2.Early use of dexamethasone increases Nr4a1 in Kupffer cells ameliorating acute liver failure in mice in a glucocorticoid receptor-dependent manner.
Jing-Wen DENG ; Qin YANG ; Xiao-Peng CAI ; Jia-Ming ZHOU ; Wei-Gao E ; Yan-Dong AN ; Qiu-Xian ZHENG ; Meng HONG ; Yan-Li REN ; Jun GUAN ; Gang WANG ; Shu-Jing LAI ; Zhi CHEN
Journal of Zhejiang University. Science. B 2020;21(9):727-739
BACKGROUND AND OBJECTIVE:
Acute liver failure (ALF) is a type of disease with high mortality and rapid progression with no specific treatment methods currently available. Glucocorticoids exert beneficial clinical effects on therapy for ALF. However, the mechanism of this effect remains unclear and when to use glucocorticoids in patients with ALF is difficult to determine. The purpose of this study was to investigate the specific immunological mechanism of dexamethasone (Dex) on treatment of ALF induced by lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) in mice.
METHODS:
Male C57BL/6 mice were given LPS and D-GaIN by intraperitoneal injection to establish an animal model of ALF. Dex was administrated to these mice and its therapeutic effect was observed. Hematoxylin and eosin (H&E) staining was used to determine liver pathology. Multicolor flow cytometry, cytometric bead array (CBA) method, and next-generation sequencing were performed to detect changes of messenger RNA (mRNA) in immune cells, cytokines, and Kupffer cells, respectively.
RESULTS:
A mouse model of ALF can be constructed successfully using LPS/D-GaIN, which causes a cytokine storm in early disease progression. Innate immune cells change markedly with progression of liver failure. Earlier use of Dex, at 0 h rather than 1 h, could significantly improve the progression of ALF induced by LPS/D-GaIN in mice. Numbers of innate immune cells, especially Kupffer cells and neutrophils, increased significantly in the Dex-treated group. In vivo experiments indicated that the therapeutic effect of Dex is exerted mainly via the glucocorticoid receptor (Gr). Sequencing of Kupffer cells revealed that Dex could increase mRNA transcription level of nuclear receptor subfamily 4 group A member 1 (Nr4a1), and that this effect disappeared after Gr inhibition.
CONCLUSIONS
In LPS/D-GaIN-induced ALF mice, early administration of Dex improved ALF by increasing the numbers of innate immune cells, especially Kupffer cells and neutrophils. Gr-dependent Nr4a1 upregulation in Kupffer cells may be an important ALF effect regulated by Dex in this process.
Animals
;
Dexamethasone/therapeutic use*
;
Disease Models, Animal
;
Kupffer Cells/physiology*
;
Liver Failure, Acute/pathology*
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Nuclear Receptor Subfamily 4, Group A, Member 1/physiology*
;
Receptors, Glucocorticoid/physiology*
3.Effect of decentration in controlling the development of myopia after orthokeratology
Gang-Yue WU ; Xian-Qiu LAI ; Xiao-Dan DAI
International Eye Science 2018;18(1):188-191
AIM:To evaluate the changes of the corneal surface morphology undergoing overnight orthokeratology treatment and assess the effect of optical center deviation in controlling the development of myopia.METHODS:This was a retrospective clinical study.One hundred and thirty-four children (134 eyes) with myopia aged 10.66 ± 1.79 years were treated with overnight orthokeratology lenses.The examinations of visual acuity,axial length and corneal topography were performed before and 3,6,12,18 and 24mo after wearing orthokeratology.The results of right eye were taken as the object of this study,SPSS19.0 for statistical analysis.RESULTS:The distance of decentration about 134 children at 3,6,12,18 and 24mo after wearing orthokeratology were 0.84±0.45mm,0.77±0.40mm,0.79± 0.41 mm,0.78±0.41 mm,and 0.79±0.42mm respectively.The difference between these groups were not statistically significant (F=1.187,P=0.319).The mean distance of decentration after orthokeratology treatment was 0.79 ± 0.35mm,the growth of axial length after 24mo was 0.32± 0.30mm,the mean distance of decentration divided into 3 groups,mild (<0.5mm) 27 eyes,medium (0.5-1.0mm)79 eyes,severe (> 1.0mm) 28 eyes,the growth of axial length frow 3 groups after 24mo were 0.45±0.34mm,0.32 ±0.28mm,0.23 ± 0.29mm,were statistically significant difference between each groups (F=3.825,P=0.024).By linear-regression analysis,the growth of axial length and the mean distance of decentration after 24mo was statistically significant difference (F =7.246,P =0.008),equation of linear regression was Y=0.478-0.194X.At 24mo after wearing orthokeratology,the mean distance of decentration about 18 eyes with monocular diplopia was 1.18±0.36mm,and 116 eyes without monocular was 0.73± 0.31mm,the distance of decentration were statistically significant difference (t=5.59,P<0.01).CONCLUSION:The degree of decentration tended to be stable after 3mo of orthokeratology treatment and influenced the effect of myopia control and visual quality.
4.Discoursing on Soxhlet extraction of ginseng using association analysis and scanning electron microscopy
Yuan YUE ; Zi-Dong QIU ; Xian-You QU ; Ai-Ping DENG ; Yuan YUAN ; Lu-Qi HUANG ; Chang-Jiang-Sheng LAI
Journal of Pharmaceutical Analysis 2018;8(5):312-317
Soxhlet extraction is a common method of sample preparation. However, there has been no discussion about the efficiency of Soxhlet extraction from different batches and the factors that cause content fluctuation. In this study, Panax ginseng was selected as a model sample. Soxhlet extraction by means of a water bath, which has always been neglected, was identified as a novel key factor in the poor repeat-ability in different batches of Soxhlet extraction, as it can affect the siphon times and reflux time, which have been positively correlated with the ginsenoside contents. By substituting round bottom flasks in the same column, the relative standard deviation of the most fluctuated compound, ginsenoside Rb1, was decreased from 24.6% to 5.02%. Scanning electron microscopy analysis confirmed that the breakdown of the surface of the ginseng powder in the Soxhlet extraction led to a better dissolution of ginsenosides, indicating that chloroform may promote the extraction of ginsenosides by disrupting the cell structure. Moreover, 70% methanol was regarded as the better solvent for extracting the ginsenosides. Overall, this work offers a practical and effective protocol for improving the accuracy and repeatability of Soxhlet extraction methodology for ginsenosides and other analytes.
5.Performance of Ultrasonic Shear Wave Elastography in Assessing Benign and Malignant Breast Lesions.
Xian-Quan SHI ; Jun-Lai LI ; Qiu-Yang LI ; Yan HUANG ; Wen-Bo WAN ; Jie TANG
Acta Academiae Medicinae Sinicae 2015;37(3):294-299
OBJECTIVETo determine the best shear wave elastography (SWE) quantitative parameters including the maximum elasticity (Emax), mean elasticity(Emean), minimum elasticity, standard deviation and ratio of Emean (Eratio) in assessing benign and malignant breast lesions.
METHODSTotally 302 breast lesions underwent conventional ultrasound and SWE. Each lesion was classified according to ultrasound Breast Imaging Reporting and Data System (BI-RADS). The receiver operating characteristic(ROC) curves were used to determine the cut-off values of SWE quantitative parameters and to suggest breast lesions as benign or malignant. The sensitivity,specificity and the Youden index (sum of sensitivity and specificity minus 1) of SWE quantitative parameters were compared,and then the sensitivity,specificity and the Youden index of the combinations of each SWE parameters in assessing breast lesions were compared.
RESULTSThe sensitivity,specificity and the Youden index of the Emax were 0.87,0.97 and 0.84,which were higher than other SWE parameters (all P<0.01). The sensitivity, specificity and the Youden index of Emax combined with ultrasound BI-RADS were 0.86,0.97 and 0.83, which were higher than other combinations (all P<0.01).
CONCLUSIONSCompared with other parameters, Emax has the best performance in assessing breast lesions. It can be used as an important quantitative indicator for the evaluation of benign and malignant breast lesions.
Breast Diseases ; Breast Neoplasms ; Elasticity ; Elasticity Imaging Techniques ; Female ; Humans ; ROC Curve ; Ultrasonography, Mammary
6.Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large B-cell lymphoma tissues.
Yuan-lin XU ; Hua-qing WANG ; Zheng-zi QIAN ; Zheng SONG ; Shi-yong ZHOU ; Hui-lai ZHANG ; Li-hua QIU ; Xian-huo WANG ; Ping WANG
Chinese Journal of Oncology 2013;35(6):450-455
OBJECTIVETo explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.
METHODSThe expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL.
RESULTSThe density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05).
CONCLUSIONSCombined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.
Humans ; Immunohistochemistry ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; Macrophages ; physiology ; Prognosis ; T-Lymphocytes, Regulatory ; physiology
7.Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.
Yun HOU ; Hua-qing WANG ; Kai FU ; Xian-ming LIU ; Hui-lai ZHANG ; Zheng-zi QIAN ; Li-hua QIU ; Wei LI ; Shi-yong ZHOU ; Lan-fang LI ; Xi-shan HAO
Chinese Journal of Oncology 2012;34(4):306-310
OBJECTIVEThe aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL).
METHODSFrom January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analyzed retrospectively.
RESULTSA total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia.
CONCLUSIONOur data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.
Adolescent ; Adult ; Aged ; Alopecia ; chemically induced ; Antibodies, Monoclonal, Murine-Derived ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Etoposide ; administration & dosage ; Fatigue ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lymphoma, B-Cell ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Retrospective Studies ; Rituximab ; Survival Rate ; Thrombocytopenia ; chemically induced ; Vinblastine ; administration & dosage ; analogs & derivatives ; Young Adult
8.Nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer.
Lan-Fang LI ; Hua-Qing WANG ; Xian-Ming LIU ; Hui-Lai ZHANG ; Li-Hua QIU ; Zheng-Zi QIAN ; Wei LI
Chinese Journal of Oncology 2011;33(8):626-628
OBJECTIVETo evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).
METHODSThe clinical data of 37 NSCLC patients who received nimotuzumab in combination with chemotherapy in Tianjin Medical University Cancer Hospital from January 2009 to October 2010 were retrospectively reviewed. Of the thirty-seven patients, 12 patients were in stage III B, 25 patients in stage IV. Twenty-four patients recived platinum-based chemotherapy in combination with nimotuzumab, 13 patients recived nonplatinum-based chemotherapy in combination with nimotuzumab. Ten patients received nimotuzumab in combination with chemotherapy as first-line regimen, 23 patients as second-line regimen, 4 patients as third-line regimen.
RESULTSOf the 37 advanced NSCLC patients who received nimotuzumab in combination with chemotherapy, the total number of chemotherapy were 137 cycles, the mean number was 3.7 cycles. One patient had complete remission (CR), 9 patients had partial remission (PR), 16 cases had stable disease (SD), and 11 patients had progressive disease (PD). The response rate (RR) was 27% and clinical benefit rate (CBR) was 70.3%. The main side effects were bone marrow suppression and gastrointestinal reactions. Grade I acneiform rash was found in one patient.
CONCLUSIONThe regimen of nimotuzumab in combination with chemotherapy can improve the response rate and was well tolerated in patients with advanced non-small cell lung cancer.
Adult ; Aged ; Agranulocytosis ; chemically induced ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Exanthema ; chemically induced ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platinum ; administration & dosage ; Remission Induction ; Retrospective Studies ; Thrombocytopenia ; chemically induced ; Vomiting ; chemically induced
9.Capecitabine combined with weekly docetaxel in Chinese patients > 65 years with anthracycline-resistant metastatic breast cancer.
Hua-Qing WANG ; Zheng-Zi QIAN ; Xian-Ming LIU ; Hui-Lai ZHANG ; Lan-Fang LI ; Li-Hua QIU ; Yun HOU ; Shi-Yong ZHOU ; Xi-Shan HAO ; Cong-Hua XIE
Chinese Medical Journal 2010;123(22):3212-3216
BACKGROUNDThere are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients.
METHODSMBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy.
RESULTSThe overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%).
CONCLUSIONSCapecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.
Aged ; Anthracyclines ; therapeutic use ; Antimetabolites, Antineoplastic ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; Capecitabine ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Drug Resistance, Neoplasm ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; therapeutic use ; Humans ; Taxoids ; administration & dosage ; therapeutic use
10.DNCE regimen for treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma.
Xian-ming LIU ; Hua-qing WANG ; Hui-lai ZHANG ; Li-hua QIU ; Wei LI ; Lan-fang LI ; Xiu-zhen CUI ; Peng-fei LIU ; Xi-shan HAO
Chinese Journal of Oncology 2008;30(10):779-782
OBJECTIVETo evaluate the efficacy and safety of DNCE [DXM, navelbine (NVB), DDP and Vp-16] regimen and DICE [dexamethasone (DXM), ifosfamide (IFO), cisplatin (DDP) and etoposide (Vp-16)] regimen in the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma (NHL).
METHODSA total of 69 patients with histopathologically proved advanced aggressive and highly aggressive NHL were randomized into trial group (32 patients treated with DNCE regimen) and control group (37 patients treated with DICE regimen). The control group was given DICE regimen: DXM 20 mg, iv d1 approximately d4; IFO 1 g/m2), iv d1 approximately d4; Mesna 400 mg, iv q8h, d1 approximately d4; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. The trial group was given DNCE regimen: DXM 20 mg, iv d1 approximately d4; NVB 25 mg/m2, iv d1 and d5; DDP 25 mg/m2, iv d1 approximately d4; Vp-16 100 mg/m2, iv d1 approximately d4; one cycle for 21 approximately 28 days. Each patient completed at least 2 cycles of treatment.
RESULTSA better efficacy was shown in the complete response rate, partial response rate, and total response rate between DNCE and DICE groups (18.8% vs. 10.8%, 37.5% vs. 35.1%, and 56.3% vs. 45.9%, respectively), but the differences were statistically non-significant (P > 0.05). The 1-, 3-, and 5-year survival rates were not significantly increased in DNCE group compared with that in DICE group (86.5% vs. 87.5%, 58.3% vs. 63.2%, 42.9% vs.38.5%, respectively, P > 0.05). The major side effects were leucopenia, thrombocytopenia, and nausea in both groups. The bone marrow depression in DNCE group was significantly slighter than that in the DICE group (P < 0.05).
CONCLUSIONThe efficacy of DNCE regimen is as good as DICE regimen, and the bone marrow toxicity is less severe in DNCE group than that in DICE regimen. Therefore, the DNCE regimen is an effective second-line salvage regimen for the treatment of refractory or relapsed aggressive and highly aggressive non-Hodgkin lymphoma.
Adolescent ; Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; adverse effects ; therapeutic use ; Dexamethasone ; administration & dosage ; adverse effects ; therapeutic use ; Etoposide ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Ifosfamide ; adverse effects ; therapeutic use ; Leukopenia ; chemically induced ; Lymphoma, Non-Hodgkin ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Salvage Therapy ; Survival Rate ; Thrombocytopenia ; chemically induced ; Vinblastine ; administration & dosage ; adverse effects ; analogs & derivatives ; Young Adult

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