Objective To explore the change of nucleoplasm distribution of glucocorticoid receptor alpha(GRα)in peripheral blood of children with primary nephrotic syndrome(PNS)during the course of the disease,aiming at evaluating the correlation between nuclear transport abnormality and different GC responses.Methods A total of 45 children with PNS were enrolled as subjects in this prospective study,and divided into steroid-sensitive nephrotic syndrome(SSNS,n=36)and steroid-resistant nephrotic syndrome(SRNS,n=9)groups,according to their response to GC.The SSNS group was further subclassified into non-frequently relapsing nephrotic syndrome(NFRNS,n=21)and frequently relapsing nephrotic syndrome(FRNS,n=15)based on relapse frequency during 12-month follow-up.Peripheral blood samples were collected before GC treatment,6-week and 6-month after GC treatment.GRα nuclear localization was detected by immunofluorescence assay,and their correlations with clinical-laboratory indicators were analyzed.Results Before the GC treatment,the average fluorescence intensity showed no significantly difference among different groups(P＞0.05),the GRαin the three groups were localized mainly in cytoplasm,and the nucleocytoplasmic ratio showed no significantly difference among the three groups(P＞0.05).6-week after the GC treatment,the average fluorescence intensity showed no significantly difference among the three groups(P＞0.05),the GRα in SSNS group were localized mainly in nucleus,while those in SRNS group were localized mainly in cytoplasm.Furthermore,nucleocytoplasmic ratio in NFRNS group and SRNS group demonstrated significant differences,while those in NFRNS group and FRNS group showed no significant difference(P＞0.05).6-month after the GC treatment,the average fluorescence intensity in NFRNS group and FRNS group showed no significant difference(P＞0.05),GRα in the two groups were localized mainly in nucleus,and their nucleocytoplasmic ratio had significantly differences(P＜0.05).The GRα nucleocytoplasmic ratio in children with PNS was negatively correlated with 24-hour urine protein(24 h-UTP),TNF-α,while positively correlated with serum albumin(Alb).Conclusion There are differences in nuclear transport ability among PNS children of SRNS,NFRNS and FRNS groups,and these differences are correlated with the differency of GC responses.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Objective To explore the change of nucleoplasm distribution of glucocorticoid receptor alpha(GRα)in peripheral blood of children with primary nephrotic syndrome(PNS)during the course of the disease,aiming at evaluating the correlation between nuclear transport abnormality and different GC responses.Methods A total of 45 children with PNS were enrolled as subjects in this prospective study,and divided into steroid-sensitive nephrotic syndrome(SSNS,n=36)and steroid-resistant nephrotic syndrome(SRNS,n=9)groups,according to their response to GC.The SSNS group was further subclassified into non-frequently relapsing nephrotic syndrome(NFRNS,n=21)and frequently relapsing nephrotic syndrome(FRNS,n=15)based on relapse frequency during 12-month follow-up.Peripheral blood samples were collected before GC treatment,6-week and 6-month after GC treatment.GRα nuclear localization was detected by immunofluorescence assay,and their correlations with clinical-laboratory indicators were analyzed.Results Before the GC treatment,the average fluorescence intensity showed no significantly difference among different groups(P＞0.05),the GRαin the three groups were localized mainly in cytoplasm,and the nucleocytoplasmic ratio showed no significantly difference among the three groups(P＞0.05).6-week after the GC treatment,the average fluorescence intensity showed no significantly difference among the three groups(P＞0.05),the GRα in SSNS group were localized mainly in nucleus,while those in SRNS group were localized mainly in cytoplasm.Furthermore,nucleocytoplasmic ratio in NFRNS group and SRNS group demonstrated significant differences,while those in NFRNS group and FRNS group showed no significant difference(P＞0.05).6-month after the GC treatment,the average fluorescence intensity in NFRNS group and FRNS group showed no significant difference(P＞0.05),GRα in the two groups were localized mainly in nucleus,and their nucleocytoplasmic ratio had significantly differences(P＜0.05).The GRα nucleocytoplasmic ratio in children with PNS was negatively correlated with 24-hour urine protein(24 h-UTP),TNF-α,while positively correlated with serum albumin(Alb).Conclusion There are differences in nuclear transport ability among PNS children of SRNS,NFRNS and FRNS groups,and these differences are correlated with the differency of GC responses.

Objective:To explore the value of ultrasound imaging characteristics combined with clinical indicators in assessing the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC).Methods:A retrospective analysis was conducted for patients who underwent pancreatic contrast-enhanced ultrasound (CEUS) from September 2017 to October 2023 at Peking Union Medical College Hospital and were diagnosed with PDAC based on pathological findings. Various parameters were recorded, including CA19-9 levels, tumor size, location, morphologic features, echogenicity, presence of internal cystic components, dilatation of the main pancreatic duct, peripheral vascular invasion, CEUS characteristics, presence or absence of liver metastasis, and treatment methods. In April 2024, patient survival information was obtained through telephone follow-up or review of medical records. Based on the results of the cox regression model analysis, a nomogram model of the risk of death was developed. The receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of the model. The calibration curves were plotted to evaluate the accuracy of the model, and clinical decision curves were used to evaluate the clinical benefit of the model.Results:This study included a total of 207 patients with PDAC. As of April 2024, 71 patients were alive and 136 died, with a median survival time of 14 months (95% CI: 12 -17). Multivariate analysis confirmed that the elevated CA19-9 ( HR=1.689, 95% CI: 1.102-2.588), tumor size >4 cm ( HR=1.641, 95% CI: 1.159-2.322), taller-than-wide shapes ( HR=1.450, 95% CI: 1.019-2.065), incomplete hypo-enhancement ( HR=1.618, 95% CI: 1.100-2.380), and liver metastasis ( HR=1.687, 95% CI: 1.175-2.423) were independent risk factors for survival in patients with PDAC. A nomogram model was further constructed for 6-month, 12-month and 3-year survival of patients with PDAC. The areas under the ROC curve were 0.679, 0.705 and 0.815, respectively. The calibration curves suggested that the model was more accurate, and the clinical decision curves showed that the model had a better clinical benefit. Conclusion:The combined use of ultrasound imaging characteristics and clinical indicators could effectively predict the prognosis of PDAC patients. Specifically, tumor size >4 cm, taller-than-wide shapes, incomplete hypo-enhancement, elevated CA19-9, and the presence of liver metastasis are correlated with poorer survival outcomes. The nomogram model constructed on the basis of these factors can be used to assess the survival of patients with PDAC.

Objective:To explore the effect of Wuqinxi combined with resistance training on cardiac function and self-care ability in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 152 CHF patients admitted to Nanjing Hospital of Chinese Medicine between September 2018 and December 2022.Pa-tients were divided into control group(n=76)and intervention group(n=76).Patients in control group received routine intervention measure combined resistance training,while those in the intervention group received additional Wuqinxi.Both groups were intervened for 6 months.The clinical total effective rate,cardiac function,self-care ability and quality of life were compared between two groups.We also compared the incidence of adverse events and readmission rate during 6-month follow-up.Results:The total effective rate of the intervention group was sig-nificantly higher than that of the control group(93.2％vs.81.1％,P=0.003).Compared with patients in the control group,those in the intervention group had significant higher left ventricular ejection fraction(LVEF)[(50.08±8.37)％vs.(43.47±8.02)％]and 6min walking distance(6MWD)[(496.76±40.54)m vs.(406.76±28.65)m](P＜0.001 both);and significant lower left ventricular end-diastolic volume(LVEDV)[(109.82±9.90)ml vs.(165.29±12.26)ml],left ventricular end-systolic volume(LVESV)[(59.09±2.69)ml vs.(72.61±3.54)ml],score of the European Heart Failure Self-care Behaviour Scale(EHFScBS)[(26.49±3.24)points vs.(35.80±4.33)points],and Minnesota Living with Heart Failure Questionnaire(MLHFQ)total score[(43.78±4.50)points vs.(56.55±4.92)points](P＜0.001 all).The total incidence of adverse events(2.8％vs.12.3％)and readmission rate(1.4％vs.11.0％)in the intervention group were significantly lower than those of the control group(P＜0.05 both).Conclusion:Wuqinxi combined with resistance training may improve clinical efficacy,cardiac function,self-care ability,reduce incidence of adverse events and readmission,then improve quality of life in CHF patients.

As a pediatric radiation oncologist, it is necessary to master and evaluate the sedative/anesthesia indications, adverse reactions and solutions and deliver whole-course management of sedation/anesthesia in pediatric radiotherapy under sedation. Although significant progress has been made in sedation/anesthesia, the psychological stress and family burden of sedation/anesthesia still exist. There is still great research potential in the field of investigating effective nonpharmacological interventions to reduce sedation/anesthesia use. In this article, the issues and challenges of sedative management and complications of pediatric radiotherapy and interventions for reducing sedation/anesthesia of radiotherapy were reviewed.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To investigate the clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Three cases of UESL diagnosed in the Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University from 2020 to 2023 were retrospectively collected. The clinical, histomorphological, immunohistochemical, and genetic profiles were reviewed and analyzed.Results:The cohort comprised of three patients, including one male and two females, aged 7, 9, and 15 years, respectively. Tumor locations were in the right lobe of the liver in two cases, and in both the right and left lobes in one case. One case exhibited tumor rupture with hemorrhage. Gross examination revealed solid tumors in gray-red fleshy appearance, with areas of hemorrhage and necrosis. Microscopically, the tumor was composed of irregularly shaped spindle and polygonal cells arranged in bundles or sheets with varying density, scattered within a myxoid matrix containing giant tumor cells and eosinophilic globules. The tumor cells were positive for Vimentin, CD56, CD68, and bcl-2, with a Ki-67 index of 30%-80%. INI1 expression was retained, while p53 exhibited a mutant pattern. CKpan, CK7, CK19, EMA, HepPar-1, Arginase-1, AFP, CD34, S-100, Myogenin, and MyoD1 were negative. All three cases harbored TP53 missense mutations. Case 1 also showed MDM2 copy number amplification (class Ⅰ mutation), and case 2 exhibited a frameshift mutation in exon 10 of TSC2 (class Ⅱ mutation). Additionally, several class Ⅲ mutations were identified in all three cases. Germline testing for tumor-related genetic variants in case 2 revealed a missense mutation in exon 12 of DICER1, an in-frame insertion mutation in exon 8 of MSH2, and a missense mutation in exon 30 of TSC2.Conclusion:UESL is a rare malignant mesenchymal tumor of the liver, predominantly affecting children, with distinctive clinicopathological features and genetic alterations. TP53 mutations may play a key role in the pathogenesis of this tumor.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*