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

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.

Objective To investigate the feasibility of using contrast-enhanced T1WI radiomics in predicting the pathological grade in rectal adenocarcinoma.Methods The MRI and pathological data of 127 patients with rectal adenocarcinoma were analyzed retrospectively.ITK-SNAP software was used to manually draw region of interest(ROI)in rectal cancer on axial T,WI enhanced images.The radiomics features were extracted by the Pyradiomics software from ROI.The task was divided into two parts:task 1("high & non-high"group)predicted the high-differentiation and moderate/low-differentiation of the tumor;task 2("moderate & low"group)predicted the tumor's moderate-differentiation and low-differentiation in"non-high"group.Maximum relevance and minimum redundancy(mRMR)method was used to screen features.The five methods including least absolute shrinkage and selection operator(LASSO),logistic regression(LR),naive Bayes(NB),random forest(RF),and support vector machine(SVM)were used to build the models,and the efficiency of each model was evaluated and compared.Results In task 1,the area under the curve(AUC)of five methods were 0.86,0.90,0.59,1.00,0.99 in the training cohort and 0.71,0.62,0.53,0.67,0.64 in the testing cohort.In task 2,the AUC of five methods in the training cohort were 0.93,0.85,0.67,0.92,0.89,and in the testing cohort were 0.86,0.80,0.50,0.78,0.71.The models constructed by LASSO in both tasks were the dominant models,the AUC of the fusion model in the testing cohort which combined with age,gender and the dominant Radiomics score(Radscore)was 0.80[95％confidence interval(CI)0.63-0.96]in task 1,and the accuracy,sensitivity and specificity were 78.94％,77.78％,and 79.31％respectively.They were 0.89(95％CI 0.74-1.00),90.00％,95.65％,and 71.43％,respectively in task 2.The calibration curves showed that the fusion models had a good goodness of fit.Conclusion Based on the establishment of two dichotomous models,the radiomics based on the contrast-enhanced T1 WI is feasible in predicting the high,moderate and low differentiation degree of rectal adenocarcinoma.

Purpose: The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. Methods: A total of 70 patients who underwent surgery for endometrial lesions at the authors’ hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. Results: Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). Conclusion Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.

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.

Objective To compare the survival outcomes of bladder cancer with non-pure urothelium(BCa with n-pU)and bladder cancer with pure urothelium(BCa with pU)treated with robot-assisted radical cystectomy(RARC).Methods Clinical data of BCa patients treated with RARC in Nanjing Drum Tower Hospital during Oct.2014 and Mar.2022 were retrospectively analyzed.The patients were divided into n-pU group and pU group.After the baseline differences between groups were balanced with propensity score matching(PSM),the overall survival(OS)and recurrence-free survival(RFS)curve were plotted using Kaplan-Meier method and compared using Log-rank test.Univariate and multivariate analysis were performed with Cox model to identify the influencing factors of prognosis.Based on the results,a secondary grouping was performed to compare the survival differences between subgroups and further investigate the prognostic factors.Results After PSM,there were 53 pairs of BCa patients.There were no significant differences in the baseline data between the pU and n-pU groups(P＜0.05).Regardless of T stage,there were no significant differences in OS and RFS between the two groups(P=0.217,P=0.109).Univariate Cox regression analysis showed that T stage(＞T2)was a significant risk factor of OS and RFS(P＜0.05).In the early pathological stage(≤T2),there were no significant differences in OS and RFS(P=0.565,P=0.344).In the advanced pathological stage(＞T2),the OS and RFS of n-pU were significantly worse than those of pU patients(P=0.025,P=0.034).Conclusion The prognosis of BCa patients with n-pU who received RARC is significantly correlated with pathological status.At＞T2 stage,n-pU patients have worse prognosis than pU patients in the same pathological status.