AIM:To characterize the distribution of persistent fetal vasculature(PFV)subtypes and to evaluate corneal astigmatism(CA)in children with unilateral PFV.METHODS:The medical records of patients diagnosed with PFV betwe...AIM:To characterize the distribution of persistent fetal vasculature(PFV)subtypes and to evaluate corneal astigmatism(CA)in children with unilateral PFV.METHODS:The medical records of patients diagnosed with PFV between January 2014 and August 2021 were retrospectively reviewed.Corneal keratometry parameters were measured using IOLMaster or a handheld keratometer.Differences in CA between the affected and fellow eyes were analyzed in 52 unilateral PFV patients with available examination data.RESULTS:Totally 133 patients diagnosed with PFV were retrospectively reviewed.The male-to-female ratio was 73/60.Median age at surgery was 38.03mo(interquartile range 58.27mo).Among the PFV patients,32(24.06%)had anterior PFV,2(1.50%)had posterior PFV,and 99(74.44%)had combined anterior-posterior PFV.Mild combined PFV was the most common subtype.In unilateral PFV cases,the mean CA in the affected eye was 2.29±1.11 D,and 59.62%(31 eyes)had CA≥2.0 D.The mean CA in the affected eyes was significantly higher than in the fellow eyes(1.37±0.77 D;P<0.001).Among PFV-affected eyes with CA≥2.0 D,the steepest corneal meridian was vertically oriented in 30 cases(96.77%),while only 1 case(3.23%)had the steepest meridian oriented horizontally.CONCLUSION:In children with unilateral PFV,CA is significantly higher in the affected eyes than in the fellow eyes,and the steepest corneal meridian was predominantly oriented vertically.展开更多
Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusiv...Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.展开更多
Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.It is widely distributed in the central and peripheral nervous systems.Whether and how GDF-15 modulates nociceptive s...Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.It is widely distributed in the central and peripheral nervous systems.Whether and how GDF-15 modulates nociceptive signaling remains unclear.Behaviorally,we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats.Electrophysiologically,we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia(DRG)neurons.Furthermore,GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents,and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction.GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels,suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel.Immunohistochemistry results showed that activin receptor-like kinase-2(ALK2)was widely expressed in DRG medium-and small-diameter neurons,and some of them were Nav1.8-positive.Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors.Inhibition of PKA and ERK,but not PKC,blocked the inhibitory effect of GDF-15 on Nav1.8 currents.These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK,which mediate the peripheral analgesia of GDF-15.展开更多
The high mortality rate in hepatocellular carcinoma(HCC)is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage,with surgical treatment options unavailable...The high mortality rate in hepatocellular carcinoma(HCC)is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage,with surgical treatment options unavailable.Conversion therapy,which involves both locoregional and systemic treatments,has the potential to downstage tumors in selected patients with initially unresectable HCC,thereby making surgical treatment a possibility and potentially increasing long-term survival.To optimize the conversion rate,it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative effort.In this review article,we summarize the clinical experience and evidence for conversion therapy in patients with‘potentially resectable’HCC from four perspectives:1)defining the target population for conversion therapy,2)selecting the appropriate conversion strategy,placing emphasis on the utilization of combination therapy that exhibits a significant objective response rate,3)determining the timing and urgency of surgical resection,4)promoting the adoption of a multidisciplinary team model.The authors are optimistic that with the continuous progress in treatment and a deeper understanding of HCC,the success rate of HCC conversion therapy will increase,and the overall survival of HCC patients will be prolonged.展开更多
Objective: To investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). Methods: One hundred and four patients diagnos...Objective: To investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). Methods: One hundred and four patients diagnosed with ENKTCL at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China from November 1991 to September 2011 were included in the study. The clini-copathological features and their correlations with disease prognosis were evaluated in these patients. Results: The number of effective follow-up cases was 56 (53.8％) by the end of last follow-up in October 2015. Univariate survival analysisshowedthatgranzymeB,perforin,andBcl-2expressionwassignificantlyassociatedwithapoorprognosisinENKTCL(P= 0.033, 0.004, and 0.034, respectively), whereas platelet-derived growth factor receptor-alpha (PDGFRA) expression was significantly associated withabetterprognosis(P= 0.034).Ki-67overexpression(≥50％)wassignificantlyassociatedwithapoorprognosis(P= 0.017).Different treatment approaches were also associated with prognosis (P = 0.014); specifically, the efficacies of combination treatments including chemotherapy and radiotherapy, and autologous hematopoietic stem cell transplantation were significantly better than those involving radiotherapy and chemotherapy alone. Patient gender, age, tumor location, staging, the presence of B symptoms, pretreatment lactate dehydrogenase levels, and β2-microglobulin levels were not associated with the prognosis of ENKTCL (P > 0.05). However, multivariate analyses showed that the treatment approach and all the immune markers were not independent prognostic factors for ENKTCL. Conclusion: Granzyme B, perforin, and Bcl-2 expression and Ki-67 overexpression (≥50％) might be adverse prognostic factors for ENKTCL, whereas PDGFRA-positivity suggested a better disease prognosis. In addition, different treatment approaches might be closely related to patient prognosis.展开更多
基金Supported by the National Natural Science Foundation of China(No.82070942,No.81970780,No.81770907,No.81670835).
文摘AIM:To characterize the distribution of persistent fetal vasculature(PFV)subtypes and to evaluate corneal astigmatism(CA)in children with unilateral PFV.METHODS:The medical records of patients diagnosed with PFV between January 2014 and August 2021 were retrospectively reviewed.Corneal keratometry parameters were measured using IOLMaster or a handheld keratometer.Differences in CA between the affected and fellow eyes were analyzed in 52 unilateral PFV patients with available examination data.RESULTS:Totally 133 patients diagnosed with PFV were retrospectively reviewed.The male-to-female ratio was 73/60.Median age at surgery was 38.03mo(interquartile range 58.27mo).Among the PFV patients,32(24.06%)had anterior PFV,2(1.50%)had posterior PFV,and 99(74.44%)had combined anterior-posterior PFV.Mild combined PFV was the most common subtype.In unilateral PFV cases,the mean CA in the affected eye was 2.29±1.11 D,and 59.62%(31 eyes)had CA≥2.0 D.The mean CA in the affected eyes was significantly higher than in the fellow eyes(1.37±0.77 D;P<0.001).Among PFV-affected eyes with CA≥2.0 D,the steepest corneal meridian was vertically oriented in 30 cases(96.77%),while only 1 case(3.23%)had the steepest meridian oriented horizontally.CONCLUSION:In children with unilateral PFV,CA is significantly higher in the affected eyes than in the fellow eyes,and the steepest corneal meridian was predominantly oriented vertically.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010403,Ning Lyu)Natural Science Foundation of Guangdong Province,China(No.1914050001553,Dong Chen).
文摘Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.
基金This work was supported by the National Natural Science Foundation of China(82021002,31771164,and 31930042)the National Key R&D Program of China(2017YFB0403803)+1 种基金the Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Zhang Jiang Laboratory.
文摘Growth differentiation factor 15(GDF-15)is a member of the transforming growth factor-βsuperfamily.It is widely distributed in the central and peripheral nervous systems.Whether and how GDF-15 modulates nociceptive signaling remains unclear.Behaviorally,we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats.Electrophysiologically,we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia(DRG)neurons.Furthermore,GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents,and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction.GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels,suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel.Immunohistochemistry results showed that activin receptor-like kinase-2(ALK2)was widely expressed in DRG medium-and small-diameter neurons,and some of them were Nav1.8-positive.Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors.Inhibition of PKA and ERK,but not PKC,blocked the inhibitory effect of GDF-15 on Nav1.8 currents.These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK,which mediate the peripheral analgesia of GDF-15.
基金Supported by the National Natural Science Foundation of China(No.82072022 and No.81771956,MZ)the Guang-Dong Basic and Applied Basic Research Foundation(No.2021A1515010403,NL).
文摘The high mortality rate in hepatocellular carcinoma(HCC)is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage,with surgical treatment options unavailable.Conversion therapy,which involves both locoregional and systemic treatments,has the potential to downstage tumors in selected patients with initially unresectable HCC,thereby making surgical treatment a possibility and potentially increasing long-term survival.To optimize the conversion rate,it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative effort.In this review article,we summarize the clinical experience and evidence for conversion therapy in patients with‘potentially resectable’HCC from four perspectives:1)defining the target population for conversion therapy,2)selecting the appropriate conversion strategy,placing emphasis on the utilization of combination therapy that exhibits a significant objective response rate,3)determining the timing and urgency of surgical resection,4)promoting the adoption of a multidisciplinary team model.The authors are optimistic that with the continuous progress in treatment and a deeper understanding of HCC,the success rate of HCC conversion therapy will increase,and the overall survival of HCC patients will be prolonged.
文摘Objective: To investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). Methods: One hundred and four patients diagnosed with ENKTCL at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China from November 1991 to September 2011 were included in the study. The clini-copathological features and their correlations with disease prognosis were evaluated in these patients. Results: The number of effective follow-up cases was 56 (53.8％) by the end of last follow-up in October 2015. Univariate survival analysisshowedthatgranzymeB,perforin,andBcl-2expressionwassignificantlyassociatedwithapoorprognosisinENKTCL(P= 0.033, 0.004, and 0.034, respectively), whereas platelet-derived growth factor receptor-alpha (PDGFRA) expression was significantly associated withabetterprognosis(P= 0.034).Ki-67overexpression(≥50％)wassignificantlyassociatedwithapoorprognosis(P= 0.017).Different treatment approaches were also associated with prognosis (P = 0.014); specifically, the efficacies of combination treatments including chemotherapy and radiotherapy, and autologous hematopoietic stem cell transplantation were significantly better than those involving radiotherapy and chemotherapy alone. Patient gender, age, tumor location, staging, the presence of B symptoms, pretreatment lactate dehydrogenase levels, and β2-microglobulin levels were not associated with the prognosis of ENKTCL (P > 0.05). However, multivariate analyses showed that the treatment approach and all the immune markers were not independent prognostic factors for ENKTCL. Conclusion: Granzyme B, perforin, and Bcl-2 expression and Ki-67 overexpression (≥50％) might be adverse prognostic factors for ENKTCL, whereas PDGFRA-positivity suggested a better disease prognosis. In addition, different treatment approaches might be closely related to patient prognosis.
