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Background: Coccidioidomycosis results from airborne infections caused by either Coccidioides immitis or C. posadasii. Both are pathogenic fungi that live in desert soil in the New World and can infect normal hosts, but most infections are self-limited. Disseminated infections occur in approximately 5% of cases and may prove fatal. Mouse models of the disease have identified strains that are resistant (e.g. DBA/2) or susceptible (e.g. C57BL/6) to these pathogens. However, the genetic and immunological basis for this difference has not been fully characterized. Results: Microarray technology was used to identify genes that were differentially expressed in lung tissue between resistant DBA/2 and sensitive C57BL/6 mice after infection with C. immitis. Differentially expressed genes were mapped onto biological pathways, gene ontologies, and protein interaction networks, which revealed that innate immune responses mediated by Type II interferon (i.e., IFNG) and the signal transducer and activator of transcription 1 (STAT1) contribute to the resistant phenotype. In addition, upregulation of hypoxia inducible factor 1A (HIF1A), possibly as part of a larger inflammatory response mediated by tumor necrosis factor alpha (TNFA), may also contribute to resistance. Microarray gene expression was confirmed by real-time quantitative PCR for a subset of 12 genes, which revealed that IFNG HIF1A and TNFA, among others, were significantly differentially expressed between the two strains at day 14 post-infection. Conclusion: These results confirm the finding that DBA/2 mice express more Type II interferon and interferon stimulated genes than genetically susceptible strains and suggest that differential expression of HIF1A may also play a role in protection. [ABSTRACT FROM AUTHOR]

Background: It has been reported that some single nucleotide polymorphisms (SNPs) of the angiotensin converting enzyme (ACE) gene and the endothelial nitric oxide synthase (eNOS) gene are associated with the development of systemic lupus erythematosus (SLE) and the progression of nephropathy. The aim of this study was to evaluate the possible association between six SNPs (A-5466C, T-3892C, A-240T, C1237T, G2215A and A2350G) of the ACE gene and two SNPs (T-786C and G894T) of the eNOS gene with lupus nephropathy in a northern Chinese population. Methods: In this study, 225 patients with lupus nephropathy were compared to 232 healthy controls, matched by gender, age and ethnicity. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, the genotypes of the eight selected SNPs were determined by the method of PCR-RFLP; the haplotypes were inferred using PHASE 2.1. The associations between the SNPs and the risk of lupus nephropathy were analyzed using Chi-square test and Logistic regression with SPSS13.0 software. Results: Statistically significant differences of the allele frequency distribution of three SNPs (A-5466C, A2350G and G894T) were observed between cases and controls (P < 0.05). Among the 53 haplotypes identified, the frequencies of five haplotypes (CTTCGA, ACTTAA, ACATGG, ACACGG and ATTCGA) were significantly different between cases and controls (P < 0.05). Conclusions: Our study indicated an association between the risk of lupus nephropathy and the sequence variations of both the ACE gene and the eNOS gene, which may play an important role in the pathogenesis of lupus nephropathy in the northern Chinese population. Further studies are warranted to validate our findings. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "NA plasmid HIV vaccine design, number of doses, participant gender, and body mass index affect T-cell responses across HIV vaccine clinical trials," by C. Morgan and colleagues is presented.

Objective: To analyze the influencing factors and treatment options of cervical spondylotic myelopathy (CSM) complicated with traumatic central cord syndrome (TCCS)., Methods: A total of 243 patients with CSM admitted to our hospital from January 2021 to September 2022 were retrospectively analyzed, and then divided into the control group (n = 152) and the observation group (n = 91) according to the presence or absence of concurrent TCCS. The clinical data and imaging data of the two groups were compared, and multivariate logistic regression was used to analyze the influencing factors of CSM complicated with TCCS. Patients in the observation group were further divided into the zero notch anterior cervical interbody fusion device (Zero-P) group (n = 45) and the cervical spine locking plate (CSLP) group (n = 46) according to the treatment mode, and the perioperative indexes of the two groups were compared. The treatment effects were evaluated by the American Spinal Injury Association (ASIA) and the Japanese Orthopedic Association (JOA) before surgery, 1 week after surgery and 6 months after surgery. The height of intervertebral space and the cervical lordosis angle were measured., Results: Multivariate logistic regression analysis showed that the injury mechanism (hyperextension injury), hand muscle weakness, cervical instability, age, degree of cervical spinal stenosis, degree of cervical spinal cord compression, and changes in intramedullary high signal were the risk factors, while the type of compression (soft), ASIA score and JOA score were the protective factor for CSM complicated with TCCS (P < 0.05). Patients in Zero-P group had much shorter operation time and hospitalization time than these in CSLP group (P < 0.05). The cervical lordosis angle and intervertebral space height at 1 week and 6 months after operation in the two groups were both largely higher than these before operation, and the cervical lordosis angle and intervertebral space height in the Zero-P group were significantly higher than these in the CSLP group one week after surgery (P < 0.05). The ASIA score and JOA score were obviously increased in the two groups 1 week and 6 months after surgery, and the ASIA score and JOA score in the Zero-P group were significantly higher than these in the CSLP group at 1 week after surgery (P < 0.05)., Conclusion: The mechanism of TCCS in CSM is still controversial, which it is generally believed to be caused by cervical hyperextension injury. The clinical symptoms are diverse, and the treatment methods are also different. This study shows that the mechanism of injury, type of compression, hand muscle weakness, cervical instability, age, cervical stenosis compression, and intramedullary high signal changes are all risk factors for CSM complicated with TCCS. Early identification of risk factors and targeted interventions can effectively reduce the complicated rate of TCCS. Zero-P and CSLP surgical fixation have good efficacy in the treatment of TCCS, and there is little difference in efficacy between the two. However, Zero-P fixation surgery has the advantages of short operation time and fast postoperative recovery., (© 2024. The Author(s).)

Background: Evidence shows that full mycoheterotrophs and holoparasites often have reduced plastid genomes with rampant gene loss, elevated substitution rates, and deeply altered to conventional evolution in mitochondrial genomes, but mechanisms of cytonuclear evolution is unknown. Endoparasitic Sapria himalayana and mycoheterotrophic Gastrodia and Platanthera guangdongensis represent different heterotrophic types, providing a basis to illustrate cytonuclear evolution. Here, we focused on nuclear-encoded plastid / mitochondrial (N-pt / mt) -targeting protein complexes, including caseinolytic protease (ClpP), ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo), oxidative phosphorylation system (OXPHOS), DNA recombination, replication, and repair (DNA-RRR) system, and pentatricopeptide repeat (PPR) proteins, to identify evolutionary drivers for cytonuclear interaction., Results: The severity of gene loss of N-pt PPR and pt-RRR genes was positively associated with increased degree of heterotrophy in full mycoheterotrophs and S. himalayana, while N-mt PPR and mt-RRR genes were retained. Substitution rates of organellar and nuclear genes encoding N-pt/mt subunits in protein complexes were evaluated, cytonuclear coevolution was identified in S. himalayana, whereas disproportionate rates of evolution were observed in the OXPHOS complex in full mycoheterotrophs, only slight accelerations in substitution rates were identified in N-mt genes of full mycoheterotrophs., Conclusions: Nuclear compensatory evolution was identified in protein complexes encoded by plastid and N-pt genes. Selection shaping codon preferences, functional constraint, mt-RRR gene regulation, and post-transcriptional regulation of PPR genes all facilitate mito-nuclear evolution. Our study enriches our understanding of genomic coevolution scenarios in fully heterotrophic plants., (© 2024. The Author(s).)

Background: Malaria-associated acute lung injury/acute respiratory distress syndrome (MA-ALI/ARDS) is a fatal complication of Plasmodium falciparum infection that is partially triggered by macrophage recruitment and polarization. As reported, copper exposure increases the risk of malaria infection, and copper accumulation-induced cuproptosis triggers M1 macrophage polarization. It is thus hypothesized that cuproptosis could act as a critical mediator in the pathogenesis of MA-ALI/ARDS, but its underlying mechanism remains unclear. The present study aimed to explore the role of cuproptosis in the severity of murine MA-ALI/ARDS., Methods: We utilized an experimental model of MA-ALI/ARDS using female C57BL/6 mice with P. berghei ANKA infection, and treated these animals with the potent copper ion carrier disulfiram (DSF) or copper ion chelator tetrathiomolybdate (TTM). The RAW 264.7 macrophages, which were stimulated with infected red blood cells (iRBCs) in vitro, were also targeted with DSF-CuCl 2 or TTM-CuCl 2 to further investigate the underlying mechanism., Results: Our findings showed a dramatic elevation in the amount of copper and the expression of SLC31A1 (a copper influx transporter) and FDX1 (a key positive regulator of cuproptosis) but displayed a notable reduction in the expression of ATP7A (a copper efflux transporter) in the lung tissue of experimental MA-ALI/ARDS mice. Compared to the P. berghei ANKA-infected control group, mice that were administered DSF exhibited a remarkable increase in parasitemia/lung parasite burden, total protein concentrations in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, vascular leakage, and pathological changes in lung tissue. Strikingly, the experimental MA-ALI/ARDS mice with DSF treatment also demonstrated dramatically elevated copper levels, expression of SLC31A1 and FDX1, numbers of CD86 + , CD68 + , SLC31A1 + -CD68 + , and FDX1 + -CD68 + macrophages, and messenger RNA (mRNA) levels of pro-inflammatory cytokines (tumor necrosis factor [TNF-α] and inducible nitric oxide synthase [iNOS]) in lung tissue, but showed a remarkable decrease in body weight, survival time, expression of ATP7A, number of CD206 + macrophages, and mRNA levels of anti-inflammatory cytokines (transforming growth factor beta [TGF-β] and interleukin 10 [IL-10]). In contrast, TTM treatment reversed these changes in the infected mice. Similarly, the in vitro experiment showed a notable elevation in the mRNA levels of SLC31A1, FDX1, CD86, TNF-α, and iNOS in iRBC-stimulated RAW 264.7 cells targeted with DSF-CuCl 2 , but triggered a remarkable decline in the mRNA levels of ATP7A, CD206, TGF-β, and IL-10. In contrast, TTM-CuCl 2 treatment also reversed these trends in the iRBC-stimulated RAW 264.7 cells., Conclusions: Our data demonstrate that the activation of cuproptosis with DSF aggravated the severity of MA-ALI/ARDS by partially inducing M1 polarization of pulmonary macrophages, while inhibition of cuproptosis with TTM contrarily ameliorated the severity of MA-ALI/ARDS by promoting macrophage M2 polarization. Our findings suggest that blockage of cuproptosis could be a potential therapeutic strategy for treatment of MA-ALI/ARDS., (© 2024. The Author(s).)

Background: Neoadjuvant chemotherapy (NAC) for breast cancer enables pathological complete response (pCR) in patients initially diagnosed with axillary lymph node metastases, potentially obviating the need for axillary lymph node dissection (ALND). Current targeted axillary dissection (TAD) techniques, guided by traditional tissue markers placed prior to NAC, face challenges such as marker loss and high costs. Carbon nanoparticle suspension injection (CNSI) offers a stable and reliable alternative for marking, which could enhance the TAD procedure. This study aims to evaluate the feasibility and accuracy of different TAD strategies using CNSIs and to explore their clinical utility in locally advanced breast cancer., Methods: This prospective, multicenter, randomized controlled trial will enroll 126 biopsy-proven breast cancer patients with suspicious axillary lymph node metastases (cN1-2a) who achieve ycN0 status following NAC. Participants will be randomized in a 1:1:1 ratio to undergo TAD guided by: [1] conventional tissue clips (CG-TAD); [2] CNSI lymph node marking (CN-LNM); or [3] peritumoral CNSI mapping (PCN-MAP). Primary endpoints include retrieval rate of marked lymph nodes, number of sentinel and marked lymph nodes, concordance rates, and complication rates. Secondary endpoints encompass regional and distant recurrence rates, survival outcomes, surgical duration, postoperative complications, quality of life scores, and margin status in breast-conserving surgery. Statistical analyses will adhere strictly to the CONSORT guidelines., Discussion: This study aims to evaluate the feasibility and accuracy of CNSI for targeted axillary dissection in breast cancer patients following neoadjuvant chemotherapy and to explore its clinical significance in reducing surgical complications and costs, as well as improving surgical precision., Trial Registration: Clinicaltrials.gov, NCT04744506, Registered 27 December 2020, Updated 24 September 2024. Protocol Version Ver 1.2, 17/9/2024., (© 2024. The Author(s).)

Background: In the domain of forensic science, the application of kinship identification and mixture deconvolution techniques are of critical importance, providing robust scientific evidence for the resolution of complex cases. Microhaplotypes, as the emerging class of genetic markers, have been widely studied in forensics due to their high polymorphisms and excellent stability., Results and Discussion: In this research, a novel and high-efficient panel integrating 33 microhaplotype loci along with a sex-determining locus was developed by the next generation sequencing technology. In addition, we also assessed its forensic utility and delved into its capacity for kinship analysis and mixture deconvolution. The average effective number of alleles (Ae) of the 33 microhaplotype loci in the Guizhou Han population was 6.06, and the Ae values of 30 loci were greater than 5. The cumulative power of discrimination and cumulative power of exclusion values of the novel panel in the Guizhou Han population were 1-5.6 × 10 - 43 and 1-1.6 × 10 - 15 , respectively. In the simulated kinship analysis, the panel could effectively distinguish between parent-child, full-sibling, half-sibling, grandfather-grandson, aunt-nephew and unrelated individuals, but uncertainty rates clearly increased when distinguishing between first cousins and unrelated individuals. For the mixtures, the novel panel had demonstrated excellent performance in estimating the number of contributors of mixtures with 1 to 5 contributors in combination with the machine learning methods., Conclusions: In summary, we have developed a small and high-efficient panel for forensic genetics, which could provide novel insights into forensic complex kinships testing and mixture deconvolution., (© 2024. The Author(s).)

Background: 11β-hydroxylase deficiency (11β-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11β-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11β-OHD., Methods: Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants., Results: Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM&#95;000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269-143,957,579 (hg19) with the insertion of 'ACAG' (NM&#95;000497.4:c.954 + 78&#95;980delinsACAG), which was in trans with CYP11B1: c.281 C > T., Conclusions: Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11β-OHD genetic diagnosis and carrier sequencing., (© 2024. The Author(s).)

Background: Whole genome sequencing (WGS) is becoming increasingly prevalent for molecular diagnosis, staging and prognosis because of its declining costs and the ability to detect nearly all genes associated with a patient's disease. The currently widely accepted variant calling pipeline, GATK, is limited in terms of its computational speed and efficiency, which cannot meet the growing analysis needs., Results: Here, we propose a fast and accurate DNASeq variant calling workflow that is purely composed of tools from LUSH toolkit. The precision and recall measurements indicate that both the LUSH and GATK pipelines exhibit high levels of consistency, with precision and recall rates exceeding 99% on the 30x NA12878 dataset. In terms of processing speed, the LUSH pipeline outperforms the GATK pipeline, completing 30x WGS data analysis in just 1.6 h, which is approximately 17 times faster than GATK. Notably, the LUSH&#95;HC tool completes the processing from BAM to VCF in just 12 min, which is around 76 times faster than GATK., Conclusion: These findings suggest that the LUSH pipeline is a highly promising alternative to the GATK pipeline for WGS data analysis, with the potential to significantly improve bedside analysis of acutely ill patients, large-scale cohort data analysis, and high-throughput variant calling in crop breeding programs. Furthermore, the LUSH pipeline is highly scalable and easily deployable, allowing it to be readily applied to various scenarios such as clinical diagnosis and genomic research., (© 2024. The Author(s).)

Background: The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk., Methods: We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups., Results: Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for "CC" started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort., Conclusion: The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice., (© 2024. The Author(s).)

Background: Ochratoxin A (OTA) is a toxin widely found in aquafeed ingredients, and hypoxia is a common problem in fish farming. In practice, aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA, but no studies exist in this area. This research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin (CUR)., Methods: A total of 720 healthy juvenile grass carp (11.06 ± 0.05 g) were selected and assigned randomly to 4 experimental groups: control group (without OTA and CUR), 1.2 mg/kg OTA group, 400 mg/kg CUR group, and 1.2 mg/kg OTA + 400 mg/kg CUR group with three replicates each for 60 d. Subsequently, 32 fish were selected, divided into normoxia (18 fish) and hypoxia (18 fish) groups, and subjected to hypoxia stress for 96 h., Results: CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacuolation and nuclear excursion. The alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3, 8, 9, Bax, and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2, and attenuation of endoplasmic reticulum stress (ERS) by reducing Grp78 expression and chop levels. This may be attributed to the fact that the addition of CUR increased the levels of catalase (CAT) and glutathione reductase (GSH), increased antioxidant capacity, and ensured the proper functioning of respiratory chain complexes I and II, which in turn reduced the high production of reactive oxygen species (ROS), thus alleviating apoptosis and ERS., Conclusions: In conclusion, our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and hypoxia. This study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals., (© 2024. The Author(s).)

Aim: This study aimed to compile data on the effectiveness of music therapy for patients undergoing cardiothoracic surgery., Background: After cardiac and thoracic surgery, patients often experience physiological and psychological complications, such as anxiety, pain, stress, depression and changes in vital signs, which have a great impact on prognosis., Methods: A systematic search of six databases was performed to identify randomized controlled trials investigating music therapy and cardiothoracic surgery. The data were extracted from the qualified research, the data without heterogeneity were analysed by random-effects model (REM) meta-analysis, and the data with heterogeneity were analysed by fixed-effects model (FEM) meta-analysis. We evaluated anxiety, pain, duration of mechanical ventilation, hospital length of stay, stress hormones, opioid consumption, and vital signs, including heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), diastolic blood pressure (DBP), and systolic blood pressure (SBP) after cardiothoracic surgery. The meta-analysis and sensitivity analysis were performed with RevMan 5.4 and Stata 14 software, and trial sequential analysis was conducted using TSA 0.9.5.10 Beta software. This study was conducted in accordance with the PRISMA guidelines and was registered with PROSPERO., Results: The study included 24 randomized controlled trials with a total of 1576 patients. Our analysis showed that music therapy can significantly reduce the anxiety scores (SMD= -0.74, 95% CI [-0.96, -0.53], p < 0.01) and pain scores (SMD= -1.21, 95% CI [-1.78, -0.65], p < 0.01) of patients after cardiothoracic surgery. Compared with the control group, music therapy dramatically raised postoperative SpO2 (SMD = 0.75, 95% CI [0.11, 1.39], p = 0.02). In addition, the experimental group had significant statistical significance in reducing HR, SBP and opioid consumption. However, there was no significant difference in respiratory rate, stress hormones, diastolic blood pressure, length of hospital stay, or the duration of mechanical ventilation between the two groups., Conclusions: Music therapy can significantly reduce anxiety, pain, HR, SBP, and postoperative opioid use and even improve SpO2 in patients who undergo cardiothoracic surgery. Music therapy has a positive effect on patients after cardiothoracic surgery with few side effects, so it is promising for use in clinics., Trial Registration: RROSPERO (registration number: CRD42023424602)., (© 2024. The Author(s).)

Background: Cardiac maladaptive remodeling is one of the leading causes of heart failure with highly complicated pathogeneses. The E3 ligase tripartite motif containing 35 (TRIM35) has been identified as a crucial regulator governing cellular growth, immune responses, and metabolism. Nonetheless, the role of TRIM35 in fibroblasts in cardiac remodeling remains elusive., Methods: Heart tissues from human donors were used to verify tissue-specific expression of TRIM35. Fibroblast-specific Trim35 gene knockout mice (Trim35 cKO ) were used to investigate the function of TRIM35 in fibroblasts. Cardiac function, morphology, and molecular changes in the heart tissues were analyzed after transverse aortic constriction (TAC) surgery. The mechanisms by which TRIM35 regulates fibroblast phenotypes were elucidated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA sequencing (RNA-Seq). These findings were further validated through the use of adenoviral and adeno-associated viral transfection systems, as well as the mTORC1 inhibitor Rapamycin., Results: TRIM35 expression is primarily up-regulated in cardiac fibroblasts in both murine and human fibrotic hearts, and responds to TGF-β1 stimulation. Specific deletion of TRIM35 in cardiac fibroblasts significantly improves cardiac fibrosis and hypertrophy. Consistently, the overexpression of TRIM35 promotes fibroblast proliferation, migration, and differentiation. Through paracrine signaling, it induces hypertrophic growth of cardiomyocytes. Mechanistically, we found that TRIM35 interacts with, ubiquitinates, and up-regulates the amino acid transporter SLC7A5, which enhances amino acid transport and activates the mTORC1 signaling pathway. Furthermore, overexpression of SLC7A5 significantly reverses the reduced cardiac fibrosis and hypertrophy caused by conditional knockout of TRIM35., Conclusion: Our findings demonstrate a novel role of fibroblast-TRIM35 in cardiac remodeling and uncover the mechanism underlying SLC7A5-mediated amino acid transport and mTORC1 activation. These results provide a potential novel therapeutic target for treating cardiac remodeling., (© 2024. The Author(s).)

Background: This study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients., Methods: Data from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2-3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics., Results: Admission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95% CI: 0.706-0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958-1.084, p = 0.552). In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality compared with those SBP ≤ 120mmHg (adjusted HR: 0.653; 95% CI: 0.495-0.862; p = 0.003). In addition, subgroups analysis with Killip class I-II showed SBP ≤ 120mmHg was still associated with increased risk of mortality., Conclusion: The present study revealed admission SBP above 120 mmHg was associated with higher SR,30-d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment., Trial Registration: ClinicalTrials.gov (NCT04996901), 07/27/2021., (© 2024. The Author(s).)

Background: Base excess (BE) is associated with mortality from many diseases. However, the relationship between BE and mortality in patients with ischemic stroke remains uncertain. Our aim is to investigate the relationship between BE values upon admission to the ICU and mortality rates in critically ill stroke patients., Methods: The current study enrolled 1,572 patients with ischemic stroke (863 males and 709 females). The associations of BE with intensive care unit (ICU), hospital, 28-day, and 1-year mortalities were assessed using multivariable logistic regression or Cox proportional hazards model. The potential impact of the Sequential Organ Failure Assessment (SOFA) score (< 5 or ≥ 5) on the prognostic value of BE was further evaluated with interaction and subgroup analyses., Results: BE values less than - 3 mmol/L, greater than 3 mmol/L, and within - 3 to 3 mmol/L (normal BE) were observed in 316 (20.1%), 175 (11.1%), and 1,081 (68.8%) patients, respectively. The restricted cubic splines analyses revealed that a U-shaped curve between BE and the mortality risk. Multivariable analysis indicated that patients with low BE (<-3 mmol/L) had higher rates of ICU mortality (odds ratio [OR], 1.829; 95% confidence interval [CI], 1.281-2.612; P = 0.001), hospital mortality (OR, 1.484; 95% CI, 1.077-2.045; P = 0.016), 28-day mortality (hazard ratio [HR], 1.522; 95% CI, 1.200-1.929; P = 0.001), and 1-year mortality (HR, 1.399; 95% CI, 1.148-1.705; P = 0.001) than patients with normal BE. Subgroup analyses showed consistent results pertaining to SOFA scores ≥ 5., Conclusions: In critically ill patients with ischemic stroke, an initial BE of <-3 mmol/L at ICU admission may indicate an increased risk of ICU, hospital, 28-day, and 1-year mortalities., (© 2024. The Author(s).)

Background: Renal epithelioid angiomyolipoma is a rare and unique subtype of classic angiomyolipoma, characterized by the presence of epithelioid cells. It often presents with nonspecific symptoms and can be easily misdiagnosed due to its similarity to renal cell carcinoma and classic angiomyolipoma in clinical and radiological features. This case report is significant for its demonstration of the challenges in diagnosing epithelioid angiomyolipoma and its emphasis on the importance of accurate differentiation from renal cell carcinoma and classic angiomyolipoma., Case Presentation: A 58-year-old Asian female presented with sudden left flank pain and was initially diagnosed with a malignant renal tumor based on imaging studies. She underwent laparoscopic radical nephrectomy, and postoperative histopathology confirmed the diagnosis of epithelioid angiomyolipoma. The patient recovered well and is currently in good health with regular follow-ups. This case highlights the diagnostic challenges, with a focus on the clinical, radiological, and histopathological features that eventually led to the identification of epithelioid angiomyolipoma., Conclusions: Epithelioid angiomyolipoma is easily misdiagnosed in clinical work. When dealing with these patients, it is necessary to make a comprehensive diagnosis based on clinical symptoms, imaging manifestations, and pathological characteristics., (© 2024. The Author(s).)

Background: A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS., Methods: We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups., Results: Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P < 0.001). The diagnostic yield of cryobiopsy specimens from the UTB group was significantly higher compared to the thin bronchoscope group (54.0% vs. 30.1%, respectively; p = 0.006). Univariate analysis demonstrated that the cryobiopsy diagnostic yields of the UTB group were significantly higher for lesions ≤ 20 mm, benign lesions, upper lobe lesions, lesions located lateral one-third from the hilum, and lesions without bronchus sign., Conclusions: Ultrathin bronchoscopy combined with cryobiopsy has a superior ultrasound localization rate and diagnostic yield compared to a combination of cryobiopsy and thin bronchoscopy., (© 2024. The Author(s).)

Background: As assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score's prognostic value and survival time in patients with FIGO stage IIB-IIIB cervical cancer treated with radiotherapy., Methods: In this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score's predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS)., Results: The cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54-5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52-5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis., Conclusion: The CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy., (© 2024. The Author(s).)

Background: After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders., Methods: This multi-center cohort study conducted at the Third People's Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis., Results: No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO 2 % between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO 2 % between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups., Conclusions: High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet., (© 2024. The Author(s).)

Background: Methionine (Met) is the only sulfur-containing amino acid among animal essential amino acids, and methionine deficiency (MD) causes tissue damage and cell death in animals. The common modes of cell death include apoptosis, autophagy, pyroptosis, necroptosis. However, the studies about the major modes of cell death caused by MD have not been reported, which worth further study., Methods: Primary hepatocytes from grass carp were isolated and treated with different doses of Met (0, 0.5, 1, 1.5, 2, 2.5 mmol/L) to examine the expression of apoptosis, pyroptosis, autophagy and necroptosis-related proteins. Based on this, we subsequently modeled pyroptosis using lipopolysaccharides and nigericin sodium salt, then autophagy inhibitors chloroquine (CQ), AMP-activated protein kinase (AMPK) inhibitors compound C (CC) and reactive oxygen species (ROS) scavengers N-acetyl-L-cysteine (NAC) were further used to examine the expression of proteins related to pyroptosis, autophagy and AMPK pathway in MD-treated cells respectively., Results: MD up-regulated B-cell lymphoma protein 2 (Bax), microtubule-associated protein 1 light chain 3 II (LC3 II), and down-regulated the protein expression levels of B-cell lymphoma-2 (Bcl-2), sequestosome 1 (p62), cleaved-caspase-1, cleaved-interleukin (IL)-1β, and receptor-interacting protein kinase (RIP) 1 in hepatocytes, while it did not significantly affect RIP3. In addition, MD significantly increased the protein expression of liver kinase B1 (LKB1), p-AMPK, and Unc-51-like kinase 1 (ULK1) without significant effect on p-target of rapamycin. Subsequently, the use of CQ increased the protein expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved-caspase-1, and cleaved-IL-1β inhibited by MD; the use of CC significantly decreased the protein expression of MD-induced LC3 II and increased the protein expression of MD-suppressed p62; then the use of NAC decreased the MD-induced p-AMPK protein expression., Conclusion: MD promoted autophagy and apoptosis, but inhibited pyroptosis and necroptosis. MD inhibited pyroptosis may be related regarding the promotion of autophagy. MD activated AMPK by inducing ROS production which in turn promoted autophagy. These results could provide partial theoretical basis for the possible mechanisms of Met in ensuring the normal structure and function of animal organs. Furthermore, ferroptosis is closely related to redox states, it is worth investigating whether MD affects ferroptosis in hepatocytes., (© 2024. The Author(s).)

Objective: This Study aims to investigate the risk factors of hypoglycemia in neonates through meta-analysis., Method: PubMed, Embase, Cochrane library, and Web of science databases were searched for case-control studies on risk factors for neonatal hypoglycemia. The search was done up to 1st October 2023 and Stata 15.0 was used for data analysis., Results: A total of 12 published studies were included, including 991 neonates in the hypoglycemic group and 4388 neonates in the non-hypoglycemic group. Meta-analysis results suggested caesarean section [OR = 1.90 95%CI (1.23, 2.92)], small gestational age[OR = 2.88, 95%CI (1.59, 5.20)], gestational diabetes [OR = 1.65, 95%CI (1.11, 2.46)], gestational hypertension[OR = 2,79, 95%CI (1.78, 4.35)] and respiratory distress syndrome[OR = 5.33, 95%CI (2.22, 12.84)] were risk factors for neonatal hypoglycemia., Conclusion: Based on the current study, we found that caesarean section, small gestational age, gestational diabetes, gestational hypertension, respiratory distress syndrome are risk factors for neonatal hypoglycemia., Prospero Registration Number: CRD42023472974., (© 2024. The Author(s).)

Objective: Tongue squamous cell carcinoma (TSCC) accounts for 43.4% of oral cancers in China and has a poor prognosis. This study aimed to explore whether radiomics features extracted from preoperative magnetic resonance imaging (MRI) could predict overall survival (OS) in patients with TSCC., Methods: The clinical imaging data of 232 patients with pathologically confirmed TSCC at Xiangyang No. 1 People's Hospital were retrospectively analyzed from February 2010 to October 2022. Based on 2-10 years of follow-up, patients were categorized into two groups: control (healthy survival, n = 148) and research (adverse events: recurrence or metastasis-related death, n = 84). A training and a test set were established using a 7:3 ratio and a time node. Radiomics features were extracted from axial T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging (DWI) sequences. The corresponding radiomics scores were generated using the least absolute shrinkage and selection operator algorithm. Kaplan-Meier and multivariate Cox regression analyses were used to screen for independent factors affecting adverse events in patients with TSCC using clinical and pathological results. A novel nomogram was established to predict the probability of adverse events and OS in patients with TSCC., Results: The incidence of adverse events within 2-10 years after surgery was 36.21%. Kaplan-Meier analysis revealed that hot pot consumption, betel nut chewing, platelet-lymphocyte ratio, drug use, neutrophil-lymphocyte ratio, Radscore, and other factors impacted TSCC survival. Multivariate Cox regression analysis revealed that the clinical stage (P < 0.001), hot pot consumption (P < 0.001), Radscore 1 (P = 0.01), and Radscore 2 (P < 0.001) were independent factors affecting TSCC-OS. The same result was validated by the XGBoost algorithm. The nomogram based on the aforementioned factors exhibited good discrimination (C-index 0.86/0.81) and calibration (P > 0.05) in the training and test sets, accurately predicting the risk of adverse events and survival., Conclusion: The nomogram constructed using clinical data and MRI radiomics parameters may accurately predict TSCC-OS noninvasively, thereby assisting clinicians in promptly modifying treatment strategies to improve patient prognosis., (© 2024. The Author(s).)

Background: Depression represents a frequent mental health challenge in individuals with fractures, negatively impacting their recuperation and overall well-being. The purpose of this research was to formulate and corroborate a prognostic framework for pinpointing depression risk among fracture sufferers by utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020 and a separate hospital-based group., Methods: We analyzed records from 1,748 individuals with fractures documented in the NHANES database spanning 2005 to 2020, of which 362 were diagnosed with depression, as indicated by a Patient Health Questionnaire-9 (PHQ-9) score of 10 or higher. An additional validation group comprised 360 fracture patients sourced from a medical center. Considered variables for prediction encompassed demographic details, lifestyle habits, past medical conditions, and laboratory results. The method of least absolute shrinkage and selection operator (LASSO) regression facilitated the narrowing down of variables, while multivariate logistic regression was employed to pinpoint significant predictors. To assist in prediction, a nomogram was designed and subsequently validated., Results: Five independent predictors were identified: drinking, insomnia, poverty-to-income ratio, education level, and white blood cell count. The nomogram showed good discrimination in the NHANES cohorts (training area under the curve (AUC) 0.734, validation AUC 0.740) and hospital-based external validation (AUC 0.711). Calibration curves and decision analysis supported its predictive accuracy and clinical value., Conclusion: The constructed nomogram offers a precise and clinically relevant instrument for forecasting depression risk in patients with fractures, facilitating the early detection of individuals at high risk and enabling prompt intervention., (© 2024. The Author(s).)

Objectives: To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive., Methods: Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05)., Results: The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na., Conclusions: The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive., (© 2024. The Author(s).)

Background: Osteoarthritis is a prevalent musculoskeletal condition, but the role of specific serum biomarkers, such as calcium, vitamin D, and C-reactive protein (CRP), in predicting mortality among individuals with osteoarthritis remains unclear., Methods: This observational study analyzed longitudinal data from over 500,000 participants in the UK Biobank, identifying those with osteoarthritis using ICD-9/10 codes or self-reported history. We performed multivariable cox-regression and flexible parametric survival model (FPSM) for survival analysis, with adjustments made through the inverse probability of treatment weight (IPTW) for baseline covariates identified by directed acyclic graphs (DAGs)., Results: Of the 49,082 osteoarthritis population, the average age was 60.69 years, with 58.7% being female. During the follow-up period exceeding 15 years, a total of 5,522 people with osteoarthritis died. High serum calcium levels, compared to normal serum calcium levels, were significantly associated with all-cause mortality (hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11, 1.59), cardiovascular diseases (CVD)-related deaths (HR 1.55, 95% CI 1.05, 2.29), and other deaths (HR 1.59, 95% CI 1.20, 2.11). Low serum calcium levels, compared to normal serum calcium levels, was linked with CVD-related deaths (HR 2.06, 95% CI 1.02, 4.14). Vitamin D insufficiency, compared to sufficient vitamin D levels, was correlated with all-cause mortality (HR 1.22, 95% CI 1.13, 1.33), CVD-related deaths (HR 1.43, 95% CI 1.20, 1.72), and other deaths (HR 1.26, 95% CI 1.09, 1.45) but not with cancer-related deaths. High serum CRP levels, compared to normal CRP levels, were associated with all outcomes (all-cause mortality: HR 1.22, 95% CI 1.12, 1.33; CVD-related death: HR 1.24, 95%CI 1.03, 1.49; cancer-related death: HR 1.23, 95% CI 1.09, 1.40; other deaths: HR 1.19, 95%CI 1.03, 1.38)., Conclusions: Both high and low serum calcium levels, elevated CRP, and vitamin D insufficiency are potential predictors of increased mortality risk in the osteoarthritis population. These findings emphasize the importance of monitoring and possibly addressing these serum biomarkers in osteoarthritis populations to improve long-term outcomes. Further studies are needed to understand the underlying mechanisms and to propose therapeutic interventions., (© 2024. The Author(s).)

Backgroud: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes., Methods: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes., Results: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed., Conclusions: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P., (© 2024. The Author(s).)

Objectives: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +)., Methods: The triage performance of liquid-based cytology (LBC) and the PAX1 m /JAM3 m test for detecting CIN3 + were compared., Results: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1 m /JAM3 m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1 m /JAM3 m ( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1 m /JAM3 m (+). Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1 m /JAM3 m (+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1 m /JAM3 m (+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%)., Conclusions: In non-16/18 hrHPV(+) women, PAX1 m /JAM3 m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity., (© 2024. The Author(s).)

Background: Necrotizing enterocolitis (NEC) is a complex disease characterized by gastrointestinal inflammation and is one of the most common gastrointestinal emergencies in neonates. Mild to moderate cases of NEC require medical treatment, whereas severe cases necessitate surgical intervention. However, evidence for surgical indications is limited and largely dependent on the surgeon's experience, leading to variability in outcomes. The primary aim of this study is to identify the risk factors for surgical intervention in neonatal NEC, which will aid in predicting the optimal timing for surgical intervention., Methods: A literature search was conducted in PubMed, Embase, and Web of Science databases for case-control studies exploring risk factors for NEC requiring surgical intervention. The search was completed on June 16, 2024, and data analysis was performed using R Studio 4.3.2., Results: 18 studies were included, comprising 1,104 cases in the surgery group and 1,686 in the medical treatment group. The meta-analysis indicated that high C-reactive protein (CRP) levels [OR = 1.42, 95% CI (1.01, 1.99)], lower gestational age [OR = 0.52, 95% CI (0.3, 0.91)], sepsis [OR = 2.94, 95% CI (1.87, 4.60)], coagulation disorder [OR = 3.45, 95% CI (1.81, 6.58)], lack of enteral feeding [OR = 3.18, 95% CI (1.37, 7.35)], and hyponatremia [OR = 1.22, 95% CI (1.07, 1.39)] are significant risk factors for surgical treatment in neonatal NEC., Conclusions: High CRP levels, coagulation disorders, sepsis, lower gestational age, lack of enteral feeding, and hyponatremia are significant risk factors for surgical intervention in neonatal NEC. These findings have potential clinical significance for predicting surgical risk., (© 2024. The Author(s).)

Background: Glioblastoma is characterized by high aggressiveness, frequent recurrence, and poor prognosis. Histone acetylation-associated genes have been implicated in its occurrence and development, yet their predictive ability in glioblastoma prognosis remains unclear., Results: This study constructs a histone acetylation risk model using Cox and LASSO regression analyses to evaluate glioblastoma prognosis. We assessed the model's prognostic ability with univariate and multivariate Cox regression analyses. Additionally, immune infiltration was evaluated using ESTIMATE and TIMER algorithms, and the SubMAP algorithm was utilized to predict responses to CTLA4 inhibitor. Multiple drug databases were applied to assess drug sensitivity in high- and low-risk groups. Our results indicate that the histone acetylation risk model is independent and reliable in predicting prognosis., Conclusions: Low-risk patients showed higher immune activity and longer overall survival, suggesting anti-CTLA4 immunotherapy suitability, while high-risk patients might benefit more from chemotherapy. This model could guide personalized therapy selection for glioblastoma patients., (© 2024. The Author(s).)

Objective: This study aimed to investigate the serum levels of neuron-specific enolase (NSE) in sepsis-associated encephalopathy (SAE) and perform a meta-analysis to assess the diagnostic and prognostic potential of serum NSE in SAE patients., Methods: We searched English and Chinese databases for studies related to SAE that reported serum NSE levels until November 2023. We extracted information from these studies including the first author and year of publication, the number of samples, the gender and age of patients, the collection time of blood samples in patients, the assay method of serum NSE, the study methods, and the levels of serum NSE with units of ng/mL. The quality assessment of diagnostic accuracy studies 2 (QUADAS-2) tool was used to evaluate the study quality. A meta-analysis was performed using Review Manager version 5.3, employing either a random effects model or a fixed effects model., Results: A total of 17 studies were included in the final meta-analysis, including 682 SAE patients and 946 NE patients. The meta-analysis demonstrated significantly higher serum NSE levels in SAE patients compared to NE patients (Z = 5.97, P < 0.001, MD = 7.79, 95%CI 5.23-10.34), irrespective of the method used for serum NSE detection (Z = 6.15, P < 0.001, mean difference [MD] = 7.75, 95%CI 5.28-10.22) and the study methods (Z = 5.97, P < 0.001, MD = 7.79, 95%CI 5.23-10.34). Furthermore, sepsis patients with a favorable outcome showed significantly lower levels of serum NSE compared to those with an unfavorable outcome (death or adverse neurological outcomes) (Z = 5.44, P < 0.001, MD = - 5.34, 95%CI - 7.26-3.42)., Conclusion: The Serum level of NSE in SAE patients was significantly higher than that in septic patients without encephalopathy. The higher the serum NSE level in SAE patients, the higher their mortality rate and incidence of adverse neurological outcomes., (© 2024. The Author(s).)

Background: To identify the sensitivity, specificity, and overall diagnostic accuracy of infrared thermography in diagnosing lumbosacral radicular pain., Methods: Patients sequentially presenting with lower extremity pain were enrolled. A clinical certainty score ranging from 0 to 10 was used to assess the likelihood of lumbosacral radicular pain, with higher scores indicating higher likelihood. Infrared Thermography scans were performed and the temperature difference (ΔT) was calculated as ΔT = T1 - T2, where T2 represents the skin temperature of the most painful area on the affected limb and T1 represents the skin temperature of the same area on the unaffected limb. Upon discharge from the hospital, two independent doctors diagnosed lumbosacral radicular pain based on intraoperative findings, surgical effectiveness, and medical records., Results: A total of 162 patients were included in the study, with the adjudicated golden standard diagnosis revealing that 101 (62%) patients had lumbosacral radicular pain, while the lower extremity pain in 61 patients was attributed to other diseases. The optimal diagnostic value for ΔT was identified to fall between 0.8℃ and 2.2℃, with a corresponding diagnostic accuracy, sensitivity, and specificity of 80%, 89%, and 66% respectively. The diagnostic accuracy, sensitivity, and specificity for the clinical certainty score were reported as 69%, 62%, and 79% respectively. Combining the clinical certainty score with ΔT yielded a diagnostic accuracy, sensitivity, and specificity of 84%, 77%, and 88% respectively., Conclusion: Infrared thermography proves to be a highly sensitive tool for diagnosing lumbosacral radicular pain. It offers additional diagnostic value in cases where general clinical evaluation may not provide conclusive results., Trial Registration: ChiCTR2300078786, 19/22/2023., (© 2024. The Author(s).)

Background: This study aims to explore the bidirectional causal relationship between immune cell phenotypes and chronic periodontitis using a Mendelian randomization framework., Materials and Methods: Through a two-sample Mendelian randomization analysis, this research examined genetic data related to 731 immune cell traits and chronic periodontitis. Instrumental variables were chosen based on their genetic links to either immune traits or periodontitis. Various statistical techniques, including MR-Egger regression, weighted median, and inverse-variance weighted (IVW) analysis, were employed to determine the causal connections., Results: Predominantly using the IVW method, 26 distinct immune phenotypes were identified as potentially influencing periodontitis (P < 0.05). Conversely, periodontitis potentially affected 33 different immune phenotypes (P < 0.05). The results for pleiotropy and sensitivity tests were stable. However, these associations lost significance after adjusting for the False Discovery Rate., Conclusion: This study uncovers a complex bidirectional causal relationship between certain immune cell phenotypes and chronic periodontitis, underscoring the intricate interaction between the immune system and the pathogenesis of periodontal disease., (© 2024. The Author(s).)

Background: Urinary concerns increase with age impacting health and quality of life. The aims of this study were to describe: (1) urinary concerns as an age-related change (ARC); (2) the challenges of urinary concerns; (3) adaptation strategies used to manage urinary concerns; and (4) the value of engaging with aging (EWA) as a framework to promote self-management of urinary concerns., Methods: Data was used from semi-structured interviews with 29 older adults (mean age 77 years). An iterative coding process was used. A codebook was developed based on a-priori themes derived from the EWA framework, our previous publication, and a line-by-line coding of one of the transcripts. As the analysis progressed, additional codes emerged, enriching the codebook., Results: Six themes emerged: (1) the participants' experiences; (2) responses to urinary concerns, (3) adaptation and management strategies; (4) knowledge and understanding of urinary concerns; (5) available capacities and resources; and (6) the impact of the COVID-19 pandemic on urinary concerns. Participants tended to address their urinary concerns by adjusting routines, medication schedules, or diet patterns. They tried to secure restroom locations or use tools or reminders to resolve their urinary concerns. COVID-19 led to increased inconvenience for older adults to engage in outdoor activities due to the closure of public restrooms., Conclusions: Our in-depth qualitative analysis found that participants developed personalized adjustments to address their needs and abilities to their urinary concerns. These findings offer insights into the individual aging experience, which will further enhance our understanding and advancement of person-centered care., (© 2024. The Author(s).)

Background: There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity., Methods: We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity., Results: A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08]., Conclusions: This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile., (© 2024. The Author(s).)

Background: Digestive system cancers represent a significant global health challenge and are attributed to a combination of demographic and lifestyle changes. Lipidomics has emerged as a pivotal area in cancer research, suggesting that alterations in lipid metabolism are closely linked to cancer development. However, the causal relationship between specific lipid profiles and digestive system cancer risk remains unclear., Methods: Using a two-sample Mendelian randomization (MR) approach, we elucidated the causal relationships between lipidomic profiles and the risk of five types of digestive system cancer: stomach, liver, esophageal, pancreatic, and colorectal cancers. The aim of this study was to investigate the effect impact of developing lipid profiles on the risk of digestive system cancers utilizing data from public databases such as the GWAS Catalog and the UK Biobank. The inverse‒variance weighted (IVW) method and other strict MR methods were used to evaluate the potential causal links. In addition, we performed sensitivity analyses and reverse MR analyses to ensure the robustness of the results., Results: Significant causal relationships were identified between certain lipidomic traits and the risk of developing digestive system cancers. Elevated sphingomyelin (d40:1) levels were associated with a reduced risk of developing gastric cancer (odds ratio (OR) = 0.68, P < 0.001), while elevated levels of phosphatidylcholine (16:1&#95;20:4) increased the risk of developing esophageal cancer (OR = 1.31, P = 0.02). Conversely, phosphatidylcholine (18:2&#95;0:0) had a protective effect against colorectal cancer (OR = 0.86, P = 0.036). The bidirectional analysis did not suggest reverse causality between cancer risk and lipid levels. Strict MR methods demonstrated the robustness of the above causal relationships., Conclusion: Our findings underscore the significant causal relationships between specific lipidomic traits and the risk of developing various digestive system cancers, highlighting the potential of lipid profiles in informing cancer prevention and treatment strategies. These results reinforce the value of MR in unraveling complex lipid-cancer interactions, offering new avenues for research and clinical application., (© 2024. The Author(s).)

Background: Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China., Methods: A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies., Results: The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587-0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484-0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606-0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491-0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively)., Conclusions: These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting., (© 2024. The Author(s).)

Background: Investigating novel therapeutic strategies for colorectal cancer (CRC) is imperative. However, there is limited research on the use of drugs to target peripheral blood immune cells in this context. To address this gap, we performed a two-sample Mendelian randomization (MR) analysis to identify potential therapeutic targets for CRC., Methods: We applied two-sample MR to identify the causal relationship between peripheral blood immune cells and CRC. GWAS data were obtained from the IEU OPEN GWAS project. Based on the implications from the MR results, we conducted a comprehensive database search and genetic analysis to explore potential underlying mechanisms. We predicted miRNAs for each gene and employed extensive research for potential therapeutic applications., Results: We have identified causal associations between two peripheral immune cells and colorectal cancer. Activated & resting Treg %CD4 + cell was positively associated with the risks of CRC, while DN (CD4-CD8-) %leukocyte cell exhibited a protective role in tumor progression. NEK7 (NIMA related kinase 7) and LHX9 (LIM homeobox 9) expressed in Treg cells were positively associated with CRC risks and may play a vital role in carcinogenesis., Conclusions: This study identified causal relationship between peripheral immune cell and CRC. Treg and DN T cells were implicated to own promoting and inhibiting effects on CRC progression respectively. NEK7 and LHX9 in Treg cells were identified as potential biotarget for antitumor therapies., (© 2024. The Author(s).)

Background: The accurate prediction of pregnancy outcomes in in vitro fertilization (IVF) cycles is crucial. While several studies have been conducted on the predictive power of serum estradiol (E 2 ) and β-hCG concentrations post-embryo transfer (ET) for pregnancy outcomes, there is debate on the predictive value of E 2 . The objective of this study was to investigate the predictive efficacy of combining serum E 2 and β-hCG levels on early reproductive outcomes 12 days after embryo transfer., Methods: A total of 1521 patients with β-hCG positive values on day 12 following frozen-thawed embryo transfer (FET) with natural endometrial preparation cycles (NCs) were gathered in affiliated Women's Hospital of Jiangnan University. Using logistic regression, the relationship between pregnancy outcome and early serum E 2 and β-hCG concentrations was examined. The receiver-operating characteristic (ROC) analysis was used to assess the predictive accuracy of the serum E 2 and β-hCG concentrations., Results: Notable distinctions were observed in the serum E 2 and β-hCG levels on the twelfth day following FET with NCs between the groups classified as clinical pregnancy group (CP Group) and biochemical pregnancy group (BP Group). In addition, the cutoff values for E 2 and β-hCG on day 12 following FET with NCs in cleavage embryo group (CE Group) were 129.25 pg/mL and 156.60 mIU/mL, respectively. The threshold values for E 2 and β-hCG for the blastocyst group (B Group) were 174.45 pg/mL and 217.70 mIU/mL. Serum E 2 day12 and β-hCG day12 were found to be substantially linked with clinical pregnancy by logistic regression analysis., Conclusions: Serum E 2 and β-hCG concentrations were found to be significantly different between the CP Group and BP Group in infertility women underwent FET with NCs. Our retrospective cohort study's findings suggest that the combination of early E 2 and β-hCG levels on day 12 post-FET could be used as a predictive tool to evaluate the likelihood of both positive and negative pregnancy outcomes in FET with NCs., (© 2024. The Author(s).)

Background: There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient., Methods: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated., Results: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited., Conclusions: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings., (© 2024. The Author(s).)

Objectives: To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children., Study Design: This study retrospectively analyzed the clinical characteristics, laboratory and pathological findings, and recurrence status of children diagnosed with HNL at a single center in China from January 2018 to May 2023. Logistic regression analysis was employed to identify predictors of HNL recurrence., Results: 181 Chinese children with histopathologically confirmed HNL were enrolled (121 males and 60 females). The mean age was 9.3 ± 2.9 years. The most prominent clinical features were fever (98.9%) and cervical lymphadenopathy (98.3%). Aseptic meningitis was the most frequent complication (38.5%), while hemophagocytic lymphohistiocytosis and autoimmune disease were rare (1.7% and 1.2%, respectively). Recurrence occurred in 12.7% of patients. Erythrocyte sedimentation rate (> 30 mm/h) was the significant predictors of HNL recurrence, with odds ratios of 6.107, respectively., Conclusion: Our study demonstrates that fever and cervical lymphadenopathy are the most frequent clinical manifestations of HNL in Chinese children, which often coexist with aseptic meningitis. HNL patients with risk factors require follow-up for recurrence., (© 2024. The Author(s).)

Background: Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation., Methods: In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium., Results: Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD., Conclusions: In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted., (© 2024. The Author(s).)

Background: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety., Methods: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators., Results: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544)., Conclusion: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results., Trial Registration: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42023388860 ., (© 2024. The Author(s).)

Background: To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT)., Methods: Total of 143 EC patients in the authors' hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad&#95;score), dosiomics score (Dos&#95;score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated., Results: Models with Rad&#95;score&#95;Lung&Overlap and Dos&#95;score&#95;Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad&#95;score, and Dos&#95;score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively., Conclusion: CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT., (© 2024. The Author(s).)

Background: Continuous peripheral nerve blocks are widely used for anesthesia and postoperative analgesia in lower limb surgeries. The authors aimed to develop a novel continuous sacral plexus block procedure for analgesia during total knee arthroplasty., Methods: The study comprised two stages. In Stage I, the authors built upon previous theories and technological innovations to develop a novel continuous sacral plexus block method, ultrasound-guided continuous parasacral ischial plane block (UGCPIPB) and subsequently conducted a proof-of-concept study to assess its effectiveness and feasibility. Stage II involved a historical control study to compare clinical outcomes between patients undergoing this new procedure and those receiving the conventional procedure., Results: The study observed a 90% success rate in catheter placement. On postoperative day (POD) 1, POD2, and POD3, the median visual analog scale (VAS) scores were 3 (range, 1.5-3.5), 2.5 (1.6-3.2), and 2.7 (1.3-3.4), respectively. Furthermore, 96.3% of the catheters remained in place until POD3, as confirmed by ultrasound. The study revealed a significant increase in skin temperature and peak systolic velocity of the anterior tibial artery on the blocked side compared with those on the non-blocked side. Complications included catheter clogging in one patient and leakage at the insertion site in two patients. In Stage II, the novel technique was found to be more successful than conventional techniques, with a lower catheter displacement rate than the conventional procedure for continuous sciatic nerve block., Conclusion: UGCPIPB proved to be an effective procedure and safe for analgesia in total knee arthroplasty., Chinese Clinical Trial Registry Number: ChiCTR2300068902., (© 2024. The Author(s).)