged ≥75 years and identify the risk factors of in-hospital death. Methods A total of 141 consecutive patients aged ≥75 years who were admitted to the hospital between 12th and 19th February 2020. In-hospital death, clinical characteristics and laboratory findings on admission were obtained from medical records. The final follow-up observation was on the 31st March 2020. Results The median age was 81 years (84 female, 59.6%). Thirty-eight (27%) patients were classified as severe or critical cases. 18 (12.8%) patients had died in hospital and the remaining 123 were discharged. Patients who died were more likely to present with fever (38.9% vs. 7.3%); low percutaneous oxygen saturation (SpO2) (55.6% vs. 7.3%); reduced lymphocytes (72.2% vs. 35.8%) and platelets (27.8% vs. 4.1%); and increased D-dimer (94.4% vs. 42.3%), creatinine (50.0% vs. 22.0%), lactic dehydrogenase (LDH) (77.8% vs. 30.1%), high sensitivity troponin I (hs-TnI) (72.2% vs. 14.6%), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (72.2% vs. 6.5%; all P 37.3 °C (OR = 80.5, 95% CI 4.6 to 1407.6, P = 0.003), SpO2 ≤ 90% (OR = 70.1, 95% CI 4.6 to 1060.4, P = 0.002), and NT-proBNP> 1800 ng/L (OR = 273.5, 95% CI 14.7 to 5104.8, P

Acute inflammation often contributes to the increased arrhythmogenesis in the cardiomyocytes. We investigated the protective effects of pravastatin on calcium disorders induced by acute administration of pro-inflammatory cytokines in isolated ventricular myocytes and its underlying mechanisms. Wild-type mice were intraperitoneally injected for five days with either pravastatin 20 mg/kg per day or an equal volume of normal saline. Cytosol Ca2+ handling was studied in freshly isolated ventricular myocytes after acute exposure of interleukin-6 (IL-6) (1 ng/ml) for 120 min by Ionoptix and confocal microscopy. Acute administration of clinically relevant concentrations of IL-6 disturbed calcium handling in ventricular myocytes, which presented as decreased amplitudes, prolonged decay times of Ca2+ transients, and reduced sarcoplasmic reticulum (SR) calcium stores. The frequency of spontaneous Ca2+ release, including calcium sparks and spontaneous calcium waves, was dramatically enhanced in the setting of IL-6. Notably, the pretreatment of pravastatin alleviated disturbed Ca2+ cycling, reduced spontaneous Ca2+ leakage induced by IL-6. Mitochondrial ROS pathway may constitute the underlying mechanism of the protective effects of pravastatin. Pravastatin protected the cardiomyocytes against calcium disorders induced by IL-6 via the mitochondrial ROS pathway, which suggests that pravastatin may represent a promising auxiliary therapeutic strategy for cardiac injury under acute inflammation.

Background: Elderly adults with atrial fibrillation (AF) are at increased risk of frailty and thromboembolic complications. However, studies on the prevalence of frailty in AF patients and data on the relationship between frailty and the use of anticoagulants are limited. Methods: We conducted a cross-sectional study involving 500 participants. Patients aged 65 years or older were consecutively selected from the Chinese Atrial Fibrillation Registry study. The patient’s frailty status was assessed with use of the Canadian Study of Health and Aging Clinical Frailty Scale. We assessed the prevalence of and factors associated with frailty, and how frailty affects anticoagulant therapy. Results: In 500 elderly adults with AF (age 75.2±6.7 years; 51.6% female), 201 patients (40.2%) were frail. The prevalence of frailty was higher in females (P=0.002) and increased with age and CHA 2 DS 2 -VASc score (P for trend less than 0.001 for both). The factors associated with frailty were a history of heart failure (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.39–4.14), female sex (OR 2.09, 95% CI 1.27–3.43), and advanced age (OR 1.13, 95% CI 1.09–1.17). Frail patients were significantly less likely to have ever been prescribed anticoagulants compared with nonfrail patients (81.7 vs. 54.9%, P

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe yet rare inherited arrhythmia disorder. The cornerstone of CPVT medical therapy is the use of β-blockers; 30% of patients with CPVT do not respond well to optimal β-blocker treatment. Studies have shown that flecainide effectively prevents life-threatening arrhythmias in CPVT. Flecainide is a class IC antiarrhythmic drug blocking cardiac sodium channels. RyR2 inhibition is proposed as the principal mechanism of antiarrhythmic action of flecainide in CPVT, while it is highly debated. In this article, we review the current progress of this issue.

Background. There exist sex differences in the clinical profile, management, and outcome of atrial fibrillation (AF). Catheter ablation of AF has become a first-line therapy and has markedly made headway over the recent decades. Little is known about sex differences and temporal trends in hospitalization for catheter ablation of AF in the real-world setting. Methods. We retrospectively retrieved medical records of patients at Beijing Anzhen Hospital between January 2005 and December 2019. The patients undergoing catheter ablation of AF were enrolled. Demographical and clinical data were compared between sexes. The temporal trends of sex differences were evaluated. Results. We identified 13502 male patients (66.8%) and 6713 female patients (33.2%). The number of patients undergoing AF ablation had remarkably increased over time, but no sex differences were observed (p=0.17). The median age of women was five years older than that of men (p

The constantly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) fuel the worldwide coronavirus disease (COVID-19) pandemic. The spike protein is essential for the SARS-CoV-2 viral entry and thus has been extensively targeted by therapeutic antibodies. However, mutations along the spike in SARS-CoV-2 VOC and Omicron subvariants have caused more rapid spread and strong antigenic drifts, rendering most of the current antibodies ineffective. Hence, understanding and targeting the molecular mechanism of spike activation is of great interest in curbing the spread and development of new therapeutic approaches. In this review, we summarize the conserved features of spike-mediated viral entry in various SARS-CoV-2 VOC and highlight the converging proteolytic processes involved in priming and activating the spike. We also summarize the roles of innate immune factors in preventing spike-driven membrane fusion and provide outlines for the identification of novel therapeutics against coronavirus infections.

Flaxseed meal (FSM) is rich in protein, α-linolenic acid, dietary fiber, flaxseed gum, and other bioactive substances. The total protein content of these components is up to 30%. Thus, FSM can be used as a high-quality protein feed resource. However, due to the presence of anti-nutritional factors, such as cyanogenic glycosides (CGs), phytic acid, anti-vitamin B6 factor, and other anti-nutritional factors, the application of FSM is restricted in animal diets. Recently, the interest in decreasing anti-nutritional factors and improving the nutritional value of FSM has been increasing in the field of animal nutrition. Therefore, this paper reviews the nutritional components, anti-nutritional factors, and the CG detoxification methods of FSM as well as its application in livestock and poultry, in order to provide a theoretical reference for the application of FSM in animal husbandry.

Chenodeoxycholic acid (CDCA), a primary bile acid (BA), has been demonstrated to play an important role as a signaling molecule in various physiological functions. However, the role of CDCA in regulating intestinal epithelial cell (IEC) function remains largely unknown. Herein, porcine intestinal epithelial cells (IPEC-J2) were used as an in vitro model to investigate the effects of CDCA on IEC proliferation and explore the underlying mechanisms. IPEC-J2 cells were treated with CDCA, and flow cytometry and transcriptome analysis were adopted to investigate the effects and potential molecular mechanisms of CDCA on the proliferation of IECs. Our results indicated that adding 50 μmol/L of CDCA in the media significantly increased the proliferation of IPEC-J2 cells. In addition, CDCA treatment also hindered cell apoptosis, increased the proportion of G0/G1 phase cells in the cell cycle progression, reduced intracellular ROS, and MDA levels, and increased mitochondrial membrane potential, antioxidation enzyme activity (T-AOC and CAT), and intracellular ATP level (p < 0.05). RNA-seq results showed that CDCA significantly upregulated the expression of genes related to cell cycle progression (Cyclin-dependent kinase 1 (CDK1), cyclin G2 (CCNG2), cell-cycle progression gene 1 (CCPG1), Bcl-2 interacting protein 5 (BNIP5), etc.) and downregulated the expression of genes related to mitochondrial biogenesis (ND1, ND2, COX3, ATP6, etc.). Further KEGG pathway enrichment analysis showed that CDCA significantly enriched the signaling pathways of DNA replication, cell cycle, and p53. Collectively, this study demonstrated that CDCA could promote IPEC-J2 proliferation by regulating cell cycle progression and mitochondrial function. These findings provide a new strategy for promoting the intestinal health of pigs by regulating intestinal BA metabolism.

Glutinous cytoplasmic male sterile (CMS) line is necessary to select hybrid glutinous rice combination with high yield and quality. To develop glutinous CMS with low amylose content, in this study, we firstly knocked out the granule-bound starch synthase OsWaxy in 209B using CRISPR/Cas9 mediated genome editing technology and successfully obtained a glutinous maintainer line WX209B. Comparing with maintainer line 209B, WX209B showed decreased amylose contents and similar agronomic characters. And then, through one generation of hybridization and two generations of backcrossing with WX209B as the male parent and 209A as the female parent, the glutinous CMS line WX209A was successfully achieved. Our study provides a strategy to efficiently breed for the glutinous cytoplasmic male sterile line by combining CRISPR/Cas9-mediated gene editing technology with conventional backcross breeding method in a short period, which prepares the ground for further breeding of hybrid glutinous rice variety.

Pingwu Fuzhuan brick tea (PWT), a distinctive post-fermentation tea originated from Pingwu region of Sichuan province in China, is a popular “western road” border-selling tea. In this study, we investigated characteristics and chemical compositions of PWT, together with comparing its physicochemical properties with other regions of Fuzhuan brick teas (FBTs). Firstly, inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the geographical origin of FBTs, and the profiles of mineral elements were subjected to principal component analysis (PCA) to evaluate the differences among FBTs. Results from ICP-MS showed that the compositions of mineral elements from PWT, Hunan FBT (HNT), Shaanxi FBT (SNT), and Guizhou FBT (GZT) were distinctly different. The four different types of FBTs were clearly distinguished according to the results of PCA. Furthermore, all FBT samples were assessed for physicochemical properties and heatmap method was applied to data analysis. It was found that the total colour difference was highly distinct when compared PWT with HNT, SNT and GZT. Moreover, most of contents of biochemical compounds (gallic acid, catechins, free amino acids, alkaloids and volatile components) in PWT were lower compared to others except for total essential amino acids, GABA, aldehydes and acids.