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Study on the mechanism of P22077 to improve pulmonary fibrosis in mice by down-regulating β-catenin pathway
Author:Hu Die Zhao Dong Huang Jizhen Wu Lei
keyword:Pulmonary fibrosis ; Alveolar epithelial cells ; P22077 ; Ubiquitin-specific protease 7 ; β-catenin ; Epithelial-mesenchymal transition ; Mice
Objective To observe the effects and potential mechanisms of the ubiquitin-specific protease 7(USP7) inhibitor P22077 on epithelial-mesenchymal transition(EMT) in alveolar epithelial cells and on pulmonary fibrosis in mice. Methods The experiment was conducted in the Central Laboratory of Renmin Hospital of Wuhan University from October 2023 to December 2024. Forty C57BL/6 mice were randomly divided into control group, model group, P22077-L group, and P22077-H group. A mouse pulmonary fibrosis model was established by intratracheal instillation of bleomycin(2 mg/kg). Different doses of P22077 were administered intraperitoneally to mice in the P22077-L(10 mg·kg-1·d-1) and P22077-H(15 mg·kg-1·d-1) groups starting from day 7. On day 28, bronchoalveolar lavage fluid and lung tissue were collected. Pathological changes in lung tissue were observed by HE staining and Masson staining. The expression of USP7, β-catenin, E-cadherin, and α-SMA in lung tissue was detected by Western blot. Immunohistochemical staining was used to detect the expression of α-SMA and E-cadherin in mouse lung tissue. ELISA was used to measure the levels of inflammatory factors(TGF-β1, IL-1β, IL-6, TNF-α) in bronchoalveolar lavage fluid. For the cell experiment, groups included control group, model group, and P22077 group. Mouse alveolar epithelial cells(MLE12) were treated with TGF-β1(10 μg/L) to establish a cell model, and the P22077 group was treated with both TGF-β1 and P22077(10 μmol/L). After cell collection, the expression of USP7, β-catenin, E-cadherin, and α-SMA was detected by Western blot. Results Compared with the model group, HE and Masson staining showed that P22077 reduced lung tissue inflammation and fibrosis in a dose-dependent manner. Compared with the bleomycin(Blm) group, the protein expression of USP7, β-catenin, and α-SMA in lung tissue of the P22077-H group was significantly decreased, while E-cadherin expression was significantly increased, and inflammatory factor levels in bronchoalveolar lavage fluid were downregulated. In cell experiments, compared with the TGF-β1 group, the expression of USP7, β-catenin, and α-SMA in MLE12 cells of the P22077 group was significantly decreased, while E-cadherin expression was significantly increased. Conclusions P22077 can effectively inhibit EMT in alveolar epithelial cells and ameliorate pulmonary fibrosis in mice, and this effect is associated with downregulation of the β-catenin pathway.
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Meta-analysis of opioid-free anesthesia for postoperative analgesia and prognosis in different types of surgery
Author:Lu Hongcheng Sha Kaiyuan Yang Bin Zhang Yue Ou Cehua
keyword:Opioid-free anesthesia ; Postoperative recovery ; Postoperative nausea and vomiting ; Postoperative opioid consumption ; Meta-analysis
Objective To evaluate the efficacy and feasibility of opioid free anesthesia(OFA) for postoperative analgesia and prognosis in different types of surgeries.Methods Search Cochrane Library PubMed, Embase, China National Knowledge Infrastructure, Wanfang Database, and VIP Database. Include randomized controlled trials(RCTs) published between the period of self-establishment and March 2023, where at least one study group did not use opioid drugs before surgery, during anesthesia induction, and before anesthesia recovery. The main outcome measures were postoperative pain scores at 2 and 24 hours, and the secondary outcome measures were extubation time, PACU exit time after anesthesia, incidence of postoperative nausea and vomiting(PONV), opioid dosage, postoperative OFA, and opioid based recovery quality score. Conduct a meta-analysis of the included studies using Revman5.3 software on the Cochrane Collaboration Network. Perform heterogeneity tests on the included literature using Q-value statistical tests and I2 tests. Calculate statistics using fixed effects or random effects models based on inter study heterogeneity, and perform qualitative analysis on data that cannot be subjected to meta-analysis. Results Thirty-seven RCTs were ultimately included, with a total of 2695 patients. Compared with opioid anesthesia, postoperative 24-hour pain score(MD=-0.73, 95%CI-0.92--0.54, I2=61.5%,P=0.0097),PACU extubation time(MD=0.40,95%CI-0.58-1.37, I2=92.6%,P<0.0001), the postoperative opioid dosage(MD=-2.51, 95%CI-3.26--1.77,I2=79.3%,P<0.001) decreased. OFA has no clinically significant effect on postoperative extubation time, the incidence of PONV, 2-hour postoperative pain score, and postoperative recovery quality score. Conclusion OFA can improve the prognosis of weight loss surgery, gynecological and breast surgery, and has no adverse effects on patient safety and pain management.
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Cat scratch disease combined with reactivation of human herpesvirus: A case report and literature review
Author:Yang Guangyu Wang Luna Ni Jie Chu Chengbiao Sha Dujuan
keyword: Cat scratch disease ; Human herpesvirus 6 ; Metagenomics ; Diagnosis ; Treatment
This paper reports a case of co-infection with Bartonella henselae and human herpesvirus 6(HHV-6), along with a review of relevant literature.
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A case of congenital adrenal hyperplasia with 17α-Hydroxylase deficiency and literature review
Author:Su Man Wang Cuiying Jiang Meng
keyword:Congenital adrenal hyperplasia ; 17α-Hydroxylase Deficiency ; Diagnosis ; Treatment
This article reports the clinical data of an adult patient with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency and provides a literature review.
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Research progress on Rhizoma Nardostachyos and its compounds in the treatment of cardiovascular diseases
Author:Wang Ying Liu Rui Zhou Yabin
keyword:Cardiovascular diseases ; Rhizoma Nardostachyos ; Chemical constituents ; Research progress
In recent years, the extensive clinical application of Rhizoma Nardostachyos has drawn increasing attention to its therapeutic potential in cardiovascular diseases. Rhizoma Nardostachyos(also known as Nardostachys sinensis), a traditional Chinese medicine and a second-class protected Tibetan medicinal herb in China, contains various active compounds including coumarins, terpenoids, lignans, and flavonoids. This review summarizes current research on Rhizoma Nardostachyos and its active compounds in the treatment of cardiovascular diseases, aiming to provide insights for further clinical studies on its application in this field.