ABSTRACT
Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.
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Ubiquitin-specific proteases (USPs) have been proved to play important roles in the progression of diabetic retinopathy. In this study, we explored the role of USP5 and its possible mechanisms in diabetic retinopathy development. Cell proliferation, apoptosis, inflammation and oxidative stress were determined using CCK-8 assay, EdU staining assay, flow cytometry, and ELISA, respectively. The mRNA and protein expression of ROBO4 and USP5 were measured through RT-qPCR and western blot, respectively. Co-IP and deubiquitination assay were conducted to evaluate the interaction between ROBO4 and USP5. The results showed that high glucose (HG) stimulation significantly led to HRPE cell damage as described by suppressing proliferation, and promoting oxidative stress, inflammation and apoptosis. ROBO4 was markedly increased in diabetic retinopathy plasma samples and HG-triggered HRPE cells. Depletion of ROBO4 could alleviate HG-caused HRPE cell damage. USP5 was also significantly elevated in diabetic retinopathy plasma samples and HG-triggered HRPE cells. USP5 overexpression aggravated HG-induced HRPE cell damage. USP5 stabilized ROBO4 through deubiquitination. Moreover, USP5 knockdown decreased ROBO4 expression to mitigate HG-triggered cell damage in HRPE cells. USP5 stabilized ROBO4 via deubiquitination to repress cell proliferation, and facilitate inflammation, cell apoptosis and oxidative stress in HG-treated HRPE cells, thereby promoting the development of diabetic retinopathy.
Subject(s)
Diabetic Retinopathy , Receptors, Cell Surface , Ubiquitination , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Humans , Receptors, Cell Surface/metabolism , Apoptosis , Ubiquitin-Specific Proteases/metabolism , Ubiquitin-Specific Proteases/genetics , Cell Proliferation , Oxidative Stress , Animals , Glucose/metabolism , Glucose/pharmacology , Cell Line , Roundabout ProteinsABSTRACT
OBJECTIVE: Drug resistance greatly limits the therapeutic effect of a drug. This study aimed to explore the role of long noncoding RNA ZFAS1 in Donafenib resistance of hepatocellular carcinoma (HCC) cells. METHODS: The expression of CREB3, ZFAS1, and p65 in HCC cell lines was measured by RT-qPCR and western blotting. After transfection with sh-ZFAS1, sh-CREB3, or sh-CREB3 + oe-p65 in Donafenib-resistent (DR) HCC cell lines, the transfection efficiency was evaluated by RT-qPCR and western blotting. The proliferation and IC50 to Donafenib of HCC cell lines was examined by MTT assay. Cell proliferation and apoptosis were examined by colony formation and flow cytometry assays. Then, the correlation amongst CREB3, ZFAS1, LSD1/CoREST, and p65 was analysed by ChIP, dual-luciferase reporter gene, and RIP assays. RESULTS: ZFAS1, CREB3, and p65 were upregulated in HepG2-DR and Huh7-DR cells. Silencing of ZFAS1 or CREB3 enhanced the sensitivity of HCC cells to Donafenib, inhibited cell proliferation and IC50, and increased cell apoptosis, which were reversed by p65 overexpression. Mechanistically, CREB3 bound to ZFAS1 promoter to augment ZFAS1 transcriptional expression, and ZFAS1 recruited LSD1/CoREST to the p65 promoter region to decrease H3K4 methylation and elevate p65 transcriptional expression. CONCLUSION: CREB3 overexpression contributed to Donafenib resistance in HCC cells by activating the ZFAS1/p65 axis.
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Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."
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Background: Lenvatinib combined with programmed cell death protein-1 inhibitor has achieved good survival results in the treatment of hepatocellular carcinoma with portal vein tumor thrombus. Transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) has attracted attention because of its high response rate and favorable survival rate in patients with liver cancer and portal vein tumor thrombus. This study aimed to compare the efficacy and safety of Lenvatinib combined with programmed cell death protein-1 inhibitor plus transarterial chemoembolization or hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma with portal vein tumor thrombus. Method: We searched PubMed, Embase and the Cochrane Library for studies. These included randomized controlled trials or clinical trials of Lenvatinib plus programmed cell death protein-1 inhibitor plus transarterial chemoembolization or hepatic arterial infusion chemotherapy (intervention group) versus Lenvatinib plus programmed cell death protein-1 inhibitor or Lenvatinib plus transarterial chemoembolization/hepatic arterial infusion chemotherapy or Lenvatinib alone (control group) in liver cancer with portal vein tumor thrombus The primary outcomes were overall survival and progression-free time, and the secondary outcomes were response rate and the rate of adverse events. According to the heterogeneity among different studies, Revman5.4 was used to conduct fixed effect or random effect model analysis. Results: Five clinical trials were included, including 311 cases in the intervention group and 309 cases in the control group. In terms of efficacy, compared with the control group, the overall survival (HR=1.88, 95%CI: 1.57-2.25, P < 0.00001) and progression-free survival (HR=1.62, 95%CI: 1.41-1.86, P < 0.00001), better efficacy, and better disease response than the control group. In terms of safety, the risk of treatment-related adverse events in the intervention group was higher than that in the control group, and White Blood cell count decreased (RR=0.72, 95%CI: 0.38-1.37, P=0.32), Platelet count decreased (RR=0.99, 95%CI: 0.65-1.51, P=0.96) and Total bilirubin increased (RR=0.86, 95%CI: Increased) 0.88-1.28, P=0.46) were lower than those in the control group, and the rest were higher than those in the control group, and the differences in some results were statistically significant. Conclusions: Transarterial chemoembolization or hepatic arterial infusion chemotherapy combined with Lenvatinib plus programmed cell death protein-1 inhibitor can effectively delay the progression, prolong the survival period and improve the quality of life of liver cancer patients with portal vein tumor thrombus.
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Purpose: To evaluate short-term effectiveness and safety of computed tomography (CT)-guided radioactive iodine-125 (125I) seed implantation (CTRISI) for treating adrenal metastases. Material and methods: A total of 50 consecutive patients with adrenal metastases were enrolled retrospectively. Among them, 18 patients received CTRISI, and 18 received 3D-conformal radiotherapy (3D-CRT) treatment. The remaining 14 patients without any treatments served as a control group. Follow-up CT was performed at 6 weeks, 3 months, and 6 months after treatment. Tumor responses and complications were evaluated. Results: At 6 weeks, control rate in control group (complete response [CR] + partial response [PR]) was 0, and in the CTRISI group (CR + PR, 84.41%), it was significantly higher than that in the 3D-CRT group (CR + PR, 44.44%). Local control rates with CTRISI at 3 and 6 months were 68.42% and 57.89%, respectively. No severe complications were observed after CTRISI. Conclusions: CTRISI is an effective and safe method for short-term treatment of adrenal metastases. Our findings suggest that CTRISI can safely and effectively be used for adrenal metastases patients as short-term treatment. Further survival studies with longer follow-up are warranted to validate our results.
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BACKGROUND: In this study, we compared the efficacy of Ahmed, Ex-PRESS, and trabeculectomy to provide a reference for determining surgical schemes for glaucoma patients undergoing external drainage surgery in clinical practice. METHODS: We performed a literature search for studies on the treatment of primary and secondary glaucoma with three types of external drainage surgery (Ahmed, Ex-PRESS, and trabeculectomy). As at April 24, 2021, seven electronic databases were searched for randomized controlled trials comparing any two of Ahmed, Ex-PRESS, and trabeculectomy in the treatment of glaucoma. The Cochrane tool was also adopted to evaluate the risk of bias in these trials. The relative risk (RR) with 95% confidence interval (CI), and weighted mean difference (WMD) were determined and compared indirectly using R software. RESULTS: A total of 14 randomized controlled trials were included in this study, involving 866 eyes of 808 patients. As for the intraocular pressure (IOP) after 3 months, trabeculectomy did not contribute to better improvement than Ahmed (WMD =0.014; 95% CI: -0.14-0.18) and Ex-PRESS (WMD =0.014; 95% CI: -0.072-0.097). However, there was a significant difference in the IOP 1 year between trabeculectomy and Ex-PRESS (WMD =0.097; 95% CI: 0.0080-0.18), with the latter achieving a favorable improvement effect. Meanwhile, the complete success (CS) of trabeculectomy was significantly lower than that of Ex-PRESS (RR =0.73; 95% CI: 0.57-0.93). In addition, Ex-PRESS was superior to Ahmed (WMD =-0.48; 95% CI: -0.89 to -0.084) in terms of a decreased number of post-operative medications. DISCUSSION: For glaucoma patients who are required to receive external drainage surgery, Ex-PRESS could achieve a significant effect on the IOP 1 year and CS, as well as a marked decrease in the number of post-operative medications used, compared with the other two types of surgery. In terms of the efficacy at least 1 year after surgery, Ex-PRESS should be one of the preferred methods for external drainage.
Subject(s)
Glaucoma Drainage Implants , Glaucoma , Trabeculectomy , Glaucoma/surgery , Humans , Intraocular Pressure , Network Meta-Analysis , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Background: This study aimed to compare the therapeutic efficacy and the side effects of different endostar administration methods in patients with advanced malignancy who underwent second-line chemotherapy. Methods: 98 patients with advanced malignancies were divided into 2 groups based on the delivery methods of endostar, including drip intravenous administration of endostar (DE) group and continuous intravenous administration of endostar (CE) group. Response rate (RR), disease control rate (DCR), and quality of life (QOL) of the patients were examined to evaluate the therapeutic efficacy, and toxicity reactions were analyzed to evaluate the adverse effects. Results: Compared with the DE group, the therapeutic efficacy of CE has been slightly improved, but the difference did not reach statistical significance (P > 0.05). Additionally, no different incidence rate was observed in toxic reactions, including leukopenia, thrombocytopenia, nausea and vomiting, diarrhea, and hepatic function damage, between the DE and CE groups (P > 0.05). Conclusion: In conclusion, no significant difference was observed between the traditional intravenous drip of endostar group and the intravenous drip followed by continuous pumping of endostar group in the patients with advanced malignancies.
Subject(s)
Lung Neoplasms , Quality of Life , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Endostatins/adverse effects , Humans , Lung Neoplasms/pathology , Neoplasm Staging , Recombinant ProteinsABSTRACT
OBJECTIVES: This retrospective cohort study investigated the efficacy of routine intravenous chemotherapy (the control group), transcatheter arterial infusion (TAI) chemotherapy, and TAI combined with radioactive particles as therapeutic methods for advanced body/tail pancreatic cancer by assessing the short-term and overall survival rates. METHODS: We screened our prospective database for patients with advanced body/tail pancreatic cancer, which tumor deemed unresectable, and no other confirmed malignant tumors, patients were assigned into 3 groups according to their treatment: routine intravenous chemotherapy, TAI, and TAI combined with radioactive particles. RESULTS: The median survival time was 6 months in the control group, 10 months in the TAI group, and 13 months in the TAI combined group. The Kaplan-Meier estimates of the overall survival among the 3 groups, indicating that there is significant difference among 3 groups (P < 0.000). The clinical remission rates were 17.5% in the control group, 41.5% in the TAI group, and 48.0% in the TAI combined group. Covariates analyzed showed that different treatment methods and times affected the results significantly (P < 0.002). CONCLUSIONS: In the treatment of advanced body/tail pancreatic cancer, TAI and TAI combined with radioactive particles significantly improved the clinical outcomes in patients compared with routine intravenous chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Iodine Radioisotopes/therapeutic use , Outcome Assessment, Health Care/statistics & numerical data , Pancreatic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Catheters , Chemoradiotherapy/methods , Female , Humans , Infusions, Intra-Arterial/methods , Kaplan-Meier Estimate , Male , Middle Aged , Outcome Assessment, Health Care/methods , Retrospective StudiesABSTRACT
MicroRNA-4458 (miR-4458) has been reported to be associated with several cancers including non-small-cell lung cancer (NSCLC), while its role in tumor immunity remains unclear. The purpose of the current research was to explore the anti-tumor immunity of miR-4458 in NSCLC. The results showed that the expression level of miR-4458 decreased and STAT3 increased in NSCLC tissues and cells. For in vitro experiments, miR-4458 mimics suppressed cell proliferation and decreased the expression level of PD-L1. Moreover, STAT3 was confirmed as a target gene of miR-4458. Upregulation of STAT3 level ameliorated the inhibitive effects of miR-4458 on cells proliferation and PD-L1 expression in cells. For in vivo studies, overexpression of miR-4458 hindered tumor growth, decreased the proportion of PD-1+ T cells, the expression of PD-L1 and IL-10, upregulated the proportion of CD4+ T, CD8+ T cells as well as the expression of IFN-γ and IL-2, which were all reversed by overexpression of STAT3, and the effects of STAT3 were counteracted after knockdown of PD-L1. MiR-4458 overexpression enhanced anti-tumor immunity via targeting STAT3 to block the PD-L1/PD-1 pathway.
Subject(s)
B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , MicroRNAs/genetics , STAT3 Transcription Factor/genetics , A549 Cells , Animals , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Case-Control Studies , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice , Neoplasm Transplantation , T-Lymphocytes/immunologyABSTRACT
PURPOSE: To investigate changes in retinal oximetry and the diameter of retinal vasculature in patients with chronic kidney disease (CKD) and relationships between retinal vasculature and the estimated glomerular filtration rate (eGFR), provide a scientific basis for the early detection and diagnosis of CKD. METHODS: Eighty-three patients with CKD and 103 healthy individuals were included after providing informed consent. All participants were examined using a noninvasive technology (Oxymap Inc., Reykjavik, Iceland) for measuring the arterial (SaO2 ) and venous (SvO2 ) oxygen saturation and the arteriovenous difference in oxygen saturation (Sa-vO2 ). The corresponding retinal vessel diameters of these arterioles (D-A) and venules (D-V) were measured. The eGFR of patients with CKD was calculated from the serum creatinine concentration. RESULTS: In general, patients with CKD had higher mean SaO2 values than healthy individuals (100.15 ± 4.68% versus 97.14 ± 4.22%; p < 0.001, mean ± SD). The mean SaO2 in the superior temporal, superior nasal and inferior nasal quadrants significantly increased. There was no significant difference measured in the SvO2 when patients with CKD (63.66 ± 5.29%) and healthy individuals (62.70 ± 5.27%) were compared. The mean Sa-vO2 of the CKD group (36.49 ± 4.98%) was increased compared with normal subjects (34.44 ± 4.76%) (p = 0.005). The retinal arteriole diameter was narrower in patients with CKD than in normal individuals (117.53 ± 14.88 µm versus 126.87 ± 14.98 µm; p < 0.001, mean ± SD), and the arteriovenous ratio was smaller than in normal individuals (0.71 ± 0.09 versus 0.77 ± 0.09; p < 0.001, mean ± SD). Pearson's two-tailed correlation showed a significant correlation between the SaO2 and eGFR (R = -0.363, p = 0.001), and narrower retinal arterial calibre was significantly associated with a lower eGFR (R = 0.415, p < 0.001). CONCLUSION: Based on our results, there were alterations in retinal oxygen saturation and vascular diameter in patients with CKD. Further studies are needed to determine whether such changes play a role in the development of CKD.
Subject(s)
Oxygen/blood , Renal Insufficiency, Chronic/blood , Retinal Vessels/pathology , Adult , Case-Control Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Oxygen Consumption , Prospective Studies , Regional Blood Flow , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathologyABSTRACT
BACKGROUND: Percutaneous transhepatic biliary drainage is an alternative treatment for patients with malignant distal biliary obstruction. The aim of this study was to investigate the occurrence of pancreatitis in patients who had undergone percutaneous placement of a biliary stent and to assess the risk factors for pancreatitis and the treatment outcomes. METHODS: From January 2010 to October 2016, 980 patients in our hospital who underwent percutaneous placements of self-expandable metallic stents for obstructive jaundice were retrospectively analyzed. The incidence of pancreatitis and risk factors were assessed by univariate and multivariate logistic regression analysis. Therapeutics, such as somatostatin, which were also adminstrated to release the symptom and promote the restoration of normal function of pancreas, were also analyzed. RESULTS: Pancreatitis occurred in 45 (4.6%) patients. One patient died from severe acute pancreatitis. Multivariate logistic regression analysis showed that common bile duct stent placement was the only independent risk factor that related to pancreatitis (odds ratio = 2.096, 95% CI: 1.248-5.379; P = 0.002). By using somatostatin, the concentrations of serum amylase and lipase were decreased in 44 patients with pancreatitis. No major complications were found during the treatment. CONCLUSIONS: Pancreatitis is a relatively low complication of percutaneous placement of biliary stents. The common bile duct stent placement is the only independent risk factor that related to pancreatitis. In this case, the percutaneous transhepatic biliary drainage is a preferred method for treatment. Furthermore, somatostatin is a secure and efficacious method to release the symptom and promote the restoration of pancreatic function.
Subject(s)
Drainage/adverse effects , Drainage/instrumentation , Jaundice, Obstructive/therapy , Pancreatitis/epidemiology , Self Expandable Metallic Stents , Aged , China/epidemiology , Female , Humans , Incidence , Jaundice, Obstructive/diagnostic imaging , Jaundice, Obstructive/epidemiology , Male , Middle Aged , Pancreatitis/diagnostic imaging , Pancreatitis/drug therapy , Retrospective Studies , Risk Assessment , Risk Factors , Somatostatin/therapeutic use , Time Factors , Treatment OutcomeABSTRACT
Hepatocellular carcinoma (HCC) is the most prominent form of presentation in liver cancer. It is also the fourth most common cause of cancer-associated deaths globally. The role of nucleus accumbens associated protein-1 (NACC-1) has been evaluated in several cancers. This protein is a transcriptional regulator that regulates a number of significant cellular processes. In the current study, we aimed to understand the role of NACC-1 in HCC. Primarily, we measured the expression of NACC-1 using quantitative real time polymerase chain reaction and western blot analysis. We knocked down the expression of NACC-1 in HCC cell lines Huh7 and HepG2 by transferring a commercially synthesized small interfering RNA and explored the impact of NACC-1 knockdown on cellular growth, migration, invasion, and chemoresistance to doxorubicin. Through bioinformatic analysis, we identified NACC-1 as a potential target of miR-760. Using a dual reporter luciferase assay, we confirmed the predicted target and assessed miR-760-mediated regulation of NACC-1 and rescue of tumorigenic phenotypes. We observed increased expression of NACC-1 in HCC. Furthermore, knockdown of NACC-1 resulted in reduced cell proliferation and invasion and increased susceptibility to doxorubicin-mediated chemosensitivity. Overexpression of miR-760 in HCC cell lines rescued NACC-1-mediated migration and invasion. We revealed that miR-760 regulated NACC-1 expression in HCC. Our data indicated that both miR-760 and NACC-1 could be used as prognostic markers, and miR-760 may have therapeutic benefits for HCC and other cancers.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , MicroRNAs/metabolism , Neoplasm Proteins/metabolism , Repressor Proteins/metabolism , Adult , Aged , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Female , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Male , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/genetics , RNA, Long Noncoding/genetics , RNA, Small Interfering/metabolism , Repressor Proteins/geneticsABSTRACT
BACKGROUND: The high incidence of Diabetes mellitus (DM) has become a serious challenge for the global epidemic. Increased blood glucose leads to abnormal ocular surface structure and metabolic disorder in patients. DM is a high-risk factor for dry eye disease (DED), with high incidence and increased difficulty in treatment. The disease can cause discomfort, visual impairment, tear film instability and ocular surface damage, and even cause corneal erosion in severe cases, which has a serious impact on people's daily life. Traditional Chinese Medicine (TCM) plays an important role in the evaluation and treatment of DM and its complications. However, whether TCM treatment could improve the treatment efficacy of DM suffering from DED remains poorly understood. OBJECTIVE: To investigate the curative effect of TCM for the alleviation of clinical symptoms in Diabetic patients with DED, and to evaluate its long-term efficacy. METHODS: This trial is a single-case randomized, single-blind, placebo-controlled study. A total of 12 subjects will be recruited in this trial. The trial is divided into three cycles, and one cycle has 2 treatment periods. There is a washout period at each adjacent treatment stage. TCM individualized treatment and placebo will be randomized during the treatment period. The test period will last for 29 weeks, with 4 weeks for each treatment period and 1 week for each washout period to minimize carryover effects. Subjects will be selected by the researcher strictly in accordance with the inclusion and exclusion criteria. The outcomes will evaluate the efficacy of treatment by changes in the various observation indicators. DISCUSSION: This study will realize a patient-centered outcome approach necessary to provide clinical researchers with the evidence that TCM treatment can effectively improve the objective indicators of the eye and systemic symptoms in Diabetic patients with DED. TRIAL REGISTRATION: This study has been registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn, No. ChiCTR1900024481), (October, 2019).
Subject(s)
Diabetes Complications/therapy , Dry Eye Syndromes/therapy , Medicine, Chinese Traditional/methods , Female , Humans , Male , Patient-Centered Care/methods , Randomized Controlled Trials as Topic , Single-Blind MethodABSTRACT
BACKGROUND: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. SUMMARY: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. KEY MESSAGES: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019.
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AIM: To evaluate the effects of atropine 0.01% on slowing myopia progression. METHODS: We searched for relevant studies in the Cochrane Library, PubMed, Embase, Ovid, CBM, CNKI, VIP and Wan Fang Data in Chinese. A supplementary search was conducted in OpenGrey (System for Information on Grey Literature in Europe), the ISRCTN registry, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from the dates of inception to June 30, 2018. RESULTS: Seven randomized controlled trials (RCTs) with a total of 1079 subjects were included (505 in the atropine 0.01% group and 574 in the control group). The results showed that the atropine 0.01% group exhibited significantly greater control of axial growth than the control group [MD=-0.12, 95%CI (-0.19, -0.06)]. There was also a statistically significant difference between the atropine 0.01% and control groups in the changes in axial length [MD=-0.14, 95%CI (-0.25, -0.03)], but the quality of evidence was low. There were no significant differences between the atropine 0.01% and control groups in the overall effect with respect to diopter value, change in diopter, distance vision and intraocular pressure [MD=0.08, 95%CI (-0.27, 0.42); MD=0.09, 95%CI (-0.17, 0.36); MD= -0.01, 95%CI (-0.02, 0.00); MD=0.08, 95%CI (-0.56,0.40)]. The sensitivity analysis showed that the conclusion of the Meta-analysis is relatively stable. With respect to adverse events, there were significant differences between the atropine 0.01% and control groups [OR=0.26, 95%CI (0.11, 0.61)]. CONCLUSION: Based on the available evidence, atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.
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Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies that is present with progressive vision loss, night blindness, visual field reduction, and retinal pigmentation of the fundus. RP is an uncommon but clinically important disease. It is progressive and potentially blinding, and to date, no cure for RP has been identified and clinical interventions to retard disease progression are limited. Because of the nature of this disease, there has been great interest in the development of therapeutic interventions that may prevent its progression or restore the loss of visual function. Studies have indicated a possible role of vitamins and minerals in preventing the progression of RP: vitamin A has been reported to have an important role in the function of retinal photoreceptors; lutein is assumed to play a preventive role in fundus diseases; and docosahexaenoic acid, which is found within photoreceptor cell membranes, may have a functional role in preventing the progression of RP. Therefore, this study aimed to systematically review data from randomized clinical trials (RCTs) evaluating the safety and efficacy of vitamins and mineral supplements for the treatment of RP. We searched through relevant trials in the Cochrane Library, PubMed, Embase, Ovid, AMED, OpenGrey, ISRCTN registry, http://ClinicalTrials.gov, and the WHO ICTRP ranging from the respective dates of foundation to June 18, 2018. We reviewed eight randomized control trials (RCTs) with data for 1231 patients. The results indicated that patients with RP may experience delayed disease progression with vitamin and mineral supplementation. In a broader sense, this review suggests that the future trials on RP patients should consider more vitamins or mineral supplements and other outcome measures from the trials included in this review.
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BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.
ABSTRACT
The liver is the most common site of colorectal cancer metastases. The present study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) with raltitrexed and oxaliplatin for colorectal liver metastases in a prospective, multicenter, single-arm trial conducted in 12 hospitals from different areas in China. A total of 90 patients with colorectal liver metastases were enrolled and treated by TACE with raltitrexed 4 mg and oxaliplatin 100 mg, followed by embolotherapy with 50 mg oxaliplatin and 5-20 ml lipiodol, administered every 28 days for four cycles. Patients were followed up every 3 months after the treatment and up to 12 months. The primary endpoint was time to progression. For the full analysis set (FAS), the median time to progression and overall survival were 9.1 and 17.8 months, respectively. The disease control rate in FAS was 71 (78.9%). Grade 3 or 4 adverse events were reported for 24 (26.7%) out of all 90 patients. Grade 3 thrombocytopenia, transglutaminase abnormality, and decreased neutrophil were observed in eight (8.9%), six (6.7%), and five (5.6%) patients, respectively. No unexpected adverse events or toxic deaths were observed. TACE with raltitrexed plus oxaliplatin is feasible, clinically beneficial, and well tolerated with low-grade toxicity for colorectal cancer patients with liver metastases.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemoembolization, Therapeutic/methods , Colorectal Neoplasms/therapy , Liver Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoembolization, Therapeutic/adverse effects , China , Colorectal Neoplasms/pathology , Disease Progression , Ethiodized Oil/administration & dosage , Female , Follow-Up Studies , Humans , Liver Neoplasms/secondary , Male , Middle Aged , Oxaliplatin/administration & dosage , Prospective Studies , Quinazolines/administration & dosage , Survival , Thiophenes/administration & dosageABSTRACT
PURPOSE: We aimed to investigate the roles of microRNA-425 (miR-425) in lung adenocarcinoma, as well as its possible regulatory mechanism. MATERIALS AND METHODS: The miR-425 expression in lung adenocarcinoma tissues and cells was determined. The regulatory relationship between miR-425 and IL-6/STAT3 signaling was investigated. In addition, miR-425 was downexpressed in H1299 cells, and its effects on cell proliferation and apoptosis were determined. Furthermore, the target relationship between miR-425 and A disintegrin and metalloproteinases 9 (ADAM9) in lung adenocarcinoma cells was explored. RESULTS: The miR-425 was significantly downregulated in lung adenocarcinoma tissues and cells and was markedly inhibited by IL-6/STAT3 signaling. In addition, miR-425 expression was successfully overexpressed by transfection with pre-miR-425. Overexpression of miR-425 decreased the proliferation and colony formation of H1299 cells and promoted cell apoptosis markedly. Moreover, ADAM9 was revealed as a target of miR-425, and ADAM9 expression was negatively regulated by miR-425. CONCLUSION: Our findings indicate that downregulation of miR-425 caused by IL-6/STAT3 signaling leads to loss of ADAM9 targeting, results in enhanced ADAM9 expression, and contributes to the development of lung adenocarcinoma. Thus, increasing miR-425 may be a promising therapeutic strategy for this disease.