Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis / 中国中药杂志

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

Study on insecticide resistance of Culex pipiens pallens in southwest region of Shandong Province / 中国血吸虫病防治杂志

Objective To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. Methods The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. Results The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43–557.54, 118.17–445.33, 6.44–19.00, 2.37–8.10, and 0.88–2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 – 456.95, 190.56 – 292.37, 123.32 – 319.24, and 192.31 – 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87–108.36) . Conclusions After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Chigger Mite (Acari: Trombiculidae) Survey of Rodents in Shandong Province, Northern China

Chigger mites are parasites of rodents and other vertebrates, invertebrates, and other arthropods, and are the only vectors of scrub typhus, in addition to other zoonoses. Therefore, investigating their distribution, diversity, and seasonal abundance is important for public health. Rodent surveillance was conducted at 6 districts in Shandong Province, northern China (114–112°E, 34–38°N), from January to December 2011. Overall, 225/286 (78.7%) rodents captured were infested with chigger mites. A total of 451 chigger mites were identified as belonging to 5 most commonly collected species and 3 genera in 1 family. Leptotrombidium scutellare and Leptotrombidium intermedia were the most commonly collected chigger mites. L. scutellare (66.2%, 36.7%, and 49.0%) was the most frequently collected chigger mite from Apodemus agrarius, Rattus norvegicus, and Microtus fortis, respectively, whereas L. intermedia (61.5% and 63.2%) was the most frequently collected chigger mite from Cricetulus triton and Mus musculus, respectively. This study demonstrated a relatively high prevalence of chigger mites that varied seasonally in Shandong Province, China.

The Correlation between DDVP Resistance of Culex pipiens pattens and Esterase Activity / 中国寄生虫学与寄生虫病杂志

Objective To detect the resistance index and esterase activity of each generation of DDVP-resistant Culex mosquitoes and analyze the relationship between insecticide resistance and esterase. Methods WHO bioassay and micro-plate measurement were used for the detection. Results The resistance index increased to 12.17 after 43 generations' insecticide selection compared to 1.00 as sensitive isolate. The nonspecific esterase(NSE) activity of the mosquitoes became strengthened with the extension of the generations, and the individual frequency of those with OD values no less than 0.9 increased gradually, consistent basically to the bioassay. The AChE average inhibition rate decreased with the extended generation and increased resistance, and the individual frequency of those with inhibition rate less than 30% became strengthened with the extension of generations, showing a positive correlation. Conclusion The activity of NSE and AChE shows a correlation with DDVP resistance.