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.

Objective:To summarize Chinese materia medica with estrogen-activity based on data mining and analyze their characteristics.Methods:Literature was retrieved from CNKI, Wanfang Data, Chongqing VIP, CBM, PubMed and Web of Science from the establishment of the databases to June 30, 2024, and Chinese materia medica with estrogenic activity were screened. Excel 2021 and KH Coder 3.0 software were used to perform statistical and network co-occurrence analysis on the efficacy classification of Chinese materia medica, properties, tastes and meridians, screening methods for estrogen activity, and applications.Results:Totally 121 kinds of Chinese materia medica with estrogen-activity were included in total. The efficacy classifications were mostly tonic medicines, heat-clearing medicines and blood circulation promoting drugs. The properties were mainly warm and neutral, the tastes were mainly sweet and bitter, and the meridians were mainly the liver, kidney and spleen meridians. The network co-occurrence analysis of the efficacy classification, properties, tastes and tropism meridians showed that the clustering relationship of tonic medicine-neutral-sweet-liver-kidney was the most obvious. The screening methods mainly included MCF-7 cell proliferation and uterine weight gain experiments. Their applications mainly covered osteoporosis, perimenopausal syndrome, lipid metabolism disorder, and premature ovarian failure, etc.Conclusions:Chinese materia medica with estrogen-activity or their components act on estrogen target cells or organs to exert estrogen-like or antagonistic estrogenic effects. This kind of Chinese materia medica can regulate the body's qi, blood, yin and yang, the function of organs and the fullness of Tiangui, as well as the Chong meridian and Conception Vessel, thus improving human growth and development, reproduction and aging. In the future, it is suggested to explore their effective components, mechanisms, bidirectional effect and safety on the basis of guiding clinical medication with the theory of TCM, combining with modern medical research techniques and evidence-based medical research.

Objective To analyze the impact of chronic obstructive pulmonary disease(COPD)on coronary plaque burden in elderly patients.Methods A total of 120 COPD patients admitted to the Hongqi Hospital Affiliated to Mudanjiang Medical University from January 2022 to December 2024 were prospectively enrolled and served as the COPD group.Another 120 healthy volunteers were recruited as the control group during the same period.The general clinical data and coronary plaque burden were compared between the two groups.Pearson linear correlation analysis was used to investigate the correlation between forced expiratory volume in the first second(FEV1)and coronary plaque burden as well as left ventricular ejection fraction(LVEF).Multiple linear regression analysis was employed to identify the influencing factors of total coronary plaque bur-den and calcified plaque burden.Results The COPD group had significantly larger smoking ratio and higher levels of high-sensitivity C-reactive protein(hs-CRP)and IL-6,but obviously lower LVEF and FEV1 levels than the control group(P＜0.01).Notably increased total coronary plaque burden(38.30±8.22 vs 24.61±5.56,P＜0.01),calcified plaque burden(21.11±6.57 vs 12.54±3.65,P＜0.01)and non-calcified plaque burden(17.19±5.39 vs 12.07±3.92,P＜0.01)were observed in the COPD group than the control group.FEV1 was negatively correlated with coro-nary plaque burden,calcified plaque burden,and non-calcified plaque burden,and positively corre-lated with LVEF(P＜0.01).Multiple linear regression analysis showed that FEV1 and IL-6 were influencing factors for both total coronary plaque burden(P＜0.01)and coronary calcified plaque burden(P＜0.01),and FEV1 was an influencing factor of non-calcified plaque burden in coronary arteries(P＜0.01).Conclusion COPD promotes the development of coronary plaque burden.So,for COPD patients,it is necessary to strengthen the monitoring and early prevention of coronary plaque burden.

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.

Objective To analyze the impact of chronic obstructive pulmonary disease(COPD)on coronary plaque burden in elderly patients.Methods A total of 120 COPD patients admitted to the Hongqi Hospital Affiliated to Mudanjiang Medical University from January 2022 to December 2024 were prospectively enrolled and served as the COPD group.Another 120 healthy volunteers were recruited as the control group during the same period.The general clinical data and coronary plaque burden were compared between the two groups.Pearson linear correlation analysis was used to investigate the correlation between forced expiratory volume in the first second(FEV1)and coronary plaque burden as well as left ventricular ejection fraction(LVEF).Multiple linear regression analysis was employed to identify the influencing factors of total coronary plaque bur-den and calcified plaque burden.Results The COPD group had significantly larger smoking ratio and higher levels of high-sensitivity C-reactive protein(hs-CRP)and IL-6,but obviously lower LVEF and FEV1 levels than the control group(P＜0.01).Notably increased total coronary plaque burden(38.30±8.22 vs 24.61±5.56,P＜0.01),calcified plaque burden(21.11±6.57 vs 12.54±3.65,P＜0.01)and non-calcified plaque burden(17.19±5.39 vs 12.07±3.92,P＜0.01)were observed in the COPD group than the control group.FEV1 was negatively correlated with coro-nary plaque burden,calcified plaque burden,and non-calcified plaque burden,and positively corre-lated with LVEF(P＜0.01).Multiple linear regression analysis showed that FEV1 and IL-6 were influencing factors for both total coronary plaque burden(P＜0.01)and coronary calcified plaque burden(P＜0.01),and FEV1 was an influencing factor of non-calcified plaque burden in coronary arteries(P＜0.01).Conclusion COPD promotes the development of coronary plaque burden.So,for COPD patients,it is necessary to strengthen the monitoring and early prevention of coronary plaque burden.

Objective:To analyze the factors associated with the occurrence of dysphagia after endoscopic submucosal dissection(ESD) treatment in patients with early esophageal cancer or precancerous lesions, and to explore their clinical predictive value.Methods:From March 1, 2020 to March 31, 2021, 35 patients diagnosed with early esophageal cancer or precancerous lesions without dysphagia before ESD treatment were recruited. All the patients were followed up for 2 years after ESD, and were divided into the non-dysphagia group (22 cases) and dysphagia group (13 cases) according to the occurrence of postoperative dysphagia. The demographic characteristics(such as gender and age), ESD-related data (such as the range of circumferential resection), the parameters of high resolution esophageal manometry such as distal contraction integral(DCI), the amplitude of peristaltic waves in various esophageal segments, and the psychological states such as self-rating anxiety scale (SAS) scores of the 2 groups were analyzed. Multivariate logistic regression was used to analyze the independent influencing factors for the occurrence of dysphagia after ESD and receiver operating characteristic curve (ROC) of the independent risk factors was plotted to assess the diagnostic efficacy.Results:The result of multivariate logistic regression analysis showed that the range of circumferential resection ( OR=23.881, 95% confidence interval (95% CI) 4.073 to 140.022), the SAS score ( OR=1.157, 95% CI 1.029 to 1.300), the mean value of DCI ( OR=0.864, 95% CI 0.750 to 0.995) and the maximum value of DCI ( OR=0.914, 95% CI 0.837 to 0.998) were independent influencing factors for postoperative dysphagia (all P<0.05).The result of ROC analysis showed that the area under the curve for the range of circumferential resection predicting dysphagia after ESD was 0.895 (95% CI 0.788 to 0.987, P<0.001), with an optimal cut-off value of 72.50, and the area under the curve for SAS score was 0.811 (95% CI 0.660 to 0.962, P=0.001), with an optimal cut-off value of 34.38. Conclusions:Reduced distal esophageal pressure, and(or) contractile weakness may contribute to dysphagia after ESD. Postoperative dysphagia risk increases when the range of circumferential esophageal resection exceeds 72.5% of the lumen circumference or the SAS score is over 34.

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.

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 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 The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.