Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

ObjectiveGliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm. This study aims to further clarify the classification method and clinical significance of CST morphological changes in these patients. MethodsThis retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed. Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Then we classified patients according to preoperative assessment of tumor-induced morphological changes, and analyze postoperative motor function for each category. ResultsPostoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%). ConclusionWe have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

Helicobacter pylori(HP)infection is a Class Ⅰ carcinogen in gastric cancer,closely related to the occurrence of gastric cancer.Many studies have shown that HP eradication has a preventive effect on gastric cancer.However,2.7%-6.1%of patients with early gastric cancer who have been eradicated after endoscopic submucosal dissection(ESD)can still develop metachronous gastric cancer(MGC),and the mechanism of its occurrence is still unclear.In this review,the atrophy of gastric mucosa and intestinal metaplasia cannot be completely reversed after HP eradication,the excessive proliferation of gastric mucosa epithelial cells,the accumulation of genetic abnormalities,the homeostasis imbalance of the epigenetic group,changes in immune microenvironment,the abnormality of stem cells in gastric mucosa,chromatin accessibility,and changes in chromosome remodeling were discussed in the mechanism of carcinogenesis caused by the above molecular changes after ESD and HP eradication in early gastric cancer.

Objective To investigate the clinical efficacy of transjugular intrahepatic portosystemic shunt(TIPS)combined with indwelling catheter-directed thrombolysis for the treatment of portal vein thrombosis(PVT).Methods The clinical efficacy of 307 patients with portal hypertension complicated by PVT,who received successful TIPS combined with indwelling catheter-directed thrombolysis at the Affiliated Beijing Shijitan Hospital of Capital Medical University of China between January 2016 and December 2019,were retrospectively analyzed.Before and after TIPS,the inferior vena cava pressure(IVCP)and portal vein pressure(PVP)were measured,and the pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis portal pressure gradient(PPG,PPG=PVP-IVCP)was separately calculated.Reexamination of portal venography DSA was performed to determine the degree of PVT disappearance and whether the shunt was unobstructed.All patients were followed up for one year.Results The pre-TIPS,post-TIPS(before thrombolysis),and post-thrombolysis mean PPG was(24.50±6.91)mmHg,(18.51±5.11)mmHg,and(10.17±3.97)mmHg,respectively.The post-thrombolysis mean PPG was strikingly lower than the pre-thrombolysis values,the differences were statistically significant(P＜0.001).Among the 307 patients,complete disappearance of PVT was observed in 221(72.3%),remarkable reduction of PVT in 86(27.7%),and no invalid result was seen.The patients having complete patency of the shunt flow accounted for 85.7%of the 307 patients(261/307),and the patients having partial patency of the shunt flow accounted for 14.3%of the 307 patients(46/307).Forty-two patients developed complications,and no death occurred.All patients were followed up for one year,and the main clinical symptoms were improved or completely disappeared.Among the 307 patients,an increase in thrombus volume was found in 17(5.5%)when compared to their postoperative values,which returned to the first-time postoperative level after local treatment of the thrombus via the TIPS shunt combined with catheter-directed thrombolysis.Within one year after TIPS and thrombolysis,overt hepatic encephalopathy(OHE)occurred in 54 patients(17.6%,54/307).One patient died of hepatic failure 9 months after TIPS,another patient died of cerebral hemorrhage 11 months after TIPS,and all the remaining patients were alive.Conclusion For patients with portal hypertension complicated by PVT,TIPS combined with indwelling catheter-directed thrombolysis is clinically safe and effective.The standardized,systematic management of the whole therapeutic process should be strengthened.(J Intervent Radiol,2024,32:22-27)

This article reviews the concept, evaluation tools, current situation, influencing factors and promotion strategies of nurses′ remote health care readiness, in an effort to provide reference for nursing managers to construct intervention programs to improve the level of nurses′ remote health care readiness, to promote the successful development of remote healthcare and the sinking of high-quality nursing resources.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.

Objective:To investigate the clinical efficacy of bilateral V-Y advancement island flaps on buttocks in repairing postoperative defects in patients with perianal Paget′s disease.Methods:From January 2009 to January 2021, a retrospective analysis was performed on clinical data collected from 13 patients with perianal Paget′s disease, whose perianal defects resulting from the tumor resection were reconstructed with bilateral V-Y advancement island flaps on the buttocks in the Department of Dermatology, Hangzhou Third People′s Hospital. The postoperative recovery of the buttocks and the effects on the defecation function were evaluated.Results:The areas of perianal defects in 13 cases ranged from 4.8 cm × 5.6 cm to 12.2 cm × 6.4 cm. All defects were successfully repaired by using the bilateral V-Y advancement island flaps, and all surgical wounds healed primarily. One case first received temporary ileostomy, and then received ileostomy closure 3 months later, resulting in the recovery of defecation function; in another 1 case of perianal Paget′s disease comorbid with rectal cancer, the permanent sigmoid colostomy was performed to divert feces, and the defecation function was lost. After the follow-up for 1 - 6 years, the buttocks were symmetrical in shape in all the 13 patients, and 12 with preserved anus had normal defecation function. No tumor recurrence was observed in 12 patients without other malignant tumors after the operation, while 3 patients experienced mild anal stenosis without anal mucosa eversion or wound dehiscence; 1 patient with perianal Paget′s disease complicated by anal canal adenocarcinoma developed bilateral inguinal lymph node and internal iliac lymph node metastasis 1 year after the operation, and died 6 months later.Conclusion:The bilateral V-Y advancement island flaps on the buttocks have the advantages of reliable blood supply and sufficient advancement mobility, and can be used to repair large skin defects around the anus.

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female ; Humans ; Retrospective Studies ; Gonadal Dysgenesis, 46,XY/surgery* ; Gonadoblastoma/surgery* ; Neoplasms, Germ Cell and Embryonal/surgery* ; Ovarian Neoplasms/pathology*

ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg^-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg^-1） and model groups （50， 100， 150 mg·kg^-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the C_max and AUC in the tumor significantly increased， T_max shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg^-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.