Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To investigate the value of the virtual monoenergetic image (VMI) obtained by a new dual-layer detector spectral CT combined with metal artifact reduction algorithms(O-MAR) in reduction of different types of artifacts caused by 125I seeds implantation and in improvement of the post-operative CT image quality. Methods:This was a cross-sectional study. Thirty-five patients who underwent dual-layer detector spectral CT scanning of the chest and abdomen after 125I seeds implantation were retrospectively included at the First Affiliated Hospital of Zhengzhou University from March to September 2022. The spectral data were collected and reconstructed into conventional CT image (CI), VMI image (50-150 keV, 20 keV/level), CI+O-MAR image, and VMI+O-MAR image (50-150 keV, 20 keV/level). The artifacts′ removal effects and image quality improvement in each group were evaluated. Two slices with the strongest artifacts were selected for analysis for each patient, resulting in a total of 70 slices. Objective indicators including artifact index (AI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of soft tissue regions affected by artifacts were measured and calculated. Subjective indicators including the overcorrected artifacts and new artifacts, the different forms of artifacts, the diagnosis of artifacts, and the image quality were assessed. One-way analysis of variance was used for comparisons among multiple groups. Paired t test was used to compare the quantitative indicators between the combined O-MAR group and the non-O-MAR group. Kappa statistics was used to evaluate the consistency between observers. Results:In high/low-density artifacts (ROI H/L), the AI values in all groups showed decrease with increasing VMI keV. In artifact-affected tissue (ROI T), SNR of the CI/VMI (70-150 keV)+O-MAR group were significantly higher than those of the CI/VMI group ( P<0.05), CNR of the CI/VMI(50-150 keV)+O-MAR group were significantly higher than those of the CI/VMI group ( P<0.05). Both overcorrection and new artifacts mainly presented in VMI 50 keV and VMI 70 keV groups; Compared with VMI (50-70 keV) group, significantly less numbers of overcorrection and new artifacts were found in VMI (50-70 keV)+O-MAR group ( P<0.05); regarding the comparison of artifact types, with the VMI keV increasing, the number of a-type banded artifacts gradually decreased on images with high-density artifacts, reaching a minimum of 3 in the VMI 150 keV+O-MAR group; while the number of e-type artifacts with little or no artifacts increased, with the highest number of 23 in the VMI 150 keV+O-MAR group. The total number of high-density artifacts in each type decreased with increasing VMI keV. As VMI keV increased, the diagnostic and image quality scores of high-density artifacts in each group were significantly higher than those of low-density artifacts in the VMI+O-MAR group ( P<0.05). Conclusions:VMI combined with O-MAR can significantly improve the objective and subjective image quality of follow-up CT imaging after 125I seed implantation, enhancing lesion visibility and diagnostic confidence. Additionally, VMI+O-MAR showed more pronounced correction effect on high-density artifacts.

Objective:To investigate the effect of fecal microbiota transplantation(FMT)on unilateral ureteral obstruction(UUO)-induced renal fibrosis in mice.Methods:Male C57BL/6J mice were randomly divided into the control group,UUO group,UUO+FMT group and myeloid-derived suppressor cells(MDSCs)transfer group.The latter 3 groups were constructed renal fibrosis models by UUO,the UUO+FMT group received FMT from control mice after UUO surgery,and the MDSCs transfer group underwent splenectomy and intravenous injection of MDSCs from the peripheral blood of the UUO+FMT group.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.TNF-α and IL-10 expression levels were detected by real-time fluorescence quantitative PCR(qRT-PCR),Western blot and immunofluorescence staining.Results:HE staining showed that the renal tissue structure of the control group was normal.The UUO group showed significant dilatation of renal tubules accompanied by obvious inflammatory cell infiltration.However,the renal lesions in the UUO+FMT group and MDSCs transfer group were significantly improved compared with those in the UUO group.Masson staining showed that the positive area of collagen deposition significantly increased in the UUO group compared with the control group,while the positive area of collagen deposition decreased in the UUO+FMT group and MDSCs transfer group compared with the UUO group.The results of qRT-PCR,Western blot and immunofluorescence showed that the expression levels of TNF-α and IL-10 were elevated in renal tissues of the UUO group compared with the control group.Compared with the UUO group,the expression level of TNF-α decreased while IL-10 increased in the UUO+FMT group and MDSCs transfer group.Conclusions:FMT reduces the expression of TNF-α and increase the expression of IL-10 in the kidney of UUO mice,and alleviates renal fibrosis.FMT may exert a nephroprotective effect by regulating MDSCs.

Objective:To investigate the iodine nutritional status, prevalence and distribution characteristics of thyroid nodules among children and adolescents in Jurong City, Jiangsu Province, and study the risk factors for thyroid nodules in children and adolescents.Methods:In 2021, a cluster sampling method was used to select one primary and one secondary school in the urban and rural areas of Jurong City, ≥150 children and adolescents were selected as survey respondents from each school on a class-by-class basis, including third-grade children in primary schools and seventh-grade adolescents in secondary schools. The basic information and mental health status of survey respondents were collected by basic information questionnaires and Children's Anxiety Related Emotional Disorders Screening Form (SCARED). Water samples were collected from schools where survey respondents were enrolled and from townships where schools were located, and the iodine content in the water were tested. At the same time, household salt and urine samples from survey respondents were collected to test the salt iodine and urine iodine. Thyroid volume and thyroid nodules were measured using B-ultrasound method to analyze goiter (swelling of the thyroid gland) and thyroid nodules. The Cochran-Armitage trend test method was applied for trend analysis, and a multivariate logistic regression model was used to analyze the risk factors for thyroid nodules.Results:A total of 710 children and adolescents (370 males and 340 females) were surveyed, including 347 children (169 males and 178 females) and 363 adolescents (201 males and 162 females). A total of 14 water samples were collected, with an iodine content range of 8.98 to 10.82 μg/L and a median iodine content of 9.98 μg/L. A total of 710 edible salt samples were tested, with a salt iodine content of (20.94 ± 1.94) mg/kg, an iodine salt coverage rate of 100.00%, and a qualified iodine salt consumption rate of 97.46% (692/710). A total of 710 urine samples were tested, with a median urine iodine of 288.13 μg/L, median urinary iodine for boys and girls was 310.29 and 245.12 μg/L, respectively, and the difference between the two was statistically significant ( Z = - 5.91, P < 0.001). A total of 710 children and adolescents were tested by B-ultrasound, and the detection rate of goiter and thyroid nodules was 2.25% (16/710) and 25.07% (178/710). There was no significant upward trend in the detection rate of thyroid nodules with age (χ 2trend = 0.45, P = 0.651). The detection rates of thyroid nodules in boys and girls were 20.00% (74/370) and 30.59% (104/340), respectively, and the difference between the two was statistically significant (χ 2 = 10.57, P < 0.001). Multivariate logistic regression analysis indicated that female students who participated in extracurricular tutoring/interest classes in the past month were two influencing factors for thyroid nodules in children and adolescents ( OR = 1.76, 1.54, 95% CI: 1.25 - 2.49, 1.09 - 2.17, P < 0.05). Conclusions:The iodized salt coverage rate, qualified iodized salt consumption rate, and goiter rate in children and adolescents in Jurong City have all reached the elimination standard for iodine deficiency disorders, and their iodine nutrition is at a super-appropriate level. However, the external environment of Jurong City is still iodine-deficient. The detection rate of thyroid nodules in children and adolescents is at a high level. Female students and those who have participated in extracurricular tutoring/interest classes in the past month are risk factors for thyroid nodules in children and adolescents.

Objective To explore the impact of δ-catenin expression level on resting-state brain function in breast cancer patients.Methods Totally 104 female breast cancer patients were prospectively enrolled and divided into δ-catenin high expression group(DH group,n=51)and δ-catenin low expression group(DL group,n=53)according to δ-catenin expression level,while 36 female healthy volunteers were selected as controls(control group).Neuropsychological tests were performed,and resting-state functional MRI(rs-fMRI)were acquired,then parameters of brain function,including amplitude of low frequency fluctuation(ALFF),fractional ALFF(fALFF),regional homogeneity(ReHo)and functional connectivity strength(FCS)of brain regions with differences among groups were obtained.Spearman correlation analysis was used to evaluate the correlations of function parameters of brain regions with general data and neuropsychological test scores.Results Significant differences of fALFF,ReHo and FCS values were found among 3 groups(familywise error rate[FWE]correction,all P＜0.05).fALFF value of left inferior temporal gyrus in DH and DL groups were both higher than that in control group(FWE correction,both P＜0.05),ReHo value of right inferior temporal gyrus in DH group,as well as of right middle temporal gyrus,right inferior temporal gyrus and right fusiform gyrus in DL group were all lower than that in control group(FWE correction,all P＜0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus,left calcarine fissure surrounding cortex and left inferior temporal gyrus in DH group were all higher than that in DL group(FWE correction,all P＜0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus and left calcarine fissure surrounding cortex in DH group were all higher than that in control group(FWE correction,all P＜0.05),while FSC value of left lingual gyrus,left lenticular nucleus and left putamen were both higher than that in control group(FWE correction,both P＜0.05).In brain regions with different fMRI indexes between DH group and DL group,FSC values were lowly positively correlated with CogPCA results(r=0.313,P＜0.05).In brain regions with different fMRI indexes between DH group and control group,fALFF value were lowly positively correlated with trail making test A(TMT A)and trail making test B(TMT B)(r=0.301,0.310,both P＜0.05),ReHo values were lowly negatively correlated with TMT B(r=-0.307,P＜0.05),FCS values were weakly/lowly positively correlated with TMT A and TMT B(r=0.282,0.309,both P＜0.05)and lowly negatively correlated with results of digital symbol substitution test(DSST)(r=-0.363,P＜0.05).In brain regions with different fMRI indexes between DL group and control group,fALFF values were weakly/lowly negatively correlated with results of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),auditory verbal learning test(AVLT)short-term memory and DSST(r=-0.399,-0.362,-0.344,-0.288,all P＜0.05).Conclusion The expression level of δ-catenin had certain impact on brain function of breast cancer patients,resulted in asymmetry changes of brain network in bilateral hemispheres,as well as memory loss through affecting left inferior temporal gyrus,left lenticular nucleus,left putamen and left fusiform gyrus.

Objective:To compare image quality and diagnostic parameters of whole-brain CT perfusion scans under different scanning conditions and assess the utility of deep learning image reconstruction algorithm (DLIR) in reducing tube current during low-dose scans.Methods:Method A total of 105 patients with suspected acute ischemic stroke (AIS) were prospectively enrolled in the First Affiliated Hospital of Zhengzhou University from March, 2022 to March, 203 and their baseline information was recorded. All patients underwent head non-contrast CT and CT perfusion (CTP) examinations. CTP scanning was performed at 80 kV in two groups with the tube current of 150 mA (regular dose) and 100 mA (low dose), respectively. The CTP images of 150 mA group were reconstructed using filtered back-projection algorithm as well as adaptive statistical iterative reconstruction-V (ASIR-V) at 40% and 80% strength levels, which were denoted as groups A-C. The CTP images of 100 mA group were reconstructed using ASIR-V80%, DLIR-M, and DLIR-H, which were denoted as groups D-F. Clinical baseline characteristics and radiation doses were compared between the two groups under different scanning conditions. Furthermore, we assessed the subjective and objective image quality, conventional perfusion parameters, and abnormal perfusion parameters of AIS patients across the six groups of reconstructed CTP images.Results:Under the scanning conditions of 150 mA and 100 mA, 47 and 48 patients were diagnosed with AIS, respectively. There were no significant differences in the baseline characteristics between the two groups. However, there was a significant difference in the mean effective radiation dose (5.71 mSv vs. 3.80 mSv, t = 2 768.30, P < 0.001). The standard deviation (SD) of noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of gray matter (GM) and white matter (WM) were significantly different among the six groups of reconstructed images ( F = 40.58-212.13, P < 0.001). In GM, the SD values in groups C, D, and F were lower than those in other groups ( P < 0.05), and the SNR values in groups C and F were higher than those in other groups ( P < 0.05). In WM, the SD and SNR values in groups C and F were significantly different from those in other groups ( P < 0.05). Additionally, CNR values in groups C and F were higher than those in other groups ( P < 0.05). There was no significant difference in subjective scores among groups B, C, and F ( P > 0.05). Regarding perfusion parameters in the brain GM, groups D and E had lower cerebral blood volume (CBV) values compared to groups A to C ( P < 0.05), and group F had lower CBV values than group B ( P < 0.05). In the brain WM, group D had consistently lower mean transit time (MTT) values compared to the other groups ( P < 0.05). Notably, there were no significant differences in AIS lesion detection rates and relevant diagnostic parameters across the six image groups. Conclusions:Low-tube current CTP scan combined with the DLIR-H algorithm can enhance image quality without affecting perfusion parameters such as CBV and MTT, while reducing radiation dose by 30%. This algorithm can be routinely applied in brain CTP examinations.

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
Rats ; Animals ; Doxorubicin/adverse effects* ; Nephrotic Syndrome ; AMP-Activated Protein Kinases/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

ObjectiveTo analyze the application of telerehabilitation in patients with coronary heart disease (CHD) based on the theories and methods of the International Classification of Functioning, Disability and Health (ICF). MethodsLiteratures on the application of telerehabilitation in patients with CHD from databases of PubMed, Web of Science, CNKI, and Wanfang data were retrieved from establishment to May 5th, 2022. Scoping review methods were used to analyze the intervention measures, evaluation methods and indicators, rehabilitation outcomes, and influencing factors on patients with CHD based on ICF. ResultsA total of 4 172 literatures were retrieved, and 15 of them from five countries were enrolled. They were almost published in journals on medical and public health, from 2015 to 2022. The main elements of telerehabilitation included nine items: the establishment of telerehabilitation group, the establishment of personal health profiles, physical activity, exercise monitoring, provision of relevant knowledge, communication and guidance from professionals, provision of psychological support, self-report and supervision and reminder of medical staff. According to the ICF framework, telerehabilitation promoted the function of patients with CHD mainly in body function (including b1 mental functions, b4 function of the cardiovascular, hematological, immunological and respiratory systems, b5 functions of the digestive, metabolic and endocrine systems, and b7 neuromusculoskeletal and movement-related functions) and activity and participation (including d2 general tasks and demands, d4 mobility, d7 interpersonal interactions and relationships, d8 major life areas, and d9 community, social and civic life). The factors affecting the activity and participation of patients with CHD contained environmental factors and personal factors, mainly including e1 products and technology, e3 support and relationships, e4 attitudes, and e5 service, systems and policies. ConclusionThis paper summarized nine items of telerehabilitation for patients with CHD, and analyzed the effects and related influencing factors of telerehabilitation on patients with CHD based on ICF.