AIM:This study aims to investigate how nuclear factor E2-related factor 2(Nrf2)influences the proliferation of primary rat pulmonary artery smooth muscle cells(PASMCs)under CoCl2-induced hypoxic conditions,spe-cifically through the aerobic glycolysis pathway,and to elucidate its potential mechanisms of action.METHODS:Prima-ry Sprague-Dawley(SD)rat PASMCs were isolated via enzymatic digestion and exposed to 200 μmol/L CoCl2 to establish a chemical hypoxia cell model.Experiments were conducted at various time points(0,6,24 and 48 h)to assess changes in the protein expression of key aerobic glycolysis enzymes[pyruvate kinase M2(PKM2),lactate dehydrogenase A(LDHA)and monocarboxylate transporter 4(MCT4)]and proliferating cell nuclear antigen(PCNA)in PASMCs subjected to CoCl2 stimulation.The optimal concentrations of the Nrf2 activator dimethyl fumarate(DMF)and the inhibitor ML385 were de-termined using Western blot analysis.Subsequently,the cells were divided into four groups:normoxic control(NC)group,CoCl2 group,CoCl2+DMF group,and NC+ML385 group.The proliferation and migration abilities,along with the protein expression levels of HIF-1α,Nrf2,and key aerobic glycolysis enzymes,were assessed in PASMCs from each group.RESULTS:In the hypoxic model of rat PASMCs induced by CoCl2,Nrf2 protein levels significantly decreased over time(P<0.05),while the levels of key enzymes and PCNA protein significantly increased(P<0.05).Furthermore,the migratory capability of PASMCs was markedly enhanced(P<0.05).Under DMF intervention,the protein expression of key aerobic glycolysis enzymes decreased significantly,along with a reduction in the proliferation and migration abilities of rat PASMCs(P<0.05).Conversely,the experimental results showed opposite trends when Nrf2 expression was inhibit-ed by ML385(P<0.05).CONCLUSION:Nrf2 plays a crucial role in mitigating the proliferation and migration of chemi-cally hypoxic primary rat PASMCs by downregulating aerobic glycolysis.

AIM:This study aims to investigate how nuclear factor E2-related factor 2(Nrf2)influences the proliferation of primary rat pulmonary artery smooth muscle cells(PASMCs)under CoCl2-induced hypoxic conditions,spe-cifically through the aerobic glycolysis pathway,and to elucidate its potential mechanisms of action.METHODS:Prima-ry Sprague-Dawley(SD)rat PASMCs were isolated via enzymatic digestion and exposed to 200 μmol/L CoCl2 to establish a chemical hypoxia cell model.Experiments were conducted at various time points(0,6,24 and 48 h)to assess changes in the protein expression of key aerobic glycolysis enzymes[pyruvate kinase M2(PKM2),lactate dehydrogenase A(LDHA)and monocarboxylate transporter 4(MCT4)]and proliferating cell nuclear antigen(PCNA)in PASMCs subjected to CoCl2 stimulation.The optimal concentrations of the Nrf2 activator dimethyl fumarate(DMF)and the inhibitor ML385 were de-termined using Western blot analysis.Subsequently,the cells were divided into four groups:normoxic control(NC)group,CoCl2 group,CoCl2+DMF group,and NC+ML385 group.The proliferation and migration abilities,along with the protein expression levels of HIF-1α,Nrf2,and key aerobic glycolysis enzymes,were assessed in PASMCs from each group.RESULTS:In the hypoxic model of rat PASMCs induced by CoCl2,Nrf2 protein levels significantly decreased over time(P<0.05),while the levels of key enzymes and PCNA protein significantly increased(P<0.05).Furthermore,the migratory capability of PASMCs was markedly enhanced(P<0.05).Under DMF intervention,the protein expression of key aerobic glycolysis enzymes decreased significantly,along with a reduction in the proliferation and migration abilities of rat PASMCs(P<0.05).Conversely,the experimental results showed opposite trends when Nrf2 expression was inhibit-ed by ML385(P<0.05).CONCLUSION:Nrf2 plays a crucial role in mitigating the proliferation and migration of chemi-cally hypoxic primary rat PASMCs by downregulating aerobic glycolysis.

ObjectiveTo observe the effectivenss and safety of Yiqi Huoxue Formula （益气活血方） combined with surgery and sequential therapy of estrogen and progesterone for the treatment of intrauterine adhesion with syndrome of qi deficiency and blood stasis. MethodsSixty-four patients with intrauterine adhesions were recruited in Guang'anmen Hospital， China Academy of Chinese Medical Sciences during 1st June 2021 to 31st December 2022， and they were randomly divided into two groups， with 32 patients in each group， all receiving transcervical resection of adhesions （TCRA）. The control group was treated with sequential therapy of estrogen and progesterone after surgery， taking 1 tablet orally daily， estradiol tablets for the first 14 days， and estradiol dydrogesterone tablets for the last 14 days. In the treatment group， the postoperative treatment was combined with Yiqi Huoxue Formula on the basis of the treatment in the control group， and 1 dose was taken daily. The treatment course of both groups was 3 months. We observed the clinical effectiveness， syndrome scores of traditional Chinese Medicine （TCM）， endometrial thickness， uterine adhesion score， menstrual flow points， and the re-adhesion rate and pregnancy rate 3 months after the end of treatment of the two groups， and conducted evaluation on safety. ResultsThe total clinical effectiveness rates of the treatment group and the control group were 90.63% and 75.00%， respectively， significantly better in the treatment group （P＜0.05）. The endometrial thickness and menstrual flow of patients in both groups increased after treatment， and the scores of uterine adhesion and TCM syndrome scores decreased significantly （P＜0.05 or P＜0.01）. After treatment， the uterine adhesion score and TCM syndrome scores of the treatment group decreased significantly compared with the control group （P＜0.05）. The 6-month postoperative pregnancy rate in the treatment group was 37.50%， higher than the 12.50% in the control group （P＜0.05）. The re-adhesion rate was 3.13% in the treatment group and 9.38% in the control group， and the difference between the two groups was not statistically significant （P＞0.05）. No adverse events occurred in both groups. ConclusionYiqi Huoxue Formula combined with surgery and sequential therapy of estrogen and progesterone for treating intrauterine adhesion patients with syndrome of qi deficiency and blood stasis can promote endometrial recovery， increase menstrual flow， improve patients' clinical symptoms， and improve pregnancy rate， showing certain clinical effectiveness and safety.

Objective To construct curcumin pyrazole derivative by the reaction of diketone of curcumin and benzylhydrazine based on the above structure-activity relationship,and to explore its antioxidant activity to provide experimental basis for the development of curcumin antioxidant derivative.Methods Curcumin-N-substituted pyrazole derivative was synthesized from curcumin and benzylhydrazine.The structures of the derivative were confirmed by infrared spectroscopy(IR),nuclear magnetic resonance spectroscopy(1H-NMR,13C-NMR)and LC-MS.The antioxidant activity in vitro of the derivative was evaluated by determination of curcumin and its pyrazole derivative scavenging ability for 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid(ABTS)free radical.Results Curcumin pyrazole derivative was successfully synthesized.Curcumin and its pyrazole derivative showed good free radical scavenging effects in the range of 4.6-73.6,6.25-100 μg·mL-1,respectively,with a significant dose-effect relationship.The half-maximal inhibition(IC50)values of curcumin and its pyrazole derivatives determined by DPPH method were 14.24,40.37 μg·mL-1,respectively,while the IC50 values of curcumin and its pyrazole derivatives determined by ABTS method were 36.65,19.26 μg·mL-1,respectively.Conclusion The antioxidant activity of β-dione of curcumin was retained through the substitution of the pyrazole ring,and the curcumin pyrazole derivative deserves further investigation as a potential antioxidant.

Objective To compare the clinical efficacy and pregnancy outcomes of CO2 laser and loop electrosurgical excision procedure(LEEP)surgery in the treatment of cervical high-grade squamous intraepithelial lesion(HSIL)in women of childbearing age.Methods Patients with cervical HSIL of appropriate reproductive age(20-34 years old)who underwent satisfied colposcope,subsequently treated with laser or LEEP between Jan 2019 and Dec 2021 in Obstetrics and Gynecology Hospital,Fudan University were collected.All the patients were interpreted as transformation zone(TZ)type 1/2,and colposcopy biopsy diagnosed as cervical high-grade squamous intraepithelial lesion(HSIL)and received laser or LEEP according to the physician's advice and the patient's wishes.The effectiveness of the two surgeries was evaluated,and postoperative cytology,HPV result,and colposcopic pathology were compared.We monitored the surgical pregnancy rate,pregnancy complications,and pregnancy results after the surgery.Results A total of 566 cases,including 233 laser cases and 333 LEEP cases,were enrolled.There was no significant difference between the two groups in terms of preoperative cytology,HPV distribution,or the length of cervical canal.After 6 months of surgery,91.5%of patients who underwent laser therapy and 86.9%of those who underwent LEEP had normal cytology.The histology cure rate was 91.5%and the HPV conversion rate was 74.6%in both groups.The results of cytology,HPV,and colposcopic pathology had no significant difference between the two groups.The length of postoperative cervical canal was significantly longer in laser group than that in LEEP group[(29.09±3.15)mm vs.(27.05±3.84)mm,P<0.001].There was no statistically significant difference in postoperative pregnancy rate and pregnancy outcome between the two groups.Conclusion Laser ablation and LEEP produce comparable effects pregnancy outcomes in cervical HSIL patients with TZ types 1 and 2,while LEEP has pathologic feedback,so its misdiagnosis of invasive cancer reduce.

Cholangiocarcinoma is a malignant tumor with biliary epithelial features.The early diagnosis of cholangiocarcinoma is currently difficult and the treatment outcomes are poor.Its microenvironment includes abundant fibrotic mesenchyme and a variety of cell types,which promote the development and metastasis of cholangiocarcinoma by interacting with tumor cells through mechanisms such as facilitating migration,suppressing the immune response,and inducing angiogenesis and lymphangiogenesis.Immunotherapy is an important tumor treatment approach,and immunotherapy for cholangiocarcinoma has made some progress.This article reviews the characteristics of the immune microenvironment of cholangiocarcinoma,its relationship with immunotherapy,and cutting-edge therapeutic strategies.

Objective To systematically evaluate the efficacy of traditional Chinese medicine(TCM)in the treatment of recurrent spontaneous abortion and their regulatory effects of levels of peripheral blood Th17 cells and Treg cells.Methods Computer retrieval of CNKI,WanFang,VIP,SinoMed,FMRS,PubMed,Cochrane Library,Embase,Web of science and other databases were carried out.RCTS related to the regulation of Th17 and Treg cells by TCM in the treatment of recurrent spontaneous abortion,published from the establishment of the database to June 2023 were screened.Two reviewers evaluated the quality of the literature according to the Cochrane handbook.RevMan5.4 software was used for Meta-Analysis.Results A total of 10 studies that involved 1 052 patients were included.The Meta-Analysis results showed that compared to the control group,the effective rate[RR=1.20,95%CI(1.11,1.30),P＜0.000 01],live birth rate[RR=1.32,95%CI(1.16,1.50),P＜0.000 01]and the reduction of adverse drug reactions[RR=0.34,95%CI(0.14,0.83),P=0.02]were significantly improved by the intervention of TCM.After treatment with TCM,the expression of Th17 cells was decreased[MD=-0.71,95%CI(-1.01,-0.41),P＜0.000 01],and the expression of Treg cells was increased[SMD=1.21,95%CI(0.80,1.62),P＜0.000 01].The ratio of Th17/Treg cells was decreased[SMD=-2.62,95%CI(-4.09,-1.14),P=0.000 5].Conclusion TCM used for post-pregnancy or before and after pregnancy can significantly improve the clinical symptoms and live birth rate of patients with recurrent spontaneous abortion,wihch showed high safety.Moreover,TCM can reduce the expression of Th17 cells,up-regulate the expression of Treg cells and regulate the immune balance of Th17/Treg cells,which is conducive to embryonic development after pregnancy.

Aim To investigate the mechanism of Pi- ezol in the phenotypic changes of rat coronary arterial smooth muscle cells ( CASMCs) induced by high hydrostatic pressure.Methods CASMCs were isolated from Wistar rats and stimulated for 24 h at 0, 120 and 180 mmHg, respectively.The expressions of Piezol , contractile phenotvpe-related proteins including Cavl.2 ,SM-MHC ,cx-SMA and synthetic phenotvpe-re- lated proteins including OPN , MMP-2, Coll al were detected by Western blot.The effect of calcium influx mediated by Piezol was detected by Laser confocal mi- j j croscopy.CASMCs were treated with Piezol agonist Yodal , inhibitor GsMTx4 and Piezol-siHNA , respectively and the expressions of contractile phenotvpe and synthetic phenotvpe-related proteins were detected by Western blot.Results Compared with control ( 0 mmHg) , the expressions of Piezol , OPN, MMP-2 and Collal increased, but the expressions of Cavl.2,SM- MHC and cx-SMA decreased in 120 mmHg as well as 180 mmHg group.After stimulated by 180 mmHg high pressure, Piezol-mediated calcium influx was stronger than that in 0 mmHg group, hut decreased after Piezol knockdown.Treated with Yodal at 0 mmHg, the expression of contractile phenotvpe-related protein decreased while the expression of synthetic phenotvpe-re- lated protein increased compared with DMSO group..\Jfter using GsMTx4 to inhibit or siRNA to knockdown Piezol at 180 mmHg,the expression of contractile phe- notvpe-related protein increased and the expression of synthetic phenotype-related protein decreased compared with the control group.Conclusion Piezol promotes the transition from contractile phenotvpe to syn-thetic phenotvpe of CASMCs induced by high hydrostatic pressure.

Aim To investigate the role of calcium-independent phospholipase A2(iPLA2)in calcium regu-lation of intrarenal artery smooth muscle contraction.Methods The method of measuring the tension of isolated arterioles was used to explore the effect of bromoenol lactone(BEL), a specific inhibitor of iPLA2, on the tension of the intrarenal arteries in mice induced by different calcium channels, and the laser confocal calcium measurement technology was used to investigate the effect of BEL on the intracellular calcium influx mediated by arachidonic acid-mediated calcium channels.Results The intrarenal artery concentration dependent contractile response induced by the vasoconstrictors phenylephrine and 5-hydroxy tryptamine was inhibited by BEL(P<0.01).The contraction curve induced by CaCl2 was also inhibited by BEL(P<0.05).In the calcium-free K-H solution incubated with nifedipine, the intrarenal artery vasoconstriction caused by the release of sarcoplasmic reticulum calcium and the calcium influx of the SOC channel induced by CaCl2 was inhibited by BEL(P<0.05).BEL significantly inhibited the external calcium influx mediated by the ARC channel of human aortic smooth muscle cell lines incubated with nifedipine(P<0.01).Conclusions iPLA2 mediates the contractile response of intrarenal arteries by regulating the functions of L-type calcium channels, sarcoplasmic reticulum calcium release, SOC channels and ARC channels.

Objective:To explore the effect of narrative nursing in patients with retinal detachment undergoing surgery.Methods:From February 2020 to August 2021, 40 patients with retinal detachment who underwent surgical treatment in the Department of Geriatrics and Ophthalmology of Beijing Tongren Hospital, Capital Medical University were selected as the research object by the convenient sampling method. According to the random number table method, the patients were divided into the observation group and the control group, 20 cases in each. The patients in the control group were given routine nursing, and the patients in the observation group received narrative nursing on this basis. Before and after the intervention, Self-Rating Anxiety Scale (SAS) , Self-Rating Depression Scale (SDS) , Memorial University of Newfoundland Scale of Happiness (MUNSH) , and Generic Quality of Life Inventory-74 (GQOLI-74) were used to investigate the two groups of patients. The hospitalization time and complications of the two groups of patients were recorded.Results:At discharge, the SAS and SDS scores of the observation group were lower than those of the control group, the GQOLI-74 and MUNSH scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.01) . The hospitalization time of the observation group was shorter than that of the control group, and the difference was statistically significant ( P<0.05) . There was no significant difference in the number of cases of postoperative intraocular hypertension between the two groups ( P>0.05) . Conclusions:Narrative nursing can effectively relieve anxiety and depression in patients with retinal detachment surgery, improve patients' well-being and quality of life, and shorten hospitalization time.