1.Analysis of three encephalitis cases with double positive for N-methyl-D-aspartate receptor and myelinating oligodendrocyte glycoprotein antibodies
Lin ZHU ; Li JIANG ; Long YU ; Jian WU ; Mengmei YIN ; Junwen HUANG ; Cancan MA
Journal of Clinical Medicine in Practice 2024;28(2):49-54
Objective To observe the clinical manifestations of 3 cases with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis antibody overlapping syndrome (MNOS), aiming to expand the understanding of the clinical spectrum of such syndromes. Methods Retrospective analysis was performed on the data of 3 patients with MNOS who were positive for both MOG antibodies and NMDAR antibodies. Clinical features, neuroimaging characteristics, and outcomes were collected, and cell-based assay (CBA) technique was used for diagnosis. Results One case presented both positive MOG antibodies and NMDAR antibodies, but the clinical manifestations were typical symptoms of anti-NMDAR encephalitis. In one case, the clinical and cranial magnetic resonance imaging (MRI) features of demyelinating disease recurred after anti-NMDAR encephalitis, with atypical symptoms of MNOS such as numbness and weakness in limbs, blurred vision, and diplopia. The last case presented both positive MOG antibodies and NMDAR antibodies, but the clinical manifestations were typical symptoms of anti-NMDAR encephalitis. In MNOS, MOG antibody-associated disease and anti-NMDAR encephalitis may appear simultaneously or sequentially, with epilepsy being the most common symptom. Cranial MRI findings showed that the patients presented and mainly involved supratentorial lesions, which may also involve the brainstem, but no spinal cord lesions were found. All patients showed slightly abnormal cerebrospinal fluid. Patients showed a good response to first-line immunotherapy during the acute phase of the disease, with a favorable prognosis. But most patients were prone to relapse. Conclusion In MNOS patients, anti-NMDAR encephalitis may present with clinical and(or)MRI features of demyelinating disease simultaneously or sequentially. The clinical manifestations of patients are complex and diverse. Patients with atypical symptoms require to improving the understanding of MNOS and timely treatment.
2.A case report with anti-IgLON family member 5 antibody-related encephalopathy
Yong PENG ; Cancan MA ; Lin ZHU ; Beilei CHEN ; Mengmei YIN ; Jian WU ; Long YU ; Wenzhe HOU
Journal of Clinical Medicine in Practice 2024;28(2):55-59
This study reported a 50-year-old female patient who was diagnosed with anti-IgLON family member 5 (anti-IgLON5) antibody-related encephalopathy, presented with cognitive and sleep disorders, autonomic dysfunction and seizures, positive serum IgLON5 antibody but negative cerebrospinal fluid IgLON5 antibody, negative human leukocyte antigen (HLA) by genetic testing, and was diagnosed as anti-IgLON5 antibody-related encephalopathy. After hospital admission, the patient was given intravenous methylprednisolone combined with immunoglobulin immunotherapy, donepezil for improvement of cognition, sodium valproate and oxcarbazepine for prevention and treatment of epileptic seizures, and finally her symptoms improved significantly.
3.RASAL2 promotes pancreatic cancer vasculogenic mimicry through AKT/β-catenin pathway
Bao YANG ; Feibai MA ; Weikun QIAN ; Cancan ZHOU ; Zheng WANG ; Yangyang YUE
Tumor 2024;44(11):1104-1115
Objective:To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.Methods:The clinical proteomic tumor analysis consortium(CPTAC)database was used to analyze the expression of RASAL2 in pancreatic cancer,and immunohistochemical method was used to detect the expression of RASAL2,β-catenin and Vimentin in pancreatic cancer and adjacent tissues.In the pancreatic cancer cell line,after lentivirus infection knockdown and overexpression of RASAL2,transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression,and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells;The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.Results:The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue.Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated,and the expression of β-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated.The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion.After knocking down RASAL2 expression in pancreatic cancer cell PANC-1,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased,and the formation of vasculogenic mimicry structure was inhibited;After overexpression of RASAL2 in pancreatic cancer cell BxPC-3,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased,promoting the formation of vasculogenic mimicry.Conclusion:The effect of RASAL2 on vasculogenic mimicry in pancreatic cancer cells is related to AKT/β-catenin signaling pathway.
4.Clinical,electroencephalographic,and imaging features of neurosyphilis with epileptic seizures
Cancan MA ; Xibin ZHANG ; Jian WU
Journal of Apoplexy and Nervous Diseases 2024;41(7):631-636
Objective To summarize the characteristics of neurosyphilis with epileptic seizures.Methods We retrospectively analyzed the clinical,laboratory,electroencephalographic,and imaging characteristics of eight patients with neurosyphilis with epileptic seizures treated in the Department of Neurology,Subei People's Hospital,Yangzhou Uni-versity from May 2018 to May 2022.Results There were five males and three females.The time from the first epileptic seizure to admission ranged from one day to six months.Two patients presented with only epileptic seizures,while six and four patients also had cognitive impairment and psychiatric symptoms,respectively.Regarding clinical types,six were parenchymatous neurosyphilis and two were meningovascular neurosyphilis.Seizure types included one case of focal sei-zures,five cases of focal to bilateral tonic-clonic seizures,and two cases of generalized seizures.Video electroencephalog-raphy detected abnormalities in seven cases:background slowing,slow rhythms,epileptiform discharges,and periodic lat-eralized epileptiform discharges(PLEDs);among them,four cases showed PLEDs,and one showed focal fast activity be-ginning in the left temporal lobe.All the eight patients were positive for serum and cerebrospinal fluid(CSF)Treponema pallidum particle agglutination test and the toluidine red unheated serum test(TRUST);and six were positive for CSF TRUST/the rapid plasma reagin test,while two were negative for CSF TRUST.CSF testing showed elevated pressure levels in four cases,elevated protein levels in four cases,and elevated leukocyte counts in six cases.Cranial magnetic resonance imaging findings of the eight patients showed abnormal signals predominantly in the temporal lobe,cerebral atrophy,hydro-cephalus,and ischemic infarcts or white matter lesions.Arterial spin labeling of five patients revealed hyperperfusion in three patients and hypoperfusion in two patients.The patients were treated with penicillin or ceftriaxone as well as antiepi-leptic drugs and symptomatic treatment,achieving good prognoses in six cases but poor outcomes in two cases.Conclusion For patients with epilepsy accompanied by cognitive impairment and mental disorders,we should be alert to the possibility of neurosyphilis after excluding other neurological diseases.Electroencephalography and imaging examinations can help assess the severity and prognosis of neurosyphi-lis,and early active treatment can improve outcome.
5.Analysis of ocular objective torsion and near stereopsis function in primary superior oblique overaction
Yi LU ; Lianhong ZHOU ; Cancan ZHANG ; Yuanjin LI ; Runting MA ; Wenping LI ; Qi GONG ; Lurun YU ; Diewenjie HU
International Eye Science 2024;24(10):1663-1667
AIM: To investigate the relationship between objective ocular torsion and near stereopsis in patients with primary superior oblique overaction(PSOOA).METHODS: Retrospective study. A total of 59 strabismus patients with PSOOA who underwent strabismus surgery at Renmin Hospital of Wuhan University between January 2019 and November 2023 were collected. Based on the collected fundus photographs and the position of the fovea relative to the horizontal line through the optic disc, the eyes were categorized as incyclotorsion, excyclotorsion, or no cyclotorsion. Additionally, the fovea-disc angle(FDA)and the relationship between objective ocular torsion status, FDA, and near stereopsis function in the patients were further measured and analyzed.RESULTS: Totally 59 patients(92 eyes)showed superior oblique overaction. There were no cases of excyclotorsion, 32 cases with no cyclotorsion, and 27 cases with incyclotorsion. The total binocular FDA was significantly smaller in the no-cyclotorsion group compared with the incyclotorsion group(2.83°±2.89° vs 16.12°±5.74°, P<0.001). The preservation rates of near stereopsis were 66% and 15% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P<0.001), and the preservation rates of fine near stereopsis were 38% and 11% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P=0.02). Among all patients, near stereopsis was correlated with total binocular FDA(r=-0.526, P<0.001), with the strongest correlation observed with the FDA of the incyclotorsion(r=-0.546, P<0.001). In the incyclotorsion group, there was no correlation between near stereopsis and total binocular FDA(r=-0.366, P=0.060), with a negative correlation between near stereopsis and the FDA of both the incyclotorsion and the overaction(r=-0.424, P=0.028; r=-0.485, P=0.010). In the no-cyclotorsion group, near stereopsis was not correlated with total binocular FDA, incyclotorsion FDA, or overaction FDA.CONCLUSION:PSOOA patients with incyclotorsion have a lower preservation rate of near stereopsis than those without cyclotorsion. Near stereopsis function of patients with PSOOA is negatively correlated with total binocular FDA, especially the greater the FDA of the incyclotorsion and overaction, the worse the near-stereoscopic function.
6.RASAL2 promotes pancreatic cancer vasculogenic mimicry through AKT/β-catenin pathway
Bao YANG ; Feibai MA ; Weikun QIAN ; Cancan ZHOU ; Zheng WANG ; Yangyang YUE
Tumor 2024;44(11):1104-1115
Objective:To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.Methods:The clinical proteomic tumor analysis consortium(CPTAC)database was used to analyze the expression of RASAL2 in pancreatic cancer,and immunohistochemical method was used to detect the expression of RASAL2,β-catenin and Vimentin in pancreatic cancer and adjacent tissues.In the pancreatic cancer cell line,after lentivirus infection knockdown and overexpression of RASAL2,transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression,and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells;The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.Results:The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue.Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated,and the expression of β-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated.The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion.After knocking down RASAL2 expression in pancreatic cancer cell PANC-1,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased,and the formation of vasculogenic mimicry structure was inhibited;After overexpression of RASAL2 in pancreatic cancer cell BxPC-3,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased,promoting the formation of vasculogenic mimicry.Conclusion:The effect of RASAL2 on vasculogenic mimicry in pancreatic cancer cells is related to AKT/β-catenin signaling pathway.
7.Clinical characteristics analysis of acute pancreatitis
Qiqi WANG ; Yali CHENG ; Cancan ZHOU ; Mengyuan GONG ; Haonan LIU ; Zheng WANG ; Qingyong MA ; Zheng WU
Chinese Journal of Digestive Surgery 2023;22(S1):38-43
Objective:To analyze the clinical characteristics of acute pancreatitis.Methods:The retrospective case-control study was conducted. The clinical data of 558 patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from June 2015 to June 2023 were collected. There were 352 males and 206 females, aged (46±15)years. Observation indicators: (1) general situations of acute pancreatitis patients; (2) etiology of acute pancreatitis patients; (3) severity of acute pancreatitis patients; (4) chronic diseases in acute pan-creatitis patients; (5) complications in acute pancreatitis patients; (6) subgroup analysis of patients with recurrent acute pancreatitis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Bonferroni correction was used for pairwise comparison. Results:(1) General situations of acute pancreatitis patients. There were significant differences in gender, age, total duration of hospital stay, smoking, and alcohol consumption between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (2) Etiology of acute pancreatitis patients. There were significant differences in gallstones and hyperlipidemia between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (3) Severity of acute pancreatitis patients. Of the 443 patients with first episode of acute pancreatitis and 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pan-creatitis were 320 and 83, 24 and 9, 99 and 23, showing no significant difference between them ( P>0.05). (4) Chronic diseases in acute pancreatitis patients. There were significant differences in com-plication as hyperlipidemia, fatty liver and diabetes between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (5) Complications in acute pancrea-titis patients. There was no significant difference in terms of acute necrotic collection, acute peripan-creatic fluid accumulation, walled-off necrosis, pancreatic pseudocyst, infectious pancreatic necrosis, systemic inflammatory response syndrome, respiratory system complications, circulatory system complications, renal complications, sepsis, abdominal compartment syndrome, or pancreatic ence-phalopathy between the first episode of acute pancreatitis patients and the recurrent acute pancrea-titis patients ( P>0.05). (6) Subgroup analysis of patients with recurrent acute pancreatitis. ① Combination with chronic diseases. Of the 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pancreatitis were 83, 9, 23, and there were 25, 8, 11 cases of them with hyperlipidemia, respectively, showing a significant difference among them ( P<0.05). ② Complications. Of the 115 patients with recurrent acute pancreatitis, there were 44 cases with hyperlipidemia and 71 cases without hyper-lipidemia, and there were significant differences in acute peripancreatic fluid accumulation and renal complications between them ( P<0.05). Conclusions:Recurrent acute pancreatitis is more common in males. Compared with first episode of acute pancreatitis, cases with recurrent acute pancreatitis usually have younger age, shorter total duration of hospital stay, higher proportion of smoking and drinking. The etiology of recurrent acute pancreatitis is composed of lower levels of biliary diseases and higher levels of hyperlipidemia. Patients with recurrent acute pancreatitis have higher proportion of comorbidities as hyperlipidemia, fatty liver and diabetes. There was no signifi-cant difference in the incidence of complications between first episode of acute pancreatitis and recurrent acute pancreatitis. Compared with recurrent acute pancreatitis patients without concomi-tant hyperlipidemia, recurrent acute pancreatitis patients with concomitant hyperlipidemia are more prone to acute peripancreatic fluid accumulation and renal complications.
8.Synergistic effects of resveratrol with gemcitabine in pancreatic cancer chemotherapy by inhibiting PARP1
Shuai WU ; Cancan ZHOU ; Liang HAN ; Qingyong MA ; Zheng WU
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(6):850-855
【Objective】 To investigate the effects of resveratrol on gemcitabine chemotherapy in pancreatic cancer and the possible molecular mechanism. 【Methods】 Gemcitabine resistant cell lines were screened by continuous low concentration increasing induction. High-throughput RNA-seq was used to analyze the differential expression enrichment pathway, COMET assay was used to detect DNA damage, Western blotting was used to detect related pathway indicators, and Chou-Talalay was used to calculate drug combination synergistic index. AutoDock predicts docking targets for small molecules and proteins. 【Results】 DNA damage repair related pathways were activated in drug-resistant cell lines compared with their parents. Resveratrol enhanced the DNA damage effects induced by gemcitabine (P<0.01). Resveratrol inhibited the expression of PARP1, a key molecule of DNA damage repair, and played a synergic effect with gemcitabine (CI<1). Resveratrol has docking targets with the CAT domain of PARP1. 【Conclusion】 Resveratrol can inhibit PARP1, a key molecule of chemotherapy resistance, and has a synergistic effect with gemcitabine in pancreatic cancer chemotherapy.
9.Establishment of the fingerprint of Temurin- 5 powder and content determination of 4 components
Cancan SUN ; Jing ZHOU ; Tuerhong SUBIYINUER ; Guizhi MA
China Pharmacy 2022;33(4):452-457
OBJECTIVE To establish the fing erprint of Temurin- 5 powder,conduct chemical pattern recognition analysis ,and determine the contents of 4 components simultaneously. METHODS The fingerprints of 10 batches of Temurin- 5 powder were established and similarity evaluation was performed by using high performance liquid chromatography (HPLC)combined with the Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine (2012 edition);common peaks were identified by comparing with mixed substance control. The common peaks were analyzed by systematic cluster analysis and principal component analysis with SPSS 26.0 software. The HPLC method was used to determine the contents of gallic acid , geniposide,chlorogenic acid and ellagic acid in 10 batches of samples. RESULTS A total of 15 common peaks were identified from the fingerprints of 10 batches of Temurin-5 powder,and the similarity was 0.997-0.999. It was identified that peak 1 was gallic acid ,peak 3 was geniposide ,peak 5 was chlorogenic acid and peak 12 was ellagic acid. Among the 10 batches of samples , S4 and S 9 were grouped into one category ,S6-S8 were grouped into one category ,and the other batches of samples were grouped into one category. The accumulative variance contribution rate of first three principal components was 89.245%. The linear ranges of gallic acid ,geniposide,chlorogenic acid and ellagic acid were 5.55-177.5,15.98-511.5,2.56-82.0 and 13.48-431.5 μg/mL, respectively. RSDs of precision ,stability(24 h)and repeatability tests were all less than 2%(n=6 or n=7). The average recoveries were 101.56%,102.21%,98.60% and 96.62%,respectively,RSDs were 1.90%,1.61%,1.58% and 1.73%(n=6). Average contents of above components were 5.03-5.64,10.38-12.16,1.40-1.69,6.47-7.11 mg/g,respectively. CONCLUSIONS The established fingerprint is stable and feasible ,and the content determination method meets the relevant regulations. Combined with chemical pattern recognition analysis ,it can be used for the quality control of Temurin- 5 powder.
10.HIV-1 latency reactivation by VP-16
Cancan CHEN ; Weiqi ZHANG ; Hanyu MA ; Ying TUO
Chinese Journal of Experimental and Clinical Virology 2022;36(1):8-14
Objective:To explore the effect of the etoposide (VP-16) on the reactivation of human immunodeficiency virus (HIV-1) from latent infection and study its potential molecular mechanism.Methods:The HIV-1 latently infected cell line J-Lat was treated with DMSO, VP-16 and vorinostat (SAHA), flow cytometry was used to detect the positive ratio of green fluorescent protein (GFP) in J-Lat, which can reflect the efficacy of high concentration VP-16 on reactivation. Then the reactivation efficiency of VP-16 on HIV-1 latently infected cells at different concentration and treatment time was measured by flow cytometry. The expression of CD25, CD69 and interleukin-6 (IL-6) of the VP-16-treated J-Lat cells were also detected in the same way. The effect of VP-16 on the transcription of long terminal repeat (LTR) was tested using a dual-luciferase reporter assay. The protein expression of the silent information regulator 1 (SIRT1) and the acetylated nuclear factor κB (NF-κB) p65 under the effect of VP-16 was checked by western blot (WB). Lentivirus-mediated SIRT1 short-hairpin RNA (SIRT1-shRNA) was employed to knock down SIRT1, and then tested for efficiency of reactivation.Results:The results of flow cytometry showed that VP-16 specifically reactivated HIV-1 latently infected J-Lat cells in a concentration and time-dependent manner. Meanwhile, the expression of CD25 and CD69 was upregulated to a certain extent, but the expression of IL-6 was not affected. Dual-luciferase reporter assay suggested that VP-16 positively regulated the transcription of HIV-1 LTR through NF-κB signaling pathway. WB results indicated that VP-16 can inhibit the protein expression of SIRT1 and promote the acetylation of NF-κB p65. Lentivirus-mediated SIRT1-shRNA successfully knocked down the mRNA and protein expression of SIRT1, and reactivated the HIV-1 latency effectively.Conclusions:VP-16 upregulates the acetylation of NF-κB p65 by inhibiting the expression of SIRT1, which subsequently promotes the transcription of HIV-1 LTR and reactivates the latent HIV-1 infection.


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