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Abstract Purpose Total Hip Arthroplasty (THA) is the primary treatment for hip diseases today. Nevertheless, total hip arthroplasty has its challenges, and one of these challenges is the potential for incorrect execution of the preoperative planning process. Such errors can lead to complications such as loosening and instability of the prosthesis and leg length discrepancy. In this study, we used human phantoms to investigate the influence of pelvic and femoral factors on prosthesis size selection in the preoperative planning of total hip arthroplasty and to provide a reference standard for clinical imaging in preoperative planning of total hip arthroplasty. Methods In this experiment, we utilised a custom-made experimental device that enabled us to manipulate the movement of the pelvis and femur in various directions. The device also incorporated sensors to control the angle of movement. By obtaining X-rays from different positions and angles, we were able to determine the size of the prosthesis based on the 2D preoperative planning generated by the mediCAD software. Results When the pelvis was in a nonneutral position, the size of the acetabular cup varied within a range of three sizes. Similarly, when the femur was in a nonneutral position, the size of the femoral stem varied within a range of two sizes. The movement of the pelvis and femur in the coronal plane, relative to the neutral position, did not impact the selection of the prosthesis size. However, the motion of the pelvis and femur in the sagittal and transverse planes had a notable effect. Conclusion The selection of the prosthesis size for preoperative planning can be significantly influenced by specific positions of the pelvis and femur. It is crucial for the radiographer to ensure that the pelvis and femur maintain a standard neutral position, particularly in the sagittal and transverse planes, during the image acquisition process.

Abstract Background Transmitted drug resistance (TDR) increases the risk of antiretroviral therapy (ART) failure in HIV-1 patients. This study investigated the molecular epidemiology of TDR and its transmission networks among newly diagnosed HIV-1 patients in Wenzhou, China. Methods We enrolled 1878 ART-naive HIV-1 patients from January 2020 to October 2023. TDR was evaluated using the Stanford University HIV Drug Resistance Database. We performed phylogenetic analysis, genotyping, transmission clustering, and population-based TDR-related factor analysis. Results Among 1782 patients with successful genotyping, TDR prevalence was 5.7%. Multivariable analysis identified CRF08_BC subtype (adjusted odds ratio [aOR] 18.59, 95% CI 3.79-336.18, p = 0.004), CD4 > 500 cells/mm³ (aOR 2.19, 95% CI 1.16–4.03, p = 0.013), and year 2023 (aOR 1.83, 95% CI 1.11–4.89, p = 0.039) as factors associated with higher TDR risk. The most prevalent NNRTI mutations were K103N, E138A, and V179E. Seven TDR transmission clusters were identified, notably one with V179D that expanded during 2020–2023. Conclusions While TDR prevalence in Wenzhou remained lower than in other Chinese regions, an upward trend was observed. Most resistant individuals were in transmission clusters, predominantly middle-aged and elderly. NNRTI resistance was severe and concentrated in efavirenz, nevirapine, and rilpivirine. Enhanced HIV surveillance and wider free antiretroviral options are crucial to control drug-resistant HIV spread in Wenzhou.

Abstract Background Cervical cancer is the fourth leading cause of cancer-related death among women worldwide, and effective therapeutic strategies for its treatment are limited. Recent studies have indicated that ferroptosis, a form of regulated cell death, is a promising therapeutic strategy. KLF14 has been shown to regulate both cell proliferation and apoptosis in cervical cancer. However, its role in modulating lipid peroxidation and ferroptosis remains largely unexplored and enigmatic. Methods SiHa and HeLa cells were transduced with lentiviral vectors to overexpress KLF14. Protein levels were analyzed via western blotting and immunohistochemistry (IHC). LDH assays, calcein-AM/propidium iodide (PI) staining, and generation of cell growth curves using a real-time cell analysis (RTCA) system were used to detect cell damage and proliferation. Cellular ROS, lipid ROS, transmission electron microscopy (TEM), and Fe2+ assays and a xenograft mouse model were used to measure the level of ferroptosis. Proteomics combined with bioinformatics methods was used to screen target genes regulated by KLF14, and CUT&Tag and dual-luciferase assays confirmed the repression of GPX4 by KLF14 via direct binding to its promoter. Results KLF14 is abnormally expressed in various tumors and downregulated in cervical cancer. Overexpression of KLF14 induced ferroptosis and inhibited cell proliferation in vitro as well as xenograft tumorigenicity in vivo. Mechanistic studies revealed that KLF14 binds to the promoter of GPX4, suppressing its transcriptional activity and thereby decreasing its expression, which contributes to the induction of ferroptosis. Truncation and point mutation analyses of the GPX4 promoter revealed multiple binding sites for KLF14 within the − 1000 bp to + 35 bp region, which are responsible for its inhibitory effect on GPX4 transcription. Additionally, deletion of the zinc finger motif in KLF14 abolished its inhibitory effect on GPX4 promoter activity and cell proliferation. Conclusion Our data revealed a previously unidentified function of KLF14 in promoting ferroptosis, which results in the suppression of cell proliferation. Mechanistically, we revealed a novel regulatory mechanism by which KLF14 targets GPX4. These findings suggest a novel strategy to induce ferroptosis through the targeting of KLF14 in human cervical cancer cells.

Abstract Background Structural variations (SVs) are key genetic contributors to neurodevelopmental disorders (NDDs). Exome sequencing (ES), the current first-line tool for genetic testing of NDDs, falls short in SVs detection. This diagnostic gap is being actively addressed by new methods such as optical genome mapping (OGM). Methods This study evaluated the utility of combining OGM and RNA-seq in the detection and interpretation of SVs in ES-negative NDDs. OGM was performed in 43 patients with NDDs with inconclusive ES results. Candidate SVs were selected based on disease association and pathogenicity evaluation, and further validated or reconstructed by alternative methods, including long-read sequencing for a complex rearrangement event. RNA-Seq was performed on blood samples from patients with candidate SVs to facilitate interpretation of pathogenicity. Results OGM detected four candidate SVs, and RNA-seq confirmed the pathogenicity of three SVs in the patient cohort. This combined approach solved three cases—two cases with de novo SVs in genes associated with autosomal dominant NDDs, including a deletion encompassing the promoter and 5′UTR of MBD5 and an intragenic duplication of PAFAH1B1, and a third case possessing an intragenic duplication in trans with a pathogenic single-nucleotide variant of PLA2G6, associated with autosomal recessive NDDs. The expression alteration of the affected genes and the tandem positioning of two intragenic duplications were confirmed by RNA-seq. In the fourth case, OGM detected a complex rearrangement involving chromosomes 2 and 6, much more complex than the de novo t(2:6)(q13;q15) indicated by conventional cytogenetic analysis. Reconstruction showed that 17 segments of 6q15 spanning 9.3 Mb were disarranged and joined 2q11.2, with four breakpoints detected in the 5′ and 3′ non-coding region of the NDD-associated gene SYNCRIP. RNA-seq revealed largely preserved SYNCRIP expression, leaving the pathogenicity of this complex rearrangement event uncertain. Conclusions SVs in ES-negative NDDs can be identified by OGM, which is particularly useful for SVs in non-coding regions not covered by ES. OGM helps to construct complex SVs and provides information on the location and orientation of duplications, which is crucial for pathogenicity interpretation. The integration of RNA-seq facilitates the interpretation of the functional consequences of SVs at the transcriptional level. These findings demonstrate the utility and feasibility of combining OGM and RNA-seq in ES-negative cases with NDDs.

Objective To explore the factors that affect the coordinated development of blood banks and apheresis plasma collection banks (hereinafter referred to as plasma banks), and explore feasible measures for the coordinated development of blood banks and plasma banks. Methods The blood information management system and blood source information management system were used to retrieve related data of blood and plasma donation from 9 cities in Shandong province from 2017 to 2021. The number of blood donors and plasma donors and the intersection of them were analyzed. The data analysis was performed using chi-square test, and a questionnaire survey was conducted to investigate the policies and information status, as well as expectations for coordinated development for blood and plasma donation. Results From 2017 to 2021, the total number of blood donors in 9 cities was higher than that of plasma donors, both have been increasing year by year, and the increase in plasma donors was significantly higher than that of blood donors (131.78% vs 23.90%, P

Abstract To explore the advantages and disadvantages of 3D Slicer reconstruction and 3D printing localization combined with transcranial neuroendoscope in the surgical treatment of deep cerebral micro cavernous hemangiomas. Method The clinical data of patients with deep cerebral micro cavernous hemangiomas treated by our hospital from June 2022 to February 2023 using 3D Slicer reconstruction and 3D printing localization technology combined with transcranial endoscopic surgery were retrospectively analyzed. A total of 5 cases with complete data were collected, including 2 males and 3 females, aged 9–59 years. All 5 patients had deep supratentorial cavernous hemangiomas with a diameter of less than 1.5 cm, and had clinical symptoms such as headache or epilepsy, and had been diagnosed by CT or MRI. Repeated bleeding from small cavernous hemangiomas in the deep brain can lead to clinical symptoms such as recurrent headache and epilepsy, and is required surgical treatment. However, cavernous hemangiomas often have smaller lesions and are difficult to locate in the deep part. Without neuronavigation, surgery can become extremely difficult. Our team’s newly developed 3D Slicer reconstruction and 3D printing localization technology which could provide new options for surgical treatment of small cavernous hemangiomas or other small lesions in the deep brain, but its accuracy and safety still need to be verified by further clinical research.

Abstract Objective Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add‐on ASMs for the treatment of focal epilepsy using network meta‐analysis. Methods Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment‐emergent adverse events (TEAEs) and individual TEAEs were assessed. “Gemtc” 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI). Results Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00–5.70) and 100% for rufinamide (2.03; 95% CI: 0.54–11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56–323.9) and zonisamide (10.63; 95% CI: 1.37–261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7–0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94–1.1; SUCRA: 0.885067) for overall TEAE compared with other medications. Significance All approved ASMs were effective as add‐on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom. Plain Language Summary This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.

Abstract. Sepsis poses a health challenge globally owing to markedly high rates of morbidity and mortality. Despite employing bundle therapy over two decades, approaches including transient organ supportive therapy and clinical trials focusing on signaling pathways have failed in effectively reversing multiple organ failure in patients with sepsis. Prompt and appropriate perioperative management for surgical patients with concurrent sepsis is urgent. Consequently, innovative therapies focusing on remedying organ injuries are necessitated. Cell therapy has emerged as a promising therapeutic avenue for repairing local damage to vital organs and restoring homeostasis during perioperative treatment for sepsis. Given the pivotal role of immune cell responses in the pathogenesis of sepsis, stem cell-based interventions that primarily modulate immune responses by interacting with multiple immune cells have progressed into clinical trials. The strides made in single-cell sequencing and gene-editing technologies have advanced the understanding of disease-specific immune responses in sepsis. Chimeric antigen receptor (CAR)-immune cell therapy offers an intriguing option for the treatment of sepsis. This review provides a concise overview of immune cell therapy, its current status, and the strides made in the context of sepsis research, discussing potential strategies for the management of patients with sepsis during perioperative stages.

Abstract The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.

Pheretima is a popular healthy food, but Pheretima and related foods have specific stenchy odor, especially after decocting or warm soaking, the odor is intense, resulting in nausea and vomiting. This indicates that the release of stenchy odor components is intensified when Pheretima was exposed to hot water. It is urgent to study the composition and release pattern of the stenchy odor components of Pheretima. In this study, a series of samples with different odors were prepared by the combination of SFE-CO2 and warm soaking. The results showed that the fishy and smoky odor of Pheretima were heavier, attributed to the components such as dimethyl trisulfide, TMA, and guaiacol. When Pheretima was exposed to hot water, the fishy odor increased sharply. Dimethyl trisulfide and TMA were the key odor components, especially the exposure of TMA increased by 2∼3 times after warm soaking. The volatilization rate of n-hexanal, TMA, dimethyl trisulfide and other components was found to be highly volatile, and the volatilization rate at 75 °C was 2.5 times that at room temperature. This study proved for the first time that stenchy odor substances include two categories: water-soluble and liposoluble. And found that the water-soluble odor components accelerate their exposure and volatilization in warm water, which is the scientific principle of “Pheretima smells worse exposed to water”.

PurposeThis study aimed to compare the efficacy of [18F]AlF-NOTA-FAPI-04 PET/CT with that of [18F]FDG PET/CT for detecting postoperative recurrence in patients with gastric cancer.MethodsThis single-center retrospective clinical study was performed at Hunan Cancer Hospital between December 2020 and June 2022. The participants underwent both [18F]AlF-NOTA-FAPI-04 and [18F]FDG within 14 days. Histopathologic examination, morphological imaging, and/or follow-up imaging were used as a reference for the final diagnosis. We recorded the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of [18F]AlF-NOTA-FAPI-04 and [18F]FDG PET/CT for detecting local recurrence, lymph node metastasis and distant metastasis. The SUVmax and background ratio (TBR) of local recurrence and metastases between [18F]FDG and [18F]AlF-NOTA-FAPI-04 PET/CT were compared using paired-sample t tests.ResultsForty-seven patients (27 males, aged 25–68 years) with gastric cancer after curative resection (27 with adenocarcinoma, 17 with signet ring cell carcinoma and 4 with mucinous adenocarcinoma) were included in the study. [18F]AlF-NOTA-FAPI-04 accumulation was significantly greater than that of [18F]FDG in terms of local recurrence (SUVmax, 11.65 vs 3.48, p< 0.0001; TBR, 12.93 vs 2.94, p< 0.0001), lymph node metastasis (SUVmax, 13.45 vs 3.05, p=0.003875; TBR, 12.43 vs 2.21, p=0.001661), and distant metastasis (SUVmax, 11.89 vs 2.96, p < 0.0001; TBR, 13.32 vs 2.32, p< 0.0001). Despite no statistical comparison was made with [18F]FDG, [18F]AlF-NOTA-FAPI-04 imaging exhibited high levels of sensitivity, specificity, PPV, NPV, and accuracy for detecting postoperative local recurrence, lymph node metastasis, and distant metastasis in patients with gastric cancer.Conclusion[18F]AlF-NOTA-FAPI-04 has demonstrated potential for more accurate tumor re-evaluation in GC, thus enhancing treatment decision-making.

ABSTRACT: This study aimed to investigate the developmental change of body growth and gene expression related to fatty acid uptake and oxidation in the yolk sac membrane (YSM) and jejunum during embryogenesis in Muscovy ducks. The weights of embryos and yolk sac (YS) (5 embryos per replicate, n = 6) were recorded on embryonic days (E)16, E19, E22, E25, E28, E31, and the day of hatch (DOH). The fat and fatty acid contents in YSM, jejunal histology, and gene expression related to fatty acid metabolism in YSM and jejunum were determined in each sampling time. Among the nonlinear models, the maximum growth is estimated at 2.83 (E22.5), 2.67 (E22.1), and 2.60 (E21.3) g/d using logistic, Gompertz, and Von Bertalanffy models, respectively. The weight of YS, and ether extract-free YS as well as the amounts of fat and fatty acids in YS decreased (P < 0.05) linearly, whereas the villus height, crypt depth, villus height/crypt depth, and musculature thickness in jejunum increased (P < 0.05) linearly during embryogenesis. The mRNA expression of CD36, SLC27A4, and FABP1 related to fatty acid uptake as well as the mRNA and protein expressions of PPARα and CPT1 related to fatty acid oxidation increased in a quadratic manner (P < 0.05) in both YS and jejunum, and the maximum values were achieved during E25 to E28. In conclusion, the maximum growth rate of Muscovy duck embryos was estimated at 2.60 to 2.83 g/d on E21.3 to E23.5, while the accumulations of lipid and fatty acid in YS were decreased in association with the increased absorptive area of morphological structures in jejunum. The gene and protein expression involved in fatty acid metabolism displayed a similar enhancement pattern between YSM and jejunum during E25 to E28, suggesting that fatty acid utilization could be strengthened to meet the energy demand for embryonic development.

Diabetes, a metabolic disease caused by abnormally high levels of blood glucose, has a high prevalence rate worldwide and causes a series of complications, including coronary heart disease, stroke, peripheral vascular disease, end-stage renal disease, and retinopathy. Small-molecule compounds have been developed as drugs for the treatment of diabetes because of their oral advantages. Insulin secretagogues are a class of small-molecule drugs used to treat diabetes, and include sulfonylureas, non-sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and other novel small-molecule insulin secretagogues. However, many small-molecule compounds cause different side effects, posing huge challenges to drug monotherapy and drug selection. Therefore, the use of different small-molecule drugs must be improved. This article reviews the mechanism, advantages, limitations, and potential risks of small-molecule insulin secretagogues to provide future research directions on small-molecule drugs for the treatment of diabetes.

Abstract Wound infection is a worldwide health issue that not only brings large detrimental effects to people’s physical and mental health, but also causes substantial economic burdens to society. By using traditional surgical debridement and antibiotic therapy, patients generally suffer more pain and are at risk of recurring infections. Thus, the development of non-antibiotic treatment methods is desperately needed. Currently, the emerging of flexible wound dressings with physiological signal detection, inactivated infectious pathogen, and wound-healing promoting properties has exhibited immense potential for the treatment of infected wound. Among various dressings, MXene‐based flexible electronic materials as wound dressings with special electroactive, mechanical, photophysical, and biological performances possess a broad application prospect in healthcare. In this review, the challenges of infected wound management are introduced. Next, the types of MXene-based flexible materials and wound infection features are outlined. Then the recent advance of MXene-based flexible materials for infected wound detection and treatment is summarized. Lastly, the predicaments, prospects, and future directions of MXene-based flexible materials for infected wound management are discussed.

Abstract Background The main cause of anesthesia-related deaths is the failure to manage difficult airways. Difficult laryngoscopic exposure is a major cause of unsuccessful management of difficult airways. Inadequate preoperative airway assessment hinders the clinical management of difficult airways cases, emphasizing the critical need for accurate identification of difficult airways. Currently, no definitive and reliable indicators are available to predict a difficult airway. Our study aims to predict laryngoscope exposure risk factors by combining ultrasonically measured upper airway anatomic parameters with physical examination indicators. Methods Patients aged 18 to 75 years, classified as American Standards Association (ASA) I-III, and scheduled for elective general anesthesia with endotracheal intubation were included. All patients received the upper airway and ultrasonographic measurements. After anesthesia induction, laryngoscope exposure was analyzed using the Cormack-Lehane grading system, with Grades III and IV as indicative of difficult laryngoscopy. Univariate and multivariate logistic regression analyses were performed to identify reliable indicators for predicting difficult laryngoscopy. Receiver Operating Characteristic (ROC) curve analysis was utilized to assess the predictive performance of each indicator. Results A total of 1120 patients finished the study, with 710 cases found in Grade I laryngoscopic exposure group, 360 cases in Grade II group, and 50 cases in Grade III group. There was no case observed in Grade IV group, thereby resulting in an incidence of difficult laryngoscopy of 4.46%. Univariate logistic regression analysis revealed that several parameters including age, Body Mass Index (BMI), neck circumference, neck mobility, snoring intensity, as well as ultrasound measurements of the pre-epiglottic space and thyromental distance were identified as significant risk factors for difficult laryngoscopy (P

Objective(s): Salidroside (SAL), an active ingredient purified from the medicinal plant Rhodiola rosea, has anti-inflammatory, anti-oxidant, anticancer, and neuroprotective properties. The study aims to examine SAL’s protective role in liver damage brought on by lipopolysaccharide (LPS). Materials and Methods: Six to eight-week-old male C57BL/6 wild-type mice were intraperitoneally treated with 10 mg/kg LPS for 24 hr and 50 mg/kg SAL two hours before LPS administration. Mice were categorized into control, LPS, and LPS + SAL groups. To evaluate liver injury, biochemical and TUNNEL staining test studies were performed. The Elisa assay analyzed interleukin- 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) pro-inflammatory cytokine expression levels. RT-qPCR and western blotting measured mRNA and protein expression of SIRT1, NF-кB, NLRP3, cleaved caspase-1, and GSDMD, respectively.Results: Analysis of the serum alanine/aspartate aminotransferases (ALT/AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) revealed that SAL protected against hepatotoxicity induced by LPS. The pathological evaluation of the liver supported the protection provided by SAL. SAL treatment reversed IL-1β, TNF-α, and IL-6 pro-inflammatory cytokines after being induced by LPS (all, P

Objective To observe the efficacy of secukinumab in the treatment of severe plaque psoriasis with abnormal liver function and the changes in liver function after the treatment. Methods Seven patients with severe plaque psoriasis with abnormal liver function were subcutaneously given secukinumab 300 mg/time, once-weekly from weeks 0 to 4, followed by once every 4 weeks. Routine blood test, liver and kidney functions, blood lipids and glucose were tested at weeks 1, 2, 3, and 4, and every 4 weeks thereafter until week 32. At the same time, the psoriatic lesion area and severity index (PASI), physician global assessment (PGA), and dermatology life quality index (DLQI) were recorded to assess the efficacy and safety. Results The PASI scores, PGA scores and DLQI were changed significantly from the baseline at all time points (P

Objective To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. Methods A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. Results The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P

Objective To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. Methods A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. Results The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P

Objective To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. Methods A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. Results The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P

Objective To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. Methods Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. Results A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. Conclusion A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level

Abstract Background Posterior cortical atrophy (PCA) is a form of dementia that frequently displays significant visual dysfunction and relatively preserved cognitive and executive functions, thus hindering early diagnosis and treatment. This study aimed to investigate possible fundus markers in PCA patients and compare them with those of typical Alzheimer’s disease (AD) patients to seek potential diagnostic patterns. Methods Age-matched PCA and AD patients and healthy controls (HC) completed optometry, intraocular pressure measurement, neuropsychologic assessments, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) examination in one visit. Overall, six outcomes of thicknesses of various retinal layers and seven outcomes of the retinal microvascular network were calculated. After adjusting for age, sex, and years of education, the OCT and OCTA results were analyzed using analysis of covariance and generalized linear models. Correlation analyses were performed using Spearman correlation, and ROC curves were plotted. Results Twelve PCA patients, nineteen AD patients, and thirty HC, aged 45–80 years were included. Fifty HC, thirty AD, and twenty PCA eyes were available for foveal avascular zone (FAZ) area analysis; forty-nine HC, thirty-four AD, and eighteen PCA eyes were available for OCT and OCTA assessments. PCA patients had thinner retinal nerve fiber layer and ganglion cell layer + inner plexiform layer than HC in the 0–3 mm circle and 1–3 mm ring. Few structural differences were observed between the AD group and the other two groups. The flow area of the superficial capillary plexus and the intermediate capillary plexus was smaller in the PCA group than in the HC group in the 0–1 mm circle, 0–3 mm circle. MMSE performed better than any combination of optical parameters in identifying AD and PCA from HC (AUC = 1), while the combination of MoCA, retinal thickness and vascular density of ICP in the 1-3 mm ring, with flow area of ICP in the 0-1 mm circle showed the strongest ability to distinguish PCA from AD (AUC = 0.944). Conclusions PCA patients exhibited similar impairment patterns to AD patients in the fundus structure and microvascular network. OCTA may aid in the non-invasive detection of AD and PCA, but still remains to be substantiated.

Abstract The frequent occurrence of extreme weather events is one of the future prospects of climate change, and how ecosystems respond to extreme drought is crucial for response to climate change. Taking the extreme drought event in the Tropic of Cancer (Yunnan section) during 2009–2010 as a case study, used the standardized precipitation evapotranspiration index to analyse the impact of extreme drought on enhanced vegetation index (EVI), leaf area index (LAI) and gross primary productivity (GPP), and to analyzed the post extreme drought vegetation recovery status. The results indicate the following: (1) Due to the cumulative effects of drought and vegetation phenology, vegetation growth in the months of March to May in 2010 was more severely affected. (2) Compared to EVI and LAI, GPP is more sensitive to drought and can accurately indicate areas where drought has impacted vegetation. (3) Following an extreme drought event, 70% of the vegetation can recover within 3 months, while 2.87–6.57% of the vegetation will remain unrecovered after 6 months. (4) Cropland and grassland show the strongest response, with longer recovery times, while woodland and shrubland exhibit weaker responses and shorter recovery times. This study provides a reference for the effects of extreme drought on vegetation.

Abstract Background Osteoarthritis (OA) represents a prominent etiology of considerable pain and disability, and conventional imaging methods lack sensitivity in diagnosing certain types of OA. Therefore, there is a need to identify highly sensitive and efficient biomarkers for OA diagnosis. Zinc ions feature in the pathogenesis of OA. This work aimed to investugate the role of zinc metabolism-related genes (ZMRGs) in OA and the diagnostic characteristics of key genes. Methods We obtained datasets GSE169077 and GSE55235 from the Gene Expression Omnibus (GEO) and obtained ZMRGs from MSigDB. Differential expression analysis was conducted on the GSE169077 dataset using the limma R package to identify differentially expressed genes (DEGs), and the intersection of DEGs and ZMRGs yielded zinc metabolism differential expression-related genes (ZMRGs-DEGs). The clusterProfiler R package was employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of ZMRGs-DEGs. Potential small molecule drugs were predicted using the CMap database, and immune cell infiltration and function in OA individuals were analyzed using the ssGSEA method. Protein-protein interaction (PPI) networks were constructed to detect Hub genes among ZMRGs-DEGs. Hub gene expression levels were analyzed in the GSE169077 and GSE55235 datasets, and their diagnostic characteristics were assessed using receiver operating characteristic (ROC) curves. The gene-miRNA interaction network of Hub genes was explored using the gene-miRNA interaction network website. Results We identified 842 DEGs in the GSE169077 dataset, and their intersection with ZMRGs resulted in 46 ZMRGs-DEGs. ZMRGs-DEGs were primarily enriched in functions such as collagen catabolic processes, extracellular matrix organization, metallopeptidase activity, and pathways like the IL-17 signaling pathway, Nitrogen metabolism, and Relaxin signaling pathway. Ten potential small-molecule drugs were predicted using the CMap database. OA patients exhibited distinct immune cell abundance and function compared to healthy individuals. We identified 4 Hub genes (MMP2, MMP3, MMP9, MMP13) through the PPI network, which were highly expressed in OA and demonstrated good diagnostic performance. Furthermore, two closely related miRNAs for each of the 4 Hub genes were identified. Conclusion 4 Hub genes were identified as potential diagnostic biomarkers and therapeutic targets for OA.

Abstract Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Abstract Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation state right after stimulation. Many theoretical and experimental works have focused on the cellular and molecular basis of the acute neural response to magnetic field. However, effects of magnetic stimulation can still last after the termination of the magnetic stimulation (named “carry-over effects”), which could generate profound effects to the outcome of the stimulation. However, the cellular and molecular mechanisms of carry-over effects are largely unknown, which renders the neural modulation practice using magnetic stimulation unpredictable. Here, we investigated carry-over effects at the cellular level, using the combination of micro-magnetic stimulation (µMS), electrophysiology, and computation modeling. We found that high frequency magnetic stimulation could lead to immediate neural inhibition in ganglion neurons from Aplysia californica, as well as persistent, carry-over inhibition after withdrawing the magnetic stimulus. Carry-over effects were found in the neurons that fired action potentials under a variety of conditions. The carry-over effects were also observed in the neurons when the magnetic field was applied across the ganglion sheath. The state of the neuron, specifically synaptic input and membrane potential fluctuation, plays a significant role in generating the carry-over effects after magnetic stimulation. To elucidate the cellular mechanisms of such carry-over effects under magnetic stimulation, we simulated a single neuron under magnetic stimulation with multi-compartment modeling. The model successfully replicated the carry-over effects in the neuron, and revealed that the carry-over effect was due to the dysfunction of the ion channel dynamics that were responsible for the initiation and sustaining of membrane excitability. A virtual voltage-clamp experiment revealed a compromised Na conductance and enhanced K conductance post magnetic stimulation, rendering the neurons incapable of generating action potentials and, therefore, leading to the carry over effects. Finally, both simulation and experimental results demonstrated that the carry-over effects could be controlled by disturbing the membrane potential during the post-stimulus inhibition period. Delineating the cellular and ion channel mechanisms underlying carry-over effects could provide insights to the clinical outcomes in brain stimulation using TMS and other modalities. This research incentivizes the development of novel neural engineering or pharmacological approaches to better control the carry-over effects for optimized clinical outcomes.

ABSTRACT: This study aimed to probe if xylooligosaccharide (XOS) could act as an antimetabolite to impact the cell cycle and antibiotic tolerance of avian pathogenic Escherichia coli (APEC). We firstly measured the bacteriostasis of XOS against APEC O78 and its effect on the growth of APEC O78 growing on different medium. Afterwards, the effects of XOS on xylose operon activation along with the cell cycle and antibiotic tolerance of APEC O78 were analyzed. The results showed that XOS caused no inhibitory circle against APEC O78 and did not affect (P > 0.05) the growth of APEC O78 growing on LB medium. Besides, APEC O78 was unable to grow on M9 medium (carbon-free) added with XOS. However, XOS exerted a similar role as xylose in increasing (P < 0.05) the expression of certain xylose operon genes including xylose isomerase (XylA)-encoding gene (xylA) and xylose-binding periplasmic protein (XylF)-encoding gene (xylF) in APEC O78. The molecular docking simulation revealed that the major monomer components (xylobiose, xylotriose and xylotetraose) of XOS had stable binding potentials to both XylA and XylF proteins of E. coli, as supported by the low binding free energy and the formation of considerable hydrogen bonds between them. The subsequent analysis showed that XOS altered certain cell cycle-related genes expression, especially elevated (P < 0.05) nrdB expression and decreased ihfB expression to a degree. Moreover, XOS played a similar role as 2-deoxy-glucose (a glucose analogue serving as a typical antimetabolite) in lowering (P < 0.05) the number of ampicillin-tolerant APEC O78. Collectively, XOS had no direct bacteriostasis against APEC and could not be metabolized/utilized by APEC O78. However, it might become an analogue of xylose and then activate xylose transport- and metabolism-related proteins in APEC O78, thus functioning as a potential antimetabolite and exerting antimetabolic actions. This could at least partially interpret the observed roles of XOS in interfering with the cell cycle and diminishing the antibiotic tolerance of APEC O78. The above findings expand the knowledges about the functions of XOS and provide a basis for exploring novel strategies to reduce the antibiotic tolerance of APEC.

BackgroundMost head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at an advanced local stage. While immunotherapy has improved survival rates, only a minority of patients respond durably to targeted immunotherapies, posing substantial clinical challenges. We investigated the heterogeneity of the tumor microenvironment in HNSCC cohorts before and after immunotherapy by analyzing single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing datasets retrieved from public databases.MethodsWe constructed a single-cell transcriptome landscape of HNSCC patients before and after immunotherapy and analyzed the cellular composition, developmental trajectories, gene regulatory networks, and communication patterns of different cell type subpopulations. Additionally, we assessed the expression levels of relevant indicators in HNSCC cells via western blot, ELISA, and fluorescent probe techniques.ResultsAt the single-cell level, we identified a subpopulation of TP63+ SLC7A5+ HNSCC that exhibited a ferroptosis-resistant phenotype. This subpopulation suppresses ferroptosis in malignant cells through the transcriptional upregulation of SLC7A5 mediated by high TP63 expression, thereby promoting tumor growth and resistance to immunotherapy. The experimental results demonstrated that the overexpression of TP63 upregulated the expression of SLC7A5 and suppressed the concentrations of Fe2+ and ROS in HNSCC cells. By integrating bulk transcriptome data, we developed a clinical scoring model based on TP63 and SLC7A5, which are closely associated with tumor stage, revealing the significant prognostic efficacy of the TP63+ SLC7A5+ HNSCC-mediated ferroptosis mechanism in HNSCC patients.ConclusionOur research elucidates the TME in HNSCC before and after immunotherapy, revealing a novel mechanism by which TP63+ SLC7A5+ HNSCC inhibits ferroptosis and enhances tumor resistance via TP63-induced SLC7A5 upregulation. These insights lay the foundation for the development of more effective treatments for HNSCC.

Our research team previously reported the immunomodulatory effects of kombucha fermentation liquid. This study investigated the protective effects of turmeric kombucha (TK) against lipopolysaccharide (LPS)-induced sepsis and its impact on the intestinal microbiota of mice. A turmeric culture medium without kombucha served as the control (TW). Non-targeted metabolomics analysis was employed to analyze the compositional differences between TK and TW. Qualitative analysis identified 590 unique metabolites that distinguished TK from TW. TK improved survival from 40 to 90%, enhanced thermoregulation, and reduced pro-inflammatory factor expression and inflammatory cell infiltration in the lung tissue, suppressing the NF-κB signaling pathway. TK also altered the microbiome, promoting Allobaculum growth. Our findings shed light on the protective effects and underlying mechanisms of TK in mitigating LPS-induced sepsis, highlighting TK as a promising anti-inflammatory agent and revealing new functions of kombucha prepared through traditional fermentation methods.

Background and importance: Explore the techniques, advantages and disadvantages of 3D Slicer reconstruction combined with transcranial neuroendoscopy in cerebrospinal fluid rhinorrhea surgery. Clinical presentation: We collected complete clinical data of two patients with cerebrospinal fluid rhinorrhea who underwent minimally invasive surgery using 3D Slicer reconstruction combined with transcranial neuroendoscopy through the supraorbital eyebrow arch keyhole approach in our hospital from June 2022 to May 2023. The patients were one male and one female, aged 50 and 63 years old. At the same time, a retrospective summary of relevant literature at home and abroad in recent years was conducted. 1 case had spontaneous cerebrospinal fluid rhinorrhea with secondary cribriform plate lesion, and the other 1 case had traumatic cerebrospinal fluid rhinorrhea. Both 2 patients were ineffective after long-term conservative treatment, and ultimately recovered after detailed preoperative evaluation and preparation and surgical treatment. Conclusion: Cerebrospinal fluid rhinorrhea is a challenging disease in neurosurgery, and improper management can lead to serious complications such as meningitis. Our team used 3D Slicer reconstruction combined with transcranial endoscopic minimally invasive keyhole surgery to treat cerebrospinal fluid rhinorrhea, achieving good results, proving that this combined technology has certain advantages and is a new surgical technique worth promoting. However, the widespread application and promotion of this technology in anterior skull base surgery still require comprehensive and reliable prospective clinical studies to test.

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignancy characterized by a high incidence and recurrence rate. 5-methylcytosine (m5C) RNA modification is a common alteration affecting cancer progression; however, how m5C operates within the tumor microenvironment of HNSCC remains to be elucidated. Methods: We conducted Nanopore sequencing on 3 pairs of cancer and paracancerous tissues from mid- and late-stage HNSCC, obtaining 132 upregulated genes (transcriptomically upregulated, m5C elevated) and 129 downregulated genes (transcriptomically downregulated, m5C reduced). Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed; a differential gene interaction network (PPI) was constructed, revealing the interactions of each gene with others in the network. Co-expression analysis was performed on the genes within the PPI, unveiling their expression and regulatory relationships. Through GSVA analysis, variations in related pathways under different states were identified. Furthermore, results of m5C in lncRNA were screened, followed by target gene prediction. Results: Sequencing results from the 3 pairs of mid- and late-stage HNSCC cancer and paracancerous tissues demonstrated that RPS27A, RPL8, and the lncRNAs including differentiation antagonizing nonprotein coding RNA (DANCR), DCST1 antisense RNA 1 (CCDC144NL-AS1), Growth Arrest-Specific Transcript 5 (GAS5), Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), and Small Nucleolar RNA Host Gene 3 (SNHG3), etc., under m5Cregulation, have close connections with surrounding genes. The differentially m5Cmodified genes are primarily involved in ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, immunity, and other life processes; pathways like mitochondrial protein import and photodynamic therapy induced unfolded protein response are upregulated in the tumor, while pathways, including the classic P53, are suppressed. Analysis on m5C-regulated long non-coding RNAs (lncRNAs) revealed tight associations with RPS27A and RPL8 as well. Conclusion: Our study identifies the key factors and signaling pathways involving m5C in HNSCC. The findings suggest that ribosome-related genes might regulate ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, and immune response through m5C RNA modification by means like hypoxia and ferroptosis, thereby playing a pivotal role in the onset and progression of HNSCC. Hence, attention should be paid to the role of ribosomes in HNSCC. These findings may facilitate the precision and individualized treatment of patients with mid- and late-stage HNSCC in clinical settings.

PurposeWe evaluated the clinical effect of utilizing a Limberg rhomboid flap graft in conjunction with Enhanced Recovery After Surgery (ERAS) protocols for the management of pilonidal sinus in the sacrococcygeal region to demonstrate the feasibility of applying ERAS to the treatment of pilonidal sinus.MethodsBetween January 2010 and August 2018, prospective data analysis was undertaken on 109 patients who received surgical treatment for pilonidal sinus in the sacrococcygeal region at the Department of Colorectal and Anal Surgery, Jingzhou Hospital affiliated to Yangtze University, and Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine. The patients were randomly separated into two groups based onoperation technique: the control group (pilonidal sinus resection with primary suture) and the observation group (pilonidal sinus resection with Limberg flap graft). Some patients in the above two groups received ERAS after surgery, which included early feeding and early ambulation, etc. Therefore, we further subdivided each group into group A (without ERAS) and group B (with ERAS) according to whether they received ERAS. Comparative analysis was conducted to assess differences in pertinent data before and after surgery across the respective groups.ResultsThe length of postoperative hospitalization was shorter and wound dehiscence was more common in control group B than in control group A [(9.00 ± 1.20) vs. (11.07 ± 1.78), 26.7% (8/30) vs. 7.1% (2/28), P

ObjectiveTo explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II).Materials and MethodsA total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM.ResultsThere were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p

BackgroundT lymphocytes, integral to the adaptive immune system, wield pivotal influence in bolstering anti-tumor responses, and are strictly regulated by ubiquitination modification. The objective of this investigation was to devise a novel prognostic and immunotherapeutic efficacy predictor for hepatocellular carcinoma patients utilizing T cell-related ubiquitination genes (TCRUG).MethodThe single-cell RNA sequencing (scRNA-seq) data and bulk RNA data of HCC patients are derived from the GEO database and TCGA database. Based on the processing of scRNA-seq, T cell marker genes are obtained and TCRUG is obtained. Further combined with WGCNA, differential analysis, univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis to filter and screen TCRUG. Finally construct a riskscore for predicting the prognosis of HCC patients, the predictive effect of which is validated in the GEO dataset. In addition, we also studied the correlation between riskscore and immunotherapy efficacy. Finally, the oncogenic role of UBE2E1 in HCC was explored through various in vitro experiments.ResultBased on patients’ scRNA-seq data, we finally obtained 3050 T cell marker genes. Combined with bulk RNA data and clinical data from the TCGA database, we constructed a riskscore that accurately predicts the prognosis of HCC patients. This riskscore is an independent prognostic factor for HCC and is used to construct a convenient column chart. In addition, we found that the high-risk group is more suitable for immunotherapy. Finally, the proliferation, migration, and invasion abilities of HCC cells significantly decreased after UBE2E1 expression reduction.ConclusionThis study developed a riskscore based on TCRUG that can accurately and stably predict the prognosis of HCC patients. This riskscore is also effective in predicting the immune therapy response of HCC patients.

Traditional methods for water quality assessment often overlook the uncertainty of water quality data during the sample collection process, leading to limitations in their application. Therefore, this study combines the comprehensive water quality index (CWQI) method and the improved CWQI method based on CRITIC with the Monte Carlo method to evaluate the water quality in the Weishui Reservoir watershed. The results indicate that (1) there is a noticeable difference in water quality between the Shaxiping and Dayanzui sampling points. The water quality at the Shaxiping sampling point is excellent, with a water quality classification of Class I. In contrast, the water quality at the Dayanzui sampling point is comparatively poorer, with an average water quality classification of Class III. (2) Sensitivity analysis shows that TN, NH4+-N, and TP are more sensitive than other indicators, suggesting that they are the primary factors influencing the evaluation results. (3) Compared to the traditional CWQI method, combining the CRITIC-based improved CWQI method with the Monte Carlo method is more scientifically rigorous. It considers the variety of evaluation indicators, allocates weights rationally, and provides evaluation results that align better with seasonal variations, resulting in higher discriminative power. HIGHLIGHTS A new model integrating Monte Carlo simulation, CRITC methods, and CWQI was proposed to assess water quality in Weishui Reservoir.; Compared with the conventional model (CWQI), the new model leads to more reasonable results.; The key parameters affecting water quality in Weishui Reservoir are TN, TP, and NH4+-N.;

Abstract Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HTDRN neurons from naïve female mice. Notably, this higher sensitivity was blunted by 17β-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERα and ERβ are expressed in 5-HTDRN neurons, whereas ERα agonist depolarizes and ERβ agonist hyperpolarizes 5-HTDRN neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HTDRN neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs’ inhibitory effects on ethanol-induced burst firing of 5-HTDRN neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERα- or ERβ-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERα/β to prevent alcohol-induced activation of 5-HTDRN neurons, which in return leads to higher binge alcohol drinking.

It is significant for harbor management and ship safety to obtain more precise location and shape information from ship instance segmentation. Ships often encounter mutual occlusion during navigation in busy harbors and nearshore locations, affecting the accuracy of target segmentation. However, existing approaches for instance segmentation rarely consider the ship occlusion. To improve the segmentation performance of occluded ships, we propose an improved instance segmentation method (RFFSCPNet) based on Residual Feature Fusion and Ship Contour Predictor. Firstly, residual feature fusion module is presented to deeply integrate features at diverse scales and levels to promote global spatial correlation in ship context and eliminate conflicts across semantic contexts. Secondly, a ship contour predictor is developed to enhance the capacity to capture contour features and improve the accuracy of segmentation mask predictions by obtaining finer boundaries. Furthermore, a new loss function is proposed to produce smooth and clear masks to solve mask overflow and discontinuity problems. Finally, an occluded ship segmentation dataset is collected and labeled for occluded ship segmentation, which contains 4369 real and simulated occlusion ship images with 14325 fine instance mask annotations. Experiments on the occluded ship dataset show that the proposed network increased by 7.90%, 5.31, 3.96% and 2.61% AP higher than Mask R-CNN, Blendmask, SparseNet and CondInst, respectively. The results demonstrate that the RFFSCPNet can achieve more precise segmentation in occluded ship scenes.

Abstract Introduction Circular RNAs (CircRNA) have emerged as an interest of research in recent years due to its regulatory role in various kinds of cancers of human body. Esophageal squamous cell carcinoma (ESCC) is one of the major disease subtype in Asian countries, including China. CircRNAs are formed by back-splicing covalently joined 3′- and 5′- ends rather than canonical splicing and are found to have binding affinity with miRNAs that conjointly contribute to oncogenesis. Materials and methods 4 pairs of normal, cancer adjacent tissues and cancer tissues were analyzed by high-throughput RNA sequencing and 84 differentially upregulated circRNAs were detected in cancer tissues. hsa_circ_0032746 was silenced by siRNA and lentivirus and then further proliferation, migration and invasion were performed by CCK-8 and transwell assays. Bioinformatic analysis predicted binding affinity of circRNA/miRNA/mRNA axis. Results After qPCR validation, we selected a novel upregulated hsa_circ_0032746 to explore its biogenetic functions which showed high expression in cancer tissues but not in cancer adjacent tissues. The clinicopathological relation of hsa_circ_0032746 showed positive correlation with the tumor location (P = 0.026) and gender (P = 0.05). We also predicted that hsa_circ_0032746 could sponge with microRNA. Bioinformatic analysis predicted 11 microRNA response element (MRE) sequences of hsa_circ_0032746 and dual luciferase reporter assay confirmed binding affinity with miR4270 evidencing further study of circRNA/miRNA role. The knockdown of hsa_circ_0032746 by siRNA and lentivirus demonstrated that proliferation, invasion and migration of ESCC were inhibited in vitro and vivo experiments. Bioinformatic analysis further predicted MCM3 as a target of miR-4270 and was found upregulated in ESCC upon validation. miR4270 mimic decreased the level of hsa_circ_0032746 and MCM3 while further rescue experiments demonstrated that hsa_circ_0032746 was dependent on miR4270/MCM3 axis on the development process of ESCC. Conclusion We revealed for the first time that circ_0032746/mir4270/MCM3 contributes in proliferation, migration and invasion of ESCC and could have potential prognostic and therapeutic significance.

Abstract Objective To explore the surgical techniques, advantages, and disadvantages of neuroendoscopic telovelar approach in the treatment of brainstem and fourth ventricle lesions. Methods The clinical data of 5 patients treated by neuroendoscopic telovelar approach from March 2020 to March 2022 were analyzed retrospectively. Results Among the 5 patients, there were 3 cavernous hemangiomas in pontine arm and 2 tumors in brainstem and fourth ventricle. All patients could successfully complete the operation, and 4 patients recovered well, other 1 patient discharged automatically for serious complications of other systems after the operation. Conclusion The telovelar approach has gained popularity as a safe and effective strategy for lesions in fourth ventricular and brainstem. However, without removing the posterior arch of the atlas, it is difficult to enter the upper part of the fourth ventricle under a microscope. Transcranial neuroendoscopy can effectively compensate for the shortcomings of microscopy, whether used as an auxiliary measure for microsurgery or alone with proficient endoscopic techniques, it will provide greater application in minimally invasive surgery for fourth ventricle and brainstem lesions. By utilizing the excellent degree of freedom of transcranial neuroendoscopy, there is no need to open the posterior arch of the atlas, making the surgery more minimally invasive. However, the sample size of this study is small, and it was completed under the very mature neuroendoscopic technology of our team. Its general safety and practicality still require extensive clinical research validation.

This study was conducted to investigate the protective effects of xylooligosaccharide (XOS) on the growth performance and intestinal health of broilers challenged by avian pathogenic Escherichia coli (APEC). A total of 144 newly hatched male Lingnan yellow-feathered broilers were randomly divided into three groups (six replicates/group): a control (CON) group, an APEC group and an XOS group (APEC-challenged broilers supplemented with 1600 mg/kg XOS). Birds in the APEC and XOS groups were orally challenged with APEC from 7 to 12 d of age. Growth performance and intestinal health-related parameters were determined on d 13 and 17. The reductions (p < 0.05) in final body weight, average daily gain and elevation (p < 0.05) in intestinal APEC colonization in challenged broilers were counteracted by the XOS addition, which also alleviated the APEC-induced reductions (p < 0.05) in jejunal goblet cell count and density in broilers on d 17. Supplementing with XOS increased (p < 0.05) jejunal villus height and crypt depth, coupled with occludin and zonula occluden-1 expression, on d 17, and diminished the change (p < 0.05) in the jejunal inflammatory cytokine expression profile in a time-dependent manner. Moreover, cecal counts of total bacteria and Lactobacillus in challenged broilers were augmented (p < 0.05) by the XOS addition, which also mitigated APEC-induced reductions (p < 0.05) in cecal acetate, butyrate and valerate concentrations in broilers on d 13 or 17. Supplementing with XOS blocked the increases (p < 0.05) in the expression of cecal E. coli virulence genes relA and ompR on d 13 along with the expression of fimH and csgA on d 17. XOS alleviated APEC-induced growth retardation and intestinal disruption in broilers partially by restraining the intestinal colonization of APEC. Furthermore, the improvements in cecal microbiota and fermentation pattern, along with attenuation of cecal E. coli virulence resulting from XOS supplementation, could also support the maintenance of intestinal health in APEC-challenged broilers.

ABSTRACT: Ammonia (NH3) is a toxic gas that in intensive poultry houses, damages the poultry health and induces various diseases. This study investigated the effects of NH3 exposure (0, 15, 30, and 45 ppm) on growth performance, serum biochemical indexes, antioxidative indicators, tracheal and lung impairments in Pekin ducks. A total of 288 one-day-old Pekin male ducks were randomly allocated to 4 groups with 6 replicates and slaughtered after the 21-d test period. Our results showed that 45 ppm NH3 significantly reduced the average daily feed intake (ADFI) of Pekin ducks. Ammonia exposure significantly reduced liver, lung, kidney, and heart indexes, and lowered the relative weight of the ileum. With the increasing of in-house NH3, serum NH3 and uric acid (UA) concentrations of ducks were significantly increased, as well as liver malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX-Px) contents. High NH3 also induced trachea and lung injury, thereby increasing levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) in the lung, and decreasing the mRNA expressions of zonula occludens 1 (ZO-1) and claudin 3 (CLDN3) in the lung. In conclusion, in-house NH3 decrease the growth performance in ducks, induce trachea and lung injuries and meanwhile increase the compensatory antioxidant activity for host protection.

Curcumin is a natural molecule widely tested in preclinical and clinical studies due to its antioxidant and anti-inflammatory activity. Nevertheless, its high hydrophobicity and low bioavailability limit in vivo applications. To overcome curcumin´s drawbacks, small extracellular vesicles (sEVs) have emerged as potential drug delivery systems due to their non-immunogenicity, nanometric size and amphiphilic composition. This work presents curcumin cargo into milk sEV structure and further in vitro and in vivo evaluation as a therapeutic nanoplatform. The encapsulation of curcumin into sEV was performed by two methodologies under physiological conditions: a passive incorporation and active cargo employing saponin. Loaded sEVs (sEVCurPas and sEVCurAc) were fully characterized by physicochemical techniques, confirming that neither methodology affects the morphology or size of the nanoparticles (sEV: 113.3±5.1 nm, sEVCurPas: 127.0±4.5 nm and sEVCurAc: 98.5±3.6 nm). Through the active approach with saponin (sEVCurAc), a three-fold higher cargo was obtained (433.5 µg/mL) in comparison with the passive approach (129.1 µg/mL). These sEVCurAc were further evaluated in vitro by metabolic activity assay (MTT), confocal microscopy, and flow cytometry, showing a higher cytotoxic effect in the tumoral cells RAW264.7 and HepG2 than in primary hepatocytes, specially at high doses of sEVCurAc (4%, 15% and 30% of viability). In vivo evaluation in an experimental model of liver fibrosis confirmed sEVCurAc therapeutic effects, leading to a significant decrease of serum markers of liver damage (ALT) (557 U/L to 338 U/L with sEVCurAc therapy) and a tendency towards decreased liver fibrogenesis and extracellular matrix (ECM) deposition.

Abstract Introduction Bloodstream infection (BSI) is a significant factor contributing to hospitalization and high mortality rates among human immunodeficiency virus(HIV)-positive patients. Therefore, the timely detection of this condition is of utmost importance. Blood culture is considered the gold standard for diagnosing BSIs. Currently, BD BACTEC™ Plus Aerobic/F culture bottles and the BD BACTEC™ Myco/F Lytic culture bottles can be used for blood culture. This study aimed to evaluate the efficacy of two different types of culture bottles in diagnosing BSIs in patients with HIV. Methods A retrospective analysis was conducted on HIV-positive patients hospitalized in the Infection Department of Wenzhou Central Hospital between July 2019 and October 2021. A total of 246 pairs of blood samples were included, consisting of an aerobic culture vial and a Myco/F culture vial. Blood culture results and clinical diagnosis were utilized to identify the presence of BSI. Results Out of 246 cases, 84 cases had positive blood cultures. Fungal BSIs, particularly Talaromyces marneffei BSIs, were the most prevalent among patients with HIV. The positive rate of Myco/F culture bottles (89.29%) was significantly higher compared with aerobic culture bottles (69.05%; P = 0.001). In the diagnosis of fungal BSIs, the positive rate of Myco/F culture bottles was 88.57%, which was significantly higher than that of aerobic culture bottles (72.86%; P = 0.018). The Myco/F culture bottle has more advantages in diagnosing T alaromyces marneffei BSIs (P=0.028). In addition, mycobacteria were exclusively detected in Myco/F culture bottles. Conclusions Fungal BSIs are the predominant type of infections in HIV-positive patients. Myco/F culture bottles exhibit noteworthy attributes of high positive rate in diagnosing HIV combined with BSI. These advantages are conducive to obtaining accurate culture results and minimizing missed diagnoses.

Abstract Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1β treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1β treatment promoted inflammatory factor secretion in chondrocytes, promoted cell apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1β effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1β induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression.

Abstract Background Fear of falling is a potential consequence for older adults who have experienced a fall. Whether such psychological concerns related to falls, in turn, affect physical function? Especially those who have a history of falling but have not been diagnosed with anxiety, depression, or both. This study aimed to clarify the effects of early psychological changes on the physical function of older patients. Methods The 111 participants with falling history were divided into the poor physical function (PPF) group with the Short Physical Performance Battery (SPPB) ≤ 9 and the good physical function (GPF) group with SPPB > 9. Their physical function was assessed through 4-m gait speed (4MGS), five times sit-to-stand test (FTSST), grip strength, and Timed Up and Go tests TUGT. Their mental state was assessed by the self-rating anxiety/depression scale (SAS/SDS). Results (1) SAS/SDS scores were negatively correlated with the SPPB score, gait speed, and maximum grip strength (males). (2) Multivariate logistic regression analysis showed that the SPPB score was subject to such independent influence factors: cerebrovascular disease (OR = 11.805; P = 0.005), normal ratio of grip strength (OR = 0.046; P = 0.016), TUGT (OR = 1.717; P

This study aimed to investigate the potential mitigating effects of N-acyl homoserine lactonase (AHLase) on the virulence of Salmonella typhimurium and its induction of intestinal damages in broilers. In vitro study was firstly conducted to examine if AHLase treatment could attenuate the virulence of S. typhimurium. Then, an in vivo experiment was performed by allocating 240 broiler chicks at 1 d old into 3 groups (8 replicates per group): negative control (NC), positive control (PC), and PC supplemented with 10,000 U/kg AHLase. All chicks except those in NC were orally challenged by S. typhimurium from 8 to 10 d of age. Parameters were measured on d 11 and 21. The results showed that treatment with 1 U/mL AHLase suppressed the biofilm-forming ability (including biofilm biomass, extracellular DNA secretion and biofilm formation-related gene expression), together with swarming motility and adhesive capacity of S. typhimurium. Supplemental 10,000 U/kg AHLase counteracted S. typhimurium-induced impairments (P 0.05) serum diamine oxidase activity of broilers. Noticeably, S. typhimurium challenge caused little change in the mRNA expression of ileal inflammatory cytokines except for an increase (P

In this paper, targeting the problem that it is difficult to deal with the time-varying sideslip angle of an underactuated unmanned surface vehicle (USV), a line–of–sight (LOS) guidance law based on an improved extended state observer (ESO) is proposed. A reduced-order ESO is introduced into the identification of the sideslip angle caused by the environmental disturbance, which ensures a fast and accurate estimation of the sideslip angle. This enables the USV to follow the reference path with high precision, despite external disturbances from wind, waves, and currents. These unknown disturbances are modeled as drift, which the modified ESO-based LOS guidance law compensates for using the ESO. In the guidance subsystem incorporating the reduced-order state observer, the observer estimation and track errors are proved uniformly ultimately bounded. Simulation and experimental results are presented to validate the effectiveness of the proposed method. The simulation and comparison results demonstrate that the proposed ELOS guidance can help a USV track different types of paths quickly and smoothly. Additionally, the experimental results confirm the feasibility of the method.

Abstract It is crucial for archaeological investigations to identify the category of cultural relics by analyzing their chemical composition. This study analyzed the chemical composition distribution of glass cultural relics and applied distance discriminant analysis methods to classify them into two categories. Through stepwise regression, four key feature factors ( $${SiO}_{2}, {K}_{2}O, PbO$$ SiO 2 , K 2 O , P b O , and the presence of weathering on the artifact's surface) were selected from a total of 15 features, including surface weathering. Aside from using columnar table analysis to determine weathering on the surface of the artifact and correlations between categories, and using Spearman correlation coefficients to select key feature factors such as $${SiO}_{2}, {K}_{2}O, PbO, BaO, and \,SrO$$ SiO 2 , K 2 O , P b O , B a O , a n d S r O from 14 total feature factors (excluding weathering on the surface), we established a Mahalanobis distance discriminant model to differentiate unknown glass artifacts. Results indicate that Spearman-Mahalanobis distance discrimination outperformed stepwise regression-Mahalanobis distance discrimination, with an overall accuracy of 99.10% for the former and 98.69% for the latter in identifying high-potassium glass or lead-barium glass.

Abstract Background With the increasing availability of chest computed tomography (CT), the detection of small pulmonary nodules has become more common, facilitating the development of lung segmental resection. However, anatomical variations of the bronchi are common, particularly in the right upper lobe of the lung. Case presentation We report a case of thoracoscopic resection of the posterior segment of the right upper lobe of the lung. Preoperatively, the nodule was believed to be located in the superior segment of the right lower lobe. However, intraoperative exploration revealed that the nodule was located in the posterior segment of the right upper lobe, further showing that the bronchi of the posterior segment of the right lung opened into the bronchus intermedius. The procedure was completed uneventfully. Postoperative retrospective three-dimensional (3D) reconstruction of the lung CT images confirmed that the bronchi of the posterior segment of the right upper lobe originated from the bronchus intermedius. Conclusions This rare case highlights the importance of 3D reconstruction to guide accurate segmentectomy in patients with anatomic variations.