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ObjectiveThe aim of this study was to develop a population pharmacokinetic model for ceftazidime in critically ill children in the pediatric intensive care unit (PICU) and optimize an appropriate dosing regimen for this population.MethodsWe performed a prospective pharmacokinetic study on critically ill children aged 0.03–15 years. A population pharmacokinetic model was developed using the NLME program. Statistical and graphical methods were used to assess the stability and predictive performance of the model. Monte Carlo simulations were conducted to determine the optimal ceftazidime dosing regimen to achieve 70% fT > minimum inhibitory concentration (MIC).ResultsThis study included 88 critically ill children and 100 ceftazidime serum concentrations. The pharmacokinetic characteristics of ceftazidime were best described by a one-compartment linear elimination model. The weight and estimated glomerular filtration rate (eGFR) were determinant covariates for the clearance (CL) of ceftazidime. The recommended ceftazidime dosage regimens achieved a probability of target attainment (PTA) >90% for critically ill children at MIC values of 2, 4, and 8 mg/L. For bacterial infection at an MIC of 16 mg/L, it is difficult to achieve effective pharmacodynamic (PD) targets in vivo with the commonly used dose of ceftazidime.ConclusionThe population pharmacokinetic model of ceftazidime was established in critically ill children. Based on this model, we recommend evidence-based, individualized dosing regimens for subgroups with different weights and renal functions. The current daily dosage for children adequately meets the treatment requirements for MICs of 2, 4, and 8 mg/L, while for bacterial infection at an MIC of 16 mg/L, an elevated dosage regimen may be required.Clinical Trial Registrationhttps://www.medicalresearch.org.cn/login, Identifier MR-42-22-000220.

BackgroundTo identify risk factors for progression, acute exacerbation (AE), and the development of rapidly progressive interstitial lung disease (RP-ILD) in Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD).MethodsWe systematically searched PubMed, EMBASE, Scopus, the Cochrane Library, and Web of Science databases to identify eligible cohort studies up until January 01, 2024. Two reviewers independently screened the literature and extracted data. We employed the Newcastle-Ottawa Scale (NOS) to assess study quality and performed meta-analyses using STATA software.ResultsThis review included 50 studies. For progression, 28 studies were included, four significant risk factors were identified: male (OR = 1.97, 95% CI 1.26–3.08, p

PurposeThis study aims to optimize neoadjuvant radiotherapy target area for locally advanced rectal cancer (LARC) patients undergoing total neoadjuvant therapy (TNT) by examining local recurrence patterns.Methods and materialsWe retrospectively analyzed the clinical data of rectal cancer patients who undergone local recurrence after surgery. Recurrence sites were categorized and compared with initial diagnosis imaging, focusing on visible and suspicious lesions.ResultsOf the 126 patients who met our criteria, 186 lesions were analyzed. Within these, 75.40% of cases (95/126) and 83.33% of lesions (155/186) were located within the pelvic cavity. Conversely, 3.97% of cases (5/126) and 3.33% of lesions (6/186) occurred outside the pelvic cavity. Additionally, 20.63% of cases (26/126) and 13.44% of lesions (25/186) were found in both regions. Recurrences were predominantly observed in mesenteric regions (MR) (40.86%, 76/186) and presacral regions (PR) (32.26%, 60/186). In addition, 86.51% of patients (109/126) had recurrent lesions in HRA and the suspected lesions areas. Further analysis showed that initial CEA levels and adjuvant therapy types were identified as independent predictors for recurrence in MR/PR and initially suspected lesions. 86.51% of patients had recurrent lesions in HRA and the suspected lesions areasConclusionThe MR, PR, and areas of initial suspicious lesions are high-risk zones for post-surgical recurrence of LARC. Exploratory study of involved-field irradiation (IFI) can be carried out in the context of TNT in LARC.

Clinical symptoms of Parkinson’s disease (PD) are classified into motor and non-motor symptoms. Mental disorders, especially depression, are one of the major non-motor manifestations of PD. However, the underlying mechanisms remain poorly understood. In the present study, 21 neurotransmitters associated with mental disorders were measured in serum samples from patients and controls using the ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) assay. Additionally, five clinical scales—the MDS Unified Parkinson’s Disease Rating Scale (UPDRS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD)—were used to evaluate the severity of both motor and non-motor symptoms in PD patients. Analysis of neurotransmitter metabolism revealed significant changes in the tryptophan (Trp) metabolic pathway in PD patients. Specifically, levels of Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM), and 5-methoxyltryptamine (MeOTA) were substantially decreased. Additionally, three other excitation/inhibiting amino acids—glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp)—also declined. Moreover, neurotransmitter conversion ratios, such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp), and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic insights into disrupted neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK) were negatively correlated with UPDRS scores, while 5-hydroxytryptamine (5-HT) and GABA levels were negatively correlated with non-motor symptoms in PD patients. In summary, this study elucidates, for the first time, the potential association and dynamics between altered neurotransmitter metabolism and the etiology of PD in terms of motor and non-motor functions. These findings offer novel biomarkers and therapeutic targets for the treatment of PD.

BackgroundCOVID-19 is a respiratory disease, and its symptoms may be affected by the upper airways of adolescents.ObjectiveTo investigate the effect of parameters of adolescents’ upper airways on COVID-19 symptom severity.MethodsThis retrospective study was performed from January to March 2022 at the Hospital of Stomatology, Xi’an Jiaotong University, Xi’an, China. The inclusion criteria were patients who started orthodontic treatment for the first time, who experienced initial onset of laboratory-confirmed COVID-19, and who received two intramuscular doses of the SARS-CoV-2 vaccine. Participants’ COVID-19 symptom severity was recorded by a questionnaire including seven different dimensions. The three-dimensional parameters of the upper airway were obtained by cone beam computed tomography (CBCT) and measured by Dolphin Imaging software by blinded orthodontic investigators. The correlation between COVID-19 symptom severity and three-dimensional upper airway parameters was analyzed.Results64 males (46.4%) and 74 females (53.6%) were included in the study, with the median age of 9.5 years. The severity score of dimension 3 (headache, muscle pain, fatigue, shortness of breath, diarrhea and smell affects) showed a linear relationship with age. Spearman's rank correlation showed that the severity score of dimension 1 (nasal symptoms) was negatively correlated with nasal volume (r = −0.325). The severity score of dimension 6 was negatively correlated with the height of the nasopharynx (r = −0.325) and positively correlated with the horizontal-to-vertical ratio of the oropharynx (r = 0.385).Conclusions and relevanceThe COVID-19 symptom severity was aggravated with the increase of age. Nasal and throat pain and dry mouth was negatively correlated with nasal volume and nasopharyngeal height. The COVID-19 symptom severity among individuals is relavant to age and upper airway.

ObjectivesTo evaluate the diagnostic accuracy of the quantitative flow ratio (QFR) for hemodynamic exploration of intracranial atherosclerotic stenosis, using the invasive cerebrovascular pressure ratio (CVPR) and resting full-cycle ratio (RFR) as reference standards.Materials and methodsPatients with symptomatic unifocal intracranial atherosclerotic stenosis were included. The CVPR was defined as the ratio of the proximal and distal pressures. All patients underwent angioplasty under general anesthesia. The QFR was calculated based on digital subtraction angiography. Using the CVPR as a reference, we compared its correlation with the QFR across different degrees and locations of stenosis.ResultsThe CVPR and QFR were measured in 34 vessels of 32 patients. The QFR demonstrated a high correlation and excellent agreement(r = 0.8227, p 80%, the QFR showed a high correlation (r = 0.8812, p

PurposeTo evaluate the effects of clear corneal incision (CCI) location and morphology on corneal surgically induced astigmatism (SIA) and higher-order aberrations (HOAs) in patients receiving implantable collamer lens (ICL V4c) implantation.MethodsThis retrospective study classified right eyes that underwent ICL implantation into two groups based on temporal or superior CCI. The Pentacam HR analyzer was used to measure the corneal astigmatism and HOAs. Analysis of the clear corneal incision (CCI) morphology, including incision width (Angle-W), incision length (IL), incision angles (Angle-En/Ex), and distance from the incision to corneal apex (Dis-En/Ex), was conducted using anterior segment optical coherence tomography (AS-OCT).ResultsThere were 75 eyes in the temporal CCI group and 47 eyes in the superior CCI group. Both groups showed satisfactory safety and efficacy postoperatively. In the temporal CCI group, Dis-En and Dis-Ex were considerably longer, whereas the superior CCI group displayed a significantly wider Angle-W. The anterior and posterior corneal SIA were comparable in both groups. Anterior corneal SIA was significantly correlated to Dis-En and Dis-Ex in the superior CCI group. Superior CCI caused a notable rise in corneal Z (3, 3), while temporal CCI led to increased Z (3, 1). CCI morphology was correlated to corneal Z (4, −4) and Z (4, 4) in the superior CCI group.ConclusionCCI locations caused slight variations in postoperative corneal SIA and HOAs following ICL implantation. Optimal postoperative visual outcomes may be better achieved with a CCI design featuring an increased distance from the corneal centroid and a decreased Angle-W.

BackgroundProgress in developing artificial intelligence (AI) products represented by large language models (LLMs) such as OpenAI’s ChatGPT has sparked enthusiasm for their potential use in mental health practice. However, the perspectives on the integration of LLMs within mental health practice remain an underreported topic. Therefore, this study aimed to explore how mental health and AI experts conceptualize LLMs and perceive the use of integrating LLMs into mental health practice.MethodIn February–April 2024, online semi-structured interviews were conducted with 21 experts (12 psychiatrists, 7 mental health nurses, 2 researchers in medical artificial intelligence) from four provinces in China, using snowballing and purposive selection sampling. Respondents’ discussions about their perspectives and expectations of integrating LLMs in mental health were analyzed with conventional content analysis.ResultsFour themes and eleven sub-themes emerged from this study. Firstly, participants discussed the (1) practice and application reform brought by LLMs into mental health (fair access to mental health services, enhancement of patient participation, improvement in work efficiency and quality), and then analyzed the (2) technological-mental health gap (misleading information, lack of professional nuance and depth, user risk). Based on these points, they provided a range of (3) prerequisites for the integration of LLMs in mental health (training and competence, guidelines for use and management, patient engagement and transparency) and expressed their (4) expectations for future developments (reasonable allocation of workload, upgrades and revamps of LLMs).ConclusionThese findings provide valuable insights into integrating LLMs within mental health practice, offering critical guidance for institutions to effectively implement, manage, and optimize these tools, thereby enhancing the quality and accessibility of mental health services.

PurposeTo investigate the application value of the neutrophil to lymphocyte count ratio (NLR) in the prognostic analysis of intrahepatic cholangiocarcinoma (ICC) after radical resection, and to offer guidance for the individualized perioperative diagnosis and treatment of ICC.MethodsThe clinical data of 360 patients diagnosed with ICC following radical surgery were retrospectively analyzed. The cut-off value of NLR was calculated using the minimum p-value method, and then divided into High-NLR (H-NLR) group and Low-NLR (L-NLR) group according to the NLR cut-off value. The prognostic value of NLR in ICC was analyzed. Subsequently, the patients were divided into the hepatolithiasis-related intrahepatic cholangiocarcinoma (HICC) group and the non-hepatolithiasis-related intrahepatic cholangiocarcinoma (NHICC) group based on whether they combined with hepatolithiasis. Multiple regression models were constructed based on NLR and clinicopathological indicators to verify the application value of prognostic models in the survival and recurrence of ICC patients after radical surgery.ResultsThe cut-off value of NLR was 2.36, and the survival analysis disclosed that overall ICC patients with NLR ≥ 2.36 manifested a poor 5-year survival rate and a higher tumor recurrence rate (p

BackgroundInterstitial Lung Disease (ILD) represents the most common extra-articular manifestation of Rheumatoid Arthritis (RA) and is a major cause of mortality. This study aims to identify and evaluate biomarkers associated with Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD).MethodsWe searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for studies related to biomarkers of RA-ILD up until October 7, 2023. The Newcastle-Ottawa Scale (NOS) and standards recommended by the Agency for Healthcare Research and Quality (AHRQ) were used for quality assessment, and meta-analysis was conducted using Stata18.0 software.ResultsA total of 98 articles were assessed for quality, 48 of which were included in the meta-analysis. 83 studies were of high quality, and 15 were of moderate quality. The meta-analysis showed significant differences in biomarkers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody, Rheumatoid Factor (RF), Krebs von den Lungen-6 (KL-6), Surfactant Protein D (SP-D), Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 19-9 (CA19-9), Matrix Metalloproteinase-7 (MMP-7), C-X-C Motif Chemokine Ligand 10 (CXCL-10), and Neutrophil-to-Lymphocyte Ratio (NLR) between RA-ILD patients and RA patients. However, Platelet-to-Lymphocyte Ratio [Platelet-to-Lymphocyte Ratio (PLR)], Cancer Antigen 125 [Cancer Antigen 125 (CA-125)], and Cancer Antigen 153 [Cancer Antigen 153 (CA-153)] did not show significant differences between the two groups. KL-6, MMP-7, and Human Epididymis Protein 4 (HE4) are negatively correlated with lung function, and KL-6 is associated with the prognosis of RA-ILD.ConclusionsBiomarkers hold promising clinical value for prediction, diagnosis, severity assessment, and prognosis evaluation in RA-ILD. However, these findings need to be validated through multicenter, large-sample, prospective cohort studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023448372.

ObjectiveCerebrospinal fluid biomarkers are challenging to use for diagnosing mild cognitive impairment (MCI) in large populations, and there is an urgent need for new blood biomarkers. The aim of this study is to investigate whether astrocyte activation is correlated with hippocampal atrophy, and to assess the potential of glial fibrillary acidic protein (GFAP) as a biomarker for diagnosing MCI among community-dwelling older individuals.MethodsThis cross-sectional study included 107 older adults. The levels of GFAP in serum were measured, and the volumetric assessment of gray matter within hippocampal subregions was conducted using Voxel-Based Morphometry (VBM). The relationship between hippocampal subregion volume and blood biomarkers were analyzed using partial correlation. The effectiveness of blood biomarkers in differentiating MCI was assessed using a receiver operating characteristic (ROC) curve.ResultsWe found that serum GFAP levels were significantly elevated in the MCI group compared to the cognitively normal (CN) group. Additionally, individuals with MCI exhibited a reduction gray matter volume in specific hippocampal subregions. Notably, the right dentate gyrus (DG) and right cornu ammonis (CA) subregions were found to be effective for distinguishing MCI patients from CN individuals. Serum levels of GFAP demonstrate a sensitivity of 65.9% and a specificity of 75.6% in differentiating patients with MCI from CN individuals.ConclusionSpecific atrophy within hippocampal subregions has been observed in the brains of community-dwelling elderly individuals. Elevated levels of circulating GFAP may serve as a sensitive peripheral biomarker indicative of hippocampal-specific cognitive alterations in patients with MCI.

In the pursuit of sustainable construction practices, the utilization of recycled concrete has emerged as a pivotal strategy, distinguished by its commitment to resource conservation and environmental stewardship. Nevertheless, the inherent micro-porosity and micro-cracking within the old mortar of recycled concrete may lead to weak bonding performance at the interfacial transition zone, culminating in diminished strength, reduced density, and elevated water absorption rates compared to conventional concrete, which critically impairs its performance in cold climates subjected to freeze-thaw cycles. Consequently, this paper provides a structured examination of the frost resistance properties of recycled concrete subjected to freeze-thaw cycling. Initially, the study delineates the mechanisms of frost-induced damage in recycled concrete by synthesizing the degradation pathways observed in both conventional and recycled concrete during freeze-thaw exposure. Subsequently, a detailed analysis is conducted to identify the pivotal factors affecting frost resistance, encompassing the proportion and moisture affinity of recycled aggregates, the addition of silica fume and fly ash, the water-to-cement ratio, and the degree of water saturation. In the final segment, the study compiles and reviews the strategies for bolstering the frost resistance of recycled concrete, including the incorporation of air-entraining admixtures, fiber reinforcement, and aggregate modification approaches. The objective of this research is to offer a thorough comprehension of recycled concrete, with a concentration on the mechanisms of frost damage, the critical determinants of frost resistance, and interventions to augment its resilience against freezing conditions. On this basis, the present paper, in conjunction with the characteristics and current research status of recycled concrete, proposes recommendations for the application of recycled concrete in cold regions. This review is anticipated to facilitate researchers in gaining a comprehensive understanding of the freeze-thaw characteristics of recycled concrete and the measures to enhance its frost resistance. Furthermore, it aims to assist engineering and technical personnel in selecting appropriate treatment methods to improve the frost resistance of recycled concrete in cold regions, thereby promoting the practical engineering application of recycled concrete in such areas.

Ensuring representativeness of collected samples is the most critical requirement of water sampling. Unmanned surface vehicles (USVs) have been widely adopted in water sampling, but current USV sampling path planning tend to overemphasize path optimization, neglecting the representative samples collection. This study proposed a modified A* algorithm that combined remote sensing technique while considering both path length and the representativeness of collected samples. Water quality parameters were initially retrieved using satellite remote sensing imagery and a deep belief network model, with the parameter value incorporated as coefficient Q in the heuristic function of A* algorithm. The adjustment coefficient k was then introduced into the coefficient Q to optimize the trade-off between sampling representativeness and path length. To evaluate the effectiveness of this algorithm, Chlorophyll-a concentration (Chl-a) was employed as the test parameter, with Chaohu Lake as the study area. Results showed that the algorithm was effective in collecting more representative samples in real-world conditions. As the coefficient k increased, the representativeness of collected samples enhanced, indicated by the Chl-a closely approximating the overall mean Chl-a and exhibiting a gradient distribution. This enhancement was also associated with increased path length. This study is significant in USV water sampling and water environment protection.

Brucella abortus (B.abortus) is a zoonotic bacterial pathogen that causes chronic host infections. The eradication of brucellosis using antibiotic therapy is often incomplete or slow. In a mouse model, the predominance of alternatively activated macrophages (also known as M2) plays an essential role in sustaining chronic infection. The underlying functional mechanism by which M2 sustains chronic infection remains unclear. Here, we show that B. abortus can enter M2 via triggering receptor expressed on myeloid cells 2 (TREM2) and promotes the upregulation of TREM2 expression of M2 in a type IV secretion system (T4SS)-dependent manner. Increased TREM2 enhances B. abortus growth within M2 by suppressing intracellular ROS production, preventing M2 pyroptosis via suppression of mitochondrial ROS (mROS), and promoting M2 proliferation by increasing β-catenin expression. In line with these results, downregulation of TREM2 expression suppressed B. abortus intracellular growth and M2 proliferation and induced M2 pyroptosis. In our mouse model, upregulation of TREM2 expression sustained the accumulation of M2 and B. abortus chronic infection, whereas downregulation of TREM2 expression restricted M2 proliferation and chronic infection. Collectively, our results suggest that targeting TREM2 may be a potential adjunct to antibiotic therapy for the prevention of chronic Brucella infection.

Shellfish cultivation is a sustainable method of providing human food and can help remove large amounts of CO2 from the atmosphere. Over the last two decades, longline-based structures have dominated farming systems. So far, the innovative technologies for open-ocean shellfish farming remain stagnant and need to be developed. As such, this paper preliminarily studies the operation and survivability abilities of an innovative shellfish farm under extreme wave conditions. To that end, an efficient numerical scheme with a robust implicit finite element method is established. First, the numerical modeling of a single module of the shellfish farm is conducted and the numerical results are verified against physical model tests. Then, the numerical modeling is implemented in a full-scale shellfish farm containing nine floating rafts with suspended lantern nets in a 3×3 configuration exposed to extreme wave conditions. Different angles of wave attack and shellfish rafts with and without lantern nets are fully considered, allowing an assessment of the operation and survivability abilities of the shellfish farm under extreme wave conditions in various situations. The results highlight that the angle of wave attack significantly affected the energy absorption of the mooring system. Moreover, non-linear instability such as subharmonics, which existed in the motion dynamics, can be manipulated to avoid resonant motions. This study provides insights into the evaluation of the safety design of a shellfish farm at both operational and survivability levels. The numerical method can also model other advanced offshore marine structures with multi-modules, such as floating bridges, airports, and even floating energy islands.

BackgroundMonoclonal antibodies against programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) have emerged as critical tools in cancer treatment. However, concerns regarding their potential cutaneous and mucosal toxicity, along with severe complications, have drawn clinical attention. Further research is warranted to investigate the adverse reactions and treatment strategies associated with PD-1 monoclonal antibodies.MethodsWe present a detailed case report of a laryngeal cancer patient who developed toxic epidermal necrolysis (TEN) after treatment with PD-1 monoclonal antibody. We analyzed the etiology, diagnosis, and treatment approaches by integrating clinical manifestations, pathological examinations, and literature research.ResultsAfter PD-1 monoclonal antibody therapy, the patient exhibited systemic rash, bullae, and epidermal detachment, which subsequently involved the tracheal and bronchial mucosa, resulting in dyspnea. The patient recovered after treatments with steroids, macrolides, immunoglobulins, and etanercept, along with repeated removal of scabs via bronchoscopy. Literature reviewing suggests a potential association between PD-1 monoclonal antibodies and the pathogenesis of Steven Johnson’s Syndrome (SJS) and Toxic epidermal necrolysis (TEN), possibly due to immune dysregulation. Treatment consists of immediate discontinuation of suspicious drugs, essential supportive therapy, and systemic corticosteroid administration, with the addition of immunosuppressants and/or immunoglobulins needed.ConclusionThe mucocutaneous toxicity induced by PD-1 monoclonal antibodies is not limited to the surface of the skin but also in deep mucosal layers, potentially leading to life-threatening complications. Therefore, when using PD-1 monoclonal antibodies, clinicians should closely monitor adverse events and apply appropriate treatments as soon as possible to prevent severe complications.

BackgroundAsiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression.MethodsBehavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA.ResultsThis study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic–pituitary–adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis.ConclusionsThese results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model.

ObjectiveRadical hysterectomy has been established as the standard treatment for early stage cervical cancers. Despite numerous efforts to standardize the technique for radical hysterectomy across varying extents of tumor invasion, success has been inconsistent. Total Müllerian Compartment Resection (TMCR), an ontogenetic compartment-based oncologic surgery initially developed for open procedures by Professor Höckel, offers a standardized approach applicable to all patients with locally confined tumors. This method holds promise for achieving thorough oncologic clearance while maintaining acceptable complication rates. Moreover, robotic-assisted surgery may further reduce morbidity compared to open surgery. In this context, we provide a detailed step-by-step description of robotically assisted Total Müllerian Compartment resection (R-TMCR) for cervical cancer and present feasibility data from a cohort of 20 patients.Subjects and methods20 patients with stage IA1-IB2 cervical cancer, robot-assisted resection of the Müllerian embryonic compartment was undertaken. Key metrics such as operative duration, intraoperative blood loss, and postoperative complication rates were meticulously recorded and analyzed.ResultsThe duration of the surgery varied from 185 to 500 minutes, with intraoperative blood loss ranging between 5 mL and 300 mL. Postoperative hemoglobin levels dropped by -15 to 40 g/L from their preoperative values. Notably, there were no instances necessitating conversion to open surgery, and no intraoperative complications occurred. The rate of postoperative complications was 0%. Over the follow-up period, which averaged 18 months, there were no observed locoregional recurrences of cervical cancer, nor were there any deaths attributed to cervical cancer during this time.ConclusionThe application of robotic Müllerian compartment resection in the surgical treatment of cervical cancer is both safe and feasible. Utilizing robotic technology enables more precise and refined surgical outcomes. Combining embryonic compartment-based radical hysterectomy with the principles of membrane anatomy can standardize and optimize the surgical process, helping surgeons master radical hysterectomy more quickly and effectively.

IntroductionThe advent of bevacizumab has considerably transformed the therapeutic landscape for non-small cell lung cancer (NSCLC) patients devoid of specific genetic mutations. A pivotal milestone has been reached with the recent approval of a bevacizumab biosimilar, following rigorous phase III clinical investigations, poised to augment NSCLC therapeutic strategies.MethodsThis retrospective analysis encompasses a large-scale study conducted between January 2021 and December 2023, involving 1058 NSCLC patients (metastatic or locally advanced stages). The research design entailed a comparative assessment of the safety and efficacy profiles of combined therapies using the original bevacizumab and its biosimilar, adhering to RECIST v1.1 criteria. Adverse event grading was standardized using the National Cancer Institute’s CTCAE v5.0.ResultsNotably, the biosimilar demonstrated an objective response rate (ORR) of 29.79% in 606 patients, closely paralleling the 27.41% ORR observed in 452 patients receiving the original drug, with insignificant risk differences (-0.03) and a risk ratio of 0.987, affirming equivalence. Progression-free survival (PFS) was influenced by radiation status, treatment lines, and regimen combinations, while dosage intensity and genetic factors had negligible impacts. The incidence of treatment-emergent adverse events (TEAEs) was slightly higher in the biosimilar group (75.11%) versus the original drug group (72.78%), with grade 3 or more severe TEAEs occurring in 23.6% and 18.5% of patients, respectively (Detailed criteria for the definition and assessment of TEAEs have been added to the Methods section, including the use of the National Cancer Institute’s CTCAE v5.0 for grading).ConclusionsThe study affirms that bevacizumab biosimilars offer equivalent therapeutic efficacy and a similar safety profile to the originator product in the management of locally advanced or metastatic NSCLC. The tolerability of the toxicity profile, coupled with the absence of unforeseen adverse reactions, underscores the viability of biosimilar bevacizumab as a valuable addition to NSCLC treatment regimens. These findings also imply potential benefits for a broader patient population beyond clinical trial confines through the adoption of biosimilar beta-adrenergic blocking agents.

Primary hepatoid adenocarcinoma of the lung (HAL) is an exceptionally rare subtype of lung cancer that mimics the morphology and biological behavior of hepatocellular carcinoma. Although reports in the literature are limited, HAL is known for its high malignancy and poor prognosis, thus drawing increasing attention. We present the case of a patient with a mass-like consolidation with central necrosis initially misdiagnosed as inflammation at another medical institution despite a percutaneous lung biopsy. After ineffective anti-inflammatory treatment, she was referred to our hospital. We performed another lung biopsy, obtaining five samples from different angles, and eventually diagnosed her with HAL. Surprisingly, her serum alpha-fetoprotein (AFP) levels were extraordinarily high, leading to the successful diagnosis of HAL. Here, we present a case report and a related literature review.

BackgroundSystemic inflammatory response represented by C-reactive protein to albumin ratio (CAR) was shown to be associated with long-term outcome in patients with hepatocellular carcinoma (HCC). We conducted a meta-analysis to investigate the prognostic value of preoperative CAR in patients undergoing hepatectomy for HCC.MethodsWe searched four databases (PubMed, Embase, Scopus and Cochrane Library) from inception to May 10th, 2024. Studies investigating the prognostic value of preoperative CAR in HCC patients after hepatectomy. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Data from individual studies were aggregated to calculate the pooled hazard ratio (HR) using a random-effects model.ResultsA total of 11 studies included 4,066 patients were finally analyzed in the meta-analysis. Overall, the higher preoperative CAR was associated with poorer OS (HR 1.92, 95% CI 1.67 to 2.22, I2 = 0%) and DFS (HR 1.79, 95% CI 1.59 to 2.02, I2 = 0%) rate. Furthermore, subgroup analyses indicated that CAR could be a prognostic biomarker for patients with HCC regardless of regions and cut-off value.ConclusionOur meta-analysis indicates that higher preoperative CAR level is associated with poorer OS and DFS, it may be a good prognostic marker of survival outcomes after hepatectomy in patients with HCC. However, future prospective trials are necessary to validate the conclusion.Systematic review registrationThe study protocol was registered in the Open Science Framework (https://osf.io/uavt8).

IntroductionMyocardial ischemia/reperfusion (I/R) injury remains a major obstacle in cardiovascular therapies. Hydrogen sulfide (H2S) shows promise for mitigating I/R injury, but conventional delivery methods, such as NaHS injections or adenovirus-mediated CSE gene therapy, face low efficiency and systemic side effects. This study explores the use of angiotensin 1 (AT1) peptide-conjugated CdSe/ZnS quantum dots (QDs) for targeted delivery of cystathionine-γ-lyase (CSE) plasmids to the myocardium, aiming to boost local H2S production and minimize I/R injury.MethodsCdSe/ZnS QDs were conjugated with AT1 peptides to create a nanocarrier system capable of delivering the CSE plasmid specifically to the myocardium. In vivo fluorescence imaging confirmed heart-specific accumulation. Myocardial infarct size, cardiac function, cell death, and oxidative stress were evaluated. Endoplasmic reticulum stress and mitophagy markers, including CHOP/GRP78/eIF2α, were analyzed, and the CHOP gene's role was further assessed using an adenovirus vector.ResultsThe AT1-conjugated nanocarriers significantly increased CSE expression in the myocardium, as confirmed by fluorescence imaging, without affecting other organs. This localized delivery reduced myocardial infarct size, improved cardiac function, and decreased oxidative stress and cell death. Importantly, a reduction in endoplasmic reticulum stress and mitophagy markers was observed, suggesting that cardioprotection was mediated via the CHOP/GRP78/eIF2α signaling pathway. Reintroduction of CHOP using an adenovirus vector reversed these protective effects, confirming the pathway's involvement.DiscussionThis study demonstrates that AT1 peptide-conjugated QDs can effectively deliver CSE plasmids to the heart, providing significant protection against I/R injury through enhanced localized H2S production. This approach offers a promising, targeted, and side-effect-free therapy for myocardial I/R injury, with potential for clinical translation.

ObjectiveHigh-risk human papillomavirus (HPV) is a carcinogenic virus associated with nearly all cases of cervical cancer, as well as an increasing number of anal and oral cancers. The two carcinogenic proteins of HPV, E6 and E7, can immortalize keratinocytes and are essential for HPV-related cellular transformation. Currently, the global regulatory effects of these oncogenic proteins on the host proteome are not fully understood, and further exploration of the functions and carcinogenic mechanisms of E6 and E7 proteins is needed.MethodsWe used a previously established platform in our laboratory for constructing recombinant adenoviral plasmids expressing the HPV16 E7 gene to further construct recombinant virus particles expressing HPV16/18 E6, E7, and both E6 and E7 genes. These recombinant viruses were used to infect C33A cells to achieve sustained expression of the HPV16/18 E6/E7 genes. Subsequently, total RNA was extracted and RNA-Seq technology was employed for transcriptome sequencing to identify differentially expressed genes associated with HPV infection in cervical cancer.ResultsRNA-Seq analysis revealed that overexpression of the HPV16/18 E6/E7 genes upregulated GP6, CD36, HDAC6, ESPL1, and DNMT3B among the differentially expressed genes (DEGs) associated with cervical cancer. Spearman correlation analysis revealed a statistically significant correlation between the HDAC6 and DNMT3B genes and key pathways, including DNA replication, tumor proliferation signature, G2M checkpoint, p53 pathways, and PI3K/AKT/mTOR signaling pathways. Further, qRT-PCR and Western blot analyses indicated that both HPV16/18 E7 can upregulate the expression of HDAC6 and DNMT3B, genes associated with HPV infection-related cervical cancer.ConclusionThe successful expression of HPV16/18 E6/E7 in cells indicates that the recombinant viruses retain the replication and infection capabilities of Ad4. Furthermore, the recombinant viruses expressing HPV16/18 E7 can upregulate the HDAC6 and DNMT3B genes involved in cervical cancer pathways, thereby influencing the cell cycle. Additionally, HDAC6 and DNMT3B are emerging as important therapeutic targets for cancer. This study lays the foundation for further exploration of the oncogenic mechanisms of HPV E6/E7 and may provide new directions for the treatment of HPV-related cancers.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated response to infection in the body. Effective treatment of sepsis poses a significant challenge in today’s clinical field. In recent years, enteral nutrition has garnered significant attention as an essential supportive therapeutic strategy. Serving as a means to provide ample nutritional support directly through the gastrointestinal tract, enteral nutrition not only addresses the nutritional depletion caused by the disease but also holds potential advantages in regulating immune function, maintaining intestinal mucosal barrier integrity, and promoting tissue repair. This article delves into the latest advancements of enteral nutrition in the treatment of sepsis, with a particular focus on its application effectiveness in clinical practice, potential mechanisms, and challenges faced. By examining relevant basic and clinical research, the aim is to provide a deeper understanding of nutritional therapy for sepsis patients and offer valuable insights for future research and clinical practice.

IntroductionThere is no established scoring model focused on viral hepatitis patients to predict the prognosis after transjugular intrahepatic portosystemic shunt (TIPS). We aimed to develop and validate a novel model based on the largest cohort for better prediction of both short-term (1 year) and long-term (3 years) postoperative prognoses after TIPS in viral hepatitis cirrhosis-related portal hypertension patients.MethodsA total of 925 viral hepatitis cirrhosis-related portal hypertension patients who underwent TIPS from nine hospitals were divided into the training and external validation cohorts. A novel Viral-associated Index of Post-TIPS score (VIPs) model was developed after performing Cox regression analysis. The VIPs model was compared to five previous models, namely, Child–Pugh, MELD, ALBI, CCG, and FIPS. Furthermore, X-tile software was used to stratify patients into low-, medium-, and high-risk groups.ResultsThe VIPs model included age, ascites, albumin, prothrombin time, total bilirubin, and sodium for post-TIPS prognosis prediction. The model demonstrated satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of 0.781/0.774 (1 year/3 years) in the training cohort and 0.771/0.775 (1 year/3 years) in the external validation cohort, respectively.DiscussionWe first developed and externally validated a novel VIPs model for better prediction of both short-term and long-term postoperative prognoses after TIPS in Chinese patients with viral hepatitis cirrhosis-related portal hypertension.

This study aims to refine the fracture characterization of three-point bending semi-circular specimens used in rock fracture toughness assessments. The primary objective is to improve the accuracy of such evaluations by developing numerical simulations of specimens with pre-engineered cracks of varying geometries. Numerical simulations were conducted using the finite element method. The interaction integral method was employed to quantify the stress intensity factors (SIFs) and T-stress at crack tips. Initially, the model’s accuracy was validated by replicating stress singularities at crack tips in a benchmark circular disk with a central straight crack. Following validation, dimensionless fracture parameters specific to the three-point bending semi-circular specimens were calibrated. The numerical results demonstrate that the dimensionless stress intensity factor (YI) increases with both the relative crack length (a/R) and the spacing between support points. Notably, for relative crack lengths a/R ≤ 0.5, the dimensionless T-stress assumes negative values, initially decreasing and then increasing as the relative crack length increases. The findings of this study provide valuable insights into the fracture behavior of three-point bending semi-circular specimens with pre-engineered cracks. Based on the observed trends in the dimensionless fracture parameters, it is recommended that relative crack lengths within the range of 0.2–0.6 be used to maintain the accuracy of rock fracture toughness tests. The finite element method used in this study serves as a robust tool for calibrating fracture parameters, thereby laying a strong foundation for the application of these specimens in rock fracture toughness evaluations.

IntroductionWarming caused by greenhouse gas (GHG) emissions has become a global environmental issue of widespread concern, and China, as a responsible power, has the pressing task of reducing carbon emissions. China is one of the world’s major beef producers and consumers, and at the same time, beef cattle, as a large livestock, is the largest source of GHG emissions in the livestock industry.MethodsThis study considered the panel data of 31 provinces in China from 2008 to 2022. The kernel density estimation and Dagum Gini coefficient were used to analyze the spatiotemporal dynamic evolution patterns and influencing factors of carbon emissions from China’s beef cattle farming industry.Results(1) The carbon emission trajectory of beef cattle production follows a distinctive “ascend-descend-ascend” three-phase pattern. By 2022, the sector’s cumulative carbon emissions had burgeoned by 37.62% relative to 2008, reflecting an average annual escalation of 2.31%. Despite the overall upward trend in carbon emissions, significant regional differences were observed. The Central Plains region has witnessed a consistent decline, in stark contrast to the Southwest and Northeast regions, which have emerged as hotspots for heightened carbon emissions and intensified emission densities within China’s beef cattle production landscape, underscoring the intensifying significance of carbon mitigation measures. (2) The kernel density curve shows an overall rightward shift with a specific gradient effect on carbon emissions. In addition, the range of the right drag of the curve in 2022 was significantly reduced, which laterally reflects the narrowing of the difference between the provinces with the highest and lowest carbon emissions from beef cattle farming. The principal source of variance in the overall carbon emissions from beef cattle production is the disparities between regions, which accounts for an average annual contribution rate of 52.52%. Conversely, the within-region contribution rates have remained relatively stable, while those for the intensity of transvariation have witnessed a substantial rise, with annual averages of 18.31 and 28.96%, respectively. (3) Regarding the factors influencing carbon emissions reduction, environmental regulations and production efficiency significantly drive carbon emissions reduction in beef cattle farming.DiscussionRelevant government departments should actively guide farmers toward green production, establish perfect policies and regulations for low-carbon beef cattle farming, and promote low-carbon beef cattle farming models based on local conditions.

BackgroundOvarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined.MethodsRelevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells.ResultsA six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells.ConclusionOur study identified potential biomarkers for the six-TRLs model related to the prognosis of OC.

IntroductionIn the 2020s, particularly following 2022, the Chinese government introduced a series of initiatives to foster the development of the prepared dishes sector, accompanied by substantial investments from industrial capital. Consequently, China’s prepared dishes industry has experienced rapid growth. Nevertheless, this swift expansion has elicited varied public opinions, particularly concerning the potential health effects of prepared dishes. Therefore, this study aims to gather and analyze comments from social media on prepared dishes using machine learning techniques. The objective is to ascertain the perspectives of the Chinese populace on the health implications of consuming prepared dishes.MethodsSocial media comments, characterized by their broad distribution, objectivity, and timeliness, served as the primary data source for this study. Initially, the data underwent preprocessing to ensure its suitability for analysis. Subsequent steps in this study involved conducting sentiment analysis and employing the BERTopic model for topic clustering. These methods aimed to identify the principal concerns of the public regarding the impact of prepared dishes on health. The final phase of the study involved a comparative analysis of changes in public sentiment and thematic focus across different time frames. This approach provides a dynamic view of evolving public perceptions related to the health implications of prepared dishes.ResultsThis study analyzed over 600,000 comments gathered from various social media platforms from mid-July 2022 to the end of March 2024. Following data preprocessing, 200,993 comments were assessed for sentiment, revealing that more than 64% exhibited negative emotions. Subsequent topic clustering using the BERTopic model identified that 11 of the top 50 topics were related to public health concerns. These topics primarily scrutinized the safety of prepared dish production processes, raw materials, packaging materials, and additives. Moreover, significant public’s interest was in the right to informed consumption across different contexts. Notably, the most pronounced public opposition emerged regarding introducing prepared dishes into primary and secondary school canteens, with criticisms directed at the negligence of educational authorities and the ethics of manufacturers. Additionally, there were strong recommendations for media organizations to play a more active role in monitoring public opinion and for government agencies to enhance regulatory oversight.ConclusionThe findings of this study indicate that more than half of the Chinese public maintain a negative perception towards prepared dishes, particularly concerning about health implications. Chinese individuals display considerable sensitivity and intense reactions to news and events related to prepared dishes. Consequently, the study recommends that manufacturers directly address public psychological perceptions, proactively enhance production processes and service quality, and increase transparency in public communications to improve corporate image and people acceptance of prepared dishes. Additionally, supervisory and regulatory efforts must be intensified by media organizations and governmental bodies, fostering the healthy development of the prepared food industry in China.

BackgroundInterleukin-1 receptor-associated kinase 3 (IRAK3) modulates neuroinflammation. This study aimed to determine the prognostic role of serum IRAK3 in acute intracerebral hemorrhage (ICH).MethodsIn this prospective observational cohort study, 152 patients with supratentorial ICH, along with 63 healthy controls, were recruited. Serum IRAK3 levels were measured at the time of enrollment for controls, at admission for all patients, and on poststroke days 1, 3, 5, 7, 10, and 15 in a subset of 63 patients. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Poststroke 6-month modified Rankin Scale (mRS) scores were registered, with scores of 3–6 representing a poor prognosis. Multivariate models were established to investigate severity correlation and prognosis association.ResultsSerum IRAK3 levels were significantly elevated at the admission of patients, peaked at day 1, plateaued at day 3, gradually declined until day 15, and were substantially higher over the first 15 days poststroke than in controls. Admission serum IRAK3 levels were independently associated with NIHSS scores, hematoma volume, and 6-month mRS scores in a multivariate linear regression model. They were linearly correlated with the risk of poor prognosis in a restricted cubic spline analysis and were independently predictive of poor prognosis in a binary logistic regression model. Additionally, they demonstrated strong prognostic ability in the receiver operating characteristic curve analysis. Using subgroup analysis, no interactions were found between admission serum IRAK3 levels and some routine variables, such as age, gender, hypertension, and diabetes mellitus. Moreover, the model combining admission serum IRAK3, NIHSS scores, and hematoma volume demonstrated stability and clinical value in calibration and decision curve analyses.ConclusionA significant increase in serum IRAK3 levels during the early phase after ICH, strongly correlated with disease severity, is independently associated with a poor 6-month prognosis, establishing serum IRAK3 as a valuable prognostic biomarker for ICH.

Perilla oil from the medicinal crop Perilla frutescens possess a wide range of biological activities and is generally used as an edible oil in many countries. The molecular basis for its formation is of particular relevance to perilla and its breeders. Here in the present study, four PfFAD2 genes were identified in different perilla cultivars, PF40 and PF70, with distinct oil content levels, respectively. Their function was characterized in engineered yeast strain, and among them, PfFAD2-1PF40, PfFAD2-1PF70 had no LA biosynthesis ability, while PfFAD2-2PF40 in cultivar with high oil content levels possessed higher catalytic activity than PfFAD2-2PF70. Key amino acid residues responsible for the enhanced catalytic activity of PfFAD2-2PF40 was identified as residue R221 through sequence alignment, molecular docking, and site-directed mutation studies. Moreover, another four amino acid residues influencing PfFAD2 catalytic activity were discovered through random mutation analysis. This study lays a theoretical foundation for the genetic improvement of high-oil-content perilla cultivars and the biosynthesis of LA and its derivatives.

IntroductionThe prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen.MethodsFifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT.ResultsFour patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group.ConclusionThe anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.

IntroductionMesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs.MethodsIn this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16).ResultsThe median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events.DiscussionThese finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).

IntroductionPostpartum endometritis is a prevalent reproductive disorder in bovines, leading to a prolonged open period, infertility, and other complications. While Lactobacillus strains can mitigate these conditions by reducing uterine inflammation, their effectiveness is limited due to a lack of direct anti microbial action and extended treatment duration. This study aimed to construct a recombinant Lactobacillus johnsonii strain expressing bovine Granulocyte-macrophage colony-stimulating factor (GM-CSF) to evaluate its potential in reducing postpartum uterine inflammation.MethodsThe recombinant Lactobacillus johnsonii strain was engineered to express bovine GM-CSF and administered to pregnant mice via vaginal perfusion. Postpartum endometritis was induced using E. coli infection, and the protective effects of the engineered strain were assessed. Inflammatory markers (IL-6, IL-1β, TNF-α), myeloperoxidase (MPO) activity, and nitric oxide (NO) concentration were measured. Histological examination was performed to evaluate uterine morphology and pathological damage.ResultsThe recombinant L. johnsonii strain expressing GM-CSF significantly reduced inflammation levels induced by E. coli infection in the uterus. This reduction was evidenced by decreased expression of IL-6, IL-1β, TNF-α, as well as reduced MPO activity and NO concentration. Histological examination revealed improved uterine morphology and reduced pathological damage in mice treated with the recombinant GM-CSF strain. Crucially, the recombinant strain also exerts beneficial effects on bovine endometritis by reducing levels of inflammatory cytokines, suggesting a beneficial effect on clinical bovine endometritis.ConclusionThe recombinant Lactobacillus johnsonii expressing GM-CSF demonstrated protective effects against postpartum endometritis in bovines by reducing inflammatory cytokines. The findings indicate the potential clinical application of this engineered strain in preventing postpartum uterine inflammation, offering a novel and effective protective option for related disorders and improving bovine reproductive efficiency.

Fatty acid desaturases (FADs) are rate-limiting enzymes for the biosynthesis of highly unsaturated fatty acids (HUFAs). As a new member of the FAD family, Fad6 and its roles remain unclear in various teleost fishes. In this study, we identified a fad6 gene from yellow catfish (ycfad6) and determined its spatiotemporal expression patterns and responses to different initial diets and nutritional status in yellow catfish. Our results showed that the open reading frame (ORF) of ycfad6 was 1,080 bp in length, encoding a protein of 359 amino acids. Multiple protein sequences alignment proved that fad6 is highly conserved among diverse vertebrates. Meanwhile, phylogenetic analysis revealed that Southern catfish and yellow catfish were clustered into one branch, supporting evolutionary consistence between the fad6 gene and fish morphology. Moreover, comparisons of genomic synteny and gene structure revealed functional and evolutionary conservation of the fad6 gene in various teleost fishes. Tissue distribution analysis by quantitative RT-PCR demonstrated that the ycfad6 gene was extensively expressed in examined tissues, with higher transcription levels in the heart and liver. Meanwhile, ycfad6 gene was widely expressed in various developmental stages, indicating Fad6 may play important roles in HUFA biosynthesis at early developmental stages in yellow catfish. Functional experiments verified that the transcription of ycfad6 decreased significantly with the extension of feeding time (with egg yolk or Artemia nauplii) at the early developmental stages, indicating that a diet rich in HUFA can remarkably inhibit the transcription of ycfad6 in yellow catfish. In addition, ycfad6 transcription was significantly reduced after a short-term (24-h) or long-term food deprivation (1-week) and then continued to decrease during refeeding, suggesting that nutritional states can affect the transcription of ycfad6, which further regulates the metabolism of HUFAs. Anyway, these fundamental findings provide basic references for further investigating evolutionary and physiological functions of the fad6 gene in yellow catfish as well as in other teleost fishes.

Microbiota in the reproductive tract of cattle play a vital role in maintaining normal reproduction. However, the information on microbiota in different parts of reproductive tracts with different genetic background is few. The aim of the present study was to describe and compare the microbiota in vagina, cervix and uterus of Yanbian cattle and Yanhuang cattle. The results showed that microbial diversity increases from the vagina to the uterus. The top three bacterial phyla in bovine reproductive tract were Proteobacteria, Firmicutes and Bacteroidetes, accounting for more than 85%. From the vagina to the uterus, the relative abundance of Proteobacteria gradually decreased, while that of Firmicutes gradually increased. Phylum-level Firmicutes and genus-level UCG_010 were significantly enriched in the uterus of Yanbian cattle and Yanhuang cattle. Comparing the same parts of the two breeds, it was found that there was no significant difference in alpha diversity, but significant differences in beta diversity. In addition, microbiota with significant differences in the relative abundance of the reproductive tract were found. These findings lay a foundation for a comprehensive understanding of the structure of the genital tract microbiota of cows and its regulatory mechanisms.

IntroductionPlanting without mulching can eliminate the residual film pollution caused by the long-term use of plastic film covers, but it will increase soil moisture evaporation and heat loss and severely reduce water use efficiency and cotton productivity in cotton (Gossypium hirsutum L.) fields in arid regions. It is unclear whether the advantages of subsurface drip irrigation and nighttime irrigation can be leveraged to reduce the amount of irrigation applied in fields, improve the soil and leaf hydrothermal environments, and increase the synchronicity of yield and water use efficiency (WUE).MethodsTherefore, in a two-year field experiment (2019-2020), cotton was grown under different irrigation treatments (I5, 3753 m3 ha-1; I4, 3477 m3 ha-1; I3, 3201 m3 ha-1; I2, 2925 m3 ha-1; and I1, 2649 m3 ha-1). The soil volumetric moisture content, soil temperature, leaf relative water content (RWC), daily changes in gas exchange parameters, lint yield, and WUE were evaluated.Results and discussionThe results showed that reducing irrigation can reduce the soil volumetric moisture content (0-40 cm soil layer), increase the soil temperature and soil temperature conductivity, and increase the leaf temperature, intercellular carbon dioxide concentration (Ci), and WUE; however, reducing irrigation is not conducive to increasing the leaf RWC, net photosynthetic rate (Pn), stomatal conductance (Gs), or transpiration rate (Tr). There was no significant difference in WUE between the I3 and I4 treatments from 8:00 to 20:00, but the lint yield in these treatments increased by 2.8-12.2% compared to that in the I5 treatment, with no significant difference between the I3 and I4 treatments. In addition, a related analysis revealed that the positive effects of the leaf hydrothermal environment on the Pn and soil temperature on the WUE occurs during the same period (10:00-16:00). Overall, an irrigation amount of 3201-3477 m3 ha-1 applied with a subsurface nighttime irrigation system without mulching can enhance the soil moisture content and soil temperature, maintain a high photosynthetic capacity, and increase the lint yield and WUE. These results revealed that the negative impacts of plastic film contamination in arid areas can be alleviated.

Plant height (PH) is a crucial trait for strengthening lodging resistance and boosting yield in foxtail millet. To identify quantitative trait loci (QTL) and candidate genes associated with PH, we first developed a genetic map using a recombinant inbred line (RIL) population derived from a cross between Aininghuang and Jingu 21. Then, PH phenotyping data and four variations of best linear unbiased prediction (BLUP) were collected from nine environments and three development stages. Next, QTL mapping was conducted using both unconditional and conditional QTL methods. Subsequently, candidate genes were predicted via transcriptome analysis of parental samples at three developmental stages. The results revealed that the genetic map, based on re-sequencing, consisted of 4,360 bin markers spanning 1,016.06 cM with an average genetic distance of 0.23 cM. A total of 19 unconditional QTL, accounting for 5.23%–35.36% of the phenotypic variation explained (PVE), which included 7 major and 4 stable QTL, were identified. Meanwhile, 13 conditional QTL, explaining 5.88%–40.35% of PVE, including 5 major and 3 stable QTL, were discovered. Furthermore, four consistent and stable QTL were identified. Finally, eight candidate genes were predicted through RNA-seq and weighted gene co-expression network analysis (WGCNA). Those findings provide a crucial foundation for understanding the genetic mechanisms underlying PH development and facilitate molecular marker-assisted breeding of ideal plant types in foxtail millet.

The ‘Okitsu No. 58’ citrus variety is highly prone to fruit cracking, which jeopardizes yield and results in economic losses. In this study, we investigated the impacts of spraying 5 distinct concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 g/L) of chelated calcium (Ca) or silicon (Si) fertilizers at the young fruit stage (60-90 days after flowering, DAF) on fruit cracking and quality in the citrus variety ‘Okitsu No. 58’. The results showed either Ca or Si fertilizer treatments reduced fruit cracking. We found that all Ca and partial Si treatments (0.4 and 0.5 g/L) significantly promoted the accumulation of Ca content in the peel. Notably, Ca or Si treatments significantly reduced polygalacturonase (PG) activity and inhibited the production of water-soluble pectin (WSP) in the peel. Additionally, Ca or Si treatments elevated the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content of the peels. Changes in these parameters likely contributed to strengthening the durability of peel cell wall constituents, thus enhancing the fruit’s resistance to fruit cracking. Overall, except for the C3 (0.3 g/L of Ca), Ca or Si fertilizers contributed to fruit conventional quality, mainly in terms of higher soluble sugars (SS) and SS/TA (titratable acid). Therefore, our findings will provide a reference for the prevention and control of citrus fruit cracking and the development of new fertilizers.

Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV’s exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.

To ensure the safe operation and dispatching control of a low-voltage distributed photovoltaic (PV) power distribution network (PDN), the load forecasting problem of the PDN is studied in this study. Based on deep learning technology, this paper proposes a robot-assisted load forecasting method for low-voltage distributed photovoltaic power distribution networks using enhanced long short-term memory (LSTM). This method employs the frequency domain decomposition (FDD) to obtain boundary points and incorporates a dense layer following the LSTM layer to better extract data features. The LSTM is used to predict low-frequency and high-frequency components separately, enabling the model to precisely capture the voltage variation patterns across different frequency components, thereby achieving high-precision voltage prediction. By verifying the historical operation data set of a low-voltage distributed PV-PDN in Guangdong Province, experimental results demonstrate that the proposed “FDD+LSTM” model outperforms both recurrent neural network and support vector machine models in terms of prediction accuracy on both time scales of 1 h and 4 h. Precisely forecast the voltage in different seasons and time scales, which has a certain value in promoting the development of the PDN and related technology industry chain.

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear.Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches.Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound–target–pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models.Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis.Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

BackgroundEarly enteral nutrition (EN) is recommended for sepsis management, but its optimal timing and clinical benefits remain uncertain. This study evaluates whether early EN improves outcomes compared to delayed EN in patients with sepsis.MethodsWe analyzed data of septic patients from the MIMIC-IV 2.2 database, focusing on those in the Medical Intensive Care Unit (MICU) and Surgical Intensive Care Unit (SICU). Patients who initiated EN within 3 days were classified into the early EN group, while those who started EN between 3 and 7 days were classified into the delayed EN group. Propensity score matching was used to compare outcomes between the groups.ResultsAmong 1,111 patients, 786 (70.7%) were in the early EN group and 325 (29.3%) were in the delayed EN group. Before propensity score matching, the early EN group demonstrated lower mortality (crude OR = 0.694; 95% CI: 0.514–0.936; p = 0.018) and shorter ICU stays (8.3 [5.2, 12.3] vs. 10.0 [7.5, 14.2] days; p

BackgroundPrevious observational studies have shown a correlation between leisure sedentary behaviors (LSB) and physical activity (PA) with the incidence of obstructive sleep apnea (OSA). However, the causal associations remain unknown. Therefore, our study used bidirectional two-sample Mendelian randomization (MR) to identify potential causal relationships between LSB/PA and OSA.MethodsWe sourced genetic variation data for LSB and PA from the UK Biobank, while data on OSA were collected from the FinnGen study. The primary analysis method employed was the inverse variance weighted (IVW) approach, complemented by the weighted median and MR-Egger methods. For sensitivity analyses, we conducted Cochran’s Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis.ResultsIVW analyses showed that genetically predicted leisure television watching (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.09–1.75, p = 0.007) and computer use (OR = 1.48, 95% CI = 1.15–1.92, p = 0.002) significantly increased the risk of OSA. Conversely, self-reported vigorous physical activity (VPA) (OR = 0.33, 95% CI = 0.11–0.98, p = 0.046) may reduce the risk of OSA. No causal effects on OSA risk were observed for driving or self-reported moderate-to-vigorous physical activity. Furthermore, the reverse MR analysis indicated no significant causal relationship between OSA and any LSB/PA phenotype. Sensitivity tests showed no significant heterogeneity or horizontal pleiotropy.ConclusionThis study suggests that leisurely television watching and computer use are risk factors for OSA, while VPA may be a protective factor. Additionally, OSA does not affect PA or LSB levels. We recommend reducing sedentary activities, particularly television watching and computer use, and prioritizing VPA to reduce the risk of OSA. Further research in diverse populations and settings is needed to validate these findings.

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir’s inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient’s acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

BackgroundPost-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD.MethodsA total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment.ResultsThere were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p