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Abstract Background Tracheobronchial mucormycosis is a fatal opportunistic infection that mainly causes airway stenosis and is difficult to manage clinically. Case presentation We report a case of severe tracheal stenosis caused by tracheobronchial mucormycosis in a 37-year-old female with a history of hyperthyroidism. She developed agranulopenia after oral methimazole administration and subsequently experienced asthma with dyspnea. Bronchoscopy, sputum culture, colony mass spectrometry, and microscopic cotton orchid staining confirmed tracheobronchial mucormycosis. The patient received venous-venous extracorporeal membrane oxygenation (VV-ECMO) and prolonged intratracheal instillation of amphotericin B (AmBD), combined with amphotericin B liposome (L-AmB) and isavuconazole intravenous infusion, ultimately resulting in successful treatment. Conclusion VV-ECMO combined with prolonged intratracheal instillation of AmBD is an effective method for the treatment of tracheobronchial mucormycosis.

Abstract Background Epidemiological studies investigating the association between flavonoid intake and bone mineral density (BMD) draw inconsistent conclusions. Our study aims to investigate the association between flavonoid intake and BMD and osteoporosis and the mediating role of composite dietary antioxidant index (CDAI) in their relationship using data from the National Health and Nutrition Examination Survey (NHANES). Methods The study assessed the relationship between flavonoid intake and femur BMD and osteoporosis in 10,225 individuals from NHANES 2007–2010 and 2017–2018. Multivariable linear regression analyses were used to detect the association between flavonoid intake and femur BMD in adult Americans. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between flavonoid intake and their subclasses and osteoporosis risk in individuals 20 years or older. We explored the mediating role of CDAI in the association between flavonoid intake and BMD. Results In fully adjusted multivariable regression analyses, compared with people in the first quartile, people in the fourth quartile of total flavonoid intake have a higher BMD at total femur (0.013, 95% CI: 0.004, 0.022, P = 0.001), femur neck (0.010, 95% CI: 0.004, 0.017, P = 0.001), trochanter (0.010, 95% CI: 0.004, 0.017, P = 0.001), and intertrochanter (0.012, 95% CI: 0.003, 0.020, P = 0.006). The positive relationship between flavonoid intake and femur BMD was present in both sexes. Furthermore, we found that people in the fourth quartile of total flavonoid intake have a lower risk of osteoporosis compared with the first quartile (OR = 0.686, 95% CI: 0.528–0.890, P = 0.005). RCS found a linear inverse relationship between total flavonoid intake and osteoporosis in individuals ≥ 20 years (Overall P = 0.015, nonlinear P = 0.086). Moreover, CDAI partially mediates the association of total flavonoid intake with femur BMD. Conclusions Our findings suggest that higher flavonoid intake is associated with higher BMD and lower risk of osteoporosis in Americans. Furthermore, we found distinct associations between different flavonoid subclasses and osteoporosis risk. More studies with stronger evidence are needed to explore the causal association between flavonoid intake and bone health and their underlying mechanisms.

Abstract Background A given movement requires precise coordination of multiple muscles under the control of center nervous system. However, detailed knowledge about the changing characteristics of neuromuscular control for multi-muscle coordination in post-stroke hemiplegic patients during standing is still lacking. This study aimed to investigate the hemiplegia-linked neuromuscular dysfunction during standing from the perspective of multi-muscle dynamical coordination by utilizing a novel network approach – weighted recurrence network (WRN). Methods Ten male hemiplegic patients with first-ever stroke and 10 age-matched healthy male adults were instructed to stand on a platform quietly for 30 s with eyes opened and eyes closed, respectively. The WRN was constructed based on the surface electromyography signals of 16 muscles from trunk, hips, thighs and calves. Relevant topological parameters, including clustering coefficient (C) and average shortest path length (L), were extracted to evaluate the dynamical coordination of multiple muscles. A measure of node centrality in network theory, degree of centrality (DC), was innovatively introduced to assess the contribution of single muscle in the multi-muscle dynamical coordination. The standing-related assessment metric, center of pressure (COP), was provided by the platform directly. Results Results showed that the post-stroke hemiplegic patients stood with remarkably higher similarity of muscle activation and more coupled intermuscular dynamics, characterized by higher C and lower L than the healthy subjects (p

Abstract Background It is very important to provide the correct nursing care for patients with intracerebral hemorrhage (ICH), but the level of critical care needs in patients with intracerebral hemorrhage is not clear. The purpose of this study is to establish a risk model based on the epidemiological and clinical characteristics of ICH patients, to help identify the critical care needs of ICH patients. Methods The clinical data of ICH patients from January 2018 to September 2023 were analyzed retrospectively. The full cohort was used to derive the clinical prediction model and the model was internally validated with bootstrapping. Discrimination and calibration were assessed using the area under curve (AUC) and the Hosmer-Lemeshow tests, respectively. Results 611 patients with ICH were included for model development. 61.21% (374/611) ICH patients had received critical care interventions. The influencing factors included in the model were Glasgow Coma Scale (GCS) score, intraventricular hemorrhage, past blood pressure control, systolic blood pressure on admission and bleeding volume. The model’s goodness-of-fit was evaluated, which yielded a high area under the curve (AUC) value of 0.943, indicating a good fit. For the purpose of model validation, a cohort of 260 patients with ICH was utilized. The model demonstrated a Youden’s index of 0.750, with a sensitivity of 90.56% and a specificity of 78.22%. Conclusion GCS, systolic blood pressure, intraventricular hemorrhage, bleeding volume and past blood pressure control are the main factors affecting the critical care needs of patients with ICH. This study has deduced a clinical predictive model with good discrimination and calibration to provide scoring criteria for clinical health care providers to accurately evaluate and identify the critical care needs of ICH patients, to improve the rational integration and allocation of medical resources.

Abstract Background Valvular heart disease is the third most common cardiovascular disease; it significantly diminishes patients’ quality of life and imposes burdens on individuals, families, and healthcare systems. In recent years, psycho-cardiology has emerged as a prominent field in which to explore the link between mental illness and heart disease. This mixed-method study aims to assess the effectiveness of the WCPP, which includes hospital-to-home transitional care, remote intelligent monitoring, and decision aids, in improving the physical and mental health of patients. Methods A mixed-method study was conducted at a cardiac valve interventional surgery (CVIS) center in Southwest China. A total of 154 CVIS patients participated, with the intervention group receiving the WCPP and the control group following the traditional CVIS management program. Both groups were followed up at 1, 3, 6, and 12 months. The primary outcome is measured via the Chinese version of the 36-item Short Form Health Survey (SF-36). The Secondary outcomes included the 6-min walk test (6MWT), modified Barthel index (MBI), major adverse cardiovascular events (MACE), patient satisfaction, and length of hospital stay (LOS). Additionally, qualitative research will assess the psychological state and experiences of the patients. Discussion Our study is one of the few involving patients with CVIS and the first to apply psycho-cardiology through a full-process management platform. The study population is predominantly from Southwest China and includes a diverse range of demographic and socioeconomic backgrounds. Upon completion, this study will provide valuable insights into the use of a remote, full-process management platform for CVIS patients. Trial registration Chinese Clinical Trial Registry ChiCTR2400081052. Registered on 21 February 2024. The trial complies with the SPIRIT and CONSORT guidelines.

Abstract As a powerful eukaryotic expression vector, the baculovirus expression vector system (BEVS) is widely applied to the production of heterogeneous proteins for research and pharmaceutical purposes, while optimization of BEVS remains a work in progress for membrane or secreted protein expression. In this study, the impact of the signal peptide (SP) derived from Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 protein on protein expression, secretion, and the endoplasmic reticulum-associated degradation (ERAD) pathway were investigated in BmN cells and BEVS. Transient expression studies in BmN cells revealed that SP alters the localization and expression levels of recombinant proteins, reducing intracellular accumulation while enhancing secretion efficiency. Quantitative analysis demonstrated that SP-mediated secretion was markedly higher compared to controls, albeit with lower total expression levels. Further exploration into SP-mediated ERAD pathway activation showed increased expression of BiP and other ERAD-associated genes (PDI, UFD1, S1P, and ASK1), correlating with higher SP-driven protein expression levels. RNA interference (RNAi) experiments elucidated that knockdown of ERAD-associated genes enhances both the secretion efficiency of SP-guided proteins and the infectivity of BmNPV. Particularly, interference with BiP demonstrated the most pronounced effect on protein secretion enhancement. Viral infection experiments further supported these findings, showing upregulated ERAD-associated genes during BmNPV infection, indicating their role in viral protein processing and infectivity. In conclusion, this study elucidates the complex interplay between SP-mediated protein secretion, ERAD pathway activation, and viral infectivity in BmNPV-infected cells. These insights suggest strategies for optimizing recombinant protein production and viral protein processing in baculovirus expression systems, with potential implications for biotechnological and biomedical applications. Further research could refine our understanding and manipulation of protein secretion pathways in insect cell-based expression systems.

Abstract Background Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) caused infections of high mortality and brought a serious impact on public health. This study aims to evaluate the epidemiology, resistance and virulence characteristics of CR-hvKP and to identify potential drivers of cross-regional transmission in different regions of China, in order to provide a basis for developing targeted prevention measures. Methods Clinical K. pneumoniae strains were collected from Jiujiang and Nanchang in Jiangxi province between November 2021 to June 2022. Clinical data of patients (age, sex, source of infection, and diagnosis) were also gathered. We characterized these strains for their genetic relatedness using PFGE, antimicrobial and virulence plasmid structures using whole-genome sequencing, and toxicity using Galleria mellonella infection model. Results Among 609 strains, 45 (7.4%) CR-hvKP were identified, while the strains. isolated from Nanchang and Jiujiang accounted for 10.05% (36/358) and 3.59% (9/251). We observed that ST11-KL64 CR-hvKP had an overwhelming epidemic dominance in these two regions. Significant genetic diversity was identified among all ST11-KL64 CR-hvKP cross-regional transmission between Nanchang and Jiujiang and this diversity served as the primary driver of the dissemination of clonal groups. Virulence genes profile revealed that ST11-KL64 CR-hvKP might harbour incomplete pLVPK-like plasmids and primarily evolved from CRKP by acquiring the hypervirulence plasmid. We found the predominance of truncated-IncFIB/IncHI1B type virulence plasmids with a 25 kb fragment deletion that encoded iroBCDN clusters. Conclusion ST11-KL64 is the most cross-regional prevalent type CR-hvKPs in Jiangxi province, which mainly evolved from CRKPs by acquiring a truncated-IncHI1B/IncFIB virulence plasmid with the deletion of iroBCDN. Stricter surveillance and control measures are urgently needed to prevent the epidemic transmission of ST11-KL64 CR-hvKP.

Abstract Background To investigate the association of vitamin D receptor (VDR) gene polymorphism with caries risk in children(

Abstract Objective The purpose of this study was to compare the analgesic effects of intercostal nerve block (ICNB) and local anesthetic infiltration (LAI) on postoperative pain and recovery following thoracoscopic resection of pulmonary bullae. Methods A total of 160 patients undergoing thoracoscopic pulmonary bullae resection were randomly assigned to receive either ICNB (n = 80) or LAI (n = 80). An experienced anesthesiologist administered ultrasound guided ICNB at the T4 and T7 levels with 5 mL of 0.375% ropivacaine hydrochloride for the ICNB group. Instead, the LAI group received 10 mL of the same concentration of ropivacaine hydrochloride at the same concentration used for ICNB for infiltration anesthesia at the incision sites. Out of the initial cohort, 146 patients completed the study (ICNB group, n = 71; LAI group, n = 75). The collected data included preoperative clinical characteristics, visual analog scale (VAS) scores for pain at various time points post-surgery (6, 12, 24, 48, and 72 h). Additionally, the Quality of Recovery-15 (QoR-15) questionnaire was administered 24 h after surgery, and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Results No significant differences were found in drainage volume, use of additional analgesics, duration of chest tube placement, or hospital stay between the two groups. However, the ICNB group had significantly lower VAS scores and QoR-15 scores 24 h postoperatively (p

Abstract Background Chimeric antigen receptor (CAR)-T therapy has emerged as a promising treatment for hematologic malignancies. However, cytopenia remains one of the most frequent and challenging adverse effects of this therapy. Methods We conducted a retrospective analysis of 26 patients with relapsed/refractory aggressive B-cell lymphoma who received CAR-T therapy at our center. Subsequently, to investigate measures to address cytopenias following CAR-T therapy, we isolated and generated murine CAR-T cells and bone marrow-derived mesenchymal stem cells (MSCs), establishing a murine syngeneic CAR-T therapy model. We assessed the impact of MSC infusion on hematopoietic recovery post-CAR-T therapy by evaluating complete blood count, bone marrow hematopoietic stem cells and their subpopulations, bone marrow histomorphology, and hematopoiesis-related genes. Results All patients experienced cytopenias to varying degrees, with complete lineage involvement in half of the patients. Grade ≥ 3 cytopenias were observed in 88.46% of the patients. CAR-T therapy was associated with a higher incidence of biphasic, late-onset, or prolonged cytopenias. Survival analysis indicated that neutropenia and lymphopenia tended to be associated with better prognosis, whereas thrombocytopenia tended to be related to poorer outcomes. Through animal experiments, we discovered that MSCs infusion boosted HSCs and their long-term subpopulations, enhancing hematopoietic recovery, particularly in the megakaryocyte lineage, and mitigating bone marrow damage. Importantly, both in vitro and in vivo experiments demonstrated that MSCs did not compromise the activity or antitumor efficacy of CAR-T cells. Conclusions Our findings propose MSCs infusion as a promising strategy to address cytopenias, particularly thrombocytopenia, after CAR-T therapy. This approach could help overcome certain limitations of cellular immunotherapy by enhancing hematopoietic recovery without compromising the efficacy of CAR-T cells. Highlights 1 Cytopenia is a frequently observed adverse effect following CAR-T therapy, and it is often characterized by biphasic and prolonged patterns. 2 MSCs play a critical role in promoting hematopoietic recovery and mitigating bone marrow damage in a murine model of CAR-T therapy 3 The activity and antitumor efficacy of CAR-T cells were not impaired by MSCs. Graphical Abstract

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. Case presentation We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. Conclusions The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

Abstract Background and Objective Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. Methods Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. Results A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (β: -51.19, 95% CI: -75.41 to -26.97, P

Abstract Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.

Abstract Background Rating scales and linear indices of surface electromyography (sEMG) cannot quantify all neuromuscular conditions associated with ankle-foot dysfunction in hemiplegic patients. This study aimed to reveal potential neuromuscular conditions of ankle-foot dysfunction in hemiplegic patients by nonlinear network indices of sEMG. Methods Fourteen male patients with hemiplegia and 10 age- and sex-matched healthy male adults were recruited and tested in static standing position. The characteristics of the root mean square (RMS), median frequency (MF), and three nonlinear indices, the clustering coefficient (C), the average shortest path length (L), and the degree centrality (DC), of eight groups of muscles in bilateral calves were observed. Results Compared to those of the control group, the RMS of the medial gastrocnemius (MG), flexor digitorum longus (FDL), and extensor digitorum longus (EDL) on the affected side were significantly lower (P

Abstract Background Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. Method Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. Results Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. Conclusion This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

Abstract Background Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. Methods and results The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). Conclusions In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.

Abstract Background TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants. Methods Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed. Results TTN c.38,876–2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases. Conclusions Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.

Abstract Background Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. Methods The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. Results The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. Conclusion COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.

Abstract Background Residual risk assessment for acute coronary syndrome (ACS) patients after sufficient medical management remains challenging. The usefulness of measuring high-sensitivity C-reactive protein (hsCRP) and remnant cholesterol (RC) in assessing the level of residual inflammation risk (RIR) and residual cholesterol risk (RCR) for risk stratification in these patients needs to be evaluated. Methods Patients admitted for ACS on statin treatment who underwent percutaneous coronary intervention (PCI) between March 2016 and March 2019 were enrolled in the analysis. The included patients were stratified based on the levels of hsCRP and RC during hospitalization. The primary outcome was ischemic events at 12 months, defined as a composite of cardiac death, myocardial infarction, or stroke. The secondary outcomes included 12-month all-cause death and cardiac death. Results Among the 5778 patients, the median hsCRP concentration was 2.60 mg/L and the median RC concentration was 24.98 mg/dL. The RIR was significantly associated with ischemic events (highest hsCRP tertile vs. lowest hsCRP tertile, adjusted hazard ratio [aHR]: 1.52, 95% confidence interval [CI]: 1.01–2.30, P = 0.046), cardiac death (aHR: 1.77, 95% CI:1.02–3.07, P = 0.0418) and all-cause death (aHR: 2.00, 95% CI: 1.24–3.24, P = 0.0048). The RCR was also significantly associated with these outcomes, with corresponding values for the highest tertile of RC were 1.81 (1.21–2.73, P = 0.0043), 2.76 (1.57–4.86, P = 0.0004), and 1.72 (1.09–2.73, P = 0.0208), respectively. The risks of ischemic events (aHR: 2.80, 95% CI: 1.75–4.49, P

Abstract Background Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). Case presentation We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. Conclusions Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.

Abstract Background We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. Case presentation A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. Conclusions To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Abstract Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.

Abstract Background Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans. Methods This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013–2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD. Results This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (β= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P

Abstract Background Previous studies have shown that the relationship between high-density lipoprotein cholesterol (HDL-C) and stroke is controversial, and the association between the platelet/high-density lipoprotein cholesterol ratio (PHR), a novel marker for inflammation and hypercoagulability states, and stroke has not been established. Methods This study presents an analysis of cross-sectional data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). Stroke history, HDL-C levels, and platelet counts were obtained during cross-sectional surveys. The PHR was calculated as the ratio of the number of platelets to HDL-C concentration. Weighted logistic regression was used to assess the associations of HDL-C and the PHR with stroke. Nonlinearity of this relationship was determined through restricted cubic splines (RCSs) and two-piecewise linear regression for identifying inflection points. Furthermore, Cox regression was utilized to prospectively analyze the associations of the PHR and HDL-C concentration with cardiovascular disease (CVD) mortality in stroke survivors. Results A total of 27,301 eligible participants were included in the study; mean age, 47.28 years and 50.57% were female, among whom 1,040 had a history of stroke. After full adjustment, the odds ratio (OR) of stroke associated with a per standard deviation (SD) increase in the PHR was estimated at 1.13 (95% confidence interval (CI): 1.03 − 1.24, P = 0.01), and the OR of stroke associated with a per SD increase in HDL-C was 0.95 (95% CI: 0.86–1.05, P = 0.30). The RCS indicated a nonlinear relationship for both variables (P PHR = 0.018 and P HDL-C = 0.003), and further piecewise linear regression identified inflection points at PHR = 223.684 and HDL-C = 1.4 mmol/L. Segmental regression indicated that in the PHR ≥ 223.684 segment, the estimated OR of stroke associated with a per-SD increase in the PHR was 1.20 (95% CI: 1.09 − 1.31, P 0.05). Furthermore, Cox regression and RCS showed that a per-SD increase in the PHR was linearly associated with a greater risk of CVD mortality among stroke survivors (HR: 1.14, 95% CI: 1.06 − 1.22, P

Abstract Background Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. Methods LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. Results The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. Conclusions MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

Abstract Background Glycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of ‘Gan Cao’ in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed. Results This research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata. Conclusion Compared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.

Abstract Background Thymus mongolicus (family Lamiaceae) is a Thyme subshrub with strong aroma and remarkable environmental adaptability. Limited genomic information limits the use of this plant. Results Chromosome-level 605.2 Mb genome of T. mongolicus was generated, with 96.28% anchored to 12 pseudochromosomes. The repetitive sequences were dominant, accounting for 70.98%, and 32,593 protein-coding genes were predicted. Synteny analysis revealed that Lamiaceae species generally underwent two rounds of whole genome duplication; moreover, species-specific genome duplication was identified. A recent LTR retrotransposon burst and tandem duplication might play important roles in the formation of the Thymus genome. Using comparative genomic analysis, phylogenetic tree of seven Lamiaceae species was constructed, which revealed that Thyme plants evolved recently in the family. Under the phylogenetic framework, we performed functional enrichment analysis of the genes on nodes that contained the most gene duplication events (> 50% support) and of relevant significant expanded gene families. These genes were highly associated with environmental adaptation and biosynthesis of secondary metabolites. Combined transcriptome and metabolome analyses revealed that Peroxidases, Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferases, and 4-coumarate-CoA ligases genes were the essential regulators of the phenylpropanoid–flavonoid pathway. Their catalytic products (e.g., apigenin, naringenin chalcone, and several apigenin-related compounds) might be responsible for the environmental tolerance and aromatic properties of T. mongolicus. Conclusion This study enhanced the understanding of the genomic evolution of T. mongolicus, enabling further exploration of its unique traits and applications, and contributed to the understanding of Lamiaceae genomics and evolutionary biology.

Abstract Diabetic nephropathy (DN), one of the more prevalent microvascular complications in patients diagnosed with diabetes mellitus, is attributed as the main cause of end-stage renal disease (ESRD). Lipotoxicity in podocytes caused by hyperglycemia has been recognised as a significant pathology change, resulting in the deterioration of the glomerular filtration barrier. Research has demonstrated how dapagliflozin, a kind of SGLT2i, exhibits a multifaceted and powerful protective effect in DN, entirely independent of the hypoglycemic effect, with the specific mechanism verified. In this present study, we found that dapagliflozin has the potential to alleviate apoptosis and restore cytoskeleton triggered by high glucose (HG) in vivo and in vitro. We also discovered that dapagliflozin could mitigate podocyte cholesterol accumulation by restoring the expression of ABCA1, which is the key pathway for cholesterol outflows. This research also mechanistically demonstrates that the protective effect of dapagliflozin can be mediated by KLF-5, which is the upstream transcription factor of ABCA1. Taken together, our data suggest that dapagliflozin offers significant potential in alleviating podocyte injury and cholesterol accumulation triggered by high glucose. In terms of the mechanism, we herein reveal that dapagliflozin could accelerate cholesterol efflux by restoring the expression of ABCA1, which is directly regulated by KLF-5.

Abstract Background Radiofrequency catheter ablation (RFCA) may lead to decreased quality of life (QOL) and increased anxiety and depression in patients with paroxysmal supraventricular tachycardia (PSVT), possibly due to the lack of selectivity of the ablation tissue and the long ablation time. In recent years, pulsed field ablation (PFA) has been used for the first time in China to treat PSVT patients because of its ability to ablate abnormal tissue sites in a precise and transient manner. This study was conducted to compare the effects of PFA and RFCA on QOL and psychological symptoms of PSVT patients. Methods We have designed a single-center, randomized, single-blind, standard-controlled trial. A total of 50 participants who met the eligibility criteria would be randomly allocated into the PFA group or RFCA group in a 1:1 ratio. All participants were assessed using the 36-Item Short-Form Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS) at pre-procedure (T0), post-procedure (T1), and 3 months post-procedure (T2). The SPSS 21.0 software was used to analyze the data through Wilcoxon and Fisher’s exact tests and repeated measures ANOVA. Results Twenty-five in the PFA group and 24 in the RFCA group completed the trial. SF-36: (1) Between-group comparison: At T1, PFA group had significantly higher SF-36 scores on physiological function (PF) and general health (GH) than RFCA group, with a treatment difference of 5.61 points and 18.51 points(P 0.05). (2) Within-group comparison: The HADS scores of the PFA and RFCA groups were statistically significant at T2 compared to T0 and T1 (P

Abstract Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched men [56 years, healthy control, compensated, early (ascites and lactulose use) and advanced decompensated cirrhosis (ascites and rifaximin use)]. Cell type proportions, differential gene expressions, cell-type specific pathway analysis using IPA, and cellular crosstalk dynamics were compared. Stem cells, enterocytes and Paneth cells were lowest in advanced decompensation. Immune cells like naive CD4 + T cells were lowest while ITGAE + cells were highest in advanced decompensation patients. MECOM had lowest expression in stem cells in advanced decompensation. Defensin and mucin sulfation gene (PAPSS2) which can stabilize the mucus barrier expression were lowest while IL1, IL6 and TNF-related genes were significantly upregulated in the enterocytes, goblet, and Paneth cells in decompensated subjects. IPA analysis showed higher inflammatory pathways in enterocytes, stem, goblet, and Paneth cells in decompensated patients. Cellular crosstalk analysis showed that desmosome, protease-activated receptors, and cadherin-catenin complex interactions were most perturbed in decompensated patients. In summary, the snRNAseq of the human terminal ileum in 4 subjects (1 control and three cirrhosis) identified multidimensional alteration in the intestinal barrier with lower stem cells and altered gene expression focused on inflammation, mucin sulfation and cell–cell interactions with cirrhosis decompensation.

Abstract Introduction Dilated cardiomyopathy (DCM) is characterized by the enlargement of the left ventricle or biventricular, accompanied by myocardial systolic dysfunction. Chlamydia psittacosis (CP) is a zoonotic pathogen, which can cause severe pneumonia, respiratory failure, and acute organ dysfunction. The deterioration of DCM caused by CP infection is extremely rare, and few cases of successful management were reported. Case presentation We reported a 67-year-old male patient with DCM and chronic heart failure. Who was admitted to ICU with severe pneumonia, acute hypoxemic respiratory failure, acute decompensated heart failure, arrhythmia, and cardiogenic shock. Mechanical ventilation (MV) and venous-arterial extracorporeal membrane oxygenation (VA-ECMO) were established for respiratory and circulatory support. Broncho alveolar lavage fluid(BALF)was collected for culture and metagenomics next-generation sequencing (mNGS) test. Repeated mNGS tests indicated the high possibility of CP pneumonia, thereafter, moxifloxacin and doxycycline were prescribed. After targeted antibiotics and organ support treatment, pneumonia, respiratory and circulatory failure were gradually resolved, patient was successfully weaned from MV and VA-ECMO. Finally, the patient was recovered and discharged alive. Conclusions Severe respiratory and circulatory failure caused by CP infection in DCM patients is a rare life-threatening clinical condition. Early accurate diagnosis, targeted antibiotic therapy, coupled with extracorporeal life support posed positive impact on the patient’s disease course and outcome.

Abstract Purpose To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. Methods This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. Results The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. Conclusion GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.

Abstract Background and aims Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2−/− mice) and elucidate the underlying mechanisms. Methods Mdr2−/−mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical analyses were used to assess fibrotic liver injury severity. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by BBR in the liver. The expression levels of key genes involved in regulating hepatic fibrosis, bile duct proliferation, inflammation, and bile acid metabolism were validated by qRT-PCR or Western blot analysis. The bile acid composition and levels in the serum, liver, small intestine, and feces and tissue distribution of BBR were measured by LC–MS/MS. Intestinal inflammation and injury were assessed by gene expression profiling and histological analysis. The impact on the gut microbiome was assessed using 16S rRNA gene sequencing. Results BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E, Picro-Sirius Red, and CK19 IHC staining. RNAseq and qRT-PCR analyses indicated a substantial inhibition of fibrotic and inflammatory gene expression. BBR also mitigated ER stress by downregulating Chop, Atf4 and Xbp-1 expression. In addition, BBR modulated bile acid metabolism by altering key gene expressions in the liver and small intestine, resulting in restored bile acid homeostasis characterized by reduced total bile acids in serum, liver, and small intestine and increased fecal excretion. Furthermore, BBR significantly improved intestinal barrier function and reduced bacterial translocation by modulating the gut microbiota. Conclusion BBR effectively attenuates cholestatic liver injury, suggesting its potential as a therapeutic agent for PSC and other cholestatic liver diseases.

Abstract Background While prior studies have established a close association between the use of social network sites (SNSs) and materialistic values, there is limited understanding of the mediating and moderating mechanisms related to important self-related processes, such as self-control and self-acceptance. This paper explores whether and how these factors play a role in comprehending online behavior. One could state that frequent SNS use may pose a risk of virtual addiction, may be related to decreased self-control capacity, and may increase attention to material information on SNS, thereby making it more likely that users affiliate with behaviors associated with materialistic values. In contrast, self-acceptance, as a stable self-process indicating a genuine alignment with one’s true self and the ability to make decisions based on inner needs, may be related with reduced engagement in complex information on SNSs. Consequently, this could serve as a buffer against excessive SNS use and its potential associations with issues of self-control and materialistic values. Methods A total of 706 Chinese college students were surveyed in a cross-sectional study. They completed self-report questionnaires including the WeChat use intensity scale, the Material Value Scale, the Trait Self-control Scale, and the Self-acceptance Questionnaire. A moderated mediation model was examined to test predictions. Results SNS use intensity was positively associated with materialistic values, and self-control partially mediated this association. That is, higher intensity SNS users are more likely lower in self-control, which relates to stronger materialistic values. In addition, the indirect effect through self-control was moderated by self-acceptance, such that this indirect effect was significant only for individuals with low levels of self-acceptance. Conclusions This study reveals that self-acceptance may be a protective factor that helps to mitigate excessive SNS use and its potential effects on self-control and materialistic values. It further suggests that psychological interventions targeting the enhancement of self-acceptance and self-control could hold promise in alleviating the negative association between SNS use and materialistic values.

Abstract Due to self-incompatibility (SI) prevents self-fertilization, natural or artificial cross-pollination has been conducted in many orchards to stabilize fruit yield. However, it is still puzzled which routes of self S-RNase arresting pollen tube growth. Herein, 17 COBRA genes were isolated from pear genome. Of these genes, the pollen-specifically expressed PbCOB.A.1 and PbCOB.A.2 positively mediates pollen tube growth. The promoters of PbCOB.A.1 and/or PbCOB.A.2 were bound and activated by PbABF.E.2 (an ABRE-binding factor) and PbC2H2.K16.2 (a C2H2-type zinc finger protein). Notably, the expressions of PbCOB.A.1, PbCOB.A.2, and PbC2H2.K16.2 were repressed by self S-RNase, suggesting that self S-RNase reduces the expression of PbCOB.A.1 and PbCOB.A.2 by decreasing the expression of their upstream factors, such as PbC2H2.K16.2, to arrest pollen tube growth. PbCOB.A.1 or PbCOB.A.2 accelerates the growth of pollen tubes treated by self S-RNase, but can hardly affect level of reactive oxygen species and deploymerization of actin cytoskeleton in pollen tubes and cannot physically interact with any reported proteins involved in SI. These results indicate that PbCOB.A.1 and PbCOB.A.2 may not relieve S-RNase toxicity in incompatible pollen tube. The information provides a new route to elucidate the arresting pollen tube growth during SI reaction. Graphical Abstract

Abstract Background There is currently no objective and accurate clinical assessment of reticular neuromuscular control in healthy subjects or patients with upper motor neuron injury. As a result, clinical dysfunctions of neuromuscular control could just be semi-quantified, efficacies and mechanisms of various therapies for neuromuscular control improving are difficult to verify. Methods Fourteen healthy participants were required to maintain standing balance in the kinetostatics model of Gusu Constraint Standing Training (GCST). A backward and upward constraint force was applied to their trunk at 0°, 20° and 25°, respectively. The multiplex recurrence network (MRN) was applied to analyze the surface electromyography signals of 16 muscles of bilateral lower limbs during the tests. Different levels of MRN network indices were utilized to assess reticular neuromuscular control. Results Compared with the 0° test, the MRN indices related to muscle coordination of bilateral lower limbs, of unilateral lower limb and of inter limbs showed significant increase when participants stood in 20° and 25° tests (P

Abstract Background Working memory may affect the athletes’ visual search ability. Objective: This study aimed to examine the differences in the performance of visual search tasks among basketball players of varying sport levels, considering the influence of different object working memory loads. Method: This study recruited forty-two participants who were divided into three groups based on the classification of elite athletes: competitive elite, semi-elite, and novice. Results: Objective working memory load significantly impacts the accuracy of visual search, reaction time, and gaze fixation in basketball players. In the visual search task of the basketball sports scene, the inclusion of object working memory load led to a significant decrease in the accuracy of visual search, a significant increase in reaction time, a significant increase in the number of fixation points, and a more complex gaze trajectory. In a visual search task with object working memory load, the difference in reaction time between basketball players of different sport levels was observed during the search initiation time and scanning time, with higher sport levels associated with shorter reaction times. The effect of object working memory load on the eye movement phase of visual search varied among basketball players of different sport levels. For the novice group, the effect was on the reaction time during the verification phase, while for the semi-elite and competitive elite groups, the effect was on the reaction time during the scanning phase. Conclusion: The effect of object working memory load on visual search varied among basketball players of different sport levels.

Abstract Background Mechanical ventilation can cause acute atrophy and injury in the diaphragm, which are related to adverse clinical results. However, the underlying mechanisms of ventilation-induced diaphragm dysfunction (VIDD) have not been well elucidated. The current study aimed to explore the role of cellular senescence in VIDD. Methods A total of twelve New Zealand rabbits were randomly divided into 2 groups: (1) spontaneously breathing anaesthetized animals (the CON group) and (2) mechanically ventilated animals (for 48 h) in V-ACV mode (the MV group). Respiratory parameters were collected during ventilation. Diaphragm were collected for further analyses. Results Compared to those in the CON group, the percentage and density of sarcomere disruption in the MV group were much higher (p

Abstract Background Cannabis sativa, a dioecious plant that has been cultivated worldwide for thousands of years, is known for its secondary metabolites, especially cannabinoids, which possess several medicinal effects. In this study, we investigated the autopolyploidization effects on the biosynthesis and accumulation of these metabolites, transcriptomic and metabolomic analyses were performed to explore the gene expression and metabolic variations in industrial hemp autotetraploids and their diploid progenitors. Results Through these analyses, we obtained 1,663 differentially expressed metabolites and 1,103 differentially expressed genes. Integrative analysis revealed that phenylpropanoid and terpenoid biosynthesis were regulated by polyploidization. No substantial differences were found in the cannabidiol or tetrahydrocannabinol content between tetraploids and diploids. Following polyploidization, some transcription factors, including nine bHLH and eight MYB transcription factors, affected the metabolic biosynthesis as regulators. Additionally, several pivotal catalytic genes, such as flavonol synthase/flavanone 3-hydroxylase, related to the phenylpropanoid metabolic pathway, were identified as being modulated by polyploidization. Conclusions This study enhances the overall understanding of the impact of autopolyploidization in C. sativa and the findings may encourage the application of polyploid breeding for increasing the content of important secondary metabolites in industrial hemp.

Abstract Background The 70-gene signature (70-GS, MammaPrint) test has been recommended by the main guidelines to evaluate prognosis and chemotherapy benefit of hormonal receptor positive human epidermal receptor 2 negative (HR + /Her2−) early breast cancer (BC). However, this expensive assay is not always accessible and affordable worldwide. Based on our previous study, we established nomogram models to predict the binary and quartile categorized risk of 70-GS. Methods We retrospectively analyzed a consecutive cohort of 150 female patients with HR + /Her2− BC and eligible 70-GS test. Comparison of 40 parameters including the patients’ medical history risk factors, imaging features and clinicopathological characteristics was performed between patients with high risk (N = 62) and low risk (N = 88) of 70-GS test, whereas risk calculations from established models including Clinical Treatment Score Post-5 years (CTS5), Immunohistochemistry 3 (IHC3) and Nottingham Prognostic Index (NPI) were also compared between high vs low binary risk of 70-GS and among ultra-high (N = 12), high (N = 50), low (N = 65) and ultra-low (N = 23) quartile categorized risk of 70-GS. The data of 150 patients were randomly split by 4:1 ratio with training set of 120 patients and testing set 30 patients. Univariate analyses and multivariate logistic regression were performed to establish the two nomogram models to predict the the binary and quartile categorized risk of 70-GS. Results Compared to 70-GS low-risk patients, the high-risk patients had significantly less cardiovascular co-morbidity (p = 0.034), more grade 3 BC (p = 0.006), lower progesterone receptor (PR) positive percentage (p = 0.007), more Ki67 high BC (≥ 20%, p

Abstract Background The elderly with severe infection increased dramatically in intensive care unit (ICU). Proper antimicrobial therapy help improve the prognosis. Linezolid, as an antimicrobial drug, is commonly utilized to treat patients infected with methicillin-resistant S. aureus and vancomycin-resistant enterococci. Clinical evidence suggests elderly patients prone to linezolid overexposure. Here, we describe the results of three years’ linezolid adjustment experiences according to therapeutic drug monitoring (TDM), especially in the oldest old. Methods Linezolid therapeutic drug monitoring data were collected between January 2020 and November 2022 from patients who were admitted to ICU and treated with linezolid. All the patients started with a dosage of 600 mg, twice daily. The first TMD was carried out ten minutes before the seventh administration. The dosage adjustment was determined by the doctor according to the first TMD and patients' condition, and the repeated TDM was conducted as required. The dosage adjustment in different age group was recorded. Laboratory data were compared between the old and the oldest old. The high mortality risk of the oldest old was also explored. Results Data of 556 linezolid TDM from 330 patients were collected. Among which, 31.6%, 54.8%, and 75% of patients had supra-therapeutic linezolid trough concentrations at the first TDM assessment in different age group, leading to the dosage adjustment rate of 31.0%, 40.3%, 68.8% respectively. The linezolid dosage adjustments according to TDM help to reach therapeutic concentration. The oldest old was in high risk of linezolid overexposure with lowercreatinine clearance. The norepinephrine maximum dosage but not linezolid Cmin was associated with 28-day mortality in the oldest old. Conclusions Elderly patients with linezolid conventional 600 mg twice-daily dose might be at a high risk of overexposure, especially in the oldest old. The linezolid dosage adjustments according to TDM help reach the therapeutic concentration. The high mortality of the oldest old was not related with initial linezolid overexposure.

Abstract Background In the diagnosis of bloodstream infection (BSI), various inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL), white blood cell count (WBC), neutrophil percentage (NE%), platelet count (PLT), and erythrocyte sedimentation rate (ESR) have been extensively utilized. However, their specific roles in distinguishing BSI from local bacterial infection (LBI) and in classifying BSI pathogens remain uncertain. Methods A historical cohort study was conducted, involving the enrollment of 505 patients with BSI and 102 patients with LBI. To validate the reliability of the clinical data obtained from this cohort, mouse models of BSI were utilized. Results Our findings revealed that patients with BSI had significantly higher levels of inflammatory markers, including CRP, PCT, IL-6, IL-10, WBC, NE%, and ESR, compared to those with LBI (p

Abstract Objective To predict the very early recurrence (VER) of patients with intrahepatic cholangiocarcinoma (ICC) based on TLSs and MVI status, and further perform prognosis stratifications. Methods A total of 160, 51 ICC patients from two institutions between May 2012 and July 2022 were retrospectively included as training, external validation cohort. Clinical, radiological and pathological variables were evaluated and collected. Univariate and multivariate analysis were applied to select the significant factors related to VER of ICC. The factors selected were combined to perform stratification of overall survival (OS) using the Kaplan-Meier method with the log-rank test. Results Overall, 39 patients (24.4%) had VER, whereas 121 (75.6%) did not (non-VER group). In the training cohort, the median OS was 40.5 months (95% CIs: 33.2–47.7 months). The VER group showed significantly worse OS than the non-VER group (median OS: 14.8, 95% CI:11.6–18.0 months vs. 53.4, 34.3–72.6 months; p

Abstract Background Neoadjuvant radiotherapy has been used as the standard treatment of colorectal cancer (CRC). However, radiotherapy resistance often results in treatment failure. To identify radioresistant genes will provide novel targets for combined treatments and prognostic markers. Methods Through high content screening and tissue array from CRC patients who are resistant or sensitive to radiotherapy, we identified a potent resistant gene SUMO specific peptidase 5 (SENP5). Then, the effect of SENP5 on radiosensitivity was investigated by CCK8, clone formation, comet assay, immunofluorescence and flow cytometric analysis of apoptosis and cell cycle to investigate the effect of SENP5 on radiosensitivity. SUMO-proteomic mass spectrometry combined with co-immunoprecipitation assay were used to identify the targets of SENP5. Patient-derived organoids (PDO) and xenograft (PDX) models were used to explore the possibility of clinical application. Results We identified SENP5 as a potent radioresistant gene through high content screening and CRC patients tissue array analysis. Patients with high SENP5 expression showed increased resistance to radiotherapy. In vitro and in vivo experiments demonstrated that SENP5 knockdown significantly increased radiosensitivity in CRC cells. SENP5 was further demonstrated essential for efficient DNA damage repair in homologous recombination (HR) dependent manner. Through SUMO mass spectrometry analysis, we characterized H2AZ as a deSUMOylation substrate of SENP5, and depicted the SUMOylation balance of H2AZ in HR repair and cancer resistance. By using PDO and PDX models, we found targeting SENP5 significantly increased the therapeutic efficacy of radiotherapy. Conclusion Our findings revealed novel role of SENP5 in HR mediated DNA damage repair and cancer resistance, which could be applied as potent prognostic marker and intervention target for cancer radiotherapy.

Abstract The objective of this study was to synthesize and characterize pharmaceutical characteristics of florfenicol sustained-release granules (FSRGs) in vitro and in vivo. FSRGs were synthesized using monostearate, polyethylene glycol 4000 and starch. In vitro dissolution profiles were studied using the rotating basket method in pH 1.2 HCl solution and pH 4.3 acetate buffer. Twenty-four male healthy Landrace×Yorkshire pigs were equally divided into three groups and administered a 20 mg/kg i.v bolus of florfenicol solution and dosed orally with FSRGs in the fasting and fed states. The Higuchi model was the best fit for the drug release profile in pH 1.2 and pH 4.3 media, and the mechanism of drug dissolution was governed by both diffusion and dissolution. We established a level A in vitro - in vivo correlation for FSRGs and the in vivo profile of the FSRGs can be estimated by the in vitro drug release.

Abstract Background The number of pneumocystis pneumonia (PCP) cases is increasing in immunocompromised patients without human immunodeficiency virus infection (HIV), causing serious morbidity with high mortality. Trimethoprim/sulfamethoxazole (TMP/SMZ) monotherapy has limited effectiveness in the treatment of PCP. Clinical data on whether initial caspofungin plus TMP/SMZ for this disease is superior to monotherapy in non-HIV-infected patients are limited. We aimed to compare the clinical effectiveness of these regimens for severe PCP in non-HIV patients. Methods A retrospective study reviewed 104 non-HIV-infected patients with confirmed PCP in the intensive care unit between January 2016 and December 2021. Eleven patients were excluded from the study because TMP/SMZ could not be used due to severe hematologic disorders or clinical data were missing. All enrolled patients were divided into three groups according to different treatment strategies: Group 1 received TMP/SMZ monotherapy, Group 2 received caspofungin combined with TMP/SMZ as first-line therapy, and Group 3 initially received TMP/SMZ monotherapy and later received caspofungin as salvage therapy. The clinical characteristics and outcomes were compared among the groups. Results A total of 93 patients met the criteria. The overall positive response rate of anti-PCP treatment was 58.06%, and the overall 90-day all-cause mortality rate was 49.46%. The median APACHE II score was 21.44. The concurrent infection rate was 74.19%, among whom 15.05% (n = 14) of those patients had pulmonary aspergillosis, 21.05% (n = 20) had bacteremia, and 23.65% (n = 22) had CMV infections. The patients who received initial caspofungin combination with TMP/SMZ had the best positive response rate (76.74%) compared to others (p = 0.001). Furthermore, the group that received initial caspofungin combined with TMP/SMZ had a 90-day all-cause mortality rate (39.53%) that was significantly different from that of the shift group (65.51%, p = 0.024), but this rate showed no statistically significant difference compared with that in the monotherapy group (48.62%, p = 0.322). None of the patients had serious adverse events from caspofungin therapy. Conclusions For non-HIV-infected patients with severe PCP, initial combination therapy with caspofungin and TMP/SMZ is a promising first-line treatment option compared with TMP/SMZ monotherapy and combination therapy as salvage therapy.

Abstract Background Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of therapeutic LIPUS in improving lung inflammation in hospitalized patients with viral pneumonia. Methods Sixty eligible participants with clinically confirmed viral pneumonia will be assigned to either (1) intervention group (LIPUS stimulus), (2) control group (null stimulus), or (3) self-control group (LIPUS stimulated areas versus non-stimulated areas). The primary outcome will be the difference in the extent of absorption and dissipation of lung inflammation on computed tomography. Secondary outcomes include changes in lung inflammation on ultrasonography images, pulmonary function, blood gas analysis, fingertip arterial oxygen saturation, serum inflammatory factor levels, the sputum excretion volume, time to the disappearance of pulmonary rales, pneumonia status score, and course of pneumonia. Adverse events will be recorded. Discussion This study is the first clinical study of the efficacy of therapeutic LIPUS in the treatment of viral pneumonia. Given that the current clinical recovery mainly depends on the body’s self-limiting and conventional symptomatic treatment, LIPUS, as a new therapy method, might be a major advance in the treatment of viral pneumonia. Trial registration ChiCTR2200059550 Chinese Clinical Trial Registry, May 3, 2022.

Abstract Background Circulating tumor cells (CTCs) are important biological indicators of the lung cancer prognosis, and CTC counting and typing may provide helpful biological information for the diagnosis and treatment of lung cancer. Methods The CTC count in blood before and after radiotherapy was detected by the CanPatrol™ CTC analysis system, and the CTC subtypes and the expression of hTERT before and after radiotherapy were detected by multiple in situ hybridization. The CTC count was calculated as the number of cells per 5 mL of blood. Results The CTC positivity rate in patients with tumors before radiotherapy was 98.44%. Epithelial–mesenchymal CTCs (EMCTCs) were more common in patients with lung adenocarcinoma and squamous carcinoma than in patients with small cell lung cancer (P = 0.027). The total CTCs (TCTCs), EMCTCs, and mesenchymal CTCs (MCTCs) counts were significantly higher in patients with TNM stage III and IV tumors (P 1 (P = 0.022 and P = 0.024, respectively). The TCTCs and EMCTCs counts before and after radiotherapy affected the overall response rate (ORR) (P