OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Objective To explore the effect of intraoperative mild hyperventilation on postoperative shoulder pain(PLSP)in patients undergoing gynecological laparoscopic surgery.Methods Eighty-two pa-tients,aged 18-64 years,BMI 18.5-32.0 kg/m2,ASA physical status Ⅰ or Ⅱ,who underwent gyneco-logical laparoscopic surgery from January to September 2023 were selected.According to the random number table method,the patients were divided into two groups:observation group and control group,41 patients in each group.The observation group was given mild hyperventilation during the operation to maintain PETCO230-33 mmHg,and the control group was treated with conventional mechanical ventilation to maintain PETCO2 35-40 mmHg.The incidence of PLSP and VAS pain score of PLSP were recorded 12,24,48,72 hours,and 1 week after operation.The results of arterial blood gas analysis were recorded before anesthesia induction,15 minutes after pneumoperitoneum,at the end of operation,and 24 hours after operation.The intraoperative consumption of propofol and remifentanil,extubation time,bradycardia(HR＜50 beats/mi-nute),and intraoperative hypotension(SBP＜90 mmHg)were recorded.The occurrence of adverse reac-tions such as nausea and vomiting within 72 hours after operation and the requirement for rescue analgesia within 1 week after operation were recorded.Results Compared with the control group,the incidence of PLSP and VAS pain scores 12,24,48,72 hours,and 1 week after operation in the observation group were significantly reduced(P＜0.05),and PaCO2 15 minutes after pneumoperitoneum and at the end of opera-tion were significantly reduced(P＜0.05).There were no significant differences between the two groups in intraoperative consumption of propofol and remifentanil,extubation time,incidence of intraoperative brady-cardia and hypotension,incidence of nausea and vomiting within 72 hours after surgery,and requirement for rescue analgesia within 1 week after surgery.Conclusion Mild hyperventilation in gynecological laparo-scopic surgery can effectively reduce the incidence of PLSP and the degree of pain within 1 week after sur-gery,and does not increase the related adverse reactions within 72 hours after surgery.

Objective To investigate the effect of esketamine on postoperative analgesia,stress response and serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)levels in children undergoing tonsillectomy(TE)combined with endoscopic-assisted transoral adenoidectomy(ETA).Methods 98 children with tonsil and adenoid hypertrophy from January 2023 to August 2023.They were divided into two groups randomly,with 49 cases in each group.Children in both groups received the same TE plus ETA treatment,and were given the same anesthesia induction and maintenance.The observation group was given 0.5 mg/kg of esketamine injection intravenously 20 min before the operation ended,while the control group same dose of normal saline intravenously.The operation and anesthesia recovery were observed in the two groups.The scores of the face,legs,activity,cry,consolability behavioral tool(FLACC)and pediatric anesthesia emergence delirium scale(PAED)were compared between the two groups immediately after extubation(T1),10 min after extubation(T2),20 min after extubation(T3),30 min after extubation(T4)and 60 min after extubation(T5).The stress response indicators and inflammatory reaction mediators were tested at the time entering the operating room(T0)and T5 time points.And the two groups were also compared in terms of adverse reactions.Results There were no significant differences in surgical duration,extubation time,wake-up time and length of postanesthesia care unit(PACU)stay between the two groups(P＞0.05).The FLACC and PAED scores at T1,T2,T3,T4 and T5 time points in observation group were lower than those of the control group,the differences were statistically significant(P＜0.05).The serum cortisol(Cor),angiotensin Ⅱ(Ang Ⅱ),tumor necrosis factor-α(TNF-α)and interleukin-iβ(IL-1β)levels of the two groups at T5 time point were higher than those at T0 time point,the differences were statistically significant(P＜0.05).At T5 time point,the levels of serum Cor,Ang Ⅱ,TNF-α and IL-1β in observation group were lower than those of the control group,the differences were statistically significant(P＜0.05).The incidence of adverse reactions in observation group was significantly lower than that in control group,the difference was statistically significant(8.16％and 24.49％,P＜0.05).Conclusion Application of esketamine in the operation of TE combined with ETA in children can achieve exert good sedative and analgesic outcomes,and effectively reduce the stress response and inflammatory reaction caused by surgical trauma in children.