Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To explore the prognostic value of monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in assessing patients with heart failure with reduced ejection fraction (HFrEF).Methods:Patients with HFrEF (LVEF<40%) admitted to the TEDA International Cardiovascular Disease Hospital between 2 January 2019 and 15 January 2023 were selected. The MHR levels were recorded at admission in patients with HFrEF who were followed up regularly for 12 months. The major adverse cardiovascular events (cardiac death and readmission for heart failure) were defined as poor prognosis. Multivariate Cox regression was used to analyze factors associated with poor prognosis. The receiver operator characteristic (ROC) curves were used to assess the diagnostic value of MHR for poor prognosis. The DeLong test was used to analyze whether there was a difference in the effectiveness of MHR and BNP for detecting poor prognosis. The critical value grouping for poor prognosis was evaluated by MHR, and survival analyses were performed using Kaplan-Meier.Results:A total of 286 subjects were enrolled in the study, including 206 males and 80 females, with a median age ( Q1, Q3) of 67 (58, 74) years. Multivariate Cox regression showed that MHR ( HR=1.482, 95% CI:1.015-2.164) and BNP ( HR=1.001, 95% CI:1.000-1.001) were associated with poor prognosis in patients with HFrEF. The area under the ROC curve for the adjunctive diagnostic value of MHR, BNP and the combination of both for poor prognosis in patients with HFrEF was 0.709, 0.738 and 0.769, respectively. The critical values were 0.486, 1 090 pg/ml and 0.41, respectively. The DeLong test showed no differences in the validity of MHR, BNP and their combination for detecting poor prognosis. Kaplan Meier survival analysis of 12-month follow-up showed that the time for poor prognosis in HFrEF patients with MHR>0.486 group (8.645 months) was significantly shorter than that in MHR≤0.486 group (10.296 months, P<0.001), and the risk of poor prognosis in MHR>0.486 group was 2.843 times higher than that in MHR≤0.486 group ( HR=2.843, 95% CI:1.867-4.327). Conclusion:MHR can be an indicator of poor prognosis in patients with HFrEF.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To explore the prognostic value of monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in assessing patients with heart failure with reduced ejection fraction (HFrEF).Methods:Patients with HFrEF (LVEF<40%) admitted to the TEDA International Cardiovascular Disease Hospital between 2 January 2019 and 15 January 2023 were selected. The MHR levels were recorded at admission in patients with HFrEF who were followed up regularly for 12 months. The major adverse cardiovascular events (cardiac death and readmission for heart failure) were defined as poor prognosis. Multivariate Cox regression was used to analyze factors associated with poor prognosis. The receiver operator characteristic (ROC) curves were used to assess the diagnostic value of MHR for poor prognosis. The DeLong test was used to analyze whether there was a difference in the effectiveness of MHR and BNP for detecting poor prognosis. The critical value grouping for poor prognosis was evaluated by MHR, and survival analyses were performed using Kaplan-Meier.Results:A total of 286 subjects were enrolled in the study, including 206 males and 80 females, with a median age ( Q1, Q3) of 67 (58, 74) years. Multivariate Cox regression showed that MHR ( HR=1.482, 95% CI:1.015-2.164) and BNP ( HR=1.001, 95% CI:1.000-1.001) were associated with poor prognosis in patients with HFrEF. The area under the ROC curve for the adjunctive diagnostic value of MHR, BNP and the combination of both for poor prognosis in patients with HFrEF was 0.709, 0.738 and 0.769, respectively. The critical values were 0.486, 1 090 pg/ml and 0.41, respectively. The DeLong test showed no differences in the validity of MHR, BNP and their combination for detecting poor prognosis. Kaplan Meier survival analysis of 12-month follow-up showed that the time for poor prognosis in HFrEF patients with MHR>0.486 group (8.645 months) was significantly shorter than that in MHR≤0.486 group (10.296 months, P<0.001), and the risk of poor prognosis in MHR>0.486 group was 2.843 times higher than that in MHR≤0.486 group ( HR=2.843, 95% CI:1.867-4.327). Conclusion:MHR can be an indicator of poor prognosis in patients with HFrEF.

Objective To explore the relationship between the digital transformation of public hospitals and hospital quality and safety management,providing evidence for hospital digital transformation development and policy formulation.Methods Hospital management data from Shanghai municipal hospitals were collected,and a questionnaire was used to assess the current state of digital transformation.A panel regression of time-fixed effects analysis was performed to examine the correlation between various digital transformation variables and quality and safety performance in 8 Shanghai municipal hospitals from January 2023 to May 2024.Results Hospital digital system construction,digital service level,digital investment and digital research are significantly positively correlated with patient safety and service efficiency,and negatively correlated with the incidence of negative safety events in readmissions,venous thromboembolism and unplanned reoperation.The level of digital services was associated with a reduction in average length of stay.Increased digital investment was associated with not only decreased proportion of medication costs,but also an increase in the proportion of consumable costs,other categories of expenditures,and finally average costs.Conclusion While digital transformation improves hospital quality and safety,it also leads to an increased disease burden for patients.Therefore,further evidence is needed to analyze the cost-effectiveness of different digital transformation pathways.

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.