BACKGROUND:Quercetin has anti-inflammatory,anti-cancer,anti-oxidation,anti-aging,anti-depression and other pharmacological effects,and has high medicinal value.Quercetin can promote wound healing in normal rats,but few drugs with quercetin as the main component have been developed,which limits its wide application in clinical practice. OBJECTIVE:To investigate the application effect of quercetin-carboxymethyl chitosan hydrogel on diabetic wound in rats by loading quercetin with hydrogel material. METHODS:(1)Carboxymethyl chitosan hydrogels and quercetin-carboxymethyl chitosan hydrogels were prepared respectively,and the micromorphology and in vitro drug release properties of the hydrogels were characterized.(2)Cell experiment:Mouse L929 fibroblasts were cultured in four groups.The blank control group was cultured conventionally.Carboxymethyl chitosan hydrogel,quercetin solution and quercetin-carboxymethyl chitosan hydrogel were added to pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively,to detect cell proliferation and migration ability.(3)Animal experiments:Diabetic models were established in 80 SD rats.After successful modeling,full-layer skin defect wounds with a diameter of 2 cm were made on the back of rats,and these models were randomly divided into four groups.Normal saline,carboxymethyl chitosan hydrogel,quercetin solution,and quercetin-carboxymethyl chitosan hydrogel were injected into the wounds of blank control group,pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively.Each group contained 20 animals,which were bound with sterile gauze.Wound healing,pathological morphology,expression of inflammatory factors,and angiogenesis were observed after operation. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the microstructures of the two hydrogels were similar,both showed loose porous network structure,and quercetin-carboxymethyl chitosan hydrogels had good drug release performance in vitro.(2)Compared with blank control group,the cell proliferation and mobility of the other three groups were increased(P<0.05).The cell proliferation and mobility of drug-loaded hydrogel group were higher than those of pure hydrogel group and drug group(P<0.05).(3)The wound healing rate of the drug-loaded hydrogel group was higher than that of the other three groups at 5 and 11 days after operation.The wound healing rate of rats in the hydrogel group,pure hydrogel group,and drug group reached 100%18 days after operation,which was higher than that in the blank control group(P<0.05).Hematoxylin-eosin staining showed that intact skin and skin appendages were visible on the wounds of rats in the drug-loaded hydrogel group 18 days after surgery,while intact skin and skin appendages were visible on the wounds of rats in the blank control group,pure hydrogel group,and drug group 25 days after surgery.The levels of tumor necrosis factor α and interleukin-6 in the drug-loaded hydrogel group were lower than those in the blank control group at 5,11,and 18 days after surgery(P<0.05),and the levels of transforming growth factor β1 at 11 and 18 days after surgery were lower than those in the blank control group(P<0.05).The mRNA expressions of CD31 and vascular endothelial growth factor α in the drug-loaded hydrogel group were higher than those in the other three groups at 11 and 18 days after operation(P<0.05).(4)These findings indicate that quercetin in quercetin carboxymethyl chitosan hydrogel can regulate inflammatory response,accelerate angiogenesis,promote the proliferation and migration of fibroblasts,and enhance the healing of diabetic wounds in rats.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

The neuropeptide Y receptors system is a receptor-ligand system composed of neuropeptide Y and its receptors, which is represented by two subtypes, including Y1 receptor (Y1R) and Y2 receptor (Y2R). The system is widely involved in pain modulation in mammals. These receptors are G protein-coupled receptors, participating in neuronal membrane signaling. Neuropeptide Y receptors distribute in the pain-related regions of the central nervous system, play a variety of roles in maintains neuronal activity of pain transmission, relate to the specificity of distribution. At the spinal level, Y1R plays an analgesic role, whereas Y2R is usually related to pain-promoting. The system can also take part in cerebral pain modulation at different nuclei.

Objective To analyze the physiologically active substances, named amino acid neurotransmitters, ATP and Ca2+ in rat spinal synaptosomes. Methods The spinal synaptosome was extracted by discontinuous Percoll density gradient centrifugation from a female Sprague-Dawley rat. The amino acid neurotransmitters were determined with high performance liquid chromatography, ATP content, Na+-K+-ATPase activity, Ca2+-Mg2+-ATPase activity and total ATPase activity with ultraviolet spectrophotometer, and Ca2+ concentration with fluorescence spectrophotometer. Results The amino acid neurotransmitters contained mainly aspartic acid, glycine, glutamic acid and r-aminobutyric acid. The concentration of ATP was about 414.7461 μmol/mg, total ATPase activity > Na+-K+-ATPase activity > Ca2+-Mg2+-ATPasese activity. The concentration of Ca2+ could be calculated from absorbancy directly. Conclusion The rat spinal synaptosome contains a variety of physiologically active substances, which can be accurately analyzed to explore their activities.

Purpose To detect the expression of CD90 in invasive ductal breast carcinoma with different molecular subtypes and to explore its clinical significance.Methods The expression of CD90,ER,PR,Ki-67 and HER-2 were detected in 80 cases of invasive ductal breast carcinoma tissue and 20 cases of breast benign lesion with immunohistochemical method.The relationship between CD90 and clinicopathological parameters were analyzed.Results The positive expression rate of CD90 in invasive ductal breast carcinoma and breast benign lesion tissues were 62.5％ and 20.0％,respectively (P ＜0.001).The expression of CD90 in invasive ductal breast carcinoma was correlated with lymph node metastasis (P ＜ 0.05),but not with age,tumor size,TNM staging and histological grade (P ＞ 0.05).Among different molecular subtypes,CD90 expression level in Luminal A type was the lowest (40.0％),and the level in triple negative type was the highest (82.4％) (P ＜0.05).CD90 expression level was negatively correlated with ER (r=-0.342,P＜0.05) orPR (r=-0.374,P＜0.05) expression level,but not with Ki-67 (r =0.084,P ＞ 0.05).Condusion The over-expression of CD90 is related with molecular subtypes of breast carcinoma,and its high expression suggests a poor prognosis.

To evaluate the effect of impeller design on pump hemolysis, five impellers with different number of vanes or different vane angles were manufactured and tested in one pump for hemolysis comparison. The impellers are made to have the same dimension and same logarithmic spiral vane from which coincide with the stream surfaces in the pump, according to the analytical and three-dimensional design method developed by the authors. Consequently, an impeller with 6 vanes and 30 degrees vane angle has the lowest hemolysis index. This result agrees with the theoretical analyses of other investigators searching optimal number of vanes and vane angle to achieve the highest efficiency of the pump.
Heart-Assist Devices ; adverse effects ; Hemolysis ; Humans ; In Vitro Techniques ; Prosthesis Design

For long-term application of the rotary pumps, it is necessary to solve the problems of bearing wear and thrombosis along the bearing. Currently, many investigators choose the magnetic bearing to realize zero-friction and no contact between the rotor and stator; the former avoids the mechanical wear and the latter eliminates the possibility of thrombus formation. We tried and found that it is difficult to apply a magnetic bearing to rotary pump without disturbing its simplicity, reliability and implantable; therefore, we have developed a much simpler and much more creative approach to achieving the same results. Instead of the sliding bearing, a rolling bearing has been devised for the pump; its friction is about 1/15 of the sliding bearing. Furthermore, a wear-proof material of ultra-high-molecular weight polythene has been adopted in making the rollers, their anti-wear property in 8 times better than that of metal. Thereby, the service life of the bearing has extended to several years. For preventing the thrombus formation along the bearing, the impeller reciprocation axially as the impeller changes its rotating speed periodically to produce a pulsatile flow. The reciprocation is a result of the effects of a magnetic force between the motor rotor and stator, and a hydraulic force between the blood flow and the impeller. Similar to piston pump, the oscillating impeller can make the blood in and out of the bearing, resulting in wash-out once a circle. This is obviously beneficial to preventing thrombosis along the bearing and in the pump. The endurance tests with saline of this novel pump demonstrated a durability of the device. It promises to be able to assist the circulation of the patients permanently and to be able to replace the heart transplantation in the future.
Heart-Assist Devices ; Magnetics ; instrumentation ; Prosthesis Design ; Thrombosis ; prevention & control

Magnetic bearing has no mechanical contact between the rotor and stator. And a rotary pump with magnetic bearing has therefore no mechanical wear and thrombosis due to bearing. The available magnetic bearings, however, are devised with electric magnets, need complicated control and remarkable energy consumption. Resultantly, it is difficult to apply an electric magnetic bearing to rotary pump without disturbing its simplicity, implantability and reliability. The authors have developed a levitated impeller pump merely with permanent magnets. The rotor is supported by permanent magnetic forces radially. On one side of the rotor, the impeller is fixed; and on the other side of the rotor, the driven magnets are mounted. Opposite to this driven magnets, a driving motor coil with iron corn magnets is fastened to the motor axis. Thereafter, the motor drives the rotor via a rotating magnetic field. By laboratory tests with saline, if the rotor stands still or rotates under 4,000 rpm, the rotor has one-point contact axially with the driving motor coil. The contacting point is located in the center of the rotor. As the rotating speed increases gradually to more than 4,000 rpm, the rotor will detache from the stator axially. Then the rotor will be fully levitated. Since the axial levitation is produced by hydraulic force and the driven magnets have a gyro-effect, the rotor rotates very steadly during levitation. As a left ventricular assist device, the pump works in a rotating speed range of 5,000-8,000 rpm, the levitation of the impeller hence is ensured by practical use of the pump.
Equipment Design ; Heart-Assist Devices ; Magnetics ; instrumentation

The author's implantable pulsatile impeller pump can assist the circulation of the calves for several months. The termination of the experiments was related to wear of the mechanical bearing, which resulted in vibration of the rotor and pump failure. It seemedas if the experiments could have lasted inde finitelyif the bearing had not failed. To solve the problem of bearing wear, a specially devised rolling bearing was investigated and applied to the impellerp ump. Its service life is more than 10 years due to the wear-proof roller made of ultra-high-molecular weight polythene. This newly devised impeller heart promises to have long-term and permanent applications. Compared with the magnetic bearing, the rolling bearing has the advantages of simpler construction and control, no consumption of energy, and better reliability.