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ObjectiveIn China, lung cancer ranks first in both incidence and mortality among all malignant tumors. Non-small cell lung cancer (NSCLC) constitutes the vast majority of cases, accounting for 80% to 85% of cases. Immune checkpoint inhibitors (ICIs), either as monotherapies or combined with other treatments, have become the standard first-line therapy for NSCLC patients. This study aimed to establish a nomogram model for NSCLC patients receiving immunotherapy incorporating demographic information, clinical characteristics, and laboratory indicators.MethodsFrom January 1, 2019, to December 31, 2022, a prospective longitudinal cohort study involving 1321 patients with NSCLC undergoing immunotherapy was conducted at Chongqing University Cancer Hospital. Clinical and pathological characteristics, as well as follow-up data, were collected and analyzed. To explore prognostic factors affecting overall survival (OS), a Cox regression model was used to test the significance of various variables. Independent prognostic indicators were identified through multivariate analysis and then used to construct a nomogram prediction model. To validate the accuracy and practicality of this model, the concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.ResultIn the final model, 11 variables from the training cohort were identified as independent risk factors for patients with NSCLC: age, KPS score, BMI, diabetes, targeted therapy, Hb, WBC, LDH, CRP, PLR, and LMR. The C-index for OS in the training cohort was 0.717 (95% CI, 0.689–0.745) and 0.704 (95% CI, 0.660–0.750) in the validation cohort. Calibration curves for survival probability showed good concordance between the nomogram predictions and actual observations. The AUCs for 1-year, 2-year, and 3-year OS in the training cohort were 0.724, 0.764, and 0.79, respectively, and 0.725, 0.736, and 0.818 in the validation cohort. DCA demonstrated that the nomogram model had a greater overall net benefit.ConclusionA prognostic model for OS in NSCLC patients receiving immunotherapy was established, providing a simple and reliable tool for predicting patient survival (https://icisnsclc.shinyapps.io/DynNomapp/). This model offers valuable guidance for clinicians in making treatment decisions and recommendations.

Effective management of sediment transport in water bodies is crucial for maintaining navigational channels and reducing siltation in harbors. This study introduces the first effort in the development of a Field Instrument for Measuring Bed Erosion Response based on microcosmic analysis. The device is designed to automatically measure the sediment bed responses under a series of selected bed shear stresses to determine the critical bed shear stresses for sediment incipient motion and the erosion rates for selected excess bed shear stresses. Numerical simulations were conducted using computational fluid dynamics software (FLUENT) to ensure a reasonable and uniform distribution of the selected bed shear stress across the sediment bed. A lab version of this device was also built and tested using granular sandy sediments and the results were validated against the Shields curve for incipient motion. During this test, however, a problem of sandy bed liquefaction at the bed center was identified because of the pumping out of water at top center. For enhancing the device performances, modifications of the pumping intake were made to eliminate the liquefaction problem. Further a lab test on kaolinite beds with three consolidated durations also demonstrated the capability of this improved device. The study confirms the basic design parameters of the improved device, including the optimal rotating speeds of its pump and disk motors, which are critical for achieving the desired erosion dynamics. These results highlight the potential of the device to significantly improve the precision and efficiency of sediment transport studies in natural aquatic environments.

ObjectiveTo investigate the association between plasma total homocysteine (tHcy) levels and behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies (DLB) patients.MethodsA total of 82 DLB patients and 134 age-matched healthy controls were included in this study. DLB patients were assessed using the Mini-Mental Status Examination (MMSE), the Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Plasma tHcy, serum vitamin B12, and folate levels were measured in all study participants. We used Spearman’s rank correlation test to analyze the association between tHcy concentrations and NPI scores, MMSE, CDR, and the duration of dementia in DLB patients.ResultsClinically significant BPSD was present in 92.7% of DLB patients. The most frequent BPSD were hallucinations (30.4%), apathy (30.4%), and delusions (26.8%). Elevated plasma tHcy levels were significantly associated with total NPI scores in DLB patients, particularly in 10 NPI sub-domains, except for agitation/aggression and disinhibition. No statistically significant association was found between plasma tHcy levels and MMSE, CDR, or dementia duration.LimitationsLongitudinal studies with larger sample sizes are required to further explore the relationship between tHcy levels and BPSD in DLB patients as the disease progresses.ConclusionOur study highlighted the high incidence of BPSD and was the first to show that BPSD is associated with elevated plasma tHcy levels in DLB patients in China. These results support the hypothesis that controlling homocysteine levels could offer a new direction for managing BPSD.

This study addresses the unclear understanding of the primary factors controlling fluid mobility in the tuff reservoirs of the Huoshiling Formation from the Dehui Fault Depression, southeastern Songliao Basin. Through physical property analysis, X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), thin section (TS), pressure-controlled porosimetry (PCP), rate-controlled porosimetry (RCP), and nuclear magnetic resonance experiments (NMR) on ten tuff samples, we conducted a comprehensive and in-depth exploration of the influencing factors that control the mobility of reservoir fluids. The results indicate: 1) The primary mineral types in the tuff reservoirs are quartz, feldspar, and clay minerals, with porosity predominantly characterized by dissolution pores and intergranular pores; 2) Based on the morphology of PCP intrusion curves, the tuff samples from the study area can be categorized into three types, with reservoir quality progressively deteriorating from Type I to Type III; 3) Compared to the movable fluids saturation (MFS), movable fluids porosity (MFP) is more suitable for characterizing fluid mobility. The mobility of fluids is influenced by various factors such as mineral composition, physical property, pore-throat connectivity, pore type and heterogeneity. MFS and MFP show a positive correlation with permeability, the content of quartz and feldspar, median pore-throat radius (R50), average throat radius (ATR), average pore-throat radius ratio (APT), T2 cutoff value (T2-C), average throat radius (RT), sorting coefficient (SC), and intergranular pore dominate space (Inter-DS), while a negative correlation with the content of calcite and clay minerals, average pore-throat radius ratio, and the fractal dimension from NMR (DNMR). This study elucidates the influencing factors of fluid mobility in tuff reservoirs, which has important reference significance for the scientific development of this type of gas reservoir.

ObjectivePolycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that impacts 8-13% of women in their reproductive years. However, the drugs commonly used to treat PCOS are often prescribed off-label and may carry potential side effects. This study aimed to investigate the therapeutic effects of curcumin in a PCOS rat model.Materials and methodsA PCOS rat model was established through daily subcutaneous injection of 60 mg/kg body weight of dehydroepiandrosterone (DHEA) for 21 days. The PCOS rats received a daily intragastric dose of 50 mg/kg body weight of curcumin for another 21 days. Ovarian morphological changes, estrous cycle changes, and hormone level changes were measured to evaluate the therapeutic effectiveness of curcumin in PCOS rats. Oxidative stress markers in the ovaries were analyzed to explore the mechanisms of curcumin in PCOS rats.ResultsThis study demonstrated that curcumin alleviated insulin resistance and significantly reduced serum levels of estradiol (p = 0.02), luteinizing hormone (p = 0.009), testosterone (p = 0.003), and the LH/FSH ratio (p = 0.008) in PCOS rats. Curcumin also restored normal ovarian morphology and the estrous cycle in these rats. Furthermore, curcumin treatment significantly decreased levels of oxidative stress markers, including malondialdehyde (p = 0.004) and reactive oxygen species (p = 0.005), while increasing antioxidant levels such as superoxide dismutase (p = 0.04), glutathione peroxidase (p = 0.002), and glutathione (p = 0.02) in ovarian tissues. Additionally, curcumin significantly upregulated PPAR-γ in the ovarian tissues of PCOS rats.ConclusionThis study demonstrates that curcumin effectively restores ovarian morphology, hormone levels, and estrous cycles in PCOS rats. These effects may be linked to its ability to reduce oxidative stress in ovaries via the upregulation of PPAR-γ. Curcumin shows promise as a potential drug for the treatment of PCOS.

Introduction/backgroundVibrio cholerae is the causative agent of the human intestinal infectious disease cholera, which includes a variety of serogroups. However, there have been very few cases of hepatic space-occupying lesions associated with this infection. Currently, there are various methods for detecting this pathogen, including metagenomic sequencing, which enables quicker and more accurate identification. In this study, metagenomic sequencing is employed to accurately identify non-O1/O139 Vibrio cholerae infections by analyzing the genetic material present in clinical samples.Presentation of caseA 75-year-old man presented with diarrhea and fever after consuming crabs. The initial treatment improved the diarrhea, but a liver abscess developed later. Magnetic resonance imaging (MRI) of the liver revealed a hepatic space-occupying lesion. Upon further investigation, a Gram-negative, rod-shaped bacterium was cultured from the patient’s liver puncture fluid, and Vibrio cholerae was detected in the same fluid using metagenomic next-generation sequencing (mNGS). The pathogen was confirmed to be non-O1/non-O139 Vibrio cholerae (NOVC) using polymerase chain reaction (PCR). Following treatment with piperacillin/tazobactam sodium and moxifloxacin, the patient’s body temperature returned to normal, the liver abscess improved significantly, and he was subsequently discharged from the hospital.DiscussionThis case study describes an elderly male patient with a hepatic space-occupying lesion. Multiple cultures of specimens failed to identify the underlying cause; however, advanced techniques such as mNGS and PCR confirmed an NOVC infection. This indicates that mNGS can serve as a valuable tool in diagnosing cases of unexplained liver infections.ConclusionThe use of mNGS is significant for detecting and clinically diagnosing infectious pathogens in patients with unexplained space-occupying lesions.

BackgroundFollowing the Chinese guidelines’ recommendation to completely cancel routine cephalosporin skin tests, the choice of cephalosporin as surgical prophylactic medication was affected. This was due to the limited cognition of the predictive value of cephalosporin skin test or the desire to avoid medical disputes. The aim of this retrospective study was to evaluate whether the pharmacist-led perioperative antibiotic prophylaxis model could improve clinicians’ medical behavior in choosing cephalosporin antibiotics for surgical prophylaxis.MethodsFrom July 2021 to May 2022, a retrospective analysis was conducted on the selection of surgical preventive medication, skin test, postoperative infection and adverse drug reactions in foot and ankle surgery. The study was divided into three period: the rountine cephalosporin skin test period (Period I: Skin Test), the period when the routine cephalosporin skin test was cancelled but the pharmacist did not intervene (Period II: Cancel Skin Test), and the period when the pharmacist-led perioperative antibiotic prophylaxis was implemented after the cancellation of the cephalosporin skin test (Period III: Pharmacist Intervention).ResultsA total of 1,583 patients were enrolled in this study. There was no significant difference in the utilization rate of cefuroxime between the routine skin test stage and the skin test cancelled stage [74.92% (Period I) vs. 74.54% (Period II), P > 0.05]. However, in the pharmacist intervention stage, the usage rate of cefuroxime significantly increased compared to the initial stage when the skin test was cancelled [87.07% (Period III) vs. 74.54% (Period II), P < 0.05]. The use of cephalosporins also increased in patients with self-reported beta-lactam allergies between these stages [41.94% (Period III) vs. 3.22% (Period II), P < 0.05)]. There was no significant difference in the incidence of postoperative infection and adverse drug reactions among the three periods.ConclusionThe pharmacist-led perioperative antibiotic prophylaxis model can significantly improve the medical behavior of clinicians in choosing cephalosporin antibiotics as surgical prophylactic medication and optimize the perioperative medication plan.

BackgroundLeft-behind children (LBC) refer to those who have been separated from at least one parent for six months or more due to parental migration for work. This phenomenon poses a significant threat to the mental health of over 61 million LBC in China. This study aims to compare the prevalence of mental health symptoms between LBC and non-left-behind children (non-LBC) and to explore the predictive effect of bullying victimization on adolescent mental health problems.MethodsIn 2019, we conducted a cross-sectional analysis involving 28,036 children and adolescents in Mianyang City, Sichuan Province, China, with ages ranging from 8 to 19 years. Mental health symptoms were assessed using the 7-item Generalized Anxiety Disorder (GAD-7) scale and the 9-item Patient Health Questionnaire (PHQ-9). The Delaware Bullying Victimization Scale-Student (DBVS-S) was employed to gather data on experiences of bullying victimization. Information on self-injury was collected by inquiring whether participants had engaged in self-injurious behavior and the reasons for such behavior. Multivariable logistic regression was utilized to analyze the risk and protective factors associated with mental health symptoms, with a particular focus on different types of bullying victimization.ResultsCompared to non-left-behind children (non-LBC), left-behind children (LBC) exhibited a higher prevalence of mental health issues: anxiety symptoms (24.0% vs. 18.0%, p

Asthma has become one of the most serious chronic respiratory diseases threatening people's lives worldwide. The pathogenesis of asthma is complex and driven by numerous cells and their interactions, which contribute to its genetic and phenotypic heterogeneity. The clinical characteristic is insufficient for the precision of patient classification and therapies; thus, a combination of the functional or pathophysiological mechanism and clinical phenotype proposes a new concept called “asthma endophenotype” representing various patient subtypes defined by distinct pathophysiological mechanisms. High-throughput omics approaches including genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome enable us to investigate the pathogenetic heterogeneity of diverse endophenotypes and the underlying mechanisms from different angles. In this review, we provide a comprehensive overview of the roles of diverse cell types in the pathophysiology and heterogeneity of asthma and present a current perspective on their contribution into the bidirectional interaction between airway inflammation and airway remodeling. We next discussed how integrated analysis of multi-omics data via machine learning can systematically characterize the molecular and biological profiles of genetic heterogeneity of asthma phenotype. The current application of multi-omics approaches on patient stratification and therapies will be described. Integrating multi-omics and clinical data will provide more insights into the key pathogenic mechanism in asthma heterogeneity and reshape the strategies for asthma management and treatment.

Gas hydrates are globally acknowledged as a significant strategic alternative energy source, and there is a consensus on the necessity to enhance their exploration. However, gas hydrates are highly prone to decomposition under variations in external environmental conditions, which can result in subsea methane seepage activities. Consequently, investigating subsea methane seepage activities holds substantial theoretical and practical significance for exploring gas hydrates. This paper evaluates the history of methane seepage activities in the Qiongdongnan Basin (QDNB) by analyzing the carbon and oxygen isotopic characteristics of benthic foraminifera and the geochemical properties of pore water from gravity sediment cores at sites QH-CL4 and QH-CL40. The results indicate that since the Marine isotope stage2 (MIS2), continuous micro-methane seepage activity has been present in the QDNB, characterized by a slight negative deviation in the carbon isotopes of benthic foraminifera. Methane seepage activity intensified during 14.6 ka BP and between 19.64–23.22 ka BP. This increase is thought to be associated with rising seawater temperature during the Bølling–Allerød interstadial and declining sea level during the Last Glacial Maximum, respectively. Moreover, current geochemical characteristics of pore water reveal strong methane seepage activity, with flux as high as 28.968 mmol·m-²·a-¹. This ongoing activity has led to gas hydrate formation within shallow layers while also causing negative deviations in pore water salinity.

BackgroundThe early detection and intervention of liver fibrosis (LF) in patients with chronic liver disease is critical to their management. The accuracy of serum Mac-2 binding protein glycosylation isomer (M2BPGi) in the diagnosis of LF remains controversial. This study aimed to comprehensively assess the value of serum M2BPGi in diagnosing LF.MethodsThe PubMed, Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched. The effect values were combined using a random-effects model. Meta-regression and subgroup analysis were used to explore the sources of heterogeneity. In addition, publication bias assessment and sensitivity analysis were conducted.ResultsThis study includes 12 studies with 2,416 patients. The pooled sensitivity, specificity, and AUROC of M2BPGi in the diagnosis of significant fibrosis (≥F2) were 0.65 (95% CI: 0.57–0.71), 0.79 (95% CI: 0.72–0.84), and 0.78 (95% CI: 0.74–0.81), respectively, while those for predicting extensive fibrosis (≥F3) were 0.76 (95% CI: 0.71–0.80), 0.75 (95% CI: 0.68–0.81), and 0.81 (95% CI: 0.77–0.84). Sensitivity analysis indicated stable results in this study. The disease type, cut-off values, study country, average age, and male proportion were the sources of heterogeneity in diagnosing significant fibrosis of M2BPGi (p < 0.05). Sample size, disease type, study country, publication year, cut-off values, average age, and male proportion were important sources of heterogeneity in diagnosing extensive fibrosis (p < 0.05).ConclusionSerum M2BPGi has good diagnostic performance for significant fibrosis and extensive fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), or nonalcoholic fatty liver disease (NAFLD) and is an effective, non-invasive, and convenient marker.Systematic Review Registrationhttps://inplasy.com/inplasy-2023-10-0086/.

Goiter related to excessive iodine nutrition remains a significant public health issue in some countries. There has been no reported study on long noncoding RNAs (lncRNAs) related to goiters. In this study, goiter was induced by drinking water with excess iodine for 10 or 20 weeks in Kunming mice. Whole transcriptome sequencing results showed that LNC89 expression increased in mice goiter tissues compared to normal thyroid tissues and higher in 20 weeks goiter tissues than in 10 weeks goiter tissues, which were identified by qRT−PCR. Cooperate with human-mouse homologous gene conversion, a new LNC89/LNC60-Col11a2 axis was predicted by LncTar and expression correlation analysis based on whole transcriptome sequencing results. Increased Col11a2 expression was also identified by qRT−PCR and Western blot in the mice goiter tissues. In the human normal thyroid cell line Nthy-ori-3 treated with KI03, LNC60 and Col11a2 expression increased with promoted cell viability, which were reversed by siLNC60 treatment. Furthermore, LNC60 and Col11a2 mRNA levels were found increased in peripheral blood of nodular goiter patients from high water iodine areas of China and have high diagnostic values for nodular goiter while AUC of LNC60 and Col11a2 are 89.97% and 84.85%, respectively. In conclusion, the novel LNC89/LNC60-Col11a2 axis may be involved in the progression of goiter related to iodine excess, providing potential biomarkers and therapeutic targets in the future.

BackgroundBurns are a global health issue causing significant mortality and high medical costs. Non-pharmacological interventions such as music therapy and virtual reality (VR) therapy have shown potential in alleviating pain and anxiety in burn patients. This study systematically evaluates the impact of these interventions using a network meta-analysis.MethodsA systematic review and network meta-analysis were conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD42024566536). Searches in PubMed, Cochrane Library, Web of Science, and Embase up to November 22, 2023, identified randomized controlled trials (RCTs) involving music therapy or VR therapy in burn patients. The Cochrane Risk of Bias Tool (2.0) assessed study quality. Data were analyzed using StataMP-64 software.ResultsSeventeen RCTs with 1,119 burn patients were included. Both music therapy and VR therapy significantly reduced pain and anxiety compared to control groups. Music therapy was more effective for pain reduction (SUCRA: 85.4%), while VR therapy was superior for anxiety relief (SUCRA: 79.5%).ConclusionMusic therapy and VR therapy effectively reduce pain and anxiety in burn patients. Integrating these interventions into burn care can enhance patient outcomes. Further research is needed to confirm these findings and optimize individualized treatment plans.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42024566536).

IntroductionN-phenyl-2-(aniline) analog N53 is a previously discovered dual inhibitor of Topo I and COX-2, which exhibited significant anti-colon cancer activity in vitro, but the poor solubility and moderate anti-cancer activity in vivo hindered its further development.MethodsTo rectify the suboptimal drug properties of N53, a series of salt forms were developed and further evaluated through in vivo and in vitro experiments.ResultsThe hydrochloride (N53·HCl) has a well-characterized crystal structure and its solubility reached 540.1 μg/mL, which is nearly 1,700 times higher than that of N53 (0.32 μg/mL). Increasing the N53 solubility consistently promotes its effective concentration, further enhancing the COX-2/Topo I inhibitory activity and the anti-tumor activity in vitro (IC50 values of 2.95 ± 0.08 μM for HT29 cells, 7.99 ± 0.85 μM for RKO cells, 10.94 ± 1.30 μM for HCT116 cells), as well as the anti-proliferative and pro-apoptotic activity. Meanwhile, its oral pharmacokinetic property in vivo is also improved. The elimination half-life (T1/2) is prolonged from 10.78 to 22.29 h, the maximum plasma concentration (Cmax) is increased 2-fold, and the area under the plasma drug concentration-time curve (AUC0–∞) is increased 3-fold. In colon cancer xenograft mouse models, the tumor inhibition rate of N53·HCl was 53.7%, superior to that of N53 (34.7%). Moreover, the results of HE staining showed that N53·HCl had no obvious toxic effects and side effects on other organs, indicating that it was safe in vivo.DiscussionThis study demonstrated that N53·HCl exhibits superior pharmacokinetic properties, anti-colon cancer efficacy, and safety, providing a promising drug candidate for colon cancer therapy.

Herpesviruses are a family of double-stranded DNA viruses with a tegument structure and a genome composed of a single sequence and terminal repeat (TR) sequences. The herpesvirus UL14 gene encodes the protein UL14 (pUL14), which has various subcellular localizations and plays a vital role in regulating immediate–early (IE) gene transcription and expression, influences the intracellular localization patterns of several proteins belonging to the capsid and the DNA packaging machinery, participates in secondary envelopment, and influences viral particle release. Additionally, pUL14 has roles in maintaining cellular homeostasis and preventing apoptosis. This review discusses how pUL14 engages in the life cycle of herpesviruses and provides new ideas for further research on pUL14’s function in viral infection.

Peptide hormones regulate plant development, growth, and stress responses. Sulfated peptides represent a class of proteins that undergo posttranslational modification by tyrosylprotein sulfotransferase (TPST), followed by specific enzymatic cleavage to generate mature peptides. This process contributes to the formation of various bioactive peptides, including PSKs (PHYTOSULFOKINEs), PSYs (PLANT PEPTIDE CONTAINING SULFATED TYROSINE), CIFs (CASPARIAN STRIP INTEGRITY FACTOR), and RGFs (ROOT MERISTEM GROWTH FACTOR). In the past three decades, significant progress has been made in understanding the molecular mechanisms of sulfated peptides that regulate plant development, growth, and stress responses. In this review, we explore the sequence properties of precursors, posttranslational modifications, peptide receptors, and signal transduction pathways of the sulfated peptides, analyzing their functions in plants. The cross-talk between PSK/RGF peptides and other phytohormones, such as brassinosteroids, auxin, salicylic acid, abscisic acid, gibberellins, ethylene, and jasmonic acid, is also described. The significance of sulfated peptides in crops and their potential application for enhancing crop productivity are discussed, along with future research directions in the study of sulfated peptides.

ObjectiveWe aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM).MethodsThis open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology–European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti–signal recognition particle (SRP) and anti–3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events.ResultsThe seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1–5) years, P = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, P = 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, P = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, P = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache.ConclusionsDespite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features.

Vegetables are important economic crops globally, and their production has approximately doubled over the past 20 years. Globally, vegetables account for 13% of the harvested area but consume 25% of the fertilizer, leading to serious environmental impacts. However, the quantitative evaluation of vegetable production systems in subtropical plateau lake basins and the establishment of optimal management practices to further reduce environmental risks are still lacking. Using the life cycle assessment method, this study quantified the global warming, eutrophication, acidification, and energy depletion potential of vegetable production in a subtropical plateau lake basin in China based on data from 183 farmer surveys. Our results indicated that vegetable production in the study area, the Erhai Lake Basin, was high but came at a high environmental cost, mainly due to low fertilizer efficiency and high nutrient loss. Root vegetables have relatively high environmental costs due to the significant environmental impacts of fertilizer production, transportation, and application. A comprehensive analysis showed that the vegetable production in this region exhibited low economic and net ecosystem economic benefits, with ranges of 7.88–8.91 × 103 and 7.35–8.69 × 103 $ ha−1, respectively. Scenario analysis showed that adopting strategies that comprehensively consider soil, crop, and nutrient conditions for vegetable production can reduce environmental costs (with reductions in global warming potential (GWP), eutrophication potential (EP), acidification potential (AP), and energy depletion potential (EDP) by 10.6–28.2%, 65.1–73.5%, 64.5–71.9%, 47.8–70.4%, respectively) compared with the current practices of farmers. This study highlighted the importance of optimizing nutrient management in vegetable production based on farmers’ practices, which can achieve more yield with less environmental impacts and thereby avoid the “trade-off” effect between productivity and environmental sustainability.

IntroductionThe rapid advances in marine engineering projects are exacerbating environmental pressures on bay ecosystems. This study utilized the MIKE 21 model to evaluate the impacts of such projects in Laizhou Bay (LZB) on hydrodynamic conditions and the spread of dissolved inorganic nitrogen (DIN) from riverine inputs.ResultsThe results indicated an expansion of 80.77 km2 in areas with DIN concentrations surpassing 0.5 mg/L 2 months after input from the Yellow River, with increased levels in the southern Yellow River Delta. Decreased flow velocities adjacent to the wave barriers at the Xiaoqing River estuary impeded lateral DIN dispersion, resulting in a 0.93 mg/L increase in DIN concentrations at the river mouth. After the construction of marine engineering projects (2020), significant alterations in the coastline of LZB have markedly modified hydrodynamic characteristics near marine structures, altering DIN dispersion patterns.ConclusionThis study provides crucial information for the management of pollutants at estuaries, understanding dispersion mechanisms, and evaluating the feasibility and environmental compatibility of marine engineering projects.

BackgroundFei-Yan-Qing-Hua decoction (FYQHD) is derived from the well-known Ma Xing Shi Gan decoction, which was documented in Zhang Zhong Jing’s “Treatise on Exogenous Febrile Disease” during the Han Dynasty. Although FYQHD has been used in the treatment of pneumonia and has demonstrated clinical efficacy for decades, the underlying mechanism by which FYQHD protects against influenza virus infection through modulation of gut flora remains unclear. Here, we examined the regulatory impacts of FYQHD on an influenza virus-infected mouse model and explored the mechanisms involved.MethodsAn infectious mouse model was created by intranasal instillation of influenza A virus (IAV). The effectiveness of FYQHD was assessed through various measures, including weight loss, lung wet/dry ratio, oxidative stress levels, viral load in lung tissues, and intestinal injuries. Changes in gut microbiota and SCFA production were also examined.ResultsThe results showed that FYQHD significantly reduced viral load, increased the production of type I interferon (IFN-I), and restored the integrity of the intestinal barrier following IAV challenge. Additionally, FYQHD significantly corrected the dysbiosis of gut microbiota induced by influenza virus infection, enhancing the abundance of SCFA-producing bacteria and acetate production. However, the depletion of gut microbiota significantly attenuated the protective effects of FYQHD against influenza virus infection. In vitro, the antiviral effect of acetate was demonstrated through the upregulation of concentrations of IFN-β.ConclusionFYQHD attenuates influenza virus-induced lung and intestinal injuries by boosting the host antiviral response through increasing the abundance of Lachnospiraceae_NK4A136 and Roseburia, along with elevated acetate levels. The study advances our understanding of the therapeutic mechanisms of FYQHD and provides a theoretical basis for the application of FYQHD in the treatment of influenza.

BackgroundThe prevalence of depression among university and college students in China is nearly one-quarter. This study aimed to investigate the knowledge, attitudes and practices (KAP) among medical students toward depression management. Depression, a significant public health issue, has a substantial impact on students, with a reported prevalence of 23.8% among university and college students in China.MethodsThis web-based cross-sectional study was conducted between January 2023 and October 2023 at three medical universities in China. A self-administered questionnaire collected demographic information and assessed medical students’ KAP on depression management.ResultsA total of 632 participants were enrolled in this study from three medical universities. Among them, 383 (60.60%) were female, and the participants were aged 20.17 years on average (SD ± 1.80). Most of their family members (521, 82.44%) were not in the medical profession. Using a validated 15-point knowledge scale, a 50-point attitude scale, and a 30-point practice scale, which covered areas such as symptom recognition, treatment approaches, and stigma related to depression, the mean knowledge, attitudes and practices scores were 10.55 ± 3.36 (possible range: 0–15), 41.72 ± 4.45 (possible range: 10–50) and 19.79 ± 5.44 (possible range: 6–30), respectively. Males had lower knowledge (p = 0.003). Only children had higher practice (p = 0.034). Urban residents had higher attitudes (p = 0.046). Higher income linked to better practice (p = 0.047). Freshmen scored higher across all KAP (p

Salix psammophila, commonly known as the sandlive willow, is a vital shrub species within the Salicaceae family, particularly significant for its ecological role in regions susceptible to desertification and sandy soils. In this study, we assembled the complete S. psammophila mitochondrial genome using Pacbio HiFi third-generation sequencing data. The genome was found to be a typical single circular structure, with a total length of 715,555 bp and a GC content of 44.89%. We annotated 33 unique protein-coding genes (PCGs), which included 24 core mitochondrial genes and 9 variable genes, as well as 18 tRNA genes (5 of which were multicopy genes) and 3 rRNA genes. Comparative analysis of the PCGs from the mitochondrial genomes of S. psammophila, Populus deltoides, Populus simonii, Salix wilsonii, and Salix suchowensis revealed that these genes are relatively conserved within the Salicaceae family, with variability primarily occurring in the ribosomal protein genes. The absence of the rps14, which encodes a ribosomal protein, may have played a role in the evolution of stress tolerance in Salicaceae plants. Additionally, we identified 232 SSRs, 19 tandem repeat sequences, and 236 dispersed repeat sequences in the S. psammophila mitochondrial genome, with palindromic and forward repeats being the most abundant. The longest palindromic repeat measured 260 bp, while the longest forward repeat was 86,068 bp. Furthermore, 324 potential RNA editing sites were discovered, all involving C-to-U edits, with the nad4 having the highest number of edits. These findings provide valuable insights into the phylogenetic and genetic research of Salicaceae plants.

Shade has a direct impact on photosynthesis and production of plants. Exposure to shade significantly reduces crops yields. Identifying shade-tolerant genomic loci and soybean varieties is crucial for improving soybean yields. In this study, we applied a shade treatment (30% light reduction) to a natural soybean population consisting of 264 accessions, and measured several traits, including the first pod height, plant height, pod number per plant, grain weight per plant, branch number, and main stem node number. Additionally, we performed GWAS on these six traits with and without shade treatment, as well as on the shade tolerance coefficients (STCs) of the six traits. As a result, we identified five shade-tolerance varieties, 733 SNPs and four candidate genes over two years. Furthermore, we developed four kompetitive allele-specific PCR (KASP) makers for the STC of S18_1766721, S09_48870909, S19_49517336, S18_3429732. This study provides valuable genetic resources for breeding soybean shade tolerance and offers new insights into the theoretical research on soybean shade tolerance.

Water resource carrying capacity is a critical measure of the ability of water resources within a region to support social, ecological, and economic scales. This study establishes an evaluation index system for the water resource carrying capacity of Golmud City and calculates the weights of the indices using the Analytic Hierarchy Process (AHP). Based on an analysis of the current status of Golmud’s socio-economic development, agriculture, and water resource utilization, a simulation model based on system dynamics is constructed. By setting 162 different scenario plans and normalizing the simulation results, the development trend of Golmud City’s water resource carrying capacity is studied, and an evaluation is made for the sustainable development of water resources in Golmud City. Using data from 2001 to 2018 as the basic data, a carrying capacity analysis of water resources for the future from 2019 to 2030 is conducted. The study reveals that continuing the current development pattern will lead to unsustainable water resource carrying capacity. Among the scenarios aimed at coordinated development in all aspects, the best water resource carrying index is achieved, reaching 0.698 by 2030. By analyzing the development trend of the water resource carrying capacity index, existing problems in the utilization of water resources in Golmud City are identified, and feasible strategies for the sustainable use of water resources in Golmud City are proposed.

BackgroundRituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate.MethodsThis study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess “Improved clinical status” and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment.ResultsA total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84–96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of −1.69 (95% CI: −2.21 to −1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80–97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of −1.51 (95% CI: −0.80 to −2.21, Z = 4.50, P < 0.001). In the muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89–100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of −2.31 (95% CI: −2.99 to −1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma.ConclusionOur meta-analysis shows that low-dose RTX is both effective and safe for treating MG.Systematic Review RegistrationPROSPERO, identifier: CRD42024509951.

ObjectiveThis study is aimed to evaluate the efficacy and safety of PD-1 inhibitors combined with neoadjuvant chemotherapy in patients with locally advanced hypopharyngeal and oropharyngeal cancer prior to surgical resection.MethodsThis retrospective analysis included 42 patients diagnosed with locally advanced hypopharyngeal and oropharyngeal cancer. The efficacy, safety, survival, and laryngeal preservation rate were evaluated.ResultsA total of 42 patients were included in this retrospective analysis, of whom 28 had hypopharyngeal cancer and 14 had oropharyngeal cancer. Of the 42 patients, 14 (33.3%) achieved a pathological complete response (PCR) at the primary site, 20 (47.6%) achieved a major pathological response (MPR), and 8 (19%) had an incomplete pathological response (IPR) at the primary lesion. A PCR at both the primary site and the neck lymph nodes was observed in 9 patients (21.4%). The laryngeal preservation rate was 92.9% (26/28) in patients with hypopharyngeal cancer. The median follow-up time was 10.5 months. The median progression-free survival (PFS) was 26.42 months (95% CI, 23.416–29.424), and the median overall survival (OS) was 27.1 months (95% CI, 24.316–29.884). The 1-year PFS rate was 83.1%, and the 1-year OS rate was 85.9%.ConclusionCombination therapy with PD-1 inhibitors and neoadjuvant chemotherapy has demonstrated superior efficacy and safety as a preoperative treatment for locally advanced hypopharyngeal and oropharyngeal cancer. Notably, this treatment regimen does not increase the risk of severe postoperative complications and has shown promising results in improving laryngeal preservation rates.

Mood disorders, including major depressive disorder and bipolar disorder, have a profound impact on more than 300 million people worldwide. It has been demonstrated mood disorders were closely associated with deviations in biogenic amine metabolites, which are involved in numerous critical physiological processes. The peripheral and central alteration of biogenic amine metabolites in patients may be one of the potential pathogeneses of mood disorders. This review provides a concise overview of the latest research on biogenic amine metabolites in mood disorders, such as histamine, kynurenine, and creatine. Further studies need larger sample sizes and multi-center collaboration. Investigating the changes of biogenic amine metabolites in mood disorders can provide biological foundation for diagnosis, offer guidance for more potent treatments, and aid in elucidating the biological mechanisms underlying mood disorders.

BackgroundPrimary and secondary school teachers are a high-risk group for job burnout, and how to alleviate their job burnout has become an increasingly urgent issue. Previous studies have paid less attention to the differential effects of the bidirectional interaction between work and family on the job burnout of the teachers. This study aim to explore the different impact of work–family conflict and family–work conflict on job burnout among primary and secondary school teachers, as well as its underlying mechanisms.MethodsThis study selected 2,184 primary and secondary school teachers in China (Mage = 37.26; SD = 9.40) as participants using a random sampling method. Using the SPSS Process 4.0 macro plugin constructed a moderated mediation model, the study explored the relationships between two different forms of work–family conflict, depression, cognitive reappraisal, and job burnout.ResultsThe study results indicated that both forms of work–family conflict were significantly positively related to the job burnout, and this relationship was influenced by the mediating role of depression. Furthermore, cognitive reappraisal moderated the relationship between depression and job burnout.ConclusionThis study revealed the potential pathways influencing job burnout among primary and secondary school teachers in the Chinese cultural context. Focusing on and alleviating work–family conflicts for primary and secondary school teachers is crucial for mitigating their occupational burnout. Additionally, teachers should also carefully and reasonably use cognitive reappraisal as an emotional regulation strategy to adjust the impact of depression on occupational burnout.

During the construction of cable joints, three common defects may occur on the XLPE surface: scratches, moisture exposure, and adhered contaminated particles. To evaluate the impact of these defects on joint performance, this paper establishes a sheet model of XLPE insulation in cable joints to analyze the changes in the electric field under different defects and explore the influence of different defects on the electric field and breakdown voltage. Results of the study reveal that the electric field at the scratch site on XLPE produces severe distortion, being 1.6 times that of non-scratch areas. When exposed to moisture, the more conductive impurities present in the adhered contaminated water on the XLPE surface, the higher the conductivity of the contaminated water, thereby increasing its conductive performance and the electric field strength, which is 1.22–1.4 times that of the non-moist interface. When particles adhere to the XLPE surface, severe distortion occurs at the particle-interface electric field, approximately 1.5 times that of the defect-free interface. Scratches have the most significant impact on the electric field of XLPE insulation. Experimental results also demonstrate that the breakdown voltage without defects is 129.6 kV, while the breakdown voltage with scratch defects is 59.1 kV, moisture defects is 69.7 kV, and particle contamination defects is 59.2 kV, with scratches having the most significant impact on the breakdown voltage of XLPE insulation. These findings provide important insights into the influence of different defects on the insulation performance of cable joints.

Drought stress poses increasingly serious threats to agricultural production in the era of global climate change. Arbuscular mycorrhizal (AM) fungi are well-recognized biostimulants promoting plant tolerance to drought stress. Lipids are indispensable for AM fungal colonization, however, the involvement of lipid metabolism in the drought tolerance conferred by AM fungi is largely unknown. In this study, we inoculated Poncirus trifoliata (L.) with Rhizophagus irregularis DAOM197198 under no drought stress, medium drought stress and severe drought stress, with non-inoculation under respective treatments as control. Results indicated that AM fungal inoculation significantly promoted the drought tolerance of P. trifoliata (L.), with the effect size decreasing along with drought severity. Moreover, the effect size was significantly related to arbuscule abundance. Fatty acid profiling showed that the arbuscule abundance was determined by the AM-specific phospholipids (PLs), whose biosynthesis and delivery were inhibited by drought stress as revealed by qRT-PCR of FatM, RAM1 and STR/STR2. More interestingly, AM fungal inoculation increased the lipid allocation to total PLs and the unsaturation rate of total neutral lipids (NLs), probably indicating the involvement of non-AM-specific lipids in the increased drought tolerance. Taken together, our results demonstrate that lipid metabolism in AM mediates the increased drought tolerance conferred by AM fungal inoculation, with AM-specific and non-AM-specific lipids functioning therein in different ways.

ObjectiveThis study aims to assess the early to mid-term clinical efficacy of expanded polytetrafluoroethylene (ePTFE) trileaflet valved conduits in pediatric right ventricular outflow tract reconstruction for congenital heart disease.MethodsWe conducted a retrospective analysis of pediatric patients who underwent right ventricular outflow tract (RVOT) reconstruction using ePTFE trileaflet valved conduits at two cardiac centers in China, between January 2017 and June 2023. The main assessment criterion was the functionality of the prosthetic pulmonary valve conduit.ResultsA total of 162 pediatric patients were included, with follow-up periods ranging from 0.1 to 5 years post-discharge, and a median follow-up duration of 1 year (interquartile range: 1, 2). Three patients (1.9%) required re-operation due to conduit obstruction. During follow-up, pulmonary valve flow velocities were recorded as 4 m/s in 4 patient (2.5%). Mild pulmonary valve regurgitation was noted in 148 patients (91.4%), and moderate pulmonary valve regurgitation was noted in 14 patients (8.6%), with no instances of more than moderate pulmonary valve regurgitation.ConclusionThe ePTFE trileaflet valved conduit, known for its accessibility and simplicity in manufacturing, demonstrates favorable early to mid-term clinical outcomes in pediatric RVOT reconstruction.

In the case of resistance-inductance lines in PV station area, the problem of voltage overstep is easy to occur. This article proposes a reactive power compensation control method to improve the voltage stability in the photovoltaic power plant area, which addresses the problem of voltage at the point of common coupling (PCC) exceeding the upper limit due to resistance circuits and exceeding the lower limit due to relatively insufficient reactive power output when the output active power is high. The idea is to achieve dynamic adjustment of PCC voltage by paralleling a static reactive power generator (SVG) at the grid connection point and using a variable droop control method. In addition, a reactive power optimization method based on improved particle swarm optimization (IPSO) algorithm is proposed to address the changes in power flow caused by photovoltaic integration in the distribution network system. The proposed improvement method not only effectively reduces network losses but also significantly improves voltage stability.

The comprehensive effects of nanoparticles and coexisting heavy metals on plant growth are still unclear, especially in soil medium. The single and combined effects of multiwall carbon nanotubes (MWCNTs) and cadmium (Cd) on rice (Oryza sativa L.) growth were examined in this study through a 4 months pot experiment in 2022. Rice plants were exposed to different concentrations of MWCNTs (100 and 500 mg kg−1) in the presence of 5.0 mg kg−1 Cd stress. At the tillering stage, the 500 mg kg−1 MWCNTs addition reduced plant height by 8.0% and increased soluble protein content in the leaves by 13.7%, demonstrating that a single MWCNTs had a slight negative impact on rice growth. When exposed to Cd stress, the inclusion of 500 mg kg−1 MWCNTs led to a 6.7%–9.0% decrease in bioavailable Cd level in soil, resulting in considerable reductions in Cd content in roots (23.4%–29.9%), shoots (24.5%–28.3%) and grains (28.3%–66.2%). Compared to the single Cd treatment, the O. sativa L. leaves treated with Cd and MWCNTs (500 mg kg−1) had considerably reduced levels of malondialdehyde (MDA), soluble protein, and activities of antioxidant enzymes (POD, CAT, and SOD). The findings of this study indicated that appropriate concentrations of MWCNTs application in soil could alleviate Cd-induced toxicity on rice growth.

Donkey meat is characterized by a high content of proteins, essential amino acids, and unsaturated fatty acids and is low in fat, cholesterol, and calories. Thus, it is considered a high-quality source of meat. Based on the data from PubMed and Web of science within past 10 years, this review summarizes the factors affecting the quality of donkey meat and its nutritional value, including breed, genetics, gender, age, muscle type, feeding regimen, storage and processing conditions. Breed, gender, age, and feeding regimen mainly affect the quality of donkey meat by influencing its intramuscular fat content and carcass quality. Meanwhile, the tenderness and flavor of donkey meat depend on the muscle type, storage and processing conditions. Genetics, on the other hand, fundamentally affect donkey meat quality by influencing the polymorphism of genes. These findings provide valuable insights and guidance for producers, consumers, and decision-makers in the donkey meat industry, promoting the development of more effective marketing strategies and the improvement of meat quality, thereby enabling the expansion and progress of the entire industry.

BackgroundPulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored.MethodsNetwork analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-β1 (TGF-β1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2’s effects against PF.ResultsNetwork analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway.ConclusionLG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

Diabetic wounds are a severe complication of diabetes, characterized by persistent, non-healing ulcers due to disrupted wound-healing mechanisms in a hyperglycemic environment. Key factors in the pathogenesis of these chronic wounds include unresolved inflammation and antioxidant defense imbalances. The cystine/glutamate antiporter SLC7A11 (xCT) is crucial for cystine import, glutathione production, and antioxidant protection, positioning it as a vital regulator of diabetic wound healing. Recent studies underscore the role of SLC7A11 in modulating immune responses and oxidative stress in diabetic wounds. Moreover, SLC7A11 influences critical processes such as insulin secretion and the mTOR signaling pathway, both of which are implicated in delayed wound healing. This review explores the mechanisms regulating SLC7A11 and its impact on immune response, antioxidant defenses, insulin secretion, and mTOR pathways in diabetic wounds. Additionally, we highlight the current advancements in targeting SLC7A11 for treating related diseases and conceptualize its potential applications and value in diabetic wound treatment strategies, along with the challenges encountered in this context.

ObjectivesThe aim of this study is to explore the expression of inflammatory cytokines (ICs) in Fabry disease (FD), the correlation between ICs and FD phenotypes, and the impact of enzyme replacement therapy (ERT) on IC expression.MethodsWe recruited 67 FD patients and 44 healthy controls (HCs) and detected concentrations of the following ICs: interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-β. We also analyzed the impact of ERT on IC expression in FD patients and the relationship between IC expression and sex, genotype, phenotype, disease burden, and biomarkers.ResultsMost ICs were significantly higher in FD patients than in HCs. A number of ICs were positively correlated with clinical aspects, including disease burden (Mainz Severity Score Index [MSSI]) and cardiac and renal markers. IL-8 was higher in the high MSSI (P-adj=0.026*) than in the low MSSI.ConclusionsICs were upregulated in FD patients, indicating the role of the innate immune process in FD etiology. ERT ameliorated FD-related inflammatory activation, at least to some extent. IC expression was positively correlated with disease burden and clinical markers in FD. Our findings indicated that the inflammatory pathway may be a promising therapeutic target for FD.

BackgroundLeft bundle branch area pacing (LBBAP) has become an alternative method for cardiac resynchronization therapy. Various modes of LBBAP have been determined, including left bundle trunk pacing (LBTP), left anterior branch pacing (LAFP) and left posterior branch pacing (LPFP). However, whether the outcomes of various pacing modes differ in heart failure (HF) patients is still unclear. This study aimed to compare the electrophysiological characteristics and echocardiographic response rate among those distinct modes of LBBAP.MethodsHF patients undergoing successful LBBAP were retrospectively included. Distinct modes of pacing were determined based on paced QRS morphology. The fluoroscopic images were collected to compare the lead tip position between the groups. The electrocardiograms (ECG) before and after LBBAP were used to measure the depolarization (QRS duration [QRSd] and the interventricular delay [IVD]), and the repolarization parameters [QTc, TpeakTend(TpTe), and TpTe/QTc]. The left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) of patients were also recorded. In addition, the lead parameters and certain complications were compared.ResultsA total of 64 HF patients were finally included, consisting of 16 (25.0%) patients in the LBTP group, 22 (34.4%) patients in the LAFP group, and 26 (40.6%) patients in the LPFP group. The distribution features of LBBAP lead tips were significantly related to pacing modes: LBTP was more likely to be in zone 4 while LAFP or LPFP was prone to locate in zone 5. After LBBAP, the ventricular ECG parameters were significantly improved, regardless of pacing modes. Besides, the LVEF of the patients was significantly increased (P 0.05). In addition, the lead parameters remained stable and no significant difference was observed among groups.ConclusionLPFP was the main pacing mode among HF patients after LBBAP. The paced QRS morphology was significantly related to the position of lead tips. After LBBAP, the ventricular depolarization synchronization and repolarization stability were both significantly improved, regardless of pacing modes. There was no significant difference in the echocardiographic response rate among distinct LBBAP modes.

The discovery of natural products derived from marine sources has demonstrated a consistent upward trajectory for the decade of 2011-2020, holding significant promise for the development of novel drugs and many other marine bioproducts. In recent years, the spotlight has shifted away from marine sponges (Porifera) towards marine microorganisms as the primary source of discovery. Despite reports of marine sponges spanning 20 different orders and being the subject of 769 papers between 2011 and 2020, they only contributed to 19.29% of all new compounds discovered, in contrast to 51.94% by marine microorganisms and phytoplankton. 563 new compounds were reported from marine sponge-associated microbes, more than doubling the number for the previous decade (2001-2010). It heralds a positive outlook for a sustainable resource strategy as the extraction of bioactive compounds produced by pure cultures of sponge-associated microbes could overcome supply challenges that arise with isolation from host sponges for the same compound. However, the application of novel marine natural products (MNPs) remains challenging due to the limited yield of compounds from large amounts of sponges. This review covers the literature published between 2011 and 2020, focusing on MNPs isolated from marine sponges. A total of 2603 new compounds are documented, detailing their chemical classification, biological activities, source country or geographic locations, and the taxonomic information of the source organisms, including order, family, genus, and species.

To address the issue of high NOx emission from the combustion chamber, this work optimized the industrial machine structure to enhance the combustion performance. The analysis results indicated that the flue gas recirculation (FGR) could effectively reduce the combustion temperature and the distribution of high-temperature regions in the machine chamber, thereby suppressing NOx formation without affecting the gas velocity inside the chamber. Based on the simulation analysis, the FGR technology was applied to modifying the machine structure and evaluated the modification effect in real-world application. It is found that after adding FGR, the oxygen content at the furnace outlet decreased from 13.8% to 10.5%, the NOx emission from the furnace decreased from 80 mg/m3 to 18 mg/m3, and the natural gas consumption decreased by more than 17%. These results demonstrate a significant impact on energy saving and emission reduction after optimizing the machine structure, which can provide a reference basis for subsequent researchers in this field.

BackgroundThe stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting.MethodsWe conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality.Results2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure.ConclusionsOur research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

BackgroundPatients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients.MethodsThe 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed.ResultsCompared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively.ConclusionOur study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity.

Prior research has indicated that bisphosphonates (BPs) can improve periodontal disease because of their anti-osteoporosis properties. In vitro studies have shown that BPs induce cytotoxicity, inhibit wound healing, and thus affect periodontal disease. Denosumab and BPs have alternative indications. BP and denosumab are not known to correlate with gingival disorders. We assessed such a relationship by applying Bayesian and nonproportional analyses to data in the US FDA Adverse Event Reporting System (FAERS) database. The study analyzed BPs and denosumab-reported incidents with preferred terms found in the narrow Standardized MedDRA Queries for gingival disorders. A total of 5863 reported cases of gingival disorders were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, and zoledronate) and denosumab. More than 15% of patients with gingival disorders related to BPs and denosumab other than denosumab were hospitalized over short- or long-term periods. Our findings indicated BPs and denosumab had significant reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) with respect to gingival disorders. Pamidronate had the highest association (ROR = 64.58, PRR = 57.99, IC = 5.71), while the weakest association was found with denosumab (ROR = 3.61, PRR = 3.60, IC = 1.77). Significant associations were found between the six drugs and gingival pain, gingival recession, gingivitis, periodontal disease, and periodontitis. In conclusion, our comprehensive overview of the correlations, clinical characteristics, and prognoses of BPs and denosumab-related gingival disorders suggests that these issues deserve continued surveillance and appropriate management.

ObjectiveThe aim of this study was to compare hematological parameters pre- and early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN).MethodsPatients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve.ResultsThe study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (−0.02, CI: −0.88 to 3.48 vs. −0.04, CI: −0.83 to 2.24). Among hematological parameters, lower post-chemotherapy lymphocyte count (OR 0.942, CI: 0.934–0.949), change percentage of platelet (OR 0.965, CI: 0.955–0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011–1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002–1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275.ConclusionPeri-chemotherapy hematological markers improve the prediction of FN.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly significant infectious disease that poses a substantial threat to the global pig industry. In recent years, the NADC30-like strain has gradually emerged as prevalent in China, causing a profound impact on the country’s pig farming industry. Therefore, it is important to conduct an in-depth study on the characteristics and gene functions of the NADC30-like strain. An infectious cDNA clone is an indispensable tool for investigating the functions of viral genes. In this current study, we successfully isolated a NADC30-like strain and constructed its full-length infectious cDNA clone. The utilization of this clone will facilitate our investigation into the viral replication, pathogenesis, and immune response associated with the PRRSV NADC30-like strain.

The Shandong Peninsula, the largest peninsula in China, is situated at the estuary of the Yellow River and is bordered by both the Bohai Sea and the Yellow Sea. This region is renowned for its rich plant diversity. However, the historical origins of these plant species remain poorly understood. This study analyzed 2410 shared species from 865 genera and 161 families distributed across Shandong and its nine adjacent regions to investigate the floristic diversity of the Shandong Peninsula. These regions were considered as operational taxonomic units (OTUs), with the shared species serving as the basis for each OTU. Hierarchical cluster analyses were performed to assess their floristic similarity, employing the Bray-Curtis distance algorithm and the UPGMA clustering method. The results revealed that the ten regions were grouped into three clusters, delineated by the Yellow River. Notably, the floristic similarity of the Shandong Peninsula was found to be more closely aligned with regions south of the Yellow River, despite Shandong historical connection to Liaoning in the north. These findings underscore the barrier effect of the Yellow River and provide insights into the formation of biotic diversity patterns between northern and eastern China.

Panax ginseng (P. ginseng), a traditional and highly valued botanical drug, has been used for thousands of years and is known around the world for its uses in food, medicine, and healthcare. The comprehensive study of P. ginseng is crucial for the quality assurance of medicinal materials and optimal resource utilization. Despite being present in trace amounts, P. ginseng volatile oil has a wide range of chemical metabolites with important medicinal potential. The volatile oil has shown promise in defending the cardiovascular system, as well as in terms of its ability of antibacterial, anti-aging, anti-platelet coagulation, anti-inflammatory, support the nervous system nutritionally, and shield it from harm. Due to its low composition and lack of thorough investigation, P. ginseng volatile oil’s therapeutic applicability is still restricted although it exhibited many benefits. This review aims to provide insights into the chemical composition, extraction processes, pharmacological effects, and mechanisms of action of P. ginseng volatile oil, and to provide theoretical support and guidelines for future research and clinical application.

ObjectiveThe mental health issues of individuals with coronavirus disease 2019 (COVID-19) are currently widespread. Traditional Chinese exercise (Daoyin) plays an important role in relieving patients’ psychological problems. This study aims to assess the efficacy of Daoyin in mitigating mental health issues among individuals diagnosed with COVID-19.MethodsPubMed, the Cochrane library, Embase, CNKI, Wanfang, VIP database, and SinoMed were searched from their inception to October 2023. Two researchers independently selected the eligible studies. The analysis and presentation of the findings were conducted using Review Manager 5.2 software. The data were analyzed using mean difference (MD), inverse variance, and 95% confidence intervals (CIs).ResultsA total of 12 studies (N = 1291) were included in this study. The results showed that Daoyin can significantly reduce the scores of the Self-Rating Anxiety Scale (SAS: MD = −13.03, 95% CI −19.56 to −6.49, P

BackgroundObesity is widely recognized for its role in predisposing individuals to a spectrum of chronic health conditions. Emerging preliminary evidence points to the potential benefits of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in enhancing various health outcomes among those with obesity and associated disorders.ObjectiveThis systematic review was designed to assess the effectiveness of Lo-TENS for managing obesity and its related chronic diseases.MethodsFor this systematic review, we included randomized controlled trials that evaluated the impact of Lo-TENS on individuals with obesity and its associated chronic diseases.ResultsEight trials encompassing 671 participants and spanning three unique populations: essential hypertension (EH), type 2 diabetes mellitus (T2DM), and obesity were deemed eligible for inclusion in this review. Compared to baseline measurements, Lo-TENS demonstrated a tendency to positively affect blood pressure in individuals with EH and metabolic parameters in those with T2DM. Nonetheless, the efficacy of Lo-TENS in treating obesity is not yet clear when contrasted with a no-intervention control group. When compared with other intervention modalities, three of the trials reported less favorable results.ConclusionsAlthough Lo-TENS did not consistently surpass other treatments or yield substantial improvements, it generally provided greater benefits than the majority of placebo controls. This suggests that Lo-TENS could potentially serve as a beneficial adjunctive therapy in the management of obesity and its associated conditions. However, given the limited number of trials assessed, the elevated risk of bias within these studies, and the scarce evidence currently available, it is too early to reach definitive conclusions. Caution should be exercised when interpreting the current findings. There is an imperative for further high-quality research to thoroughly investigate and substantiate the efficacy of Lo-TENS in relation to obesity and its related disorders.