In vivo manufacture and manipulation of CAR-T cells for better druggability.

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.

Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors.

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as a potent immunotherapy and has made significant success in hematologic malignancies by eliciting antigen-specific immune responses. However, response rates of CAR-T cell therapy against solid tumors with immunosuppressive microenvironments remain limited. Co-engineering strategies are advancing methods to overcome immunosuppressive barriers and enhance antitumor responses. Here, we engineered an IL-2 mutein co-engineered CAR-T for the improvement of CAR-T cells against solid tumors and the efficient inhibition of solid tumors. We equipped the CAR-T cells with co-expressing both tumor antigen-targeted CAR and a mutated human interleukin-2 (IL-2m), conferring enhanced CAR-T cells fitness in vitro, reshaped immune-excluded TME, enhanced CAR-T infiltration in solid tumors, and improved tumor control without significant systemic toxicity. Overall, this subject demonstrates the universal CAR-T cells armed strategy for the development and optimization of CAR-T cells against solid tumors.

Development and validation of an ultrasound-based deep learning radiomics nomogram for predicting the malignant risk of ovarian tumours.

BACKGROUND: The timely identification and management of ovarian cancer are critical determinants of patient prognosis. In this study, we developed and validated a deep learning radiomics nomogram (DLR_Nomogram) based on ultrasound (US) imaging to accurately predict the malignant risk of ovarian tumours and compared the diagnostic performance of the DLR_Nomogram to that of the ovarian-adnexal reporting and data system (O-RADS). METHODS: This study encompasses two research tasks. Patients were randomly divided into training and testing sets in an 8:2 ratio for both tasks. In task 1, we assessed the malignancy risk of 849 patients with ovarian tumours. In task 2, we evaluated the malignancy risk of 391 patients with O-RADS 4 and O-RADS 5 ovarian neoplasms. Three models were developed and validated to predict the risk of malignancy in ovarian tumours. The predicted outcomes of the models for each sample were merged to form a new feature set that was utilised as an input for the logistic regression (LR) model for constructing a combined model, visualised as the DLR_Nomogram. Then, the diagnostic performance of these models was evaluated by the receiver operating characteristic curve (ROC). RESULTS: The DLR_Nomogram demonstrated superior predictive performance in predicting the malignant risk of ovarian tumours, as evidenced by area under the ROC curve (AUC) values of 0.985 and 0.928 for the training and testing sets of task 1, respectively. The AUC value of its testing set was lower than that of the O-RADS; however, the difference was not statistically significant. The DLR_Nomogram exhibited the highest AUC values of 0.955 and 0.869 in the training and testing sets of task 2, respectively. The DLR_Nomogram showed satisfactory fitting performance for both tasks in Hosmer-Lemeshow testing. Decision curve analysis demonstrated that the DLR_Nomogram yielded greater net clinical benefits for predicting malignant ovarian tumours within a specific range of threshold values. CONCLUSIONS: The US-based DLR_Nomogram has shown the capability to accurately predict the malignant risk of ovarian tumours, exhibiting a predictive efficacy comparable to that of O-RADS.

Recent developments in the use of nanocrystals to improve bioavailability of APIs.

Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies. However, issues such as safety and stability still stand that need to be addressed for further development of nanocrystal formulations, and significant gaps do exist in research in various fields in this pharmaceutical arena. This paper presents a systematic overview of the advanced development of nanocrystals, ranging from the preparation approaches of nanocrystals with which the bioavailability of poorly water-soluble drugs is improved, critical properties of nanocrystals and associated characterization techniques, the recent development of nanocrystals with different administration routes, the advantages and associated limitations of nanocrystal formulations, the mechanisms of physical instability, and the enhanced dissolution performance, to the future perspectives, with a final view to shed more light on the future development of nanocrystals as a means of optimizing the bioavailability of drug candidates. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Left Ventricular Remodelling Associated with the Transient Elevated [68Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

BACKGROUND: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. METHODS: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. RESULTS: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). CONCLUSIONS: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.

Brain stimulation over the left DLPFC enhances motivation for effortful rewards in patients with major depressive disorder.

BACKGROUND: Amotivation is a typical feature in major depressive disorder (MDD), which produces reduced willingness to exert effort. The dorsolateral prefrontal cortex (DLPFC) is a crucial structure in goal-directed actions and therefore is a potential target in modulating effortful motivation. However, it remains unclear whether the intervention is effective for patients with MDD. METHODS: We employed transcranial magnetic stimulation (TMS), computational modelling and event-related potentials (ERPs) to reveal the causal relationship between the left DLPFC and motivation for effortful rewards in MDD. Fifty patients underwent both active and sham TMS sessions, each followed by performing an Effort-Expenditure for Rewards Task, during which participants chose and implemented between low-effort/low-reward and high-effort/high-reward options. RESULTS: The patients showed increased willingness to exert effort for rewards during the DLPFC facilitated session, compared with the sham session. They also had a trend in larger P3 amplitude for motivated attention toward chosen options, larger CNV during preparing for effort exertion, and larger SPN during anticipating a high reward. Besides, while behavior indexes for effortful choices were negatively related to depression severity in the sham session, this correlation was weakened in the active stimulation session. CONCLUSIONS: These findings provide behavioral, computational, and neural evidence for the left DLPFC on effortful motivation for rewards. Facilitated DLPFC improves motor preparation and value anticipation after making decisions especially for highly effortful rewards in MDD. Facilitated DLPFC also has a potential function in enhancing motivated attention during cost-benefit trade-off. This neuromodulation effect provides a potential treatment for improving motivation in clinics.

Enhancing ventrolateral prefrontal cortex activation mitigates social pain and modifies subsequent social attitudes: Insights from TMS and fMRI.

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

Machine-learning-based models to predict cardiovascular risk using oculomics and clinic variables in KNHANES.

BACKGROUND: Recent researches have found a strong correlation between the triglyceride-glucose (TyG) index or the atherogenic index of plasma (AIP) and cardiovascular disease (CVD) risk. However, there is a lack of research on non-invasive and rapid prediction of cardiovascular risk. We aimed to develop and validate a machine-learning model for predicting cardiovascular risk based on variables encompassing clinical questionnaires and oculomics. METHODS: We collected data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training dataset (80% from the year 2008 to 2011 KNHANES) was used for machine learning model development, with internal validation using the remaining 20%. An external validation dataset from the year 2012 assessed the model's predictive capacity for TyG-index or AIP in new cases. We included 32122 participants in the final dataset. Machine learning models used 25 algorithms were trained on oculomics measurements and clinical questionnaires to predict the range of TyG-index and AIP. The area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score were used to evaluate the performance of our machine learning models. RESULTS: Based on large-scale cohort studies, we determined TyG-index cut-off points at 8.0, 8.75 (upper one-third values), 8.93 (upper one-fourth values), and AIP cut-offs at 0.318, 0.34. Values surpassing these thresholds indicated elevated cardiovascular risk. The best-performing algorithm revealed TyG-index cut-offs at 8.0, 8.75, and 8.93 with internal validation AUCs of 0.812, 0.873, and 0.911, respectively. External validation AUCs were 0.809, 0.863, and 0.901. For AIP at 0.34, internal and external validation achieved similar AUCs of 0.849 and 0.842. Slightly lower performance was seen for the 0.318 cut-off, with AUCs of 0.844 and 0.836. Significant gender-based variations were noted for TyG-index at 8 (male AUC=0.832, female AUC=0.790) and 8.75 (male AUC=0.874, female AUC=0.862) and AIP at 0.318 (male AUC=0.853, female AUC=0.825) and 0.34 (male AUC=0.858, female AUC=0.831). Gender similarity in AUC (male AUC=0.907 versus female AUC=0.906) was observed only when the TyG-index cut-off point equals 8.93. CONCLUSION: We have established a simple and effective non-invasive machine learning model that has good clinical value for predicting cardiovascular risk in the general population.

Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. METHODS: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. RESULTS: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. CONCLUSIONS: The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

Spherization indices measured by resting SPECT improve risk stratification in patients with ischemia with non-obstructive coronary artery disease (INOCA).

BACKGROUND: The prevalence of ischemia with non-obstructive coronary artery disease (INOCA) is substantial, but its risk stratification has been suboptimal. Resting SPECT myocardial perfusion imaging (MPI) could provide useful heart information including spherical indices. We aimed to evaluate the prognostic value of spherical indices in individuals with INOCA. RESULTS: During a median follow-up of 47.2 ± 20.8 months, 49 (17.2%) patients experienced major adverse cardiac events (MACE). Compared to those without MACE, those with MACE had a higher shape index (SI) (0.60 ± 0.07 vs. 0.58 ± 0.06; P = 0.028) and a lower E2 (eccentricity index calculated by the QPS) (0.81 ± 0.05 vs. 0.83 ± 0.04; P = 0.019). MACE event-free survival analysis revealed significant differences in the SI and E2 among all patients (all log-rank P < 0.01). Multivariate Cox analysis showed abnormal SI (HR: 2.73, 95% CI 1.44-5.18, P = 0.002) and E2 (HR: 1.94, 95% CI 1.08-3.48, P = 0.026) were both independent predictors for MACE when they were put into the same model, respectively. The incorporation of the SI into the baseline model demonstrated a significant improvement in the predictive accuracy for MACEs (P = 0.026), whereas E2 did not exhibit a similar improvement (P > 0.05). CONCLUSION: For patients with INOCA, spherical indices (especially the SI) were associated with long-term MACE, which could be a preferable indicator for risk stratification and prognostic prediction.

The use of PET/MRI in radiotherapy.

Positron emission tomography/magnetic resonance imaging (PET/MRI) is a hybrid imaging technique that quantitatively combines the metabolic and functional data from positron emission tomography (PET) with anatomical and physiological information from MRI. As PET/MRI technology has advanced, its applications in cancer care have expanded. Recent studies have demonstrated that PET/MRI provides unique advantages in the field of radiotherapy and has become invaluable in guiding precision radiotherapy techniques. This review discusses the rationale and clinical evidence supporting the use of PET/MRI for radiation positioning, target delineation, efficacy evaluation, and patient surveillance.Critical relevance statement This article critically assesses the transformative role of PET/MRI in advancing precision radiotherapy, providing essential insights into improved radiation positioning, target delineation, efficacy evaluation, and patient surveillance in clinical radiology practice.Key points• The emergence of PET/MRI will be a key bridge for precise radiotherapy.• PET/MRI has unique advantages in the whole process of radiotherapy.• New tracers and nanoparticle probes will broaden the use of PET/MRI in radiation.• PET/MRI will be utilized more frequently for radiotherapy.

Efficient natural plasmid transformation of Vibrio natriegens enables zero-capital molecular biology.

The fast-growing microbe Vibrio natriegens is capable of natural transformation where it draws DNA in from media via an active process under physiological conditions. Using an engineered strain with a genomic copy of the master competence regulator tfoX from Vibrio cholerae in combination with a new minimal competence media (MCM) that uses acetate as an energy source, we demonstrate naturally competent cells which are created, transformed, and recovered entirely in the same media, without exchange or addition of fresh media. Cells are naturally competent to plasmids, recombination with linear DNA, and cotransformation of both to select for scarless and markerless genomic edits. The entire process is simple and inexpensive, requiring no capital equipment for an entirely room temperature process (zero capital protocol, 104 cfu/µg), or just an incubator (high-efficiency protocol, 105-6 cfu/µg). These cells retain their naturally competent state when frozen and are transformable immediately upon thawing like a typical chemical or electrochemical competent cell. Since the optimized transformation protocol requires only 50 min of hands-on time, and V. natriegens grows quickly even on plates, a transformation started at 9 AM yields abundant culturable single colonies by 5 PM. Further, because all stages of transformation occur in the same media, and the process can be arbitrarily scaled in volume, this natural competence strain and media could be ideal for automated directed evolution applications. As a result, naturally competent V. natriegens could compete with Escherichia coli as an excellent chassis for low-cost and highly scalable synthetic biology.

Immunophenotyping with high-dimensional flow cytometry identifies Treg cell subsets associated with recurrence in papillary thyroid carcinoma.

The activation of Treg cell subsets is critical for the prognosis of tumor patients; however, their heterogeneity and disease association in papillary thyroid carcinoma (PTC) need further investigation. We performed high-dimensional flow cytometry for immunophenotyping on thyroid tissues and matched peripheral blood samples from patients with multinodular goiters or PTC. We analyzed CD4+ T cell and Treg cell phenotypes and compared the recurrence-free survival of PTC patients with different Treg cell subset characteristics using TCGA. Furthermore, PTC recurrent and non-recurrent group were compared by multiplex immunohistochemistry. High-dimensional flow cytometry and bioinformatics analysis revealed an enrichment of Tregs in tumors compared with multinodular goiters and peripheral blood specimens. Moreover, effector Tregs (e-Tregs) as well as FOXP3+ non-Tregs were enriched in tumor samples, and the expression of CD39, PD-1, and CD103 increased on tumor Tregs. TCGA data analysis showed that individuals with CD39hi PD-1loCD103loe-Treghi and CD39loPD-1loCD103hie-Treghi expression patterns had a high recurrence rate. According to the multiplex immunohistochemistry and analysis, compared with non-recurrent group, the proportion of high recurrence rate effector Treg clusters (CD39+PD-1-CD103- plus CD39-PD-1-CD103+) was increased in recurrent patients. Overall, our results highlight the potential of e-Treg subsets as future immunotherapy targets for PTC recurrence.

High purity of human secreted phospholipase A2 group IIE in Pichia pastoris using basal salts medium comparison with YPD medium.

Secreted phospholipase A2s (sPLA2s) are a group of enzymes with 6-8 disulfide bonds that participate in numerous physiological processes by catalyzing the hydrolysis of phospholipids at the sn-2 position. Due to their high content of disulfide bonds and hydrolytic activity toward cell membranes, obtaining the protein of sPLA2s in the soluble and active form is challenging, which hampers their functional study. In this study, one member of recombinant human sPLA2s, tag-free group IIE (GIIE), was expressed in Pichia pastoris. The protein GIIE was purified from the crude culture supernatant by a two-step chromatography procedure, a combination of cation exchange and size-exclusion chromatography. In the shake flask fermentation, Protein of GIIE with higher purity was successfully obtained, using basal salts medium (BSM) instead of YPD medium. In the large-scale fermentation, each liter of BSM produced a final yield of 1.2 mg pure protein GIIE. This protocol will facilitate further research of GIIE and provide references for the production of other sPLA2 members.

Network pharmacology combined with an animal model to reveal the material basis and mechanism of Amomum villosum in alleviating constipation in mice.

Constipation is a prevalent gastrointestinal disorder, with its prevalence showing an annual upward trend. There are many factors involved in the occurrence of constipation, such as abnormal smooth muscle contraction and disorders of gastrointestinal hormone secretion. Amomum villosum (A. villosum) has been proven to be effective in improving digestive system diseases, but there is no report on improving constipation. Therefore, we used network pharmacology prediction combined with animal experiments to explore the key active components of A. villosum and their pharmacological mechanisms. The results of network pharmacological prediction showed that ß-sitosterol was the key laxative compound of A. villosum, which may play a laxative role by activating the adrenoceptor alpha 1 A-myosin light chain (ADRA1A-MLC) pathway. Further animal experiments showed that ß-sitosterol could significantly shorten the time to first black stool; increase faecal weight, faecal number, and faecal water content; and promote gastrointestinal motility. ß-sitosterol may promote intestinal motility by upregulating the expression of ADRA1A and myosin light chain 9 (Myl9) mRNA and protein in the colon, thereby activating the ADRA1A-MLC signalling pathway. In addition, it is possible to improve constipation symptoms by regulating serum neurotransmitters and gastrointestinal motility-related factors, such as the serum content of 5-hydroxytryptamine (5-HT) and acetylcholinesterase (AchE) and the mRNA expression of 5-hydroxytryptamine receptor 4 (5-HT4), stem cell factor (SCF), stem cell factor receptor (c-Kit) and smooth muscle myosin light chain kinase (smMLCK) in the colon. These results lay a foundation for the application of A. villosum and ß-sitosterol in constipation.

Let-7c-5p Down Regulates the Proliferation of Colorectal Cancer Through the MAPK-ERK-Signaling Pathway.

Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancers. Rapid cell proliferation is the leading cause of cancer-related death in CRC. MicroRNAs (miRNAs) have been identified to play essential roles in the proliferation of CRC. Differential expression of let-7c-5p in CRC was assessed using a GEO dataset, and confirmed through RT-qPCR using CRC subject tissues. Let-7c-5p-overexpressing HCT8 cell line was constructed by transfecting let-7c-5p. Bioinformatics analysis identified that DUSP7 is the target gene of let-7c-5p. Further experimental assays, including Cell Counting Kit-8 (CCK8), EdU staining, cell colony, and Western Blot assays, confirmed the target genes and pathway of let-7c-5p. Receiver operator characteristic curve (ROC) analysis was performed to evaluate the diagnostic value of let-7c-5p for CRC. Finally, survival analysis was performed to determine the effect of DUSP7 and let-7c-5p on the prognosis of CRC patients. RT-qPCR analysis showed that the expression level of let-7c-5p was significantly increased in CRC subject tissues compared to the adjacent tissue. Overexpression of let-7c-5p promoted cell proliferation in HCT8 cell line. Furthermore, the MAPK-ERK pathway's protein expression of p-ERK1/2 was downregulated, while the ratio of Bcl-2/Bax was increased by let-7c-5p transfection in HCT 8. ROC analysis demonstrated that the expressive level of let-7c-5p had higher diagnostic value for CRC. Survival curve analysis indicated that high expression of DUSP7 and low expression of let-7c-5p were associated with poor prognosis in CRC patients. The findings suggest that let-7c-5p exerts an antitumor function by inhibiting the DUSP7-mediated MAPK-ERK pathway. Both DUSP7 and let-7c-5p have the potential to serve as prognostic biomarkers in CRC patients.

Randomized controlled trial on the effects of mindfulness-based respiratory decompression therapy in claustrophobic patients undergoing MRI inspection.

Background: Claustrophobia is a psychological disease. It is estimated to occur in 2.1-14.3% of all magnetic resonance imaging (MRI) examinations. Mindfulness decompression is an effective means to treat and reduce fear and anxiety. There is a rare report on the application of mindfulness-based stress reduction therapy in the magnetic resonance examinations of patients with claustrophobia to date. Purpose: The purpose of this study is to explore the intervention effect of mindfulness respiratory decompression therapy on the MRI inspection of patients with claustrophobia. Methods: A total of 86 patients with claustrophobia requiring MRI in our hospital from January 2018 to December 2020 were divided into two groups. The control group was given routine psychological nursing, and the observation group was given a mindfulness breathing technique on the basis of the control group. Before and after the intervention, we compared the intervention effect, satisfaction with nurses' psychological intervention technique, severe autonomic nervous symptoms during the examination, self-rating anxiety scale (SAS) scores, and profile of mood states revised (POMS-R) scores. Results: The total effective rate of intervention in the observation group was 90.90%, which was significantly higher (χ2 = 6.857, p = 0.00004) than that in the control group (26.19%). Severe autonomic nervous symptoms in the observation group were significantly lower than those in the control group (p < 0.05). After the intervention, SAS scores and POMS-R scores in the observation group decreased with statistical significance (p < 0.05). Conclusion: Mindfulness respiratory decompression therapy can effectively help claustrophobic patients complete an MRI examination, which may be worthy of wide promotion and application in the clinic.

99mTc-DTPA Renal Dynamic Imaging for Evaluating the Function of Duplex Kidneys in Adult Patients

Background: This study aimed to explore technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamicimaging to evaluate duplex kidney function in adult patients.Subjects and Methods: We retrospectively analyzed the clinical data of 25 patients with duplex kidneys who underwent 99mTc-DTPA renal dynamic imaging between June 2011 and March 2023 at our hospital. Patients in the duplex kidney group (n = 25)were divided into renogram normal (n = 9) and abnormal (n = 16) groups according to the imaging data. Additionally, normalpatients were selected as the control group (n = 25). After imaging, the region of interest of the kidneys was delineated, andrenography was performed. Renography can provide renal function parameters, including glomerular filtration rate (GFR),Tmax, T1/2, renal clearance, and the GFR ratio of the duplex renal segment (upper renal moiety).Results: Compared with the control group, the serum creatinine level in the duplex kidney group was higher (p = 0.025), GFRwas lower (p = 0.001), and patients with impaired renal function were mainly in the abnormal renography group (p = 0.001). Inthe duplex kidney group, the GFR (p = 0.026) and renal clearance (p = 0.006) of the affected kidneys were lower than those of thecontralateral kidneys, and Tmax (p = 0.025) was higher than that of the contralateral kidneys. There were no differences in renalfunction indicators of duplex renal segments with different GFR ratios. However, when the GFR ratio exceeded 50%, the renalfunction tended to decline.Conclusions: 99mTc-DTPA renal dynamic imaging was found useful to evaluate the total renal function, split renal function,and upper urinary tract patency in patients with duplex kidneys. Patients with abnormal renography results had worse renalfunction, and those with poor renal clearance in the affected renal moiety required surgical treatment. (AU)