Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg^-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg^-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Extracorporeal membrane oxygenation (ECMO), a kind of life support technology that can replace lung and heart function, is widely used in critical respiratory and circulatory exhaustion. Because of the serious diseases and the use of interventional catheters, patients receiving ECMO life support are often administrated with broad-spectrum antimicrobial agents, which increase the risk of fungal infection. Fungal infection during ECMO can increase mortality. How to effectively control fungal infection is a thorny problem faced by clinicians. During the treatment of ECMO, the patient's physiological status, ECMO oxygenation membrane, circulation pipeline and other factors may change the pharmacokinetic profiles of antifungal drugs, thereby affect the clinical efficacy of drugs. This artical reviews the pharmacokinetic characteristics of antifungal drugs during ECMO support, in order to provide references for clinical antifungal treatment.

Background::NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients with NOTCH1 mutation have shown an unfavorable survival and a poor response to chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused by NOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Methods::The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.Results::RNA splicing was found to play a vital part in NOTCH1-mutated CLL cells; hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primary NOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition. Conclusion::Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis in NOTCH1- mutated CLL cells, which might partly account for the poor prognosis of patients with NOTCH1 mutation.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

Objective To evaluate the diagnostic value of quantitative detection of cytomegalovirus (CMV) DNA from different sources [plasma, sputum and bronchoalveolar lavage fluid(BALF)] for CMV pneumonia after allogeneic hematopoietic stem cell transplantation. Methods Clinical data of 405 recipients undergoing allogeneic hematopoietic stem cell transplantation were retrospectively analyzed. Among them, 19 recipients diagnosed with CMV pneumonia were assigned into the CMV pneumonia group, and 229 recipients with CMV viremia alone, 11 recipients without CMV pneumonia who received fiberoptic bronchoscopy and 16 recipients diagnosed with bacterial or fungal pneumonia based on pathogenic evidence receiving sputum culture were assigned into the control A, B and C groups, respectively. The incidence of CMV pneumonia was summarized. The CMV DNA load of specimens from different sources (plasma, sputum and BALF) of recipients with CMV pneumonia was analyzed. The clinical prognosis of recipients with CMV pneumonia was evaluated. Results Among 405 recipients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases developed CMV pneumonia, and the overall incidence of CMV pneumonia was 4.7%(19/405). The CMV DNA load in the plasma, sputum and BALF of recipients with CMV pneumonia was higher than those in the control A, B and C groups (all P < 0.05). In the 19 recipients, 12 cases were cured after antiviral treatment and 7 died from treatment failure(3 cases abandoned treatment). The fatality was 37%(7/19). Conclusions Quantitative detection of CMV DNA in the plasma, sputum and BALF may increase the diagnostic rate of CMV pneumonia, thereby improving clinical prognosis of recipients undergoing allogeneic hematopoietic stem cell transplantation.

The aim of the present study was to investigate the effects and mechanisms of lidocaine on lipopolysaccharide(LPS)-induced matrix metalloproteinase(MMP)-9 and MMP-2 activity in plasma, and the effects of lidocaine on LPS-induced acute lung injury(ALI). Mice were pretreated with lidocaine(2, 4, 8 mg/kg )for 30 minutes, and then treated with 10 mg/kg LPS(ip)for 12 h to induce ALI. The 7-day survival rate and lung wet/dry weight ratio of mice were monitored. Phosphorylation level of p38 was measured by western blot. The activity of MMP-9 and MMP-2 in plasma was evaluated by gelatin zymography. The results showed that pretreatment with lidocaine could significantly reduce the death rate of ALI mice as well as the lung wet/dry weight ratio in a dose-dependent manner and suppress the activity of MMP-9 and MMP-2 in plasma. Moreover, lidocaine also markedly inhibited LPS-induced upregulation of p-p38 in a dose-dependent manner. In conclusion, lidocaine alleviated LPS-induced acute lung injury by suppressing MMP-9 and MMP-2 activity.

Objective:To investigate the diagnosis and treatment of cancer patients in the prefectural and municipal hospitals in Sichuan province during the outbreak of 2019 novel coronavirus disease (COVID-19) epidemic, and analyze the impact of the epidemic on the hospitalization and treatment of cancer patients, aiming to provide reference for the diagnosis and treatment of cancer patients by medical institutions in different provinces.Methods:The prefectural and municipal hospitals in Sichuan province were investigated in the form of questionnaire.Results:A survey was conducted in 37 prefecture-level large and medium-sized hospitals in Sichuan province, of which Grade 3A hospitals accounted for 78.4%. Among the investigated hospitals, the hospitals whose hospitalization index of oncology patients and radiotherapy index of radiotherapy patients were< 1 after the first-class response were 83.7% and 93.1%, respectively. Hospitals with normal or delayed chemotherapy within one-week consisted of 54.1%, and 89.7% of the hospitals received normal radiotherapy or delayed radiotherapy within one-week after the Spring Festival. After the second-class response, the proportion of hospitals with oncology patients and radiotherapy patients that increased after the first-class response was 78.4% and 79.3%, respectively.Conclusions:Under the guidance of the State Council, the Sichuan Provincial Party Committee and the Provincial Government, Health Commission of Sichuan Province, and the municipal health commissions at various levels and under the joint efforts of medical institutions and front-line medical staff from Department of Oncology, a majority of cancer patients admitted to prefectural and municipal hospitals in Sichuan province can receive active and effective treatment during the outbreak of COVID-19 epidemic.

Objective To investigate the clinical efficacy of pretreatment regimen containing idarubicin (IDA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk refractory leukemia. Methods A total of 116 patients with high-risk refractory leukemia who received allo-HSCT treated with 7 types of IDA-containing pretreatment regimes were enrolled in this study. The implantation rate of 116 recipients was summed up. The 2-year overall survival (OS), 2-year disease free survival (DFS), cumulative recurrence rate, recurrent mortality, transplantation related mortality (TRM), cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were statistically analyzed by Kaplan-Meier survival curve. Results All 116 recipients successfully implanted. The median follow-up time was 28 (7-70) months. Among them, 64 recipients survived, the 2-year OS was 55.2%, 2-year DFS was 51.7%, 2-year recurrent mortality was 23.3% and 2-year TRM was 18.1%. Among 116 recipients, 72 cases suffered from aGVHD. The 2-year cumulative incidence rate of aGVHD was 62.1% including 20 cases of grade Ⅲ-Ⅳ aGVHD, the 2-year cumulative incidence rate was 17.2%. Among 116 recipients, 59 cases presented with cGVHD. The 2-year cumulative incidence rate was 55.4%, of which the 2-year cumulative incidence rate of extensive cGVHD was 14.7%. Among 116 recipients, 30 cases recurred with a 2-year cumulative recurrence rate of 25.9%. Conclusions IDA-containingpretreatment regime has high safety and effectiveness, and can be used as an effective pretreatment regime for transplantation preprocessing in patients with high-risk refractory leukemia.

Objective To investigate the effects of Tianxiang capsule on Neurotransmitters and Hormone Level of rats with motion sickness. Methods Male SD rats were randomly divided into six groups, including blank control group, model control group, positive drug control group, low-dose, mid-dose and high-dose Tianxiang capsule groups with the method of random digital table, and every group had 10 mice. Except the normal group, the rats in the other groups were intragastrically pre-administered for 1 hour, and the low, medium and high doses of Tianxiang capsule were 0.91, 1.82, 3.64 g/kg, the positive drug control group was given scopolamine 1 mg/kg, and then the rat motion sickness model was induced by a rotary stimulation device. After the modeling, the feces, urine, standing hair, trembling were immediately observed and recorded, and the halo response index of the rats was calculated. The blood from the heart puncture was taken and the vestibular nucleus were put on the ice. Then, the content of histamine (HIS) in the vestibular nucleus and plasma was detected by ELISA. The expression of plasma cortisol (Cort) and arginine vasopressin (AVP) were measured by radioimmunoassay. Results Compared with the model control group, the motion sickness index of rats with low, medium and high doses of Tianxiang capsule (6.56 ± 2.16, 6.10 ± 1.35, 4.46 ± 2.50 vs. 8.90 ± 2.61) significantly decreased (P<0.05 or P<0.01). The HIS content in the vestibular nucleus (12.70 ± 3.86 μg/L, 11.45 ± 1.57 μg/L, 10.02 ± 1.30 μg/L vs. 17.50 ± 4.82 μg/L) significantly decreased (P<0.05 or P<0.01). The plasma content of HIS (4.24 ± 1.75 μg/L vs. 7.69 ± 3.06 μg/L), Cort (286.90 ± 8.72 ng/ml vs. 329.26 ± 29.04 ng/ml) and AVP (16.54 ± 2.48 pg/ml vs. 22.35 ± 3.08 pg/ml) in the high doses of Tianxiang capsule significantly decreased (P<0.05 or P<0.01). Conclusions The Tianxiang capsule could effectively reduce the motion sickness index of rats with motion sicknes, which might be related to the down-regulation of HIS in Vestibule Nucleus and HIS, Cort and AVP in plasma.

Objective: To validate the prognostic value of chronic lymphocytic leukemia-international prognostic index (CLL-IPI) for Chinese CLL patients. Methods: Two hundred and fifteen CLL patients who were initially diagnosed and treated in Jiangsu Province Hospital from January 2002 to November 2017 were included in the retrospective analysis. Risk stratification and prognosis were evaluated by CLL-IPI scoring system. Results: ①Of the 215 patients, 143 were males and 72 were females, with a median age of 60 (16-85) years old. The median treatment-free survival (TFS) and overall survival (OS) was 16 months (4-24 months) and 180 months (145-215 months), respectively. ② The median TFS for low (n=60), intermediate (n=50), high (n=45) and very high risk group (n=60) according to the CLL-IPI scoring system was 56, 15, 12 and 5 months, respectively (P<0.001). ③ The median follow-up was 48 months (1-192 months). The median OS for low risk group was not reached and for intermediate, high, and very high risk group was 180, 89 and 74 months, respectively. The estimated 5-year OS rate was 97.6%, 83.7%, 67.8% and 55.2%, respectively (P<0.001). ④ Multivariate analysis indicated that unmutated immunoglobulin heavy chain variable region (IGHV) gene and β₂-microglobulin>3.5 mg/L(P<0.001) were independent prognostic factors of TFS, while TP53 deletion and/or mutation(P=0.008), unmutated IGHV (P=0.017) and age>65 years(P=0.045) were independent prognostic factors of OS. Conclusion CLL-IPI is the powerful tool for risk stratification in Chinese CLL patients.