Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.

Objective To investigate the relationship between nasal colonization of Staphylococcus aureus(SA) and nosocomial infection in intensive care unit(ICU), and observe the therapeutic effect of Anerdian III in nasal decolonizaion. Methods Bacterial cultures were made by means of nasal swabs among inpatients whom the occurrence of nosocomial infection were observed.Patients with SA colonization were randomly divided into two groups:control and treatment.Control group were given regular treatment, and treatment group were administered Anerdian III in addition to regular treatment.Then the clearance rate of SA and the occurrence of nosocomial infection of two groups were observed. Results A total of 751 patients were enrolled, of whom 108(14.4%) were with nosocomial infection and 85(11.3%) with SA nasal colonization. Methicillin resistant Staphylococcus aureus ( MRSA ) was detected in 33 patients (4.4%).The nosocomial infection rate of patients with MRSA colonization was 51.5%, which was significantly higher than those in patients with other bacterial colonization(P<0.05).The SA clearance rate in treatment group was significantly higher than that in control group(81.4% vs.42.8%,P<0.05).The nosocomial infection rate in treatment group was significantly lower than that in control group ( 16 .3% vs. 40.5%,P <0.05).After decolonization treatment,the nosocomial infection rate of patients with MRSA colonization was significantly lower than that in control group(25.0% vs.76.5%,P <0.05). Conclusion The incidence rate of nosocomial infection in patients with MRSA nasal colonization is markedly increased in ICU, and the decolonization treatment by Anerdian III increases the clearance rate of nasal SA and decreases the incidence rate of nosocomial infection.

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

AIMTo discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice.

METHODSThe heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting.

RESULTSAfter treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice.

CONCLUSIONPitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.

Angiogenesis Inducing Agents ; pharmacology ; Animals ; Heterozygote ; Ischemia ; Male ; Mice ; Mice, Knockout ; Quinolines ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

Adult ; Bone Plates ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; instrumentation ; Humans ; Humeral Fractures ; diagnostic imaging ; physiopathology ; surgery ; Male ; Middle Aged ; Radiography

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.

Objective:To analyze the total expendition,developmental changes and flow of the total cost of traditional Chinese medicine(TCM)in China from 2016 to 2021,and to study the development of the total cost of TCM in different medical institutions.Methods:Institutional flow method and case-base aggregation method were used to account for the total TCM costs.Results:From 2016 to 2021,the total amount of total TCM costs flowed to TCM-type hospitals was the highest in China,the proportion of total TCM costs in primary healthcare organizations was increased,and TCM-type clinics and outpatient clinics were developed more rapidly.The share of Chinese medicine drug costs in total Chinese medicine costs has been declined,and the share of county hospitals in their total health costs has been risen overall Conclusion:In the future,it would increase the TCM investment,attach importance to the development of TCM services in non-Chinese medicine hospitals,improve the capacity of primary Chinese medicine services,continue to consolidate the policy of"strengthening the primary",and maintain the rapid development of Chinese medicine clinics and outpatient clinics;the value of Chinese medicine technical labor should be emphasized,and the driving force of county hospitals should be brought into full play.