Trigeminal Neuralgia (TN) refers to recurrent severe paroxysmal pain in the distribution area of the trigeminal nerve, which seriously affects the quality of life of patients. This research applied the chronic constriction injury of the infraorbital nerve (CCI—ION) approach to induce an animal model of TN in rats. The mechanical pain threshold of each group of rats was determined postoperatively; the expression of P2X7 receptor in trigeminal ganglion (TG) was assessed by qRT-PCR, immunofluorescence and Western blot; and the changes of the proinflammatory cytokines IL-1β and TNF-α in serum of rats were detected by ELISA. The results showed that the administration of palmatine in the TN rats could reduce the mechanical pain threshold, significantly decrease the expression of P2X7 receptor in TG, and lower the serum concentrations of IL-1β and TNF-α, compared to the sham group. In addition, the phosphorylation level of p38 in TG of TN rats was significantly decreased after treatment with palmatine. Likewise, inhibition of P2X7 expression by shRNA treatment could effectively counteract the adversary changes of pain sensitivity, IL-1β and TNF-α production, and p38 phosphorylation in TN rats. Our data suggest that palmatine may alleviate mechanical facial pain in TN rats possibly by reducing the expression of P2X7 receptor in TG of TN rats, which may be attributable to inhibiting p38 phosphorylation and reducing the release of IL-1β and TNF-α.

Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1β, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1β and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.

Objective: Systematic review of the association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene 1858 and 1123 sites single nucleotide polymorphism (SNP) with the susceptibility of primary immune thrombocytopenia (ITP).Method: Database searched includes PubMed, Embase, Web of Science, CNKI, CBM, VIP and WanFang Data. The retrieval period is from the establishment of the database to 30 June 2021. After screening articles according to inclusion and exclusion criteria, the data were extracted and methodological quality of the included studies was evaluated. Meta-analysis was performed using RevMan 5.4 and Stata 16.0 software. The combined OR value and its 95%CI were calculated. Sensitivity analysis and publication bias assessment were performed. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software.Results: A total of 10 studies with 10 articles were included, with a total of 932 cases and 2,112 controls. The results of meta-analysis showed that for SNP1858, the susceptibility of TT genotype to ITP was 5.01 times higher than CC genotype [95%CI (1.81, 13.86), p = 0.002]. For SNP1123, G allele carriers were more susceptible to ITP than C allele carriers [OR = 1.23, 95%CI (1.05, 1.45), p = 0.01], and GG genotype carriers were 1.51 times more susceptible to ITP than CC genotype carriers [95%CI (1.11, 2.06), p = 0.009]. Although the results are statistically significant, the results of sensitivity analysis showed certain limitations of stability, and the TSA analysis still indicated the possibility of false positive. No significant publication bias was observed.Conclusion: PTPN22 gene SNP1858 (rs2476601) and SNP1123 (rs2488457) polymorphisms are associated with susceptibility to primary immune thrombocytopenia. Due to the limitation of the number and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

Our study is aimed to access the efficacy and safety outcomes for coronavirus disease 2019 (COVID‐19) patients treated with Paxlovid. According to inclusion and exclusion criteria, databases were used to retrieve articles from 1 January 2020 to 1 January 2023. Article screening, quality evaluation and data extraction were completed and cross‐checked. The meta‐analysis and trial sequential analysis (TSA) were conducted using RevMan, StataMP, and TSA software. A total of 42 original articles were included. Overall meta‐analysis results showed that for death, hospitalisation, death or hospitalisation, emergency department (ED) visit, intensive care unit (ICU) admission, and extra oxygen requirement outcomes, every odds ratio (OR) was <1 and p < 0.05. For rebound outcome, the OR was >1 and p > 0.05. For adverse events (AEs) outcome, the OR was >1 and p < 0.05. In conclusion, Paxlovid effectively reduced the risks of death, hospitalisation, death or hospitalisation, ED visit, ICU admission, and extra oxygen requirement. There was no significant statistical difference considering rebound, but people should pay attention to possible AEs. However, for rebound and AEs outcomes, observations in certain subgroups suggested conclusions contrary to the overall meta‐analysis. Trial sequential analysis indicated these two outcomes have a risk of false negative or false positive conclusions, so additional original studies are needed for further validation.