The molecular epidemiological characteristics of 1,4,[5],12:i:-Salmonella in Jiangsu Province were analyzed through whole genome sequencing(WGS).The distribution characteristics of related genes were obtained on the basis of anno-tated drug-resistant genes and plasmid types in the whole genome.Analysis of the molecular epidemiological characteristics of strains with cgMLST revealed possible modes of transmission of quinolone resistance in 1,4,[5],12:i:-Salmonella.Eleven cat-egories of antibiotic resistance genes(ARGs)were annotated among the fluoroquinolone-resistant strains.The detection rate of aminoglycoside ARGs was highest(100％).Twelve quinolone-resistant strains(92.3％)carried the IncHI2/IncHI2A plasmid type.PMQR gene analysis of various strains indicated that the strains from the United States and Europe carried six types of PMQR genes,and the detection rate of qnrB19 was highest.The Jiangsu strains carried three PMQR gene types,and the de-tection rate of aac(6')-Ib-cr was highest(11.84％).Analysis of cgMLST loci from different countries/regions revealed three main epidemic clusters.Some isolates from Jiangsu province might have the same evolutionary origin as some isolates from Eu-rope and the United States,and national/regional differences were observed in the PMQR gene carriage level.

This study aims to prepare altrenogest extended-release tablets,evaluate their quality and establish a content determination method.The hydrophilic gel skeleton type,dosage and core thick-ness of altrenogest extended-release tablets were used as the investigating factors,and the release degree of the tablets was used as the investigating index,the prescription process of altrenogest ex-tended-release tablets was optimized by one-factor screening and central combinatorial design re-sponse surface method,and quality evaluation was carried out,the in vitro release model was es-tablished,and a high-performance liquid chromatography(HPLC)assay method was set up for the determination of altrenogest extended-release tablets.The results showed that the optimal pre-scription of altrenogest extended-release tablets was 2％as the main drug,70％as the solubilizer,0.5％as the lubricant,19.1％as the filler,8.4％as the hydrophilic gel skeleton material,and the thickness of the tablets was 3.8 mm.The in vitro drug release conformed to the Higuchi model,and the altrenogest showed a good linear relationship with the R2=0.999 98 in the range of 10-80 mg/L.The optimized process for the extended-release tablets was stable and had a good quality.The extended-release tablets were stable and had significant slow-release effect.The HPLC method is accurate and reliable and can be used for the determination of altrenogest in extended-release tablets.

Albendazole sulfoxide and ivermectin compound pouring agent were prepared with dime-thyl sulfoxide and 1,2-propanediol as solvents.The central composite design response surface method was used to optimize the formula of pouring agent.Franz diffusion cell method was used to investigate the transdermal performance of pouring agent in vitro.The permeation amounts of the two drugs were determined by HPLC.The best formula of pouring agent was ivermectin 0.5％,al-bendazole sulfoxide 5％,dimethyl sulfoxide 52％,propylene glycol 39％,and the rest was 100％anhydrous ethanol.The cumulative permeation amounts of ivermectin and albendazole sulfoxide were up to 20.78 μg/cm2 and 249.02 μg/cm2,respectively.The in vitro release model of the two drugs accords with the first-order kinetic equation.There is a good linear relationship between al-bendazole sulfoxide and ivermectin in the range of 1-100 mg/L and the peak area.The precision and stability RSD of the two methods are less than 2％.The preparation process of albendazole sul-foxide compound pouring agent is simple,stable and easy to pour.The established HPLC method is simple and accurate,and can be used for the determination of albendazole sulfoxide and ivermectin in pouring agent.

Aim To investigate the effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration(RAS-RH)on oxidative stress and inflammatory injury of human umbilical vein endothelial cells(HUVECs)induced by ionizing radiation.Methods The model of HUVECs damage induced by 6 Gy X-rays was estab-lished.HUVECs were treated with different concentra-tions of RAS-RH(100,200,400 μg·L-1).The proliferative activity of HUVECs was detected by CCK-8 method,the structural changes of mitochondria were observed by transmission electron microscope,the level of ROS was detected by DCFH-DA probe,the change of intracellular mitochondrial membrane potential was detected by JC-1 kit,and the apoptosis and cycle were detected by flow cytometry.The contents of IL-6 and TNF-α in cells were detected by ELISA.The activities of MDA,CAT,SOD and GSH-PX were detected by biochemical kit.The gene expression levels of Nrf2,HO-1,NF-κB,eNOS and IL-6 were detected by qRT-PCR,and the expression levels of Nrf2,HO-1,eNOS,NF-κB,p-NF-κB and IL-6 protein were detected by Western blot.Results Compared with the model group,RAS-RH could increase the activity of HUVECs induced by ionizing radiation,decrease the rate of ap-optosis,decrease the level of intracellular ROS,re-duce the injury of intracellular mitochondria,increase the level of mitochondrial membrane potential,promote the expression of Nrf2,HO-1 and eNOS,and inhibit the expression of NF-κB and IL-6.Conclusions RAS-RH has anti-radiation,antioxidant and anti-in-flammatory effects,which may reduce the oxidative stress and inflammatory damage of HUVECs induced by ionizing radiation by activating the activity of Nrf2/HO-1 signal pathway,thus promoting the activity of cell proliferation.

The incidence of blood tumors is getting higher and higher. In addition to traditional chemoradiotherapy, in recent years, with the development of nuclear medicine technology and nuclide, nuclide therapy is playing an increasingly important role in the treatment of blood tumors. At present, the main research on the treatment of blood tumors focuses on acute myeloid leukemia (AML), but progress has also been made in other blood tumors. 213Bi and 225Ac-labeled monoclonal antibodies have achieved good results in blood tumors. 225Ac has overcome the short half-life of 213Bi and the problems of transportation and preservation. However, there are still many problems to be solved in the clinical use of α particles. This article reviews the progress of α-particle therapy in blood system, in order to provide a broader idea for the treatment of blood tumors.

Objective:To determine the relationship between tibial plateau stresses and malunion by exploring the changes in mechanical conduction in the knee joint after malunion of Hoffa fracture of the tibial plateau.Methods:This study selected 28 knee joint specimens treated with formalin for preservation, half of which were from male and half from female individuals with an age of (51.4±9.5) years. Their structures were intact, and flexion-extension activities normal. X-ray examinations excluded osteoporosis, tuberculosis, and diseases that could have potentially affected bone quality. The knee specimens were divided into a control group (intact tibia) ( n=4) and 6 groups of tibial plateau Hoffa fracture malunion model: 3 vertical malunion groups (groups V1, V2, and V3, with a vertical displacement of 1, 2, and 3 mm, respectively, n=4) and 3 separation malunion groups (groups S3, S5, and S7, with a separation displacement of 3, 5, and 7 mm, respectively), with half males and half females in each group. After a 600N vertical load was applied at passive knee flexions at 0°, 30°, 60°, 90°, and 120°, the stress levels in the medial and lateral compartments of the knee joint were measured using pressure-sensitive films. Results:Under a vertical load of 600 N, when the knee joint was in a neutral position (flexion of 0°), the differences in the medial and lateral tibial plateau stress values were not statistically significant between the malunion models groups and the control group ( P>0.05). When the knee flexion increased to 30°, the medial tibial plateau stress in the V3 and S7 groups was significantly greater than that in the control group ( P<0.05). At a knee flexion of 60°, the medial plateau stress was significantly greater in the V3, S5 and S7 groups than that in the control group, and the differences were significantly greater than the comparisons at a knee flexion of 30° (all P<0.05). When the knee flexion was 90°, the medial plateau stress in the V2, V3, S5 and S7 groups was significantly greater than that in the control group ( P<0.05), but the lateral tibial plateau stress in the V3 group was significantly smaller than that in the control group ( P<0.05). When the knee flexion was further increased to 120°, the differences in the medial and lateral plateau stress values were statistically significant between all the malunion groups and the control group ( P<0.05), and the differences significantly greater than the comparisons at a knee flexion of 90° (all P<0.05). Under a vertical load of 600 N, the differences in the stresses on the medial and lateral plateaus were not statistically significant between the control group and all the malunion groups at a knee flexion of 0° ( P>0.05). When the knee flexion increased to 30°, the difference between the medial and lateral stresses was not statistically significant in the control group ( P>0.05), but was statistically significant in the V3 and S7 groups ( P<0.05). When the knee flexion reached 60°, 90°, and 120°, the differences between the medial and lateral tibial plateau stresses in all the groups were statistically significant ( P<0.05). Conclusions:The peak knee stresses after malunion of Hoffa fracture of the tibial plateau correlate with the severity of malunion and knee flexion angles. The mechanical properties are not significantly different between a mild malunion knee and a normal knee, but a significant displacement (vertical displacement >2 mm and separation displacement ≥5 mm) may increase the peak knee stresses to increase the risk of knee osteoarthritis. When the severity of malunion is certain, an increase in knee flexion angle increases the difference in the peak stress between the medial and lateral tibial plateaus, thus increasing the risk of knee osteoarthritis.

During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Objective To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China,and to explore the feasibility of applying this method to deter-mine whether an individual is 18 years or older.Methods A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population,and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method,and the age distribution of the samples at each stage was analyzed using descriptive statistics.Results Stages 0,1,2 and 3 first appeared in 16.88,19.18,21.91 and 25.44 years for males and in 17.47,20.91,22.01 and 26.01 years for females.In all samples,individuals at stages 1 to 3 were over 18 years old.Conclusion It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

Aim To investigate the involvement and mechanism of miR-619-5p in the proliferation, migration and invasion of human breast cancer cells. Methods The expression of miR-619-5p in breast cancer and normal breast tissue and cells was detected using bioinformatic analysis or qRT-PCR. After transfection with miR-619-5p mimics or inhibitors, the expression of miR-619-5p and EMT-related molecule mRNA was determined by qRT-PCR. Cell proliferation was detected using CCK-8 assay; cell migration and invasion capacity was estimated by the wound healing assay and Transwell assay. The protein levels of EMT-related molecules were analyzed by Western blot. The target genes of miR-619-5p were analyzed by bioinformatic a-nalysis, and a preliminary analysis of the potential target gene CREB1 was carried out. Results miR-619-5p was low expressed in breast cancer tissues and breast cancer cells. Compared with the control group, over-expression of miR-619-5p resulted in up-regula-tion of miR-619-5p expression levels and EMT epithelial markers, down-regulation of pro-EMT molecules and mesenchymal markers, impairment of cell proliferation, migration and invasion, and down-regulation of CREB1 expression. The results of the low miR-619-5p expression group were opposite to the above results. Conclusions In breast cancer tissue and cells, miR-619-5p expression is lower. miR-619-5p inhibits the proliferation, migration, invasion and EMT of breast cancer cells, and its possible mechanism of the effects may be targeting CREB1.