OBJECTIVE: To investigate the efficacy and safety of chidamide combined with DICE regimen (cisplatin+ ifosfamide + etoposide + dexamethasone) for relapsed/refractory diffuse large B-cell lymphome(R/R DLBCL). METHODS: The clinical data of 31 R/R DLBCL patients treated by chidamide combined with DICE regimen in the Hematology Department of the Fourth Hospital of Hebei Medical University from October 2016 to October 2020 were retrospectively analyzed. The clinical efficacy and adverse events were observed. RESULTS: Among the 31 patients, 20 were male and 11 were female. The median age of the patients was 55 (range: 27-71) years old, 21 cases were < 60 years old, 10 cases were ≥60 years old. 26 cases were refractory and 5 cases were relapsed. There were 13 cases of germinal center B-cell like (GCB), 17 cases of non-GCB, and 1 case had missing Hans type. There were 17 cases of double-expression lymphoma (DEL) and 14 cases of non-DEL. The complete response rate of patients was 38.7%(12/31), the overall response rate was 67.7%(21/31). The median progression-free survival time and the median overall survival time were 9.8(95%CI : 4.048-15.552) months, 13.9(95%CI : 9.294-18.506) months, respectively. Multipvariate analysis showed that GCB and DEL reduced the risk of disease recurrence in R/R DLBCL patients. The main grade 3/4 hematological adverse events in this study were thrombocytopenia, agranulocytosis, anemia and leukopenia. CONCLUSION The chidamide combined with DICE regimen is effective in the treatment of R/R DLBCL, and hematological adverse events should be closely monitored.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Female ; Male ; Adult ; Aged ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Benzamides/administration & dosage* ; Aminopyridines/administration & dosage* ; Etoposide/therapeutic use* ; Cisplatin/administration & dosage* ; Ifosfamide/administration & dosage* ; Dexamethasone/therapeutic use*

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P＜0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136～2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102～1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Purpose::To assess the value of the driving pressure variation rate (ΔP%) in predicting the outcome of weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome.Methods::In this case-control study, a total of 35 patients with moderate-severe acute respiratory distress syndrome were admitted to the intensive care unit between January 2022 and December 2022 and received invasive mechanical ventilation for at least 48 h were enrolled. Patients were divided into successful weaning group and failed weaning group depending on whether they could be removed from ventilator support within 14 days. Outcome measures including driving pressure, PaO 2:FiO 2, and positive end-expiratory pressure, etc. were assessed every 24 h from day 0 to day 14 until successful weaning was achieved. The measurement data of non-normal distribution were presented as median (Q 1, Q 3), and the differences between groups were compared by Wilcoxon rank sum test. And categorical data use the Chi-square test or Fisher's exact test to compare. The predictive value of ΔP% in predicting the outcome of weaning from the ventilator was analyzed using receiver operating characteristic curves. Results::Of the total 35 patients included in the study, 17 were successful vs. 18 failed in weaning from a ventilator after 14 days of mechanical ventilation. The cut-off values of the median ΔP% measured by Operator 1 vs. Operator 2 in the first 4 days were ≥ 4.17% and 4.55%, respectively ( p < 0.001), with the area under curve of 0.804 (sensitivity of 88.2%, specificity of 64.7%) and 0.770 (sensitivity of 88.2%, specificity of 64.7%), respectively. There was a significant difference in mechanical ventilation duration between the successful weaning group and the failure weaning group (8 (6, 13) vs. 12 (7.5, 17.3), p = 0.043). The incidence of ventilator-associated pneumonia in the successful weaning group was significantly lower than in the failed weaning group (0.2‰ vs. 2.3‰, p = 0.001). There was a significant difference noted between these 2 groups in the 28-day mortality (11.8% vs. 66.7%, p = 0.003). Conclusion::The median ΔP% in the first 4 days of mechanical ventilation showed good predictive performance in predicting the outcome of weaning from mechanical ventilation within 14 days. Further study is needed to confirm this finding.

Chemokines and their receptors play crucial roles in nervous system diseases,among which the CXC chemokine receptor 3(CXCR3)is an important mediator of intercellular communication.CXCR3 not only participates in inflammatory chemotaxis and malignant behaviors of tumor cells but also regulates the neurologic diseases.CXCR3 and its ligands directly or indirectly contribute to neuroinflammation and neuroimmunity,and potentially serve as therapeutic targets for diseases like multiple sclerosis,Alzheimer's disease,and glioma and so on.This review discusses the expression and impact of CXCR3 and its ligands in neurological diseases such as multiple sclerosis,neurologic tumors,neurodegenerative diseases,and neuropathic pain,as well as their associations with CXCR3 ligands.Understanding the mechanisms linking CXCR3 to these diseases could facilitate its potential as an early diagnostic biomarker and a target for drug intervention,and provide the basis of studying the occurrence and developmant of nervous system disease.

Objective To investigate the effect and mechanism of lycium barbarum polysaccharide(LBP)on hepatocyte injury induced by homocysteine(Hcy).Methods Normal C3H/An mouse hepatocytes(NCTC 1469)were cultured in vitro and treated with different concentrations of Hcy(0,50,100,200,500 μmol/L).The optimal concentrations of Hcy-treated NCTC 1469 cells were detected by MTT assay.When the cells reached the logarithmic growth stage,the conditions were set up as follows:(1)control group(cultured with DMEM medium supplemented with 10%horse serum)and Hcy group(treated with 100 μmol/L Hcy solution for 48 h),and the cells were collected.Cell viability staining was used to detect apoptosis,aspartate aminotransferase(AST)/alanine aminotransferase(ALT)activity detection kit was used to detect AST and ALT activities,RT-qPCR was used to detect the expression levels of YAP1,DNMT1,DNMT3a and DNMT3b mRAN,and Western blotting was used to detect the expression of YAP1 protein,nested methylation specific PCR(nMS-PCR)was used to detect DNA methylation rates in the YAP1 promoter region.(2)Control group,LBP group,Hcy group and Hcy+LBP group.LBP group was treated with 4 mg/ml LBP solution for 2 h,Hcy group and Hcy+LBP group were treated with 100 μmol/L Hcy solution for 48 h,and Hcy+LBP group was treated with 4 mg/ml LBP solution at 46 h,and the cells were collected.The expression levels of YAP1,DNMT1,DNMT3a and DNMT3b mRAN were detected by RT-qPCR;the expression of YAP1,Bax and Bcl-2 proteins was detected by Western blotting;AST/ALT activity detection kit was used to detect AST and ALT activities.Prediction of DNA methylation CpG islands in YAP1 promoter region by bioinformatics.Results NCTC 1469 cells were treated with 100 μmol/L Hcy according to the results of MTT assay.Compared with control group,the apoptosis rate of Hcy group increased(P<0.01),the activities of ALT and AST increased(P<0.001),the mRAN and protein expression levels of YAP1 decreased(P<0.001),and the methylation rate of YAP1 promoter region increased(P<0.01),the mRNA expression levels of DNMT1,DNMT3a and DNMT3b increased(P<0.01 or P<0.001).Compared with Hcy group,the mRNA expression levels of DNMT1,DNMT3a and DNMT3b in the Hcy+LBP group decreased(P<0.001),the mRAN and protein expression levels of YAP1 significantly increased(P<0.01 or P<0.001).In addition,in the Hcy+LBP group,cells showed significantly elevated of Bcl-2 protein(P<0.001),but decreased Bax protein(P<0.001),and decreased activities of ALT and AST(P<0.001).Conclusions The decrease of YAP1 expression may be the key process of Hcy induced injury of NCTC 1469 cells,and the methylation of the YAP1 promoter region may be the molecular mechanism of Hcy induced YAP1 expression change.LBP may improve NCTC 1469 cell damage induced by Hcy by positively regulating YAP1 expression.