Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities.

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 µM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 µM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Splicing factor hnRNPA1 regulates alternative splicing of LOXL2 to enhance the production of LOXL2Δ13.

Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and has the ability to catalyze the cross-linking of extracellular matrix collagen and elastin. High expression of LOXL2 is related to tumor cell proliferation, invasion, and metastasis. LOXL2 contains 14 exons. Previous studies have found that LOXL2 has abnormal alternative splicing and exon skipping in a variety of tissues and cells, resulting in a new alternatively spliced isoform denoted LOXL2Δ13. LOXL2Δ13 lacks LOXL2WT exon 13, but its encoded protein has greater ability to induce tumor cell proliferation, invasion, and metastasis. However, the molecular events that produce LOXL2Δ13 are still unclear. In this study, we found that overexpression of the splicing factor hnRNPA1 in cells can regulate the alternative splicing of LOXL2 and increase the expression of LOXL2Δ13. The exonic splicing silencer exists at the 3' splice site and 5' splice site of LOXL2 exon 13. HnRNPA1 can bind to the exonic splicing silencer and inhibit the inclusion of exon 13. The RRM domain of hnRNPA1 and phosphorylation of hnRNPA1 at S91 and S95 are important for the regulation of LOXL2 alternative splicing. These results show that hnRNPA1 is a splicing factor that enhances the production of LOXL2Δ13.

Analysis of Influencing Factors and Strategies for Premature Breast Development in Female Children based on Logistic Regression Analysis: A Randomized Double-blind Controlled Clinical Trial.

Objective: To investigate and analyze the influencing factors of simple early breast development in girls, to discover the dangers and triggers of PT conversion to ICPP, and the time point of transformation in order to detect and prevent the occurrence of transformation in advance and reduce the incidence of idiopathic central precocious puberty. Ensure children's physical and mental health and normal growth and development. Methods: A total of 50 children with PT admitted to our hospital from April 2019 to December 2020 were included in the study group, and 50 children with physical examination during the same period were selected as the control group. All children were tested for vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., and IGFBp-3 at 3, 6, 9 and 12 months after the diagnosis of PT. Results: Vitamin D levels decreased in the child, indicating that vitamin D deficiency was closely related to the age of breast development in ICPP girls and may be related to serum P-FSH, P-LH and E2 levels. Increased levels of IGFBp-3 indicate that these indicators are involved in the onset of ICPP. Children have a higher BMI, watch idol dramas or play mobile games longer, often eat snacks containing preservatives, have a fishy diet, are more irritable and sensitive, and dry stools are also risk factors affecting the early development of simple breasts in girls. Conclusion: The influencing factors leading to simple, early breast development in girls include vitamin D, androstenedione, dehydroepiandrosterone, 17-hydroxyprogesterone, leptin, IGF-I., IGFBp-3, and should be combined with the progression of breast Tanner staging (complete regression, recurrent, and persistent), height growth rate, bone age, Uterine and ovarian B ultrasound, sex hormones, etc., warn of the conversion of PT to ICPP, and ensure children's physical and mental health and normal growth and development.

CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

CD39hi identifies an exhausted tumor-reactive CD8+ T cell population associated with tumor progression in human gastric cancer.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Oxidative stress is associated with Aß accumulation in chronic sleep deprivation model.

Amyloid-ß (Aß) accumulation is the main pathological change in Alzheimer's disease (AD), which results from the imbalance of production and clearance of Aß in the brain. Our previous study found that chronic sleep deprivation (CSD) led to the deposition of Aß in the brain by disrupting the balance of Aß production and clearance, but the specific mechanism was not clear. In the present study, we investigated the effects of oxidative stress on Aß accumulation in CSD rats. We found that the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after CSD, while superoxide dismutase (SOD) decreased in the brain. Furthermore, the serum ROS was elevated and SOD declined after CSD. The levels of oxidative stress in the brain were significantly correlated with ß-site APP-cleaving enzyme 1 (BACE1), low-density lipoprotein receptor-related protein-1 (LRP1), and receptor of advanced glycation end products (RAGE) levels in hippocampus and prefrontal lobe, and the concentration of serum oxidative mediators were strongly correlated with plasma levels of soluble LRP1 (sLRP1) and soluble RAGE (sRAGE). These results suggested that the oxidative stress in the brain and serum may involved in the CSD-induced Aß accumulation. The underlying mechanism may be associated with disrupting the balance of Aß production and clearance.

Analysis of goitrogenic effect of goitrogen in food / 中华地方病学杂志

Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.

Correlation between expressions of serum COL1A1/2 and intracranial aneurysm rupture / 局解手术学杂志

Objective To detect the levels of serum collagen type Ⅰ alpha 1 chain(COL1A1)and collagen type Ⅰ alpha 2 chain(COL1A2)in patients with intracranial aneurysm(IA),and explore their correlations with aneurysm rupture.Methods A total of 110 IA patients admitted to our hospital were regarded as the IA group and another 100 volunteers who underwent physical examination in our hospital were regarded as the control group.The expression levels of serum COL1A1 and COL1A2 were detected by ELISA.The IA patients were divided into the ruptured group(n=66)and unruptured group(n=44)according to the presence or absence of aneurysm rupture,and the clinical data and expression levels of serum COL1A1 and COL1A2 were compared between the two groups.The expression levels of serum COL1A1 and COL1A2 in patients with different Hunt-Hess grades were compared.The risk factors of aneurysm rupture in patients with IA were analyzed by multivariate Logistic regression analysis.The predictive value of serum COL1A1 and COL1A2 for aneurysm rupture in patients with IA were evaluated by receiver operating characteristic(ROC)curve.The correlation of serum COL1A1 and COL1A2 with Hunt-Hess grade for patients in rupture group was analyzed by Spearman correlation analysis.Results The expression levels of serum COL1A1 and COL1A2 for patients in the IA group were significantly higher than those in the control group(P<0.05).The number of patients with hypertension,diabetes mellitus,hyperlipidemia,aneurysm diameter>10 mm,and the expression levels of serum COL1A1 and COL1A2 in the rupture group were significantly more/higher than those in the unruptured group(P<0.05).The expression levels of serum COL1A1 and COL1A2 in patients with Hunt-Hess grades from Ⅲ to Ⅳ were significantly higher than those in patients with grades from Ⅰ to Ⅱ(P<0.05).The expression levels of serum COL1A1 and COL1A2 for patients in the rupture group were positively correlated with Hunt-Hess grade(r=0.562,0.414,P<0.05).Multivariate Logistic regression analysis showed that hypertension,diabetes mellitus,aneurysm diameter>10 mm,and increased expression levels of COL1A1 and COL1A2 were risk factors for aneurysm rupture in IA patients(P<0.05).The area under the curve(AUC)of aneurysm rupture predicted by serum COL1A1 and COL1A2 together was significantly higher than that predicted by COL1A1 alone(Z=1.905,P=0.028)and COL1A2 alone(Z=1.754,P=0.040).Conclusion The increased expression levels of serum COL1A1 and COL1A2 are risk factors for aneurysm rupture in patients with IA,and their combined prediction of aneurysm rupture in IA patients has certain clinical value.

Differential Diagnosis of Dynamic Contrast-Enhanced-MRI-Based Radiomics Model for Granulomatous Mastitis and Breast Cancer / 中国医学影像学杂志

Purpose To investigate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in the differential diagnosis of granulomatous mastitis and breast cancer.Materials and Methods The MRI data of 82 patients with granulomatous mastitis or breast cancer confirmed by pathology in Xiyuan Hospital of China Academy of Chinese Medical Sciences from February 2019 to January 2022 were retrospectively collected.Based on the first phase of DCE-MRI,the regions of interest(ROI)were delineated layer by layer by semi-automatic segmentation method and manual segmentation method,respectively.99 ROI were randomly assigned to 69 in training groups and 30 in test groups.The consistency difference between the two methods was compared.The original data extracted by the semi-automatic segmentation method were screened by correlation analysis and multi-factor Logistic regression.Six kinds of classifiers(Logistic regression,support vector machine,naive Bayes,decision tree,random forest,K nearest neighbor)were used to construct prediction models,and the differences in diagnostic efficiency,accuracy,sensitivity and specificity of each model were evaluated.Results A total of 99 lesions(n=37 cases with granulomatous mastitis and n=62 cases with breast cancer)were segmented from 82 patients.The radiomics data extracted by the two ROI segmentation methods had poor consistency between groups[Intraclass correlation coefficient=0.68(0.51,0.78)].Among the six prediction models constructed from the data extracted by the semi-automatic segmentation method,the diagnostic performance of the Logistic regression model and the support vector machine model was significantly better than those of other models,and the Logistic regression model had the best diagnostic performance and stability(training group:area under the curve 0.928,accuracy rate 0.855,sensitivity 0.837,specificity 0.885;test group:area under the curve 0.933,accuracy 0.833,sensitivity 0.895,specificity 0.727,respectively).Conclusion Radiomics based on DCE-MRI can provide high value for the differential diagnosis of granulomatous mastitis and breast cancer.The semi-automatic segmentation method is more recommended for the segmentation method of ROI.The prediction model constructed by Logistic regression and support vector machine shows better diagnostic efficiency and stability.

Correlation study of carotid artery plaque components and CT cerebral perfusion by the analysis of CT energy spectrum imaging / 中国医学装备

Objective:To quantitatively analyze the plaque components of carotid artery through energy spectrum computed tomography angiography(CTA),and to measure the blood flow perfusion in the blood-supply area of carotid artery through CT perfusion(CTP),so as to explore the relationship among plaque component,the degree of luminal stenosis and cerebral blood flow perfusion.Methods:A total of 68 patients with unilateral plaques of carotid artery and severe vascular stenosis who were screened and diagnosed by ultrasound and CTA in Xiyuan Hospital from December 2017 to July 2019 were selected,and all patients underwent CTA examination and CTP examination.North American symptomatic carotid endarterectomy test(NASCET)method was used to measure the degree of carotid stenosis.The GE AW 4.7 post-process workstation was used to conduct analyses of energy spectrum and cerebral perfusion for the plaque component.And then,the slope of energy spectrum curve and the effective atomic number were obtained.At the same time,the cerebral blood volume(CBV),cerebral blood flow(CBF),time to peak(TTP)and mean transit time(MTT)of contrast agent in blood-supplying area of anterior cerebral artery(ACA)and middle cerebral artery(MCA)at the side of lesion were measured.Results:A total of 68 measured plaques of 68 patients met the condition,including 44 vulnerable plaques(including lipid plaques and mixed plaques)and 24 stable plaques(fibrous plaques).The average slopes of the energy spectrum curves of vulnerable plaque and stable plaque were respectively 0.45±0.45 and 1.15±0.39,and the differences were significant(t=2.413,P<0.05).The averagely effective atomic numbers of vulnerable plaques and stable plaques were respectively 7.21±1.06 and 8.01±0.63,and the difference were significant(t=2.548,P<0.05).The average TTP values of the ACA at the side of lesion of vulnerable plaques and stable plaques were respectively(12.20±1.61)S and(13.59±2.79)S,and the difference was significant(t=-2.607,P<0.05).The mean MTT values of the ACA at the side of lesion of vulnerable plaques and stable plaques were respectively(5.07±1.66)S and(6.09±2.19)S,and the difference was significant(t=-2.177,P<0.05).The degree of vascular stenosis at the side of lesion was positively correlated with TTP and MTT in blood-supplying area of middle cerebral artery(MCA)at the side of lesion(r=0.537,0.465,P<0.05),and that was negatively correlated with CBF values in blood-supplying areas of ACA and MCA at the side of lesion(r=-0.281,-0.569,P<0.05),respectively.The slope of the energy spectrum curve of carotid plaque was positively correlated with the TTP values in blood-supplying areas of ACA and MCA at the side of lesion(r=0.242,0.246,P<0.05),respectively.Conclusion:CT spectral imaging can quantitatively analyze the displayed components of carotid atherosclerotic plaque,and the degree of vascular stenosis can affect the blood flow perfusion of cerebral tissue,and the delays of TTP and MTT are more easily caused by vulnerable plaque,and the TTP of them is more sensitivity.

Comparison of a single palmar lateral transverse approach versus the modified Henry approach in locking plate fixation of distal radius fractures / 中华创伤骨科杂志

Objective:To compare the clinical efficacy between a single palmar lateral transverse approach and the modified Henry approach in the locking plate fixation for distal radius fractures.Methods:A retrospective study was conducted to analyze the data of 82 patients with distal radius fracture who had undergone locking plate fixation through either a single palmar lateral approach or the modified Henry approach between January 2016 and December 2022 at Department of Traumatic Orthopaedics, Taihe Hospital, Affiliated to Hubei University of Medicine. There were 25 males and 57 females, with an age of (53.8±12.7) years. Based on the difference in surgical approach, the patients were divided into a single transverse approach group ( n=42) and a modified Henry approach group ( n=40). The 2 groups were compared in terms of injury cause, injury location, time from injury to surgery, AO fracture classification, tourniquet time during surgery, incision length, fracture reduction, Patient and Observer Scar Assessment Scale (PSAS & OSAS) and Disability of the Arm, Shoulder, and Hand (DASH) score at the last follow-up, and complications after surgery. Results:There were no statistically significant differences in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (8.2±3.5) months. Follow-ups revealed one case of injury to the palmar cutaneous branch of the median nerve but no other complications like infection, non-union, internal fixation failure, or tendon injury in the single transverse approach group. The single transverse approach group was significantly superior over the modified Henry approach group in incision length [(2.4±0.9) cm versus (5.3±1.6) cm], OSAS (8.1±4.2 versus 10.3±5.7), and PSAS (10.1±5.8 versus 14.7±6.4) ( P<0.05). There were no significant differences between the 2 groups in tourniquet time, fracture reduction quality, and DASH score at the last follow-up ( P>0.05). Conclusion:In locking plate fixation for distal radius fractures, in comparison with the modified Henry approach, a single palmar lateral approach is more minimally invasive so that more aesthetically pleasing outcomes can be achieved to facilitate patients' rapid return to work and society.

Effect of ankyrin-repeat domain-containing protein 22 on human hepatoma cells and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the effect of ankyrin-repeat domain-containing protein 22 （ANKRD22） on the proliferation， invasion， and migration of human hepatoma cells and its molecular mechanism. MethodsThe TCGA database was used to analyze the expression level of ANKRD22 in normal liver tissue and hepatocellular carcinoma tissue and its association with prognosis. Western Blot and qRT-PCR were used to measure the expression of ANKRD22 in human normal liver cells （L-02） and human hepatoma cells （Huh7， HepG2， MHCC-97H， SK-HEP-1， and SMMC-7721）； CCK-8 assay， EdU， wound healing assay， and Transwell assay were used to observe the effect of ANKRD22 on the proliferation， invasion， and migration of hepatoma cells； Western Blot was used to investigate the association of ANKRD22 with cyclins and EMT-related proteins； KEGG and ssGSEA analyses were performed to investigate the mechanism of action of ANKRD22 in hepatoma cells， and related experiments were conducted for validation. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the TCGA database， the expression level of ANKRD22 in hepatoma tissue was significantly higher than that in normal liver tissue （t=5.083， P<0.05）， and the patients with a high expression level of ANKRD22 had longer overall survival and disease-related survival than those with a low expression level of ANKRD22 （P<0.05）. The expression level of ANKRD22 in various human hepatoma cell lines was higher than that in human normal liver cells （all P<0.05）. Cell proliferation assay showed that the ANKRD22 overexpression group had significantly higher EdU positive rate and proliferation rate than the Vector group （t=19.60 and 6.72， both P<0.001）， and compared with the si-NC group， the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower EdU positive rate and proliferation rate （all P<0.001）. Compared with the Vector group， the overexpression group had significantly higher expression levels of Cyclin E1， Cyclin D1， CDK7， and CDK4 （t=3.54， 4.95， 6.34， and 5.19， all P<0.01）， and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group （all P<0.001）. The overexpression group had a significantly lower expression level of P27 than the Vector group （t=6.12， P<0.001）， and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group （both P<0.001）. Invasion and migration experiments showed that compared with the Vector group， the ANKRD22 overexpression group had significantly higher migration rate and number of crossings through the membrane （migration group and invasion group） （t=5.01， 25.60， and 3.67， all P<0.05）， and compared with the si-NC group， thesi-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower migration rate and number of crossings through the membrane （migration group and invasion group） （all P<0.01）. The overexpression group had significantly higher expression levels of N-cadherin， Vimentin， and Snail than the Vector group （t=12.13， 8.85， and 13.97， all P<0.001）， and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group （all P<0.001）； the overexpression group had a significantly lower expression level of E-cadherin than the Vector group （t=4.98， P<0.01）， and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group （both P<0.001）. The KEGG enrichment analysis and the ssGSEA analysis showed that ANKRD22 was associated with the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma， and the overexpression group had significantly higher expression levels of p-AKT/AKT， p-PI3K/PI3K， and p-mTOR/mTOR than the Vector group （t=12.21， 3.43， and 9.75， all P<0.01）， and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group （all P<0.001）. ConclusionANKRD22 is highly expressed in hepatoma cells and can promote the proliferation， invasion， and migration of hepatoma cells and the activation of the PI3K/AKT/mTOR signaling pathway.

Icariin ameliorates viral myocarditis by inhibiting TLR4-mediated ferroptosis

@#Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.

Exercise intervention prescription for postmenopausal women with nonalcoholic fatty liver disease and related comorbidities / 临床肝胆病杂志

The prevalence rate of nonalcoholic fatty liver disease （NAFLD） in postmenopausal women is significantly higher than that in premenopausal women and even exceeds that in men of the same age group， and exercise intervention remains an effective method for the prevention and treatment of NAFLD in postmenopausal women. In addition， postmenopausal women with NAFLD often have comorbidities such as sarcopenia， osteoporosis， cardiovascular diseases， and diabetes， which requires targeted exercise prescriptions and proactive intervention for potential comorbidities. Through a literature review， this article provides targeted recommendations for exercise intervention prescriptions in postmenopausal women with NAFLD and related comorbidities.

A Retrospective Study on the Qianyang Fengsui Dan Combined with Flying Needle Therapy in the Treatment of Kidney-Yang Deficiency Type of Insomnia / 广州中医药大学学报

Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.

Research on Automatic Microalgae Detection System Based on Deep Learning / 生物化学与生物物理进展

ObjectiveThe scale of microalgae farming industry is huge. During farming, it is easy for microalgae to be affected by miscellaneous bacteria and other contaminants. Because of that, periodic test is necessary to ensure the growth of microalgae. Present microscopy imaging and spectral analysis methods have higher requirements for experiment personnel, equipment and sites, for which it is unable to achieve real-time portable detection. For the purpose of real-time portable microalgae detection, a real-time microalgae detection system of low detection requirement and fast detection speed is needed. MethodsThis study has developed a microalgae detection system based on deep learning. A microscopy imaging device based on bright field was constructed. With imaged captured from the device, a neural network based on YOLOv3 was trained and deployed on microcomputer, thus realizing real-time portable microalgae detection. This study has also improved the feature extraction network by introducing cross-region residual connection and attention mechanism and replacing optimizer with Adam optimizer using multistage and multimethod strategy. ResultsWith cross-region residual connection, the mAP value reached 0.92. Compared with manual result, the detection error was 2.47%. ConclusionThe system could achieve real-time portable microalgae detection and provide relatively accurate detection result, so it can be applied to periodic test in microalgae farming.

Retinal Thinning as a Marker of Disease Severity in Progressive Supranuclear Palsy

Objective@#Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. @*Methods@#We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. @*Results@#The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. @*Conclusion@#The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

Proliferation and metabolic patterns of smooth muscle cells during construction of tissue-engineered blood vessels / 中国组织工程研究

BACKGROUND:Seed cells are seeded on three-dimensional scaffold materials,and three-dimensional culture in bioreactors is a common in vitro tissue engineering culture method,but the changes in cell proliferation and metabolic patterns in bioengineered blood vessel construction are still unclear. OBJECTIVE:To explore the metabolic changes of cells such as oxygen consumption and their causes during the whole process of biological vascular tissue construction by in vitro bioreactor. METHODS:The self-built vascular bioreactor system was used as the platform;bovine vascular smooth muscle cells were used as the seed cells,and a conventional CO2 incubator provided the external gas environment for the cultivation process.Seed cells were seeded on a tubular porous polyglycolic acid scaffold material for three-dimensional culture,and the whole process included a one-week resting period and a seven-week pulsating tensile stress stimulation loading period.A non-invasive monitoring system was built,and the optical dissolved oxygen patch method was used to monitor the changes of dissolved oxygen in the culture solution in the reactor,and the glucose consumption and lactic acid production were measured by regular sampling.CCK-8 assay was used to determine the proliferation of smooth muscle cells on polyglycolic acid three-dimensional scaffold materials.Nicotinamide adenine dinucleotide oxidation state and reduction state ratio(NAD+/NADH)was utilized to understand cell proliferation and metabolism in the early stage of culture.RT-qPCR and western blot assay were applied to detect the expression of proliferation-related genes(Ki67)and glycolysis-related genes(GLUT-1,LDHA). RESULTS AND CONCLUSION:(1)The dissolved oxygen level in the culture solution was(4.314±0.380)mg/L from the cell injection to the end of the resting period(the first week),and gradually stabilized at(1.960±0.866)mg/L after the tensile stress stimulation(the last seven weeks);the two had significant changes(P<0.05).(2)The ratio of glucose consumption to lactic acid production in the cell culture medium YL/G increased rapidly after the cells were injected,and the highest value was above 1 on the fifth day,and then slow down to 0.5(The mean value of YL/G in the resting period was 0.89 and the mean value in the pressurized period was 0.57,P<0.05).(3)CCK-8 assay results showed that A450 value gradually increased after the cells were injected,and reached the highest value on the fifth day,reaching 3.17,and then slowly decreased.At the same time,it was found that Ki67 mRNA was up-regulated on the third day of culture,and then declined.The expression level of Ki67 protein was higher from the third day to the fifth day.(4)The detection of NAD+/NADH showed that the increase was obvious from the fifth to the seventh day after the injection of cells,and the expression of glycolysis-related genes(GLUT-1 and LDHA)was up-regulated and changed synchronously,and the relative expression was higher in the first five days.(5)The results showed that the tissue-engineered blood vessels were constructed using the vascular bioreactor and the smooth muscle cells in the early stage mainly proliferated and exhibited a metabolic feature of low oxygen consumption.The metabolic characteristics of high oxygen consumption were observed during the pulsatile tensile stress stimulation stage.

Effects of dietary restriction combined with different exercises on inflammatory factors and gut microbiota in obese children / 中国学校卫生

Objective@#To compare the effects of aerobic exercise, resistance training, and a combination of aerobic exercise and resistance training (combined exercise) with dietary restrictions on inflammatory factors and gut microbiota in obese children, so as to provide the reference for improving the health level of obese children.@*Methods@#From August to September 2022, a total of 70 obese children aged 10-12 from the Affiliated Experimental Primary School of Minjiang Normal University were recruited through online notifications and WeChat distribution through parent groups. Participants were divided into dietary restriction (DR, n=18) group, aerobic exercise combined with dietary restriction (AE+DR, n=18) group, resistance training combined with dietary restriction (RT+DR, n=17) group and combined exercise combined with dietary restriction (ART+DR, n=17) group,through random number table method. From September to November 2022, each group received different interventions.The daily dietary intake of calories in the DR group was determined according to resting energy consumption. The AE+DR group intervention mainly included skipping rope, aerobics exercises, jogging and sports games, and were maintained for each session lasting 50 minutes. For RT+DR group, the exercise intensity of resistance training was (65%-85%) maximum strength, with a total of 10 actions. The ART+DR group included resistance training (20 minutes), aerobic exercise (20 minutes), preparation and relaxation phases for 5 minutes each. The DR and exercise intervention was administered for 8 weeks (4 times a week for Monday, Tuesday, Thursday and Friday). Before and after different intervention methods, serum inflammatory factors were detected by enzymelinked immunosorbent assay (ELISA) and intestinal flora was calculated by plate colony counting method.@*Results@#Compared to those before intervention, the levels of serum TNF-α, IL-6 and CRP, and the contents of enterococcus and escherichia coli in the faeces significantly decreased, while the contents of lactobacillus and bifidobacterium in the faeces significantly increased after intervention (t=7.19，7.15，4.57，5.42，5.15，-3.51，-7.30；5.14，3.64，3.02，3.27，5.00，-3.09，-3.75；7.10，10.86，7.74，10.92，9.26，-6.63，-6.33，P<0.05) in AE+DR, RT+DR and ART+DR groups. The levels of serum TNF-α and CRP and enterococcus decreased significantly, and the contents of lactobacillus and bifidobacterium in the faeces increased significantly after intervention (t=2.74, 2.22, 2.14, -2.21, -2.81, P<0.05) in the DR Group. After 8 weeks of intervention with different methods, the change differences of enterococcus, escherichia coli, lactobacillus, bifidobacterium in the faeces, and serum TNF-α, IL-6 and CRP levels were statistically significantin the four groups of obese children (H=22.22, 23.75, 13.44, 28.33, 18.02, 33.64, 25.14, P<0.01). In addition, the decreases of enterococcus in the faeces and serum TNF-α, IL-6, CRP levels, and the increases of lactobacillus in the faeces were significantly higher than those in the other three groups.@*Conclusions@#Dietary restriction alone or combined with different exercises bring beneficial changes in the inflammatory factors and gut microbiota indicators in obese children. Combined exercise,as well as aerobic exercise combined with dietary restrictions are more reasonable and effective in obese children.