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@#Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.
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@#Abstract: Objective To understand the distribution and drug resistance of bacteria in clinical blood culture specimens in Ningxia in recent years, and to provide a basis for the prevention and treatment of bloodstream infection diseases. Methods The blood culture isolation bacteria and drug resistance of Ningxia bacterial resistance monitoring network hospitals from 2018 to 2020 were statistically analyzed by WHONET5.6 software. Results In the past three years, a total of 6 757 strains of bacteria were isolated from blood samples, including 3 697 strains (54.7%) of gram-negative bacteria and 3 060 (45.3%) of gram-positive bacteria. Among the gram-negative bacteria, Escherichia coli (2 074 strains,30.7%), Klebsiella pneumoniae (696 strains), Pseudomonas aeruginosa (139 strains), and Acinetobacter baumannii (121 strains). Among the gram-positive bacteria, coagulase-negative Staphylococcus (1 691 strains,25.0%), Staphylococcus aureus (442 strains), Streptococcus spp. (431 strains), Enterococcus spp. (379 strains). Resistance to Escherichia coli and Klebsiella pneumoniae was 56.6% and 22.6% against third-generation cephalosporins, and resistance to carbapenems was 1.0% and 3.7%, respectively. Pseudomonas aeruginosa and Acinetobacter baumannii were resistant to carbapenems at 9.0%（12/139） and 80.7%（71/121）. Methicillin-resistant Staphylococcus aureus (MRSA) was detected at 26.8%, methicillin-resistant coagulase-negative Staphylococcus was detected at 70%, and no Staphylococcus bacteria resistant to vancomycin and linezolid were found. For three years, only 1 strain of vancomycin-resistant Enterococcus faecalis was detected, and no linezolid-resistant Staphylococcus and Enterococcus were detected. Conclusions Ningxia clinical blood specimen isolates of Escherichia coli, coagulase-negative Staphylococcus, and Klebsiella pneumoniae are more common. Among them, the resistance rate of Escherichia coli and Klebsiella pneumoniae to the third generation of cephalosporins is relatively stable, and the resistance rate to carbapenems is low. Acinetobacter baumannii is highly resistant to carbapenems, and methicillin-resistant Staphylococcus aureus detection rates are on the rise and should be closely monitored.
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Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/β-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/β-catenin signaling pathway in vitro. Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo. Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor β1 (TGF-β1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/β-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-β1-induced EMT and activating the Wnt/β-catenin pathway.
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Humans , Animals , Female , Uterine Diseases , Transforming Growth Factor beta1 , Epithelial-Mesenchymal Transition , Estrogens , Wnt Signaling PathwayABSTRACT
The Ruanjian Sanjie Decoction (RSD) is a traditional Chinese medicine (TCM) formulation consisting of Spica Prunellae, Pseudobulbus Cremastrae Seu Pleiones, Concha Ostreae and Semen Coicis, and widely used as an adjuvant in anti-cancer therapy. The aim of this study was to determine the effects of RSD on the extracellular matrix (ECM) of tumors, and on the efficacy of anti-cancer nano-formulations in a tumor-bearing mouse model. The mice were treated with triptolide encapsulated in PEG-modified liposomes (TP-PEG-LPs), either alone or in combination with RSD. The combination treatment significantly retarded tumor growth relative to the untreated controls, indicating the potent adjuvant effect of RSD in targeted anti-cancer therapy. In addition, RSD also reduced the amount of total collagen and collagen I and increased that of collagen III in the tumor ECM, along with decreasing the expression of the pro-angiogenic VEGF. Finally, even high doses of RSD did not significantly affect the liver and kidney function or body weight, indicating low toxicity.
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Objective To explore the risk factors of systemic inflammatory response syndrome crisis (SIRS) after percutaneous nephrolithotomy (PCNL) in China. Methods Databases of CNKI, CBM, WanFan and VIP were searched to retrieve studies about systemic inflammatory response syndrome after percutaneous nephrolithotomy to October, 2016. Results 18 studies involving 5,323 patients were included. The results of meta-analysis showed that:a) univariate analysis indicated that renal insufficiency [O(R) =2.78, 95%CI (1.96 to 3.95), P = 0.000], preoperative positive urine culture [O(R) = 3.41, 95%CI (1.89 to 6.15), P = 0.000], preoperative routine urine leucocyte positive [O(R) = 3.78, 95%CI (3.02 to 4.72), P = 0.000], diabetes mellitus [O(R) = 2.14, 95%CI (1.33 to 3.45), P = 0.002], pelvic positive urine culture [O(R)= 5.14, 95%CI (2.46 to 10.73), P = 0.000] and operation time ≥120 min [O(R) = 2.31, 95%CI (1.40 to 3.82), P = 0.001] were the risk factors of SIRS; b) multivariate analysis showed that, preoperative positive urine culture [O(R) = 6.83, 95%CI (2.82 to 16.57), P = 0.000], preoperative routine urine leucocyte positive [O(R) = 5.43, 95%CI (3.51 to 8.41), P = 0.000], diabetes mellitus [O(R) = 2.85, 95%CI (1.45 to 5.58), P = 0.002], pelvic positive urine culture [O(R) = 4.30, 95%CI (1.30 to 14.21), P = 0.020] and operation time ≥120 min [O(R) = 2.72, 95%CI (1.62 to 4.59), P = 0.000] were the independent risk factors of MCAT. Conclusion The independent risk factors of SIRS for patients after PCNL are diabetes mellitus, preoperative positive urine culture, preoperative routine urine leucocyte positive, pelvic positive urine culture and operation time. However, due to the quantity and low quality of the included literature, the conclusion needs the support from high quality studies.
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Objective To explore the risk factors of systemic inflammatory response syndrome crisis (SIRS) after percutaneous nephrolithotomy (PCNL) in China. Methods Databases of CNKI, CBM, WanFan and VIP were searched to retrieve studies about systemic inflammatory response syndrome after percutaneous nephrolithotomy to October, 2016. Results 18 studies involving 5,323 patients were included. The results of meta-analysis showed that:a) univariate analysis indicated that renal insufficiency [O(R) =2.78, 95%CI (1.96 to 3.95), P = 0.000], preoperative positive urine culture [O(R) = 3.41, 95%CI (1.89 to 6.15), P = 0.000], preoperative routine urine leucocyte positive [O(R) = 3.78, 95%CI (3.02 to 4.72), P = 0.000], diabetes mellitus [O(R) = 2.14, 95%CI (1.33 to 3.45), P = 0.002], pelvic positive urine culture [O(R)= 5.14, 95%CI (2.46 to 10.73), P = 0.000] and operation time ≥120 min [O(R) = 2.31, 95%CI (1.40 to 3.82), P = 0.001] were the risk factors of SIRS; b) multivariate analysis showed that, preoperative positive urine culture [O(R) = 6.83, 95%CI (2.82 to 16.57), P = 0.000], preoperative routine urine leucocyte positive [O(R) = 5.43, 95%CI (3.51 to 8.41), P = 0.000], diabetes mellitus [O(R) = 2.85, 95%CI (1.45 to 5.58), P = 0.002], pelvic positive urine culture [O(R) = 4.30, 95%CI (1.30 to 14.21), P = 0.020] and operation time ≥120 min [O(R) = 2.72, 95%CI (1.62 to 4.59), P = 0.000] were the independent risk factors of MCAT. Conclusion The independent risk factors of SIRS for patients after PCNL are diabetes mellitus, preoperative positive urine culture, preoperative routine urine leucocyte positive, pelvic positive urine culture and operation time. However, due to the quantity and low quality of the included literature, the conclusion needs the support from high quality studies.
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OBJECTIVES: To study the relation between genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the susceptibility of colorectal cancer. METHODS: We conducted a case-control study with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C genotypes were detected by the PCR-RFLP method. RESULTS: (1) When men and women were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or their alleles were not significantly different between controls and colon cancer or rectal cancer cases. No significant relation was observed between MTHFR C677T or A1298C polymorphisms and colon or rectal cancer susceptibility. (2) Among males, individuals who had MTHFR C677T T/T genotype were at a significantly higher risk of developing colon cancer (age-, residence-, smoking-, alcohol drinking-, tea consumption-adjusted OR=2.15, 95%CI: 1.07-4.33) compared with those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A genotypes were at an increased risk of developing colon cancer (adjusted OR=2.64, 95%CI: 1.20-5.81) compared with those with C677T C allele and A1298C A/A genotypes among males. On the contrary, individuals who had C677T T/T and A1298C A/A genotypes were at an decreased risk of developing rectal cancer (adjusted OR=0.47, 95%CI: 0.22-1.03). CONCLUSIONS: These results in the present study suggested that polymorphisms of the MTHFR C677T could influence susceptibility to colon or rectal cancer and that there was a coordinated effect between MTHFR A1298C A/A and C677T T/T genotypes among males.