Search

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

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.

[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.

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.

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

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.

OBJECTIVE: Accumulating studies have reported that circular RNAs (circRNAs) can act as novel prognostic biomarkers in multiple malignant tumors. Here, we conducted a study to investigate the potential function and molecular mechanism of action of hsa_circ_0010882 in gastric cancer (GC). PATIENTS AND METHODS: The expression of hsa_circ_0010882 in the plasma of GC patients and in GC cell lines was verified by qRT-PCR. Its association with overall survival of GC patients was then analyzed by statistical analysis. Gainof- function and loss-of-function assays were used to investigate the physiological function of hsa_circ_0010882 in GC cells in vitro in the context of proliferation, apoptosis, migration, and invasion. Moreover, the molecular mechanism of action of hsa_circ_0010882 was predicted using online databases and a literature review. A Western blot assay was used to detect the levels of proteins in the PI3K/Akt/mTOR signaling pathway. RESULTS: We found that hsa_circ_0010882 expression was significantly upregulated in the plasma of GC patients and GC cell lines. Increased expression of hsa_circ_0010882 was significantly correlated with tumor size and histological grade. In addition, GC patients with higher expression of hsa_circ_0010882 had significantly lower overall survival than patients with lower expression of hsa_circ_0010882. Multivariate analysis showed that hsa_circ_0010882 expression could be an independent prognostic factor for overall survival. The proliferation, migration, and invasiveness of GC cell lines were inhibited following hsa_circ_0010882 knockdown, while GC cellular apoptosis increased. Further, overexpression of hsa_circ_0010882 leads to increased proliferation, migration, and invasiveness of GC cell lines. While apoptosis was higher in the GC cell line group with low expressing hsa_circ_0010882 than the control group, no significant difference in apoptosis was detected between the hsa_circ_0010882 overexpressing and the control group. Finally, a mechanistic analysis demonstrated that the hsa_circ_0010882 was positively associated with PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Hsa_circ_0010882, as an oncogenic molecule, is highly expressed in the plasma of patients with GC and is associated with poor prognosis. It plays an important role in proliferation, migration, and invasive genotypes of GC cell lines via regulation of the PI3K/Akt/mTOR signaling pathway. Additionally, it might be a potential prognostic biomarker for GC patients. [ABSTRACT FROM AUTHOR]

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.

Copyright of West Indian Medical Journal is the property of West Indian Medical Journal (WIMJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.

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.

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]

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

Leveraging X-rays to initiate prolonged luminescence (radio-afterglow) and stimulate radiodynamic 1 O 2 production from optical agents provides opportunities for diagnosis and therapy at tissue depths inaccessible to light. However, X-ray-responsive organic luminescent materials are rare due to their intrinsic low X-ray conversion efficiency. Here we report a cascade X-ray energy converting approach to develop organic radio-afterglow nanoprobes (RANPs) for cancer theranostics. RANPs comprise a radiowave absorber that down-converts X-ray energy to emit radioluminescence, which is transferred to a radiosensitizer to produce singlet oxygen ( 1 O 2 ). 1 O 2 then reacts with a radio-afterglow substrate to generate an active intermediate that simultaneously decomposes to emit radio-afterglow. Through finetuning such a cascade, intraparticle radioluminescence energy transfer and the 1 O 2 transfer process, RANPs possess tunable wavelengths and long half-lives, and generate radio-afterglow and 1 O 2 at tissue depths of up to 15 cm. Moreover, we developed a biomarker-activatable nanoprobe (tRANP) that produces a tumour-specific radio-afterglow signal, leading to ultrasensitive detection and the possibility of surgical removal of diminutive tumours (1 mm 3 ) under an X-ray dosage 20 times lower than inorganic materials. The efficient radiodynamic 1 O 2 generation of tRANP permits complete tumour eradication at an X-ray dosage lower than clinical radiotherapy and a drug dosage one to two orders of magnitude lower than most existing inorganic agents, leading to prolonged survival rates with minimized radiation-related adverse effects. Thus, our work reveals a generic approach to address the lack of organic radiotheranostic materials and provides molecular design towards precision cancer radiotherapy., Competing Interests: Competing interests The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 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.)

Proteolysis targeting chimeras (PROTACs) represent a transformative class of therapeutic agents that leverage the intrinsic protein degradation machinery to modulate the hemostasis of key disease-associated proteins selectively. Although several PROTACs have been approved for clinical application, suboptimal therapeutic efficacy and potential adverse side effects remain challenging. Benefiting from the enhanced targeted delivery, reduced systemic toxicity, and improved bioavailability, nanomedicines can be tailored with precision to integrate with PROTACs which hold significant potential to facilitate PROTAC nanomedicines (nano-PROTACs) for clinical translation with enhanced efficacy and reduced side effects. In this review, we provide an overview of the recent progress in the convergence of nanotechnology with PROTAC design, leveraging the inherent properties of nanomaterials, such as lipids, polymers, inorganic nanoparticles, nanohydrogels, proteins, and nucleic acids, for precise PROTAC delivery. Additionally, we discuss the various categories of PROTAC targets and provide insights into their clinical translational potential, alongside the challenges that need to be addressed.

Although an increasing number of people are now committed to pursuing a healthy diet, it remains unclear how mental health changes during this process. The present study aimed to examine the combined effect of healthy dietary intention and behavior on depression and anxiety across two sub-studies. This study consisted of two parts: a cross-sectional survey (Study 1) involving 1,433 college students and an 11-day daily diary study (Study 2) with 117 college students. Polynomial regression and response surface analysis indicated that in cases of congruence, individuals' intention and behavior align at a high level and were associated with lower levels of depression and anxiety in the motivational phase but were not found similar association in the volitional phase. In cases of incongruence, individuals with high intention-low behavior tend to experience lower levels of depression and anxiety in the motivational phase. However, individuals with high intention-low behavior tend to experience higher levels of depression and anxiety in the volitional phase. These findings not only enrich the current understanding of diet and health but also contribute to the development of holistic strategies for promoting a healthy diet., (© 2024 International Association of Applied Psychology. Published by John Wiley & Sons Ltd.)

Optical imaging is an indispensable tool for non-invasive visualization of biomolecules in living organisms, thereby offering a sensitive approach for disease diagnosis and image-guided disease treatment. Single-lock activatable optical probes (SOPs) that specifically switch on optical signals in the presence of biomarkers-of-interest have shown both higher detection sensitivity and imaging quality as compared to conventional "always-on" optical probes. However, such SOPs can still show "false-positive" results in disease diagnosis due to non-specific biomarker expression in healthy tissues. By contrast, multi-lock activatable optical probes (MOPs) that simultaneously detect multiple biomarkers-of-interest could improve detection specificity towards certain biomolecular events or pathological conditions. In this Review, we discuss the recent advancements of enzyme-responsive MOPs, with a focus on their biomedical applications. The higher detection specificity of MOPs could in turn enhance disease diagnosis accuracy and improve treatment efficacy in image-guided disease therapy with minimal toxicity in the surrounding healthy tissues. Finally, we discuss the current challenges and suggest future applications of MOPs.

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.)

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: 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).)

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.

The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles' elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)