1.Multicenter study on the efficacy and safety of 3 kinds of Cephalosporin for injection from centralized procurement or non-centralized procurement
Lu LIU ; Cangsang SONG ; Xingde LI ; Yuqin DENG ; Panpan MAO ; Hanshu ZHANG ; Yanzhen DONG ; Yaoyao CHENG
China Pharmacy 2024;35(7):825-830
OBJECTIVE To compare the efficacy and safety of Cefazolin sodium for injection, Cefuroxime sodium for injection, and Ceftazidime for injection from nationally organized centralized drug procurement (hereinafter referred to as “centralized procurement”) and non-centralized procurement in patients with bacterial infection. METHODS The case data of hospitalized patients who had used 3 kinds of Cephalosporins for injection from centralized procurement or non-centralized procurement in the treatment of bacterial infections were retrospectively collected from 19 medical institutions in Kunming from January 2020 to September 2022. After balancing the baseline differences between the groups with the propensity score matching method, the effectiveness and safety differences of 3 kinds of Cephalosporins for injection from centralized procurement or non- centralized procurement were compared respectively. RESULTS After balancing the baseline differences among the groups, 394 cases in each group of Cefazolin sodium for injection from centralized procurement or non-centralized procurement, 472 cases in each group of Cefuroxime sodium for injection from centralized procurement or non-centralized procurement, 504 cases in group of Ceftazidime for injection from centralized procurement and 590 cases in group of non-centralized procurement were included in the analysis. In terms of effectiveness, there were no significant differences in clinical response rate, 72 h response rate, bacterial clearance rate, and the recovery rate of body temperature, white blood cell count, neutrophil count, neutrophil percentage, C-reactive protein, procalcitonin recovery between the centralized procurement group and non-centralized procurement group of Cefazolin sodium for injection and Cefuroxime sodium for injection (P>0.05). The proportion of patients in centralized procurement group of Ceftazidime for injection with C-reactive protein restored to normal reference range was significantly higher than that in non-centralized procurement group (46.9% vs. 27.9%, P<0.05), but there were no statistically significant differences in other effectiveness indicators among groups (P>0.05). In terms of safety, there was no statistical difference in the incidence of adverse drug reactions between centralized procurement group and non-centralized procurement group of 3 kinds of Cephalosporins for injection (P>0.05); the incidence of platelet count reduction in centralized procurement group of Cefazolin sodium for injection was significantly higher than non-centralized procurement group (20.7% vs. 7.1%, P<0.05), the incidence of eosinophilia elevation in centralized procurement group of Ceftazidime for injection was significantly higher than non-centralized procurement group (5.3% vs. 1.9%, P<0.05). In addition, there was no statistically significant difference in the abnormal rates of other laboratory indicators among the three types of injection Cephalosporins (P> 0.05). CONCLUSIONS The efficacy of 3 kinds of Cephalosporin for injection from centralized procurement is not inferior to non- centralized procurement varieties, and the safety is equivalent to that of non-centralized procurement varieties.
2.Evaluation of the safety and efficacy of mitomycin C-perfluorooctyl bromide liposome nanoparticles in the treatment of human pterygium fibroblasts
Tao LI ; Lingshan LIAO ; Shenglan ZHU ; Juan TANG ; Xiaoli WU ; Qilin FANG ; Ying LI ; Biao LI ; Qin TIAN ; Junmei WAN ; Yi YANG ; Yueyue TAN ; Jiaqian LI ; Juan DU ; Yan ZHOU ; Dan ZHANG ; Xingde LIU
Recent Advances in Ophthalmology 2024;44(2):100-105
Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)%and(34.27±2.04)%,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)%in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)%]was significantly higher than that in the MMC group[(51.62±3.28)%].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P<0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.
3.Safety and efficacy of mitomycin nanoparticles in inhibiting scar proliferation after glaucoma filtration surgery
Ying LI ; Juan TANG ; Changfen LI ; Qilin FANG ; Xingde LIU ; Dan ZHANG ; Tingting ZHANG ; Xiaoli WU ; Tao LI
International Eye Science 2024;24(11):1708-1714
AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.
4.Serum Metabolomics Analysis of Baicalein for Prevention and Treatment of Radiation-Induced Intestinal Damage in Mice Based on GC-MS
Yejin ZHU ; Xinping WANG ; Qianyi WANG ; Jun HE ; Xingde ZHANG ; Chao JIANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(7):702-709
OBJECTIVE To investigate the changes in serum metabolites of mice with radiation-induced intestinal injury under the intervention of baicalein and the changing characteristics of endogenous biological small molecules during the process of baicalein's participation in the prevention and treatment of radiation-induced intestinal injury through the metabolomics method based on GC-MS technology,in order to explore the potential regulatory mechanism of baicalein.METHODS A mouse radioactive intestinal injury model was established and randomly divided into normal control group,model group,low-dose baicalein group and high-dose baica-lein group.Baicalein was administered by gavage.Gas chromatography-mass spectrometry(GC-MS)technology was used to analyze the serum samples of mice in each group,and differential metabolites were screened through partial least squares-discriminant analysis(PLS-DA).Potential metabolic pathways were analyzed with MetaboAnalyst.RESULTS The pathological sections of mouse intesti-nal tissue showed that the high-dose and low-dose baicalein groups had a certain protective effect on radiation-induced intestinal dam-age.Metabolomic analysis showed that there were significant differences in the metabolic profiles of the blank control group,model group,low-dose and high-dose baicalein administration groups.After intragastric administration of baicalein,the endogenous metabo-lites in mice with radiation intestinal injury tended to normalize.The study screened out a total of 11 potential metabolic markers and 5 related metabolic pathways,among which pathways related to glucose metabolism,glutathione pathway,and ammonia metabolism were particularly significant.CONCLUSION Baicalein has a certain preventive and therapeutic effect on radiation-induced intestinal in-jury;baicalein participates in glucose metabolism and glutathione metabolism,and improving the endogenous substance disorder caused by radiation is its potential mechanism of action.
5.Analysis of predictive accuracy and its influential factors of three individualized administration tools for tacroli-mus after kidney transplantation
Guohui WANG ; Xingde LI ; Ya PAN ; Panpan MAO ; Hanshu ZHANG ; Xuejiao MA ; Cangsang SONG
China Pharmacy 2024;35(24):3023-3028
OBJECTIVE To evaluate the accuracy of three individualized drug delivery tools, i.e. JPKD, SmartDose and NextDose, in predicting tacrolimus dose and blood concentration after kidney transplantation, and analyze the influential factors of prediction accuracy. METHODS The clinical data of adult hospitalized patients treated with tacrolimus after kidney transplantation from January 2021 to June 2023 were retrospectively collected. Three individualized dosing tools, i.e. JPKD, SmartDose and NextDose, were used to predict the dose and plasma concentration of tacrolimus. The absolute prediction error (APE) and prediction error (PE) between the measured value and the predicted value, and prediction success rate were calculated (APE<30% indicating a good forecast). Pearson assay or Spearman assay was used to analyze the correlation between the predicted dosage and actual dosage, as well as the predicted and measured blood concentration values using three software; univariate analysis was used to investigate the influential factors for prediction accuracy of JPKD, SmartDose and NextDose. RESULTS A total of 110 hospitalized patients were included in this study, and tacrolimus doses and plasma concentrations were monitored. The predicted doses of JPKD, SmartDose and NextDose were (2.0±0.7), (2.7±1.9), (1.8±0.8) mg, their measured value was (1.9±0.6) mg, and the correlation coefficients between the predicted values and the measured value were 0.841, 0.450, 0.247 (P<0.001); the median APEs were 6.00%, 52.07% and 30.40%, and the median PEs were 5.00%, 18.50% and -3.50%; the prediction success rates were 98.45%, 30.05% and 49.22%. The predicted values of tacrolimus concentrations using JPKD, SmartDose, NextDose were (6.74±3.36), (6.93±5.02), 9.00(5.80±12.60) ng/mL, the measured value was 8.64(7.11,9.77) ng/mL, and the correlation coefficients between the predicted values and the measured value were 0.997 (P<0.001), -0.066 (P=0.360), 0.920 (P<0.001). The median APEs were 5.54%, 45.91% and 35.56%, and PEs were -4.94% (median), -17.050% (median) and 36.93% (average value); the prediction success rates were 97.93%, 32.64% and 37.31%. Univariate analysis showed that the dosage, blood concentration, body weight, transplantation time and others were related to the prediction accuracy (P<0.05). CONCLUSIONS The good prediction rates of tacrolimus dose and blood concentration in kidney transplant patients using three personalized drug delivery tools, from high to low, are JPKD, NextDose, and SmartDose, suggesting that JPKD can be prioritized in clinical use.
6.Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury
Ganchun ZHANG ; Wen LIU ; Xinli SONG ; Xingde LIU ; Wanfen SHU ; Qin QIN ; Hongxin WANG
China Pharmacy 2023;34(17):2063-2068
OBJECTIVE To study the improvement effects of Shaoyao gancao decoction (SGD) on acute lung injury (ALI) in rats and its effects on the intestinal flora. METHODS Sixty SD rats were randomly divided into normal group (CON group, normal saline), model group (MOD group, normal saline), positive control group (DEX group, 5 mg/kg dexamethasone), SGD low-dose, medium-dose and high-dose groups (SGD-L, SGD-M, SGD-H groups, 5.8, 11.6, 23.2 g/kg, calculated by crude drug), with 10 rats in each group. Each group was given relevant medicine 10 mL/kg intragastrically, for 7 consecutive days. Thirty minutes after the last administration, CON group was given constant volume of normal saline via airway infusion, and other groups were given lipopolysaccharide (5 mg/kg) via airway infusion to induce ALI model. After 12 hours of modeling, the lung tissue wet/dry weight ratio was calculated, and the contents of interleukin 1β (IL-1β), IL-6 and tumor necrosis factor α(TNF-α) in rat bronchial alveolar lavage fluid (BALF) were all detected; the pathological changes of lung tissue were observed after hematoxylin-eosin staining. The intestinal flora of rat feces was analyzed by 16S rRNA sequencing technology, and the correlation of differential bacteria genera with inflammatory factors was also analyzed. RESULTS Compared with MOD group, the infiltration of inflammatory cells in the lung tissue of rats in each SGD dose group was decreased, and the thickening of alveolar septum and pulmonary edema improved; lung tissue wet/dry weight ratio, the levels of IL-1β, IL-6 and TNF-α in BALF significantly decreased (P<0.05 or P<0.01). SGD (low dose) could improve the intestinal flora disorder in ALI rats, restore the diversity and richness of intestinal flora, regulate the structure of flora, reduce the abundance of Lactobacillus, Streptococcus and Escherichia-Shigella, and increase the abundance of Firmicutes, Lachnospira, Ruminococcus, Clostridia,Dubosiella and Akkermansia. Through correlation analysis, it was found that the relative abundance of Lactobacillus, Streptococcus and Escherichia-Shigella was positively related to the levels of inflammatory factor IL-1β, IL-6 and TNF-α (P<0.05 or P<0.01). The relative abundance of Lachnospira, Dubosiella, Firmicutes was significantly negatively correlated with the levels of inflammatory factors mentioned above (P<0.05 or P<0.01). CONCLUSIONS SGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.
7.Correlation Between SLCO1B3 Gene Polymorphism and Plasma Concentration of Tacrolimus in Renal Transplant Recipients
Hanshu ZHANG ; Cangsang SONG ; Xingde LI ; Jinwei YANG ; Panpan MAO ; Guohui WANG ; Xuejiao MA
Chinese Journal of Modern Applied Pharmacy 2023;40(23):3297-3300
OBJECTIVE To explore the correlation between SLCO1B3 gene polymorphisms and early postoperative tacrolimus concentrations in renal transplant recipients. METHODS A total of 68 patients who underwent kidney transplantation in the First Hospital of Kunming were selected, tacrolimus plasma concentrations were monitored by chemoluminescence, CYP3A5*3, SLCO1B3 T334G and G699A gene polymorphisms were detected by polymerase chain reaction, and genotyping was performed to analyze the correlation between each genotype and tacrolimus plasma concentrations. RESULTS Different genotypes of CYP3A5*3 had significant effects on postoperative tacrolimus plasma concentration and standardized plasma concentration(P<0.05), and different genotypes of SLCO1B3 T334G and G699A gene loci had no significant effect on postoperative tacrolimus plasma concentration and standardized plasma concentration. CONCLUSION Compared with CYP3A5*3/*3 genotype, CYP3A5*1 allele carriers need to reach the same tacrolimus concentration to increase tacrolimus dose. SLCO1B3 T334G and G699A gene polymorphisms has no effect on tacrolimus plasma concentration in the early stage after renal transplantation.
8.Research progress on the role of miR-155 in rejection of organ transplantation
Yang ZHANG ; Jinwei YANG ; Xingde LI ; Xuejiao MA ; Hanshu ZHANG ; Cangsang SONG
Organ Transplantation 2022;13(5):666-
Rejection has constantly been an unresolved challenge in the field of organ transplantation. The research on the mechanism of rejection plays a significant role in improving the efficacy of organ transplantation and enhancing the survival rate of graft. The innate and specific immune responses of the human body jointly participate in the graft rejection, leading to graft injury. In recent years, multiple researchers have conducted in-depth studies on the mechanism underlying the role of microRNA (miR) in regulating rejection. Among them, miR-155 has been widely considered as a key factor involved in immune regulation. The expression level and functional status of miR-155 may be intimately associated with the occurrence of rejection, which may become a new target for overcoming rejection. In this article, relevant studies on the role of miR-155 in regulating key immune cells in innate and specific immune responses were reviewed, aiming to provide novel ideas for the development of new immunosuppressants and rejection therapy.
9.Study on the “property-effect”correlation material basis of Taohe chengqi decoction in removing blood stasis and purging heat
Wanfen SHU ; Wen LIU ; Xinli SONG ; Xingde LIU ; Ganchun ZHANG ; Qin QIN ; Hongxin WANG
China Pharmacy 2022;33(22):2706-2711
OBJECTIVE To study the “property-effect” correlation material basis of the classic famous prescription Taohe chengqi decoction in removing blood stasis and purging heat. METHODS The rat model of blood storage syndrome was established to investigate the effects of Taohe chengqi decoction (17.29 g/kg) and its property grouping components [bitter-cold property group (Rhei Radix et Rhizoma+Natrii Sulfas) 9.43 g/kg, pungent-warm property group (Cinnamomi Ramulus+Persicae Semen) 4.71 g/kg, sweet-flat property group (Glycyrrhizae Radix et Rhizoma) 3.14 g/kg] on coagulation indexes (prothrombin time, prothrombin activity, activated partial thrombin time, fibrinogen, thrombin time and endothelin-1) and inflammation indicators (C- reactive protein, tumor necrosis factor-α and superoxide dismutase) in rats. On the basis of determining the dominant property groups, ultra-performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry was used to identify the components. The molecular docking was performed, and the components with binding energy ≤-5.0 kcal/mol were selected as the basis of “property-effect” correlation material basis. RESULTS Taohe chengqi decoction total prescription group and pungent-warm property group could significantly improve the coagulation indexes of model rats (P<0.05 or P<0.01), and the total prescription group and bitter-cold property group could significantly improve the inflammation indexes of model rats (P<0.05 or P<0.01). The pungent-warm property group was the dominant property group for removing blood stasis,and the bitter-cold property group was the dominant property group for purging heat. Thirty-two and thirty-five components were identified from the pungent-warm property group and bitter-cold property group, respectively. With binding energy ≤-5.0 kcal/mol, there were 10 components (abscisic acid, 3,4-dihydroxypheny- lethanol, procyanidin B1, etc.) in the pungent-warm property group and 13 components (baicalein, aloe-emodin, demethylwedelolactone, etc.) in the bitter-cold property group. CONCLUSIONS Taohe chengqi decoction has the effect of removing blood stasis and purging heat, and its material basis comes from pungent-warm property group (Cinnamomi Ramulus, Persicae Semen) and bitter-cold property group (Rhei Radix et Rhizoma, Natrii Sulfas) respectively.
10.Research progress on the gene polymorphism of tacrolimus transporter in organ transplantation
Hanshu ZHANG ; Cangsang SONG ; Yang ZHANG ; Xingde LI
Organ Transplantation 2021;12(4):496-
Tacrolimus (Tac) is a commonly used immunosuppressant after organ transplantation, which has high immunosuppressive efficacy. However, the pharmacokinetics of Tac significantly differ among individuals, and gene polymorphism is the main influencing factor. In recent years, the gene polymorphism of drug transporter has become a novel research hotspot. Nevertheless, the effect of the gene polymorphism of transporter on Tac pharmacokinetics remains controversial. Consequently, the correlation between the gene polymorphism of transporter and Tac blood concentration plays a significant role in guiding Tac-based individualized immunosuppressive therapy. In this article, the research progresses on the gene polymorphism of adenosine triphosphate-binding cassette (ABC) transporter and solute carrier (SLC) transporter in organ transplantation was reviewed. The correlation between the gene polymorphism of transporter and Tac blood concentration was summarized, aiming to provide reference for Tac-based individualized therapy.


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