Single-nuclei RNA sequencing uncovers heterogenous transcriptional signatures in Parkinson's disease associated with nuclear receptor-related factor 1 defect

Previous studies have found that deficiency in nuclear receptor-related factor 1(Nurr1),which participates in the development,differentiation,survival,and degeneration of dopaminergic neurons,is associated with Parkinson s disease,but the mechanism of action is perplexing.Here,we first asce rtained the repercussion of knocking down Nurr1 by pe rforming liquid chromatography coupled with tandem mass spectrometry.We found that 231 genes were highly expressed in dopaminergic neurons with Nurr1 deficiency,14 of which were linked to the Parkinson’s disease pathway based on Kyoto Encyclopedia of Genes and Genomes analysis.To better understand how Nurr1 deficiency autonomously invokes the decline of dopaminergic neurons and elicits Parkinson’s disease symptoms,we performed single-nuclei RNA sequencing in a Nurr1 LV-shRNA mouse model.The results revealed cellular heterogeneity in the substantia nigra and a number of activated genes,the preponderance of which encode components of the major histocompatibility Ⅱ complex.Cd74,H2-Ab1,H2-Aα,H2-Eb1,Lyz2,Mrc1,Slc6α3,Slc47α1,Ms4α4b,and Ptprc2 were the top 10 diffe rentially expressed genes.Immunofluorescence staining showed that,after Nurr1knockdown,the number of CD74-immunoreactive cells in mouse brain tissue was markedly increased.In addition,Cd74 expression was increased in a mouse model of Parkinson’s disease induced by treatment with 6-hydroxydopamine.Ta ken togethe r,our res ults suggest that Nurr1 deficiency results in an increase in Cd74 expression,thereby leading to the destruction of dopaminergic neuro ns.These findings provide a potential therapeutic target for the treatment of Parkinson’s disease.

Prostate lymphoma with renal obstruction;reflections on diagnosis and treatment:Two case reports

BACKGROUND Prostate lymphoma has no characteristic clinical symptomatology,is often misdiagnosed,and currently,clinical case reports of this disease are relatively rare.The disease develops rapidly and is not sensitive to conventional treatment.A delay in the treatment of hydronephrosis may lead to renal function injury,often causing physical discomfort and rapid deterioration with the disease.This paper presents two patients with lymphoma of prostate origin,followed by a summary of the literature concerning the identification and treatment of such patients.CASE SUMMARY This paper reports on the cases of two patients with prostate lymphoma admitted to the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,one of whom died of the disease 2 mo after diagnosis,while the other was treated promptly,and his tumor was significantly reduced at the 6-mo follow-up.CONCLUSION The literature shows that prostate lymphoma is often seen as a benign prostate disease during its pathogenesis,even though primary prostate lymphoma enlarges rapidly and diffusely with the invasion of surrounding tissues and organs.In addition,prostate-specific antigen levels are not elevated and are not specific.There are no significant features in single imaging either,but during dynamic observation of imaging,it can be found that the lymphoma is diffusely enlarged locally and that systemic symptoms metastasize rapidly.The two cases of rare prostate lymphoma reported herein provide a reference for clinical decision making,and the authors conclude that early nephrostomy to relieve the obstruction plus chemotherapy is the most convenient and effective treatment option for the patient.

Application of 3D reconstruction for surgical treatment of hepatic alveolar echinococcosis

AIM: To evaluate the reliability and accuracy of threedimensional(3D) reconstruction for liver resection in patients with hepatic alveolar echinococcosis(HAE).METHODS: One-hundred and six consecutive patients with HAE underwent hepatectomy at our hospital between May 2011 and January 2015. Fifty-nine patients underwent preoperative 3D reconstruction and "virtual" 3D liver resection before surgery(Group A). Another 47 patients used conventional imaging methods for preoperative assessment(Group B). Outcomes of hepatectomy were compared between the two groups.RESULTS: There was no significant difference in preoperative data between the two groups. Compared with patients in Group B, those in Group A had a significantly shorter operation time(227.1 ± 51.4 vs 304.6 ± 88.1 min; P < 0.05), less intraoperative blood loss(308.1 ± 135.4 vs 458.1 ± 175.4 m L; P < 0.05), and lower requirement for intraoperative blood transfusion(186.4 ± 169.6 vs 289.4 ± 199.2 m L; P < 0.05). Estimated resection liver volumes in bothgroups had good correlation with actual graft weight(Group A: r = 0.978; Group B: r = 0.960). There was a significant higher serum level of albumin in Group A(26.3 ± 5.9 vs 22.6 ± 4.3 g/L, P < 0.05). Other postoperative laboratory parameters(serum levels of aminotransferase and bilirubin; prothrombin time) and duration of postoperative hospital stay were similar. Sixteen complications occurred in Group A and 19 in Group B. All patients were followed for 3-46(mean, 17.3) mo. There was no recurrence of lesions in Group A, but two recurrences in Group B. There were three deaths: two from cerebrovascular accident, and one from car accident.CONCLUSION: 3D reconstruction provides comprehensive and precise anatomical information for the liver. It also improves the chance of success and reduces the risk of hepatectomy in HAE.

Evaluation of intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis

BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.AIM To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.METHODS Consecutively,five experienced examiners evaluated contrast-enhanced abdominal computed tomography(CT)scans for 200 patients with hepatic AE of each of four locations(n=50)in Germany,France and China.Therefore,we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center,performed because of hepatic AE from September 21,2007 to March 21,2018.AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT(EMUC-CT).Distant extrahepatic manifestations were documented either by whole body positron emission tomography–CT or with the addition of thoracic CT and cranial magnetic resonance imaging.Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion.Statistical analysis was performed using SAS Version 9.4(SAS Institute Inc.,Cary,NC,United States).RESULTS Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe(P=0.0091).A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size(P=0.0075).Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe(P<0.0001),and vascular/biliary involvement depended on lesion size.Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations:Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88%of type IV liver lesions to 100%among type III lesions.Type IV differed significantly in these associations from types I,II,and III(P<0.0001).With respect to extrahepatic disease,the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease.In contrast,distant extrahepatic manifestations in types I–III were found to varying degrees,with a maximum of 22%for type III.CONCLUSION Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.There are intercontinental differences regarding the characteristics of AE manifestation.

Multi-phase helical CT in diagnosis of early hepatocellular carcinoma

OBJECTIVES: To analyze the characteristics of early hepatocellular carcinoma by using multi-phase helical CT and assess the value of this method. METHODS: Multi-phase helical CT findings were reviewed double-blindly by radiologists. RESULTS: Altogether 24 lesions were found in 21 patients. In plain CT, the lesions were seen as hypodense or isodense areas. After contrast enhancement, 87.5% of the lesions showed regular or irregular hyperdense enhancement, whereas 12.5% demonstrated tumor vessels in arterial phase, which became hypodensed or isodensed nodules in portal phase or the hypodensed in delayed phase. The prevalence of density changes showed a hypo-hyper-hypo and hypo-hypo pattern. CONCLUSIONS: Multi-phase helical CT could reflect the blood supply of early hepatocelluar carcinoma, and is also convenient for the differential diagnosis of hepatic cavernous angioma, metastatic tumor, hepatic nodulous hyperplasia, and hepatic inflammatory granuloma.

Antioxidation and active constituents analysis of flower residue of Rosa damascena

Objective:To make full usage of resource and turn waste into treasure,the chemical constituents and bioactivity were firstly investigated on Damask rose(Rosa damascena)flower residue(DRFR).Methods:DPPH and ABTS experiments were applied to assess the antioxidant activity of DRFR.Then,column chromatography was used to purify compounds from an antioxidation extract(DRFR-A),and the chemical structure was identified using NMR.The total phenolic acid content was measured by FolinCiocalteu colorimetric method,and the content of gallic acid of the indicator ingredient was detected by HPLC.Results:DRFR-A was found to show a high activity both on DPPH(IC5o:2.760μg/mL)and ABTS(ICso:2.258μg/mL)compared to positive control Vc,Ten compounds were isolated and identified as quercetin(1),kaempferol(2),gallic acid(3),protocatechuic acid(4),pyrogallic acid(5),2-phenylethyl 3,4,5-trihydroxybenzoate(6),methyl gallate(7),p-hydroxybenzoic acid(8),p-hydroxyphenethyl alcohol(9)and astragalin(10)from DRFR-A.Among them,pyrogallic acid,2-phenylethyl-3,4,5-trihydroxybenzoate,p-hydroxybenzoic acid and p-hydroxyphenethyl alcohol are obtained from the plant for the first time.The content of total phenolic acids and gallic acid,main ingredient in DRFR-A was determined as 63.73%and 24.67%,respectively.Conclusion:This study provides a reliable data and lays the foundation for the development and utilization of rose residue,and hence for the full utilization of rose resources.