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1.
Chinese Journal of Surgery ; (12): 156-161, 2023.
Article in Chinese | WPRIM | ID: wpr-970200

ABSTRACT

Objective: To examine the safety and efficacy of the uniportal video-assisted thoracoscopic decortication in treatment of drug-resistant tuberculosis empyema. Methods: From January 2018 to December 2020, 122 cases of tuberculous empyema treated by decortication in Department of Surgery, Wuhan Pulmonary Hospital were retrospectively analyzed, including 100 males and 22 females, aged(M(IQR)) 29.5(28.0) years (range: 13 to 70 years). According to the surgical approach and drug resistance, patients with drug-resistant tuberculosis who underwent uniportal video-assisted thoracoscopic decortication were included in group A (n=22), and those who underwent thoracotomy decortication were included in group B (n=28). Drug-sensitive patients who underwent uniportal video-assisted thoracoscopic decortication were included in group C (n=72). There was no statistical difference in the baseline data of the three groups (P>0.05). The operation, early postoperative recovery, and prognosis-related indicators were compared among three groups by Kruskal-Wallis test and χ2 test by Mann-Whitney U test and Bonferroni method between groups A and B, groups A and C. Results: The intraoperative blood loss of group A, group B, and group C was 200(475) ml, 300(200) ml, and 225(300) ml, respectively. There was no significant difference in intraoperative hemorrhage (H=2.74, P=0.254) and treatment outcome (χ2=4.76, P=0.575) among the three groups. Compared with group B, the operation time of group A (302.5(187.5) minutes vs. 200.0(60.0) minutes, U=171.0, P=0.007) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0 (2.2) months, U=146.5, P=0.032) were longer, and the postoperative drainage duration (9.5(7.8) days vs. 13.0(10.0) days, U=410.0, P=0.044), and the postoperative hospitalization time (12.0(7.8) days vs. 14.5(4.8) days, U=462.2, P=0.020) were shorter. There was no significant difference in complications between group A and group B (63.6%(14/22) vs. 71.4%(20/28), χ2=0.34, P=0.558). Compared with group C, the postoperative drainage duration of group A (9.5(7.8) days vs. 7.0(4.0) days, U=543.5, P=0.031), the postoperative hospitalization time (12.0(7.8) days vs. 9.0(4.0) days, U=533.0, P=0.031) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0(2.0) months, U=961.5, P=0.001) were longer. The operation time (302.5(187.5) minutes vs. 242.5(188.8) minutes, U=670.5, P=0.278), and complications (63.6%(14/22) vs. 40.3%(29/72), χ2=3.70, P=0.054) were not different between group A and group C. Conclusions: For drug-resistant tuberculous empyema, the uniportal video-assisted thoracoscopic decortication can achieve the same good therapeutic effect as drug-sensitive tuberculous empyema, and it is as safe as thoracotomy. At the same time, it has the advantage of minimally invasive and can accelerate the early postoperative recovery of patients.


Subject(s)
Female , Male , Humans , Empyema, Tuberculous/surgery , Retrospective Studies , Thoracic Surgery, Video-Assisted , Drainage , Blood Loss, Surgical , Tuberculosis, Multidrug-Resistant/surgery
2.
Chinese Acupuncture & Moxibustion ; (12): 821-824, 2023.
Article in Chinese | WPRIM | ID: wpr-980801

ABSTRACT

The commonly used terms "sham acupuncture" and "placebo acupuncture" in clinical acupuncture research is compared and analyzed in this article. In terms of their respective characteristics, sham acupuncture has a wider scope, including various types of acupoints, needle insertion at non-acupoint or non-insertion at acupoints, while placebo acupuncture mainly focuses on non-insertion at acupoints. Sham acupuncture mainly emphasizes the appearance similarity to real acupuncture, while placebo acupuncture emphasizes both similarity in appearance and the absence of therapeutic effects. Properly distinguishing and applying sham acupuncture and placebo acupuncture can help standardize their usage in terminology. Considering the difficulty in setting up qualified placebo acupuncture, it is suggested that researchers use the term "sham acupuncture" to describe the acupuncture control methods used in clinical research.


Subject(s)
Humans , Acupuncture Therapy , Needles , Research Personnel , Clinical Trials as Topic
3.
Chinese Acupuncture & Moxibustion ; (12): 116-118, 2022.
Article in Chinese | WPRIM | ID: wpr-927344

ABSTRACT

The progress of Chinese clinical research on acupuncture and moxibustion in recent 10 years was reviewed and analyzed, and corresponding suggestions were put forward for the current problems. In the past 10 years, Chinese clinical research on acupuncture and moxibustion has made considerable progress, mainly in the following areas: a series of internationally recognized clinical research evidences have been published, a preliminary acupuncture clinical evaluation system has formed, sham/placebo acupuncture control is widely used internationally, acupuncture clinical research norms and standards have been initially established. However, the following issues still need to be paid attention to in follow-up research: focus on the overall layout and refinement of clinical research, further improvement of clinical evaluation system, developing relevant norms for sham/placebo acupuncture setting and reporting, strengthening data sharing and platform integration, building a smooth basic and two-way transformation clinical pathway, etc.


Subject(s)
Acupuncture , Acupuncture Therapy , Medicine, Chinese Traditional , Moxibustion , Publications
4.
Chinese Journal of Pathology ; (12): 190-195, 2022.
Article in Chinese | WPRIM | ID: wpr-935503

ABSTRACT

Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.


Subject(s)
Humans , Biomarkers, Tumor/genetics , Gene Amplification , In Situ Hybridization, Fluorescence , Liposarcoma/genetics , Proto-Oncogene Proteins c-mdm2/genetics , RNA
5.
Chinese Journal of Hematology ; (12): 376-382, 2022.
Article in Chinese | WPRIM | ID: wpr-929571

ABSTRACT

Objective: To investigate the effect of CD33-targeted bi-specific and tri-specific T-cell engagers on T-cell proliferation and explore their cytotoxicity on leukemia cells. Methods: The CD33-targeted bi-specific T-cell engager (CD33-BiTE) and tri-specific T-cell engager (CD33-TriTE) expression vectors were successfully constructed and expressed through a eukaryotic cell expression system. CD33-BiTE and CD33-TriTE were purified by affinity chromatography. The effects of CD33-BiTE and CD33-TriTE on T cells were analyzed through in vitro experiments. Results: ① CD33-BiTE and CD33-TriTE were successfully constructed and purified and could compete with flow cytometry antibodies for binding to the target cells. ② After 12 days of co-culture with CD33-BiTE and CD33-TriTE, the number of human T cells were expanded to 33.89±19.46 and 81.56±23.62 folds, respectively. CD33-TriTE induced a stronger proliferation of T cells than CD33-BiTE (P<0.05) . ③ Both CD33-BiTE and CD33-TriTE induced specific dose-dependent cytotoxicity on CD33(+) leukemia cells. ④ Compared to CD33-TriTE, leukemia cells were prone to express PD-L1 when co-cultured with T cells and CD33-BiTE. CD33-TriTE induced powerful cytotoxicity on leukemia cells with high PD-L1 expression. Conclusion: CD33-BiTE and CD33-TriTE expression vectors were constructed, and fusion proteins were expressed in eukaryotic cells. Our results support the proliferative and activating effects of BiTE and TriTE on T cells. Compared to that of CD33-BiTE, CD33-TriTE induced a stronger proliferative effect on T cells and a more powerful cytotoxicity on leukemia cells with high PD-L1 expression.


Subject(s)
Humans , B7-H1 Antigen/pharmacology , Leukemia, Myeloid, Acute/metabolism , Sialic Acid Binding Ig-like Lectin 3/pharmacology , T-Lymphocytes
6.
Chinese Journal of Cardiology ; (12): 401-407, 2020.
Article in Chinese | WPRIM | ID: wpr-941123

ABSTRACT

Objective: To investigate the impact and related mechanisms of glucose fluctuations on aortic fibrosis in rats with type 1 diabetes mellitus. Methods: After injection of streptozotocin (STZ), male Sprague Dawley (SD) (8-12 weeks) rats (n=24) were randomly divided into three groups in accordance with the random number table: controlled STZ-induced diabetes (C-STZ) group (n=8); uncontrolled STZ-induced diabetes (U-STZ) group (n=8); STZ-induced diabetes with glucose fluctuations (STZ-GF) group (n=8). After three weeks, rats were sacrificed and aorta was obtained, aortic fibrosis was detected by Masson trichrome staining. The expression of collagen type 1 (collagen Ⅰ) was tested by immunofluorescence. The expression of runt-related transcription factor 2 (Runx2) was tested by immunohistochemistry. The mRNA levels of collagen Ⅰ and Runx2 were detected by quantitative real-time PCR (qRT-PCR). The protein expressions of collagen Ⅰ, Runx2 and nuclear factor (NF)-κB were determined by Western blot. Primary rat aortic smooth muscle cells (VSMCs) were cultured in three conditions: normal glucose (NG), high glucose (HG) and glucose fluctuations (GF). Cells in GF group were incubated for 72 hours with glucose alternating between 5.5 and 25 mmol/L every 12 hours. TPCA-1, the inhibitor of NF-κB, the expression of collagenⅠin different groups of cells was tested by immunofluorescence. The protein expressions of collagen Ⅰ, Runx2 and NF-κB were also determined by Western blot. Results: (1) The quantitative ratios of the area of fibrosis in the C-STZ group, U-STZ group, STZ-GF group were (8.42±0.10)%, (21.30±0.74)% and (44.39±1.09)% (P<0.05), respectively. The means of integral optical density (IOD) of collagenⅠ in the three groups were 11.92±0.88, 50.04±3.56 and 77.52±2.69, respectively (P<0.05). The mRNA levels of collagenⅠ in the three groups were 1.00±0.10, 2.02±0.28 and 2.83±0.33, respectively (P<0.05). The protein expressions of collagenⅠ in the three groups were 1.05±0.03, 2.06±0.32 and 4.93±0.25, respectively (P<0.05). (2) The average IOD of Runx2 in the three groups were 150.00±7.35, 204.84±2.32 and 391.48±7.13, respectively (P<0.05). The mRNA levels of Runx2 in the three groups were 1.02±0.02, 1.27±0.04 and 2.18±0.12, respectively (P<0.05). The protein expressions of Runx2 in the three groups were 1.03±0.01, 2.34±0.36 and 4.52±0.75, respectively (P<0.05). (3) The protein expressions of NF-κB in the three groups were 1.02±0.01, 1.96±0.13 and 2.64±0.21, respectively (P<0.05). (4) In vitro, application of inhibitor of NF-κB reversed glucose fluctuations-induced upregulation of protein levels of Col Ⅰ and Runx2 (P<0.05). Conclusion: Glucose fluctuations could aggravate aortic fibrosis through activating Runx2 via NF-κB signaling pathways.


Subject(s)
Animals , Male , Rats , Aorta , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Fibrosis , Glucose , NF-kappa B , Rats, Sprague-Dawley
7.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 148-154, 2019.
Article in Chinese | WPRIM | ID: wpr-801845

ABSTRACT

To provide theoretical basis for protection and rational use of medicinal plants resources of Orchidaceae,we investigated and studied the existing species,distribution,utilization and resources of Orchidaceae medicinal plants in Jiangxi province. Orchidaceae medicinal plants in different areas of Jiangxi province were investigated in different seasons by means of field investigation,route investigation and folk interview. Orchidaceae medicinal plants collected from field investigation as well as Orchidaceae specimens stored in the herbariums of Jiangxi scientific research institutes were studied and identified. The existing species,distribution location,quantity,medicinal value and resource utilization of Orchidaceae medicinal plants in Jiangxi province were studied and analyzed. Orchidaceae medicinal plants in herbal literatures were consulted for their category,medicinal use and other information. Relevant modern research literatures on Orchidaceae medicinal plant resources were consulted. There were 93 species of Orchidaceae medicinal plants in 37 genera in Jiangxi province, and 19 of them were new species of Orchidaceae,including 6 species in Dendrobium alone. The number of medicinal genera accounted for 71.2% of Orchidaceae genera in Jiangxi province,20.1% of Orchidaceae genera in China,76.9% of Orchidaceae species in Jiangxi province and 31.2% of Orchidaceae medicinal species in China. There are abundant resources of Orchidaceae medicinal plants in Jiangxi province,and many species of Orchidaceae medicinal plants have a high medicinal value and ornamental value. However,with the overexploitation and utilization of Orchidaceae medicinal plant resources,some wild Orchidaceae medicinal plant resources are facing exhaustion,and need to urgently strengthen scientific management and protection.

8.
Journal of Medical Postgraduates ; (12): 734-739, 2019.
Article in Chinese | WPRIM | ID: wpr-818314

ABSTRACT

Objective The recurrence rate of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) remains relatively high. The aim of this study was to investigate the predictive value of rs2200733 polymorphism for AF recurrence after RFCA. Methods Fifty-three AF patients underwent RFCA guided by the magnetic navigation system between July 2015 and September 2016 in Wuxi People’s Hospital. We obtained the baseline data on the patients, conducted genotyping for rs2200733 variants, and followed up the patients for symptoms and complications by electrocardiography (ECG) and dynamic ECG. Using Cox survival analysis, we determined the independent predictors of AF recurrence after RFCA and the sensibility and specificity of predicting AF recurrence at 12 and 24 months post-operatively. Results All the patients were Han Chinese, followed-up for 21.6 ± 9.5 months, and 25 (47.2%) of them experienced AF recurrence at 6.6 ± 5.3 months after RFCA. Kaplan-Meier survival analysis revealed a significant association between rs2200733 polymorphism and AF recurrence in the additive and recessive models (P < 0.001), and multivariate Cox analysis showed the rs2200733 polymorphism (recessive model) to be an independent predictor of post-RFCA AF recurrence (OR = 3.184, 95% CI: 1.378-7.357, P = 0.007). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of rs2200733 TT in predicting AF recurrence at 12 months were 64%, 81%, 70%, 76% and 74%, and those at 24 months were 60%, 82%, 75%, 70%, and 72%, respectively. Conclusion The rs2200733 polymorphism is an independent predictor of AF recurrence after RFCA, and its high specificity indicates that it could be used as a tool for screening Han Chinese patients with AF for RFCA.

9.
Journal of Medical Postgraduates ; (12): 790-794, 2018.
Article in Chinese | WPRIM | ID: wpr-818064

ABSTRACT

Objective The mechanisms of docosahexaenoic acid (DHA) protecting the cardiovascular system have not yet been clarified. This study was to investigate the vasorelaxative effect of 13,14-epoxy docosapentaenoic acid (13,14-EpDPE) on coronary arterioles in normal rats and its action mechanisms.Methods We isolated coronary artery smooth muscle cells (CASMCs) from normal rats by enzyme digestion, examined the open probabilities of the large conductance calcium-activated potassium (BK) channels in inside-out single channel configuration in the presence of different concentrations (0, 1, 10 and 100 pmol/L) of 13,14-EpDPE, and recorded the BK currents with the patch clamp in whole cell configuration. Then we assessed the coronary arterial relaxation by measuring dilatory responses to 13,14-EpDPE in pre-contracted tissues with or without pre-treatment with iberiotoxin.Results In the presence of 0, 1, 10 and 100 pmol/L of 13,14-EpDPE, the open probabilities of the BK channels were 0.25±0.03, 0.34±0.03, 0.44±0.06 and 0.85±0.16 (n=6), respectively, significantly increased at 100 pmol/L as compared with 0, 1 and 10 pmol/L (P<0.05). The BK channels were activated by 13,14-EpDP in a concentration-dependent manner and its half-effect concentration was (15.94±1.21) pmol/L. The current density was increased from (58.27±16.35) to (95.94±23.00) pA/pF (P=0.002) after 10 pmol/L 13,14-EpDP perfusion when the stimulation voltage was 100 mV. 13,14-EpDPE dilated the isolated coronary arterioles in a dose-dependent manner, and its effects were abolished after pre-treatment with iberiotoxin (100 nM).Conclusion 13,14-EpDPE can dilate coronary arterioles by activating BK channels in CASMCs, which might be one of the mechanisms underlying its protective effect on the cardiovascular system.

10.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 210-215, 2018.
Article in Chinese | WPRIM | ID: wpr-698229

ABSTRACT

Objective To analyze differences in gene expression profile of pituitary tissue in cervical spondylosis of vertebral artery type(CSA)model rats and explore the mechanism of adrenal gland's regulation of CSA.Methods Ten SPF male Wistar rats were randomly divided into model group and blank group.The CSA model was established by compound modeling method.The total RNA was extracted from the pituitary;the gene expression profile was detected by whole gene chip,ontology(GO),and signal pathway analysis.Results Compared with the normal group,the differential genes'expression profile analysis showed that the total number of the differential genes was 321(fold change︱ > 2,P<0.05),with 203 up-regulated genes and 118 down-regulated genes.A total of 1 294 genes rich in GO function were involved in the regulation of intercellular signal activity and nerve cell function;the stress response to external stimuli;and the regulation of coagulation function,angiogenesis, endometrial system,and cell cycle;There were 145 signal transducers,including adipocytokine signaling pathway, TGF-β signal transduction,AMPK signaling pathway,PPAR signal pathway,Wnt signaling pathway,and MAPK signal transduction pathway.Conclusion The pituitary regulates CSA mainly through the inflammatory stimulation,immune regulation,regulation of vertebral artery function,and endometrial system.

11.
China Journal of Chinese Materia Medica ; (24): 1720-1725, 2018.
Article in Chinese | WPRIM | ID: wpr-690723

ABSTRACT

Ye Tianshi and Xue Shengbai are two febrile disease specialists in same time, and for the treatment of dampness and heat, they have different medication ideas. With the help of traditional Chinese medicine(TCM), author has studied two specialists' consilias of dampness and heat, through the statistics and analysis of their medicine during the treatment of dampness and heat, summarizes the similarities and differences of Ye and Xue's medicine application's assoations and models. Ye Tianshi and Xue Shengbai were both thought that the reason of dampness and heat was damp heat pathogenic factors, for this reason, the spleen and stomach conduction disordered, They both treated from the middle-jiao of Yangming and Taiyin, focused on warm-natured medicine, cold-natured medicine, used less cool-natured and heat-natured medicine, and more bitter, pungent, sweet medicine; Ye Tianshi usually use Scutellariae Radix, Paeoniae Radix Alba, Coptidis Rhizoma, Polyporus, Poria, Alismatis Rhizoma; Xue Shengbai commonly use Poria, Citri Reticulatae Pericarpium, Magnoliae officinalis Cortex, Patchouli, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Lablab Semen Album, Puerariae Lobatae Radix, Mume Fructus, Tsaoko Fructus, Amomi Fructus, Coptidis Rhizoma and Phellodendri Chinensis Cortex. The differences between the two masters in medicine application provide a reference for the clinical treatment of dampness and heat.

12.
Chinese Traditional and Herbal Drugs ; (24): 313-317, 2018.
Article in Chinese | WPRIM | ID: wpr-852241

ABSTRACT

Objective To prepare the reservoir patch of coumarins in Angelicae Dahuricae Radix and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug’s permeation rate. Methods The reservoir patch was prepared using hydroxypropyl methylcellulose (HPMC) as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and HPLC was used to determine imperatorin content and permeation rate. The content of imperatorin was determined by HPMC. The effect of the gel consumption, the content of coumarins and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model. The release of the selected patch in vitro was investigated. Results 1% HPMC, 1% coumarins in Angelicae Dahuricae Radix, 1% Isopropyl Myristate (IPM) and 3% Azone were the best permeation of the patch. The permeation rate reached 0.713 μg/(cm2•h). The release mechanisms of the patch in vitro coincided with zero-order kinetic. Conclusion The reservoir patch of coumarins in Angelicae Dahuricae Radix had high transdermal rate and complete in vitro release. It was indicated that the patch could be expected to be an effective transdermal drug delivery system.

13.
China Journal of Chinese Materia Medica ; (24): 2391-2397, 2017.
Article in Chinese | WPRIM | ID: wpr-275119

ABSTRACT

Ye Tianshi and Xue Shengbai were both epidemic febrile diseases specialists in same time of Qing dynasty. The Traditional Chinese Medicine Inheritance Support System was used to compare and analyze the therapeutic characteristics of these two specialists in treating damp-heat type fullness or distension in stomach. Distension is commonly caused by qi stagnation accompanied with damp-heat from internal and external factors. In treatment, separation of damp and heat and removing dampness and heat from sanjiao separately were their common therapeutic principles. Both Ye Tianshi and Xue Shengbai paid much greater attention to eliminating dampness, and the herbs with bitter and pungent flavor, warm in property were usually chosen to regulate qi flow and reduce dampness. Invigorating spleen, nourishing stomach and dispersing lung were the frequently used treatment to balance the organs'harmony. The difference between specialist Ye and specialist Xue was the preference of herbs. Hou Pu (Magnoliae Officinalis Cortex), Xing Ren (Armeniacae Semen Amarum), Chen Pi (Citri Reticulatae Pericarpium), and Hua Shi (Talcum) were often used in both administrations. Besides, Ye Tianshi preferred to use Ban Xia (Pinelliae Rhizoma), Huang Qin (Scutellariae Radix), Huang Lian (Coptidis Rhizoma), Fuling, et al. Xue Shengbai on the other hand enjoyed using Fu Lingpi(Poriae Cutis), Cao Guo (Tsaoko Fructus), and Guang Huoxiang (Pogostemonis Herba), et al. In herbs compatibility, both of the two specialists were fond of using Chen Pi-Hou Pu, Hou Pu-Xing Ren. Moreover, Ye Tianshi often used Ban Xia- Xing Ren, Ban Xia-Huang Qin, and Hua Shi-Xing Ren to achieve the expected outcome of the treatment. While, Chen Pi, Fu Lingpi, and Hou Pu were the common combination with each other in Xue's cases. The similarities and differences of their administration should have the guidance in current clinical Chinese medicine practice for damp-heat type fullness or distension in stomach.

14.
Acta Pharmaceutica Sinica ; (12): 1209-2016.
Article in Chinese | WPRIM | ID: wpr-779298

ABSTRACT

Antibody-drug conjugates, constructed with monoclonal antibodies, linker and cytotoxins, have distinctive advantages over chemotherapy drugs and antibody drugs in cancer therapy. In this review, the strategy of developing ADCs, and the important progress in past decade are well summarized. The representative ADCs in the pipeline are introduced and characterized with their new features. While, perspective for future directions of ADCs is proposed.

15.
Journal of Experimental Hematology ; (6): 1427-1431, 2015.
Article in Chinese | WPRIM | ID: wpr-274022

ABSTRACT

<p><b>OBJECTIVE</b>This study was aimed to investigate the mobilization effect of HS6101 on hematopoietic cells of mice.</p><p><b>METHODS</b>The normal ICR mice were injected subcutaneously once or twice with HS6101 at 9 µg/d/mouse, or a single dose of HS6101 3, 9, 27 and 81 µg/mouse was administrated, and the mobilization effect of HS6101 in different administration times and different dosage was observed, and compared with the synergistic effects of administration of single dose of HS6101 combined with rhG-CSF (2 µg/d/mouse was injected subcutaneously for 5 consecutive days). The peripheral blood cell counts of mice were detected at different time after administration. The hematopoietic stem/progenitor cells of bone marrow and peripheral blood were detected at day 5 and 10 after administration.</p><p><b>RESULTS</b>There was no significant difference in peripheral blood cell counts after once or twice injections of HS6101 9 µg/mouse. The peripheral platelet counts dose-dependently increased in ICR mice, which accounted for 121.1% to 118.0%, 138.7% to 123.1%, 146.4% to 139.2%, and 156.2% to 168.7% (P < 0.001) after HS6101 (3, 9, 27 and 81 µg/mouse) treatments at 5 and 7 d, respectively. HS6101 (3, 9, 27 and 81 µg/mouse) showed dose-response relationship to platelets, with R value of 0.777 and 0.954 at day 5 and 7 after administration, respectively. HS6101 significantly increased numbers of hematopoietic stem/progenitor cells in both bone marrow and peripheral blood, and elevated peripheral blood leukocytes at 27 µg/mouse dose at day 5 after administration.</p><p><b>CONCLUSION</b>HS6101 has significant mobilization effect on hematopoietic stem/progenitor cells, platelets and leukocytes in mouse.</p>


Subject(s)
Animals , Mice , Blood Cell Count , Blood Platelets , Granulocyte Colony-Stimulating Factor , Pharmacology , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cells , Leukocytes , Mice, Inbred ICR
16.
Journal of Experimental Hematology ; (6): 1716-1720, 2015.
Article in Chinese | WPRIM | ID: wpr-272533

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of HS 6101 and recombinant human granulocyte colony stimulating factor (rhG-CSF) on hematopoiesis recovery of ICR mice injured by cyclophosphamide (CTX).</p><p><b>METHODS</b>A total of 103 ICR mice were divided into 4 groups, including CTX control (46 mice), HS 6101 (21 mice), rhG-CSF (18 mice) and HS 6101+rhG-CSF (18 mice), respectively. The mouse model of chemotherapy-induced haematopoietic injury was established by CTX intraperitoneal injection at a dose of 100 mg/kg once a day for 3 consecutive days. Single dose of HS 6101 (27 µg/mouse) was injected subcutaneously at 1 hour before the first administration of CTX. One day after the last CTX treatment, 2 µg/mouse of rhG-CSF was injected subcutaneously once a day for 5 consecutive days. The peripheral blood cell counts of the mice were observed once every 2 days. Hematopoietic progenitor cell colony counting and histopathological assessment of bone marrow cells were evaluated in the mice at days 4 and 9 after the first administration of CTX.</p><p><b>RESULTS</b>Both HS 6101 and rhG-CSF alone or in combination, significantly elevated the nadirs of peripheral blood leukocytes and neutrophils, increased the number of bone marrow hematopoietic progenitor cells, and stimulated the hematopoietic cell hyperplasia of bone marrow in the mice treated with CTX. The effect of HS 6101 combined with rhG-CSF was better than that of the drugs used alone.</p><p><b>CONCLUSION</b>The HS 6101 at 27 µg/mouse can significantly promote the recovery of hematopoiesis in ICR mice treated with CTX chemotherapy, and its combination with rhG-CSF shows synergistic effects.</p>


Subject(s)
Animals , Humans , Mice , Bone Marrow , Bone Marrow Cells , Cyclophosphamide , Granulocyte Colony-Stimulating Factor , Hematopoiesis , Hematopoietic Stem Cells , Leukocytes , Mice, Inbred ICR , Neutrophils , Recombinant Proteins
17.
Biomedical and Environmental Sciences ; (12): 263-271, 2015.
Article in English | WPRIM | ID: wpr-264589

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of physical activity (PA) on dyslipidemia and elevated resting heart rate (RHR) in a large-scale cross-sectional study in China.</p><p><b>METHODS</b>We recruited community-based individuals who were 40-60 years old using a cluster sampling method. The PA levels of the participants were classified as low, moderate, or high, using the International Physical Activity Questionnaire. Dyslipidemia was defined as the detection of abnormalities in lipid indicators, and 4 lipid parameters were evaluated using fasting blood samples. Multivariate logistic regression analyses were used to evaluate the associations of PA with dyslipidemia and RHR.</p><p><b>RESULTS</b>A total of 10,321 participants (38.88% men) were included in this study. The percentages of individuals with high, moderate, and low PA levels were 46.5%, 43.9%, and 9.6%, respectively. In both men and women, high PA provided odds ratios of 0.88 [95% confidence interval (CI): 0.83, 0.94] for dyslipidemia and 0.82 (95% CI: 0.73, 0.92) for elevated RHR, compared to participants with low PA.</p><p><b>CONCLUSION</b>Our data suggested that substantial health benefits (related to dyslipidemia and elevated RHR) occurred at higher intensity PA, with greater energy consumption, in middle-aged Chinese people, and particularly in men.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , China , Epidemiology , Cross-Sectional Studies , Dyslipidemias , Epidemiology , Heart Rate , Lipids , Blood , Logistic Models , Motor Activity , Odds Ratio , Risk Factors , Sex Factors
18.
Journal of Experimental Hematology ; (6): 1691-1697, 2014.
Article in Chinese | WPRIM | ID: wpr-340435

ABSTRACT

This study was purposed to investigate the protective effects of lipoprotein HS-6101(6101) on rhesus monkey total body irradiated with 7.0 Gy ⁶⁰Coγ-ray. A total of 30 health adult rhesus monkeys were randomly divided into symptomatic therapy (ST), WR2721 and HS-6101 30, 90 and 270 mg/kg groups (n = 6), the rhesus monkeys of each groups were injected with physiological saline 0.3 ml/kg, WR-2721 30 mg/kg, or HS-6101 30, 90 and 270 µg/kg, respectively. All agents were once intramuscularly injected at 1 hr prior irradiation. General observation, peripheral blood cell counts, colony forming unite assay of bone marrow hemopoietic progenitor cells, and histopathological examination were performed. The results showed that animals in symptomatic therapy group begin to die on the 13(th) day and 4 animals died within 24 days, the average survival time was 18.2 ± 4.3 days; 2 animals in WR-2717 groups died on day 15.8 and day 18.5 post irradiation respectively. 1 animal in HS-6101 270 mg/kg group died on day 35.8, all other animals survived. Nadirs of peripheral blood white blood cells, neutrophils and platelets of animals in HS-6101 treatment groups were significantly higher than those in other 2 groups including ST and WR-2721 groups, and the hemopoietic recovery were also significantly speeding up(P < 0.05 and 0.01). In vitro results showed that HS-6101 obviously promoted 7.0 Gy ⁶⁰Coγ irradiated monkey's bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies (P < 0.05 and 0.01) . Compared with symptomatic therapy and WR-2717 groups, bone marrow histopathological changes in HS-6101 treatment groups showed more active hemopoietic cell proliferation and higher density structure. It is concluded that HS-6101 90 µg/kg treatment can promote the bone marrow recovery of 7.0 Gy ⁶⁰Coγ irradiated monkey, alleviate their animal symptom, simplify the treatment measures and improve the animal survival rate. The HS-6101 shows remarkable radioprotective effects as compared with the currently internationally acknowledged radioprotectant of WR-2721.


Subject(s)
Animals , Amifostine , Blood Cell Count , Blood Platelets , Bone Marrow , Bone Marrow Cells , Hematopoietic Stem Cells , Hematopoietic System , Radiation Effects , Lipoproteins , Pharmacology , Macaca mulatta , Radiation Injuries , Drug Therapy , Survival Rate
19.
China Journal of Chinese Materia Medica ; (24): 2553-2558, 2014.
Article in Chinese | WPRIM | ID: wpr-299774

ABSTRACT

An HPLC-UV method was developed for the determination of total naringenin and total hesperetin in rat plasma after oral administration of Citrus aurantium Immaturus extracts and Zhizi Dahuang decoction. Plasma samples were pretreated with liquid-liquid extraction procedure and acid hydrolysis method was used for converting conjugated naringenin and hesperetin to their respective free forms. Plasma samples were separated on a C18 column (4.6 mm x 150 mm, 5 microm), using 0.1% phosphoric acid and methanol as mobile phase at a flow rate of 1.0 mL x min(-1) with gradient elution. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 16.0 software was used for statistical analysis. Significant differences were observed, the C(max) AUC(0-t) of total naringenin in ZS group was 73.5% and 65.9% higher than those in ZZDHD group, respectively; the C(max), AUC(0-t) of total hesperetin in ZS group was 63.5% and 119.1% higher than those in ZZDHD group, respectively. There is a obvious decrease in C(max) and AUC(0-t) of total naringenin and total hesperetin after compatibility and their pharmacokinetic characteristics changed greatly due to the combination of other herbs. The established method was rapid, sensitive, selective and accurate, and it could be applied in the determination of total naringenin and total hesperetin in rat plasma.


Subject(s)
Animals , Rats , Chromatography, High Pressure Liquid , Citrus , Chemistry , Drug Incompatibility , Drug Interactions , Drugs, Chinese Herbal , Flavanones , Pharmacokinetics , Gardenia , Chemistry , Hesperidin , Pharmacokinetics , Rats, Sprague-Dawley
20.
Acta Pharmaceutica Sinica ; (12): 622-626, 2014.
Article in Chinese | WPRIM | ID: wpr-245037

ABSTRACT

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.


Subject(s)
Animals , Humans , Antineoplastic Agents , Pharmacology , Breast Neoplasms , Metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Heterografts , Hypoxia-Inducible Factor 1 , Metabolism , Lignans , Pharmacology , Mice, Nude
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