Quantitative assessment of choroidal parameters and retinal thickness in central serous chorioretinopathy using ultra-widefield swept-source optical coherence tomography: a cross-sectional study.

OBJECTIVE: In this study, we used ultra-wide field swept-source optical coherence tomography angiography (UWF SS-OCTA) to assess changes in retinal thickness (RT) and choroidal parameters in individuals who had received a diagnosis of central serous chorioretinopathy (CSC). METHODS: The study encompassed the evaluation of 59 eyes from 47 patients with a diagnosis of CSC, alongside 33 fellow eyes and 31 eyes from healthy individuals (controls). The parameters assessed included RT, choroidal thickness (CT), choriocapillaris density, vascular density of the large choroidal vessel layer, three-dimensional choroidal vascularity index (3D-CVI), choroidal vessel volume per unit area (mCVV/a), and choroidal stroma volume per unit area (mCSV/a). RESULTS: Metrics including mCVV/a, mCSV/a, 3D-CVI, CT, and RT exhibited significantly elevated values in the eyes affected by CSC compared to those of the control group across nine subfields. Moreover, a substantial number of the subfields in both CSC-affected and fellow eyes exhibited increased values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT when compared with the control group. Additionally, acute and chronic CSC subfields demonstrated significantly elevated values for mCVV/a, mCSV/a, 3D-CVI, CT, and RT in comparison to healthy control eyes. Notably, specific subfields associated with complex and atypical forms of CSC revealed higher metrics compared to those of the control group. CONCLUSION: In conclusion, the UWF SS-OCTA proved to be a valuable tool for exploring the anatomical etiology and clinical classification and diagnosis of CSC.

Improvement of Efficiency in Kesterite Solar Cells by Intentionally Inserting a Thin MoS2 Layer into the Back Interface.

A Mo(S,Se)2 interfacial layer is formed inevitably and uncontrollably between the Mo electrode and Cu2ZnSn(S,Se)4 (CZTSSe) absorber during the selenization process, which significantly influences the performance of CZTSSe solar cells. In this work, an ultrathin MoS2 layer is intentionally inserted into Mo/CZTSSe to reduce the recombination and thus optimize the interface quality. It is revealed that the absorber exhibits a continuous and compact morphology with bigger grains and remarkably without pinholes across the surface or cross-sectional regions after MoS2 modification. Benefitting from this, the shunt resistance (RSh) of the device increased evidently from ∼395 to ∼634 Ω·cm2, and simultaneously, the reverse saturation current density (J0) realized an effective depression. As a result, the power conversion efficiency (PCE) of the MoS2-modified device reaches 9.64% via the optimization of the thickness of the MoS2 layer, indicating performance improvements with respect to the MoS2-free case. Furthermore, the main contribution to the performance improvement is derived and analyzed in detail from the increased RSh, decreased J0, and diode ideality factor. Our results suggest that the Mo/CZTSSe interface quality and performance of CZTSSe solar cells can be modulated and improved by appropriately designing and optimizing the thickness of the inserted MoS2 layer.

Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion.

AIM: To assess the long-term outcomes of treating macular edema (ME) associated with central retinal vein occlusion (CRVO) with a regimen of "5+pro re nata (PRN)". METHODS: This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO (non-iCRVO group, n=15) and ischemic CRVO (iCRVO group, n=12). The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab, followed by reinjections as needed or PRN. Retinal laser photocoagulation or intravitreal dexamethasone implants (DEX) were implemented in both groups when necessary. The best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were recorded at baseline, at 1, 2, 3, 4, 5, 6, and 12mo, and at the final visit. The efficacy rates of BCVA and CRT before and after treatment were calculated. The number of injections at each visit and the incidence of adverse events were also recorded. RESULTS: The patients, aged 59.4±15.1y, were followed up for 24.7±8.8mo (range: 15-42mo). After treatment, BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR (P=0.038) at the final visit in all patients. Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points, but there was no statistical significance (P=0.197 and 0.33, respectively). The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups (all P<0.001). The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection, 48.15% for BCVA and 62.96% for CRT after 5 consecutive injections, and 74.08% for BCVA and 100% for CRT at the end of follow up. The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups (P>0.05). Laser treatment was applied to all eyes in the iCRVO group, while only 5 patients in the non-iCRVO group. Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch. DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group. CONCLUSION: The 5+PRN anti-vascular endothelial growth factor (VEGF) regimen is found to be safe and effective for both iCRVO and non-iCRVO, especially in the iCRVO group. The best regimen for such patients needs to be further investigated. Adjuvant laser therapy and DEX are necessary in some cases.

Comprehensive Landscape of HOXA2, HOXA9, and HOXA10 as Potential Biomarkers for Predicting Progression and Prognosis in Prostate Cancer.

Prostate cancer (PCa) is recognized as a common malignancy in male patients. The homeobox A cluster (HOXA) family members have been confirmed to be implicated in the development of several types of tumors. However, the expression pattern and prognostic values of HOXA genes in PCa have not been investigated. In this study, we analyzed TCGA datasets and identified six HOXA family members which showed a dysregulated expression in PCa specimens compared with nontumor specimens. We also explored the potential mechanisms involved in the dysregulation of HOXA family members in PCa, and the results of Pearson's correlation revealed that most HOXA members were negatively related to the methylation degree. Moreover, we explored the prognostic values of HOXA family members and identified six survival-related HOXA members. Importantly, HOXA2, HOXA9, and HOXA10 were identified as critical PCa-related genes which were abnormally expressed in PCa and associated with clinical outcomes of PCa patients. Then, we explored the association between the above three genes and immune cell infiltration. We observed that the levels of HOXA2, HOXA9, and HOXA10 were associated with the levels of immune infiltration of several kinds of immune cells. Overall, our findings identified the potential values of the HOXA family for outcome prediction in PCa, which might facilitate personalized counselling and treatment in PCa.

Long-term outcomes of drusenoid pigment epithelium detachment in intermediate AMD treated with 577 nm subthreshold micropulse laser: a preliminary clinical study.

AIM: To evaluate the long-term anatomical and visual outcomes of drusenoid pigment epithelial detachment (D-PED) in intermediate age-related macular degeneration (AMD) eyes treated with 577 nm yellow subthreshold micropulse laser (SML). METHODS: In this retrospective study, 21 eyes of 16 patients with D-PED in intermediate AMD were consecutively included and assessed. All the eyes were treated with 577 nm SML in several sessions according to D-PED growth status. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) were assessed at the initial visit and after treatment. Spectral-domain optical coherence tomography (SD-OCT) was performed to evaluate the D-PED lifecycle by volumetric calculations. Regression analysis was used to determine the breakpoint, growth, and collapse rate of the D-PED lesions. The progression to advanced AMD was also documented. RESULTS: All the eyes were treated with SML for 2.9±1.0 sessions. The mean follow-up period was 25.3±12.6mo. The BCVA was stable from the baseline to final visit. All the eyes were categorized into two groups according to the anatomical changes of the D-PED lesion: the collapse group (n=6, 28.6%) and non-collapse group (n=15, 71.4%). The change in logMAR BCVA did not differ significantly between the collapse group 0.00 (-0.31, 0.85) and non-collapse group 0.00 (0.00, 0.00; P=1). Regression analysis showed that the growth rate was significantly higher in the collapse group (0.090±0.095 mm3/mo) than in the non-collapse group (0.025±0.035 mm3/mo; P<0.001). One eye (4.8%) developed macular neovascularization at 11mo after SML treatment in the non-collapse group. Three eyes (14.3%) developed geographic atrophy (GA) in the collapse group. CONCLUSION: Compared to the natural course of D-PED reported by previous studies, our results preliminarily show that SML can alleviate visual loss and possibility of progression to advanced AMD in eyes with D-PED in intermediate AMD. A controlled clinical trial needs to further verify the benefit of the intervention.

[The Clinical Characteristics and Prognosis of Patients with Acute Myeloid Leukemia Combine Paroxysmal Nocturnal Hemoglobinuria].

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with acute myeloid leukemia(AML) combined with paroxysmal nocturnal hemoglobinuria(PNH). METHODS: The clinical data of 13 AML combined with PNH patients treated in our hospital from January 2017 to May 2019 were collected and retrospective analyzed. The complete remission(CR) rate for induction chemotherapy was analyzed. The level of PNH+ cell before and after chemotherapy were tested by Paired t test. Kaplan-Meier method and multi-factorial Cox regression model were used to analyze the influencing factors of prognosis. RESULTS: Among the 13 patients, 11 (84.6%) cases were CR after first induction chemotherapy. The median overall survival(OS) time was 17 months(0-30 months), the median progression-free survival(PFS) time was 16 months(2-26 months). There were no significant difference in the number of PNH+ cell before and after chemotherapy (P＞0.05). Multivariate Cox regression analysis showed that age，sex，the level of hemoglobin, platelet were not related to the OS of the patients(P＞0.05), the level of WBC, LDH and risk stratification at first diagnosed were related to the OS of the patients（P＜0.05）. Kaplan-Meier survival analysis showed that the OS rate of AML combined with PNH patients with leukocyte lower than 10×109/L at first diagnosed was better than that of the patients with leukocyte higher than 10×109/L (P=0.0261). The OS rate of patients with low or standard risk was better than the patients with high risk group(P=0.0010). CONCLUSION: The patients of AML combined with PNH have higher CR rate after the first induction chemotherapy. The level of WBC and LDH at first diagnosed are the factors that affecting the OS of the patients. The OS of patients with WBC lower than 10×109/L, at first diagnosed low and medium risk are better than the other patients.

Clinical Characteristics and Prognostic Analysis of Multiple Myeloma with Extramedullary Disease: A SEER-Based Study.

BACKGROUND: Extramedullary disease (EMD), an infrequent manifestation of multiple myeloma (MM), can present at diagnosis or develop during the disease course. EMD can be clinically divided into bone-related EMD (EMD-B) and soft tissue-related EMD (EMD-S). The purpose of our study is to investigate the clinical characteristics, survival outcomes, and prognostic factors of MM patients with EMD. METHODS: A total of 155 MM patients with EMD were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier survival curves and log-rank test for overall survival (OS) and myeloma-specific survival (MSS) were conducted to compare each potential variable. Variables with a p value <0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) >1 representing adverse prognostic factors. RESULTS: The median age at diagnosis was 63 years old. EMD-B occurred in 99 patients (63.90%), while EMD-S occurred in 56 cases (36.10%). Patients with EMD-S had a significant survival disadvantage in MSS (HR = 1.844, 95% CI 1.117-3.042, p = 0.017) and OS (HR = 1.853, 95% CI 1.166-2.942, p = 0.009) compared to those with EMD-B. Patients with EMD interval ≤24 months were at higher risk of death than those with EMD at diagnosis in MSS (HR = 1.885, 95% CI 1.175-3.346, p = 0.042) and in OS (HR = 1.33, 95% CI 1.119-2.529, p = 0.036). Patients with EMD interval >24 months were at a lower risk of death as opposed to those with EMD at diagnosis. CONCLUSION: Age at MM diagnosis, site of EMD, and time interval from diagnosis to EMD occurrence were independent prognostic factors in MM patients with EMD. EMD-B bore a better prognosis than EMD-S.

Efficacy and safety of Shufeng Jiedu capsule in the treatment of COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) epidemic is spreading worldwide. Shufeng Jiedu capsule (SFJDC) is a commonly used drug in the treatment of COVID-19. However, there is insufficient evidence for clinical efficacy and safety. METHODS: Two authors will independently search the Chinese National Knowledge Infrastructure (CNKI), VIP database, Wanfang database, the Cochrane Library, EMBASE, PubMed and Web of Science, in English and Chinese. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Review Manager 5.3 and Stata 16.0 software will be used to analyze the eligible data. RESULTS: This protocol will conduct a systematic review and meta-analysis of literature listed above, and reliable outcomes about the clinical efficacy and safety of SFJDC in the treatment of COVID-19 will be obtained. CONCLUSIONS: These findings will provide guidance for clinicians and patients using SFJDC for COVID-19 treatment. PROSPERO REGISTRATION NUMBER: CRD42020185764.

Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology.

BACKGROUND: COVID-19 has caused a global pandemic, and there is no wonder drug for epidemic control at present. However, many clinical practices have shown that traditional Chinese medicine has played an important role in treating the outbreak. Among them, ephedra-bitter almond is a common couplet medicine in anti-COVID-19 prescriptions. This study aims to conduct an exploration of key components and mechanisms of ephedra-bitter almond anti-COVID-19 based on network pharmacology. MATERIAL AND METHODS: We collected and screened potential active components of ephedra-bitter almond based on the TCMSP Database, and we predicted targets of the components. Meanwhile, we collected relevant targets of COVID-19 through the GeneCards and CTD databases. Then, the potential targets of ephedra-bitter almond against COVID-19 were screened out. The key components, targets, biological processes, and pathways of ephedra-bitter almond anti-COVID-19 were predicted by constructing the relationship network of herb-component-target (H-C-T), protein-protein interaction (PPI), and functional enrichment. Finally, the key components and targets were docked by AutoDock Vina to explore their binding mode. RESULTS: Ephedra-bitter almond played an overall regulatory role in anti-COVID-19 via the patterns of multi-component-target-pathway. In addition, some key components of ephedra-bitter almond, such as ß-sitosterol, estrone, and stigmasterol, had high binding activity to 3CL and ACE2 by molecular docking simulation, which provided new molecular structures for new drug development of COVID-19. CONCLUSION: Ephedra-bitter almonds were used to prevent and treat COVID-19 through directly inhibiting the virus, regulating immune responses, and promoting body repair. However, this work is a prospective study based on data mining, and the findings need to be interpreted with caution.

Genotype profiles of Helicobacter pylori from gastric biopsies and strains with antimicrobial-induced resistance.

BACKGROUND AND AIMS: The genotypic method could significantly shorten the time needed to obtain antibiotic susceptibility data for Helicobacter pylori. The aim of this study was to explore the profile of H. pylori from gastric biopsies and strains with antibiotic-induced resistance. METHODS: A total of 124 gastric biopsies were used to perform gene sequencing and to perform bacterial culture and susceptibility testing. Seven susceptible strains were selected to develop resistance to clarithromycin, levofloxacin, and metronidazole. Four susceptible strains were selected to transfer candidate mutations. The genotype profiles of these groups were analyzed by sequencing analysis. The antibiotic susceptibility of these strains was detected using the E-test method. RESULTS: Phenotypic resistance to clarithromycin, levofloxacin, and metronidazole was observed in 35.5%, 40.0%, and 79.8% strains, respectively. Point mutations in 23 S rRNA, gyrA, and rdxA genes were observed in 39.5%, 38.7%, and 86.3% of gastric biopsies, respectively. The A2143G mutation in the 23S rRNA occurs in most clarithromycin-resistant samples. The A2142C point mutation showed a higher efficacy than A2142G and A2143G for inducing clarithromycin resistance. The D91N and N87K mutations in gyrA occurs in most levofloxacin-resistant samples, and double point mutations showed a higher efficacy than single mutations for inducing levofloxacin resistance. Phenotypic resistance and mutations in rdxA lacked consistency. CONCLUSION: Genotype-based gastric biopsy analysis was reliable for determining clarithromycin and levofloxacin resistance. A2143G in 23S rRNA and N87K/D91N in the gyrA gene occurred in most resistant strains. Mutations in the rdxA gene were not good indicators of metronidazole resistance.

Exploring multiple mechanisms of Qingjie Fanggan prescription for prevention and treatment of influenza based on systems pharmacology.

Influenza is a type of acute disease characterized by strong contagiousness and short incubation period, which have posed a large potential threat to public health. Traditional Chinese Medicine (TCM) advocates to the aim of combating complex diseases from a holistic view, which has shown effectiveness in anti-influenza. However, the mechanism of TCM prescription remains puzzling. Here, we applied a system pharmacology approach to reveal the underlying molecular mechanisms of Qingjie Fanggan prescription (QFP) in the prevention and treatment of influenza. In this study, we identified 228 potential active compounds by means of absorption, distribution, metabolism, and excretion (ADME) evaluation system and literature research. Then, the targets of the potential active compounds were predicted by using the WES (Weighted Ensemble Similarity) method, and the influenza-related targets were obtained according to some existing gene databases. Next, an herb-component-target network was constructed to further dissect the multi-directional therapeutic approach for QFP. Meanwhile, we also performed gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis on 344 potential targets. Finally, a target-pathway network was constructed to further dissect the core pathways and targets in treatment of influenza for QFP. And the key components and targets were docked by AutoDock Vina to explore their binding mode. All of these demonstrated that QFP had multi-scale curative activity in regulating influenza-related biological processes, which facilitates the application of traditional medicine in modern medicine.

BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis.

BACKGROUND: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. METHODS: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. RESULTS: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. CONCLUSION: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM.

Efficacy and safety of Jinhua Qinggan granules for coronavirus disease 2019 (COVID-19): A protocol of a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS)-COV2 and represents the causative agent of a potentially fatal disease. Jinhua Qinggan granules has definite effect in treating COVID-19 patients, but it has not been systematically evaluated for efficacy and safety. METHODS: Retrieved the database, including the China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Evaluate methodological quality and judge risk of bias through the Cochrane manual. RevMan 5.3 and STATA 16.0 software were used to perform the meta-analysis. RESULTS: This study will provide high-quality evidence of Jinhua Qinggan granules for COVID-19. CONCLUSION: The conclusion of this study will provide evidence to determine whether Jinhua Qinggan granules is an effective treatment for COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020182373.

Therapeutic efficacy of Qingfei Paidu decoction combined with antiviral drugs in the treatment of corona virus disease 2019: A protocol for systematic review and meta analysis.

BACKGROUND: The corona virus disease 2019 (COVID-19) has caused a global pandemic, there are no specific drugs and vaccines for epidemic control at present. More and more clinical practice shows that traditional Chinese medicine has played an important role in the outbreak. Among them, Qingfei Paidu decoction (QPD) combined with antiviral drugs can enhance the therapeutic efficacy for COVID-19. However, there is still a lack of comprehensive and systematic evidence, which urgently requires us to verify its therapeutic efficacy. Hence, we provide a protocol for systematic review and meta-analysis. METHODS: We will search the studies in MEDLINE/PubMed, China National Knowledge Infrastructure, Wanfang database, VIP database, the Cochrane Library, Chinese Biomedical Database and Chinese Science Citation Database. Searches are limited to clinical studies published in Chinese and English. Next, the quality of each study is assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Then, the outcome data are recorded and pooled by Review Manager 5.3 and STATA 16.0 software. RESULTS: The systematic review and meta-analysis aims to review and pool current clinical outcomes of QPD combined with antiviral drugs for the treatment of COVID-19. CONCLUSION: This study will provide a high-quality evidence of QPD for the treatment on COVID-19 patients. PROSPERO REGISTRATION NUMBER: CRD42020182409.

The Evaluation of a Two-Year Outcome of Intravitreal Conbercept versus Ranibizumab for Pathological Myopic Choroidal Neovascularization.

Aim: The aim of this study was to evaluate and compare the 24-month follow-up results of intravitreal conbercept with ranibizumab in the treatment of choroidal neovascularization (CNV), secondary to pathological myopia (PM). Methods: Fifty-nine patients' 64 eyes with pathological myopic CNV were retrospectively reviewed. Thirty-one eyes underwent conbercept treatment (group C) and 33 eyes underwent ranibizumab treatment (group R), respectively. No patients have received any treatment before. The main outcome of the best-corrected visual acuity (BCVA) uses an international standard visual acuity chart and is converted to the minimum resolution logarithm (LogMAR) visual acuity. Results: There were no significant differences between the two groups at the baseline statisticlly. At 24 months, the mean logMAR BCVA of group C increased from 0.95 ± 0.54 to 0.58 ± 0.39 (P < .001) and the mean central macular thickness (CMT) decreased from 280.97 ± 62.69 µm to 242.35 ± 90.39 µm (P = .033). The mean logMAR BCVA of group R increased from 0.86 ± 0.40 to 0.54 ± 0.28 (P < .001) and the mean CMT was reduced from 303.58 ± 61.95 µm to 251.82 ± 84.74 µm (P = .005). There was no significant difference in logMAR BCVA and CMT between the two groups (P = .962, P = .667, respectively). The mean number of injections was 3.94 ± 1.88 in group C and 4.06 ± 1.82 in group R (P = .788). During the follow-up period, no ocular complications and systemic adverse reactions were observed. Conclusion: Similar visual acuity and improved morphology were achieved in both groups. The two drugs were also found to be safe and effective in the treatment of pathological myopic CNV.

Therapeutic efficacy of shenmai injection as an adjuvant treatment in dilated cardiomyopathy: A protocol for systematic review.

BACKGROUND: Shenmai injection (SMI) is a Traditional Chinese Medicine patent prescription consisting of extractions from ophiopogonis radix and ginseng radix rubra. Clinical studies showed that SMI combined with conventional medicine treatment (CMT) can enhance the therapeutic efficacy for dilated cardiomyopathy (DCM). However, there is still a lack of comprehensive and systematic evidence, which urgently requires us to verify its therapeutic efficacy. Hence, we provide a protocol for systematic review and meta-analysis. METHODS: The systematic search on the MEDLINE/PubMed, China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, the Cochrane Library, Embase and Chinese Biomedical Database (CBM) in Chinese and English language with dates ranging from the earliest record to August 8, 2019. Next, the quality of each trial was assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Then, the outcome data were recorded and pooled by RevMan 5.3 software. RESULTS: The systematic review and meta-analysis aims to review and pool current clinical outcomes of SMI for the adjuvant treatment of DCM. CONCLUSION: This study will provide a high-quality evidence of SMI for the adjuvant treatment on DCM patients. PROSPERO REGISTRATION NUMBER: CRD42019146369.

Evaluation of outer retinal tubulations in diabetic macular edema underwent anti-VEGF treatment.

AIM: To investigate the incidence and subsequent changes of outer retinal tubulations (ORTs) in diabetic macular edema (DME) underwent anti-vascular endothelial growth factor (VEGF) therapy, and to assess the possibility of ORT as a biomarker of DME severity or response to anti-VEGF therapy. METHODS: This retrospective and descriptive study included a total of 228 patients (435 eyes) with DME and treated with intravitreal anti-VEGF agents between March 2016 and January 2018. Patients were divided into 2 groups according to the presence of ORTs. High-resolution spectral-domain optical coherence tomography (SD-OCT) images acquired by vertical and horizontal scans and over consecutive visits were analyzed. The evolution of ORT over time, type of fluid and subfoveal photoreceptor integrity on OCT imaging was also assessed. RESULTS: ORTs were identified in 108 eyes of 435 eyes with an overall incidence rate of 24.83% at baseline. ORTs were prone to locate adjacent to the lesions of exudation and/or cystoid edema and possibly situated in outer nuclear layer (ONL), outer plexiform layer (OPL) and/or inner nuclear layer (INL) in eyes with DME. The formation process of ORT led to focal downward displacement of OPL and INL toward RPE near the lesion. During the follow up, 45 eyes had steady ORTs and 63 eyes had dynamic variants in ORTs, including disappearance, reappearance, collapse, diminution, and enlargement. There were higher proportion of closed ORTs and fewer proportion of forming ORTs in eyes with steady ORTs, which showed a statistically significance when compared with eyes with variant ORTs (P=0.006, P=0.017, respectively). The eyes without ORTs had significantly better final best corrected visual acuity (BCVA) and more BCVA change than those eyes with ORTs in DME patients after anti-VEGF therapy (P=0.023, P=0.009, respectively). The disruption of subfoveal photoreceptor integrity in eyes with ORTs was more serious than that in eyes without ORTs (P=0.013). The proportion of stable vision in eyes with ORTs was significantly higher than that in eyes without ORTs, showing statistical significance (P=0.016). ORTs were associated with worse visual prognosis due to damage of the subfoveal photoreceptor integrity. CONCLUSION: ORTs have a high incidence and changes over time in DME with anti-VEGF treatment and may be located at various retinal layers. Persistent ORT can be as a negative biomarker of outcome of DME.

[Knockout of BMAL1 Gene Induces Apoptosis of HL-60 Cells and Inhibits its Proliferation].

OBJECTIVE: To explore the biological function of BMAL1 in human acute myeloid leukemia by means of the HL-60 cell line in whica circadian gene BMAL1 was konocked-out by the CRISPR/Cas9 technology. METHODS: Two sgRNAs for BMAL1 were designed and the PX459 knockout vectors containing the sgRNA were constructed. The activity of 2 sgRNAs was detected by T7 endonuclease I. the BMAL1 knocked out HL-60 cells were prepared by transient transfection of the target vectors into the cells. Western blot was used to detect the expression of BMAL1 protein. The apoptosis of the targeted cells was detected by flow cytometry. The proliferation status of the cells was assessed by the CCK-8 assay. RESULTS: The PX459-sgRNA vectors were successfully constructed and screened to assure the activity of the targeting vector. It was found that the expression of BMAL1 protein was not detected in BMAL1-knocked out HL- 60 cells. Further, it was shown that BMAL1 knockdout could promote the apoptosis of HL-60 cells and inhibit the cell proliferation ability. CONCLUSION: BMAL1 knocked out HL-60 cells have bean successfully established using the CRISPR/Cas9 gene editing technique, and BMAL1 knockout can promote the HL-60 cell apoptosis and inhibit its proliferation.These result reveal the biological role of the BMAL1 circadian gene in acute myeloid leukemia.

Astragaloside IV protects rat gastric mucosa against aspirin-induced damage.

Aspirin (Asp) is commonly used as an anti-inflammatory drug, but the long-term usage of Asp can lead to severe gastrointestinal damage. Thus the co-administering of Asp with another drug that can suppress its side effect while having no impact on its anti-inflammatory activity would be ideal. Astragaloside IV (AST-IV) is a natural anti-inflammatory compound that has been shown to protect rat gastric mucosa from anhydrous ethanol-inflicted damage. In this study, we investigated whether AST-IV could protect rat gastric mucosa against Asp-induced gastric mucosal damage. Wistar rats administered 150mg/kg Asp showed significant damage to the gastric mucosa, as revealed by gastric damage score and histological evaluation. However, this was largely abolished by co-administering Asp and 25mg/kg or 50mg/kg AST-IV. The protective mechanism of AST-IV involved the suppression of Asp-induced inhibition of cycloxygenase-1 (COX-1) expression, prostaglandin E2 (PGE2) production, superoxide dismutase (SOD) activity and nitric oxide (NO) production. AST-IV blocked Asp-induced inhibition of SOD activity through preventing Asp from inhibiting the expression of SOD-1, both at the mRNA and protein levels. AST-IV did not appear to interfere with the anti-inflammatory activity of Asp since COX-2 level in model gastritis rats treated with Asp plus AST-IV was equally suppressed as in model gastritis rats treated with Asp alone. The results clearly showed that AST-IV could neutralize the toxicity of Asp while having no impact on its anti-inflammatory activity. AST-IV could therefore be considered as a potential drug for relieving the side effect associated with the long-term usage of Asp.