[Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

[Application of microneedle-assisted percutaneous drug delivery system in treatment of rheumatoid arthritis:a review].

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.

Computation and molecular pharmacology to trace the anti-rheumatoid activity of Angelicae Pubescentis Radix.

BACKGROUND: The mechanism of action of Angelicae Pubescentis Radix in rheumatoid arthritis treatment is complex; the pathways and protein targets involved remain unclear. This study predicted the targets and signaling pathways of Angelicae Pubescentis Radix for rheumatoid arthritis treatment using network pharmacology and molecular docking technology and clarified its mechanism of action using in vitro cellular experiments. METHODS: Angelicae Pubescentis Radix active components and related targets were retrieved from the traditional Chinese medicine systems pharmacology database. All human proteins were mined from the global protein database, and the network of active components and targets of Angelicae Pubescentis Radix was drawn using Cytoscape 3.7.1. GeneCard, Online Mendelian Inheritance in Man, and DrugBank databases were used to mine rheumatoid arthritis-related genes. Metascape was used for Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. ß-sitosterol's molecular docking was determined using AutoDock Tools; pathway verification was performed in the Kyoto Encyclopedia of Genes and Genomes database, and the verified genes were input into the Human Protein Atlas database to observe the expression levels in various human body tissues. RESULTS: Eight main active components were screened out of Angelicae Pubescentis Radix from the traditional Chinese medicine systems pharmacology database, and 60 targets related to major active ingredients were obtained. Forty-two core pathogenic rheumatoid arthritis-related genes were screened from GeneCard and other related databases. The enrichment of the Kyoto Encyclopedia of Genes and Genomes pathway included the vascular endothelial growth factor signaling pathway that proved to be the decisive pathway for rheumatoid arthritis treatment by a high degree value. In vitro experiments confirmed that Angelicae Pubescentis Radix mainly regulated cell proliferation and survival through the vascular endothelial growth factor signaling pathway and showed significant therapeutic effects on rheumatoid arthritis. The prostaglandin endoperoxide synthase 2 gene was associated with rheumatoid arthritis via pathway verification and monitoring of human gene expression levels. CONCLUSIONS: The mechanism of the multi-component, multi-target, and multi-channel treatment of rheumatoid arthritis via Angelicae Pubescentis Radix was explored using network pharmacology and molecular docking technology, providing new thinking and research directions for future rheumatoid arthritis treatment using Angelicae Pubescentis Radix.

[Mechanism of Linderae Radix against gastric cancer based on network pharmacology and in vitro experimental validation].

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.

[Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro].

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Allium tuberosum alleviates pulmonary inflammation by inhibiting activation of innate lymphoid cells and modulating intestinal microbiota in asthmatic mice.

OBJECTIVE: This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs). METHODS: BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups. RESULTS: We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice. CONCLUSION: The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

[The anesthesiologic value of transcutaneous acupoint electrical stimulation combined with general intravenous anesthesia in endoscopic thyroidectomy patients: a clinical study].

OBJECTIVE: To explore the clinical anesthesia value of transcutaneous acupoint electrical stimulation (TAES) combined with general intravenous anesthesia in endoscopic bilateral thyroidectomy patients. METHODS: Totally 60 patients who underwent endoscopic bilateral thyroidectomy were equally randomly assigned to 2 groups, the treatment group and the control group, 30 in each group. Patients in the treatment group received TAES combined general intravenous anesthesia, while those in the control group received total intravenous anesthesia. Anesthesia was maintained by target controlled infusion of propofolum combined constant speed infusion of remifentanil in the two groups. TAES was maintained from 30 min before anesthesia induction to the end of endoscopic thyroidectomy at bilateral Hegu (L14) and Neiguan (PC6). The mean artery pressure (MAP) and heart rate (HR) were recorded at different time points of anesthesia, i.e., immediately after entry into the operating room (TO), immediately after intubation (T1), 5 min after intubation (T2), 5 min before incision (T3), 5 min after incision (T4), 30 min after inflation (T5), at the end of surgery (T6), 5 min before extubation (T7), immediately after extubation 0 (T8), and 5 min after extubation (T9). The concentration of IL-6 and TNF-alpha were measured at TO, T3, T5, and T6. The target concentration of propofol was also recorded at T3, T4, and T5. RESULTS: There was no statistical difference in the operation time between the two groups (P >0.05). Compared with TO in the same group, HR at T3-T4 decreased and increased at T8-T9, and MAP increased at T7-T9 in the treatment group; HR decreased at T3 and increased at T7-T9, MAP increased at T1, T5, T7-T9, and MAP decreased at T2-T3 in the control group. IL-6 increased at T5-T6, while TNF-alpha decreased at T6 in the two groups (P <0.01,P <0.05). Compared with the control group at the same time point, HR decreased at T6-T9, MAP decreased at T1, T4, T5, T7-T9, MAP increased at T3, and IL-6 decreased at T5-T6 in the treatment group (P <0. 05). The concentration and the total amount of propofol were significantly lower in the treatment group than in the control group (P <0.01,P <0.05). CONCLUSIONS: TAES could maintain the hemodynamics more stably and inhibit the stress response in endoscopic thyroidectomy. It also reduce the dosage of anesthetics and improve the safety of anesthesia.

Evaluation of transcutaneous electroacupoint stimulation with the train-of-four mode for preventing nausea and vomiting after laparoscopic cholecystectomy.

OBJECTIVE: To evaluate the efficacy of transcutaneous electroacupoint stimulation with a train-of-four (TOF) mode for the prevention of postoperative nausea and vomiting (PONV) in the patients undergoing laparoscopic cholecystectomy. METHODS: Ninety-six ASA Grade I - II patients scheduled for laparoscopic cholecystectomy were randomized into Neiguan (P6) electroacupoint stimulation group (treated group) and a placebo control group (placement of electrodes without electroacupoint stimulation). The anesthetic regimen was standardized by needling at Neiguan on the left side and connecting the TOF peripheral nerve stimulator. The incidence of nausea, vomiting, severity, antiemetic dosage and the degree of pain were assessed at 0, 60, 120 min, and 24 h after surgery. RESULTS: The incidence of nausea and vomiting, the dose of antiemetics and the occurrence of severe nausea were all significantly lower in the treated group compared with the control group and the score for pain was obviously reduced in patients of the treated group at 24 h post-operation (P<0.05 or P<0.01). CONCLUSION: Transcutaneous electroacupoint stimulation at P6 with the TOF mode could reduce the incidence and severity of nausea and vomiting with analgesic effects.

[Effect of electroacupuncture on bispectral index of electroencephalography in patients undergoing subtotal thyroidectomy].

OBJECTIVE: To investigate the effects of electroacupuncture on bispectral index (BIS) of electroencephalography in patients undergoing subtotal thyroidectomy. METHODS: Sixty patients were equally randomized into group A given electroacupuncture combined with cervical plexus block (CPB) and group B given CPB alone. After needling sensation was reached in bilateral "Hegu" and "Neiguan" acupoints, 5 min of high frequency electrical stimulation by electrical stimulation device followed with CPB was applied to group A, while only CPB was performed in group B. Visual analog scale (VAS) and verbal stress scale (VSS) were monitored, complication and adverse reaction were observed and BIS, mean arterial pressure (MAP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored continuously in the perioperative period. RESULTS: HR increased and BIS decreased in group A, both were lower significantly than those in group B (P < 0.01); MAP, the complementary dosage of fentanyl and lidocaine used and scores of VAS and VSS were also lower in group A than those in group B (P < 0.01). CONCLUSION: Electroacupuncture could enhance the anesthetic effect of CPB, lower the BIS value during subtotal thyroidectomy.