Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

OBJECTIVES: To evaluate the inhibitory effect of oridonin against proliferation of pancreatic cancer cells and the mechanism underlying the synergistic effect of low-intensity pulsed ultrasound (LIPUS). METHODS: PANC-1 cells treated with different concentrations of oridonin were examined for changes in cell proliferation using CCK-8 assay and in MDA, GSH and ATP levels using flow cytometry. The protein expressions of GPX4, Nrf2 and HO-1 in the treated cells were detected with Western blotting. The effect of Fer-1, a ferroptosis inhibitor, on proliferation of oridonin-treated cells were assessed, and the effects of oridonin combined with LIPUS on PIEZO1 protein expression was evalauted using Western blotting. A C57BL/6J mouse model bearing pancreatic cancer cell xenograft was established and treated with oridonin, LIPUS, or both, and the histological changes in the tumor tissues and tumor cell proliferation were examined with HE staining and immunohistochemistry for Ki67; the changes in GPX4 expression in the tumor tissues were detected using Western blotting and immunofluorescence staining. RESULTS: In PANC-1 cells, oridonin treatment significantly inhibited cell proliferation, increased intracellular Fe²⁺, ROS, and MDA levels, and decreased GSH and ATP levels. Oridonin also resulted in lowered GPX4 and increased HO-1 and Nrf2 protein expression levels in the cells. The combined treatment with LIPUS signficiantly enhanced the inhibitory effect of oridonin on PANC-1 cell viability in vitro and on xenograft growth in the mouse models, resulting also in more obvious reduction of the intensity of Ki67 staining and GPX4 protein expression and more pronounced increase of PIEZO1 protein expression in the tumor tissues in the mouse models. CONCLUSIONS LIPUS enhances the effect of oridonin to promote ferroptosis of pancreatic cancer cells by activating PIEZO1 through the Nrf2/HO-1/GPX4 pathway.
Ferroptosis/drug effects* ; Animals ; Pancreatic Neoplasms/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Cell Line, Tumor ; Mice ; Heme Oxygenase-1/metabolism* ; Diterpenes, Kaurane/pharmacology* ; Cell Proliferation/drug effects* ; Mice, Inbred C57BL ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ion Channels/metabolism* ; Ultrasonic Waves ; Signal Transduction

Objective To explore the mediating role of intolerance of uncertainty(IU)and moderating role of the negative emotion differentiation in the influence of perceived stress on anxiety among college students from a cognitive perspective.Methods A total of 271 participants were surveyed using the perceived stress scale,intolerance of uncertainty scale,depression anxiety and stress scale(Chinese version),and the test on negative emotional differentiation.SPSS 22.0 was used to perform descriptive statistics and correlation analyses and to test the moderated mediation model.Results Perceived stress affected anxiety and IU played a mediating role-perceived stress could affect anxiety through influencing IU.At the same time,the influence of IU on anxiety could be adjusted through the negative emotion differentiation.The higher the degree of negative emotion differentiation,the lower the degree of anxiety increase(β=0.17,t=5.70,P＜0.01).Conclusion It may be effective to develop training programs to reduce anxiety by regulating perceived stress,increasing acceptance of uncertainty,and improving the negative emotion differentiation,which can help individuals reduce anxiety by perceiving and adjusting anxiety-related emotional or cognitive factors in a timely manner.

Objective To design a custom 3D printed monoblock acetabular implant for reconstructing PaproskyⅢA acetabular bone defects and to analyze the stress distribution,displacement,and clinical reliability of the implant and surrounding bone using finite element analysis(FEA).Methods Bilateral hip computed tomography(CT)data of a patient with PaproskyⅢA acetabular bone defects were collected.Models were developed and analyzed using Mimics Medical 21.0,Geomagic Wrap 2021,Solidworks 2023,and ANSYS Workbench 2022 R1 softwares.The biomechanical performance of the custom 3D printed monoblock acetabular implant was simulated under a single-leg stance condition.Results The peak von Mises stress of the hip components was observed at the femoral stem,measuring 67.318 MPa.For the custom 3D printeded monoblock acetabular implant,the peak stress was located at the anterosuperior contact area between the implant and acetabular bone,measuring 6.935 MPa.The femoral stem exhibited a peak stress of 67.318 MPa at its junction with the femoral head.The liner's peak stress was 1.333 MPa near the fixation of screw 9 at the superior part of the acetabular cup.The screws showed a peak stress of 2.215 MPa at the junction with the implant.For the cortical bone,the peak stress was 9.844 MPa at the distal femur,while the cancellous bone exhibited a peak stress of 0.701 MPa at its distal connection with the femoral stem.The pelvic bone's peak stress was 8.002 MPa at the anterior transition zone between the normal acetabulum and the defect.The peak micromotion of the custom 3D printed monoblock acetabular implant at its posterosuperior area,measuring 0.114 mm.The femoral stem and head exhibited a peak micromotion of 0.132 mm at the contact interface with the acetabular liner.The micromotion range at the implant-acetabular bone interface was 0.098 mm to 0.131 mm.Conclusion Under a simulated single-leg stance condition,the stress distribution in all components and the acetabular bone surface remains below their respective yield strengths.The micromotion threshold between the acetabular cup and acetabular bone is within acceptable limits.Biomechanical analysis indicates that the patient can perform early weight-bearing rehabilitation postoperatively.However,walking or jogging rehabilitation should be approached with caution.

OBJECTIVE To systematically evaluate the therapeutic effect of acupuncture on geriatric insomnia.METHODS Randomized controlled trials(RCTs)on acupuncture in the treatment of senile insomnia were searched in CNKI,VIP,Wanfang,China Biomedical Database,PubMed,Web of science,Embase and Cochrane Library databases from inception dates to June 24,2024.Litera-ture was screened and data were extracted based on the inclusion and exclusion criteria.The literature quality was evaluated according to the risk of bias table recommended by the Cochrane Collaboration Handbook 5.1.0,and the outcome indicators were graded using the GRADE system for the quality of evidence.RevMan5.4 software was used to evaluate the quality of the included literature,and Sta-ta18.0 software was used to conduct Meta-analysis on the included literature.RESULTS A total of 18 studies involving 1399 pa-tients were included.Meta-analysis showed that:compared with the simple western medicine treatment,acupuncture in the treatment of senile insomnia patients could improve the clinical effective rate[RR=1.18,95%CI(1.13,1.24),P<0.001],reduce the total PSQI score[MD=-1.10,95%CI(-1.25,-0.96),P<0.001],daytime dysfunction[MD=-1.38,95%CI(-1.59,-1.16),P<0.001],sleep latency[MD=-0.66,95%CI(-0.86,-0.47),P<0.001],sleep duration[MD=-0.45,95%CI(-0.64,-0.25),P<0.001],sleep efficiency[MD=-0.69,95%CI(-0.89,-0.49),P<0.001],sleep disorder[MD=-1.24,95%CI(-1.47,-1.01),P<0.001],sleep quality[MD=-0.84,95%CI(-1.05,-0.64),P<0.001].GRADE classification showed that the clinical efficacy was advanced evidence;the adverse reactions were intermediate evidence;the total score of PSQI,daytime dysfunction,sleep latency,sleep efficien-cy,sleep quality and sleep disorder were low evidence;sleep time was extremely low evidence.CONCLUSION Acupuncture inter-vention in senile insomnia patients is superior to the control group in clinical efficiency and various PSQI scores.Acupuncture interven-tion is worthy of further promotion and use in clinical practice as the complementary and alternative therapy for the conventional western medication treatment of senile insomnia.However,the evidence levels of some outcome indicators are relatively low,and more high-quality RCTs with large sample sizes are still needed to increase the strength of evidence.

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and post-pancreatectomy.The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion feedback.Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement therapy.Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota.Pancreatic exocrine secretions and changes in duodenal pH as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota.In turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk.Going forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.