AIM:To investigate the features of retinal ischemic injuries in a novel mouse model with bilateral carotid artery stenosis(BCAS).METHODS:BCAS was induced with microcoil implantation in 6-8-week-old C57BL6 mice.Cerebra...AIM:To investigate the features of retinal ischemic injuries in a novel mouse model with bilateral carotid artery stenosis(BCAS).METHODS:BCAS was induced with microcoil implantation in 6-8-week-old C57BL6 mice.Cerebral blood flow was monitored at 2,7,and 28d postoperatively.Retinal morphological changes were evaluated by fundus photography and hematoxylin-eosin staining.Fluorescein fundus angiography(FFA)was performed to detect retinal vascular changes and circulation.The levels of apoptosis,activation of neurogliosis,and expression of hypoxiainducible factor(HIF)-1αin the retina were assessed by Western blotting and immunofluorescence staining,followed by retinal ganglion cell(RGC)density detection.Additionally,electrophysiological examinations including photopic negative response(PhNR)was also performed.RESULTS:The mice demonstrated an initial rapid decrease in cerebral blood flow,followed by a 4-week recovery period after BCAS.The ratio of retinal artery and vein was decreased under fundus photography and FFA.Compared with the sham mice,BCAS mice showed thinner retinal thickness on day 28.Additionally,apoptosis was increased and RGC density was decreased mainly in peripheral retinal region.Neurogliosis was mainly located in the inner retinal layers,with a stable increase in HIF-1αexpression.The dark-adapted electroretinogram showed a notable reduction in the a-,b-,and oscillatory potential(OP)wave amplitudes between days 2 and 7;this gradually recovered over the following 4wk.However,the b-and OPwave amplitudes were still significantly decreased on PhNR examination on day 28.CONCLUSION:BCAS can result in relatively mild retinal ischemia injuries in mice,mainly in the inner layer and peripheral region.Our study provides a novel animal model for investigating retinal ischemic diseases.展开更多
Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human health.Owing to challenges in early diagnosis,most patients lose the opportunity for radical treatment when diagnosed.N...Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human health.Owing to challenges in early diagnosis,most patients lose the opportunity for radical treatment when diagnosed.Nonetheless,recent advancements in cancer immunotherapy provide new directions for the treatment of HCC.For instance,monoclonal antibodies against immune check-point inhibitors(ICIs)such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC.However,tumor cells can evade the immune system through various mechanisms.With the rapid development of genetic engineering and molecular biology,various new immunotherapies have been used to treat HCC,including ICIs,chimeric antigen receptor T cells,engineered cytokines,and certain cancer vaccines.This review summarizes the current status,research progress,and future directions of different immunotherapy strategies in the treatment of HCC.展开更多
BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(H...BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.展开更多
In spectrum analysis of induction motor current, the characteristic components of broken rotor bars（BRB） fault are often submerged by the fundamental component. Although many detection methods have been proposed for...In spectrum analysis of induction motor current, the characteristic components of broken rotor bars（BRB） fault are often submerged by the fundamental component. Although many detection methods have been proposed for this problem, the frequency resolution and accuracy are not high enough so that the reliability of BRB fault detection is a ected. Thus, a new multiple signal classification（MUSIC） algorithm based on particle swarm intelligence search is developed. Since spectrum peak search in MUSIC is a multimodal optimization problem, an improved bare?bones particle swarm optimization algorithm（IBPSO） is proposed first. In the IBPSO, a modified strategy of subpopulation determination is introduced into BPSO for realizing multimodal search. And then, the new MUSIC algorithm, called IBPSO?based MUSIC, is proposed by replacing the fixed?step traversal search with IBPSO. Meanwhile, a simulation signal is used to test the e ectiveness of the proposed algorithm. The simulation results show that its frequency precision reaches 10-5, and the computational cost is only comparable to that of traditional MUSIC with 0.1 search step. Finally, the IBPSO?based MUSIC is applied in BRB fault detection of an induction motor, and the e ectiveness and superiority are proved again. The proposed research provides a modified MUSIC algorithm which has su cient frequency precision to detect BRB fault in induction motors.展开更多
BACKGROUND Primary liver cancer is one of the most common malignant tumours,while primary splenic lymphoma is a rare malignancy.Thus,cases of hepatocellular carcinoma(HCC)combined with splenic lymphoma are extremely r...BACKGROUND Primary liver cancer is one of the most common malignant tumours,while primary splenic lymphoma is a rare malignancy.Thus,cases of hepatocellular carcinoma(HCC)combined with splenic lymphoma are extremely rare.CASE SUMMARY We present a 62-year-old woman who was admitted to the Interventional Radiology Department with a lump in the spleen and liver as well as multiple enlarged lymph nodes visible by ultrasound.Contrast-enhanced computed of the abdomen revealed a circular,low-density,shallow mass(approximately 2.6 cm in diameter)in the left intrahepatic lobe and multiple round,low-density shadows in the spleen with clear boundaries(maximum diameter 7.6 cm).Based on the characteristic clinical symptoms and explicit radiological findings,the clinical diagnosis was HCC with metastasis to the liver portal,retroperitoneal lymph nodes,and spleen.After transcatheter arterial chemoembolization and sequential radiofrequency ablation,the-fetoprotein level returned to the normal range,and the hepatitis B cirrhosis improved.In addition,splenic tumour biopsy confirmed the diagnosis of primary malignant lymphoma,which went into remission after chemotherapy.CONCLUSION HCC with primary splenic non-Hodgkin lymphoma is extremely rare and easily misdiagnosed.Better understanding would facilitate early diagnosis,treatment and prognosis.展开更多
BACKGROUND Cardiac resynchronization therapy(CRT)is a well-established therapy for patients with cardiomyopathy.CASE SUMMARY The patient underwent left bundle branch area and left ventricular(reaching the left ventric...BACKGROUND Cardiac resynchronization therapy(CRT)is a well-established therapy for patients with cardiomyopathy.CASE SUMMARY The patient underwent left bundle branch area and left ventricular(reaching the left ventricular lateral vein through the coronary sinus)pacing.The optimal CRT was performed under the right bundle branch of the patient by adjusting the optimal a-v and v-v interphases to achieve the maximal benefit of the treatment.CONCLUSION The patient was diagnosed with left bundle branch block and heart failure.A left bundle branch area pacemaker assisted in correcting the complete left bundle branch block.However,the shorter QRS wave shape after pacemaker implantation through the left bundle branch area indicated a complete right bundle branch block pattern.Hence,the left bundle branch area pacemaker is not always considered as the optimal treatment.The left bundle branch pacing with the optimization of cardiac resynchronization treatment may serve as a new CRT strategy.展开更多
BACKGROUND Diabetic mastopathy is a rare benign disease in clinical practice that mainly occurs in young and middle-aged women with type 1 diabetes.It has also been reported that this disease can be found in patients ...BACKGROUND Diabetic mastopathy is a rare benign disease in clinical practice that mainly occurs in young and middle-aged women with type 1 diabetes.It has also been reported that this disease can be found in patients with type 2 diabetes and other autoimmune diseases,such as Hashimoto's thyroiditis,as well as in men.The pathogenesis of diabetic mastopathy is not yet clear,and it is easily confused with breast cancer due to their similar clinical manifestations and imaging features.CASE SUMMARY A 69-year-old female patient was admitted because of painless breast masses,with a history of type 2 diabetes.The imaging and physical examination suggested a high risk of breast cancer.Further histopathological analysis showed dense lymphocytes infiltrating around the lobules of the breast,and extensive fibrosis of the surrounding stroma.Finally,diabetic mastopathy was diagnosed.CONCLUSION The diagnosis of diabetic mastopathy in elderly patients with painless breast masses is difficult to distinguish from breast cancer,and its imaging manifestations are not specific.展开更多
Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activ...Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.展开更多
基金Supported by The State Key Program of the National Natural Science Foundation of China(No.82030027)the National Natural Science Foundation of China(No.82101123).
文摘AIM:To investigate the features of retinal ischemic injuries in a novel mouse model with bilateral carotid artery stenosis(BCAS).METHODS:BCAS was induced with microcoil implantation in 6-8-week-old C57BL6 mice.Cerebral blood flow was monitored at 2,7,and 28d postoperatively.Retinal morphological changes were evaluated by fundus photography and hematoxylin-eosin staining.Fluorescein fundus angiography(FFA)was performed to detect retinal vascular changes and circulation.The levels of apoptosis,activation of neurogliosis,and expression of hypoxiainducible factor(HIF)-1αin the retina were assessed by Western blotting and immunofluorescence staining,followed by retinal ganglion cell(RGC)density detection.Additionally,electrophysiological examinations including photopic negative response(PhNR)was also performed.RESULTS:The mice demonstrated an initial rapid decrease in cerebral blood flow,followed by a 4-week recovery period after BCAS.The ratio of retinal artery and vein was decreased under fundus photography and FFA.Compared with the sham mice,BCAS mice showed thinner retinal thickness on day 28.Additionally,apoptosis was increased and RGC density was decreased mainly in peripheral retinal region.Neurogliosis was mainly located in the inner retinal layers,with a stable increase in HIF-1αexpression.The dark-adapted electroretinogram showed a notable reduction in the a-,b-,and oscillatory potential(OP)wave amplitudes between days 2 and 7;this gradually recovered over the following 4wk.However,the b-and OPwave amplitudes were still significantly decreased on PhNR examination on day 28.CONCLUSION:BCAS can result in relatively mild retinal ischemia injuries in mice,mainly in the inner layer and peripheral region.Our study provides a novel animal model for investigating retinal ischemic diseases.
文摘Advanced hepatocellular carcinoma(HCC)is a severe malignancy that poses a serious threat to human health.Owing to challenges in early diagnosis,most patients lose the opportunity for radical treatment when diagnosed.Nonetheless,recent advancements in cancer immunotherapy provide new directions for the treatment of HCC.For instance,monoclonal antibodies against immune check-point inhibitors(ICIs)such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC.However,tumor cells can evade the immune system through various mechanisms.With the rapid development of genetic engineering and molecular biology,various new immunotherapies have been used to treat HCC,including ICIs,chimeric antigen receptor T cells,engineered cytokines,and certain cancer vaccines.This review summarizes the current status,research progress,and future directions of different immunotherapy strategies in the treatment of HCC.
文摘BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.
基金Fundamental Research Funds for the Central Universities(Grant No.2017XKQY032)
文摘In spectrum analysis of induction motor current, the characteristic components of broken rotor bars（BRB） fault are often submerged by the fundamental component. Although many detection methods have been proposed for this problem, the frequency resolution and accuracy are not high enough so that the reliability of BRB fault detection is a ected. Thus, a new multiple signal classification（MUSIC） algorithm based on particle swarm intelligence search is developed. Since spectrum peak search in MUSIC is a multimodal optimization problem, an improved bare?bones particle swarm optimization algorithm（IBPSO） is proposed first. In the IBPSO, a modified strategy of subpopulation determination is introduced into BPSO for realizing multimodal search. And then, the new MUSIC algorithm, called IBPSO?based MUSIC, is proposed by replacing the fixed?step traversal search with IBPSO. Meanwhile, a simulation signal is used to test the e ectiveness of the proposed algorithm. The simulation results show that its frequency precision reaches 10-5, and the computational cost is only comparable to that of traditional MUSIC with 0.1 search step. Finally, the IBPSO?based MUSIC is applied in BRB fault detection of an induction motor, and the e ectiveness and superiority are proved again. The proposed research provides a modified MUSIC algorithm which has su cient frequency precision to detect BRB fault in induction motors.
基金Supported by the Medical and Health Technology Plan of Zhejiang Province,No.2020KY1086 and No.2022ZH086。
文摘BACKGROUND Primary liver cancer is one of the most common malignant tumours,while primary splenic lymphoma is a rare malignancy.Thus,cases of hepatocellular carcinoma(HCC)combined with splenic lymphoma are extremely rare.CASE SUMMARY We present a 62-year-old woman who was admitted to the Interventional Radiology Department with a lump in the spleen and liver as well as multiple enlarged lymph nodes visible by ultrasound.Contrast-enhanced computed of the abdomen revealed a circular,low-density,shallow mass(approximately 2.6 cm in diameter)in the left intrahepatic lobe and multiple round,low-density shadows in the spleen with clear boundaries(maximum diameter 7.6 cm).Based on the characteristic clinical symptoms and explicit radiological findings,the clinical diagnosis was HCC with metastasis to the liver portal,retroperitoneal lymph nodes,and spleen.After transcatheter arterial chemoembolization and sequential radiofrequency ablation,the-fetoprotein level returned to the normal range,and the hepatitis B cirrhosis improved.In addition,splenic tumour biopsy confirmed the diagnosis of primary malignant lymphoma,which went into remission after chemotherapy.CONCLUSION HCC with primary splenic non-Hodgkin lymphoma is extremely rare and easily misdiagnosed.Better understanding would facilitate early diagnosis,treatment and prognosis.
文摘BACKGROUND Cardiac resynchronization therapy(CRT)is a well-established therapy for patients with cardiomyopathy.CASE SUMMARY The patient underwent left bundle branch area and left ventricular(reaching the left ventricular lateral vein through the coronary sinus)pacing.The optimal CRT was performed under the right bundle branch of the patient by adjusting the optimal a-v and v-v interphases to achieve the maximal benefit of the treatment.CONCLUSION The patient was diagnosed with left bundle branch block and heart failure.A left bundle branch area pacemaker assisted in correcting the complete left bundle branch block.However,the shorter QRS wave shape after pacemaker implantation through the left bundle branch area indicated a complete right bundle branch block pattern.Hence,the left bundle branch area pacemaker is not always considered as the optimal treatment.The left bundle branch pacing with the optimization of cardiac resynchronization treatment may serve as a new CRT strategy.
文摘BACKGROUND Diabetic mastopathy is a rare benign disease in clinical practice that mainly occurs in young and middle-aged women with type 1 diabetes.It has also been reported that this disease can be found in patients with type 2 diabetes and other autoimmune diseases,such as Hashimoto's thyroiditis,as well as in men.The pathogenesis of diabetic mastopathy is not yet clear,and it is easily confused with breast cancer due to their similar clinical manifestations and imaging features.CASE SUMMARY A 69-year-old female patient was admitted because of painless breast masses,with a history of type 2 diabetes.The imaging and physical examination suggested a high risk of breast cancer.Further histopathological analysis showed dense lymphocytes infiltrating around the lobules of the breast,and extensive fibrosis of the surrounding stroma.Finally,diabetic mastopathy was diagnosed.CONCLUSION The diagnosis of diabetic mastopathy in elderly patients with painless breast masses is difficult to distinguish from breast cancer,and its imaging manifestations are not specific.
基金financially supported by National Natural Science Foundation of China (Nos. 21971023, 22074007 and 21525206)。
文摘Evaluating the correlation between hypoxia inducible factor 1(HIF-1) and nitric oxide(NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet(LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe’s capability of imaging exogenous and endogenous NO with specific in LDs of Hep G2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.
