Objective:Radiotherapy is the primary treatment for nasopharyngeal carcinoma,but it frequently leads to radiotherapy-induced temporal lobe injury(RTLI).Magnetic resonance imaging(MRI)is the main diagnostic method for RTLI after radiotherapy for nasopharyngeal carcinoma,but it is prone to missed diagnoses.This study aims to investigate the causes of missed diagnoses of RTLI in nasopharyngeal carcinoma patients undergoing MRI after radiotherapy. Methods:Clinical and MRI data from nasopharyngeal carcinoma patients diagnosed and treated with radiotherapy at Xiangya Hospital of Central South University,from January 2010 to April 2021,were collected.Two radiologists reviewed all head and neck MRIs(including nasopharyngeal and brain MRIs)before and after radiotherapy of identify cases of late delayed response-type RTLI for the first time.If the original diagnosis of the initial RTLI in nasopharyngeal carcinoma patients did not report temporal lobe lesions,it was defined as a missed diagnosis.The first diagnosis of RTLI cases was divided into a missed diagnosis group and a non-missed diagnosis group.Clinical and imaging data were compared between the 2 groups,and multivariate logistic regression analysis was used to identify independent risk factors for MRI missed diagnoses of initial RTLI. Results:A total of 187 nasopharyngeal carcinoma with post-radiotherapy RTLI were included.The original diagnostic reports missed 120 cases and accurately diagnosed 67 cases,with an initial RTLI diagnosis accuracy rate of 35.8%and a missed diagnosis rate of 64.2%.There were statistically significant differences between the missed diagnosis group and the non-missed diagnosis group in terms of lesion size,location,presence of contralateral temporal lobe lesions,white matter high signal,cystic degeneration,hemorrhage,fluid attenuated inversion recovery(FLAIR),and examination site(all P<0.05).Multivariate logistic regression analysis showed that lesions≤25 mm,non-enhancing lesions,lesions without cystic degeneration or hemorrhage,lesions located only in the medial temporal lobe,and MRI examination only of the nasopharynx were independent risk factors for missed MRI diagnosis of initial RTLI(all P<0.05). Conclusion:The missed diagnosis of initial RTLI on MRI is mainly related to lesion size and location,imaging characteristics,and MRI examination site.

Objective To explore the effects and mechanism of Baitouweng Decoction in intestinal mucosal healing in mice with ulcerative colitis(UC)based on RIPK1/RIPK3/MLKL signaling pathway.Methods Totally 30 C57BL/6 male mice were randomly divided into control group,model group,Baitouweng Decoction group,infliximab group and combination group(Baitouweng Decoction+infliximab),with 6 mice in each group.A mouse model of UC was established by free administration of 3.5%sodium gluconate sulfate solution for 7 days.After modeling,Baitouweng Decoction group was given 8 g/kg Baitouweng Decoction solution by gavage daily,while the infliximab group was given 5 mg/kg infliximab intraperitoneal injection,the combination group was given synchronous gastric and intraperitoneal injection,while the control group and model group were given equal volume of normal saline by gavage for 7 consecutive days.The body mass of mice was recorded daily,fecal characteristics were observed,and disease activity index(DAI)score was performed,colon length was measured after intervention,ELISA was used to detect the contents of serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),RT-qPCR was used to detect mRNA expressions of RIPK1,RIPK3 and MLKL in colon tissue,Western blot and immunofluorescence staining were used to detect the expressions of RIPK1,RIPK3 and MLKL protein in colon tissue.Results Compared with the control group,the model group mice showed a decrease in body mass(P<0.01),an increase in DAI score(P<0.01),a shortened colon length(P<0.01),and an increase in serum IL-6 and TNF-α content(P<0.01);colonic mucosal was destructed,with disappearance of crypts and glandular structures,extensive infiltration of inflammatory cells,and increased pathological score of colon tissue(P<0.01);the mRNA and protein expressions of RIPK1,RIPK3 and MLKL in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the body mass of mice in each treatment group increased(P<0.01),and the DAI score decreased(P<0.01),colon length increased(P<0.01),and the contents of serum IL-6 and TNF-α decreased(P<0.05,P<0.01);the destruction of the colonic mucosal barrier was reduced,the pathological score of colon tissue was reduced(P<0.05);the expressions of RIPK1,RIPK3 and MLKL mRNA and protein in colon tissue decreased(P<0.05,P<0.01).Conclusion Baitouweng Decoction can alleviate intestinal mucosal damage and inflammation in UC mice,and its mechanism may be related to the inhibition of the RIPK1/RIPK3/MLKL signaling pathway.

Objective To investigate the effect of nicotine on coagulation in intestinal ischemia-reperfusion injury rats.Methods 32 male Sprague-dawley rats,weighing 250-300g,were randomly divided into 4 groups(n=8):sham operation group(S),intestinal ischemia-reperfusion(IR)group,nicotine(NIC)group,α7 nicotinic acetylcholine receptor(α7nAchR)antagonist group α-bungarotoxin(α-BGT)group.Intestinal IR was induced by clamping superior mesenteric artery for 45min and 120min of reperfusion.In group NIC nicotine 400μg/kg was injected intraperitoneally at 30min before superior mesenteric artery occlusion.In group α-BGT 1μg/kg was injected intraperitoneally at 15min before superior mesenteric artery occlusion.Plasma tumor necrosis factor-α(TNF-α),tissue factor(TF),antithrombin(AT),tissue plasminogen activator(tPA),fiber plasminogen activator inhibitor-1(PAI-1),D-dimer levels and platelet count(PLT)were measured after 120min reperfusion.Chiu's count was used to assess the changes in intestinal mucosal pathlolgical morphology.Results Compared with group S and group NIC,the plasma TNF-α,TF,tPA,PAI-1 and D-dimer levels were significantly increased,and plasma AT level and platelet count were significantly decreased,in group IR and group α-BGT(P<0.05),Chiu's scores were significantly increased(P<0.05).Conclusion Nicotine can inhibit the excessive activation of coagulation function in intestinal ischemia-reperfusion injury rats.Its mechanism may be related to activation of cholinergic antiinflammatory pathway,reducing the release of pro-inflammatory cytokines thereby reducing endothelial cell injury.

OBJECTIVE To establish the fingerprint of Sophora flavescens， and to screen differential components and determine their contents.　METHODS HPLC fingerprints of 12 batches of S. flavescens were established by using Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）； common peaks were identified and their similarities were evaluated. Chemical pattern recognition analysis [cluster analysis （CA），principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）] were performed with SIMCA 14.1 and SPSS 23.0 software， and differential components which influenced the quality of S. flavescens were screen with variable importance in the projection（VIP）＞1 as standard. Meanwhile， the contents of 4 kinds of differential components were determined by the same HPLC method.　RESULTS There were 17 common peaks in the fingerprints of 12 batches of S. flavescens，and their similarities were all higher than 0.96. A total of 6 common peaks were identified， i.e. oxymatrine （peak 1）， oxysophocarpine （peak 2）， matrine （peak 10）， trifolirhizin （peak 14）， kurarinone （peak 16） and norkurarinone （peak 17）. Results of CA， PCA and OPLS-DA showed that 12 batches of S. flavescens were divided into 3 categories according to producing area， i.e. S1-S7 （Shangzhou District of Shaanxi Province） were grouped into one category， S8-S10 （Yichuan County of Henan Province） into one category and S11-S12 （Chifeng City of Inner Mongolia） into one category. VIPs of matrine， norkurarinone， kurarinone and oxysophocarpine and the chemical components represented by peak 11 and 9 were all greater than 1. The contents of matrine， norkurarinone， kurarinone and oxysophocarpine in 12 batches of S. flavescens were 2.65-4.93， 1.54-3.44， 9.63-12.94 and 5.08-6.10 mg/g， respectively. CONCLUSIONS HPLC fingerprint of S. flavescens is established successfully in the study， and can be used to screen 6 differential components by combining with chemical pattern recognition analysis， which can provide reference for quality control of S. flavescens.

Perianal Paget's disease (PPD) is a rare malignant cutaneous tumor. This paper reported a case of PPD complicated by lung adenocarcinoma and anal canal cancer. The patient, a 76-year-old female, had been experiencing recurrent lower abdominal pain and perianal pruritus for the past 5 years. Upon physical examination, a cauliflower-like neoplasm in size of 5 cm×6 cm was observed on the right perianal skin, with local skin ulceration and a small amount of fluid discharge. The left perianal skin was also involved. In thoracoknee position, a hard mass was palpable in the rectal submucosa at 5-6 points 2 cm from the anal verge. Chest CT revealed multiple lesions in both lungs, indication of metastatic tumors. Further evaluation with fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) indicated multiple hypermetabolic nodules in the lungs, hypermetabolic lymph nodes throughout the body, early FDG uptake in a small patch of skin on the left hip, and increased FDG uptake in the anorectal region. Histopathological examination confirmed the diagnosis of lung adenocarcinoma. This resulted in the patient being diagnosed with PPD, lung adenocarcinoma, anal canal cancer, and systemic multiple lymph node metastasis. The combination of PPD with gastrointestinal tumors and other metachronous malignant tumors is highly prevalent. Colonoscopy, FDG-PET/CT, histopathology, and immunohistochemistry play crucial roles in early identification of local lymph node and distant involvement, facilitating the evaluation of potential malignant tumors and differential diagnosis. Treating methods for PPD are currently diverse, including postoperative combined or single chemotherapy, radiotherapy, targeted therapy, and photodynamic therapy. As trerapeutical options continue to develop, the extent and efficacy of surgery need to be reassessed.
Female ; Humans ; Aged ; Paget Disease, Extramammary/pathology* ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Adenocarcinoma of Lung/complications* ; Lung Neoplasms/complications*

Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.

Objective: To investigate the clinical characteristics, memory and neuroimaging features of nonlesional temporal lobe epilepsy (TLE-NL). Methods: Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017. The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS. Twenty healthy volunteers were also recruited. Memory assessment and high resolution magnetic resonance imaging (MRI) scanning were completed in the patients and healthy volunteers. Volume and shape of the hippocampus were compared between patients and healthy volunteers. Results: Compared with the TLE-HS, TLE-NL patients showed later seizure onset ((24.3±12.6) vs (15.8±10.3) years; t=3.684, P<0.01), shorter duration of epilepsy ((4.00 (2.00, 8.75)) vs (14.00 (7.50, 22.00)) years; Z=-4.675, P<0.01), less history of febrile convulsions (4.5% (2/44) vs 62.3% (33/53); χ²=32.270, P<0.01) and lower incidence of pharmacoresistant epilepsy (47.7% (21/44) vs 84.9% (45/53); χ²=15.282, P<0.01). However, there were no statistically significant differences between TLE-NL and TLE-HS in sex ratio, family history of epilepsy, lateralization of the epileptogenic zone, presence of aura, seizure types and seizure frequency. TLE-NL patients had normal memory quotient compared to normal controls (105.2±17.4 vs 103.8±16.2; P=1.000), while TLE-HS patients had significant memory impairment compared to normal controls (84.5±20.3 vs 103.8±16.2; P<0.01). Compared to normal controls, TLE-NL patients did not have significant alteration in hippocampal volume and shape, while TLE-HS patients had significant atrophy in the ipsilateral hippocampus ((2 953±481) mm³ vs (4 431±505) mm³; P<0.01), and shape analysis showed significant atrophy in the head and body of the hippocampus. Conclusion TLE-NL has different characteristics compared with TLE-HS, including later seizure onset, shorter duration of epilepsy, less history of febrile convulsions, better response to antiepileptic drugs, and no significant memory impairment and hippocampal atrophy.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3⁺, CD4⁺, and CD8⁺ cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.
Animals ; Apoptosis ; Aquaporin 4 ; Astrocytes ; Brain ; Brain Ischemia ; Cisterna Magna ; Drainage ; Edema ; Hippocampus ; Lymph Nodes ; Mice ; Neuroglia ; Neurons ; Prognosis ; Spasm ; Subarachnoid Hemorrhage ; tau Proteins

Objective To evaluate the effect of electro-acupuncture (EA) at Zusanli (ST36) acupoint on blood coagulation during intestinal ischemia-reperfusion (I/R) in rats.Methods Forty healthy male Sprague-Dawley rats,aged 6-8 months,weighing 250-300 g,were divided into 5 groups (n =8 each) using a random number table:sham operation group (group S),intestinal I/R group (group I/R),EA at Zusanli acupoint group (group EA),EA at non-acupoint group (group NE) and α7 nicotinic acetylcholine receptor antagonist α-bungarotoxin (α-BGT) group (group α-BGT).Intestinal I/R was induced by clamping the superior mesenteric artery for 4-5 min followed by 120 min of reperfusion.Bilateral Zusanli acupoints were stimulated with an electric stimulator (frequency 3 Hz,voltage 2-4 V,wave length 2 ms) for 30 min starting from the time point immediately after beginning of ischemia in group EA,while EA was performed at the points 5 mm lateral to the bilateral Zusanli instead in group NE.In group α-BGT,α-BGT 1 μg/kg was intraperitoneally injected at 45 min before ischemia,and the other treatments were similar to those previously described in group EA.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of the concentrations of tumor necrosis factor alpha (TNFα),tissue factor (TF),antithrombin (AT),tissue plasminogen activator (tPA),fiber plasminogen activator inhibitor-1 (PAl-l) and D-dimer in plasma (by enzyme-linked immunosorbent assay) and platelet count (PLT).The animals were sacrificed after blood sampling,the distal ileum specimens were removed for examination of the pathological changes with a light microscope,and the damage to the intestinal mucous membrane was assessed and scored according to Chin.Results Compared with group S,the concentrations of plasma TNFα,TF,tPA,PAI-1 and D-dimer were significantly increased,and the plasma AT concentration and PLT were decreased in I/R,NE and α-BGT groups,the concentrations of plasma TNFα and TF were significantly increased,and the plasma AT concentration was decreased in group EA,and Chiu's scores were significantly increased in I/R,EA,NE and α-BGT groups (P＜ 0.05).Compared with group I/R,the concentrations of plasma TNFα,TF,tPA,PAI-1 and D-dimer were significantly decreased,the plasma AT concentration and PLT were increased,and Chiu's scores were decreased in group EA (P＜0.05),and no significant change was found in the variables mentioned above in NE and α-BGT groups (P＞0.05).Compared with group EA,the concentrations of plasma TNFα,TF,tPA,PAI-1 and D-dimer were significantly increased,the plasma AT concentration and PLT were decreased,and Chiu's scores were increased in group NE (P＜0.05).Conclusion EA at Zusanli acupoint can improve blood coagulation during intestinal I/R in rats,and the mechanism is related to activating the cholinergic anti-inflammatory pathway.

Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks). Among them, five cases had no effect and two cases were seizure free recently. A case with GABRB3 (C.905A>G) had seizure controlled for 3 mouths. A case with ARX (C.700G>A) had seizure controlled for 6 mouths. Conclusion The early onset epileptic spasm with unknown reason is highly related to genetic disorders. A variety of genetic mutations, especially new mutations were found. Genetic heterogeneity of epileptic spasm is obvious.