OBJECTIVE To investigate the mechanism of artesunate increasing the sensitivity of hepatocellular carcinoma(HCC)cells to sorafenib in hypoxic microenvironment.METHODS Firstly,hypoxia-resistant HCC cell models were established.NAC(a ROS scavenger),necrostatin-1(a necrosis inhibitor),and ferrostatin-1(a ferroptosis inhibitor)were added to examine the effects of artesunate on the inhibition rate of HCC cells and the primary modes of cell death in hypoxic microenvironment by MTT assays.Intra-cellular levels of GSH,ROS,lipid peroxidation product MDA,and iron ions were measured using corresponding kits.Mitochondrial membrane potential changes were assessed using JC-1 staining.Western blot and qPCR were performed to detect the expression of fer-roptosis-related proteins after the addition of artesunate.RESULTS The sensitivity of HCC cells to sorafenib decreased under hy-poxic microenvironment,but artesunate significantly enhanced this sensitivity.Further analysis revealed that artesunate promoted sor-afenib-induced ferroptosis by increasing ROS levels in HCC cells(P<0.05,P<0.01,P<0.001).Additionally,artesunate was found to inhibit Nrf2 mRNA and protein levels(P<0.05,P<0.01,P<0.001)and downregulate HIF-1α expression(P<0.05,P<0.01,P<0.001).CONCLUSION Artesunate increases intracellular oxidative stress by inhibiting Nrf2 and HIF-1α protein levels,subse-quently induces ferroptosis and enhances the sensitivity of HCC cells to sorafenib in hypoxic microenvironment.

The incidence of age-related macular degeneration(AMD)is rising with the intensifying aging trend,be-coming a critical challenge that demands urgent solutions.Dry AMD(dAMD)accounts for approximately 80％of all AMD cases,and there is currently a lack of highly effective treatment options.In recent years,traditional Chinese medicine(TCM)has been proven to effectively treat dAMD through actions such as antioxidation,anti-apoptosis,anti-inflammation,and lipid-lowering.By reviewing domestic and international literature,this article discusses TCM monomers,extracts,and compound formulations for dAMD,analyzing their various mechanisms.Based on traditional TCM efficacy theories and in-tegrated with modern mechanisms of action,it targets the active components of TCM to elucidate the connection between effective medicinal targets of TCM and dAMD,thereby clarifying the efficacy and scientific basis of TCM monomers,com-pounds,and extracts in treating dAMD.The aim is to provide new perspectives for the prevention and clinical treatment of dAMD.

OBJECTIVE To investigate the mechanism of artesunate increasing the sensitivity of hepatocellular carcinoma(HCC)cells to sorafenib in hypoxic microenvironment.METHODS Firstly,hypoxia-resistant HCC cell models were established.NAC(a ROS scavenger),necrostatin-1(a necrosis inhibitor),and ferrostatin-1(a ferroptosis inhibitor)were added to examine the effects of artesunate on the inhibition rate of HCC cells and the primary modes of cell death in hypoxic microenvironment by MTT assays.Intra-cellular levels of GSH,ROS,lipid peroxidation product MDA,and iron ions were measured using corresponding kits.Mitochondrial membrane potential changes were assessed using JC-1 staining.Western blot and qPCR were performed to detect the expression of fer-roptosis-related proteins after the addition of artesunate.RESULTS The sensitivity of HCC cells to sorafenib decreased under hy-poxic microenvironment,but artesunate significantly enhanced this sensitivity.Further analysis revealed that artesunate promoted sor-afenib-induced ferroptosis by increasing ROS levels in HCC cells(P<0.05,P<0.01,P<0.001).Additionally,artesunate was found to inhibit Nrf2 mRNA and protein levels(P<0.05,P<0.01,P<0.001)and downregulate HIF-1α expression(P<0.05,P<0.01,P<0.001).CONCLUSION Artesunate increases intracellular oxidative stress by inhibiting Nrf2 and HIF-1α protein levels,subse-quently induces ferroptosis and enhances the sensitivity of HCC cells to sorafenib in hypoxic microenvironment.

The incidence of age-related macular degeneration(AMD)is rising with the intensifying aging trend,be-coming a critical challenge that demands urgent solutions.Dry AMD(dAMD)accounts for approximately 80％of all AMD cases,and there is currently a lack of highly effective treatment options.In recent years,traditional Chinese medicine(TCM)has been proven to effectively treat dAMD through actions such as antioxidation,anti-apoptosis,anti-inflammation,and lipid-lowering.By reviewing domestic and international literature,this article discusses TCM monomers,extracts,and compound formulations for dAMD,analyzing their various mechanisms.Based on traditional TCM efficacy theories and in-tegrated with modern mechanisms of action,it targets the active components of TCM to elucidate the connection between effective medicinal targets of TCM and dAMD,thereby clarifying the efficacy and scientific basis of TCM monomers,com-pounds,and extracts in treating dAMD.The aim is to provide new perspectives for the prevention and clinical treatment of dAMD.

Objective: To explore the pattern of change of axial length/curvatrue radius ratio (AL/CR) and associated factors in primary and secondary school students in Yunnan, so as to provide scientific basis and prospective guidance for early myopia intervention and control. Methods: A total of 685 students from grades 2 to 3 and grade 7 in 2 cities/counties in Yunnan Province were selected by multi stage stratified random cluster sampling method in 2020. All the participants were followed up twice with questionnaire of myopia related factors, uncorrected distance visual acuity, and refractive parameter measurement from October,2021 and March,2023,respectivelty. The distribution and change of AL/CR in different classes and groups were analyzed, and the influencing factos of AL/CR cumulative progression were explored using generalized linear model. Results: AL/CR ratio in primary school students was (2.95±0.09) at baseline, increased to (2.99±0.11) at the first follow up and (3.04±0.12) at the second follow up. AL/CR ratio in middle school students(3.08±0.13) at baseline, increased to (3.12±0.15) at the first follow up and (3.15±0.14) at the second follow up. The generalized linear model showed that after controlling for environmental factors, ethnicity ( β =-0.017) , cumulative progression of the SE ( β =-0.027) influenced the changes of AL/CR ratio among the primary school students, whereas the changes of AL/CR ratio were associated with baseline AL ( β =-0.005), baseline corneal curvatrue radius ( β =0.032) and cumulative progression of SE( β =-0.035) among middle school students ( P <0.05). Conclusions The AL/CR ratio of primary and secondary school students in Yunnan can be used to judge different refractive status types, but its variation is not only related to SE progression, but also affected by different ethnic groups and baseline ocular biological parameters. so the value of AL/CR application in assessing the progression of myopia needs to be further confirmed.

Objective:To discuss the effect of D-limonene on the proliferation and apoptosis of the glioblastoma(GBM)cells,and to clarify its possible mechanism.Methods:The GBM cells were divided into control group(0 mmol·L-1 D-limonene)and 0.2,0.4,0.6,0.8,and 1.0 mmol·L-1 D-limonene groups.CCK-8 method was used to detect the inhibitory rates of proliferation of the cells in various groups;clone formation assay was used to detect the clone formation rates of the cells in various groups;Annexin Ⅴ-FITC/PI method was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and poly adenosine diphosphate(ADP)-ribose polymerase(PARP)proteins in the cells in various groups;imunofluorescence method was used to detect the expression levels of cleaved Caspase-3 protein in the cells in various groups.Fifteen model mice with subcutaneous tumor xenografts were randomly divided into blank group(0 mg·kg-1·d-1 D-limonene),low dose of D-limonene group(200 mg·kg-1·d-1 D-limonene),and high dose of D-limonene group(400 mg·kg-1·d-1 D-limonene),and there were 5 mice in each group.The inhibitory rates of the tumor in vitro in various groups were calculated;HE staining and immunohistochemical staining were used to observe the morphology of subcutaneous tumor tissue of the mice in various groups and the growth curves of the tumor were drawn;immunohistochemical assay was used to detect the positive expression rates of Ki67 protein in subcutaneous tumor tissue of the mice in various groups;TUNEL staining was used to detect the apoptosis of the tumor cells in various groups.Results:In control group,the cells were spindle-shaped,in good condition,growing closely and adherently,with normal organelles and cytoplasm.After treated for 48 h,the cells in 0.6 mmol·L-1 D-limonene group showed reduced volume,intact but more permeable cell membranes,shrunken cytoplasm,internal vacuole structures,and some fragments floating in the solution.The cells in 0.8 and 1.0 mmol·L-1 D-limonene groups exhibited significant apoptotic bodies and were in an apoptotic state.The CCK-8 results showed that compared with control group,the inhibitory rates of proliferation of the U87,LN229,and GL261 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01),the inhibitory rates of proliferation of the U87 and GL261 cells were significantly increased(P<0.01).The clone formation assay results showed that compared with control group,the clone formation rates of the U87,LN229,and GL261 cells in 0.4,0.6,and 0.8 mmol·L-1 D-limonene groups were significantly decreased(P<0.05 or P<0.01).The AnnexinⅤ-FITC/PI results showed that compared with control group,after treated with D-limonene for 48 h,the apoptotic rates of the LN229 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of Bax proteins in the LN229 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01),while the expression levels of AKT and Bcl-2 proteins were significantly decreased(P<0.01),the expression level of PARP protein in the LN229 cells in 0.8 and 1.0 mmol·L-1 D-limonene group was significanthy increased(P<0.01).The immunofluorescence results showed that compared with control group,the expression levels of cleaved Caspase-3 protein in the LN229 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01).Compared with blank group,the tumor volumes of the mice in low and high doses of D-limonene groups were significantly decreased(P<0.01).Compared with blank group,the tumor weights of the mice in low and high doses of D-limonene groups were significantly decreased(P<0.05),and the inhitory rates of tumor were significantly increased(P<0.05).The tumor cells in blank group were diffusely distributed,with deepened nuclear staining and increased nucleocytoplasmic ratio;a large number of degenerated and necrotic tumor cells were observed in tumor tissue of the mice in low and high doses of D-limonene groups.Compared with blank group,the positive expression rates of Ki67 protein in tumor tissue of the mice in low and high doses of D-limonene groups were significantly decreased(P<0.01).Compared with blank group,the apoptotic rates of tumor cells of the mice in low and high doses of D-limonene groups were significantly increased(P<0.01).Conclusion:D-limonene has the inhibitory effect on the proliferation of the GBM cells;its mechanism may be related to the regulation of AKT protein expression and the activation of the Caspase-3 pathway to induce the apoptosis.

Objective:To retrieve, screen, evaluate and synthesize evidence related to the management of pregnant women during pregnancy after cervical cerclage to provide a basis for clinical practice.Methods:According to the "6S" evidence resource pyramid model, the system searched of all evidence on the management of pregnant women after cervical cerclage in databases suchas UpTo Date, BMJ Best Clinical Practice, International Guidelines Network, American Guidelines Network, World Health Organization website, Yimaitong, Metz Medical website, Clinical Guidelines website, American College of Obstetricians and Gynaecologists, Royal College of Obstetricians and Gynaecologists of the United Kingdom, Canadian College of Obstetricians and Gynaecologists, French College of Obstetricians and Gynaecologists, European Association of Perinatal Medicine, Cochrane Library, the Joanna Briggs Institute (JBI), the Centre for Evidence-Based Health Care Database, PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang Database, VIP Database, and China Biomedical Literature Database, including best dicision practices, guidelines, expert consensus, evidence summary, systematic reviews, Meta-analysis. The search time limit was the establishment of the database to March 1, 2023, and the evidence was extracted and summarized according to the theme after the two researchers independently evaluate the quality of the literature.Results:A total of 8 studies were selected, including 2 expert consensuses, 2 systematic reviews and 4 guidelines. Through literature reading, evidence extraction and classification, 23 pieces of best evidence were summarized from seven aspects: systematic management, activity management, medication management, health behavior management, pregnancy supervision, supervision of the timing of cerclage removal and supervision of psychological state.Conclusions:The best evidence quality and autuority of pregnancy management for pregnamt women after cervical cerclage surgery summarized in the study are high. It was recommended to strengthen the management of pregnant women during pregnancy after cervical cerclage, dynamically and continuously assess the pregnancy status of pregnant women, and prudently selected evidence to improve the prenatal examination process, ensure the safety of mothers and babies, and reduce the occurrence of complications. Overall, effective management of pregnant women during pregnancy after cervical cerclage required a combination of many factors to ensure the health and safety of the mother and baby.

Objective:To investigate the clinical features of chronic spontaneous urticaria (CSU) patients with angioedema (AE) .Methods:Clinical data were collected from adult outpatients with active CSU diagnosed and treated at the First Hospital of China Medical University from January 2019 to December 2021, and analyzed retrospectively. The data included gender, age, disease duration, the presence or absence of angioedema, urticaria activity score for one day, prior treatments, previous history, family history, laboratory test results, therapeutic effect, and adverse reactions. Their treatment regimens were based on the Chinese guidelines for the diagnosis and treatment of urticaria (2018) and the American guidelines for the diagnosis and management of urticaria (2014). Statistical analysis was carried out by using Mann-Whitney U test, two-independent-sample t test, Chi-square test, corrected Chi-square test, and Fisher's exact test. Results:A total of 131 CSU patients were collected, including 78 females and 53 males. Their age at the first visit was 44.6 ± 13.3 years, and the disease duration ( M[ Q1, Q3]) was 4.0 (2.0, 10.0) months. Among these CSU patients, there were 58 with AE and 73 without AE. The disease duration was significantly longer in the CSU patients with AE (6.0 [3.0, 24.0] months) than in those without AE (3.5 [2.0, 6.0] months; Z = -2.78, P = 0.005). The urticaria activity score for one day was also significantly higher in the CSU patients with AE (5.0 [3.0, 5.3] points) than in those without AE (4.0 [3.0, 5.0] points; Z = -2.63, P = 0.008). The CSU patients with AE showed a decreased proportion of patients completely controlled by licensed-dose second-generation H1-antihistamines (sgAHs) (8.6%, 5/58) compared with those without AE (24.7%, 18/73), but an increased proportion of patients uncontrolled by licensed-dose sgAHs (91.4%, 53/58) compared with those without AE (74.0%, 54/73; Z = -2.53, P = 0.011) ; there were no significant differences in the proportions of patients completely controlled or uncontrolled by updosed sgAHs alone or combinations of 2- to 4-fold equivalent-dose sgAHs, or in the proportions of patients completely controlled or uncontrolled by combination therapy with 4-fold equivalent-dose sgAHs and non-H1-antihistamines between the CSU patients with AE and those without AE ( P > 0.05) . Conclusion:Compared with the CSU patients without AE, the CSU patients with AE had a longer disease duration, higher disease activity, a lower proportion of patients completely controlled by licensed-dose sgAHs, and a higher proportion of patients uncontrolled by licensed-dose sgAHs.

BackgroundDue to the COVID-19 pandemic， both teenagers' studies and personal life are critically affected， which has resulted in a variety of mental health problems. In this regard， scholars at home and abroad have carried out a large number of research concerning adolescent mental health， of which there still exists a lack of systematic combing and review. ObjectiveTo understand the status and development trend of research on adolescent mental health during the COVID-19 pandemic at home and abroad， and to grasp the current research hotspots and trends in this field， so as to provide references for relevant research and practice in the post-epidemic era. MethodsOn October 30， 2022， we searched through China Knowledge Network Infrastructure （CNKI） and Web of Science database， and the publishing time of articles to be retrieved was limited between December 1， 2019 and October 30， 2022. Excel and CiteSpace were used to perform visual analysis on these articles in terms of number， author， institution， country and keywords of the articles. ResultsA total of 7 608 articles were included. At home and abroad， the number of papers related to adolescent mental health generally increased at first and then decreased under the pandemic situation. Compared with foreign countries， the connection and cooperation among domestic scholars and institutions was not close enough. The top three countries in the number of English literature published were the United States， Britain and China， and those in intermediary center were Tunis， Cameroon and Anguilla. The parent-child relationship and mental health of teenagers during were much concerned by scholars both at home and abroad. With the passage of time， researchers at home and abroad had shifted their focus from only negative factors to positive factors. ConclusionChinese scholars or institutions need to strengthen more domestic and international exchanges and cooperation. Scholars from different countries can carry out cross-cultural study on research topics of common concern， and continue to explore the positive psychological changes of teenagers in the post-epidemic era.［Funded by National Social Science Foundation 2020 Education Youth Project of 13th Five-Year Plan （number， CHA200259）］

OBJECTIVE：To establish fingerprint of Paliurus ramosissimus total triterpenes ，and to conduct cluster analysis and principal component analysis ，and to determine the content of the main component paliurusene. METHODS ：HPLC method was adopted. The determination was performed on Agilent PheHex column with mobile phase consisted of methanol- 0.05％ phosphoric acid solution （gradient eluetion ） at the flow rate of 1 mL/min. The detection wavelength was set at 320 nm，and column temperature was 30 ℃. The sample size was 5 μL. Using paliurusene as reference，HPLC fingerprints of 10 batches of P. ramosissimus total triterpenes were drawn. Similarity evaluation was performed by using TCM Chromatographic Fingerprint Similarity Evaluation System （2012 edition），and the common peaks were confirmed. Cluster analysis and principle component analysis were performed by using SPSS 26.0 software. The content of paliurusene was determined by same HPLC method. RESULTS：There were totally 6 common peaks in HPLC fingerprint of 10 batches of P. ramosissimus total triterpenes. The similarity was more than 0.990；one of six common peaks was identified as paliurusene. The results of cluster analysis showed that 10 batches of samples could be clustered into 4 categories，including S 1，S2，S3-S6 and S 7-S10. The results of principal component analysis showed that the accumulative variance contribution rate of primary 2 principal components was 99.430％. Comprehensive score ranking was S 1＞S9＞S8＞S7＞S10＞S2＞S3＞S5＞S6＞S4. The linear range of paliurusene concentration was 33.7-844.0 μg/mL（r＝0.999 9）. RSDs of precision ，reproducibility and stability （24 h）tests were all lower than 2％. Average recovery was 99.75％（RSD＝1.13％，n＝6）. The average contents of paliurusene in 10 batches of P. ramosissimus total triterpenes was 0.576％-0.712％. CONCLUSIONS ：Established HPLC fingerprint and content d etermination method are reliable and stable ， and can be used for the quality control of P. ramosissimus .