This paper reports the case of a 10-month-old male infant with Beckwith-Wiedemann syndrome (BWS) who presented with a reducible right inguinal mass and an empty scrotum for 10 months and was admitted for elective surgery. Preoperative ultrasonography revealed a right adrenal mass, which was pathologically diagnosed as ganglioneuroblastoma (GNB) after surgical excision. The patient exhibited characteristic features of BWS, including omphalocele, flame-shaped nevus on the forehead, bilateral earlobe creases, and embryonal tumor. Next-generation sequencing identified a heterozygous mutation in the CDKN1C gene (chr11:2905365), confirming the diagnosis of BWS. Early diagnosis, standardized management, and tumor surveillance are crucial for improving prognosis in children with BWS. Ultrasonography enables early detection of tumors and informs clinical decision-making regarding intervention.
Humans ; Beckwith-Wiedemann Syndrome/genetics* ; Male ; Ganglioneuroblastoma/complications* ; Infant ; Cyclin-Dependent Kinase Inhibitor p57/genetics* ; Mutation

Objective To investigate the therapeutic effect and mechanism of NLRP3 inflammasome inhibitor-dapansutrile(OLT1177)-against acute radiation lung injury.Methods Mice were divided into the control group,OLT1177 injection group,irradiation group,and irradiation+OLT1177 injection group.A single dose of 22 Gy whole-lung 60Co radiation was used to establish a model of acute radiation lung injury.After 6 h of radiation,OLT1177(100mg/kg,once daily)was administered intraperitoneally.After 14 consecutive days of administration,lung tissues were collected and weighed while the lung coefficient was calculated.Hematoxylin-eosin(HE)staining and F4/80 immuno-histochemical staining were used to observe the pathological changes and inflammatory cell infiltration in lung tissues.Real-time quantitative PCR(qPCR)was used to detect the transcription levels of NLRP3,IL-1β,and other mRNAs in lung tissues.Serum cytokines such as TNF-α and IL-6 were measured by cytometric bead array(CBA).The activation of Caspase-1 and IL-18 was detected by Western blotting.Results Radiation caused acute inflammation in the lung tissues of mice,manifested as edema in the lung tissues and destruction of the alveolar structure,increased macrophage infiltration,and elevated expressions of inflammatory genes NLRP3,IL-1β,TNF-α,and IL-6 in the lung tissues and higher serum levels of TNF-α,IL-6.Treatment with OLT1177 significantly improved the above symptoms induced by radiation.OLT1177 inhibited the activation of NLRP3 inflammasome downstream Caspase-1 and IL-18 induced by radiation.Conclusion OLT1177 can significantly alleviate acute radiation lung injury in mice,which may be due to its inhibition of NLRP3 inflammasome activation induced by radiation.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Objective To investigate the clinical efficacy of a compound oral sulfate solution for preoperative bowel cleansing in colonic polyp patients.Methods Patients who underwent colonoscopic polypectomy were divided into control group and treatment group according to cohort method methods.Patients in the control group were given compound polyethylene glycol electrolyte powder.They started taking it 4-6 hours before colonoscopy and completed the 4 liters of solution within 2 hours.Patients in the treatment group were given a compound oral sulfate solution.They took 1.5 liters of the solution the evening before surgery and repeated the same dosage on the day of the operation.Intestinal cleanliness was assessed using the Boston bowel preparation scale(BBPS),bowel preparation compliance,drug tolerance,patient satisfaction,and incidence of adverse drug reactions were compared between the two groups.Results Control group and treatment group each consisted of 40 cases.The total BBPS scores for the control group and treatment group were(6.68±1.19)and(7.43±1.23)points,respectively.This difference was statistically significant(P＜0.01).Medication compliance rates in the control group and treatment group were 70.00％(28 cases/40 cases)and 95.00％(38 cases/40 cases),respectively;movement compliance rates were 67.50％(27 cases/40 cases)and 97.50％(39 cases/40 cases)in the two groups,while medication tolerance rates were 67.50％(27 cases/40 cases)and 90.00％(36 cases/40 cases);patient satisfaction with bowel preparation were(1.89±0.75)and(2.42±0.43)points for the control and treatment groups,respectively;statistically significant differences were found between the control and treatment groups in all the above indicators(P＜0.05,P＜0.01,P＜0.001).The main adverse drug reactions in the control and treatment groups were nausea and vomiting,with occurrence rates of 10.00％(4 cases/40 cases)and 5.00％(2 cases/40 cases),respectively.The comparison of adverse drug reactions occurrence rate between the two groups showed no statistically significant difference(P＞0.05).Conclusion Taking compound oral sulfate solution for intestinal preparation,the intestinal cleaning effect is better than that of compound polyethylene glycol electrolyte powder,and the patient's compliance and drug tolerance are higher,and the patient's satisfaction can be effectively improved.

Objective To investigate the effects of neuronal pentraxin 2(Nptx2)on complement system,microglia activation and synaptic density in mice with Alzheimer's disease(AD).Methods Six-months-old APPswe/PS1dE9 double transgenic mice were divided into model group(intracerebroventricularly injected with AAV-Veh 1 × 1010 GC)and model+AAV-Nptx2 group(intracerebroventricularly injected with AAV-Nptx2 1 × 1010 GC),6-months-old wild-type mice were divided into control group(intracerebroventricularly injected with AAV-Veh 1 × 1010 GC)and control+AAV-Nptx2 group(intracerebroventricularly injected with AAV-Nptx2 1 x 1010 GC),with 12 mice in each group.One month later,the cognitive function of mice in each group was evaluated by Morris Water Maze test.The expression levels of Nptx2 and Iba1 proteins were measured by Western blot,the contents of complement related proteins were measured by enzyme linked immunosorbent assay,and the synaptic plasticity was evaluated by Golgi staining.Results The resident time in the platform quadrant of control,control+AAV-Nptx2,model and model+AAV-Nptx2 groups were(44.72±10.92),(53.32±10.29),(21.92±3.80)and(36.47±6.41)s;the number of crossing the platform were 10.08±2.64,9.58±3.09,2.25±1.29 and 5.92±1.38;the relative expression levels of Nptx2 protein were 0.33±0.06,0.63±0.10,0.09±0.03 and 0.57±0.22;the relative expression levels of Iba1 protein were 0.17±0.06,0.23±0.08,0.97±0.16 and 0.40±0.14;the synaptic densities were 22.75±4.27,29.25±4.78,8.25±2.99 and 23.75±4.86.Compared with the model group,the differences of above indexes in the model+AAV-Nptx2 and control groups were statistically significant(all P＜0.05).Conclusion Overexpression of Nptx2 protein can inhibit the activation of complement system,reduce the activation of microglia,and increase the synaptic density to alleviate cognitive impairment in AD mice.

Objective To analyze the stress distributions of two root canal preparation shapes of oval root canals with micro-crack.Methods Twenty single-canal mandibular premolars with oval canals were expanded to create micro-cracks.Roots were sectioned after staining.The generation and distribution of dentin micro-cracks were observed under microscope.Then a finite element(FE)model of sectioned enlarged oval canal roots with micro-cracks was established.The stress distribution of micro-crack and root were analyzed under lateral loading.Results Cracks always appeared in the buccolingual sides of oval canal roots and extended from the intracanal wall to the root surface.This was consistent with the stress concentration on the buccolingual side of the root canal wall shown by FE analysis.When micro-cracks occurred,stresses were transferred to the crack tip and the peak values increased sharply nearly 5 times.This made the cracks propagate easily along this direction,especially in the long axis direction of the tooth.Conclusions The presence of micro-cracks does not change the general stress concentration on root with two preparation morphologies of oval canals.However,the micro-crack causes an extreme stress concentration in the crack tip.This may be the mechanism of rapid propagation of microcracks into vertical root fracture,and dentists need to pay high attention.

ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease （COPD） model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide （LPS） along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank， model， and low- （L-FXY）， medium- （M-FXY）， and high-dose （H-FXY） Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke， with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling， the L-FXY， M-FXY， and H-FXY groups were administrated with Sennae Folium infusion at 5， 10， and 20 g·kg^-1， respectively， and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions （body mass， food intake， fecal water content， and anal temperature） and behaviors （grip strength test and tail suspension test） of rats in different groups were examined. The lung function， lung histopathology， D-xylose， amylase， and gastrin levels in the serum， interleukin（IL）-1β and IL-6 levels in the alveolar lavage fluid， levels of T-lymphocyte subsets （CD4⁺， CD8⁺， and CD4⁺/CD8⁺） in the peripheral blood， and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group， both the M-FXY and H-FXY groups exhibited reduced body mass and food intake （P<0.01） and increased fecal water content （P<0.01）. The anal temperature in the H-FXY group was lower than that in the blank group （P<0.01）. The grip strength decreased in the modeling groups compared with the blank group （P<0.01）， and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups （P<0.05， P<0.01）. Compared with the blank group， the modeling groups showed reduced 0.3 second forced expiratory volume （FEV_0.3）， FEV_0.3/forced vital capacity （FVC）（P<0.01）， thickening of bronchial walls， proliferation of goblet cells， and the presence of emphysematous changes. In terms of gastrointestinal function， the M-FXY and H-FXY groups had lower levels of D-xylose， gastrin， and α-amylase than the blank group （P<0.01）. Regarding the immune and inflammatory indices， the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group （P<0.01）. Compared with the blank group， the modeling groups presented lowered CD4⁺ level （P<0.01） and CD4⁺/CD8⁺ ratio （P<0.05， P<0.01） in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid （P<0.01） than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke， intratracheal instillation with LPS， and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose （10 g·kg^-1） Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.

Parkinson's disease （PD） is a progressive chronic neurodegenerative disorder with a complex pathogenesis involving oxidative stress， neuroinflammation， mitochondrial dysfunction， and other factors. Currently， the clinical treatment of PD mainly includes levodopa， dopamine receptor agonists， monoamine oxidase B inhibitors， catechol-O-methyltransferase inhibitors， and anticholinergic drugs， but there is a lack of disease-modif g therapies that can definitively improve disease progression. According to the understanding of traditional Chinese medicine （TCM）， PD is characterized by asthenia in origin and sthenia in superficiality. It is primarily caused by liver-kidney Yin deficiency， Qi-blood insufficiency， and closely related to wind， fire， phlegm， and blood stasis. Numerous clinical practices have shown that TCM has significant clinical value in the prevention and treatment of PD， the management of motor and non-motor symptoms， and the neuroprotection of dopaminergic neurons. The underlying mechanisms of TCM include antioxidative stress， anti-neuroinflammation， and regulation of mitochondrial dysfunction. This article categorized and summarized the pathogenesis of PD， systematically elucidated the pharmacological actions and molecular mechanisms of TCM monomer extracts and compounds in the prevention and treatment of PD， and provided the latest clinical research progress， aiming to provide references for the development and clinical use of TCM for PD.

Humans ; Brentuximab Vedotin ; Ki-1 Antigen ; Antineoplastic Agents ; Immunoconjugates/therapeutic use* ; Lymphoma/drug therapy*

ObjectiveTo explore the mechanism of Dendrobium huoshanense polysaccharide （DHP） against inflammatory damage of neurons in Parkinson's disease （PD） model. MethodSH-SY5Y cells were randomized into blank group， model group， and DHP group. The survival rate of cells was measured by thiazole blue（MTT） assay， and the levels of lactate dehydrogenase （LDH）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） were measured by colorimetric analysis. BV-2 microglia were classified into blank group， model group， DHP group， and MCC950 group （positive control group）， and enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. The expression of NOD-like receptor protein 3 （NLRP3）， adaptor protein apoptosis-associated dot protein （ASC）， cysteine aspartic protease-1 （Caspase-1）， and IL-1β was measured by Western blot. A total of 50 C57BL/6 mice were randomized into blank group， model group， DHP low-dose （100 mg·kg^-1） group， DHP equivalent-dose （350 mg·kg^-1） group， and MCC950 group （positive control group）， 10 mice in each group. The motor balance and coordination of C57BL/6 mice were observed by beam walking test， tail suspension test and rotarod test. The levels of Iba-1 and tyrosine hydroxylase （TH） were detected by immunofluorescence staining. The damage of dopaminergic neurons in the substantia nigra was detected by FJB staining. The levels of inflammatory factors such as IL-1β， IL-18， and TNF-α in mouse midbrain tissues were detected by ELISA and the protein levels of NLRP3， ASC， Caspase-1， and IL-1β protein were measured by Western blot. ResultCompared with the blank group， the SH-SY5Y model group showed decreased cell survival， increased levels of LDH， ROS， and MDA （P<0.05）， and decreased levels of SOD （P<0.05）. Compared with the model group， the DHP group demonstrated increased cell survival， decreased levels of LDH， ROS， and MDA （P<0.01）， and increased level of SOD （P<0.01）. Compared with the blank group， BV-2 model group had high levels of IL-1β， IL-18， and TNF-α （P<0.05） and high protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.05）. Compared with the model group， DHP and MCC950 groups demonstrated low levels of IL-1β， IL-18， and TNF-α （P<0.01） and low protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.01）. Compared with the blank group， the C57BL/6 model group displayed long time to pass the balance wood （P<0.05）， short time spent on the rod in the rotarod test （P<0.05）， high levels of IL-1β， IL-18， and TNF-α （P<0.05） and expression of Iba-1 in the midbrain substantia nigra （P<0.05）， low TH expression （P<0.05）， more positive neurons in the FJB staining （P<0.05）， and high expression of NLRP3， Caspase-1， ASC， and IL-1β proteins （P < 0.05）. Compared with the model group， the mice in the DHP and MCC950 groups had short time to pass the balance beam （P<0.01）， long time spent on the rod （P<0.01）， low levels of IL-1β， IL-18， and TNF-α （P<0.01）， low Iba-1 expression in midbrain substantia nigra （P<0.01）， high TH expression （P<0.01）， and small number of positive neurons in the midbrain substantia nigra （P<0.01）. The expression of NLRP3， ASC， and IL-1β proteins was lower in the MCC950 group （P<0.01）， and the expression of NLRP3， ASC， Caspase-1 and IL-1β proteins was lower in the DHP equivalent-dose group （P<0.01） than in the model group. ConclusionDHP has anti-oxidative stress effect. It regulates the expression of NLRP3 inflammasome and inhibits the overactivation of microglia， thereby alleviating the neuroinflammatory injury in PD and exerting the neuroprotective effect.