BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of t...BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of this combined treatment strategy in enhancing overall survival(OS)and progression-free survival(PFS)compared to monotherapies.METHODS A systematic review was conducted following the PRISMA guidelines.A comprehensive search was performed across PubMed,EMBASE,Web of Science,and the Cochrane Library up to May 8,2024.Studies were included if they compared sorafenib plus TACE to sorafenib alone or TACE alone in adults with advanced HCC.Primary outcomes were OS,PFS,response rates,and safety profiles.Data extraction and quality assessment were independently performed by two reviewers.Heterogeneity was assessed using the I^(2)statistic,and a random-effects model was applied for pooling data.Sensitivity analysis and publication bias assessment were also conducted.RESULTS A total of twelve studies involving 1174 patients met the inclusion criteria.Significant heterogeneity was observed for both OS(I^(2)=72.6%,P<0.001)and PFS(I^(2)=83.7%,P<0.001).The combined treatment of sorafenib with TACE significantly improved OS[hazard ratio(HR)=0.60,95%confidence interval(CI):0.44-0.76]and PFS(HR=0.54,95%CI:0.38-0.69).Sensitivity analysis confirmed the robustness of these findings.Funnel plots and Egger's test indicated no significant publication bias.CONCLUSION Sorafenib combined with TACE significantly enhances both OS and PFS in patients with advanced HCC compared to monotherapy.This combination therapy represents a promising approach to improving clinical outcomes in advanced liver cancer.展开更多
AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for a...AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.展开更多
AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY...AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST groups.Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western blotting.Retinal pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST successively.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay.Apoptosis was analyzed by flow cytometry.Changes in autophagosome morphology were observed by transmission electron microscopy.Quantitative polymerase chain reaction(qPCR)was used to detect NLRP3 and caspase-1.NLRP3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western blotting.IL-1βand IL-18 were measured by ELISA.RESULTS:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited autophagy.Compared with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo.CY-09 and AST may protect retina from inflammatory injury.展开更多
Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomer...Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.展开更多
Background:There is growing evidence that the gene named tumor necrosis factorα–induced protein 6(TNFAIP6)has an important role in various tumors.However,a systematic pan-cancer analysis of TNFAIP6 is lacking.Here w...Background:There is growing evidence that the gene named tumor necrosis factorα–induced protein 6(TNFAIP6)has an important role in various tumors.However,a systematic pan-cancer analysis of TNFAIP6 is lacking.Here we aimed to analyze the expression of TNFAIP6 across multiple cancers and verify its expression during the progression of colon cancer.Methods:We performed a comprehensive bioinformatics analysis to examine the expression of TNFAIP6 across 27 tumor types.GEPIA2 was used to evaluate the effect of TNFAIP6 on clinical cancer prognosis.cBioportal was used to assess TNFAIP6 mutations.The correlation between TNFAIP6 and cancer immune infiltrates was explored using TIMER2.0.The CancerSEA database was used to perform functional analysis of TNFAIP6.Metascape was used to identify TNFAIP6-related gene enrichment pathways.Immunohistochemistry was performed to detect TNFAIP6 protein expression in the colon cancer.In addition,the Comparative Toxicogenomics Database was searched for known and possible antitumor drugs that may be associated with TNFAIP6.Results:We found that,in most of the cancers included in this analysis,TNFAIP6 was highly expressed,and there is a distinct relationship between TNFAIP6 expression and cancer prognosis.TNFAIP6 expression is associated with cancer-associated fibroblasts,neutrophils,and endothelial cells.TNFAIP6 and similar genes may also be involved in the PID_VEGF_VEGFR_pathway.Immunohistochemistry revealed an increasing trend of TNFAIP6 protein expression in normal,adenoma,and colon cancer tissues.Several known and possible antitumor drugs that may be associated with TNFAIP6 were identified in the Comparative Toxicogenomics Database.These results suggest that a number of drugsmay target TNFAIP6 during cancer treatment,including cisplatin,irinotecan,resveratrol,U 0126,NSC689534,genistein,NSC668394,oxaliplatin,plerixafor,topotecan,vincristine,flutamide,doxorubicin,MRK 003,folic acid,demecolcine,tunicamycin,zoledronic acid,and schizandrin B.Conclusions:TNFAIP6 may function as an oncogene in certain cancers.Furthermore,this study provides evidence that TNFAIP6 is an important factor in colon cancer progression.展开更多
The theory of“Salt-processing enhancing drug into kidney meridian”was firstly put forward by Chen Jiamu,a medical doctor of Xin’an,in“Enlightening Primer of Materia Medica”.This theory integrates the theory of th...The theory of“Salt-processing enhancing drug into kidney meridian”was firstly put forward by Chen Jiamu,a medical doctor of Xin’an,in“Enlightening Primer of Materia Medica”.This theory integrates the theory of the five elements of Chinese medicine that the five flavors enter into the five viscera,and forms the theory of the role of the auxiliary materials of Chinese medicine concoctions.This theory is an important guiding significance for the clinical use of raw and cooked Chinese medicine tablets.At present,there are more studies on the theory of“Salt-processing enhancing drug into kidney meridian”in the literature,mainly focusing on the chemical composition,efficacy changes and the concoction mechanism of salt products of traditional Chinese medicines before and after salt preparation.There are relatively few review papers on the theory of“Salt-processing enhancing drug into kidney meridian”from the perspectives of auxiliary salt and attribution of meridians.In this paper,through reviewing relevant ancient books and literature,and on the basis of the previous review articles,this paper centers on the auxiliary salt,and conducts in-depth excavation and elaboration in terms of its sources,types,and the historical evolution of the salt production method.From the perspective of categorization,focusing on the core theory of“Kidney stores essence,governing reproduction,bone and generating marrow,water and brain”,we summarize the changes in efficacy before and after the salt preparation of kidney tonic traditional Chinese medicines,the changes in external and internal constituents as well as the scientific connotation of the concocting mechanism behind the effect-constituent changes.The scientific connotation of the concoction theory of“Salt-processing enhancing drug into kidney meridian”was initially elucidated,providing a new reference model for the study of the theory of Chinese medicine concoction attribution.展开更多
AIM:To investigate the feasibility and clinical value of magnetic resonance imaging(MRI)-MRI image fusion in assessing the ablative margin(AM) for hepatocellular carcinoma(HCC).METHODS:A newly developed ultrasound wor...AIM:To investigate the feasibility and clinical value of magnetic resonance imaging(MRI)-MRI image fusion in assessing the ablative margin(AM) for hepatocellular carcinoma(HCC).METHODS:A newly developed ultrasound workstation for MRI-MRI image fusion was used to evaluate the AM of 62 tumors in 52 HCC patients after radiofrequency ablation(RFA).The lesions were divided into two groups:group A,in which the tumor was completely ablated and 5 mm AM was achieved(n = 32);and group B,in which the tumor was completely ablated but 5 mm AM was not achieved(n = 29).To detect local tumor progression(LTP),all patients were followed every two months by contrast-enhanced ultrasound,contrast-enhanced MRI or computed tomography(CT) in the first year after RFA.Then,the follow-up interval was prolonged to every three months after the first year.RESULTS:Of the 62 tumors,MRI-MRI image fusion was successful in 61(98.4%);the remaining case had significant deformation of the liver and massive ascites after RFA.The time required for creating image fusion and AM evaluation was 15.5 ± 5.5 min(range:8-22 min) and 9.6 ± 3.2 min(range:6-14 min),respectively.The follow-up period ranged from 1-23 mo(14.2 ± 5.4 mo).In group A,no LTP was detected in 32 lesions,whereas in group B,LTP was detected in 4 of 29 tumors,which occurred at 2,7,9,and 15 mo after RFA.The frequency of LTP in group B(13.8%;4/29) was significantly higher than that in group A(0/32,P = 0.046).All of the LTPs occurred in the area in which the 5 mm AM was not achieved.CONCLUSION:The MRI-MRI image fusion using an ultrasound workstation is feasible and useful for evaluating the AM after RFA for HCC.展开更多
AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 we...AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found. CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.展开更多
The Lijiang 2.4-meter Telescope(LJT), the largest common-purpose optical telescope in China,has been available to the worldwide astronomical community since 2008. It is located at the Gaomeigu site,Lijiang Observatory...The Lijiang 2.4-meter Telescope(LJT), the largest common-purpose optical telescope in China,has been available to the worldwide astronomical community since 2008. It is located at the Gaomeigu site,Lijiang Observatory(LJO), in the southwest of China. The site has very good observational conditions.During its 10-year operation, several instruments have been equipped on the LJT. Astronomers can perform both photometric and spectral observations. The main scientific goals of LJT include recording photometric and spectral evolution of supernovae, reverberation mapping of active galactic nuclei, investigating the physical properties of binary stars and near-earth objects(comets and asteroids), and identification of exoplanets and all kinds of transients. Until now, the masses of 41 high accretion rate black holes have been measured, and more than 168 supernovae have been identified by the LJT. More than 190 papers related to the LJT have been published. In this paper, the general observation conditions of the Gaomeigu site is introduced at first. Then, the structure of the LJT is described in detail, including the optical, mechanical, motion and control system. The specification of all the instruments and some detailed parameters of the YFOSC is also presented. Finally, some important scientific results and future expectations are summarized.展开更多
Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing cl...Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells （DCs） modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells. Methods： The peripheral blood mononuclear cells （PBMCs） from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus （rhAAV/HER2） to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase （LDH） releasing assay. Results： Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [（69.86±13.41）%] and MDA-MB-453 [（78.36±10.68）%] at 40：1 （effector：target ratio, E：T）, but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 （less than 10%）. Conclusion： The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.展开更多
Objective:The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC) in peripheral blood from metastatic breast cancer patients.The primary endp...Objective:The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC) in peripheral blood from metastatic breast cancer patients.The primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival(PFS).Methods:The breast cancer cell line MCF-7 was serially diluted into the peripheral blood from 45 healthy donors to set up the sensitivity of RT-PCR assay.The expression of CK19 mRNA was amplified from both 49 patients and 45 healthy donors respectively.The CK19 protein quantity from plasma was measured by competitive inhibition ELISA assay.Results:The sensitivity of RT-PCR could reach 1/106?107 white blood cells with specificity of 95.6%.The objective response rate(ORR) of patients with CK19 mRNA-negative undertaken one cycle chemotherapy was significantly higher than those with positive(P0.0001).PFS among CK19 mRNA-negative patients was also increased,although there was no significance(P=0.098).The results of ELISA assay showed that CK19 protein was decreased significantly after one cycle chemotherapy,which gave rise to a little higher ORR(P=0.015) and increased PFS(P=0.016).Conclusion:Patients with unamplified CK19 mRNA after one cycle chemotherapy could achieve better radiographic evaluation and increased PFS,which was showed to be of consistency with the CK19 protein assay among the patients treated.展开更多
AIM：To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation（SDM） and traditional modified Early Treatment Diabetic Retinopathy Study（mETDRS）treatment pr...AIM：To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation（SDM） and traditional modified Early Treatment Diabetic Retinopathy Study（mETDRS）treatment protocol in diabetic macuiar edema（DME）.METHODS：A comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for DME.The participants were type Ⅰ or type Ⅱ diabetes mellitus with clinically significant macuiar edema treated by SDM from previously reported randomized controlled trials（RCTs）.The primary outcome measures were the changes in the best corrected visual acuity（BCVA） and the central macuiar thickness（CMT） as measured by optical coherence tomography（OCT）.The secondary outcomes were the contrast sensitivity and the damages of the retina.RESULTS：Seven studies were identified and analyzed for comparing SDM（215 eyes） with mETDRS（210 eyes）for DME.There were no statistical differences in the BCVA after treatment between the SDM and mETDRS based on the follow-up：3mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.77）,6mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.75）,12mo（MD,-0.05;95% Cl,-0.17 to 0.07;P=0.40）.Likewise,there were no statistical differences in the CMT after treatment between the SDM and mETDRS in 3mo（MD,-9.92;95% Cl,-28.69 to 8.85;P=0.30）,6mo（MD,-11.37;95% Cl,-29.65 to 6.91;P=0.22）,12mo（MD,8.44;95% Cl,-29.89 to 46.77;P=0.67）.Three RCTs suggested that SDM laser results in good preservation of contrast sensitivity as mETDRS,in two different followup evaluations：3mo（MD,0.05;95% Cl,0 to 0.09;P=0.04） and 6mo（MD,0.02;95% Cl,-0.10 to 0.14;P=0.78）.Two RCTs showed that the SDM laser treatment did less retinal damage than that mETDRS did（OR,0.05;95% Cl,0.02 to 0.13;P〈0.01）.CONCLUSION：SDM laser photocoagulation shows an equally good effect on visual acuity,contrast sensitivity,and reduction of DME as compared to conventional mETDRS protocol with less retinal damage.展开更多
A novel visually meaningful image encryption algorithm is proposed based on a hyperchaotic system and compressive sensing(CS), which aims to improve the visual security of steganographic image and decrypted quality. F...A novel visually meaningful image encryption algorithm is proposed based on a hyperchaotic system and compressive sensing(CS), which aims to improve the visual security of steganographic image and decrypted quality. First, a dynamic spiral block scrambling is designed to encrypt the sparse matrix generated by performing discrete wavelet transform(DWT)on the plain image. Then, the encrypted image is compressed and quantified to obtain the noise-like cipher image. Then the cipher image is embedded into the alpha channel of the carrier image in portable network graphics(PNG) format to generate the visually meaningful steganographic image. In our scheme, the hyperchaotic Lorenz system controlled by the hash value of plain image is utilized to construct the scrambling matrix, the measurement matrix and the embedding matrix to achieve higher security. In addition, compared with other existing encryption algorithms, the proposed PNG-based embedding method can blindly extract the cipher image, thus effectively reducing the transmission cost and storage space. Finally, the experimental results indicate that the proposed encryption algorithm has very high visual security.展开更多
基金Supported by Sichuan Science and Technology Program,No.2022YFS0625。
文摘BACKGROUND The combination of sorafenib with transarterial chemoembolization(TACE)is being investigated for its potential to improve outcomes in advanced hepatocellular carcinoma(HCC).AIM To evaluate the efficacy of this combined treatment strategy in enhancing overall survival(OS)and progression-free survival(PFS)compared to monotherapies.METHODS A systematic review was conducted following the PRISMA guidelines.A comprehensive search was performed across PubMed,EMBASE,Web of Science,and the Cochrane Library up to May 8,2024.Studies were included if they compared sorafenib plus TACE to sorafenib alone or TACE alone in adults with advanced HCC.Primary outcomes were OS,PFS,response rates,and safety profiles.Data extraction and quality assessment were independently performed by two reviewers.Heterogeneity was assessed using the I^(2)statistic,and a random-effects model was applied for pooling data.Sensitivity analysis and publication bias assessment were also conducted.RESULTS A total of twelve studies involving 1174 patients met the inclusion criteria.Significant heterogeneity was observed for both OS(I^(2)=72.6%,P<0.001)and PFS(I^(2)=83.7%,P<0.001).The combined treatment of sorafenib with TACE significantly improved OS[hazard ratio(HR)=0.60,95%confidence interval(CI):0.44-0.76]and PFS(HR=0.54,95%CI:0.38-0.69).Sensitivity analysis confirmed the robustness of these findings.Funnel plots and Egger's test indicated no significant publication bias.CONCLUSION Sorafenib combined with TACE significantly enhances both OS and PFS in patients with advanced HCC compared to monotherapy.This combination therapy represents a promising approach to improving clinical outcomes in advanced liver cancer.
基金Supported by the National Natural Science Foundation of China(No.82071888)the Natural Science Foundation of Shandong Province(No.ZR2021MH351,No.ZR2020MH074)+1 种基金the Introduction and Cultivation Project for Young Innovative Talents in Shandong ProvinceWeifang Science and Technology Development Plan(No.2021GX057).
文摘AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.
基金Supported by the National Key R&D Project(No.2018YFC1106103)Project of Sichuan Medical Association(No.S22058).
文摘AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST groups.Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western blotting.Retinal pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST successively.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay.Apoptosis was analyzed by flow cytometry.Changes in autophagosome morphology were observed by transmission electron microscopy.Quantitative polymerase chain reaction(qPCR)was used to detect NLRP3 and caspase-1.NLRP3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western blotting.IL-1βand IL-18 were measured by ELISA.RESULTS:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited autophagy.Compared with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo.CY-09 and AST may protect retina from inflammatory injury.
基金Supported by the Project of Sichuan Medical Association (No.S22058)National Key R&D Project (No.2018YFC1106103).
文摘Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.
基金funded by the Natural Science Basic Research Pro-gram of Shaanxi(no.2023-JC-QN-0876)Key Research and Development Program of Shaanxi(no.2023-YBSF-447).
文摘Background:There is growing evidence that the gene named tumor necrosis factorα–induced protein 6(TNFAIP6)has an important role in various tumors.However,a systematic pan-cancer analysis of TNFAIP6 is lacking.Here we aimed to analyze the expression of TNFAIP6 across multiple cancers and verify its expression during the progression of colon cancer.Methods:We performed a comprehensive bioinformatics analysis to examine the expression of TNFAIP6 across 27 tumor types.GEPIA2 was used to evaluate the effect of TNFAIP6 on clinical cancer prognosis.cBioportal was used to assess TNFAIP6 mutations.The correlation between TNFAIP6 and cancer immune infiltrates was explored using TIMER2.0.The CancerSEA database was used to perform functional analysis of TNFAIP6.Metascape was used to identify TNFAIP6-related gene enrichment pathways.Immunohistochemistry was performed to detect TNFAIP6 protein expression in the colon cancer.In addition,the Comparative Toxicogenomics Database was searched for known and possible antitumor drugs that may be associated with TNFAIP6.Results:We found that,in most of the cancers included in this analysis,TNFAIP6 was highly expressed,and there is a distinct relationship between TNFAIP6 expression and cancer prognosis.TNFAIP6 expression is associated with cancer-associated fibroblasts,neutrophils,and endothelial cells.TNFAIP6 and similar genes may also be involved in the PID_VEGF_VEGFR_pathway.Immunohistochemistry revealed an increasing trend of TNFAIP6 protein expression in normal,adenoma,and colon cancer tissues.Several known and possible antitumor drugs that may be associated with TNFAIP6 were identified in the Comparative Toxicogenomics Database.These results suggest that a number of drugsmay target TNFAIP6 during cancer treatment,including cisplatin,irinotecan,resveratrol,U 0126,NSC689534,genistein,NSC668394,oxaliplatin,plerixafor,topotecan,vincristine,flutamide,doxorubicin,MRK 003,folic acid,demecolcine,tunicamycin,zoledronic acid,and schizandrin B.Conclusions:TNFAIP6 may function as an oncogene in certain cancers.Furthermore,this study provides evidence that TNFAIP6 is an important factor in colon cancer progression.
基金supported by The Youth Project of the National Natural Science Foundation of China(No.82204623)Key scientific research projects in universities in Anhui Province(No.2022AH050471)+1 种基金Young Science and Technology Talents Cultivation Program of Anhui University of Traditional Chinese Medicine(No.2021qnyc04)Scientific Research Team Program of Anhui Colleges and Universities(No.2022AH010036).
文摘The theory of“Salt-processing enhancing drug into kidney meridian”was firstly put forward by Chen Jiamu,a medical doctor of Xin’an,in“Enlightening Primer of Materia Medica”.This theory integrates the theory of the five elements of Chinese medicine that the five flavors enter into the five viscera,and forms the theory of the role of the auxiliary materials of Chinese medicine concoctions.This theory is an important guiding significance for the clinical use of raw and cooked Chinese medicine tablets.At present,there are more studies on the theory of“Salt-processing enhancing drug into kidney meridian”in the literature,mainly focusing on the chemical composition,efficacy changes and the concoction mechanism of salt products of traditional Chinese medicines before and after salt preparation.There are relatively few review papers on the theory of“Salt-processing enhancing drug into kidney meridian”from the perspectives of auxiliary salt and attribution of meridians.In this paper,through reviewing relevant ancient books and literature,and on the basis of the previous review articles,this paper centers on the auxiliary salt,and conducts in-depth excavation and elaboration in terms of its sources,types,and the historical evolution of the salt production method.From the perspective of categorization,focusing on the core theory of“Kidney stores essence,governing reproduction,bone and generating marrow,water and brain”,we summarize the changes in efficacy before and after the salt preparation of kidney tonic traditional Chinese medicines,the changes in external and internal constituents as well as the scientific connotation of the concocting mechanism behind the effect-constituent changes.The scientific connotation of the concoction theory of“Salt-processing enhancing drug into kidney meridian”was initially elucidated,providing a new reference model for the study of the theory of Chinese medicine concoction attribution.
基金National Natural Science Foundation of China,No.81271669,No.81430038 and No.81301931
文摘AIM:To investigate the feasibility and clinical value of magnetic resonance imaging(MRI)-MRI image fusion in assessing the ablative margin(AM) for hepatocellular carcinoma(HCC).METHODS:A newly developed ultrasound workstation for MRI-MRI image fusion was used to evaluate the AM of 62 tumors in 52 HCC patients after radiofrequency ablation(RFA).The lesions were divided into two groups:group A,in which the tumor was completely ablated and 5 mm AM was achieved(n = 32);and group B,in which the tumor was completely ablated but 5 mm AM was not achieved(n = 29).To detect local tumor progression(LTP),all patients were followed every two months by contrast-enhanced ultrasound,contrast-enhanced MRI or computed tomography(CT) in the first year after RFA.Then,the follow-up interval was prolonged to every three months after the first year.RESULTS:Of the 62 tumors,MRI-MRI image fusion was successful in 61(98.4%);the remaining case had significant deformation of the liver and massive ascites after RFA.The time required for creating image fusion and AM evaluation was 15.5 ± 5.5 min(range:8-22 min) and 9.6 ± 3.2 min(range:6-14 min),respectively.The follow-up period ranged from 1-23 mo(14.2 ± 5.4 mo).In group A,no LTP was detected in 32 lesions,whereas in group B,LTP was detected in 4 of 29 tumors,which occurred at 2,7,9,and 15 mo after RFA.The frequency of LTP in group B(13.8%;4/29) was significantly higher than that in group A(0/32,P = 0.046).All of the LTPs occurred in the area in which the 5 mm AM was not achieved.CONCLUSION:The MRI-MRI image fusion using an ultrasound workstation is feasible and useful for evaluating the AM after RFA for HCC.
基金Supported by International Cooperation Project of the Guangzhou Science and Technology Bureau, No. 2011J5200017Guangdong Provincial Science and Technology Development Program, No. 2011B031800207
文摘AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found. CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.
基金supported by the Joint Research Fund in Astronomy (U1631127, U1631129 and U1831204) under cooperative agreement between the National Natural Science Foundation of China (NSFC) and Chinese Academy of Sciences (CAS)the National Natural Science Foundation of China (NSFC) (11473068, 11603072 and 11573067)+1 种基金the National Key R&D Program of China (2018YFA0404603)supported by the Key Laboratory for the Structure and Evolution of Celestial Objects, Chinese Academy of Sciences (CAS)
文摘The Lijiang 2.4-meter Telescope(LJT), the largest common-purpose optical telescope in China,has been available to the worldwide astronomical community since 2008. It is located at the Gaomeigu site,Lijiang Observatory(LJO), in the southwest of China. The site has very good observational conditions.During its 10-year operation, several instruments have been equipped on the LJT. Astronomers can perform both photometric and spectral observations. The main scientific goals of LJT include recording photometric and spectral evolution of supernovae, reverberation mapping of active galactic nuclei, investigating the physical properties of binary stars and near-earth objects(comets and asteroids), and identification of exoplanets and all kinds of transients. Until now, the masses of 41 high accretion rate black holes have been measured, and more than 168 supernovae have been identified by the LJT. More than 190 papers related to the LJT have been published. In this paper, the general observation conditions of the Gaomeigu site is introduced at first. Then, the structure of the LJT is described in detail, including the optical, mechanical, motion and control system. The specification of all the instruments and some detailed parameters of the YFOSC is also presented. Finally, some important scientific results and future expectations are summarized.
基金supported by the grant from the National"973"Basic Research Program of China(No.2009CB521703)Medical Oncology Leadership of Beijing Municipal Government Health Burean(No.2009-2-16)
文摘Objective： Although the development of trastuzumab has improved the outlook for women with human epidermal growth factor receptor 2 （HER2）-positive breast cancer, the resistance to anti-HER2 therapy is a growing clinical dilemma. We aim to determine whether HER2-specific T cells generated from dendritic cells （DCs） modified with HER2 gene could effectively kill the HER2-positive breast cancer cells, especially the trastuzumab-resistant cells. Methods： The peripheral blood mononuclear cells （PBMCs） from healthy donors, whose HLA haplotypes were compatible with the tumor cell lines, were transfected with reconstructive human adeno-association virus （rhAAV/HER2） to obtain the specific killing activities of T cells, and were evaluated by lactate dehydrogenase （LDH） releasing assay. Results： Trastuzumab produced a significant inhibiting effect on SK-BR-3, the IC50 was 100ng/ml. MDA-MB-453 was resistant to trastuzumab even at a concentration of 10,000 ng/ml in vitro. HER2-specific T lymphocytes killed effectively SK-BR-3 [（69.86±13.41）%] and MDA-MB-453 [（78.36±10.68）%] at 40：1 （effector：target ratio, E：T）, but had no significant cytotoxicity against HER2-negative breast cancer cell lines MDA-MB-231 or MCF-7 （less than 10%）. Conclusion： The study showed that HER2-specific T lymphocytes generated from DCs modified by rhAAV/HER2 could kill HER2-positive breast cancer cell lines in a HER2-dependent manner, and result in significantly high inhibition rates on the intrinsic trastuzumab-resistant cell line MDA-MB-453 and the tastuzumab-sensitive cell line SK-BR-3. These results imply that this immunotherapy might be a potential treatment to HER2-positive breast cancer.
基金supported by a grant from the Beijing Capital Development Foundation for Medical Sciences(No.2007-2053)
文摘Objective:The purpose of this study is to explore RT-PCR method to set up the examination platform for detecting circulating tumor cells(CTC) in peripheral blood from metastatic breast cancer patients.The primary endpoint is to find out the correlation of existence of CTC with clinical responses and progression-free survival(PFS).Methods:The breast cancer cell line MCF-7 was serially diluted into the peripheral blood from 45 healthy donors to set up the sensitivity of RT-PCR assay.The expression of CK19 mRNA was amplified from both 49 patients and 45 healthy donors respectively.The CK19 protein quantity from plasma was measured by competitive inhibition ELISA assay.Results:The sensitivity of RT-PCR could reach 1/106?107 white blood cells with specificity of 95.6%.The objective response rate(ORR) of patients with CK19 mRNA-negative undertaken one cycle chemotherapy was significantly higher than those with positive(P0.0001).PFS among CK19 mRNA-negative patients was also increased,although there was no significance(P=0.098).The results of ELISA assay showed that CK19 protein was decreased significantly after one cycle chemotherapy,which gave rise to a little higher ORR(P=0.015) and increased PFS(P=0.016).Conclusion:Patients with unamplified CK19 mRNA after one cycle chemotherapy could achieve better radiographic evaluation and increased PFS,which was showed to be of consistency with the CK19 protein assay among the patients treated.
文摘AIM：To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation（SDM） and traditional modified Early Treatment Diabetic Retinopathy Study（mETDRS）treatment protocol in diabetic macuiar edema（DME）.METHODS：A comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for DME.The participants were type Ⅰ or type Ⅱ diabetes mellitus with clinically significant macuiar edema treated by SDM from previously reported randomized controlled trials（RCTs）.The primary outcome measures were the changes in the best corrected visual acuity（BCVA） and the central macuiar thickness（CMT） as measured by optical coherence tomography（OCT）.The secondary outcomes were the contrast sensitivity and the damages of the retina.RESULTS：Seven studies were identified and analyzed for comparing SDM（215 eyes） with mETDRS（210 eyes）for DME.There were no statistical differences in the BCVA after treatment between the SDM and mETDRS based on the follow-up：3mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.77）,6mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.75）,12mo（MD,-0.05;95% Cl,-0.17 to 0.07;P=0.40）.Likewise,there were no statistical differences in the CMT after treatment between the SDM and mETDRS in 3mo（MD,-9.92;95% Cl,-28.69 to 8.85;P=0.30）,6mo（MD,-11.37;95% Cl,-29.65 to 6.91;P=0.22）,12mo（MD,8.44;95% Cl,-29.89 to 46.77;P=0.67）.Three RCTs suggested that SDM laser results in good preservation of contrast sensitivity as mETDRS,in two different followup evaluations：3mo（MD,0.05;95% Cl,0 to 0.09;P=0.04） and 6mo（MD,0.02;95% Cl,-0.10 to 0.14;P=0.78）.Two RCTs showed that the SDM laser treatment did less retinal damage than that mETDRS did（OR,0.05;95% Cl,0.02 to 0.13;P〈0.01）.CONCLUSION：SDM laser photocoagulation shows an equally good effect on visual acuity,contrast sensitivity,and reduction of DME as compared to conventional mETDRS protocol with less retinal damage.
基金supported by the National Natural Science Foundation of China (Grant No. 61672124)the Password Theory Project of the 13th Five-Year Plan National Cryptography Development Fund (Grant No. MMJJ20170203)+3 种基金Liaoning Province Science and Technology Innovation Leading Talents Program Project (Grant No. XLYC1802013)Key R&D Projects of Liaoning Province (Grant No. 2019020105JH2/103)Jinan City ‘20 Universities’ Funding Projects Introducing Innovation Team Program (Grant No. 2019GXRC031)Research Fund of Guangxi Key Lab of Multi-source Information Mining & Security (Grant No. MIMS20-M-02)。
文摘A novel visually meaningful image encryption algorithm is proposed based on a hyperchaotic system and compressive sensing(CS), which aims to improve the visual security of steganographic image and decrypted quality. First, a dynamic spiral block scrambling is designed to encrypt the sparse matrix generated by performing discrete wavelet transform(DWT)on the plain image. Then, the encrypted image is compressed and quantified to obtain the noise-like cipher image. Then the cipher image is embedded into the alpha channel of the carrier image in portable network graphics(PNG) format to generate the visually meaningful steganographic image. In our scheme, the hyperchaotic Lorenz system controlled by the hash value of plain image is utilized to construct the scrambling matrix, the measurement matrix and the embedding matrix to achieve higher security. In addition, compared with other existing encryption algorithms, the proposed PNG-based embedding method can blindly extract the cipher image, thus effectively reducing the transmission cost and storage space. Finally, the experimental results indicate that the proposed encryption algorithm has very high visual security.
