BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.
Child ; Family ; Humans ; Kidney Neoplasms/therapy* ; Progression-Free Survival ; Retrospective Studies

Objective: To explore the fitting and its influencing factors of ICU nurses. Methods: There were 268 nurses recruited from the First Affiliated Hospital of Xi′an Jiaotong University, the Ninth Hospital of Xi′an, Shaanxi Provincial People′s Hospital by convenience sampling between April and June 2018. The Fitting Scale, Social Undermining Scale, Perceived Organizational Support Scale and Supportive Communication Scale were used in the investigation. Results: The score of person-organization fit was (32.20±5.17). The score of person-job fit was (55.14±8.24), with the lowest score of supply-value fit subscale (2.58±0.48). The score of perceived organizational support, social undermining and supportive communication were (45.36±9.64), (46.27±7.48) and (68.47±11.25) respectively. Perceived organizational support, social undermining, contract nurses, and educational level could influence person- organization fit, which could explain 59.3% of the total variation. Working time, supportive communication and perceived organizational support could influence person- job fit, which could explain 47.6% of the total variation. Conclusions Nursing managers should improve the core value system of human resources management and organizational culture construction, enhance organizational support, construct humanities environment and coping strategy of undermining, provide the relevant training of interpersonal communication, and increase their organizational and job fitting.

OBJECTIVE: To investigate the expression of erythropoietin (EPO) and erythropoietin receptor (EPOR) in patients with acute leukemia (AL) and its clinical significance. METHODS: The levels of EPO and EPOR in plasma were determined by ELISA kit. mRNA expression levels of EPO and EPOR were determined by RT-RCR. The protein expression levels of EPO and EPOR were detected by Western blot. RESULTS: The EPO protein levels in marrow plasma of ALL and AML group were significantly higher than those in the control group (P＜0.05), EPOR protein levels in ALL and AML group were significantly lower than those in the control group (P＜0.05). The mRNA levels of EPO and EPOR in ALL and AML groups were significantly higher than those in the control group (P＜0.05). The mRNA levels of EPO and EPOR in the high risk ALL and AML groups were significantly higher than those in the medium, low risk group and the control group (P＜0.05). The protein expression levels of EPO and EPOR in ALL and AML groups were significantly higher than that in control group (P＜0.05). The mRNA levels of EPO and EPOR in ALL and AML groups did not correlate with hemoglobin level and erythrocyte count (P＞0.05). CONCLUSION The expressions of EPO and EPOR is higher in ALL and AML patients. The expression levels of EPO and EPOR relate with the risk of ALL and AML. High risk patients have higher expression levels of EPO and EPOR, however, the expression levels of EPO and EPOR do not correlate with hemoglobin level and erythrocyte counting.
Bone Marrow ; Erythropoietin ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; Receptors, Erythropoietin

OBJECTIVE: To investigate the effect of silencing LNK gene on the expression of EPO and EPOR in acute myeloid leukemia cells (THP-1). METHODS: THP-1 cells were cultured. The lentivirus was used as a vector to silence the LNK gene stably. After 72 hours of infection, GFP expression level was detected by the fluorescent inverted microscopy. The lentiviral Infection efficiencies were monitored by flow cytometry. The LNK silencing effect was confirmed. The mRNA expressions of EPO and EPOR were detected by RT-PCR. The protein levels of LNK, EPO and EPOR were detected by Western blot. RESULTS: At the time-point of 72 hours after lentivirus infection, the expression level of GFP was above 85% detected by fluorescent inverted microscopy. The infection efficiency was above 99% by flow cytometry. mRNA expressions of LNK, EPO and EPOR in LNK silencing group were signifycantly lower than those in control group (P＜0.05). The protein levels of LNK, EPO and EPOR in LNK silencing group were significantly lower than those in the control group (P＜0.05). CONCLUSION THP-1 cell line of LNK gene silencing has been successfully established,the LNK gene has been silenced, the expression of EPO and EPOR decrease, indicating that LNK may participate in the regulation of EPO and EPOR.
Blotting, Western ; Erythropoietin ; Gene Silencing ; Humans ; Proteins ; genetics ; Receptors, Erythropoietin ; THP-1 Cells

OBJECTIVE: To investigate the expression of STAT3 gene in patients with acute myeloid leukemia and its correlation with clinical characteristics. METHODS: The real-time quantitative RT-PCR was used to detect the level of STAT3 mRNA in bone marrow samples from 38 newly diagnosed patients with acute myeloid leukemia(AML), and its relevance with clinical characteristics and prognosis were statistically analyzed. Western blot was employed to detect the STAT3 protein level in AML patients. The bone marrow cells from 15 healthy subjects were used as control. RESULTS: At the mRNA level, the expression level of STAT3 in the AML group was significantly higher than that in control group (P<0.05). The level of STAT3 in AML group correlated positively with the risk factors of patients (P<0.01，r=0.592）. The STAT3 expression level in the high-risk group was statistically higher than that in the standard-risk group and the control group (P<0.01，P<0.01). Furthermor, there was no statistical difference between the sub-groups of AML (P>0.05). The median survival time of patients in STAT3 low expression group was logner than that in high expression group, but the difference was not statistically significant (P>0.005). The level of STAT3 protein in AML patients was significantly higher than that in control group (P<0.05）. CONCLUSION The STAT3 gene is highly expressed in AML patients, which may be used as a predictor for high-risk of AML.
Bone Marrow ; Humans ; Leukemia, Myeloid, Acute ; Prognosis ; RNA, Messenger ; STAT3 Transcription Factor ; genetics

OBJECTIVE: To investigate the effect of LNK gene silencing and overexpression on the expression of STAT3 gene in human monocytic leukemia cells (THP-1). METHODS: THP-1 cells were cultured, and the lentivirus was used as a vector to silence and overexpres the LNK gene stably. After transfection for 72 hours, the GFP expression levels were observed by inverted fluorescence microscopy. The lentiviral transfection efficiencies were detected by flow cytometry. The effects of LNK silencing and overexpression were confirmed, and the expression of STAT3 mRNA was detected by RT-PCR. The protein levels of LNK and STAT3 were detected by Western blotting. RESULTS: The GFP expression level of THP-1 cells reached more than 85% after transfection with lentivirus for 72 hours, and the transfection efficiency of cells was above 99%. mRNA expressions levels of LNK and STAT3 in LNK silencing group were signifycantly lower than those in control group, while LNK and STAT3 mRNA levels in the LNK overexpression group was significantly higher than those in control group (P＜0.05). The protein expression levels of LNK and STAT3 in LNK silencing group were significantly lower than those in control group, while that in LNK overexpression group was significantly higher than that in control group (P＜0.05). CONCLUSION The THP-1 cell line with LNK gene silencing and overexpression has been successfully established. The LNK gene silencing resulted in decrease of STAT3 expression; LNK gene overexpression and leads to inereases of STAT3 expression indicating that LNK participates in the regulation of STAT3.
Cell Line, Tumor ; Gene Silencing ; Genetic Vectors ; Humans ; Lentivirus ; Proteins ; RNA, Small Interfering ; STAT3 Transcription Factor ; metabolism ; THP-1 Cells ; Transfection

OBJECTIVETo investigate whether Artesunate(ART) can inhibit the proliferation of THP-1 cells and to explore the potential mechanism of its anti-leukemia effect.

METHODSTHP-1 cells were treated with 5 concentrations of Artesunate for 24 h, 48 h or 72 h. The viability of cells was detected with CCK-8 assay, apoptosis was assessed by using flow cytometry, and the STAT3, Caspase3 and Caspase8 protein levels were measured with Western blot .

RESULTSCompared with the control group, ART significantly inhibited the proliferation of THP-1 cells in a dose-dependent manner (r=0.9829, P<0.05). ART also increased the apoptosis of THP-1 cells. The results of Western blot showed that after treated with ART, the STAT3 protein expression in THP-1 cells was significantly down-regulated (P<0.01), and the expressions of Caspase3, cleaved Caspase3 and Caspase8 proteins were up-regulated(P<0.01).

CONCLUSIONArtesunate can inhibit the proliferation of THP-1 cells, which may relate with the down-regulation of STAT3 expression and the activation of Capase3 and Caspase8.