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Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the viability of performing initial artificial joint replacement surgery in patients presenting with unexplained elevations in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels., Methods: A cohort of 22 patients, comprising 11 cases each for knee and hip joint replacements, who underwent initial artificial joint replacement surgery between November 2020 and January 2022, was recruited. All patients exhibited elevated levels of ESR and CRP prior to surgery, the etiology of which remained undetermined. Intraoperatively, joint effusion and periarticular tissues were preserved for subsequent bacterial culture and metagenomic next-generation sequencing (mNGS). Postoperatively, a combination of intravenous and local antibiotics was administered for anti-infective management. In cases where bacterial culture and/or mNGS yielded positive results, patients were diagnosed with periprosthetic joint infections (PJI) and underwent one-stage revision; conversely, negative findings led to the discontinuation of intravenous and local antibiotics therapy., Results: Among the cohort of 22 patients, bacterial cultures yielded negative results, while mNGS identified bacterial infection in 14 patients (63.63%), viral infection in 1 patient (4.55%), and yielded negative results in 7 patients (31.82%). All surgical incisions achieved per primam. Subsequent follow-up assessments conducted for more than 1 year postoperatively revealed absence of PJI among the patients, all of whom exhibited satisfactory progress in their rehabilitation exercises. Notably, the Knee Society Score (KSS) for knee joint patients significantly improved from a preoperative mean of 48.7 ± 3.3 points to 84.3 ± 2.2 points postoperatively, whereas the Harris Hip Score for hip joint patients increased significantly from preoperative mean of 50.6 ± 3.6 points to 87.1 ± 1.6 points (P < 0.01)., Conclusion: In cases where patients present with unexplained elevations in ESR and CRP levels, primary artificial joint replacement can be undertaken following a one-stage revision approach for PJI., (© 2024. The Author(s).)

Background: In patients undergoing breast-conserving therapy without surgical clip implantation, the accuracy of tumor bed identification and the consistency of clinical target volume (CTV) delineation under computed tomography (CT) simulation remain suboptimal. This study aimed to investigate the feasibility of implementing preoperative magnetic resonance (MR) simulation on delineations by assessing interobserver variability (IOV)., Methods: Preoperative MR and postoperative CT simulations were performed in patients who underwent breast-conserving surgery with no surgical clips implanted. Custom immobilization pads were used to ensure the same supine position. Three radiation oncologists independently delineated the CTV of tumor bed on the images acquired from MR and CT simulation registration and CT simulation alone. Cavity visualization score (CVS) was assigned to each patient based on the clarity of the tumor bed on CT simulation images. IOV was indicated by generalized conformity index (CI gen ), denoted as CI gen-CT and CI gen-MR/CT , and the distance between the centroid of mass (dCOM), denoted as dCOM CT and dCOM MR/CT . The variation of IOV in different CVS subgroups was analyzed., Results: A total of 10 patients were enrolled in this study. The median and interquartile range (IQR) of maximum pathological diameter of the tumors in all patients were 1.55 (0.80-1.92) cm. No statistical significance was found between the volumes of CTVs on CT simulation and on MR/CT simulation registration images (p = 0.387). CI gen-MR/CT was significantly larger than CI gen-CT (p = 0.005). dCOM MR/CT was significantly smaller than dCOM CT (p = 0.037). The median and IQR of CVS in all patients were 2.34 (2.00-3.08). The difference of CI gen between CI gen-MR/CT and CI gen-CT was larger in the low CVS group (p = 0.016). The difference of dCOM showed a decreasing trend when CVS was lower, although it did not reach statistical significance (p = 0.095)., Conclusions: For patients who underwent breast-conserving surgery without surgical clip implantation, the use of preoperative MR simulation in delineating the CTV of tumor bed decreased the IOV among observers. The consistency of tumor bed identification was improved especially in cases where the margins of tumor bed were challenging to visualize on CT simulation images. The study findings offer potential benefits in reducing local recurrence and minimizing tissue irritation in the surrounding areas. Future investigation in a larger patient cohort to validate our results is warranted., (© 2024. The Author(s).)

Background: Congenital aniridia is a rare pan-ocular disease characterized by complete irideremia, partial iridocoloboma. The progressive nature of aniridia is frequently accompanied by secondary ocular complications such as glaucoma and aniridia-associated keratopathy, which can lead to severely impaired vision or blindness. The genetic basis of aniridia has been the subject of numerous studies, leading to the development of innovative therapeutic options based on PAX6 nonsense mutations. Specific knowledge of the genetics of aniridia has become increasingly important. To report the clinical features, elucidate the genetic etiology, and reveal the mutational spectrum of congenital aniridia in the Chinese population, sixty patients with congenital aniridia from 51 families were recruited. Candidate genes associated with developmental eye diseases were identified and analyzed using panel-based next-generation sequencing (NGS), and mutations were confirmed through polymerase chain reaction and Sanger sequencing. Multiplex ligation probe amplification (MLPA) of PAX6 and FOXC1 was performed to detect copy number variations in the patients without intragenic mutations., Results: Clinical examination revealed complete iris hypoplasia in 58 patients and partial iris hypoplasia in two patients. Additionally, two patients were diagnosed with Wilms' tumor-aniridia-genital anomalies-retardation syndrome and nephroblastoma. By combining panel-based NGS and MLPA, 43 intragenic mutations or deletions of PAX6, FOXC1, and BCOR were identified in 59 patients, including 33 point mutations (76.7%) in 43 patients and 10 deletions (23.3%) in 16 patients. The total detection rate was 98.3%. Phenotypic variation was observed between and within families., Conclusions: Variations in PAX6 and its adjacent regions were the predominant causes of aniridia in China. In addition to intragenic point mutations in PAX6, deletion of PAX6 or its adjacent genes is a common cause of congenital aniridia. Furthermore, FOXC1 is an important gene associated with congenital aniridia. The combination of panel-based NGS and MLPA significantly enhanced the detection rate of gene mutations in patients with congenital aniridia., (© 2024. The Author(s).)

Objective: To analyze the genotypes of VZV in Jiangsu province to identify vaccine strains and wild strains, providing a molecular biological background for the effective prevention and control of varicella., Method: Stratified sampling was used to collect herpes fluid or throat swab from patients diagnosed with varicella. ORF22 was carried out, and the restriction enzyme site of ORF38, ORF54 and ORF62 were detected., Results: All 207 virus strains were Clade 2 type by sequencing the PCR products of ORF22. The sequencing results showed that five SNP sites changed compared to the Dumas reference strain(Clade 1). From A to G at 37,902, from T to c at 38,055, from A to C at 38,081, and from G to A at 38,177, from G to A at 39,394. The prevalent VZV genotypes in Jiangsu is consistent with the P-Oka. The restriction enzyme site analysis of PCR amplification products from ORF38 (PstI), ORF54 (BglI), ORF62 (SmaI) showed that all 207 virus strains were wild-type. There were two different types of the wild strains, and 183 strains (88.4%) were PstI (+), BglI (+), SmaI (-). The wild strains between different regions showed no significant differences (χ 2  = 0.05, P = 0.982)., Conclusions: The prevalent VZV genotypes are Clade 2 and the prevalent virus strains are wild strains in Jiangsu Province, the primary wild strain observed is mainly PstI (+), BglI (+), SmaI (-)., (© 2024. The Author(s).)

Background and Objectives: Lung cancer is one of the prevailing malignancies worldwide. Surgical interventions hold an important position in the treatment framework for lung cancer. Pleural metastasis is often assumed to be a surgical contraindication, but not all instances of pleural metastasis can be accurately identified before surgery. The question of how to address pleural metastasis detected intraoperatively is still undecided., Methods: This retrospective study included 187 lung cancer patients who underwent surgery from 2005 to 2017 in whom pleural metastasis was discovered incidentally during the operation. Data on demographic, surgical, pathological, postoperative treatment, and survival information were collected for further analysis., Results: For patients with intraoperatively detected pleural metastasis, two independent protective prognostic factors were receiving primary tumor resection (compared to only receiving pleural nodule biopsy, HR = 0.079, p = 0.022) and receiving postoperative adjuvant chemotherapy (HR = 0.081, p < 0.001). Simultaneously, performing systematic lymph node dissection during primary tumor resection was found to be detrimental to long-term prognosis (HR = 2.375, p = 0.044). However, the resection of pleural metastatic lesions did not significantly impact patient prognosis., Conclusion: Our study supports the implementation of major tumor resection in patients with pleural metastasis detected intraoperatively but not lymph node dissection or the resection of pleural metastatic lesions. Postoperative chemotherapy is also necessary., (© 2024. The Author(s).)

Background: Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts., Methods: Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed., Results: CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients (r = 0.462 ∼ 0.636, p < 0.001)., Conclusion: Our study is the first to reveal a consistent and replicable contribution of peripheral inflammation to CP enlargement in vivo in sporadic ALS patients. Given that CP enlargement has been recently detected in other brain diseases, these findings should consider extending to other disease conditions with a peripheral inflammatory component., (© 2024. The Author(s).)

Objective: The efficacy of lymph node ratio (LNR) as a prognostic indicator in locally advanced gastric cancer (LAGC) patients underwent radical resection after neoadjuvant immunochemotherapy (NICT) remains to be demonstrated. The objective of the current retrospective study is to investigate the relationship between LNR and survival in patients with LAGC who underwent radical resection after NICT., Methods: A retrospective analysis was performed on 121 cases of LAGC in patients underwent radical resection after NICT between July 2020 and October 2023. The LNR values of the patients were divided into two groups using X-tile software. The first group, designated the low LNR group, comprised patients with LNR values of ≤ 33%. The second group, designated the high LNR group, comprised patients with LNR values of > 33%. The correlation between patient survival rates and a range of clinical and pathological variables was examined., Results: Overall, 121 patients were enrolled: 108 with low-LNR (LNR ≤ 33%) and 13 with high-LNR (LNR > 33%). A better 2-year overall survival (OS) (88.5% vs. 32.6%; p < 0.001) and progression-free survival (PFS) (80.2% vs. 23.5%; p < 0.001) were observed in patients with low LNR. A similar result was also found in those with non-pathological complete response group (non-pCR), where the 2-year OS was 87.2% vs. 32.6% (p < 0.001), and the 2-year PFS was 77.7% vs. 23.5% (p < 0.001). Compared to the pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for OS and PFS. Multivariate analysis indicated that LNR was an independent prognostic factor for both OS (HR 6.258, 95% CI 1.798-21.778; p = 0.004) and PFS (HR 3.431, 95% CI 1.341-8.780; p = 0.010), but not ypN., Conclusions: LNR may serve as a viable indicator for prognostication in LAGC patients treated with NICT., (© 2024. The Author(s).)

Schizophrenia is a severe psychiatric disorder with high heritability, characterized by positive and negative symptoms as well as cognitive abnormalities. Dysfunction in glutamate synapse is strongly implicated in the pathophysiology of schizophrenia. However, the precise role of the perturbed glutamatergic system in contributing to the cognitive abnormalities of schizophrenia at the synaptic level remains largely unknown. Although our previous work found that Opcml promotes spine maturation and Opcml-deficient mice exhibit schizophrenia-related cognitive impairments, the synaptic mechanism remains unclear. By using whole-cell patch clamp recording, we found that decreased neuronal excitability and alterations in intrinsic membrane properties of CA1 PNs in Opcml-deficient mice. Furthermore, Opcml deficiency leads to impaired glutamatergic transmission in hippocampus, which is closely related to postsynaptic AMPA/NMDA receptors dysfunction, resulting in the disturbances of E/I balance. Additionally, we found that the aripiprazole which we used to ameliorate abnormal cognitive behaviors also rescued the impaired glutamatergic transmission in Opcml-deficient mice. These findings will help to understand the synaptic mechanism in schizophrenia pathogenesis, providing insights into schizophrenia therapeutics with glutamatergic disruption., (© 2024. The Author(s).)

Background: Programmed cell death protein 1 (PD-1) blockade is essential in treating progressive colorectal cancer (CRC). However, some patients with CRC do not respond well to immunotherapy, possibly due to the exhaustion of CD8 + T cells in the tumor microenvironment. N-Acetylcysteine (NAC) can reduce CD8 + T cell exhaustion in vitro and induce their differentiation into long-lasting phenotypes, thus enhancing the anti-tumor effect of adoptive T cell transfer. However, whether NAC can be combined with PD-1 blockade in CRC treatment and how NAC regulates CD8 + T cell differentiation remain unclear. Hence, in this study, we aimed to investigate whether NAC has a synergistic effect with PD-1 blockers against CRC progression., Methods: We constructed a mouse CRC model to study the effect of NAC on tumors. The effect of NAC on CD8 + T cell differentiation and its potential mechanism were explored using cell flow assay and other studies in vitro and ex vivo., Results: We demonstrated that NAC synergized PD-1 antibodies to inhibit CRC progression in a mouse CRC model mediated by CD8 + T cells. We further found that NAC can induce TCF1 + PD1 + CD8 + T cell differentiation and reduce the formation of exhausted T cells in vitro and in vivo. Moreover, NAC enhanced the expression of Glut4 in CD8 + T cells, promoting the differentiation of TCF1 + PD1 + CD8 + T cells., Conclusions: Our study provides a novel idea for immunotherapy for clinically progressive CRC and suggests that Glut4 may be a new immunometabolic molecular target for regulating CD8 + T cell differentiation., (© 2024. The Author(s).)

Background: Despite the high cure rate of differentiated thyroid cancer (DTC), patients endure side effects from treatment and psychological distress, impacting their quality of life. The potential of mobile health (mHealth) interventions to address these issues remains unexplored. The purpose of this study is to develop an mHealth intervention based on the Multi-Theoretical Model of Health Behavior Change (MTM) and evaluate its impact on reducing anxiety, depression, fear of cancer progression, and enhancing quality of life in DTC patients., Methods: A single-blind, single-center, prospective, randomized controlled trial was conducted. One hundred and eleven consecutive DTC patients from Harbin Medical University's Fourth Hospital were enrolled from March 2023 to March 2024. Participants were randomized into a control group and an intervention group that received a 3-month mHealth intervention based on MTM theory. Outcomes were assessed using web-based questionnaires at baseline and conclusion., Results: One hundred four patients with DTC completed the study, with 7 lost to follow-up (6.3%). The intervention group experienced a significant drop in PHQ-4 scores post-MTM-mHealth intervention (P < .026), with no change in the control group, demonstrating a significant difference. The intervention group also had significantly lower anxiety (P < .015) and depression (P < .032) scores compared to controls. All PHQ-4 scores improved in the intervention group except for "Little interest or pleasure in doing things." Anxiety levels were significantly lower in the intervention group (P < .026) but remained unchanged in controls. The control group exhibited a significant increase in FCR-4 scores at follow-up, differing from the intervention group (P < 0.001). Quality of life scores did not differ at baseline but saw a significant improvement in the intervention group, while the control group experienced no significant change. The intervention group had higher VAS scores (P < .030) and greater health education satisfaction across all dimensions (P < .019)., Conclusions: The MTM-based mHealth intervention significantly benefits DTC patients by reducing anxiety, fear of cancer recurrence, and improving quality of life, though its effect on depression requires further investigation., Trial Registration: China Clinical Trial Registry ChiCTR2200064321., (© 2024. The Author(s).)

Background: Fibrosing mediastinitis (FM) is a rare yet fatal condition, caused by different triggers and frequently culminating in the obstruction of the pulmonary vasculature and airways, often leading to pulmonary hypertension and right heart failure. Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis (PVS) caused by FM. Our previous study showed as high as 24% of in-stent restenosis (ISR) in FM. However, the predictors of ISR are elusive., Objectives: We sought to identify the predictors of ISR in patients with PVS caused by extraluminal compression due to FM., Methods: We retrospectively enrolled patients with PVS-FM who underwent PTPV between July 1, 2018, and December 31, 2022. According to ISR status, patients were divided into two groups: the ISR group and the non-ISR group. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR., Results: A total of 142 stents were implanted in 134 PVs of 65 patients with PVS-FM. Over a median follow-up of 6.6 (3.4-15.7) months, 61 of 134 PVs suffered from ISR. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (odds ratio (OR): 0.79; 95% confidence interval [CI]: 0.64 to 0.98; P = 0.032), and stenosis of the corresponding pulmonary artery (Cor-PA) independently increased the risk of restenosis (OR: 3.41; 95% CI: 1.31 to 8.86; P = 0.012). The cumulative ISR was 6.3%, 21.4%, and 39.2% at the 3-, 6-, and 12-month follow-up, respectively., Conclusion: ISR is very high in PVS-FM, which is independently associated with RVD and Cor-PA stenosis., Trail Registration: Chinese Clinical Trials Register; No.: ChiCTR2000033153. URL: http://www.chictr.org.cn ., (© 2024. The Author(s).)

Background: Chronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers., Methods: We obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy., Results: After the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10 -4  ≤ P < 0.05)., Conclusion: Our study supported causal associations between CCL27, IL-12p70 and bladder cancer risk and potential associations of 7 cytokines with the risk of urologic cancers, helping us to further understand the pathogenesis of urologic cancers and providing clues for improving diagnostic accuracy and therapies., (© 2024. The Author(s).)

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC., Methods: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m 2 intravenous infusion, day 1; capecitabine 1000 mg/m 2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed., Discussion: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer., Trial Registration: This study was registered at www., Clinicaltrials: gov ., Trial Registration Number: NCT05972655. Date of registration: 31 July 2023., (© 2024. The Author(s).)

Background: The metabolism of gut microbiota produces bioactive metabolites that modulate host physiology and promote self-growth. Erysipelotrichaceae is one of the most common anaerobic microorganism families in the gut, which has been discovered to play a vital role in host metabolic disorders and inflammatory diseases. Our previous study found that N-acetylgalactosamine (GalNAc) in caecal content of pigs significantly affected the abundance of Erysipelotrichaceae strains. However, it remains unknown how GalNAc feeding in vitro culture affects the expression levels of genes in the GalNAc metabolic pathway and the concentrations of intermediate metabolites in the Erysipelotrichaceae strain. Whether GalNAc feeding should influence the metabolism of other nutrients, such as amino acids, remains unrevealed., Results: In this study, whole-genome sequence, transcriptome, and metabolome data were analyzed to assess the utilization of a Erysipelotrichaceae strain on GalNAc. The results showed the presence of a complete GalNAc catabolism pathway in the genome of this Erysipelotrichaceae strain. GalNAc feeding to this Erysipelotrichaceae strain significantly changed the expression levels of genes involved in glycolysis and tricarboxylic acid (TCA) cycle. Meanwhile, the concentrations of lactate, pyruvate, citrate, succinate and malate from the glycolysis and TCA cycle were significantly increased. In addition, transcriptome analysis indicated that the genes involved in the metabolism of amino acids were affected by GalNAc, including lysA (a gene involved in lysine biosynthesis) that was significantly down-regulated. The intracellular concentrations of 14 amino acids in the Erysipelotrichaceae strain were significantly increased after feeding GalNAc., Conclusions: Our findings comfirmed and extended our previous works that demonstrated the utilization of GalNAc by Erysipelotrichaceae strain, and explained the possible mechanism of GalNAc affecting the abundance of Erysipelotrichaceae strain in vitro., (© 2024. The Author(s).)

Background: Both microcoils and hook-wires are commonly utilized for preoperative pulmonary nodule localization due to their convenience, but it remains unclear which one should be prioritized for recommendation., Aims: To compare the safety and efficacy of microcoils and hook-wires for pulmonary nodule localization., Methods: From January 2021 to December 2021, 310 consecutive patients (113 males and 197 females) with 341 pulmonary nodules who underwent CT-guided microcoil or hook-wire localization prior to video-assisted thoracoscopic surgery (VATS) at our center were retrospectively included in this study. There were 161 patients in the microcoil group and 149 patients in the hook-wire group. The successful localization rate, complication rate, radiation exposure, and medical costs were compared between the two groups., Results: A total of 341 pulmonary nodules were localized, with a success rate of 99% (180/184) in the microcoil group and 93% (146/157) in the hook-wire group, respectively. All patients successfully underwent VATS. Multivariate analysis revealed that hook-wire localization, shorter needle depth into the lung tissue and the longer waiting time from localization to VATS were the risk factors for the localization failure. The incidences of pneumothorax in the microcoil group and hook-wire group were 34.8% (56/161) and 34.9% (52/149), respectively (P = 0.983). The incidences of pneumorrhagia were 13% (24/184) and 46.5% (73/157), respectively (P = 0.000). Multivariate analysis revealed that hook-wire localization and greater depth of needle penetration into lung tissue were risk factors for pneumorrhagia., Conclusion: Microcoil localization of pulmonary nodules is superior to hook-wire localization in terms of efficacy and safety. This finding provides insight into priority and broader promotion of microcoil localization., (© 2024. The Author(s).)

Objectives: The study aims to emphasize the clinical importance of the Deep Inspiration Breath Hold (DIBH) technique by quantifying its dosimetric advantages over Free Breathing (FB) in reducing radiation exposure to the heart, liver, and lungs for right-sided breast cancer patients. This evidence supports its potential for routine clinical use to mitigate radiation-induced toxicity., Methods: A systematic retrieval of controlled trials comparing DIBH and FB techniques in postoperative radiotherapy for right-sided breast cancer was conducted utilizing the PubMed, Embase, Cochrane Library, and Web of Science databases. The primary outcomes assessed included the doses of adjacent normal tissues (heart, liver, and lungs). Summary standardized mean differences (SMD) along with 95% confidence intervals (CI) were computed, respectively. StataMP 17 software was selected to perform data analysis., Results: The study encompassed an analysis of 313 patients derived from seven online studies, comprising 168 individuals in the DIBH group and 269 individuals in the FB group. The findings indicated that the DIBH group received significantly lower irradiation doses to the heart, liver, and lungs in comparison to the FB group, with statistical significance (heart dose: SMD = -0.63, 95% CI -0.85 to -0.41, P < 0.05; liver dose: SMD = -1.15, 95% CI -1.91 to -0.38, P < 0.05; lung dose: SMD = -0.79, 95% CI -1.23 to -0.35, P < 0.05)., Conclusion: This meta-analysis indicated that the application of DIBH during postoperative radiotherapy for right-sided breast cancer markedly decreases radiation exposure to the heart, liver, and lungs, while maintaining consistent tumor dose coverage., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Background: The association between uric acid and pulmonary embolism(PE) remains controversial, and there has been limited investigation into how uric acid influences pulmonary embolism across different age groups. Our study aimed to elucidate the relationship between uric acid levels and pulmonary embolism, considering variations across age groups., Methods: A total of 368 patients who underwent computed tomography pulmonary angiography from July 2018 to May 2022 were included in the analysis. Subsequently, the cohort was stratified by age, with separate univariate and multivariate logistic regression analyses conducted for the elderly (aged ≥ 60 years) and non-elderly (aged < 60 years), respectively., Results: The study revealed that patients with PE exhibited higher uric acid levels compared to those without (325.11 ± 137.02 vs. 298.26 ± 110.54 (umol/l), p = 0.039). This disparity persisted even after adjusting for multiple confounders (OR = 1.002, 95% CI 1.000-1.005, p = 0.042). Additionally, a notable age difference was observed between PE and non-PE patients (65.7 ± 16.12 vs. 61.42 ± 15.03 (umol/l), p = 0.009). Subsequently, upon age stratification, significant differences (p < 0.05) in serum uric acid were noted between PE and non-PE patients in both elderly and non-elderly populations. However, elevated uric acid levels were independently associated with PE only in the elderly following adjustment for multiple confounders (OR = 1.003, 95% CI 1.001-1.005, p = 0.008)., Conclusion: High uric acid levels are an independent risk factor for pulmonary embolism in the elderly (≥ 60 years)., (© 2024. The Author(s).)

Background: S100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear., Methods: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome., Results: A total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: β 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100β levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: β 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: β 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100β levels and HT was not significant in either stroke lateralization group., Conclusions: Serum S100β levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100β in judging the degree of disease and predicting prognosis., (© 2024. The Author(s).)

Importance: Vitiligo is a chronic skin disorder causing depigmentation. There is a lack of evidence-based medical evidence regarding ruxolitinib efficacy and safety for vitiligo., Objective: To assess the efficacy and safety of ruxolitinib cream in the treatment of vitiligo., Methods: The databases of PubMed, Embase, and Cochrane Library were searched. The literature screening was independently conducted by two reviewers., Data Extraction and Synthesis: For continuous variables, weighted mean difference (WMD) along with a 95% confidence interval (CI) was performed. For dichotomous outcomes, we calculated the odds ratios (ORs) or risk ratios (RRs), and their corresponding 95% CIs. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)., Main Outcomes and Measures: Symptoms, quality of life, and safety were evaluated using various measures, including the Facial Vitiligo Area Scoring Index (F-VASI), Total Vitiligo Area Scoring Index (T-VASI), Facial Body Surface Area (F-BAS), Total Body Surface Area (T-BAS) and Treatment-emergent Adverse Events (TEAEs)., Results: Three trials, involving a total of 830 participants from nine countries were included (female 388, 46.7%, male 442, 53.3%). The meta-analysis demonstrated a significant increase in the likelihood of participants achieving F-VASI75 (OR, 4.34 [95% CI 2.67-7.06]; high), F-VASI50 (OR 4.71 [95% CI 3.24-6.84]; high), T-VASI75 (OR 2.78 [95% CI 1.10-7.00]; moderate), and T-VASI50 (OR 4.47 [95% CI 2.52-7.92]; high) when compared ruxolitinib to vehicle. Ruxolitinib was associated with more lowered percentage change of F-VASI scores (MD - 32.79 [95% CI - 36.37 to - 29.21]; moderate), and T-VASI scores (MD - 20.22 [95% CI - 23.11 to - 17.33]; moderate) from baseline compared to vehicle. There may not be a significant difference in the occurrence of TEAEs between ruxolitinib and vehicle (RR 1.46 [95% CI 0.85-2.49]; high)., Conclusions: The findings suggest that ruxolitinib cream holds promise as a treatment option for vitiligo. Further long-term studies are needed to assess its sustained efficacy and safety profile., Systematic Review Registration: PROSPERO CRD42023431112., (© 2024. The Author(s).)

Background: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies., Results: Herein, we have developed a nanoplatforms Cy-NMNO@SiO 2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1 O 2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO 2 realized efficient drug loading and drug delivery., Conclusions: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules., (© 2024. The Author(s).)

Background: Spinal cord injury (SCI) results in severe, permanent functional changes and has become a global health priority due to its high incidence, cost, and disability rate. Current national epidemiological data on SCI in China are limited and outdated. This study aimed to provide a comprehensive, national cross-sectional investigation of SCI epidemiology in China., Methods: This cross-sectional study included 3055 SCI participants aged 8 to 78 years, conducted from May to September 2023. Data collected encompassed demographic characteristics, employment status, etiology, years lived with disability (YLD), family structure, caregiving status, income, health insurance, paralysis type, and health-related quality of life (HRQoL). Descriptive statistics analyses were used to assess demographic and injury characteristics. Group differences were assessed using t-tests, one-way ANOVA and Chi-square tests. Significant factors were examined using multivariate regression analysis., Results: The majority (88.9%) of respondents were aged 15 to 59 years, with a male-to-female ratio of 2.36:1. Car accidents caused 45.4% of tetraplegia cases, falls caused 35.9% of paraplegia cases, and myelitis was the leading cause of non-traumatic SCI. Among paraplegia participants, 65.5% had complete SCI, while 53.1% of tetraplegia participants had incomplete SCI. Functional improvement was reported by 9.58% of participants. Half (50.3%) of the respondents were unemployed, and 75% had incomes below the national average. HRQoL was significantly lower in the SCI population compared to controls, mainly influenced by injury site, income, age and etiology (p < 0.05)., Conclusions: SCI participants in China exhibit low HRQoL and reemployment rates. Accessible community and vocational rehabilitation programs, alongside robust public medical services, are essential for enhancing reemployment and HRQoL among SCI participants, reducing the overall disease burden., (© 2024. The Author(s).)

Background: Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP)., Methods: The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG., Results: After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 - -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 - -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 - -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 - -0.0008) in patients with POAG., Conclusions: Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk., (© 2024. The Author(s).)

Background: Multiple system atrophy (MSA) is recognized as an atypical Parkinsonian syndrome, distinguished by a more rapid progression than that observed in Parkinson's disease. Unfortunately, the prognosis for MSA remains poor, with a notable absence of globally recognized effective treatments. Although preliminary studies suggest that transcranial magnetic stimulation (TMS) could potentially alleviate clinical symptoms in MSA patients, there is a significant gap in the literature regarding the optimal stimulation parameters. Furthermore, the field lacks consensus due to the paucity of robust, large-scale, multicenter trials., Methods: This investigation is a multi-center, randomized, double-blind, sham-controlled trial. We aim to enroll 96 individuals diagnosed with MSA, categorized into Parkinsonian type (MSA-P) and cerebellar type (MSA-C) according to their predominant clinical features. Participants will be randomly allocated in a 1:1 ratio to either the TMS or sham stimulation group. Utilizing advanced navigation techniques, we will ensure precise targeting for the intervention, applying theta burst stimulation (TBS). To assess the efficacy of TBS on both motor and non-motor functions, a comprehensive evaluation will be conducted using internationally recognized clinical scales and gait analysis. To objectively assess changes in brain connectivity, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) will be employed as sensitive indicators before and after the intervention., Discussion: The primary aim of this study is to ascertain whether TBS can alleviate both motor and non-motor symptoms in patients with MSA. Additionally, a critical component of our research involves elucidating the underlying mechanisms through which TBS exerts its potential therapeutic effects., Ethics and Dissemination: All study protocols have been reviewed and approved by the First Affiliated Medical Ethics Committee of the Air Force Military Medical University (KY20232118-F-1)., Trial Registration: Chinese Clinical Trial Registry ChiCTR2300072658. Registered on 20 June 2023., (© 2024. The Author(s).)

The immune response gene 1 (IRG1) and its metabolite itaconate are implicated in modulating inflammation and oxidative stress, with potential relevance to sepsis-induced myocardial dysfunction (SIMD). This study investigates their roles in SIMD using both in vivo and in vitro models. Mice were subjected to lipopolysaccharide (LPS)-induced sepsis, and cardiac function was assessed in IRG1 knockout (IRG1-/-) and wild-type mice. Exogenous 4-octyl itaconate (4-OI) supplementation was also examined for its protective effects. In vitro, bone marrow-derived macrophages and RAW264.7 cells were treated with 4-OI following Nuclear factor, erythroid 2 like 2 (NRF2)-small interfering RNA administration to elucidate the underlying mechanisms. Our results indicate that IRG1 deficiency exacerbates myocardial injury during sepsis, while 4-OI administration preserves cardiac function and reduces inflammation. Mechanistic insights reveal that 4-OI activates the NRF2/HO-1 pathway, promoting macrophage polarization and attenuating inflammation. These findings underscore the protective role of the IRG1/itaconate axis in SIMD and suggest a therapeutic potential for 4-OI in modulating macrophage responses., (© 2024. The Author(s).)

Background: Colony stimulating factor 1 (CSF1) is generally expressed by immune cells in response to pro-inflammatory stimuli. The CSF1 receptor (CSFR) is activated by CSF1, and plays a key role in macrophage homeostasis. Furthermore, the CSF1R + macrophages maintain homeostasis in the intestinal epithelium. The aim of this study was to explore the functions of CSF1-expressing and CSF1R + macrophages in necrotizing enterocolitis (NEC), which commonly affects the ileum of neonates., Methods: In-situ CSF1 expression in the intestines of neonates with NEC or intestinal atresia (n = 4 each) was detected by immunofluorescence staining. The CSF1 levels in the intestinal crypt-derived organoid cultures were measured by ELISA. Peripheral blood monocyte-derived Mφ macrophages were co-cultured with the organoids and stimulated with lipopolysaccharide (LPS) to mimic the inflamed state of the ileum in NEC patients., Results: CSF1 was expressed in the intestinal epithelial cells of the fetal and neonatal samples, but suppressed in the NEC samples. Furthermore, CSF1 expression was downregulated in the intestinal crypt-derived organoids by LPS. CSF1R + macrophages were detected near the intestinal crypts in the non-inflamed intestines but were absent in tissues obtained from pediatric NEC patients. Peripheral blood monocyte-derived macrophages promoted intestinal organoid proliferation in vitro following CSF1 stimulation. Finally, low concentrations of LPS slightly enhanced the proliferation of organoids co-cultured with the macrophages, whereas higher doses had a significant inhibitory effect., Conclusions: Intestinal epithelial cells express CSF1 to regulate the resident macrophages, maintain epithelial homeostasis, and resist infection. The abundant CSF1R + macrophages in the fetal intestine may overexpress TNF-α upon activation of the TLR4/NF-κB pathway, resulting in epithelial damage and NEC induction., (© 2024. The Author(s).)

Objective The influence of macrovascular invasion on the therapeutic efficacy of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) in hepatocellular carcinoma (HCC) patients has not been previously reported. This study primarily examines the therapeutic effect of ALPPS in treating HCC with macrovascular invasion. Methods 89 patients who underwent ALPPS at the First Affiliated Hospital of Guangxi Medical University from December 2016 to December 2021 were included. Patients were categorized into three groups based on macrovascular invasion status: pure HCC, HCC with portal vein tumor thrombus (PVTT), and HCC with hepatic vein tumor thrombus (HVTT). Outcome measures such as postoperative complications, liver hyperplasia rates, and survival times were compared across the groups. Results The study comprised 44 patients without macrovascular invasion and 45 cases with it, including 37 PVTT and 8 HVTT cases. Patients with PVTT or HVTT had a higher rate of complications and liver failure after the first ALPPS stage compared to those without macrovascular invasion (P = 0.018, P = 0.036). This trend was also observed in the stratified analysis of severe complications. However, no significant differences were found in these outcomes after the second ALPPS stage among the groups. The volume and rate of future liver remnant proliferation between the two stages of ALPPS were not statistically different among the groups, with median overall survival times of 42, 39, and 33 months, and progression-free survival times of 30, 24, and 14 months, respectively (P = 0.412 and P = 0.281). Conclusion ALPPS for HCC with macrovascular invasion was considered safe, feasible, and effective, as it achieved therapeutic effects comparable to those in cases without macrovascular invasion., (© 2024. The Author(s).)

Background: There is a growing trend to include non-randomised studies of interventions (NRSIs) in rare events meta-analyses of randomised controlled trials (RCTs) to complement the evidence from the latter. An important consideration when combining RCTs and NRSIs is how to address potential bias and down-weighting of NRSIs in the pooled estimates. The aim of this study is to explore the use of a power prior approach in a Bayesian framework for integrating RCTs and NRSIs to assess the effect of rare events., Methods: We proposed a method of specifying the down-weighting factor based on judgments of the relative magnitude (no information, and low, moderate, serious and critical risk of bias) of the overall risk of bias for each NRSI using the ROBINS-I tool. The methods were illustrated using two meta-analyses, with particular interest in the risk of diabetic ketoacidosis (DKA) in patients using sodium/glucose cotransporter-2 (SGLT-2) inhibitors compared with active comparators, and the association between low-dose methotrexate exposure and melanoma., Results: No significant results were observed for these two analyses when the data from RCTs only were pooled (risk of DKA: OR = 0.82, 95% confidence interval (CI): 0.25-2.69; risk of melanoma: OR = 1.94, 95%CI: 0.72-5.27). When RCTs and NRSIs were directly combined without distinction in the same meta-analysis, both meta-analyses showed significant results (risk of DKA: OR = 1.50, 95%CI: 1.11-2.03; risk of melanoma: OR = 1.16, 95%CI: 1.08-1.24). Using Bayesian analysis to account for NRSI bias, there was a 90% probability of an increased risk of DKA in users receiving SGLT-2 inhibitors and an 91% probability of an increased risk of melanoma in patients using low-dose methotrexate., Conclusions: Our study showed that including NRSIs in a meta-analysis of RCTs for rare events could increase the certainty and comprehensiveness of the evidence. The estimates obtained from NRSIs are generally considered to be biased, and the possible influence of NRSIs on the certainty of the combined evidence needs to be carefully investigated., (© 2024. The Author(s).)

Background: How to mobilize nurses students' learning initiative, reduce the incidence of academic procrastination, and improve their social adaptability is a key factor in lowering nursing brain drain and improving nursing quality., Objective: To explore the mediating role of resilience in the correlation between social adaptability and academic procrastination of undergraduate nursing students., Methods: This study is a cross-sectional survey. The researchers conducted an electronic questionnaire survey of 962 nursing undergraduates in Guanzhong District, Shaanxi Province from November 2022 to April 2023, and adopted the intention sampling method. And make the following assumptions: (1) There is a significant negative correlation between academic procrastination and social adaptability. (2) Academic procrastination can directly affect the social adaptability of undergraduate nursing students, and it has a significant negative predictive effect. (3) Resilience can directly affect academic procrastination and social adaptability. At the same time, resilience plays an intermediary role between the two. In this study, the Aitken procrastination scale, the resilience scale, and the social adaptability diagnostic scale were used to evaluate undergraduate nursing students. SPSS27.0 software is used to analyze the data statistically, and the Hayes PROCESS Macro method is used to test the model., Results: The study's findings are as follows: 1) Academic procrastination significantly and negatively impacts social adaptability (c = -0.292, t = -6.407, p < 0.001). 2) Even when accounting for resilience, academic procrastination still significantly predicts lower social adaptability (c'= -0.204, t = -4.338, p < 0.001). 3) The Bootstrap method test of percentile bias correction indicates that resilience serves as a significant mediator between academic procrastination and social adaptability. Bootstrap SE = 0.018, 95% CI = (-0.124, -0.055). The indirect effect contributes to 29.79% of the total effect., Conclusion: Resilience not only directly affects the academic procrastination and social adaptability of nursing students, but also partially intermediate the relationship between academic procrastination and social adaptability., (© 2024. The Author(s).)

Background: Empagliflozin (EMPA) has demonstrated efficacy in providing cardiovascular benefits in metabolic diseases. However, the direct effect of EMPA on autophagy in obesity-related cardiac dysfunction remains unclear. Therefore, this study aimed to determine changes in cardiac autophagy during diet-induced obesity and clarify the exact mechanism by which EMPA regulates autophagic pathways., Methods: Male C57BL/6J mice were fed a 12-week high-fat diet (HFD) followed by 8 weeks of EMPA treatment. Body composition analysis and echocardiography were performed to evaluate metabolic alterations and cardiac function. Histological and immunofluorescence staining was used to evaluate potential enhancements in myocardial structure and biological function. Additionally, H9c2 cells were transfected with small interfering RNA targeting sirtuin 3 (SIRT3) and further treated with palmitic acid (PA) with or without EMPA. Autophagy-related targets were analyzed by western blotting and RT‒qPCR., Results: EMPA administration effectively ameliorated metabolic disorders and cardiac diastolic dysfunction in HFD-fed mice. EMPA prevented obesity-induced myocardial hypertrophy, fibrosis, and inflammation through the activation of SIRT3-mediated autophagosome formation. The upregulation of SIRT3 triggered by EMPA promoted the initiation of autophagy by activating AMP-activated protein kinase (AMPK) and Beclin1. Furthermore, activated SIRT3 contributed to the elongation of autophagosomes through autophagy-related 4B cysteine peptidase (ATG4B) and autophagy-related 5 (ATG5)., Conclusions: EMPA promotes SIRT3-mediated autophagosome formation to alleviate damage to the cardiac structure and function of obese mice. Activated SIRT3 initiates autophagy through AMPK/Beclin1 and further stimulates elongation of the autophagosome membrane via ATG4B/ATG5. These results provide a new explanation for the cardioprotective benefits of EMPA in obesity., (© 2024. The Author(s).)

Background: Protein-protein interactions are the primary means through which proteins carry out their functions. These interactions thus have crucial roles in life activities. The wide availability of fully sequenced animal and plant genomes has facilitated establishment of relatively complete global protein interaction networks for some model species. The genomes of cultivated and wild peanut (Arachis hypogaea L.) have also been sequenced, but the functions of most of the encoded proteins remain unclear., Results: We here used homologous mapping of validated protein interaction data from model species to generate complete peanut protein interaction networks for A. hypogaea cv. 'Tifrunner' (282,619 pairs), A. hypogaea cv. 'Shitouqi' (256,441 pairs), A. monticola (440,470 pairs), A. duranensis (136,363 pairs), and A. ipaensis (172,813 pairs). A detailed analysis was conducted for a putative disease-resistance subnetwork in the Tifrunner network to identify candidate genes and validate functional interactions. The network suggested that DX2UEH and its interacting partners may participate in peanut resistance to bacterial wilt; this was preliminarily validated with overexpression experiments in peanut., Conclusion: Our results provide valuable new information for future analyses of gene and protein functions and regulatory networks in peanut., (© 2024. The Author(s).)

Aims: To explore the effect of early initiation of self-management based on multidisciplinary education in heart failure (HF) patients., Methods: HF patients in the Cardiology Department of Beijing Hospital were consecutively enrolled from June 2022 to February 2023. In-hospital HF patients from June 2022 to October 2022 were divided into the control group, and HF patients from November 2022 to February 2023 were divided into the cardiac rehabilitation (CR) group. A series of self-management education sessions with cardiologists, pharmacologists, nutritionists, and nurses was initiated early in the CR group. Continuous strengthening education was provided during the 3 months of discharge. Patients in the control group only received education twice during hospitalization. Minnesota Living with Heart Failure Questionnaire (MLHFQ), Pittsburgh sleep quality index (PSQI), anxiety Self-rating anxiety scale (SAS), and Self-rating depression scale (SDS) were compared between the two groups. Major cardiovascular adverse events (MACEs) were recorded during follow-up., Results: A total of 91 HF patients were enrolled. There were 44 patients in the CR group and 47 in the control group. Compared with before the program, the MLHFQ and SAS scores significantly decreased at 3 months after discharge in both groups. PSQI also showed mild improvement without significant differences in both groups. Furthermore, SDS showed a significant increase in the CR group but within the normal range. MACE occurrences did not show a significant difference., Conclusion: Early initiation of self-management program based on multidisciplinary education may help improve quality of life, sleep quality, and reduce anxiety for hospitalized HF patients., (© 2024. The Author(s).)

Background: Maple is an important ornamental plant in China. With the increasing use of maple trees in landscaping, a symptom of shoot dieback has been observed in Henan province, China., Results: In this study, 28 Diaporthe isolates were obtained from symptomatic shoots of maple trees between 2020 and 2023. Phylogenetic analyses based on five loci (ITS, TEF, CAL, HIS and TUB) coupled with morphology of 12 representative isolates identified three known species (D. eres, D. pescicola and D. spinosa) and one new species, namely D. pseudoacerina sp. nov. Koch's postulates confirmed that all these species were pathogenic. Additionally, D. pseudoacerina was able to infect China wingnut (Pterocarya stenoptera), pear (Pyrus sp.), and black locust (Robinia pseudoacacia). This study marks the first report of Diaporthe spinosa and D. pescicola pathogens infecting maple trees., Conclusions: These findings enhance the existing knowledge of the taxonomy and host diversity of Diaporthe species as, while also providing valuable information for managing of maple shoot dieback in Henan Province, China., (© 2024. The Author(s).)

Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide, posing a significant public health challenge. Despite advancements in treatment strategies, prognosis for advanced CRC remains poor. Here, we investigate the role of CLK3 and its interaction with the c-Myc signaling pathway in CRC progression. Our study reveals significant overexpression of CLK3 in CRC tumor tissues, correlating with disease advancement, and demonstrates that CLK3 promotes CRC cell proliferation, mediated by its activation of MYC signaling through upregulation of c-MYC expression. In vivo experiments confirm the oncogenic role of CLK3, with its loss resulting in decreased tumor growth and c-MYC expression. These findings highlight CLK3 as a potential therapeutic target in CRC, offering insights into novel treatment strategies., (© 2024. The Author(s).)

To assess the safety of varicella vaccine (VarV) by conducting post-marketing surveillance on adverse events following immunization (AEFI) in Jiangsu Province, China., Methods: We utilized the AEFI Information System of mainland China to monitor and categorize adverse reactions associated with VarV., Results: The incidence rate of AEFI was significantly higher after the first dose (48.79/100,000 doses) compared to the second dose (45.18/100,000 doses) (χ 2  = 4.63, P = 0.031). Regional variations in AEFI incidence were observed within Jiangsu Province. Common reactions comprised 90.96% of AEFIs, while rare reactions and coincidental events accounted for 6.59% and 0.51%, respectively. Notably, there were no adverse events linked to vaccine quality, program errors, psychogenic reactions, or fatalities. Over 96% of AEFIs occurred within three days of VarV administration, with redness at the injection site (2.6 cm to 5 cm in diameter) being the most frequently observed symptom., Conclusion: VarV demonstrates a commendable safety profile. Although there was a slight increase in AEFI incidence between 2022 and 2023, common vaccine reactions were predominantly observed, and the rates of rare reactions remained very low., (© 2024. The Author(s).)

Background: Armadillo Repeat Containing X-Linked 1 (ARMCX1), a member of the ARM Repeat X-linked protein family, exerts inhibitory function in various tumors. However, its biological role in lung adenocarcinoma (LUAD) and the underlying molecular mechanisms require further exploration., Methods: LUAD tissue microarrays and bioinformatic databases were used to evaluate the relationship between ARMCX1 and clinicopathological features. The influence of ARMCX1 on LUAD cell proliferation, migration, and invasion in vitro was determined by colony formation, CCK-8, EdU incorporation, cell cycle, wound healing, and Transwell assays. The impact of ARMCX1 on LUAD cell growth and metastasis in vivo was determined by subcutaneously transplanted tumor and pulmonary metastasis assays. Western blot, immunoprecipitation, immunofluorescence, cycloheximide, and proteasome inhibitor assays were finally conducted to explore the potential underlying molecular mechanisms., Results: ARMCX1 expression was downregulated in clinical LUAD samples due to which patient prognoses were poor. Functional experiments indicated that ARMCX1 overexpression inhibited the growth and metastasis of LUAD cells in vitro and in vivo. The molecular mechanism suggested that ARMCX1 recruits the E3 ubiquitin ligase FBXW7 for mediating ubiquitinated degradation of c-Myc, suppressing its nuclear accumulation, and ultimately inactivating cell cycle and epithelial-mesenchymal transition (EMT) signals., Conclusion: ARMCX1 inhibits LUAD cell proliferation and metastasis by interacting with c-Myc and enhancing its ubiquitination and degradation. Consequently, it can act as a tumor suppressor in this disease. These results suggest that ARMCX1 is a potential target in the treatment of LUAD., (© 2024. The Author(s).)

Background: Umbilical cord blood (UCB) is a rich source of multifunctional stem cells characterized by low immunogenicity. Recent research in the fields of aging and regenerative medicine has revealed the potential of human umbilical cord blood-derived exosomes (UCB-Exos) in promoting wound healing, anti-aging, and regeneration. However, their role in neurodegenerative diseases, specifically Parkinson's disease (PD), remains unexplored. This study investigates the potential therapeutic effects and underlying mechanisms of UCB-Exos on PD., Methods: Large extracellular vesicles (LEv), Exos, and soluble fractions (SF) of human UCB plasma were extracted to investigate their effects on motor dysfunction of the MPTP-induced PD mouse model and identify the key components that improve PD symptoms. UCB-Exos were administered by the caudal vein to prevent or treat the PD mouse model. The motor function and pathological markers were detected. Differentially expressed gene and KEGG enrichment pathways were screened by transcriptome sequence. MN9D and SH-SY5Y cells were cultured and evaluated for cell viability, oxidative stress, cell cycle, and aging-related indexes by qRT-PCR, western blot, immunofluorescence, and flow cytometry. The protein expression level of the MAPK p38 and ERK1/2 signaling pathway was detected by western blot., Results: We observed that LEv, Exos, and SF all exhibited potential in ameliorating motor dysfunction in MPTP-induced PD model mice, with UCB-Exos demonstrating the most significant effect. UCB-Exos showed comparable efficacy in preventing and treating motor dysfunction, cognitive decline, and substantia nigra pathological damage in PD mice. Further investigations revealed that UCB-Exos could potentially alleviate oxidative damage, aging and degeneration, and energy metabolism disorders in neurons. Transcriptome sequencing results corroborated that genes differentially expressed due to UCB-Exos were primarily enriched in the neuroactive ligand-receptor interaction, Dopaminergic synapse, and MAPK signaling pathway. We also observed that UCB-Exos significantly inhibited the hyperphosphorylation of the MAPK p38 and ERK1/2 signaling pathways both in vitro and in vivo., Conclusions: Our study provides a comprehensive evaluation of UCB-Exos on the neuroprotective effects and suggests that inhibition of hyperphosphorylation of MAPK p38 and ERK 1/2 signaling pathways by regulating transcription levels of HspB1 and Ppef2 may be the key mechanism for UCB-Exos to improve PD-related pathological features., (© 2024. The Author(s).)

Background: Glioma is the most common brain tumor. IDH mutations occur frequently in glioma, indicating a more favorable prognosis. We aimed to explore energy metabolism-related genes in glioma to promote the research and treatment., Methods: Datasets were obtained from TCGA and GEO databases. Candidate genes were screened by differential gene expression analysis, then functional enrichment analysis was conducted on the candidate genes. PPI was also carried out to help determine the target gene. GSEA and DO analysis were conducted in the different expression level groups of the target gene. Survival analysis and immune cell infiltrating analysis were performed as well., Results: We screened 34 candidate genes and selected GLUD1 as the target gene. All candidate genes were significantly enriched in 10 KEGG pathways and 330 GO terms. GLUD1 expression was higher in IDH-mutant samples than IDH-wildtype samples, and higher in normal samples than tumor samples. Low GLUD1 expression was related to poor prognosis according to survival analysis. Most types of immune cells were negatively related to GLUD1 expression, but monocytes and activated mast cells exhibited significantly positive correlation with GLUD1 expression. GLUD1 expression was significantly related to 119 drugs and 6 immune checkpoint genes. GLUD1 was able to serve as an independent prognostic indicator of IDH-mutant glioma., Conclusion: In this study, we identified an energy metabolism-related gene GLUD1 potentially contributing to favorable clinical outcomes of IDH-mutant glioma. In glioma, GLUD1 related clinical outcomes and immune landscape were clearer, and more valuable information was provided for immunotherapy., (© 2024. The Author(s).)

The peripheral perfusion index (PI) is derived from pulse oximetry and is defined as the ratio of the pulse wave of the pulsatile portion (arteries) to the non-pulsatile portion (venous and other tissues). A growing number of clinical studies have supported the use of PI in various clinical scenarios, such as guiding hemodynamic management and serving as an indicator of outcome and organ function. In this review, we will introduce and discuss this traditional but neglected indicator of the peripheral microcirculatory perfusion. Further clinical trials are required to clarify the normal and critical values of PI for different monitoring devices in various clinical conditions, to establish different standards of PI-guided strategies, and to determine the effect of PI-guided therapy on outcome., (© 2024. The Author(s).)

Background: Prematurity-related brain injury is a common and serious complication that has long-term effects on the survival and development of affected infants. Currently, the roles of certain biomarkers such as the protein hydrolysis product SBDP145, melatonin, soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), high mobility group box 1 protein (HMGB1), and hypoxia-inducible factor 1-alpha (HIF-1α) in prematurity-related brain injury remain not fully elucidated. Our study aims to assess the significance of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in preterm infants with brain injury., Methods: 135 preterm infants admitted to our hospital from January 2020 to February 2022 were selected and divided into 78 cases in a prematurity-associated brain injury group, and 57 cases in another group of preterm infants without brain injury or other diseases according to the magnetic resonance imaging results. The levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in the two groups were analyzed. The serum concentrations of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in newborns with different severity of ventricular hemorrhage were observed, and the levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α in those with different severity of white matter brain injury were compared., Results: The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were significantly higher in the preterm combined brain injury group than in the preterm group, and melatonin levels were significantly lower than in the preterm group(P < 0.05). The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were higher in the moderate to severe group and melatonin levels were lower in the mild group of newborns with ventricular hemorrhage (P < 0.05). The levels of SBDP145, sLOX-1, HMGB1 and HIF-1α were higher in the moderate-severe group and melatonin levels were lower in the mild group in newborns with cerebral white matter injury (P < 0.05). The independent variables were SBDP145, melatonin, sLOX-1, HMGB1, HIF-1α, and the dependent variable was the prognosis of neonates with brain injury. Univariate logistic regression analysis and multivariate logistic regression analysis were performed. The results showed that the influencing factors of newborns with brain injury were SBDP145, melatonin, sLOX-1, HMGB1, HIF-1α., Conclusion: The levels of SBDP145, melatonin, sLOX-1, HMGB1 and HIF-1α were highly expressed in preterm newborns with brain injury, and the levels were higher when the condition of the newborns was more severe. These findings suggest the potential clinical utility of these biomarkers in predicting and monitoring brain injury in preterm infants, which could aid in early intervention and improve long-term outcomes., (© 2024. The Author(s).)

Background: Kiwifruit, belonging to the genus Actinidia, represents a unique fruit crop characterized by its modern cultivars being genetically diverse and exhibiting remarkable variations in morphological traits and adaptability to harsh environments. However, the genetic mechanisms underlying such morphological diversity remain largely elusive., Results: We report the high-quality genomes of five Actinidia species, including Actinidia longicarpa, A. macrosperma, A. polygama, A. reticulata, and A. rufa. Through comparative genomics analyses, we identified three whole genome duplication events shared by the Actinidia genus and uncovered rapidly evolving gene families implicated in the development of characteristic kiwifruit traits, including vitamin C (VC) content and fruit hairiness. A range of structural variations were identified, potentially contributing to the phenotypic diversity in kiwifruit. Notably, phylogenomic analyses revealed 76 cis-regulatory elements within the Actinidia genus, predominantly associated with stress responses, metabolic processes, and development. Among these, five motifs did not exhibit similarity to known plant motifs, suggesting the presence of possible novel cis-regulatory elements in kiwifruit. Construction of a pan-genome encompassing the nine Actinidia species facilitated the identification of gene DTZ79&#95;23g14810 specific to species exhibiting extraordinarily high VC content. Expression of DTZ79&#95;23g14810 is significantly correlated with the dynamics of VC concentration, and its overexpression in the transgenic roots of kiwifruit plants resulted in increased VC content., Conclusions: Collectively, the genomes and pan-genome of diverse Actinidia species not only enhance our understanding of fruit development but also provide a valuable genomic resource for facilitating the genome-based breeding of kiwifruit., (© 2024. The Author(s).)

Background: Meeting the 24-hour movement behavior (24-HMB) guideline helps enhance quality of life (QOL) of adolescents. This study aimed to assess the associations between the 24-HMB (physical activity, screen time, sleep) and QOL among adolescents with idiopathic scoliosis., Methods: A cross-sectional study was conducted between September 2021 and September 2023. 24-HMB, QOL and demographic variables were collected through a self-reported questionnaire. Linear regression models and stratified analyses were used to explore statistical associations between the 24-HMB and QOL., Results: A total of 1073 participants aged 10-18 years with a spinal Cobb angle between 10° and 40° were included. Overall, 20 participants (1.9%) met all three behavioral guidelines, and 272 participants (25.3%) met none. Compared to those who did not meet any of the guidelines, adolescents meeting both screen time and sleep duration (β = 4.10, 95% CI: 2.02-6.18, P < 0.001) and all 3 guidelines (β = 4.39, 95% CI: 0.27-8.51, P = 0.037) had higher QOL scores. Stratified analyses showed that the above associations were more pronounced in adolescents without back pain or with good self-image., Conclusions: These findings highlight the importance of adopting and maintaining healthy behavioral habits in order to improve QOL among adolescents with idiopathic scoliosis, especially in those without back pain or with good self-image., (© 2024. The Author(s).)

Background: We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance., Methods: Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab., Results: Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 μm) and NDME (mean maximum diameter = 74.70 ± 2.86 μm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001)., Conclusions: Compared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness., (© 2024. The Author(s).)

Colon adenocarcinoma (COAD) represents a significant health concern within the population. Advancing our understanding of COAD is imperative for early detection, enabling personalized treatment interventions, and facilitating the development of effective preventive measures. The coagulation system plays a role in tumor-related pathological processes; however, its specific involvement in COAD and potential contributors remain unclear. This study aimed to establish a novel risk stratification approach by analyzing coagulation related genes (CRGs) associated with COAD. Through a comprehensive bioinformatics analysis of data from public databases, we screened COAD associated CRGs and characterized the associated molecular subtypes. After a comprehensive analysis of the characteristics of each subtype, we applied differentially expressed genes in CRG subtypes to establish a new risk stratification method. Clinical subgroup analysis, immunoinfiltration analysis, therapeutic reactivity prediction and other analytical methods suggest the potential clinical value of the established risk stratification method. As one of the selected targets, the effect of MS4A4A on the proliferation and invasion of COAD was confirmed by in vitro experiments, which partially verified the reliability of bioinformatics results. Our findings delineate CRGs potentially implicated in COAD pathogenesis and offer fresh insights into the influence of the coagulation process on tumorigenesis and progression., (© 2024. The Author(s).)

Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8 + T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC., (© 2024. The Author(s).)

Background: Pars Plana Vitrectomy (PPV) combined with subretinal injection of low-dose recombinant tissue plasminogen activator (rt-PA) and intravitreal injection of Conbercept as a novel therapy for submacular hemorrhage (SMH) requires evaluation., Methods: In a retrospective interventional clinical study, 14 eyes of 14 patients with SMH underwent PPV along with rt-PA (subretinal) and Conbercept (intravitreal) injections. The main outcomes included best-corrected visual acuities (BCVAs), degrees of blood displacement, and adverse events. All patients completed at least 6-month follow-up visits., Results: Mean BCVAs significantly improved at 7 days (22.29 ± 15.35), 1 month (30.71 ± 16.42), 3 months (38.29 ± 13.72), 4 months (38.86 ± 14.15), and 6 months (41.21 ± 14.91) post-treatment compared to baseline (16.36 ± 13.97) (F = 12.89, P = 0.004). The peak improvement in BCVAs occurred at 6 months postoperatively. The procedure effectively eliminated subfoveal hemorrhages in all eyes, with clots removal and absorption occurring within one month and complete regression by 3-month follow-up visits. Postoperatively, two cases of AMD resulted in discoid scars on the fundus. No instances of rt-PA-related retinal toxicity were observed during the follow-up period., Conclusion: The combined approach of PPV with low-dose rt-PA and anti-VEGF shows promise in enhancing both vision and anatomical structure in SMH therapy. Individualized treatment plans tailored to the primary disease should be developed to optimize visual prognoses., Trial Registration: Retrospectively registered No.ChiCTR2100053034. Registration date: 10/11/2021., (© 2024. The Author(s).)