1.Key protein expressions in the insulin-like growth factor-1 signal pathway involved in the resistance of ovarian cancer to cisplatin
Meiqun JIA ; Zengyan CHEN ; Lingyan SHI ; Bin ZHAO ; Xia WU ; Yinfang WU
Chinese Journal of Clinical Oncology 2014;(5):286-290
Objective: This study aimed to detect the expression levels of the key proteins involved in the insulin-like growth factor signaling pathway of patients with ovarian cancer. These proteins include insulin-like growth factor-1 (IGF1), insulin-like growth factor-1 receptor (IGF1R), and protein kinase B (AKT). Methods: Ovarian cancer tissues were subjected to drug resistance tests using the ATP-TCA method. IGF1, IGF1R, AKT, and multidrug resistance protein2 (MRP2) expressions were detected in the sera of patients with ovarian cancer by conducting enzyme-linked immunosorbent assay. IGF1, IGF1R, and AKT protein expressions were detected in the surgical specimens by immunohistochemistry. Patients were instructed to monitor their cancer antigen 125 (CA125) levels monthly from the date a patient was discharged to the last day of chemotherapy (or until chemotherapy was completed). A color Doppler ultrasound, CT, or MRI scan was required if CA125 value is abnormal. The total follow-up time was one year. Results: IGF1, IGF1R, and AKT expressions were significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group (P =0.000 1). Immunohistochemical results showed that IGF1, IGF1R, and AKT expressions were significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group (P<0.05). The monthly CA125 values of 40 patients were obtained after chemotherapy. In the cisplatin-sensitive group, 18 of the 24 cases exhibited normal CA125 values for more than one year, and the remaining 6 cases maintained normal values for more than half a year. In the cisplatin-resistant group, 16 cases revealed higher than normal CA125 values for half a year after chemotherapy. Recurrent lesions were observed in their color Doppler ultrasound results or MRI scans. Conclusion: Cisplatin resistance in ovarian cancer is strongly correlated with the expressions of IGF1, IGF1R and AKT. IGF1 is a potential candidate for the targeted therapy of ovarian cancer.
2.Acute Toxicity Study of Solanumprocumbens Traditional Zhuang Medicine
Zengyan YANG ; Xiangpei ZHAO ; Shaofeng CHEN ; Xin HUANG ; Ruisong HUANG
Herald of Medicine 2017;36(11):1253-1254
Objective To evaluate the safety of Solanumprocumbens by studying its acute toxicity to mice. Methods The dosage of 100% death ( Dm) and 100% survive ( Dn) were determined. Five groups were set between the dosage of Dm and Dn in a 1:0.8 ratio, and then were intragastrically administrated once at the dosage of 250,200,160,128,102.4 g·kg-1 respectively.Toxicity and mortality of mice after intragastricly administration of Solanumprocumbens were observed for 14 days continuously. Results After four hours of administration, there were death in each group except the lowest dosage group (102.4 g·kg-1).Number of death of the groups 250,200,160 and 128 g·kg-1 were 10,8,6 and 3 respectively.LD50 of Solanumprocumbens was 153. 02 g · kg-1 , the 95% confidence interval was ( 136. 55, 171. 47 ) g · kg-1 . Conclusion Solanumprocumbens has a certain toxicity.More attention should be payed to its toxicity for clinical rational drug use.
3.Significance and safety of systematic lymphadenectomy in the treatment of patients with endometrial cancer
Jia SHAO ; Aiqin HE ; Zengyan CHEN
Journal of Clinical Medicine in Practice 2014;(17):91-93,99
Obj ective To explore the effect and safety of systematic lymphadenectomy on the prognosis of patients with endometrial cancer.Methods 54 patients with endometrial cancer were divided into two groups according to the type of surgery.Group A (n= 30)was treated with modified radical hysterectomy plus bilateral salpingo-oophorectomy and pelvic lymphadenectomy, while group B (n= 24 )was treated with modified radical hysterectomy plus bilateral salpingo-oophorectomy and systematic pelvic as well as para-aortic lymphadenectomy.Prognosis and post-operative complications were compared between two groups.Results The two-year recurrence and metastasis rate in group A was 40%,which was significantly higher than 12.5%in group B (P<0.05).The two-year overall survival rates in group A and group B were 70.0%and 91.7%re-spectively,and there was significant difference between two groups (P<0 .05 ).Incidence rate of incomplete intestinal obstruction in group B was significantly higher than that in group A (P <0.05).There were no significant differences in the incidence rates of lymphedema,lymphocyst, deep vein thrombosis and urethral fistula between two groups (P>0 .05 ).Conclusion Systematic pelvic and para-aortic lymphadenectomy can improve the survival rate and prognosis of patients with endometrial carcinoma,and the incidence rate of postoperative complications can be restrained in controllable scope.
4.Study on the Effect and Mechanism of Huanglian Jiedu Decoction in Improving Itching Symptoms in 1-chloro-2,4-dinitrobenzene-Induced Atopic Dermatitis Mice
Zengyan ZHANG ; Huiyuan ZHANG ; Jianhua GUAN ; Yunlong CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2023;34(12):1713-1720
Objective To investigate the effect and mechanism of Huanglian Jiedu Decoction in improving the itching symptoms of 1-chloro-2,4-dinitrobenzene(DNCB)-induced atopic dermatitis(AD)in mice.Methods Thirty-six Balb/c mice were randomly divided into normal group,model group,Dexamethasone(positive control,2.5 mg·kg-1)group and Huanglian Jiedu Decoction low-,medium-and high-dose groups(0.4,0.8 and 1.6 g·kg-1),6 mice in each group.After shaving the back of the mice,200 μL of DNCB solution was applied to the back of the mice for sensitisation(1%DNCB for 3 consecutive days)and excitation(1.5%DNCB,starting from the fourteenth day,excitation was performed once every 3 days for a total of 5 times).The stimulation and drug interventions were carried out simultaneously,and each group was administered by gavage at a set dose once daily for 14 days.The severity score of the skin lesions was calculated with reference to the Scoring Atopic Dermatitis(SCORAD),and the number of times the mice scratched within 20 minutes was recorded.The pathological changes of the lesions were observed by HE staining;mast cell infiltration was observed by toluidine blue staining;and the mRNA expression levels of thymic stromal lymphopoietin(TSLP),interleukin(IL)13,histamine H4 receptor(HRH4),and IL-31 in the lesions were detected by RT-qPCR.Results Compared with the normal group,the dorsal skin of the mice in the model group showed obvious erythema,mossification,crusting and epidermal shedding after DNCB excitation,and the severity score of the lesions was significantly increased(P<0.001);the hyperkeratosis of epidermis,the thickness of spinous layer was significantly increased(P<0.001),sponge oedema,and a large number of inflammatory cells infiltration was seen in the dermis;and the number of mast cells was significantly increased(P<0.001);the times of scratches within 20 minutes was significantly increased(P<0.01);and the mRNA expression levels of TSLP,IL-13,HRH4,and IL-31 in the skin lesion tissue were all significantly elevated(P<0.05,P<0.01).Compared with the model group,the skin lesions on the backs of mice in the low-,medium-and high-dose groups of Huanglian Jiedu Decoction were significantly improved,the mossy area was significantly reduced,the severity was significantly reduced,and the severity score of skin lesions was significantly reduced(P<0.001),and the number of mast cells and the mRNA expression levels of IL-13,HRH4,and IL-31 were significantly reduced in the skin lesion tissues(P<0.05,P<0.01,P<0.001);the thickness of the stratum spinosum was significantly reduced in the medium-and high-dose groups of Huanglian Jiedu Decoction(P<0.001),and the number of inflammatory cells in the dermis was significantly reduced;the number of scratching in mice in the high-dose group of Huanglian Jiedu Decoction was significantly reduced within 20 minutes(P<0.01),and the mRNA expression level of TSLP in the lesion tissue was significantly reduced(P<0.05).Conclusion Huanglian Jiedu Decoction can alleviate itching symptoms in AD mice,and its mechanism of action may be related to repairing the skin barrier in AD mice,attenuating the infiltration of inflammatory cells and mast cells,and down-regulating the mRNA expressions of itch-associated factors TSLP,IL-13,IL-31 and HRH4 in skin tissues.
5.Significance and safety of systematic lymphadenectomy in the treatment of patients with endometrial cancer
Jia SHAO ; Aiqin HE ; Zengyan CHEN
Journal of Clinical Medicine in Practice 2014;(17):91-93,99
Obj ective To explore the effect and safety of systematic lymphadenectomy on the prognosis of patients with endometrial cancer.Methods 54 patients with endometrial cancer were divided into two groups according to the type of surgery.Group A (n= 30)was treated with modified radical hysterectomy plus bilateral salpingo-oophorectomy and pelvic lymphadenectomy, while group B (n= 24 )was treated with modified radical hysterectomy plus bilateral salpingo-oophorectomy and systematic pelvic as well as para-aortic lymphadenectomy.Prognosis and post-operative complications were compared between two groups.Results The two-year recurrence and metastasis rate in group A was 40%,which was significantly higher than 12.5%in group B (P<0.05).The two-year overall survival rates in group A and group B were 70.0%and 91.7%re-spectively,and there was significant difference between two groups (P<0 .05 ).Incidence rate of incomplete intestinal obstruction in group B was significantly higher than that in group A (P <0.05).There were no significant differences in the incidence rates of lymphedema,lymphocyst, deep vein thrombosis and urethral fistula between two groups (P>0 .05 ).Conclusion Systematic pelvic and para-aortic lymphadenectomy can improve the survival rate and prognosis of patients with endometrial carcinoma,and the incidence rate of postoperative complications can be restrained in controllable scope.
6.Evaluation of the consistency and detection capability of seven domestic 2019-nCoV nucleic acid detection kits
Dan XIONG ; Lijuan KAN ; Mengmeng WANG ; Huamei TANG ; Wei WU ; Guiqing YANG ; Fei ZHUO ; Xiaowen DOU ; Dayang CHEN ; Xiang JI ; Zengyan ZONG ; Xiuming ZHANG
Chinese Journal of Laboratory Medicine 2020;43(8):787-793
Objective:To compare the consistency and detection capability of seven 2019-nCoV nucleic acid detection kits, and provide reference for detection method selection of clinical laboratory and diagnosis of new coronavirus pneumonia.Methods:Two batches of pharyngeal swab samples were collected from tenpatients with confirmed infection of 2019-nCoV and 10 suspected patients with negative 2019-nCoV test results during January 29 to February 5, 2020 in Shenzhen Luohu People′s Hospital. Seven kinds of kits were labeled as ato g and used for nucleic acid detection respectively to evaluate the consistency of the test results of the clinical samples. A 2019-nCoV positive specimen was selected and diluted to 5-concentration gradient plates (Level-1 to 5) with RNase-free water. The positive detection rate and intra-batch repeatability of different brands of kits were compared.Results:The negative and positive coincidence rates of twenty clinical samples tested by six kinds of kits were 100%, and the positive and negative coincidence rate was 8/10 and 10/10 for the other kit, respectively. The results of intra-batch repeatability showed the CVs of viral loads tested by these seven kits were all less than 5%. In the concentration range of Level-1 to 3, the detection capability for open reading frame (ORF)1ab gene of Kit b,d and f was lower than Kit a,c,e and g, and the detection capability of kit e and g was the highest (14/15). The detection capability for N gene of Kit a (15/15) was higher than the other 5 kits. The comprehensive analysis of the detection capability for ORF1ab and N gene showedthat Kit d had the lowest detection capability (ORF1ab:40%,N:53%), and there was no significant difference in the detection capability of Kit a, b, c, e, and f.Conclusions:There was no significant difference in the accuracy and repeatability of the seven kits for positive samples with high viral loads, and the detection performance was good; but some kits had poor detection capability for weak positive samples. It is suggested that the weak positive samples should be rechecked by at least two manufacturers′ kits to ensure the accuracy of the results.
7.Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract
Jiang HAIYAN ; Zheng BOWEN ; Hu GUANG ; Kuang LIAN ; Zhou TIANYU ; Li SIZHENG ; Chen XINYI ; Li CHUANGJUN ; Zhang DONGMING ; Zhang JINLAN ; Yang ZENGYAN ; He JIUMING ; Jin HONGTAO
Journal of Pharmaceutical Analysis 2024;14(9):1330-1346
Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.
8.Recommendations for prescription review of antipyretic-analgesics in symptomatic treatment of children with fever
Xiaohui LIU ; Xing JI ; Lihua HU ; Yuntao JIA ; Huajun SUN ; Qinghong LU ; Shengnan ZHANG ; Ruiling ZHAO ; Shunguo ZHANG ; Yanyan SUN ; Meixing YAN ; Lina HAO ; Heping CAI ; Jing XU ; Zengyan ZHU ; Hua XU ; Jing MIAO ; Xiaotong LU ; Zebin CHEN ; Hua CHENG ; Yunzhu LIN ; Ruijie CHEN ; Xin ZHAO ; Zhenguo LIU ; Junli ZHANG ; Yuwu JIANG ; Chaomin WAN ; Gen LU ; Hengmiao GAO ; Ju YIN ; Kunling SHEN ; Baoping XU ; Xiaoling WANG
Chinese Journal of Applied Clinical Pediatrics 2022;37(9):653-659
Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.
9.Efficacy and safety of Venetoclax in the treatment of 25 patients with recurrent hematologic malignancies after an allogeneic hematopoietic stem cell transplantation
Xin CHEN ; Zengyan LIU ; Rongli ZHANG ; Weihua ZHAI ; Qiaoling MA ; Aiming PANG ; Donglin YANG ; Yi HE ; Jialin WEI ; Sizhou FENG ; Mingzhe HAN ; Erlie JIANG
Chinese Journal of Hematology 2022;43(7):542-549
Objegtive:To investigate the efficacy and safety of preemptive/salvage therapy with venetoclax (VEN) in patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Retrospective analysis the clinical data of 25 patients with minimal residual disease (MRD) positive or morphological recurrence after allo-HSCT treated with VEN in the hematological Hospital of Chinese Academy of Medical Sciences from 2021.2 to 2021.11, there were 15 MRD positive patients (preemptive treatment group) and 10 morphological recurrence patients (salvage treatment group) . The dose of VEN in both groups was 400 mg/d, which was reduced to 100 mg/d when combined with azole antifungal drugs.Results:①In the preemptive group, there were 7 males and 8 females, with a median age of 32 (18-52) years; There were 13 cases of acute myeloid leukemia (AML) , 1 case of acute lymphoblastic leukemia (ALL) and 1 case of primary myelofibrosis (PMF) ; the median time from MRD positive to the application of VEN was 2.5 (0-12.5) months. The median course of treatment was 2 (1-4) . On the 7th day of the first course of treatment, the median concentration of VEN was 1945 (688-5383) μg/L. After one course of VEN treatment, MRD in 8 patients turned negative (major responses) , MRD in 4 patients decreased by 50% compared with that before treatment, 3 cases were ineffective, and the overall response rate (ORR) was 80% (12/15) . On the 7th day of treatment, 3 of the 9 patients with VEN blood concentration <1 000 μg/L or >3 000 μg/L turned negative for MRD (33.3%) , and 5 of the 6 patients with VEN blood concentration between 1000 and 3000 μg/L turned negative for MRD (83.3%) . Grade 3/4 neutropenia occurred in 5 patients (33%) and grade 3/4 thrombocytopenia occurred in 5 patients (33%) , there were no new cases of severe infection and death. ②In the salvage group, there were 7 males and 3 females, with a median age of 44 (28-59) years; there were 6 cases of AML, 2 cases of ALL, 1 case of atypical chronic myeloid leukemia (aCML) , 1 case of refractory hemopenia with multiline dysplasia (MDS-RCMD) ; the median time from relapse to application of VEN was 0 (0-1) months. The median treatment was 1 (1-2) course. The median concentration of VEN on the 7th day of the first course of treatment was 2 419 (1 200-6 155) μg/L. After one course of VEN treatment, 3 cases achieved complete remission (CR) (major responses) and 3 cases achieved partial remission (PR) , 4 cases were ineffective and the ORR was 60% (6/10) . On the 7th day of treatment, 1 of the 4 patients with VEN blood concentration >3 000 μg/L achieved CR (25%) , and 2 of the 6 patients with VEN blood concentration between 1 000 and 3 000 μg/L achieved CR (33.3%) . Grade 3/4 neutropenia and grade 3/4 thrombocytopenia occurred in 10 patients (100%) . One patient died of severe pulmonary infection. ③The median follow-up was 4.5 (1-8.5) months. The overall survival rate (OS) of the preemptive group and the salvage group were (70.2±12.7) % and (50.0± 15.8) %, respectively ( χ2=1.873, P=0.171) . The OS of patients with and without primary response to one course of VEN were (90.9±8.7) % and (36.2±14.7) % respectively ( χ2=6.843, P=0.009) . Three patients with TP53 mutation achieved the major responses after VEN treatment. Conclusion:Preemptive/salvage therapy with VEN after allo-HSCT in patients with hematological malignancies is effective and well tolerated, monitoring the concentration of VEN is expected to improve the curative effect. The prognosis of patients who fail to reach the major responses after one course of preemptive/salvage treatment with VEN is poor, so they need to switch to other treatment schemes as soon as possible.