1.Research and application of electrospinning drug delivery systems containing traditional Chinese medicine
Shuzhi ZHANG ; Pengfei QU ; Junquan HAN ; Hong WANG
Chinese Journal of Tissue Engineering Research 2024;28(17):2759-2765
BACKGROUND:Electrospun porous nanofiber exhibits excellent properties and designability.It is an effective way to control the release of traditional Chinese medicine and improve the bioavailability to design an advanced drug delivery system,which has a broad application prospect. OBJECTIVE:To review the construction methods of the electrospinning drug delivery system of traditional Chinese medicine and its related research progress in the medical field. METHODS:The literature search was performed in CNKI,PubMed,and Web of Science databases with the search terms"electrospinning,traditional Chinese medicine,drug carrier,drug delivery system,tissue engineering,dressing"in both English and Chinese for articles published from 2013 to 2023.Finally,62 articles were included in this review. RESULTS AND CONCLUSION:(1)The key elements of the electrospinning drug delivery system of Chinese medicine preparation are substrate material,traditional Chinese medicine composition,and drug loading method.(2)The preparation of the electrospinning drug delivery system of Chinese medicine can be carried out according to the application scenario and therapeutic purpose.Firstly,the types of Chinese medicine are selected,then the polymer matrix and solution suitable for them are selected,and finally,the fiber structure is designed according to the drug release requirements and the appropriate drug loading method is adopted.(3)At present,the medicinal agents used are mainly plant Chinese medicine,and there is a lack of systematic research on animal and mineral Chinese medicine.(4)Blended drug loading is the most studied and applied drug loading method,and its drug release characteristics and adaptation scenarios are constantly expanded by optimizing the physicochemical properties of the solution and selecting the diversity of loaded substances.Multilayer fibers with different compositions and properties can be prepared by coaxial,multi-axis,and sequential electrospinning methods,which have broad development prospects.(5)The early application of the electrospinning drug delivery system of Chinese medicine focused on medical dressings according to the antibacterial and hemostatic functions.In recent years,it has been studied in the field of tissue engineering because some components of traditional Chinese medicine can promote cell adhesion,proliferation,and differentiation.(6)At present,the research mainly focuses on the characterization and optimization of loading materials,processes,physicochemical properties,and biological properties,but the research on the mechanism is less.Its clinical application has not been widespread;the adverse reactions in vivo and the interaction between its degradation behavior and drug release behavior are still unknown.(7)Future studies need to consider:We should expand the application of Chinese medicine by improving the physicochemical properties and increasing the purification of Chinese medicine extracts.We need to comprehensively study the therapeutic effects and application mechanisms of Chinese medicine,and clarify the interaction of degradation behavior and drug release behavior,to achieve a more perfect combination and application of Chinese medicine and electrospinning nanofibers under a more accurate mechanism.
2.Multicenter postmarketing clinical study on using pegylated recombinant human gran-ulocyte-colony stimulating factor to prevent chemotherapy-induced neutropenia
Yuankai SHI ; Jianping XU ; Changping WU ; Yan ZHANG ; Junquan YANG ; Tao ZHOU ; Zheng LIU ; Weidong MAO ; Yiping ZHANG ; Wei WANG ; Zhonghe YU ; Lin WU ; Jianhua CHEN ; Juan WANG ; Yonghui AN ; Jianhui CAI ; Ming LIU ; Zhendong CHEN ; Qingshan LI ; Chaoying REN ; Zhiyong YANG ; Baolan LI ; Min ZHAO ; Zhefeng LIU ; Bin LIU
Chinese Journal of Clinical Oncology 2017;44(14):679-684
Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.
3.Curative Effect of Tegafur Gimeracil Oteracil Potassium Capsules Combined with Oxaliplatin in the Treat-ment of Advanced Gastric Cancer and Influence on MMP-9 Expression in Cancer Tissue
Jing ZHANG ; Zijiao ZHOU ; Shuhui YAO ; Junquan YANG ; Yaju FAN ; Yuping ZHU
China Pharmacist 2017;20(11):2015-2017
Objective:To observe the efficacy of Tegafur gimeracil oteracil potassium(Gio) capsules combined with oxaliplatin in the treatment of advanced gastric cancer,and explore its effect on matrix metalloproteinase-9 (MMP-9) expression in cancer tissues. Methods: Totally 120 patients with advanced gastric cancer were randomly divided into the observation group and the control group, and both groups were treated with neoadjuvant chemotherapy for 3 cycles as follows:the observation group was given Gio capsules and oxaliplatin,and the control group was given 5-fluorouracil combined with oxaliplatin. The short term efficacy,adverse reactions and ex-pression of MMP-9 in cancer tissue before and after the chemotherapy were observed in the two groups. Results:After the treatment, the objective response rate in the two groups had no significant difference(P>0.05);the clinical benefit rate of the observation group was significantly higher than that of the control group(P<0.05);the incidence of severe bone marrow suppression and liver and kid-ney dysfunction in the observation group was significantly lower than that in the control group(P<0.05);after the treatment,the pos-itive expression of MMP-9 in the observation group was significantly lower than that in the control group(P<0.05). Conclusion:Gio capsules combined with oxaliplatin can improve the clinical benefit rate of the patients with advanced gastric cancer,and effectively re-duce the expression of MMP-9 in cancer tissue.
4.Effect of 2-deoxy-D-glucoseon on expression of CCR5 and killing function of humanγδT cells in vitro
Lu ZHENG ; Yongqiang CHEN ; Junquan LIU ; Xiaoting Lü ; Juan ZHANG ; Leiqing SUN ; Jing XU ; Zhonghai ZHOU ; Fuxing CHEN
Chinese Journal of Immunology 2016;(1):29-32
Objective:To investigate the effect of 2-deoxy-D-glucose (2-DG) on hunmanγδT cells on the expression of CCR5 and killing function in vitro.Methods:UsingγδT medium to cultivate peripheral blood mononuclear cell( PBMCs) in vitro.After co-cultured with various concentrations of 2-DG for 48 h,the expression of CCR5 and killing activities of γδT cells for each group were detected by flow cytometry and CCK-8 methods.Results: 2-DG could not promote the growth of γδT cells with the increase in concentration from 0 μmol/L to 1.0 μmol/L and decreased thereafter.The certain concentration ( 0-2.0 μmol/L ) of 2-DG could upregulate the expression of CCR5 in dose dependent manner.Besides,at 0.5μmol/L and 1.0μmol/L of 2-DG could increase the ex-pression of CD107a and perforin and have no effect on the granzyme B.Conclusion: Human γδT cells isolated from peripheral blood treated with 2-DG could promote the expression of CCR5 and increase the killing activities at certain concentration in vitro.
5.Effects of DC loaded α-GalCer combined with tumor specific cytotoxic T lymphocytes on the growth of transplanted Heps hepatoma in mice
Peng WANG ; Zhiyong LUAN ; Junquan LIU ; Min HANG ; Jin PAN ; Nanzheng ZHANG
Journal of International Oncology 2016;43(11):806-811
Objective To investigate the effects of dendritic cells (DCs)loading alpha-Galactosylce-ramide (α-GalCer)combined with tumor specific cytotoxic T lymphocytes (CTLs)on the growth of transplanted Heps hepatoma in mice.Methods We induced the augmentation of the DC cells and T lymphocyte derived from the mice bone marrow,and enabled them to be specific CTLs.DC cells loaded α-GalCer in vitro.First we established a Heps liver cancer xenograft model,then divided the model mice into 4 groups by random number table method (n =9):control group (intravenous injection with physiological saline),CTL group,DC loadingα-Galcer group and DC loading α-Galcer combined with CTLs group.After 2 weeks of intervention,we extrac-ted the tumor tissue,weighed the tumor and calculated the inhibition rate of tumor.The expressions of Bax/Bcl-2 cells in groups of transplanted tumor tissues were detected using immunohistochemistry and Western blotting. Results The average tumor weight of CTL group,DC loading α-GalCer group and combined treatment group were (1 .07 ±0.1 5)g,(1 .1 1 ±0.1 7)g,(0.79 ±0.1 4)g,respectively.All of them were lower than that of control group (1 .69 ±0.23)g,with significant differences (t =1 4.1 76,P =0.023;t =1 2.351 ,P =0.034;t =1 8.672,P =0.000).The average tumor weight of combined treatment group was lower than those of the CTL group and DC loading α-GalCer group,with significant differences (t =1 5.236,P =0.01 2;t =1 1 .1 76, P =0.037).Compared to the CTL group (36.69%)and DC loading α-GalCer group (34.32%),the com-bined treatment group had a higher tumor inhibition rate (53.25%;P =0.034,P =0.021 ).Immunohisto-chemical assay showed that the numbers of Bax-positive cells in CTL group,DC loading α-GalCer group and combined treatment group were 35.83 ±0.75,33.67 ±0.82,41 .1 7 ±1 .1 7 respectively,and compared with the control group (21 .67 ±2.1 6),the differences were statistically significant (t =-1 3.789,P =0.002;t =-1 5.1 1 6,P =0.001 ;t =-1 7.452,P =0.000).The numbers of Bax-positive cells in combined treatment group were different with CTL group and DC loading α-GalCer group (t =-7.730,P =0.009;t =-5.872, P =0.01 1 ).The numbers of Bcl-2-positive cells in CTL group,DC loading α-GalCer group and combined treatment group were 30.83 ±0.75,31 .67 ±1 .03,25.00 ±0.89,and compared with the control group (38.67 ±1 .21 ),the differences were statistically significant (t =9.234,P =0.007;t =1 1 .738,P =0.003;t =20.608,P =0.000).The numbers of Bcl-2-positive cells in combined treatment group were different with CTL group and DC loading α-GalCer group (t =1 1 .952,P =0.003;t =1 2.223,P =0.002).Western blot-ting test results showed that the expression levels of Bax in CTL group,DC loading α-GalCer group and com-bined treatment group were 0.46 ±0.01 ,0.42 ±0.03,0.55 ±0.01 ,and compared with the control group (0.31 ±0.02),the differences were statistically significant (t =1 .035,P =0.032;t =1 .1 24,P =0.027;t =1 .425,P =0.01 0).The expression level of Bax in combined treatment group was different with CTL group and DC loading α-GalCer group (t =1 .305,P =0.01 3;t =1 .421 ,P =0.01 0).The positive expressions of Bcl-2 in CTL group,DC loading α-GalCer group and combined treatment group were 0.34 ±0.03,0.33 ± 0.02,0.24 ±0.01 ,and compared with the control group (0.46 ±0.01 ),the differences were statistically sig-nificant (t =-1 .1 23,P =0.025;t =-1 .061 ,P =0.031 ;t =1 .278,P =0.01 4);the positive expression level of Bcl-2 in combined treatment group was different with CTL group and DC loading α-GalCer group (t =1 .1 60,P =0.021 ;t =1 .21 9,P =0.01 5).Conclusion It has synergistic killing effect on transplanted Heps hepatoma in mice using DC loading α-GalCer combined with the tumor specific CTL.
6.Pretemporal transcavernous approach tailored surgery of cavernous sinus tumors: a consecutive series of 31 cases report.
Jun SU ; Xianrui YUAN ; Zijin ZHAO ; Xiangyu WANG ; Junquan WANG ; Kai XIAO ; Haoyu LI ; Chi ZHANG ; Jian YUAN ; Dingyang LIU ; Qing LIU
Chinese Journal of Surgery 2016;54(5):367-371
OBJECTIVETo investigate the indications of the pretemporal transcavernous approach for cavernous sinus tumors resection and design individually tailored surgery according to the extent of tumors and operation requirements.
METHODSA retrospective analysis of clinical data, surgical outcomes and complications in a series of 31 cases with cavernous sinus tumor operated via the individually tailored pretemporal transcavernous approach between May 2012 and September 2015 in Department of Neurosurgery, Xiangya Hospital, Central South University. There were 13 male and 18 female patients, aging from 17 to 67 years with a mean of (41±14) years. The patients included 18 cases of shwannomas, 4 cases of meningiomas, 3 cases of cavernous hemangiomas, 2 cases of invasive pituitary adenomas, 1 case of chordoma, 1 case of chondroma, 1 case of recurrent teratoma, 1 case of metastatic nasopharyngeal carcinoma. The first followed-up visit was on the 3(rd) month after surgery, and if tumor progression or recurrence was observed on MRI, the Gamma knife treatment was recommended, the patient was followed up every 6 months, otherwise the patient was followed up again 6 months later, then, every 12 months.
RESULTSGross total removal of tumors was achieved in 22 cases of 31 patients (71.0%), containing 17 cases of shwannomas, 3 cases of hemangiomas, 1 case of chondroma, 1 case of teratoma; subtotal removal in 6 cases (19.3%), including 3 cases of meningiomas, 1 case of pituitary adenoma, 1 case of chordoma, 1 case of metastatic carcinoma; partial removal in 3 cases (9.7%), comprising 1 case of meningioma, 1 case of recurrent shwannoma, 1 case of recurrent pituitary adenoma. The symptoms of cranial never aggravated in 5 cases, the new postoperative cranial never palsy was observed in 7 cases. There was no surgical mortality, intracranial hematoma, intracranial infection and cerebrospinal fluid leakage cases, ect. Twenty-eight cases were followed up for more than 3 months (3 to 40 months), 1 case of chordoma had tumor progression; the nerve function was restored in 5 cases, among the 12 cases with postoperatively new occurred or deteriorated cranial nerve paralysis.
CONCLUSIONSThe pretemporal transcavernous approach can be used to resect tumors limited in cavernous sinus or tumors simultaneously involving the cavernous sinus and its vicinity areas, it can be individually tailored based on the extent and exposure of the tumor. This approach can improve the surgical results in terms of high tumor resection rate, less complication, is an ideal approach for cavernous sinus tumor resection.
Adenoma ; surgery ; Adolescent ; Adult ; Aged ; Cavernous Sinus ; pathology ; surgery ; Chordoma ; surgery ; Female ; Hemangioma ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Meningioma ; surgery ; Middle Aged ; Neoplasm Recurrence, Local ; Pituitary Neoplasms ; surgery ; Postoperative Period ; Radiosurgery ; Retrospective Studies ; Young Adult
7.Compatibility of osteoblasts with shape memory polyurethane before and after the deformation-complex
Mao YE ; Meng LUO ; Yi ZOU ; Huawei LENG ; Junquan ZHANG
Chinese Journal of Tissue Engineering Research 2015;(52):8450-8454
BACKGROUND:Shape memory polyurethane has good physical and chemical properties and compatibility, but there are relatively few reports on the compatibility of osteoblasts before and after the deformation-complex of the shape memory polyurethane. OBJECTIVE:To observe the compatibility of osteoblasts with shape memory polyurethane before and after the deformation-complex. METHODS: Shape memory polyurethane membranes were prepared, and its stretching-solid-complex was conducted under the experimental environment, to obtain the membrane materials after the deformation-complex. The Sprague-Dawley neonatal rat osteoblasts were inoculated on the shape memory polyurethane membranes before and after the deformation-complex. After 2 hours of culture, the number of adherent cels was counted, and cel spreading was observed; cel proliferation was determined after 1-11 days of culture. RESULTS AND CONCLUSION:The adhesion amount and proliferation activity of osteoblasts on shape memory polyurethane membranes after the deformation-complex were significantly higher than those before the deformation-complex (P < 0.05). The osteoblasts presented fusiform appearance on the shape memory polyurethane membranes after deformation-complex, and cel arrangement showed a clear orientation, but a smal spreading area; while the osteoblasts presented polygonal shape on the shape memory polyurethane membranes before deformation-complex, arranged in no particular direction, and spread largely. These findings show the shape memory polyurethane has better osteoblast compatibility after the deformation-complex.
8.Relationship between expression of PCNA and COX-2 and local recurrence of tumor in early laryngeal cancer with negative surgical margins
Yuman SUN ; Junquan YANG ; Bohai CAO ; Ling ZHANG ; Baoliang WANG ; Meng WU
Chinese Journal of Clinical and Experimental Pathology 2014;(4):408-410,414
Purpose To explore the relationship between expression of PCNA and COX-2 in the early laryngeal cancer with negative surgical margins and the local recurrence of tumor. Methods Totally 63 patients with early laryngeal cancer were enrolled in this stud-y, CO2 laser surgery was adopted as treatment, the expression of PCNA and COX-2 was detected in the resected tumor tissue and surgi-cal margins, and the survival and tumor recurrence were also observed. Results The positive rate of the expression of PCNA and COX-2 in the 63 patients with early laryngeal cancer tumor tissues were 73. 02% and 71. 43%, while that in the cutting edge were 33. 33% and 30. 16%, respectively. The expression of PCNA and COX-2 in tumor tissue and cutting edge were of all positive in 41 cases and 13 cases, and the positive rate was 65. 08% and 20. 63%, respectively. In the all followed-up patients, 17 cases were detected of local recurrence, the recurrence rate was 26. 98%, and the recurrence rate in the patients with PCNA positive was 71. 43%, while in the patients with COX-2 positive was 73. 68% (P<0. 05). The combined detection of PCNA and COX-2 positive recurrence rate was significantly higher than that of single positive (P<0. 05). Conclusion PCNA and COX-2 in the early laryngeal cancer with negative surgical margins are important biological markers for the evaluation of prognosis of laryngeal cancer patients, and to formulate the subse-quent treatment regimen. The combined detection of two proteins is more reliable for postoperative management.
9.The effects of PACAP on CD4+/CD8+ T cells in rats with traumatic brain injury
Rong HUA ; Shanshan MAO ; Yongmei ZHANG ; Fuxing CHEN ; Zhonghai ZHOU ; Junquan LIU
Chinese Journal of Emergency Medicine 2012;21(6):572-576
Objective To observe the effect of pituitary adenylate cyclase activiting polypeptide (PACAP) on traumatic brain injury (TBI) and on tbeCD4+/CD8+ T cell number in blood and spleen of rats.MethodsThe male SD rats were randomly (random number) divided into sham operation group ( n =6),normal saline + TBI group ( n =6) and PACAP + TBI group ( n =6).Right parietal cortical contusion was produced by a weight-dropping method.PACAP was administered intra-cerebroventricularly in a dose of 1 μg/5 μl 20 min before TBI.Brain tissue samples were taken 24 h after trauma.The injured brain tissue of rats was examined by HE stain.The numbers of CD4+/CD8+ T cells in blood and spleen were deteced with flow cytometry.Results Edema,hemorrhage,inflammatory cell infiltration,swollen,degenerated neurons and neurons arrayed disorderly around the injured cortex in hippocampus were found under light microscope.The average numbers of CD4 + T lymphocytes counts in blood and spleen were lower ( P =0.000,P =0.005 ),and number of CD8 + T lymphocytes was higher ( P =0.01 ) in TBI rats group than those in the sham operation group.Micro-injection of PACAP into cerebroventricular attenuated the injury,significantly increased the number of CD4 + T lymphocytes in blood and spleen ( P =0.019,P =0.839),and decreased the number of CD8 + T lymphocytes.ConclusionsPretreatment with PACAP may protect against TBI via influencing periphery T cellular immune function.
10.The betulinic acid-induced human CIK cell cytotoxicity to gastric cancer cell line SGC-7901 and its mechanism
Meimei WANG ; Nanzheng ZHANG ; Fuxing CHEN ; Junquan LIU ; Zhonghai ZHOU ; Juan ZHANG
Chinese Journal of Microbiology and Immunology 2012;32(1):48-53
ObjectiveTo observe the effect of betulinic acid(BetA) on the growth of human cytokine induced killer(CIK) cells and the killing activity of CIK cells on the gastric cancer cells in vitro before and after induced by betulinic acid,explore its mechanism.MethodsPeripheral blood mononuclear cell (PBMC) were separated form the healthy and were induced with various of cytokine to become CIK cells in vitro.CIK cells were collected on the tenth day and were induced with betulinic acid in different concentrations,followed by 48 h,the colorimetric methyl thiazolyl tetrazolium(MTT) method assay the proliferation rate of human CIK cells.Flow cytometry (FCM) was used to detect the expression changes of perforin,granzyme B and CD107a of human CIK cells before and after betulinic acid-induced.Lactate dehydrogenase (LDH) release assay was used to measure the influence on cytotoxic activity of CIK cells induced by betulinic acid against gastric cancer cell line SGC-7901 in vitro.Western blot assay was used to measure the extracellular signal-regulated kinase1/2 (ERK1/2),and adapter proteins SH2-domain containing leukocyte protein of 76KD(SLP-76) and linker for activative of T cells(LAT) expression changes of human CIK cells before and after drug-induced.ResultsBetulinic acid can promote CIK cells growth when the concentration were in 0.08-10 μg/ml,the expression of perforin,granzyme B and CD107a of CIK cells were significantly higher than control group(P<0.05) when the concentration of betulinic acid were in 0.3 μg/ml.In the meanwhile,the cytotoxic activity of CIK cells in vitro against gastric cancer cell line SGC-7901 were also remarkably higher than the control group (P<0.05).The expression of SLP-76,LAT and ERK1/2 were significantly increased to a certain extent than the control group( P<0.05 ),when CIK cells were treated with betulinic acid.ConclusionThese results suggest that betulinic acid can promote CIK cells growth in some concentrations and increase the cytotoxic activity of CIK cells against gastric cancer cell line SGC-7901,its mechanism may related with two factors,on the one hand,enhancing the activity of SLP-76,LAT and ERK1/2,on the other hand,increasing the expression of perforin,granzyme B and CD107a on the surface of CIK cells.

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