immunohistochemistry

摘要： Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.

摘要： BACKGROUND Connective tissue growth factor(CTGF)is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling,inflammatory processes and fibrosis in various illnesses including cancer.AIM To investigate the role of CTGF in colorectal cancer(CRC)progression and to compare the CTGF expression with different clinicopathological parameters.METHODS Real-time polymerase chain reaction,immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16.RESULTS CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens.The higher protein expression levels showed a significant association with smoking,staging,tumor grade,invasion depth,necrosis of tumor tissue,and both lymphovascular and perineural invasion.As per the cox regression model and classification tree analysis,tumor-nodemetastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients.Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival.CONCLUSION Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients.These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

摘要： BACKGROUND The role of the hepatic nervous system in liver development remains unclear.We previously created functional human micro-hepatic tissue in mice by co-culturing human hepatic endodermal cells with endothelial and mesenchymal cells.However,they lacked Glisson’s sheath[the portal tract(PT)].The PT consists of branches of the hepatic artery(HA),portal vein,and intrahepatic bile duct(IHBD),collectively called the portal triad,together with autonomic nerves.AIM To evaluate the development of the mouse hepatic nervous network in the PT using immunohistochemistry.METHODS Liver samples from C57BL/6J mice were harvested at different developmental time periods,from embryonic day(E)10.5 to postnatal day(P)56.Thin sections of the surface cut through the hepatic hilus were examined using protein gene product 9.5(PGP9.5)and cytokeratin 19(CK19)antibodies,markers of nerve fibers(NFs),and biliary epithelial cells(BECs),respectively.The numbers of NFs and IHBDs were separately counted in a PT around the hepatic hilus(center)and the peripheral area(periphery)of the liver,comparing the average values between the center and the periphery at each developmental stage.NF-IHBD and NF-HA contacts in a PT were counted,and their relationship was quantified.SRYrelated high mobility group-box gene 9(SOX9),another BEC marker;hepatocyte nuclear factor 4α(HNF4α),a marker of hepatocytes;and Jagged-1,a Notch ligand,were also immunostained to observe the PT development.RESULTS HNF4αwas expressed in the nucleus,and Jagged-1 was diffusely positive in the primitive liver at E10.5;however,the PGP9.5 and CK19 were negative in the fetal liver.SOX9-positive cells were scattered in the periportal area in the liver at E12.5.The Jagged-1 was mainly expressed in the periportal tissue,and the number of SOX9-positive cells increased at E16.5.SOX9-positive cells constructed the ductal plate and primitive IHBDs mainly at the center,and SOX-9-positive IHBDs partly acquired CK19 positivity at the same period.PGP9.5-positive bodies were first found at E16.5 and HAs were first found at P0 in the periportal tissue of the center.Therefore,primitive PT structures were first constructed at P0 in the center.Along with remodeling of the periportal tissue,the number of CK19-positive IHBDs and PGP9.5-positive NFs gradually increased,and PTs were also formed in the periphery until P5.The numbers of NFs and IHBDs were significantly higher in the center than in the periphery from E16.5 to P5.The numbers of NFs and IHBDs reached the adult level at P28,with decreased differences between the center and periphery.NFs associated more frequently with HAs than IHBDs in PTs at the early phase after birth,after which the number of NF-IHBD contacts gradually increased.CONCLUSION Mouse hepatic NFs first emerge at the center just before birth and extend toward the periphery.The interaction between NFs and IHBDs or HAs plays important roles in the morphogenesis of PT structure.

摘要： BACKGROUND Chronic viral B hepatitis(CHB)is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis.Currently,although combinations of different laboratory methods are used in the follow-up and treatment of CHB,the failure of these procedures in some cases has led to the necessity of developing new approaches.In CHB,the intrahepatic expression pattern of viral antigens,including hepatitis B surface antigen(HBsAg),is related to different phases of inflammation.However,many studies have focused on the intracytoplasmic properties of HBsAg staining,and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIM To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODS A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study.Following diagnosis,all patients were treated with entecavir(0.5 mg)and followed up at three-month intervals.The percentage of immunohistochemical HBsAg(p-HBsAg)expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis.The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTS A positive correlation between p-HBsAg and serum levels of hepatitis B virus(HBV)DNA and HBsAg was observed(P<0.001).The p-HBsAg value was significantly higher in younger patients than in older patients.When the groups were categorized according to the hepatitis B e antigen(HBeAg)status in HBeAgpositive cases,p-HBsAg was correlated with HBV DNA,hepatitis activity index(HAI)and fibrosis scores(P<0.001).In this group,p-HBsAg and HBsAg expression patterns were also correlated with the viral response(VR)and the serological response(SR)(P<0.001).Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR(P<0.001).In HBeAg-negative patients,although HBsAg expression patterns were correlated with both HAI and fibrosis,no relationship was observed among p-HBsAg,clinicopathological factors and VR.CONCLUSION In pretreatment liver biopsies,the immunohistochemical determination of HBsAg expression by quantitative methods,beyond its distribution within the cell,may be a good predictor of the treatment response,especially in HBeAg-positive cases.

摘要： Incidence of colorectal cancer(CRC)is on rise.While approximately 70%of all CRC cases are sporadic in nature,20%-25%have familial aggregation and only<5%is hereditary in origin.Identification of individuals with hereditary predilection for CRC is critical,as it has an impact on their overall surgical management including surgical timing,approach&technique and determines the role of prophylactic surgery and outcome.This review highlights the concept of hereditary CRC,provides insight into its molecular basis,possibility of its application into clinical practice and emphasizes the current treatment strategies with surgical management,based on the available international guidelines.

摘要： BACKGROUND Post-colonoscopy colorectal cancer(CRC)rates for patients with inflammatory bowel disease(IBD)are unacceptably high.During colonoscopy,an intravenous fluorescent anti-c-MET probe may improve endoscopic detection of lesions.However,c-MET expression in IBD lesions is poorly defined,limiting translational studies.AIM To comprehensively define c-MET expression in sporadic and IBD-associated colorectal carcinogenesis.METHODS c-MET expression was immunohistochemically assessed in 319 formalin-fixed paraffin-embedded tissue specimens,colonoscopically or surgically retrieved between 1994-2017.Tissue included:30 normal colorectal biopsies,30 hyperplastic polyps(HP),31 sessile serrated lesions(SSL),55 tubular/tubulovillous adenomas with low(TA-LGD,n=32)or high grade dysplasia(TA-HGD,n=23),26 sporadic(s)-CRCs,16 quiescent IBD biopsies,11 active/inflamed IBD biopsies,18 IBDassociated dysplastic lesions(IBD-dys),and 102 IBD-CRCs.Expression was scored by two independent observers as:0=absent,1=weak,2=moderate or 3=strong.Mann-Whitney U and Kruskal-Wallis tests were used to assess significance.RESULTS Positive epithelial cytoplasmic and membranous c-MET expression was observed in all tissues,indicating there is ubiquitous expression in the colorectum.c-MET expression was weak in normal colonic epithelium compared with each of the sporadic colonic lesions,including TA-LGD(P<0.001),TA-HGD(P=0.004),HP(P<0.001),SSL(P<0.001),and s-CRC(P<0.001).Specifically,in sporadic(non-IBD)lesions,expression was stronger in TA-LGD compared with normal mucosa(P<0.001),and stronger in s-CRC compared with TA-HGD(P=0.004).However,there was no significant difference between TA-LGD and TA-HGD(P=0.852).Further,there was no difference in c-MET expression between HP and SSL(P=0.065).In IBD,expression was weaker in quiescent colonic mucosa compared with inflamed colonic mucosa(P<0.001).There was no difference between inflamed colonic mucosa and IBD-dys(P=0.512)or IBD-CRC(P=0.296).However,expression was stronger in IBD-dys(P<0.001)and IBD-CRC(P<0.001)compared with quiescent IBD colonic mucosa.CONCLUSION The characterisation of c-MET expression suggest that an intravenous probe may improve the endoscopic detection of lesions in both non-IBD patients and IBD patients with quiescent disease.

摘要： BACKGROUND No known case of neuroendocrine tumour(NET)with schwannoma has been reported.CASE SUMMARY A 63-year-old female presented to our hospital with nausea and vomiting.Upper gastrointestinal endoscopy revealed a mass in the descending part of the duodenum.Using ultrasound gastroscopy,we found that the tumour originated from the submucosa and showed low echo.We removed the tumour by electrocoagulation and sent it for pathological biopsy.CONCLUSION Immunohistochemical results showed that the mass was a rare NET with neurilemmoma.

摘要： BACKGROUND Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract(ITLPDGI),a primary tumor forming in the gastrointestinal(GI)tract,represents a rarely diagnosed clonal T-cell disease with a protracted clinical course.CASE SUMMARY This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation.Postsurgical histopathological analysis,combined with hematoxylineosin staining,immunohistochemistry and TCRβ/γ clonal gene rearrangement test,confirmed the diagnosis of CD8+ITLPD-GI.CONCLUSION Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize.So far,indolent CD8+ITLPD-GI has not been comprehensively examined.The current mini-review focused on evaluating indolent CD8+ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis,detection of genetic and epigenetic alterations,and therapeutic target identification.

摘要： BACKGROUND Myoepithelial carcinoma(MC)is a rare malignant neoplasm that mainly occurs in the salivary gland.MC can be confused with many other tumors when arising outside the salivary glands because it presents with a wide spectrum of cytomorphological and immunohistochemical features.To the best of our knowledge,esophageal MC has not been previously reported.The purpose of this study was to describe the imaging and clinicopathological features of esophageal MC to improve the understanding of the disease.CASE SUMMARY Three men and one woman diagnosed with esophageal MC were enrolled in this study.The primary clinical symptom was dysphagia.The mass was mainly located in the middle esophagus.Laboratory tests revealed that two patients who underwent tumor abnormal protein were positive.Radical resection was performed for all patients with no adjuvant therapy.Hematoxylin-eosin staining showed infiltrative growth of epithelial cells with hyperchromatic and pleomorphic nuclei toward the periphery.Immunohistochemistry showed that all patients were positive for P63,and most patients were positive for SOX-10,AE1/AE3,P40,and calponin.The Ki-67 values were all higher than 60%.Patient one died one month after discharge from an unknown cause.Patient two lost to follow-up.At patient three’s four-month review,enhanced computed tomography(CT)showed anastomosis recurrence and bilateral lung metastases.He abandoned treatment and lost to follow-up.Patient four attended review appointments regularly and remained in a good general condition.CONCLUSION Here,we present the first report of esophageal MC and review the relevant literature.Esophageal MC is more likely to occur in the middle esophagus in older patients with male dominance.A fungating type observed on CT scanning may help narrow down the differential diagnosis.Cystic change or necrosis may occur in larger lesions.The final diagnosis should be made according to the pathological examination.The treatment for MC is surgical resection,and the efficacy of chemotherapy needs to be determined with future studies.

摘要： BACKGROUND Ubiquilins(UBQLNs)are important factors for cell proteostasis maintenance.UBQLNs are involved in the modulation of the cell cycle,as well as in apoptosis,membrane receptors regulation,DNA repair,epithelial-mesenchymal transition,and mi RNA activities.They also affect the selection of double-strand break repair pathways.Abnormal UBQLNs expression can lead to many diseases,including cancer.Studies have found that the expression of Ubiquilin4(UBQLN4)is associated with the development of several tumor types.However,the association between UBQLN4 and cervical cancer has not been examined yet.AIM To investigate the expression of UBQLN4 in cervical cancer and to evaluate its correlation with disease prognosis.METHODS Immunohistochemistry was performed to examine the expression of UBQLN4 in 117 cervical cancer tissues and 32 matching pericervical tissues.Paired t-test(twotailed)was used to compare the differences between groups.We collected patients’clinical characteristics,including age,histological grade,pathologic type,lymph node metastasis,and FIGO stage(2018)and compared them by chi-square test.All patients were followed for 5.5 to 6.8 years.Kaplan-Meier method and logrank test were used to compare the differences in the overall survival(OS)and progression-free survival(PFS)among the different groups.RESULTS Overexpression of UBQLN4 was observed in 70.9%(83/117)of all cervical cancer tissues and in 15.6%(5/32)of the paired parauterine tissues.The expression of UBQLN4 was associated with lymph node metastasis,poor differentiation,and advanced stage,but the difference was not significant.Kaplan-Meier and log-rank test results suggested the high expression of UBQLN4 was associated with short OS and PFS.Regardless of UBQLN4 expression,the patient age and FIGO stage were also associated with disease prognosis.The statistically significant variables obtained from univariate the Kaplan-Meier analysis were subjected to Cox multivariate survival regression analysis,which showed that,in addition to the FIGO stage and age,UBQLN4 was also an independent prognostic marker for OS and PFS(P=0.011 and P=0.024,respectively).CONCLUSION The overexpression of UBQLN4 was associated with poor prognosis in cervical cancer.Our study proposed a novel prognostic factor and improved the existing understanding of the pathogenesis of cervical cancer.