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Yingli Wang,1,2,* Yalin Jiang,2,* Meiling Xie,1,2,* Bin Qi,2 Kunpeng Pu,2 Wenjie Du,2 Qingqing Zhang,2 Mengmeng Ma,2 Ziyong Chen,2 Yongxia Guo,2 Hui Qian,2 Kaiqin Wang,2 Tulei Tian,2 Lin Fu,3 Xiaofei Zhang2 1Bengbu Medical University Graduate School, Bengbu, Anhui, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Fu, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China, Tel +86 551 6516 7923, Email fulindev@126.com Xiaofei Zhang, Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, 236800, People’s Republic of China, Email zhangxiaofeibz@163.comBackground: Leucine-rich α-2 glycoprotein 1 (LRG1) is associated with various inflammatory lung diseases. Nevertheless, the connection between LRG1 and adult community-acquired pneumonia (CAP) individuals was still not well understood. Through a prospective cohort study, the correlations of serum LRG1 with severity and prognosis were evaluated in CAP patients.Methods: The study encompassed 327 patients who received the diagnosis of CAP. We collected fasting venous blood and clinical features. Serum LRG1 was detected by ELISA. CAP severity was assessed using various scoring systems. The prognostic outcomes were observed through follow-up visits.Results: The level of serum LRG1 at admission was gradually increased with CAP severity scores. Serum LRG1 level shown positive associations with inflammatory indices, including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Linear and logistic regression analyses suggested that serum LRG1 at admission was positively associated with severity scores and the risk of death in CAP patients. Serum LRG1 in combination with CAP severity scores significantly increased the predictive powers for severity and death compared with single serum LRG1 or severity scores.Conclusion: The study revealed positive connections of serum LRG1 levels with severity and poor prognosis in CAP patients, suggesting LRG1 partakes into the physiological processes of CAP. Serum LRG1 may be regarded as a potential biomarker in predicting the severity and death among CAP patients.Keywords: community-acquired pneumonia, LRG1, severity, outcomes, cohort study

Jie Cheng,1 Ya Liu,2 Shaojun Li,1 Kaibin Pu,1 Lin Yang,1 Liping Tan1 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of ChinaCorrespondence: Liping Tan, Tel +86-23-63630194, Email tanlp0825@hotmail.comObjective: Third-generation cephalosporin-resistant (3GC-R) bloodstream infection (BSI) is associated with poor prognosis. We investigated the incidence of and risk factors for 3GC-R Escherichia coli (E. coli) BSI in children.Methods: Patients with E. coli BSIs who were hospitalized at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for 3GC-R BSI.Results: Two hundred fifty-two children with E. coli BSIs were enrolled. The mortality rate was 11.51% (29/252). The infection rate of 3GC-R E. coli was 48.81% (123/252), and the incidence of E. coli BSI during hospitalization was 18.58 per 1000 person-days. Approximately half (47.22%, 119/252) of the children were infected with extended-spectrum beta-lactamases (ESBLs) produced by E. coli. More than one-third (37.30%, 94/252) of the children were unnecessarily administrated carbapenems. According to our logistic regression analysis, a history of carbapenem administration, an elevated Pediatric Sequential Organ Failure Assessment (pSOFA) score ≥ 2, and antimicrobial agent administration before blood culture were independently associated with 3GC-R BSI (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.08– 3.94, P=0.029; OR 2.00, 95% CI 1.10– 3.71, P=0.025, OR 1.86, 95% CI 1.02– 3.42, P=0.044, respectively).Conclusion: In this study, the incidence of 3GC-R E. coli BSI among children was retrospectively evaluated. Patients with a history of carbapenem administration, an elevated pSOFA score ≥ 2 and who were administrated antimicrobial agents before blood culture had an increased risk of 3GC-R E. coli BSI.Keywords: third-generation cephalosporin-resistant, inappropriate use of carbapenems, Escherichia coli, bloodstream infection, children

Dan Yang,1 Yongjie Yan,1 Kexue Pu1,2 1School of Medical Information, Chongqing Medical University, Chongqing, People’s Republic of China; 2Medical Data Research Institute of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Kexue Pu, Chongqing Medical University, Yuanjiagang Campus of Chongqing Medical University, No. 1 Medical College Road, Yuzhong District, Chongqing, People’s Republic of China, Tel +86 15683896497, Email pukexue@cqmu.edu.cnBackground: Allergic rhinitis (AR) is a severe and the most common chronic allergic disease, affecting 10– 40% of the world population. The effect of air pollutants on AR has been confirmed in clinical experiments.Purpose: This study aimed to quantify the association between air pollutants and daily outpatient visits for AR in Chongqing, China.Methods: Based on the data of AR outpatients in the primary urban area of Chongqing from 2016 to 2017, along with the atmospheric pollutants and meteorological data in the same period, the distributed lag nonlinear model (DLNM) and generalized additive model (GAM) were used to analyze the time-series. We examined the effects of the single and double pollutant models with a maximum lag day of 30 days. Effect estimates were described as relative risk (RR) and 95% confidence intervals (CIs) in daily outpatient visits for AR per 10 μg/m3 increases in PM2.5, PM10, SO2, NO2, O3, and per 1 mg/m3 increase in CO.Results: A single pollutant’s O3 level had an immediate positive effect on AR within two days, the relative risks (RR, 95% CI) were 1.066 (1.008– 1.127), 1.057 (1.005– 1.112) and 1.048 (1.002– 1.097). PM2.5 had a lag effect within 11– 18 days, the max relative risks (RR, 95% CI) were 1.083 (1.010– 1.160). Moreover, O3, PM2.5, PM10, SO2 and NO2 had significant effects on AR in the two-pollutant model. The RR cumulative effect of PM2.5 became more pronounced as the concentration increased. The cumulative effect of NO2 was lesser than PM2.5.Conclusion: Air pollutants were associated with the daily outpatient visits for AR, which may have considerable implications for developing tailored health policies and services to prevent AR in Chongqing and even all over the world.Keywords: allergic rhinitis, air pollution, time-series analysis, generalized additive model, distributed lag nonlinear model

[CgtA.sub.E]/[Obg.sub.E]/YhbZ is an Escherichia coli guanine nucleotide binding protein of the Obg/GTP1 subfamily whose members have been implicated in a number of cellular functions including GTP-GDP sensing, sporulation initiation, and translation. Here we describe a kinetic analysis of [CgtA.sub.E] with guanine nucleotides and show that its properties are similar to those of the Caulobacter crescentus homolog [CgtA.sub.C]. [CgtA.sub.E] binds both GTP and GDP with moderate affinity, shows high guanine nucleotide exchange rate constants for both nucleotides, and has a relatively low GTP hydrolysis rate. We show that [CgtA.sub.E] is associated predominantly with the 50S ribosomal subunit. Interestingly, [CgtA.sub.E] copurifies with SpoT, a ribosome-associated ppGpp hydrolase/synthetase involved in the stress response. The interaction between [CgtA.sub.E] and SpoT was confirmed by reciprocal coprecipitation experiments and by two-hybrid assays. These studies raise the possibility that the ribosome-associated [CgtA.sub.E] is involved in the SpoT-mediated stress response.

Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8–98.7) and 90.5% (95% CI: 81.3–95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction ( p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

Selective dorsal rhizotomy (SDR) is an effective method for the treatment of lower limb spasm, especially the advancement of intraoperative neurophysiological monitoring technology, which can make surgery more and more minimally invasive and accurate. This article reviews the surgical methods, intraoperative neurophysiological monitoring techniques, lower limb function assessment methods, surgical efficacy and postoperative complications of SDR.

Objective To investigate the optimal clinical therapy effects and prognostic factors of cerebral arteriovenous malformation (CAVM) in children following different treatment methods. Methods The clinical data of 47 children (< 18 years old) with CAVM who were admitted to Tianjin Huanhu Hospital from October 2011 to September 2022 were collected, and the multimodality treatment and prognostic factors of different grades were analyzed. Spetzler - Martin grading system and vascular nest dispersion classification were used to evaluate the risk and angiogenesis of CAVM, different treatment modalities such as microsurgery, gamma knife radiosurgery, and multi-mode therapy were used to evaluate the total resection rate, prognosis, and imaging follow-up results. Results 1) Treatment plan: among the total 47 children in this group, 35 (74.47%) received simple microsurgery, of which 10 (28.57%) suffered surgery within one week of hemorrhage, and 25 (71.43%) suffered surgery over one week; 6 (12.77%) received conservative treatment; 3 (6.38%) received gamma knife radiosurgery; 3 (6.38%) received multimodal therapy (microsurgery + interventional embolism/gamma knife radiosurgery). 2) Spetzler - Martin grading and prognosis: among the 38 patients (80.85%) of Spetzler - Martin grade Ⅰ - Ⅲ , 29 (76.32%) underwent microsurgery, one (2.63%) received multimodal therapy, and 2 (5.26%) received gamma knife radiosurgery. The total surgical resection rate was 9/9 in grade Ⅰ, 13/14 in grade Ⅱ and 6/9 in grade Ⅲ. Eight patients (21.05%) had a poor prognosis during 5 years followed-up period. There was one (2.63%) recurrence on imaging follow-up. Among 9 patients whose Spetzler-Martin grade were between Ⅳ and Ⅴ , 6 patients underwent microsurgery, 2 patients received multimodal therapy, and one received gamma knife radiosurgery. Total surgical resection rate was 4/8 in grade Ⅳ and 1/1 in grade Ⅴ, and prognosis was poor in 5 cases. 3) Diffusion classification and prognosis of malformed vascular mass: the total resection rate of dense type was 17/17, and that of diffuse type was 66.67% (16/24). The incidence of poor prognosis was 3/ 18 for dense type and 34.48% (10/29) for diffuse type. Conclusions Microsurgery resection is a relatively safe and effective method for the treatment of CAVM in children. The operation was recommended to be performed at least one week after acute hemorrhage if possible. A preoperative evaluation of surgical risks and the density of abnormal vascular clusters can assist in selecting the best treatment plan, thus could increase the total resection rate of lesions and improve the prognosis.

Cerebral cavernous malformation is the second most common vascular malformation of the central nervous system. The main clinical manifestations in children include epileptic seizure, spontaneous cerebral hemorrhage, and focal neurological deficits. The lesions are mostly single or multiple, most of which were detected incidentally. MRI has a high discrimination of cerebral cavernous malformation and is the imaging modality of choice for it. However, the pathogenesis has not been elucidated and the treatment methods still lack summary. This paper reviews the clinical characteristics and pathogenesis of cerebral cavernous malformation in children, involved clinical characteristics, imaging features, potential pathogenesis and treatment methods, to deepen the understanding of cerebral cavernous malformation for further individual treatment.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV). As an RNA virus, there are extensive variations in the genome of PRRSV, of which NSP2 and ORF5 genes are predominant. As the strains of different lineages have characteristic nucleotide sequences in ORF5, ORF5 can be used for the typing of PRRSV. ORF5 encodes the GP5 protein. GP5 protein contains multiple epitopes, which can interact with cellular receptors thus affect viral infection and replication. In recent years, molecular epidemiological investigations on PRRSV tend to reveal amino acid mutations unique to different strains. These mutations usually occur in the signal peptide coding region, non-neutralizing epitope, neutralizing epitope and transmembrane region of GP5 protein. Therefore, some studies have correlated these mutation data with the virulence and neutralization capacity of the virus. Some researchers tried to speculate about the conformational or functional changes in GP5 protein by mutation and explain this link from the structural basis of protein interaction. The tertiary structure of GP5 cannot be observed by traditional high-resolution cryo-EM and X-ray crystallography method, therefore, bioinformatics methods become the only option for related researches. In addition, GP5 can be used for the development of genetic engineering vaccines. This article reviews bioinformatics studies on GP5 protein in recent years, and summarizes the effects of GP5 protein on virus infection, replication, virulence and neutralization as well as the performance evaluation of GP5-based genetic engineering vaccines.

BackgroundThe use of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA) has long been considered the standard regimen for preventing chemotherapy-induced nausea and vomiting (CINV) prior to hematopoietic stem cell transplantation (HSCT). However, their therapeutic outcomes have been unsatisfactory. NEPA, an oral formulation combining the neurokinin-1 receptor antagonist netupitant and the 5HT3RA palonosetron, has received regulatory approval for the management of highly and moderately emetogenic chemotherapy. This study aims to compare the efficacy of NEPA with that of 5HT3RA alone in preventing CINV among patients undergoing multiday conditioning chemotherapy prior to HSCT.Patients and methodsWe conducted a retrospective analysis of patients who underwent HSCT between September 2019 and September 2022. Efficacy outcomes were assessed based on the rates of patients achieving complete response (CR: no emesis and no use of rescue medication), complete control (CC: CR without significant nausea), no vomiting, and no significant nausea.ResultsThe NEPA group consisted of 106 patients, while the 5HT3RA group included 107 patients. The NEPA group exhibited significantly higher rates of CR compared to the 5HT3RA group during the overall phase (71.7% vs. 32.7%, P

BackgroundThe prognosis of patients with peripheral T-cell (PTCL) or lymphoblastic T-cell lymphoma (T-LBL) remains poor under current conditioning regimens before receiving autologous stem cell transplantation (ASCT).MethodsPatients with PTCL or T-LBL were enrolled to receive ASCT using the conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Positron emission tomography-computed tomography (PET/CT) was used to evaluate the response to ASCT. Overall survival (OS) and progression-free survival (PFS) were employed to assess the patient outcome, and adverse events were used to assess the regimen’s safety. The survival curve was estimated via the Kaplan-Meier method.ResultsTwenty-five PTCL and 11 T-LBL patients were recruited. The median time to neutrophile and platelet engraftments was 10 days (8–13 days) and 13 days (9–31 days), respectively. The 3-year PFS and OS were 81.3 ± 7.2% and 88.5 ± 5.4% for all patients; 92.0 ± 5.4% and 81.2 ± 8.8% for PTCL patients; and both 81.8 ± 11.6% for T-LBL patients, respectively. The 3-year PFS and OS were both 92.9 ± 4.9% for patients with complete response (CR) but 50.0 ± 17.7% and 75.0 ± 15.3% for patients with non-CR, respectively. Infection was the most common non-hematological toxicity, and all toxicities were mild and controllable.ConclusionsChiCGB was a potentially effective and well-tolerated conditioning regimen to improve the prognosis of patients with aggressive T-cell lymphoma. Future randomized controlled trials are needed to assess ChiCGB as a conditioning regimen for ASCT.

We report the case of a 47-year-old male patient with pigmentation of the head, face and hands, who was initially diagnosed as having primary adrenal insufficiency (Addison’s disease). Laboratory testing, imaging and physical examination revealed subclinical hypothyroidism, high circulating prolactin and oestradiol concentrations, gynaecomastia, lymphadenopathy, splenomegaly and weakness of both lower limbs. These findings led us to consider whether a single or multiple diseases were present in this patient. Indeed, Addison’s disease can represent one aspect of a wider systemic disease. Therefore, we performed further examinations, and found high serum M protein (5.1%) and vascular endothelial growth factor [1005.30 pg/mL (normal range 0 to 142 pg/mL)] concentrations. As a consequence, we diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. Consequently, when a single disease cannot fully explain the multiple symptoms and signs of one patient, clinicians should consider the possibility of the presence of a wider syndrome and undertake more detailed diagnostic testing.

Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.

CgtAE/ObgE/YhbZ is an Escherichia coli guanine nucleotide binding protein of the Obg/GTP1 subfamily whose members have been implicated in a number of cellular functions including GTP-GDP sensing, sporulation initiation, and translation. Here we describe a kinetic analysis of CgtAE with guanine nucleotides and show that its properties are similar to those of the Caulobacter crescentus homolog CgtAC. CgtAE binds both GTP and GDP with moderate affinity, shows high guanine nucleotide exchange rate constants for both nucleotides, and has a relatively low GTP hydrolysis rate. We show that CgtAE is associated predominantly with the 50S ribosomal subunit. Interestingly, CgtAE copurifies with SpoT, a ribosome-associated ppGpp hydrolase/synthetase involved in the stress response. The interaction between CgtAE and SpoT was confirmed by reciprocal coprecipitation experiments and by two-hybrid assays. These studies raise the possibility that the ribosome-associated CgtAE is involved in the SpoT-mediated stress response. [ABSTRACT FROM AUTHOR]

BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still conflicting. Hence we performed herein the meta-analysis to comprehensively assess the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to June 15, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. Nine studies with a total number of 1582 patients were eligible for this meta-analysis. Combined HRs suggested that p210 was slightly associated with inferior event-free survival (EFS) (HR = 1.34, 95% CI 1.05-1.72). The overall survival (OS) was not significantly affected (HR = 1.15, 95% CI 0.92-1.45). In subgroup analyses, the HRs showed a trend toward adverse impact of p210 on clinical outcomes. However, the confidence intervals were not crossing the null value only in a minority of subgroups including Caucasian studies, first-generation TKI treated cohort and transplant cohort. Our findings suggested that p210 might pose a mild adverse impact on the EFS of Ph+ ALL patients. This effect might be compromised by the use of second- or third-generation TKIs. Further studies are needed to verify our conclusions.

Age-related macular degeneration (AMD) is a complex multifactorial disease with a significant genetic component. Despite extensive research efforts, the underlying molecular mechanisms remain elusive, necessitating innovative approaches to identify specific genes involved in the pathogenesis of AMD and to elucidate their functional mechanisms. A transcriptome-wide association study (TWAS) was conducted by integrating eQTL data from 49 tissues of the Genotype-Tissue Expression Project (GTEx) v8 and AMD data from FinnGen R10. The Unified Test for Molecular Signatures (UTMOST) and Functional Summary-based Imputation (FUSION) were used to evaluate gene associations with AMD across tissues and within individual tissues, respectively. Multi-marker Analysis of Genomic Annotation (MAGMA) was employed to validate results and identify reliable susceptibility genes, followed by summary data-based Mendelian randomization (SMR) and colocalization analyses to explore causal associations. The cross-tissue and single-tissue TWAS analyses identified 12 reliable AMD-associated genes. MAGMA analysis confirmed 6 of these as reliable susceptibility genes. SMR analysis provided further validation of these genes, although colocalization results were not significant. This study identified six susceptibility genes associated with the risk of AMD through a cross-tissue TWAS, providing new insights into the potential systemic regulatory mechanisms underlying AMD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Hydrocephalus is a prevalent neurological disorder, particularly impactful in older adults, characterized by high incidence and numerous complications that impose a significant burden on healthcare systems. This review aims to provide a comprehensive description of hydrocephalus pathogenesis, focusing on cellular and molecular insights derived from animal models. We also present the latest advances in hydrocephalus research and highlight potential therapeutic targets. Lastly, the review advocates the integration of findings from both animal and human studies to achieve better outcomes and examines the potential of emerging technologies. We wish to raise public attention about this disease in an aging society. Current animal models for hydrocephalus involve acquired hydrocephalus models and genetic/congenital hydrocephalus models. Studies from animals have shown that the main mechanisms of models can be broadly classified into nine types. A variety of drug-targeted therapy methods and non-surgical treatment methods have been used in clinical practice. But current treatment approaches primarily focus on symptomatic relief and intracranial pressure control rather than addressing the underlying pathological mechanisms. We call for the development of more accurate and representative animal models to achieve better outcomes and examine the potential of emerging technologies, such as artificial intelligence and neuroimaging. In summary, this review synthesizes recent findings in hydrocephalus research, identifies promising therapeutic targets and interventions, and critically evaluates the limitations of current research paradigms, aiming to align preclinical studies with clinical endpoints. Continued studies and multidisciplinary collaboration are essential to develop effective interventions and facilitate new treatments into bedside.

Although photodynamic immunotherapy represents a promising therapeutic approach against malignant tumors, its efficacy is often hampered by the hypoxia and immunosuppressive conditions within the tumor microenvironment (TME) following photodynamic therapy (PDT). In this study, we report the design guidelines towards efficient Type-I semiconducting polymer photosensitizer and modify the best-performing polymer into a hypoxia-tolerant polymeric photosensitizer prodrug (HTPS Niclo ) for cancer photo-immunotherapy. HTPS Niclo not only performs Type-I PDT process to partially overcome the limitation of hypoxic tumors in PDT by recycling oxygen but also specifically releases a Signal Transducer and Activator of Transcription-3 (STAT3) inhibitor (Niclosamide) in response to a cancer biomarker in the TME. Consequently, HTPS Niclo inhibits the phosphorylation of STAT3, and suppresses the expression of hypoxia-inducible factor-1α. The synergistic effect results in the enhanced activation of immune cells (including mature dendritic cells, cytotoxic T cells) and production of immunostimulatory cytokines compared to Type-I PDT alone. Thus, HTPS Niclo -mediated photodynamic immunotherapy enhances tumor inhibition rate from 75.53% to 91.23%, prolongs the 100% survival from 39 days to 60 days as compared to Type-I PDT alone. This study not only provides the generic approach towards design of polymer-based Type-I photosensitizers but also uncovers effective strategies to counteract the immunosuppressive TME for enhanced photo-immunotherapy in 4T1 tumor bearing female BALB/c mice., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Morchella mushroom is a nutritionally rich and rare edible fungus. The traditional cultivation model, which relies on expanding the cultivation area to meet market demand, is no longer sufficient to address the rapidly growing market demand. Enhancing the yield and quality of Morchella without increasing the cultivation area is an intractable challenge in the development of the Morchella mushroom industry. Against this backdrop, this study investigates the effects of different amounts of wood ash (WA) application on the yield and quality of Morchella , and conducts an in-depth analysis in conjunction with soil physicochemical properties and microbial communities. The results indicate that the application of WA improves both the yield and quality of Morchella , with the highest yield increase observed in the WA2 treatment (4000 kg/hm 2 ), which showed a 118.36% increase compared to the control group (CK). The application of WA also modified the physicochemical properties of the soil, significantly improving the integrated fertility index of the soil (IFI, p < 0.05). The soil microbial community structure was altered by the addition of WA. Redundancy analysis (RDA) revealed that pH and total potassium (TK) were the main environmental factors influencing the bacterial community, while pH, TK, and total nitrogen (TN) were the main factors influencing the fungal community structure. In addition, bacterial community diversity tended to increase with higher WA application rates, whereas fungal community diversity generally showed a decreasing trend. Furthermore, the relative abundance of beneficial microbial communities, such as Acidobacteriota , which promote the growth of Morchella , increased with higher WA application, while the relative abundance of detrimental microbial communities, such as Xanthomonadaceae , decreased. Partial least squares path model (PLS-PM) analysis of external factors affecting Morchella yield and quality indicated that WA application can alter soil physicochemical properties and soil microbial communities, thereby improving Morchella yield and quality. Among these factors, soil fertility was identified as the most important determinant of Morchella yield and quality.

Objectives: The aim of this study is to assess cost-effectiveness of robotic radical hysterectomy (RRH) vs laparoscopic radical hysterectomy (LRH) in early-stage cervical cancer (ECC)., Design: Model-based cost-effectiveness analysis., Setting: Based on long-term survival data, a three-state Markov model was constructed using TreeAge Pro 2022 to simulate the possible recurrence of ECC. Data on clinical efficacy and costs were derived from published literature and local databases., Participants: A hypothetical cohort of 1000 individuals diagnosed with early-stage cervical cancer (FIGO 2009 stages

A rise in blood glucose is an early warning sign of underlying pancreatic cancer (PC) and may be an indicator of genetic events in PC progression. However, there is still a lack of mechanistic research on pancreatic cancer-associated new-onset diabetes (PCAND). In the present study, we identified a gene SRI, which possesses a SNP with the potential to distinguish PCAND and Type 2 diabetes mellitus (T2DM), by machine learning on the basis of the UK Biobank database. In vitro and in vivo, sorcin overexpression induced pancreatic β-cell dysfunction. Sorcin can form a positive feedback loop with STAT3 to increase the transcription of serpin E1 and CCL5, which may directly induce β-cell dysfunction. In 88 biopsies, the expression of sorcin was elevated in PC tissues, especially in PCAND samples. Furthermore, plasma serpin E1 levels are higher in peripheral blood samples from PCAND patients than in those from T2DM patients. In conclusion, sorcin may be the key driver in PCAND, and further study on the sorcin-STAT3-serpin E1/CCL5 signaling axis may help us better understand the pathogenesis of PCAND and identify potential biomarkers., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Strategies to enhance the anti-tumor immune response of stereotactic ablative radiotherapy (SABR) at primary tumors and abscopal sites are under intensive investigation. Here we report a metabolizable binary supracluster (BSC gal ) that combines gold nanoclusters as radiosensitizing adjuvants with small interfering RNA (siRNA) targeting the immunosuppressive mediator galectin-1 (Gal-1). BSC gal comprises reversibly crosslinked cationic gold nanoclusters and siRNA complexes in a polymer matrix that biodegrades over weeks, facilitating clearance (90.3% in vivo clearance at 4 weeks) to reduce toxicity. The particle size well above the renal filtration threshold facilitates passive delivery to tumors. Using mouse models of head and neck cancer, we show that BSC gal augments the radiodynamic and immunotherapeutic effects of SABR at the primary and metastatic tumors by promoting tumor-inhibitory leukocytes, upregulating cytotoxic granzyme B and reducing immunosuppressive cell populations. It outperforms SABR plus Gal-1 antagonists, chemoradiation drug cisplatin or PD-1 inhibitor. This work presents a translatable strategy to converge focal radiosensitization with targeted immune checkpoint silencing for personalized radioimmunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The rhizosphere is enriched with diverse microflora, allowing for delving prospective microorganisms to enhance crop growth and yield for varied soil conditions. Demand for millet growth-promoting microorganisms is a contemporary need for dryland agriculture. Therefore, a detailed survey was conducted in northern Karnataka, India, to identify the millet growing areas, particularly sorghum. The rhizobacteria from the sorghum ( Sorghum bicolor L.) were assessed for promoting seed germination using the paper towel method and classified based on their efficiency. The elite isolates were positive for indole-3-acetic acid (IAA), gibberellic acid (GA), phosphate, zinc oxide solubilization, and hydrogen cyanide (HCN) production. The test isolates were antagonistic to Macrophomina phaseolina and Fusarium sp. and inhibited completely. Further evaluation of the cultures on sorghum growth-promoting attributes under pot culture conditions showed that the plants inoculated with PG-152 ( Bacillus subtilis ) recorded the highest plant height, chlorophyll content, root dry weight, shoot dry weight, and total dry weight under ideal conditions of fertilization. Two isolates, namely, PG-152 and PG-197, performing superior under pot culture conditions, were identified as Bacillus subtilis and PG-197 as Enterobacter sp., respectively, using 16S rDNA analysis. The sequences were allowed to screen open reading frames (ORF) and found several ORFs in Enterobacter cloacae and Bacillus subtilis, respectively. This study found that the rhizosphere is vital for identifying prospective isolates for biocontrol and plant growth-improving microorganisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CM declared a past co-authorship with the author NY to the handling editor., (Copyright © 2024 Chiranjeevi, Goudar, PU and Yalavarthi.)

Background: Liver cancer is a significant cause of cancer-related mortality worldwide and requires tailored treatment strategies for different types. However, preoperative accurate diagnosis of the type presents a challenge. This study aims to develop an automatic diagnostic model based on multi-phase contrast-enhanced CT (CECT) images to distinguish between hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and normal individuals., Methods: We designed a Hierarchical Long Short-Term Memory (H-LSTM) model, whose core components consist of a shared image feature extractor across phases, an internal LSTM for each phase, and an external LSTM across phases. The internal LSTM aggregates features from different layers of 2D CECT images, while the external LSTM aggregates features across different phases. H-LSTM can handle incomplete phases and varying numbers of CECT image layers, making it suitable for real-world decision support scenarios. Additionally, we applied phase augmentation techniques to process multi-phase CECT images, improving the model's robustness., Results: The H-LSTM model achieved an overall average AUROC of 0.93 (0.90, 1.00) on the test dataset, with AUROC for HCC classification reaching 0.97 (0.93, 1.00) and for ICC classification reaching 0.90 (0.78, 1.00). Comprehensive validation in scenarios with incomplete phases was performed, with the H-LSTM model consistently achieving AUROC values over 0.9., Conclusion: The proposed H-LSTM model can be employed for classification tasks involving incomplete phases of CECT images in real-world scenarios, demonstrating high performance. This highlights the potential of AI-assisted systems in achieving accurate diagnosis and treatment of liver cancer. H-LSTM offers an effective solution for processing multi-phase data and provides practical value for clinical diagnostics., (© 2024. The Author(s).)

Tumor-associated macrophages have become important biomarkers for cancer diagnosis, prognosis and therapy. The dynamic changes in macrophage subpopulations significantly impact the outcomes of cancer immunotherapy. Hence, identifying additional macrophage-related biomarkers is essential for enhancing prognostic predictions in colorectal cancer (CRC) immunotherapy. CRC single-cell RNA sequencing (scRNA-seq) data was obtained from the Gene Expression Omnibus (GEO) database. The data were processed, normalized and clustered using the 'Seurat' package. Cell types within each cluster were annotated using the 'SingleR' package. Weighted gene co-expression network analysis identified modules corresponding to specific cell types. A non-negative matrix factorization algorithm was employed to segregate different clusters based on the selected module. Differentially expressed genes (DEGs) were identified across various clusters and a prognostic model was constructed using lasso regression and Cox regression analyses. The robustness of the model was validated using The Cancer Genome Atlas (TCGA) database and GEO microarrays. Additionally, the prognosis, immune characteristics and response to immune checkpoint inhibitor (ICI) therapy were individually analyzed. The scRNA-seq data from GSE200997, consisting of 23 samples, were analyzed. Dimensionality reduction and cluster identification allowed the isolation of the primary myeloid cell subpopulations. The macrophage-related brown module was identified, which was further divided into two clusters. Using the DEGs from these clusters, a prognostic model was developed, comprising five macrophage-related genes. The robustness of the model was confirmed using microarray datasets GSE17536, GSE38832 and GSE39582, as well as TCGA cohort. Patients classified as high-risk by the present model exhibited poorer survival rates, lower tumor mutation burden, reduced microsatellite instability, lower tumor purity, more severe tumor immune dysfunction and exclusion, and less benefit from ICIs therapy compared with low-risk patients. The present prognostic model shows promise as a biomarker for risk stratification and predicting therapeutic efficacy in patients with CRC. However, further well-designed prospective studies are necessary to validate the findings., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Feng et al.)

Background: Positive regulators of T-cell function (PTFRs), integral to T-cell proliferation and activation, have been identified as potential prognostic markers in colorectal cancer (CRC). Despite this, their role within the tumor microenvironment (TME) and their response to immunotherapy are not yet fully understood., Methods: This study delved into PTFR-related CRC subtypes by analyzing four independent transcriptome datasets, emphasizing the most significant prognostic PTFRs. We identified differentially expressed genes (DEGs) between two subtypes and developed a PTFR risk model using LASSO and Cox regression methods. The model's associations with survival time, clinical features, TME characteristics, tumor mutation profiles, microsatellite instability (MSI), cancer stem cell (CSC) index, and responses to chemotherapy, targeted therapy, and immunotherapy were subsequently explored., Results: The PTFR risk model demonstrated a strong predictive capacity for CRC. It facilitated the estimation of immune cell composition, HLA expression levels, immune checkpoint expression, mutation burden, CSC index features, and the effectiveness of immunotherapy., Conclusions: This study enhances our understanding of the role of PTFRs in CRC progression and introduces an innovative assessment framework for CRC immunotherapy. This framework improves the prediction of treatment outcomes and aids in the customization of therapeutic strategies., (© 2024. The Author(s).)

Low temperature combined with low light (LL) is an important factor limiting pepper quality and yield. 'Hang Jiao No. 2' were used as experimental materials, and different concentrations of MeJA (T1 (0 μM), T2 (100 μM), T3 (150 μM), T4 (200 μM), T5 (250 μM) and T6 (300 μM)) were sprayed under LL stress to explore the positive effect of exogenous methyl jasmonate (MeJA) on peppers under LL stress. The photosynthetic properties, osmoregulatory substance, reactive oxygen species, antioxidant enzyme activities, and related gene expressions of the peppers were measured. Our results demonstrated that 200 μM MeJA treatment significantly increased chlorophyll content, light quantum flux per active RC electron transfer (Eto/RC), maximum captured photonic flux per active RC (TRo/RC), energy flux for electron transfer in the excitation cross section (Eto/CSm), energy flux captured by absorption in the excitation cross section (TRo/CSm), soluble protein, and soluble sugar content. Moreover, it significantly improved the maximum photochemical efficiency of PSII (Fv/Fm) and performance index based on absorbed light energy (PI (abs)) by 56.77% and 67.00%, respectively, and significantly decreased malondialdehyde (MDA) content and relative conductivity by 30.55% and 28.17%, respectively. Additionally, antioxidant enzyme activities were elevated, and the expression of the related genes was activated in pepper seedlings under stress, leading to a significant reduction in reactive oxygen species content. In conclusion, our findings confirmed that 200 μM MeJA could reduce the injury of LL to pepper leaves to the photosynthetic organs of pepper leaves, protect the integrity of the cell membrane, and further improve the tolerance of pepper seedlings to LL.

Photocatalysis has been proven to be an excellent technology for treating antibiotic wastewater, but the impact of each active species involved in the process on antibiotic degradation is still unclear. Therefore, the S-scheme heterojunction photocatalyst Ti 3 C 2 /g-C 3 N 4 /TiO 2 was successfully synthesized using melamine and Ti 3 C 2 as precursors by a one-step calcination method using mechanical stirring and ultrasound assistance. Its formation mechanism was studied in detail through multiple characterizations and work function calculations. The heterojunction photocatalyst not only enabled it to retain active species with strong oxidation and reduction abilities, but also significantly promoted the separation and transfer of photo-generated carriers, exhibiting an excellent degradation efficiency of 94.19 % for tetracycline (TC) within 120 min. Importantly, the priority attack sites, degradation pathways, degradation intermediates and their ecological toxicity of TC under the action of each single active species (·O 2 - , h + , ·OH) were first positively explored and evaluated through design experiments, Fukui function theory calculations, HPLC-MS, Escherichia coli toxicity experiments, and ECOSAR program. The results indicated that the preferred attack sites of ·O 2 - on TC were O20, C7, C11, O21, and N25 atoms with high f + value. The toxicity of intermediates produced by ·O 2 - was also lower than those produced by h + and ·OH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population., Design: Health economic evaluation study., Setting: The data needed to construct the model for this study were derived from published studies and other secondary sources in China., Participants: No patients participated in the study., Measures: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results., Results: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (￥29 146.26 (US$4333.17) vs ￥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ￥30 703.02 (US$4564.62) vs ￥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive)., Conclusion: For the Chinese population, when the monetary value per live birth was greater than ￥65 420 (US$9726) and ￥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The associated factors of malnutrition in children with congenital heart disease (CHD) must be evaluated to provide evidence for the treatment and care of such children., Methods: Two investigators searched the PubMed database until 25 June 2023 for literature about the associated factors of malnutrition in children with CHD. A meta-analysis of associated factors of malnutrition was performed by RevMan 5.3 software., Results: Thirteen studies involving 8,031 children with CHD were included. Pulmonary hypertension (OR = 3.81, 95% CI: 2.46-4.12), low birth weight (OR = 2.69, 95% CI: 1.25-5.77) and parents' height (OR = 2.15, 95% CI: 1.89-2.92) were the associated factors of growth retardation (all P  < 0.05). Pulmonary hypertension (OR = 3.77, 95% CI: 3.13-4.24), low birth weight (OR = 3.04, 95% CI: 2.61-4.18) and pneumonia (OR = 2.35, 95% CI: 2.08-2.83) were the associated factors of low body weight of children with CHD (all P  < 0.05)., Conclusions: Medical staff should fully understand the risk factors, strengthen nutritional support and enhance nursing care for children with CHD to reduce malnutrition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Xu, Zhu, Pu and Bian.)

Objectives: The aims of this study were to screen for phagocytosis regulator-related genes in tissue samples from children with medulloblastoma (MB) and to construct a prognostic model based on those genes., Methods: Differentially expressed genes between the MB and control groups were identified using the GSE50161 dataset from the Gene Expression Omnibus database. Prognosis-related phagocytosis regulator genes were selected from the GSE85217 dataset. Intersecting genes of the two datasets (differentially expressed prognosis-related phagocytosis regulator genes) were submitted to unsupervised cluster analysis to identify disease subtypes, after which the association between the subtypes and the immune microenvironment was analyzed. A prognostic risk score model was constructed, and functional, immune-related, and drug sensitivity analyses were performed., Results: In total, 23 differentially expressed prognosis-related phagocytosis regulator genes were identified, from which two disease subtypes (clusters 1 and 2) were classified. The prognoses of the patients in cluster 2 were significantly worse than those of the patients in cluster 1. The immune microenvironment differed significantly between the two subtypes. Finally, 10 genes ( FAM81A , EZR , NDUFB9 , RCOR1 , FOXO4 , NHLRC2 , KIF23 , PTPN6 , SMAGP , and MED13 ) were selected to establish the prognostic risk score model. The prognosis in the low-risk group was better than that in the high-risk group. The model genes NDUFB9 and PTPN6 were positively correlated with M2 macrophages., Conclusion: Ten key phagocytosis regulator genes were screened to construct a prognostic model for MB. These genes may serve as key biomarkers for predicting the prognosis of patients with this type of brain cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Studies have indicated a close association between dysbiosis of the gut microbiota and chronic sinusitis. However, the causal relationship between the gut microbiota and the risk of chronic sinusitis remains unclear., Methods: Using genome-wide association study (GWAS) data for the gut microbiota and chronic sinusitis, we conducted a two-sample Mendelian randomization (MR) study to determine the potential causal relationship between the microbiota and chronic sinusitis. We employed the inverse variance-weighted (IVW) method as the primary analytical approach to estimate the effect. Additionally, sensitivity, heterogeneity, and pleiotropy analyses were conducted to evaluate the robustness of the results. Reverse MR analysis was also applied to investigate potential reverse causality., Results: Through MR analysis, we identified 17 gut microbiota classifications that are closely associated with chronic sinusitis. However, after Bonferroni multiple correction, only class Bacilli (odds ratio: 0.785, 95% confidence interval: 0.677-0.911, p = .001, false discovery rate = 0.023) maintained a significant causal negative relationship with chronic sinusitis. Sensitivity analysis did not reveal any evidence of heterogeneity or horizontal pleiotropy. Reverse MR analysis found five gut microbiota classifications that are significantly associated with chronic sinusitis, but they were no longer significant after Bonferroni multiple correction. There was no evidence to suggest a reverse causal relationship between chronic sinusitis and class Bacilli., Conclusion: Specific gut microbiota predicted by genetics exhibit a potential causal relationship with chronic sinusitis, and class Bacilli may have a protective effect on chronic sinusitis., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

In the work, Bi 2 WO 6 /C-TiO 2 photocatalyst was successfully synthesized for the first time by loading narrow bandgap semiconductor Bi 2 WO 6 on MOF-derived carboxyl modified TiO 2 . The phase structure, morphology, photoelectric properties, surface chemical states and photocatalytic performance of the prepared photocatalysts were systematically investigated using various characterization tools. The degradation efficiency of oxytetracycline by 6BT Z-scheme heterojunction photocatalyst under visible light could reach 93.6 % within 100 min, which was related to the high light harvesting and effective separation and transfer of photo-generated carriers. Furthermore, the effects of various environmental factors in actual wastewater were further investigated, and the results showed that 6BT exhibited good adaptability, durability and resistance to interference. Unlike most works, the degradation system with a different single active species were designed and constructed based on their formation mechanism. In addition, for the first time, a positive study was conducted on the priority attack sites, intermediate products, and degradation pathways for the photocatalytic degradation of oxytetracycline by a single active species through HPLC-MS and Fukui index calculations. The toxicity changes of intermediate products produced in three different single active species oxidation systems were evaluated using toxicity assessment software tools (T.E.S.T.), Escherichia coli growth experiments, and wheat growth experiments. Among them, the intermediate products formed through O 2 - oxidation had the lowest toxicity and the main active sites it attacked were the 20C, 38O, 18C, 41O, and 55O atoms with high f + values in the oxytetracycline molecular structure. This work provided the insight into the role of each active species in the degradation of antibiotics and offered new ideas for the design and synthesis of efficient and eco-friendly photocatalysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: With the increasing demand for fertility services, it is urgent to select the most cost-effective assisted reproductive technology (ART) treatment plan and include it in medical insurance. Economic evaluation reports are an important reference for medical insurance negotiation. The aim of this study is to systematically evaluate the economic evaluation research of ART, analyze the existing shortcomings, and provide a reference for the economic evaluation of ART., Methods: PubMed, EMbase, Web of Science, Cochrane Library and ScienceDirect databases were searched for relevant articles on the economic evaluation of ART. These articles were screened, and their quality was evaluated based on the Comprehensive Health Economics Evaluation Report Standard (CHEERS 2022), and the data on the basic characteristics, model characteristics and other aspects of the included studies were summarized., Results: One hundred and two related articles were obtained in the preliminary search, but based on the inclusion criteria, 12 studies were used for the analysis, of which nine used the decision tree model. The model parameters were mainly derived from published literature and included retrospective clinical data of patients. Only two studies included direct non-medical and indirect costs in the cost measurement. Live birth rate was used as an outcome indicator in half of the studies., Conclusion: Suggesting the setting of the threshold range in the field of fertility should be actively discussed, and the monetary value of each live birth is assumed to be in a certain range when the WTP threshold for fertility is uncertain. The range of the parameter sources should be expanded. Direct non-medical and indirect costs should be included in the calculation of costs, and the analysis should be carried out from the perspective of the whole society. In the evaluation of clinical effect, the effectiveness and safety indexes should be selected for a comprehensive evaluation, thereby making the evaluation more comprehensive and reliable. At least subgroup analysis based on age stratification should be considered in the relevant economic evaluation., (© 2024. The Author(s).)

The objective of this study was to investigate self-medication behavior among Chinese adolescents aged 12-18 years and explore the factors associated with whether adolescents prioritize drug efficacy or safety when engaging in self-medication behavior. In 2021, a questionnaire investigation was conducted in the Chinese mainland using a multi-stage sampling approach. After a statistical description, logistic regression was used to analyze the factors associated with considering drug efficacy and safety. The self-medication rate among Chinese adolescents aged 12-18 years was 96.61%. Of these, 65.84% considered drug safety to be essential, while 58.72% prioritized drug efficacy. Regression analysis showed that individuals with better healthcare were more likely to consider drug efficacy an important factor. Additionally, those with a healthier family lifestyle were more likely to prioritize efficacy. When individuals engage in self-medication, those residing in urban areas and possessing advanced preventive health literacy and ample family health resources tend to prioritize drug safety to a greater extent. Conversely, those with higher monthly household incomes and only children exhibit a decreased inclination towards prioritizing safety during self-medication. Self-medication is a frequently observed practice among Chinese adolescents aged 12-18. Several factors, such as demographic and sociological characteristics, health literacy, and family health status, have been found to be associated with the extent to which adolescents prioritize medication safety and efficacy when engaging in self-medication practices. Higher levels of health literacy and better family health status were positively correlated with considering both the efficacy and safety of drugs as important factors when self-medicating., (© 2024. The Author(s).)

Background: The impact of per- and polyfluoroalkyl substances (PFAS) on constipation, as mediated through gastrointestinal absorption and perturbations to the intestinal microecology, remains poorly understood., Objective: This study seeks to explain the relationship between PFAS and constipation., Methods: A total of 2945 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were included in this study. Constipation was defined using the Bristol Stool Form Scale (BSFS) based on stool consistency. The relationship between PFAS and constipation was evaluated using weighted logistic regression and restricted cubic spline (RCS) analysis, while adjusting for confounding variables., Results: The weighted median concentration of total PFAS (ΣPFAS) was significantly lower in individuals with constipation (19.01 μg/L) compared to those without constipation (23.30 μg/L) (p < 0.0001). Subgroup analysis revealed that the cumulative effect of PFAS was more pronounced in the elderly, men, individuals with obesity, high school education or equivalent, and high-income individuals (p < 0.05). After adjusting for confounding factors, multivariable analysis demonstrated an inverse association between PFOA [OR (95% CI), 0.666(0.486,0.914)] and PFHxS [OR (95% CI), 0.699(0.482,1.015)], and constipation. None of the personal and lifestyle factors showed a significant correlation with this negative association, as confirmed by subgroup analysis and interaction testing (p for interaction > 0.05). The RCS analysis demonstrated a linear inverse relationship between PFAS levels and constipation., Conclusion: The findings of this study provide evidence of a significant inverse correlation between serum concentrations of PFAS, particularly PFOA and PFHxS, and constipation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dissipative Kerr-soliton combs are laser pulses regularly sustained by a localized solitary wave on top of a continuous-wave background inside a nonlinear resonator. Usually, the intrinsic interactions between the background light and solitons are weak and localized. Here, we demonstrate a strong interaction between the generated soliton comb and the background light in a Brillouin-Kerr microcomb system. This strong interaction enables the generation of a monostable single-soliton microcomb on a silicon chip. Also, new phenomena related to soliton physics including solitons hopping between different states as well as controlling the formations of the soliton states by the pump power, are observed owing to such strong interaction. Utilizing this monostable single-soliton microcomb, we achieve the 100% deterministic turnkey operation successfully without any feedback controls. Importantly, it allows to output turnkey ultra-low-noise microwave signals using a free-running pump., (© 2024. The Author(s).)

Due to rapid research expansion on dietary factors and development of cancer prevention guidelines, the field of dietary pattern and its relationship to cancer risk has gained more focus. Numerous epidemiology studies have reported associations between Gastric Cancer (GC) and both data-driven posteriori dietary pattern and priori dietary pattern defined by predetermined dietary indexes. As dietary patterns have evolved, a series of patterns based on biological markers has advanced, offering deeper insights into the relationship between diet and the risk of cancer. Although researches on dietary patterns and cancer risk are booming, there is limited body of literature focusing specifically on GC. In this study, we compare the similarities and differences among the specific components of dietary patterns and indices, summarize current state of knowledge regarding dietary patterns related to GC and illustrate their potential mechanisms for GC prevention. In conclusion, we offer suggestions for future research based on the emerging themes within this rapidly evolving field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pu, Feng, Tang, Yang and Xu.)

Background and Purpose: To examine the diagnostic value of imaging features in cavernous sinus hemangioma (CSH)., Materials and Methods: The clinical and imaging data of patients with pathologically confirmed CSH, cavernous sinus meningioma, trigeminal schwannoma and pituitary adenoma invading the cavernous sinus between May 2017 and May 2022 were retrospectively analyzed. The cases were divided into the CSH and non-CSH groups to summarize the magnetic resonance imaging (MRI) characteristics of CSH. Univariate χ2 analysis was performed to assess five indexes, including signal intensity on T2WI, homogeneity of T2WI, enhancement of enhanced T1, enhanced T1 with dural tail sign, and cavernous sinus swelling and extrusion sign., Results: There were significant differences in four features, including hyperintensity on T2WI, homogeneity of T2WI, T1-enhanced without meningeal tail sign, and cavernous sinus swelling and extrusion sign between the CSH and non-CSH groups, with cavernous sinus swelling and extrusion sign showing the most pronounced distinction, with a sensitivity of 100%, a specificity of 93.02%, and an accuracy of 94.23%. The four features could be jointly used as diagnostic criteria, with a sensitivity of 94.44%, a specificity of 100.00%, and an accuracy of 99.04%., Conclusion: Cavernous sinus swelling and extrusion sign is a reliable imaging index for CSH diagnosis. Homogenous hyperintensity or marked hyperintensity on T2WI, enhanced T1 without dural tail sign, and cavernous sinus swelling and extrusion sign could be jointly used as diagnostic criteria, which may improve the accuracy of CSH diagnosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy., Methods: A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes., Results: After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05)., Conclusion: For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metagenomic next-generation sequencing (mNGS) provides considerable advantages in identifying emerging and re-emerging, difficult-to-detect and co-infected pathogens; however, the clinical application of mNGS remains limited primarily due to the lack of quantitative capabilities. This study introduces a novel approach, KingCreate-Quantification (KCQ) system, for quantitative analysis of microbes in clinical specimens by mNGS, which co-sequence the target DNA extracted from the specimens along with a set of synthetic dsDNA molecules used as Internal-Standard (IS). The assay facilitates the conversion of microbial reads into their copy numbers based on IS reads utilizing a mathematical model proposed in this study. The performance of KCQ was systemically evaluated using commercial mock microbes with varying IS input amounts, different proportions of human genomic DNA, and at varying amounts of sequence analysis data. Subsequently, KCQ was applied in microbial quantitation in 36 clinical specimens including blood, bronchoalveolar lavage fluid, cerebrospinal fluid and oropharyngeal swabs. A total of 477 microbe genetic fragments were screened using the bioinformatic system. Of these 83 fragments were quantitatively compared with digital droplet PCR (ddPCR), revealing a correlation coefficient of 0.97 between the quantitative results of KCQ and ddPCR. Our study demonstrated that KCQ presents a practical approach for the quantitative analysis of microbes by mNGS in clinical samples.

Epigenetic clocks are DNA methylation-based chronological age prediction models that are commonly employed to study age-related biology. The difference between the predicted and observed age is often interpreted as a form of biological age acceleration, and many studies have measured the impact of environmental and disease-associated factors on epigenetic age. Most epigenetic clocks are fit using approaches that minimize the error between the predicted and observed chronological age, and as a result, they may not accurately model the impact of factors that moderate the relationship between the actual and epigenetic age. Here, we compare epigenetic clocks that are constructed using penalized regression methods to an evolutionary framework of epigenetic aging with the epigenetic pacemaker (EPM), which directly models DNA methylation as a function of a time-dependent epigenetic state. In simulations, we show that the value of the epigenetic state is impacted by factors such as age, sex, and cell-type composition. Next, in a dataset aggregated from previous studies, we show that the epigenetic state is also moderated by sex and the cell type. Finally, we demonstrate that the epigenetic state is also moderated by toxins in a study on polybrominated biphenyl exposure. Thus, we find that the pacemaker provides a robust framework for the study of factors that impact epigenetic age acceleration and that the effect of these factors may be obscured in traditional clocks based on linear regression models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Farrell, Hu, Lapborisuth, Pu, Snir and Pellegrini.)