Objective To study the potential of a bioderived material combined with Pluronic F-127 in vitro as a delivery vehicle for WO-1 in the bone repair therapy. Methods Bio-derived materials were fabricated and loaded with WO-1 by Pluronic F-127. Micromorphology and porosity were detected by the scanning electron microscope and the digital image analysis system respectively. The WO-1 release from the system in vitro was studied by the high performance liquid chromatography. Results Bio-derived material-WO-1 drug delivery systems were created with the interconnected pore network. Theporosity and pore size of the system were 55% and 522.43±16.75 μm respectively, compared with those of bio-derived materials, which were 75% and 623.67±12.31 μm respectively. And the main composition of the system was HA. The in vitrorelease kinetics of WO-1 revealedthat an effective therapeutic concentration(0.2-0.8 μg/ml) of WO-1 was maintained for 6 days after a high initial burst release. Conclusion The bio-derived material-WO-1 drug delivery system can be used in the bone repair therapy. However, the in vivostudy on it is still needed.
Objective To develop the plastic nano-hydroxyapatite (nano-HA)/poly (3-hydroxybutyrate-hydroxyvalerate) polyethylene glycol(PHBV-PEG) gentamicin (GM) drug delivery system(DDS)(nano-HA/PHBV-PEG-GM-DDS) for treating osteomyelitis and find its releasing character in vivo. Methods The plastic nano-HA/PHBV- PEG-GM-DDS was prepared using nanoHAas the core carrier of GM, nano-HA with PHBV and PEG as coating and plastic fibrin glue(FG) as microsphere scaffold. The morphological features of nano-HA,drug loaded nano-HA and drug loaded nano-HA/PHBVPEG microsphere were examined by electron microscope.The GM concentration in blood, cortex bone and cancellousbone was detected at 12 different time points by the method of K-B after the plastic nano-HA/PHBV-PEGGM-DDS was implanted into the femora of 36 rabbits. Its GM releasing character was assayed in vivo. Results Nano-HA was similar to a blackjack, and its length was less than 60 nm. Drug loaded nano-HA appeared natural crystal condensate, of which surface adsorbed massive GM. The average grain diameter was 200.5 nm. Drug loaded nanoHA/PHBV-PEG microsphere had a shrinkable porous structure, of which surface configuration was consistent. The average grain diameter was 34.5 μm. The GM concentration and the antibacterial annulus was in the linear correlation. The correlation coefficient was 0.998. In cortex and cancellous bone tissue, the GM concentration was about 95.50±16.50 μg/ml and 80.20±13.80 μg/ml from the plastic nano-HA/PHBV-PEG-GM-DDS on the 1st day, then decreased gradually. After 56 days of operation, the GM concentration still exceeded the minimum inhibitory concentrationfor the staphylococcus aureus, but the peak level of serum GM concentration wasunder the nephrotoxicity concentration. Conclusion Plastic nano-HA/PHBV-PEG-GM-DDS was a good drug delivery system with sustained antibiotic effect in vivo. It was an effective method for the treatment of osteomyelitis.
To develop the chitosan /polyethylene glycols succinate (CH/PEG-SA) mitomycin C (MMC) film drug del ivery system and its release effect in vitro. Methods MMC loading in composite films was determined using a UV-visible spectrophotometer. Freeze-dried films (90 mg) were immersed in 1 mL PBS buffer (pH 7.4). The concentrations ofMMC releasing in vitro were calculated refer to the standard curve of relationship between the concentrations of MMC and the value of UV-visible spectrophotometer. The curve of the concentrations of MMC releasing from the films in vitro was drawn at different time. The relationship between the films, structure and the drug releasing was revealed. Results The films showed swell ing without brittleness. The equation of Linear Regression was y=0.593x3– 2.563x2 +25.944x – 0.236 (R2=1.000). The film had a good drug del ivery capabil ity. The samples weighing 20 mg were soaked into the l iquid of PBS, the releasing concentrations of MMC were 14.961 6 μg/mL at 12 days, 14.482 4 μg/mL at 18 days and 11.409 2 μg/mL at 32 days, which was higher than ID50 of MMC (10.471 3 μg/L) to fibroblast. Then MMC was released at a low concentration. The releasing concentrations of MMC was 0.179 3 μg/ mL at 60 days until being del ivered completely. Conclusion The flexibil ity is enhanced , and the mechanical function is improved, so that there is better nature of membrane. The initial burst is avoided more effectively, and the drug releasing would be maintained for a certain time.
Objective To investigate the regulative characterisitics of growth factors on proliferation of retinal pigment epithelial (RPE) cells in vitro. Methods Primary culture and subculture of RPE cells were establised in vitro Tumor.necrosis factor-alpha;(TNF-alpha;),interleukin-1beta;(IL-1beta;) and basic fibroblast growth factor (bFGF) in different concentrations were added to the RPE cells.3 H-thymidine(3 H-TdR) incorporation and a hemocytometer measured DNA synthesis and cell number separately. Results After RPE cells were separately treated with TNF-alpha;,IL-1beta; and bFGF,DNA synthesis was increased by 2.74,2.66 and 1.69 folds and cell number was increased by 54%,22% and 7amp; (Plt;0.05) respectively. When two growth factors were combined (TNF-alpha;+bFGF, IL-1beta;+bFGF),3.14,2.84 and 2.57 folds increased DNA synthesis significantly in each group (Plt;0.05). Compared with value by effect of two growth factors,the combination effect of three growth factors (TNF-alpha;+IL-1beta;+bFGF) was still ber (Plt;0.05). Conclusion The synergism of growth factors in their action might be one of the important roles in modulating the proliferation of RPE cells. (Chin J Ocul Fundus Dis,1998,14:95-97)
Medicine is a very important health resource in China. Although numerous efforts are paid to pre-marketed medicines, little is done to address practical problems in marketed medicines. The rational use and allocation of marketed medicines remain a major concern for decision-makers in China. It has been recognized that economic evaluation is an efficient tool for prioritizing the choice, and optimizing the use of medicines. This paper has explored the methods and principles for conducting economic evaluation of marketed medicines. Different strategies will be adopted for economic evidence for marketed medicines in terms of adequacy and sufficiency.However, a standard study pathway should be applied in economic evaluation of marketed medicines. Besides, the aspects for developing economic framework and the methods for reviewing existing economic evidence are also introduced in this paper, particularly, for marketed medicines within the same therapeutic group.
ObjectiveTo investigate the risk of myocarditis caused by immune checkpoint inhibitors (ICI). MethodsThe adverse reaction (ADR) reports on myocarditis caused by atelizumab, duvalizumab, pabolizumab, and navulizumab were downloaded from the FDA Adverse Event Reporting System (FAERS) from January 1, 2014 to September 30, 2022. The relevant analysis was conducted on the gender, age, medication dosage, and occurrence time of ICI related myocarditis patients. ResultsA total of 1 892 reports of myocarditis induced by ICI were included. The proportion of myocarditis caused by ICI was higher in males than in females (1.9∶1). The incidence of myocarditis in patients with basic diseases such as diabetes and heart disease, and in the age group 65-75 was relatively high. The incidence of myocarditis caused by navulizumab was high within 30 days with the use of conventional doses, and that of the other three drugs were high within 31 to 90 days. And the incidence of myocarditis is higher when used in combination than when used alone. ConclusionDifferent varieties of ICI can lead to the occurrence of myocarditis, and male, elderly, underlying diseases, and combination therapy may be risk factors for myocarditis caused by ICI.
Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which seriously threatens the vision of patients. The pathogenesis of DR Is complex and involves many pathophysiological processes. At present, the treatment methods for DR Mainly include panretinal laser photocoagulation, vitrectomy and vitreous cavity injection, etc. However, each treatment method has certain limitations. In recent years, remarkable progress has been made in the field of drug treatment of DR, especially in anti-vascular endothelial growth factor drugs, anti-inflammatory drugs, anti-oxidative stress damage drugs, neuroprotective agents, gene therapy and stem cell therapy. These drugs not only improve the effectiveness of treatment, but also expand the range of treatment options. In addition, by carrying DR Treatment drugs on carriers such as nanoparticles, hydrogels and photosensitive materials, continuous and efficient release of drugs in the eye is achieved, thereby extending the time interval of administration and reducing the need for frequent treatment of patients. In the future, based on biomarker detection technology, it is expected to promote the development of personalized and precise treatment, which can develop more accurate treatment plans for patients and improve the efficacy.
ObjectiveTo investigate the condensate pollution in the pipeline of severe pneumonia patients undergoing mechanical ventilation.MethodsFrom January 2017 to January 2019, 120 patients with severe pneumonia treated by mechanical ventilation in our hospital were collected continuously. The lower respiratory tract secretions were collected for bacteriological examination. At the same time, the condensed water in the ventilator exhaust pipe was collected for bacteriological examination at 4, 8, 12, 16, 20 and 24 hours after tracheal intubation and mechanical ventilation. The bacterial contamination in the condensed water at different time points was analyzed and separated from the lower respiratory tract. The consistency of bacteria in secretion and drug resistance analysis of bacterial contamination in condensate water were carried out.ResultsOf the 120 patients with severe pneumonia after mechanical ventilation, isolates were cultured in the lower respiratory tract secretions of 102 patients. One strain was cultured in 88 cases, two strains were cultured in 10 cases, and three strains were cultured in 4 cases. The isolates were mainly Gram-negative bacteria (57.5%) and Gram-positive bacteria (42.5%). The most common isolates were Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter baumannii. The contamination rate of condensate water was 5.0% at 4 hours, 37.5% at 8 hours, 60.0% at 12 hours, 76.7% at 16 hours, 95.0% at 20 hours, and 100.0% at 24 hours, respectively. The bacterial contamination rate in condensate water at different time points was statistically significant (P=0.000). The pollution rate at 4 hours was significantly lower than that at 8 hours (P=0.000). Gram-negative bacteria accounted for 57.5% and Gram-positive bacteria accounted for 42.5%. The most common isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. The consistency of bacteria in lower respiratory tract and condensate water was 83.3% in severe pneumonia patients undergoing mechanical ventilation. The overall resistance of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus was higher, but the resistance to imipenem/cilastatin was lower.ConclusionsThe bacterial contamination in the condensate of patients with severe pneumonia during mechanical ventilation is serious. The pollution rate is low within 4 hours. It is consistent with the bacterial contamination in lower respiratory tract and the bacterial resistance is high.
ObjectiveTo study the distributions of virulence genes of Klebsiella pneumoniae (KP) and the distribution of hypervirulent KP (HvKP), and assess the performance of a single gene to predict HvKP.MethodsPolymerase chain reaction (PCR) method was used to analyze 12 virulence-related genes (entB, irp2, iroN, iucA, mrkD, fimH, c-rmpA, p-rmpA2, p-rmpA, wzy-K1, allS and peg-344) and drug-resistance gene blaKPC among 376 clinical KP strains collected from January 2016 to December 2018. Sequence types (ST) of KP were determined after sequencing and comparison, following the detection of 7 house-keeping genes (gapA, infB, mdh, pgi, phoE, rpoB and tonB) by PCR method. Statistical analyses were made for the distributions of virulence genes of KP and the distribution of HvKP with GraphPad Prism 8 software.ResultsAmong the 376 KP strains, the positive rates of entB, irp2, iroN, iucA, mrkD, fimH, c-rmpA, p-rmpA2, p-rmpA, wzy-K1, allS and peg-344 were 100.0%, 76.9%, 22.1%, 28.2%, 97.6%, 97.1%, 1.6%, 24.5%, 21.0%, 7.4%, 4.8% and 31.6%, respectively. The positive rates of the aforementioned virulence genes in the blaKPC-positive group (n=167) were 100.0%, 94.0%, 7.2%, 16.8%, 97.0%, 96.4%, 0.0%, 15.0%, 6.6%, 0.0%, 0.0% and 21.0%, respectively, and those in the blaKPC-negative group (n=209) were 100.0%, 63.2%, 34.0%, 37.3%, 98.1%, 97.6%, 2.9%, 32.1%, 32.5%, 13.4%, 8.6% and 40.2%, respectively; there was no statistically significant difference in entB, mrkD or fimH between the two groups (P>0.05), the positive rate of irp2 was higher in the blaKPC-positive group than that in the blaKPC-negative group (P<0.05), and the positive rates of the rest virulence-related genes were lower in the blaKPC-positive group than those in the blaKPC-negative group (P<0.05). The rate of HvKP in the blaKPC-negative group was higher than that in the blaKPC-positive group (38.3% vs. 18.0%, P<0.05). As a marker of HvKP, iucA showed high sensitivity and specificity (90.9% and 97.7%), followed by p-rmpA2 (83.6% and 100.0%) and iroN (73.6% and 99.2%). ST11 accounted for 87.4% in the blaKPC-positive group, while ST23, ST20, ST54 and ST29 were the four primary types in the blaKPC-negative group, accounting for 23.4% totally.ConclusionsDifferent virulence genes mean different distributions in KP. blaKPC-negative KP is more virulent than blaKPC-positive KP. iucA and p-rmpA2 could serve as good predicators of HvKP. Armed with extreme virulence and drug-resistance, blaKPC-positive HvKP is of great clinical concern.