Objective: To investigate whether zerumbone ( ZER) has the effect of preventing cisplatin ( Cis) -induced acute kidney injury (Cis-AKI) . Methods: The MTT method was used to detect the effect of different concentrations of ZER on the cell viability of Cis-AKI. The in vivo and in vitro models of Cis-AKI mice were estab- lished by dividing into control group , separate administration group , model group , and dose group. Western blot and immunofluorescence experiments were used to detect the expression changes of kidney injury marker-1 ( KIM- 1) , phosphorylated NF-κB p65 ( P-p65 ) , Cleaved casepase3 , receptor interacting protein kinase 1 ( RIPK1) , RIPK3 , and tumor necrosis factor-α (TNF-α) . Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of KIM-1 , TNF-α , interleukin-6 ( IL-6) , and monocyte chemoattractant protein-1(MCP-1) . Periodic acid-Schiff (PAS) staining confirmed the therapeutic effect of ZER on Cis-AKI. RNA-seq and cell thermal shift (CETSA) were used to explore possible target proteins. Results : MTT results showed that ZER could alleviate the decrease in cell viability of Cis-AKI ; in vivo and in vitro studies showed that compared with the model group , after treatment with ZER , its KIM-1 , P-p65 , Cleaved casepased3 , RIPK1 , RIPK3 , TNF -α expres- sion decreased significantly , and the mRNA expression of KIM-1 , TNF-α , IL-6 mRNA , and MCP-1 decreased. PAS staining showed that ZER had a therapeutic effect on Cis-AKI. RNA-seq and CETSA analysis showed that ZER might prevent and treat Cis-AKI by targeting the PIM1 protein. Conclusion ZER may alleviate Cis-AKI and im- prove inflammatory response and necroptosis by regulating PIM1 protein. ZER is expected to be a potential drug for the prevention and treatment of Cis-AKI.

Objective To investigate the serum levels of miR-665 and miR-144 in the elderly pa-tients with chronic heart failure(CHF)and their relationship with cardiac function.Methods A total of 120 elderly CHF patients who were diagnosed and treated in our hospital from March 2021 to March 2023 were collected and then divided into NYHA grade Ⅱ(n=39),Ⅲ(n=51)and Ⅳ(n=30)subgroups according to the results of NYHA classification.Another 120 elderly healthy volunteers during the same period were recruited as the control group.Clinical data and cardiac function indicators were collected,and the expression levels of miR-665 and miR-144 in se-rum were detected.Pearson correlation analysis was applied to analyze the relationship of miR-665 and miR-144 levels with cardiac function indicators.Results The CHF group had significantly de-creased LVEF,increased left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD),and elevated serum levels of miR-665 and miR-144 than the control group(P＜0.01).Sequentially reduced LVEF and raised LVEDD and LVESD values and serum miR-665 and miR-144 levels were observed in the patients with NYHA grades Ⅱ,Ⅲ,and Ⅳ in turn(P＜0.01).Pearson correlation analysis showed that there was a positive correlation of the serum level of miR-665 with that of miR-144 in CHF patients(r=0.693,P=0.000),of the miR-665 and miR-144 levels with LVEDD(r=0.485,r=0.507,P＜0.01)and LVESD(r=0.539,r=0.494,P＜0.01),and a negative correlation of the serum levels with LVEF(r=-0.577,r=-0.591,P＜0.01).Conclusion The serum levels of miR-665 and miR-144 are elevated in elderly CHF patients,and are closely associated with their cardiac function.

Objective:To investigate the clinical efficacy and safety of amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension.Methods:A total of 280 patients with primary hypertension who were treated at Shougang Shuigang Hospital between June 2022 and June 2023 were selected as study subjects. A clinical case-control study was conducted, and the RAND function method was utilized to randomly allocate the subjects into four groups, each receiving a different treatment: amlodipine besylate group (Group A, n = 70), benazepril hydrochloride group (Group B, n = 70), compound formulation amlodipine besylate and benazepril hydrochloride tablets group (Group C, n = 71), and amlodipine besylate plus benazepril hydrochloride group (Group D, n = 69). Relevant therapeutic indicators (blood pressure compliance rate, changes in blood pressure values) and safety indicators (adverse reactions, medication adherence) were observed. Results:The blood pressure compliance rates of Group C and Group D were 91.5% (65/71) and 89.9% (62/69), respectively. There was no statistically significant difference between the two groups ( χ2 = 1.24, P = 0.143), but both were higher than the rates of 77.1% (54/70) and 74.3% (52/70) in Group A and Group B, respectively ( χ2 = 5.68, 4.86, P = 0.004, 0.012). Before treatment, there was no statistically significant difference in systolic and diastolic blood pressure among the four groups of patients (all P > 0.05). After treatment, there was a statistically significant decrease in both systolic and diastolic blood pressure among the four groups compared with their pre-treatment levels (all P < 0.05). Specifically, Group C and Group D exhibited significant reductions in blood pressure following treatment ( t = 4.35, 5.12, 7.25, 5.86, all P < 0.05). Meanwhile, there was no statistically significant difference in systolic blood pressure between Group C and Group D after treatment ( P > 0.05), while diastolic blood pressure was lower in Group C than Group D after treatment ( t = 6.01, P < 0.05). There was a significant downward trend observed in total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels (all P < 0.05). Notably, Group B and Group D reported higher incidences of dry cough, with 15 and 10 cases, respectively, compared with Group A and Group C, which had 1 and 3 cases, respectively. These differences were statistically significant ( χ2 = 4.25, 5.04, both P < 0.05). Furthermore, the treatment compliance rates for Group A, Group B, and Group C were 72.9% (51/70), 71.4% (50/70), and 74.6% (53/71), respectively, all exceeding the 46.4% (32/69) compliance rate of Group D. These differences were also statistically significant ( χ2 = 4.68, 5.24, 4.98, all P < 0.05). Conclusion:The clinical efficacy and safety of the compound formulation amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension are superior to those of single tablets and combination therapy.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Objective : To investigate the effect of high concentration of Caerulomycin A (Cae A) on HK2 in renal tubular epithelial cells and to explore the role of cytoplasmic nucleotide⁃binding oligomerization domain⁃like receptor protein 3 (NLRP3) in this process. Methods : The effect of different concentrations of Cae A on the viability of HK2 cells was determined by MTT; the expression of kidney injury molecule (KIM⁃1) and NLRP3 was detected by real⁃time quantitative PCR , Western blot and immunofluorescence , while the effect of Cae A on the mRNA expression of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α was also measured by real⁃time quantitative PCR. HK2 cells were divided into control group , high concentration of Cae A group and high concentration of Cae A plus NLRP3 inhibitor CY⁃09 group , and the expression of KIM⁃1 and NLRP3 protein was detected by Western blot. Results : The results of MTT showed that high concentration of Cae A could inhibit HK2 cell viability. Real⁃time quantitative PCR , Western blot and immunofluorescence assays showed that high concentration of Cae A upregulated the expression of KIM⁃1 and NLRP3 , as well as the mRNA levels of IL⁃1β , IL⁃18 , IL⁃33 , MCP⁃1 , TNF⁃α , while CY⁃09 could down⁃regulate the expression of NLRP3 and KIM⁃1. Conclusion High concentration of Cae A significantly inhibited the viability of HK2 cells and induced damage and inflammatory response to HK2 with some nephrotoxicity that might be achieved via NLRP3 pathway.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Objective:To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI).Methods:The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization.Results:A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI ( OR=0.881, 95% CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group ( OR=1.401, 95% CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group ( OR=0.919, 95% CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group ( OR=1.559, 95% CI 1.130-2.150; P=0.007). Conclusion:In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

Chronic endometritis (CE) is a chronic persistent endometrial inflammation with no obvious clinical symptoms. It is mainly characterized by plasma cell infiltration in endometrial stroma and is mainly diagnosed by CD138 immunohistochemistry and hysteroscopy. Studies have found that CE affects the decidualization of endometrium and the expression of immune cells and cytokines, which is not conducive to embryo implantation, and is related to recurrent spontaneous miscarriage and repeated implantation failure. The main treatment of CE is antibiotic treatment. In recent years, endometrial mechanical stimulation and intrauterine perfusion have also become new methods for the treatment of CE.

Chronic endometritis (CE) is a chronic persistent endometrial inflammation with no obvious clinical symptoms. It is mainly characterized by plasma cell infiltration in endometrial stroma and is mainly diagnosed by CD138 immunohistochemistry and hysteroscopy. Studies have found that CE affects the decidualization of endometrium and the expression of immune cells and cytokines, which is not conducive to embryo implantation, and is related to recurrent spontaneous miscarriage and repeated implantation failure. The main treatment of CE is antibiotic treatment. In recent years, endometrial mechanical stimulation and intrauterine perfusion have also become new methods for the treatment of CE.

Objective:To evaluate the retinal differentiation ability of human induced pluripotent stem cells (hiPSCs) from various somatic cell sources.Methods:The hiPSCs lines BC1- green fluorescent protein (GFP) and Gibco obtained by blood cell reprogramming and the hiPSCs line UE017 obtained by urine cell reprogramming were used to induce retinal differentiation.The morphogenesis and development of retina were recorded with an optical microscope, and the expression of specific molecular markers of various cell subclasses in the retina was detected by immunofluorescence, and the efficiency of retinal differentiation of different cell lines was analyzed and compared.Results:All three hiPSC lines derived from blood and urine cells were able to be induced into three-dimensional (3D) retinal organoids, including neuroretina and retinal pigment epithelial cells.Retinal organoids simulated the development process of retina in vivo and gradually differentiated into all cell subtypes of retina, including retinal ganglion cells, photoreceptor cells, amacrine cells, horizontal cells, bipolar cells, Müller cells, and even formed lamellar structures.However, in terms of the efficiency of acquiring retinal organoids, the hiPSCs derived from blood were more efficient than those derived from urine. Conclusions:hiPSCs from both blood and urine somatic cells can differentiate into 3D retinal organoids, including all subtypes of retinal cells.The differentiation efficiency among lines is different.