1.Effects of ginsenoside Rg3-induced P27 expression on proliferation of human erythroleukemia K562 cells
Linna MA ; Yu LIANG ; Ranfeng CHEN
The Journal of Practical Medicine 2014;(7):1066-1069
Objective To explore the effects of ginsenoside Rg3 on the expression of P27 in human erythrol-eukemia cell line K562 and cell proliferation. Methods Human erythroleukemia cell line K562 cells were cultured to exponential phase, then K562 cells were treated with different concentrations of Rg3 (6.25, 12.5, 25, 50, and 100 μg/mL) as Rg3 group, and cells treated without Rg3 (0 μg/mL) were take as control group. After 3 days, K562 cells were observed by Wright-Giemsa staining with microscopy , the proliferation of K562 cells were examined by tetrazolium salt (MTT) assay, and the expression of P27 mRNA were detected by fluorescent quantitative RT-PCR assay. Results MTT assay showed that after treatment with Rg3,the inhibition rate (IR) of proliferation of cells in Rg3 groups were increased gradually , and the differences were significant compared with the control group (P < 0.05). The results of fluorescent quantitative RT-PCR showed the levels of P27 mRNA expression in 25,50 and 100 μg/mL Rg3 groups were significant higher than that of control group (P < 0.05). Conclusion The ginsenoside Rg3 can inhibit the proliferation of K562 cells by inducing the expression of P27.
2.CT and MRI Manifestations of Lumbar Spinal Epidural Angiolipoma
Jianbing MA ; Fangrong YU ; Fan WU ; Jia WANG ; Linna YUAN
Chinese Journal of Medical Imaging 2015;(6):428-431
Purpose To investigate the imaging features of lumbar spinal epidural angiolipoma, and to improve the imaging diagnostic capability of the disease. Materials and Methods Four patients with lumbar spinal epidural angiolipoma confirmed by pathology were recruited in the study. CT and MRI images were reviewed and the imaging characteristics including the shape, size, location, density, and signal intensity were analyzed. Results The lesions located at the right front of the spinal canal in two cases, at the left front in one case, and the residual one case located directly behind the spinal canal. The longitudinal axis of the lesions paralleled to the longitudinal axis of the spine. The dura mater spinalis was compressed and inward shifted. All of the four cases showed homogeneous iso- or hypo-density on CT without calcification or necrosis in the lesions. The maximum diameter was 3 to 5 cm. The boundary was clear and smooth. Three lesions showed dumbbell-shaped and crossed foramen, but the adjacent bone were not absorbed or destructed. One lesion showed scallop-like. On MRI, four cases displayed slightly hypointense on T1WI and hyperintense on T2WI. On STIR images, the lesions showed hyperintense with patchy low signal intensity in it. The boundary of the lesions was clear. After administration of contrast media, two lesions presented remarkably homogeneous enhancement, one lesion showed dual tail sign, and one lesion displayed pen-tip-like at the both ends. Conclusion MRI plays an important role in locating the lesion and distinguishing internal tissue components of spinal angiolipoma, which is the gold standard for the diagnosis of the tumor. CT provides excellent supplement. The Combination of CT and MRI will improve the diagnostic accuracy of the spinal angiolipoma.
3.Progression of Tripterygium wilfordii polyglycoside in mice with premature ovarian insufficiency at various time points
Linna MA ; Kun MA ; Xiaodi FAN ; Jie LUO ; Shanfeng GAO ; Jiani LI ; Han ZHANG
Chinese Journal of Comparative Medicine 2024;34(2):35-44,153
Objective Changes in relevant indexes in the mouse model of early-onset ovarian insufficiency caused by Tripterygium wilfordii polyglycoside were analyzed,and the optimal time point for intervention was determined.Methods Forty female ICR mice were randomly divided into control and A,B,C,and D model groups with eight mice in each group.The control group was gavaged with purified water for 14 days(0.01 mL/10 g),and the remaining groups were administered a Tripterygium wilfordii polyglycoside suspension(80 mg/kg,0.01 mL/10 g)for 1 day(A model group),3 days(B model group),7 days(C model group),or 14 days(D model group),and samples were collected.Body weight and wet weights of the uterus and bilateral ovaries of mice were determined in each group.Serum FSH,LH,E2,P,AMH,INH-B,and T contents were measured using enzyme-linked immunoassays.HE staining was used to observe the number and developmental status of follicles and corpus luteum at all levels in mice of each group.TUNEL staining was used to detect the apoptosis in the ovaries of mice in each group.IHC detected expression of VEGFA,CD34,and EPO proteins in the ovaries of mice in each group.mRNA expression of HIF-1α,SDF-1,and CXCR4 in each group of mice was detected by PCR.Results Compared with the control group,changes in indicators in model A mice did not meet the POI modeling standard.The ovarian index,uterine index,and body weight of mice in the B model group were decreased significantly(P<0.01),the weight of the C model group was decreased significantly(P<0.01),and the ovarian index of the D model group was decreased significantly(P<0.05).Serum contents of FSH and LH in B,C,and D model groups were increased(P<0.05,P<0.01),the E2,PROG,AMH,INH-B,and T contents were decreased(P<0.01).The numbers of basal follicles,pre-sinus follicles,sinusoidal follicles,antral follicles,preovulatory follicles,and corpus luteum were decreased significantly(P<0.05,P<0.01)and the number of atresia follicles was increased significantly(P<0.01)in B,C,and D model groups.The apoptotic area of TUNEL staining in A,B,C,and D model groups was increased significantly(P<0.05,P<0.01).Expression of CD34,VEGFA,and EPO in B,C,and D model groups was decreased significantly(P<0.05,P<0.01).mRNA expression of HIF-1α,SDF-1,and CXCR4 in A and B model groups was significantly increased(P<0.05,P<0.01).Compared with the B model group,the relevant indexes of C and D model groups were changed significantly,indicating that C and D models were more serious and tended to develop POF.Conclusions The B model group is the turning point of ovarian function from impaired POI to irreversible POF,suggesting that 3 days of administrating Tripterygium wilfordii polyglycoside is optimal to induce a POI disease model for effective drug intervention.
4.Intervention Effect and Molecular Mechanism of Dabufei Decoction in Dunhuang Formula Combined with Cisplatin on Lewis Lung Adenocarcinoma in Mice
Mengyong XIAO ; Yali LUO ; Xiaofeng QI ; Jing LUO ; Linna MA ; Linfeng RUAN ; Nini LIAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):95-104
ObjectiveTo explore the intervention effect and molecular mechanism of Dabufei decoction in Dunhuang formula combined with cisplatin on Lewis lung adenocarcinoma-bearing mice. MethodFifty C57BL/6J mice were used, with 10 randomly assigned to the blank group (without modeling), and 40 subcutaneously inoculated with Lewis cells to establish a Lewis lung adenocarcinoma-bearing mouse model. These 40 mice were randomly divided into the following four groups (with 10 mice in each group): Model group (equal volume of physiological saline), cisplatin group (5 mg·kg-1), Dabufei decoction group (14.35 g·kg-1·d-1), and Dabufei decoction combined with cisplatin group (Dabufei decoction 14.35 g·kg-1·d-1 + cisplatin 5 mg·kg-1). Each group was treated continuously for 14 days. The general condition of the mice was observed, body weight changes were recorded, and the tumor inhibition rate, spleen index, and thymus index were calculated. Peripheral blood white blood cell (WBC), platelet (PLT), and hemoglobin (HGB) were detected by routine blood tests. Flow cytometry was used to detect the expression of CD4+CD25+FoxP3+ regulatory T cells (Treg) and natural killer (NK) cells in the spleen. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were used to determine the expression of proteins and mRNA related to the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in tumor tissues. ResultCompared with the blank group, the model group showed decreased body weight (P<0.05), spleen index, and thymus index (P<0.05), decreased percentage of NK cells in the spleen (P<0.05), increased percentage of Treg cells (P<0.05), and decreased counts of WBC, PLT, and HGB (P<0.05). Compared with the model group, the Dabufei decoction group exhibited significant tumor growth inhibition, increased body weight, and reduced tumor weight (P<0.05), increased percentage of NK cells (P<0.05), decreased proportion of Treg cells (P<0.05), and increased counts of WBC, PLT, and HGB (P<0.05). In the cisplatin group, tumor growth was significantly inhibited, body weight significantly decreased (P<0.05), and tumor weight significantly reduced (P<0.05). The spleen index and thymus index decreased (P<0.05), and the percentage of Treg cells significantly decreased (P<0.05). The counts of WBC, PLT, and HGB significantly decreased (P<0.05). In the Dabufei decoction combined with cisplatin group, tumor growth was significantly inhibited, and tumor weight significantly reduced (P<0.05). The levels of phosphorylated PI3K, Akt, and mTOR proteins and mRNA in tumor tissues were significantly reduced in all medication groups (P<0.05). Compared with the cisplatin group, the Dabufei decoction combined with cisplatin group showed significantly inhibited tumor growth, reduced tumor weight (P<0.05), increased body weight (P<0.05), increased spleen index and thymus index (P<0.05), increased percentage of NK cells (P<0.05), decreased percentage of Treg cells (P<0.05), significantly increased counts of WBC, PLT, and HGB (P<0.05), and reduced levels of phosphorylated PI3K, Akt, and mTOR and their mRNA (P<0.05). ConclusionDabufei decoction combined with cisplatin has a synergistic effect with reduced toxicity, effectively regulating immune function, increasing the proportion of NK cells, reducing the proportion of Treg cells, improving bone marrow suppression, and downregulating the PI3K/Akt/mTOR signaling pathway to inhibit tumor growth in Lewis lung adenocarcinoma-bearing mice.
5.A multicenter, prospective, phaseⅡ, single-arm study on the treatment of newly diagnosed multiple myeloma with domestic bortezomib in combination with lenalidomide and dexamethasone
Linna XIE ; Xin WANG ; Qiang HE ; Hui WANG ; Ji MA ; Haiyan ZHANG ; Nan LIU ; Guitao JIE ; Taiwu XIAO ; Hao ZHANG ; Haiguo ZHANG ; Zengjun LI ; Lijie XING
Chinese Journal of Hematology 2024;45(6):571-576
Objective:To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma (NDMM) .Methods:This multicenter, prospective, single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022. All patients received domestic bortezomib in combination with lenalidomide and dexamethasone (BLD regimen), and the efficacy, prognostic factors, and safety were analyzed.Results:Among the 126 patients with NDMM, 118 completed four cycles of treatment, with an overall response rate (ORR) of 93.22% (110/118) and a ≥very good partial response (VGPR) rate of 68.64% (81/118). Ultimately, 114 patients completed at least eight cycles of treatment, with an ORR of 92.98% (106/114) and a ≥VGPR rate of 77.19% (88/114). Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen, with an ORR of 100% (18/18) and a ≥VGPR rate of 88.9% (16/18). The proportion of patients achieving ≥VGPR increased with the treatment duration, and factors such as staging and age did not significantly affect efficacy. Single-factor analysis showed that R2-ISS stage Ⅲ/Ⅳ, blood calcium >2.27 mmol/L, and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival (PFS) ( P<0.05), whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival (OS) ( P<0.001). Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS ( P=0.002). The incidence of hematologic adverse reactions was 16.7% (19/114), and nonhematologic adverse reactions were mainly mild to moderate, with no significant cardiac or renal adverse reactions observed. Conclusion:The BLD regimen is effective in treating NDMM, in which patients with high-risk genetic features are still achieving a high ≥VGPR rate, and the overall safety is good.
6.Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China
Hui WANG ; Qiang HE ; Dan LIU ; Xiuzhi DENG ; Ji MA ; Linna XIE ; Zhongliang SUN ; Cong LIU ; Rongrong ZHAO ; Ke LU ; Xiaoxia CHU ; Na GAO ; Haichen WEI ; Yanhua SUN ; Yuping ZHONG ; Lijie XING ; Haiyan ZHANG ; Hao ZHANG ; Wenwei XU ; Zengjun LI
Chinese Journal of Hematology 2023;44(7):550-554
Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.
7.Discovery of WS-157 as a highly potent, selective and orally active EGFR inhibitor.
Pengxing HE ; Shenghui NIU ; Shuai WANG ; Xiaojing SHI ; Siqi FENG ; Linna DU ; Xuyang ZHANG ; Zhilu MA ; Bin YU ; Hongmin LIU
Acta Pharmaceutica Sinica B 2019;9(6):1193-1203
EGFR tyrosine kinase inhibitor (EGFR-TKI) has been used successfully in clinic for the treatment of solid tumors. In the present study, we reported the discovery of from our in-house diverse compound library, which was validated to be a potent and selective EGFR-TKI. showed excellent inhibitory activities against EGFR (IC = 0.81 nmol/L), EGFR (IC = 1.2 nmol/L) and EGFR (IC = 1.1 nmol/L), but was less effective or even inactive against other nine kinases. also displayed excellent antiproliferative activities against a panel of human cancer cell lines, and exhibited the ability to reduce colony formation and wound healing the same as gefitinib. We found that upon oral administration showed better anti-tumor activity in A431 bearing xenograft mouse models compared to gefitinib. In addition, showed better intestinal absorption than gefitinib and had favorable pharmacokinetic properties and microsomal metabolic stability in different species. These studies indicate that has strong antitumor activity and , and could be used for the development of anti-lung cancer agent targeting EGFR.
8.Predictors and prognostic analysis of pathological complete response of axillary metastatic lymph nodes after neoadjuvant chemotherapy in breast cancer
Qin XU ; Jun YUAN ; Ping QIAN ; Linna YUAN ; Zhenyi MA ; Ziran ZHANG
China Modern Doctor 2024;62(5):30-34,39
Objective To investigate the clinicopathological factors associated with pathological complete response(pCR)of axillary metastatic lymph nodes in breast cancer patients after neoadjuvant chemotherapy(NAC),and to analyze the postoperative survival.Methods A total of 116 patients with breast cancer with axillary lymph node metastasis were collected from Jiaxing Hospital of TCM,Jiaxing Maternity and Child Health Care Hospital and The First Hospital of Jiaxing.Univariate analysis was used to analyze the relationship between clinicopathological factors and the pCR of axillary lymph node metastasis in breast cancer after NAC.Binary Logistic regression was used to analyze the independent predictors of the pCR of axillary lymph node metastasis in breast cancer after NAC.Kaplan-Meier survival curve was used to analyze the disease-free survival rate and overall survival rate of patients with and non-pCR of axillary metastatic lymph nodes.Results Among 116 patients,52 cases of axillary metastatic lymph nodes achieved pCR after NAC,accounting for 44.83%.Univariate analysis showed that age,vascular invasion,pCR of primary breast tumor,the difference of Ki67 before and after NAC,NAC regimen,and the efficacy of NAC were statistically significant between breast cancer patients with pCR and those non-pCR(P<0.05).Binary Logistic regression analysis showed that age,vascular invasion and pCR of primary breast tumor were independent predictors of pCR of axillary metastatic lymph nodes(P<0.05).The 5-year disease-free survival rate(80.40%vs.54.60%)and overall survival rate(90.4%vs.70.10%)of patients with pCR and non-pCR of axillary metastatic lymph nodes were compared.Conclusion Some breast cancer patients with axillary lymph node metastasis can reach pCR in lymph nodes after NAC.Analyzing the correlation between clinical pathological factors and pCR of axillary metastatic lymph nodes after NAC,it was found that pCR of axillary metastatic lymph nodes after NAC is related to age≤50 years old,no vascular infiltration,and primary breast tumor pCR.At the same time,it was found that patients with axillary metastatic lymph node pCR had a better prognosis than those with non-pCR.
9.Study of discrepancy in subjective and objective cognitive function in patients with depressive disorder
Linna FU ; Min WANG ; Xiao YANG ; Yikai DOU ; Jinxue WEI ; Zongling HE ; Yue YU ; Xiao CAI ; Xiaohong MA
Sichuan Mental Health 2024;37(1):26-32
BackgroundThere exist differences in the subjective and objective cognitive functions of patients with depressive disorder, ane there are limited research on influencing factors of such phenomenon currently. ObjectiveTo explore the differences in subjective and objective cognitive function in patients with depressive disorder as well as influencing factors, and to provide references for further understanding of cognitive impairment in patients with depressive disorder. MethodsA total of 77 patients with depressive disorder who received outpatient or inpatient treatment in the Fourth People's Hospital of Chengdu from January 13, 2022 to December 11, 2023 were selected for the study. These patients also met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, fifth edition(DSM-5). Various tools were employed to assess patients in this study: Montgomery-Asberg Depression Rating Scale (MADRS) for the depressive symptoms, Perceived Deficits Questionnaire for Depression (PDQ-D) and Chinese Version of Brief Neurocognitive Test Battery (C-BCT) for the subjective and objective cognitive function, Sheehan Disability Scale (SDS) for the social function, and Clinical Global Impression-Severity of Illness(CGI-SI) for the severity of patient's condition. Pearson correlation analysis was used to examine the correlation of subjective and objective cognitive function and their differences with age, years of education, MADRS total score, SDS total score, and CGI-SI score. Multiple linear regression was used to explore the influencing factors of the differences between subjective and objective cognitive function. ResultsThere was a statistically significant difference in the total PDQ-D scores and the difference of subjective and objective cognitive function (D value) between depressive patients with and without medication (t=-4.228, -2.392, P<0.05 or 0.01). There was no statistically significant correlation in subjective and objective cognitive function in patients with depressive disorder (r=-0.148, P>0.05). Negative correlations can be observed between the PDQ-D total score and age or years of education (r=-0.333, -0.369, P<0.01). The PDQ-D total score was positively correlated with MADRS total score, SDS total score and CGI-SI score (r=0.487, 0.637, 0.434, P<0.01). D value was negatively correlated with age and years of education (r=-0.411, -0.362, P<0.01), while positively correlated with MADRS total score, SDS total score and CGI-SI score (r=0.259, 0.468, 0.299, P<0.05 or 0.01). Age (β=-0.328, P<0.01) and SDS total score (β=0.409, P<0.01) were two predictive factors for D value. ConclusionThe difference between subjective and objective cognitive function among patients with depressive disorder is related to several factors including age, years of education, severity of symptoms and impairment of social function. [Funded by Surface Project of National Natural Science Foundation of China (number, 62173069); Technological Innovation 2030-Major Project of "Brain Science and Brain-Like Research" (number, 2022ZD0211700); Key R&D Support Program and Major Application Demonstration Project of Chengdu Science and Technology Bureau (number, 2022-YF09-00023-SN)]
10.Influences of Stress Distribution on Bone-Anchored Maxillary Protraction at Different Protraction Sites
Linna WANG ; Xiaoying HU ; Yang LIU ; Xiaolei GE ; Liru ZHAO ; Chunyan LIU ; Haiyan LU ; Wensheng MA
Journal of Medical Biomechanics 2022;37(1):E148-E154
Objective To evaluate the influence of stress distributions on bone-anchored maxillary protraction at different protraction sites, so as to guide patients to choose an optimal protraction site in clinic. Methods A three-dimensional (3D) finite element model of child head with implant anchorages was establised. Four protraction sites were set according to the position of implant installation. Working condition 1: the alveolar bone at the intersection of distal 2 mm of primary lateral incisor crown distal surface and gingival cervical margin to 5 mm. Working condition 2: the alveolar bone at the intersection of mesial 2 mm of maxillary first primary molar crown mesial surface and gingival cervical margin to 5 mm. Working condition 3: the alveolar bone at the intersection of mesial 2 mm of maxillary first molar crown mesial surface and gingival cervical margin to 5 mm. Working condition 4: the alveolar bone at the intersection of distal 2 mm of maxillary first molar crown distal surface and gingival cervical margin to 5 mm. The finite element models were loaded with 500 g protraction force at each side with 30° forward direction to the occlusal plane. Stress distributions on each suture were analysed. Results The maximum stress of frontomaxillary suture was in working condition 2 (1 477-28 190 Pa). The maximum stress of nasomaxillary suture was in working condition 1 (5.296-924 Pa). The maximum stress of zygomaticomaxillary suture was in working condition 4(394.7-13 130 Pa). The maximum stress of zygomaticofrontalis suture was in working condition 4 (495.2-31 690 Pa). The maximum stress of zygomaticotemporal suture was in working condition 3 (1 148-15 870 Pa). The maximum stress of medianpalatine suture was in working condition I (6.479-730 Pa). Conclusions When the protraction sites are set in distal maxillary primary lateral incisor and mesial maxillary first primary molar, it is of positive significance to improve the concave profile, especially in nose root. When the protraction sites are set in mesial or distal maxillary first molar, it is of positive significance to improve the concave profile, especially in maxillary basal bone of the midface.