Objective To investigate the role of quercetin(QUE)in ferroptosis during intestinal ischemia-reperfusion(IR)injury and elucidate its underlying mechanisms.Methods ① Potential target genes of QUE were predicted using the TCMSP,PharmMapper,and SwissTargetPredictive databases.Target genes associated with intestinal IR injury and ferroptosis were collected from GeneCards,PharmGKB,and OMIM databases.After overlapping genes were identified and analyzed,protein-protein interaction(PPI)networks were constructed using the STRING database and then visualized with Cytoscape 3.10.0.Molecular docking was performed to validate the binding conformations between QUE and key targets.② In vivo experiments were conducted to verify QUE's protective effects against intestinal IR injury.Thirty-six SPF-grade male C57BL/6J mice(6～8 weeks old,body weight:22±2 g)were randomly divided into Sham,Sham+QUE,IR,IR+QUE,IR+QUE+erastin(IR+QUE+Era),and IR+QUE+kevetrin hydrochloride(IR+QUE+KH)groups,with 6 mice in each group.Mouse model of intestinal IR injury was induced by 45 min ischemia of the superior mesenteric artery followed by 60 min reperfusion.HE staining was used to observe histopathological changes in the intestinal tissues.ELISA was employed to the serum or intestinal contents of diamine oxidase(DAO),pro-inflammatory cytokines(TNF-α,IL-6,IL-1β),and ferroptosis markers[glutathione(GSH)and Fe2+].Western blotting was utilized to detect the protein expression of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4),and tumor protein 53(p53).Results ① Network pharmacology identified 460 QUE targets,1 552 intestinal IR injury targets,and 1 967 ferroptosis-related targets,and 92 overlapping genes were identified as potential therapeutic targets.Molecular docking revealed a strong binding affinity between QUE and p53(binding energy:-6.8 kcal/mol).② In vivo experiments demonstrated that the IR+QUE group exhibited reduced intestinal damage and lower Chiu's score(P<0.05),decreased serum DAO content but elevated intestinal DAO content(P<0.05),decreased levels of TNF-α,IL-6,and IL-1β in the serum and intestinal tissues(P<0.05),reduced Fe2+accumulation,and increased GSH content(P<0.05),and up-regulated GPX4(P<0.05)and down-regulated ACSL4 and p53 expression(P<0.05)at protein level when compared with the IR group.While,the administration of ferroptosis agonist Era,or p53 agonist KH resulted in diminished therapeutic effects of QUE(P<0.05)when compared with the IR+QUE group.Conclusion QUE alleviates intestinal IR injury by inhibiting ferroptosis,which may be associated with its down-regulating p53 expression.

Objective To investigate whether remimazolam attenuates intestinal ischemia-reperfusion(I/R)injury in mice by regulating ferroptosis through connexin-43(CX43).Methods Molecular docking was applied to predict the binding affinity of remimazolam to CX43.A total of 72 SPF-grade adult male C57BL/6J mice(6～8 weeks old,weighing 20～25 g)were subjected.Thirty of them were randomly divided into sham operation group(Sham group),I/R group 1,and I/R+10,20 and 40 mg/kg remimazolam groups(RM10,RM20 and RM40 groups),with 6 mice in each group.Another 30 mice were randomly assigned into 5 groups(n=6),I/R group 2,erastin group(E group),I/R+40 mg/kg remimazolam group 2(RM40 group 2),I/R+Fer-1 group(Fer-1 group),and erastin+40 mg/kg remimazolam group(ERM group).The left 12 mice were randomly and equally grouped into I/R+RM+oe-NC group(oe-NC group)and I/R+RM+oe-CX43 group(oe-CX43 group).The Fer-1 group was given an intraperitoneal injection of 5 mg/kg Fer-1 in 1 h prior to reperfusion,the E group was given 10 mg/kg erastin intraperitoneally 1 d before modeling,and all the remimazolam groups,the oe-NC group and the oe-CX43 group were injected intravenously with corresponding doses of remimazolam 30 min pre-modeling,while the oe-NC and oe-CX43 groups were injected with empty vector virus and overexpression of CX43 vector virus,respectively,48 h before the administration of remimazolam.A mouse intestinal I/R injury model was constructed by clamping the superior mesenteric artery for 45 min and reperfusion for 30 min.The small intestine tissues were harvested and observed for pathological changes,and the intestinal mucosal damage was assessed with Chiu's score.The contents of Fe2+,total iron,malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)were detected by colorimetric assay;the production of reactive oxygen species(ROS)was determined by DHE probe;the expression of ferroptosis-related genes was determined by RT-qPCR;and the expression levels of CX43,GPX4,and SLC7A11 were detected by Western blotting.Results Molecular docking indicated that remimazolam had a binding energy of-6.699 kcal/mol with CX43 protein,suggesting good binding affinity between them.Compared with the Sham group,the I/R group 1 showed increases in Chiu's scores and CX43 expression(P<0.05),along with pathological damage to intestinal tissues,and elevated contents of Fe2+,total iron,ROS and MDA(P<0.05),and down-regulated GPX4 and SLC7A11(P<0.05).Compared with the I/R group 1,Chiu's score was reduced in the RM40 group,and CX43 was significantly down-regulated(P<0.05),contents of Fe2+,total iron,ROS,and MDA were decreased(P<0.05),and expression levels of GPX4 and SLC7A11 were enhanced(P<0.05),and severity of intestinal histological damage was attenuated in both the RM40 and Fer-1 groups.Compared with the E group,the ERM group had the decreases in CX43 expression level(P<0.05),Fe2+,total iron,ROS,and MDA contents(P<0.05),and increases in GPX4 and SLC7A11 expression levels(P<0.05),with the improvement in intestinal tissue.Compared with the oe-NC group,overexpression of CX43 resulted in the increased CX43 expression,elevated contents of Fe2+,total iron,ROS and MDA(P<0.05)and decreased expression of GPX4 and SLC7A11(P<0.05),leading to the exacerbated injury in intestinal tissue.Conclusion Remimazolam attenuates intestinal I/R injury by inhibiting ferroptosis through down-regulating CX43 expression.

Objective:To evaluate the safety and efficacy of enteromorpha prolifera enzymatic hydrolysate in alleviating scalp sensitive symptoms.Methods:The inhibitory effects of different concentrations of enteromorpha prolifera hydrolysate on tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-6, and other inflammatory factors were observed through in vitro experiments. Subsequently, the abilities to scavenge [2, 2＇-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS) and to promote proliferation of mouse fibroblasts were evaluated. A prospective study was conducted on 20 patients with scalp sensitivity at Qingdao Hiser Hospital Affiliated to Qingdao University from April 2023 to October 2023. The patients included 2 males and 18 females with an average age of (34.9±10.3) years. They were treated with a scalp essence containing 10% enteromorpha enzymatic hydrolysate for consecutive 28 days. Changes in scalp cuticle water content, transepidermal water loss (TEWL), and oil content were measured before and after 14 and 28 days of treatment. Expert interviewers assessed the skin irritation test to elucidate any undesirable side effects.Results:The results of in vitro experiments demonstrated that enteromorpha protophora enzymatic hydrolysate at different concentrations exhibited inhibitory effects on the expression of IL-1α, IL-6, and TNF-α, while it also displayed a dose-dependent ability to scavenge ABTS free radicals. Furthermore, it effectively promoted the proliferation of mouse fibroblasts, resulting in a significant increase of 43.22% in fibroblast viability when the concentration of enteromorpha protophora enzymatic hydrolysate was 0.10%. The outcomes from clinical trials revealed that after using a scalp essence containing enteromorpha protophora enzymatic hydrolysate for 14 and 28 days, there were significant improvements observed in terms of increased water content in the scalp epidermis, along with decreased oil content and TEWL value (all P< 0.001). Moreover, remarkable effective rates were achieved for treating various scalp conditions including redness (80.0%, 16/20), dandruff (80.0%, 16/20), itching (85.0%, 17/20), stinging sensation (90.0%, 18/20), and tightness (80.0%, 16/20) after using the scalp essence for 28 days. Adverse effects on the skin were not observed in any subject during the test period. Conclusions:The enzymatic hydrolysate of enteromorpha demonstrates both safety and efficacy in alleviating symptoms associated with scalp sensitivity.

Objective To understand the situation of medication treatment in out-patients with hypertension.Method 1 210 out-patients with hypertension were investigated by ourselves-made questionnaire on their medication treatment at home.Results In all of the patients,there was only 30.74% of them persisting in taking regular medication.The control rate on blood pressure was 70.96% in patients with regular taking medication and 28.99% in patients with irregular taking medication.The rates of regular taking medication in goverment staff,teachers and retirees were higher.The compliance with medication treatment was increased with the age.There was 79.83% of patients discontinued to take medication after 3-6 months of medication treatment.Conclusion The situation of medication treatment in outpatients is less optimistic.We should strengthen the blood pressure controll in outpatients of the young aged,workers and peasants.