Emodin relieves morphine-stimulated BV2 microglial activation and inflammation through the TLR4/NF-κB/NLRP3 pathway.

The objective of this study is to disclose the role of emodin, a natural anthraquinone derivative that has been proposed to suppress microglial activation and inflammation, in morphine tolerance. Here, cell counting kit-8 method assayed the viability of BV2 microglial cells treated by ascending concentrations of emodin. In emodin-pretreated BV2 microglial cells challenged with morphine with or without transfection of toll-like receptor 4 (TLR4) overexpression plasmids, transwell assay measured cell migration. Immunofluorescence staining and western blot detected the expression of microglial markers. Inflammatory levels were subjected to ELISA and western blot. BODIPY 581/591 C11 assay estimated lipid reactive oxygen species activity. Iron assay kit examined total iron content. Western blot tested the expression of ferroptosis- and TLR4/nuclear factor-kappaB (NF-κB)/NOD-like receptor 3 (NLRP3) pathway-associated proteins. Molecular docking predicted the binding affinity of emodin to TLR4. Emodin was noted to obstruct the migration, activation, inflammatory response, and ferroptosis of BV2 microglial cells induced by morphine. In addition, emodin had a high binding affinity with TLR4 and inactivated TLR4/NF-κB/NLRP3 pathway in morphine-challenged BV2 microglial cells. Upregulation of TLR4 partially countervailed the protective role of emodin against morphine-elicited BV2 microglial cell migration, activation, inflammation, and ferroptosis. Accordingly, emodin might target TLR4 and act as an inactivator of TLR4/NF-κB/NLRP3 pathway, thus inhibiting BV2 microglial activation and inflammation to mitigate morphine tolerance.

Effects of negative pressure wound therapy on surgical site wound infections after cardiac surgery: A meta-analysis.

We conducted a comprehensive analysis to evaluate the benefits of negative pressure wound therapy (NPWT) versus traditional dressings in preventing surgical site infections in patients undergoing cardiac surgery. We thoroughly examined several databases, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, Chinese Biomedical Literature Database (CBM) and Wanfang, from inception until July 2023. Two independent researchers were responsible for the literature screening, data extraction and quality assessment; analyses were performed using RevMan 5.4 software. Thirteen studies comprising 8495 patients were deemed relevant. A total of 2685 patients were treated with NPWT, whereas 5810 received conventional dressings. The findings revealed that NPWT was more effective in reducing surgical site infections after cardiac surgery than conventional dressings (4.88% vs. 5.87%, odds ratio [OR]: 0.50, 95% confidence intervals [CIs]: 0.40-0.63, p < 0.001). Additionally, NPWT was more effective in reducing deep wound infections (1.48% vs. 4.15%, OR: 0.36, 95% CI: 0.23-0.56, p < 0.001) and resulted in shorter hospital stays (SMD: -0.33, 95% CIs: -0.54 to -0.13, p = 0.001). However, the rate of superficial wound infections was not significantly affected by the method of wound care (3.72% vs. 5.51%, OR: 0.63, 95% CI: 0.32-1.23, p = 0.180). In conclusion, NPWT was shown to be advantageous in preventing postoperative infections and reducing hospital stay durations in patients undergoing cardiac surgery. Nonetheless, given the limitations in the number and quality of the included studies, further research is recommended to validate these findings.

Research Advances in Pharmacology, Safety, and Clinical Applications of Yunnan Baiyao, a Traditional Chinese Medicine Formula.

Ethnopharmacology relevance: Yunnan Baiyao (YNBY), a traditional Chinese medicine formulae, has some significant properties including activating blood circulation to dissipate blood stasis (Huo-Xue-Hua-Yu), eliminating swelling and alleviating pain (Xiao-Zhong-Zhi-Tong), and eliminating necrotic tissues and promoting granulation (Qu-Fu-Sheng-Ji). Aim of this study: This paper intends to provide a comprehensive and critical analysis of studies on YNBY, proposing new possible therapeutic directions of this formula. Materials and methods: Relevant data on YNBY were retrieved from available databases and a hand-search by searching the keywords such as "Yunnan Baiyao," "pharmacology," "toxicity," and "clinical applications." Results: Traditionally, YNBY has been used to cure hemorrhage, bruises, swelling, and pain caused by injuries in the Chinese folk. Modern pharmacological studies show that YNBY possesses pharmacological activities including hemostasis, invigorating the circulation of blood, wound healing, anti-inflammation, analgesia, antibiosis, infection prevention, and other effects. Toxicological studies demonstrate that YNBY has a certain toxicology, which is mainly caused by Aconitum alkaloids from Cao-wu (CW, Aconiti Kusnezoffii Radix). The developmental non-toxic reaction dose (NOAEL) of YNBY for embryos and fetuses is 0.5 g/kg in rats. In addition, the NOAEL for fertility and early embryo development toxicity is 4.0 g/kg in rats. Clinical trials have confirmed the safety of YNBY in a large number of patients, and adverse drug reactions (ADRs) such as abdominal pain, diarrhea, allergy, and others in very few people. YNBY is routinely used in clinic to cure bleeding, pain, swelling, upper digestive tract ulcer, postoperative wound, arthritis, mouth ulcers, ulcerative colitis, etc. Conclusions: Hemostasis is a conspicuous effect of YNBY. Except for this effect, analgesia and anti-infection may be new research directions of this formula. In addition, the in vitro and in vivo pharmacology and mechanisms of action of YNBY are encouraged as well as the pharmacokinetics of this formulae. Furthermore, the material basis of the pharmacological effects of YNBY also needs clear identification.

The Factors Affecting Orthodontic Pain with Periodontitis.

The occurrence of pain is often closely related to the psychological status, and the threshold for pain tolerance varies from patient to patient. In short, the factors affecting orthodontic pain are diverse and have individual differences. Tooth pain after the first force of intraoral malocclusion orthodontic treatment is one of the common complications of fixed orthodontic treatment, which often affects the outcome of treatment of patients with malocclusion and their subjective satisfaction with fixed orthodontic treatment. The purpose of the paper was to investigate the basic patterns and influencing factors of dental pain in fixed orthodontic patients within seven days after the initial wearing of straight arch aligners and the analysis of the effect of psychological intervention on dental pain using the visual simulation scoring method. According to the inclusion criteria of the experimental design, 89 patients who visited the Department of Orthodontics of Hospital for malocclusion were randomly divided into observation group and control group, and the observation group used chewing gum as psychological intervention, while the control group did not use any intervention. The effect of psychological intervention on periodontal pain was analyzed. The results of the paper were that all but 3 of the 89 patients had no pain, and all the patients had different degrees of dental pain at different points in time.

The Traditional Uses, Phytochemistry, Pharmacology, Toxicology, and Clinical Uses of Metagentiana Rhodantha (Franch.) T.N.Ho and S.W.Liu, an Ethnomedicine in Southwest China.

Background: Metagentiana rhodantha (Franch.) T.N.Ho and S.W.Liu (MR) belongs to Gentianales, and it is often called Hong-hua-long-dan in Chinese. Traditionally, it has been used to cure acute icteric hepatitis, sore throat, dysentery, acute gastritis, carbuncle, and furuncle based on traditional Chinese medicine (TCM) concepts. Aim of Study: This review manages to provide a critical and comprehensive analysis on the traditional uses, phytochemistry, pharmacology, toxicology, and clinical uses of MR and to evaluate the therapeutic potential of this plant. Methods: Relevant data mainly literatures on MR were selected from available database. All the papers reviewed provided evidence that the source herbs were reliably identified. Results: The heat-clearing and removing the phlegm, and purging fire and removing toxicity of MR contribute to its dispelling jaundice, and clearing lung heat and cough. The compounds isolated from this plant include iridoids and secoiridoids, phenolic acids, ketones, triterpenoids, flavonoids, benzophenone glycosides, and others. Mangiferin (MAF) is a characteristic substance from this plant. The pharmacological studies show that some extracts and compounds from MR exhibit anti-inflammatory, antinociceptive, antibacterial, hepatoprotective, cardioprotective, and other effects which are associated with the traditional uses of this plant. The toxicological studies suggest that MAF is less toxic in mice and dogs. Nowadays, Chinese patent drugs such as Feilike Jiaonang and Kangfuling Jiaonang containing MR have been used to cure cough, asthma, chronic bronchitis, dysmenorrhea, and appendagitis. Conclusion: Although the current studies provide related research information of MR, it is still necessary to systemically evaluate the chemistry, pharmacology, toxicity, and safety of the extracts or compounds from this plant before clinical trials in the future. In addition, except for lung infection-related diseases, analgesia, anti-tumor, and hypertriglycemia may be new and prior therapeutic scopes of this ethnomedicine in the future.

The Effect of Epidural Nalbuphine Combined With Ropivacaine on Epidural Analgesia During Labor: A Multicenter, Randomized, Double-blind, Controlled Study.

OBJECTIVES: The addition of a small dose of opioids during epidural labor analgesia can enhance the local analgesic effect, reduce the dose of local anaesthetic required, and minimize motor blockade. For the treatment of visceral pain, studies have shown that κ-opioid receptor agonist are more effective than µ-receptor agonists. This study compared the effectiveness of epidural nalbuphine and sufentanil in combination with ropivacaine for labor analgesia, respectively. MATERIALS AND METHODS: We conducted a prospective, randomized, double-blind, multicentre clinical trial. Parturients who requested labor pain relief were randomly assigned to either the nalbuphine group or sufentanil group. After 5 minutes of initial dose, parturients in nalbuphine group received 10 mL 0.1% ropivacaine plus 0.3 mg/mL nalbuphine solution. The sufentanil group received the same ropivacaine dose plus 0.3 µg/mL sufentanil. The primary outcome was the duration of analgesia (the time to the first requirement for additional medication). Secondary outcomes included the ropivacaine dose per hour, and adverse reactions. RESULTS: Between November 2018 and February 2019, 180 parturients were recruited for the study. The study showed that the duration of analgesia was shorter in the nalbuphine group as compared with the sufentanil group (P=0.040). The ropivacaine dose per hour in nalbuphine group 9.3 (2.4) mg was significantly greater versus sufentanil group 8.4 (2.5) mg (P=0.024). No serious adverse events directly associated with the analgesics were observed. DISCUSSION: The analgesia effects of 0.3 mg/mL nalbuphine with ropivacaine are inferior to 0.3 µg/mL sufentanil with ropivacaine in labor analgesia. No serious side effects, either in the mother or in the fetus, were observed.

[Role of P2X7 receptor in osteogenic differentiation of human periodontal ligament stem cells].

PURPOSE: To investigate the role of P2X7 receptor (P2X7r) in osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). METHODS: hPDLSCs were isolated from the premolars collected in the First Affiliated Hospital of Guiyang University of Traditional Chinese Medicine, and divided into four groups. Group A was cultured in conventional medium, group B was cultured in osteogenic induction medium, group C was cultured in osteogenic induction medium + 100 nmol/L adenosine triphosphate (ATP) solution, and group D was cultured in osteogenic induction medium + 100 nmol/L P2X7 receptor specific antagonist KN-62. After 7 days, alizarin red staining was used to observe the osteogenic effect of hPDLSCs in each group. The mRNA expression of osteocalcin (OCN), RUNX2 and P2X7r in hPDLSCs was detected by real-time PCR reaction (RT-PCR). The data were processed by SPSS 22.0 software package. RESULTS: Alisarin red staining showed that the morphology of hPDLSCs cells in group B and group C was significantly changed. The pale calcified nodules in group C were significantly more than those in group B, while very few calcified nodules were found in group A and group D. The mRNA expression of OCN, RUNX2 and P2X7r in hPDLSCs were the highest in group C, followed by group B(P<0.05), and no difference was found between group A and group D(P>0.05). CONCLUSIONS: P2X7 receptor can promote osteogenic differentiation of human periodontal ligament stem cells after being activated by ATP, which may provide a new direction for clinical treatment of periodontitis.