B12 deficiency-related glossitis is highly associated with high gastrin-17 and low pepsinogen I.

BACKGROUND: The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. METHODS: A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. RESULTS: Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. CONCLUSION: Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.

Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program

Background/Aims@#Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. @*Methods@#We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. @*Results@#The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. @*Conclusions@#Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication

Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy

Background/Aims@#Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. @*Methods@#We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. @*Results@#Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. @*Conclusions@#Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis

Objectives@#This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. @*Methods@#A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. @*Results@#The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. @*Conclusions@#This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Analysis of HUANG Feng's Medication Rules for Low Back Pain Based on Data Mining / 广州中医药大学学报

Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.

Finite element analysis of anterograde and retrograde intramedullary nail for different areas of femoral shaft fractures / 中国组织工程研究

BACKGROUND:Intramedullary nail has achieved a good clinical result in the treatment of femoral shaft fractures,but some patients still have aseptic nonunion due to mechanical instability.The femur is the longest and largest bone in the human body,but there are few studies on whether the fracture of the femur has different biomechanical results in different areas and the influence of different inserting methods on the stability of fracture fragments in different areas. OBJECTIVE:To analyze the biomechanical characteristics of anterograde and retrograde intramedullary nails in the treatment of different areas of femoral shaft fractures,and to evaluate the best way of insertion to reduce the incidence of nonunion. METHODS:CT data of a healthy volunteer were selected to import into the software of Mimics 19.0 and Geomagic studio 2017 to extract and optimize the three-dimensional model of the right femur.The anterograde and retrograde intramedullary nail models were built with Solidworks 2017 software and assembled with femoral shaft fracture models at different fracture areas according to standard surgical techniques.The models were imported into Abaqus 2017 software in STEP format to set material attribute parameters,boundary conditions,load and submit calculation,and the results were viewed in the visualization module.Among them,the antegrade and retrograde intramedullary nails of the upper femoral shaft fracture were A1 and A2 models,B1 and B2 models in the middle segment,and C1 and C2 models in the lower segment. RESULTS AND CONCLUSION:(1)In models A1,B1 and C2,the overall stress distribution of the femur was more uniform,and the placement,the displacement and angle of the fracture site,and inversion angle of the proximal femoral bone fragment were smaller.(2)For the upper and middle femoral shaft fractures,the anterograde intramedullary nail has a better biomechanical effect.For lower femoral shaft fractures,a retrograde intramedullary nail is preferable.

Efficacy of rituximab therapy for 10 patients suffering from systemic lupus erythematosus with intestinal involvement / 中华内科杂志

We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.

Gastric cancer derived exosomal THBS1 enhanced Vγ9Vδ2 T-cell function through activating RIG-I-like receptor signaling pathway in a N6-methyladenosine methylation dependent manner.

Gamma delta (γδ) T-cell-based immunotherapy has shown favorable safety and clinical response in patients with multiple types of cancer. However, its efficiency in treating patients with solid tumors remains limited. In the current study, we investigated the function and molecular mechanism underlying gastric cancer (GC) cell-derived exosomal THBS1 in the regulation of Vγ9Vδ2 T cells. We found that GC cell-derived exosomal THBS1 markedly enhanced the cytotoxicity of Vγ9Vδ2 T cells against GC cells and the production of IFN-γ, TNF-α, perforin and granzyme B in vitro and elevated the killing effects of Vγ9Vδ2 T cells on GC cells in vivo. Mechanistically, exosomal THBS1 could regulate METTL3-or IGF2BP2-mediated m6A modification, further activating the RIG-I-like receptor signaling pathway in Vγ9Vδ2 T cells. Moreover, blocking the RIG-I-like receptor signaling pathway reversed the effects of exosomal THBS1 on the function of Vγ9Vδ2 T cells. In addition, THBS1 was expressed at low levels in GC tissues and was associated with an unfavorable prognosis in GC patients. In sum, our findings indicate that exosomal THBS1 derived from GC cells enhanced the function of Vγ9Vδ2 T cells by activating the RIG-I-like signaling pathway in a m6A methylation-dependent manner. Targeting the exosomal THBS1/m6A/RIG-I axis may have important implications for GC immunotherapy based on Vγ9Vδ2 T cells.

Adherence, belief, and knowledge about oral anticoagulants in patients with bioprosthetic heart valve replacement: a cross-sectional study.

Aims: To investigate adherence to oral anticoagulants among patients after mechanical heart valve (BHV) replacement and further examine the mediating role of medication belief in the relationship between knowledge and medication adherence. Background: The number of patients who undergo BHV replacement has increased in recent years. Short-term anticoagulant therapy is recommended for patients after BHV replacement. However, little is known about adherence to oral anticoagulant therapy and the underlying mechanisms among patients with BHV replacement. Methods: A cross-sectional study was conducted between September 2022 and November 2022. A convenience sample of 323 patients who underwent BHV replacement was recruited from a tertiary public hospital in Southwest China. Data were collected by using the 8-item Morisky Medication Adherence Scale, Beliefs about Medicines Questionnaire-specific, and the Knowledge of Anticoagulation Questionnaire. The mediation model was tested by Hayes's PROCESS macro. The STROBE checklist was used. Results: Approximately 17.3% of participants had low adherence, 47.1% had medium adherence, and only 35.6% reported high adherence to oral anticoagulants. Knowledge and necessity beliefs were positively related to medication adherence, while concern beliefs were negatively correlated with medication adherence. Medication belief mediated the relationship between knowledge and adherence to oral anticoagulants. Conclusion: Patients with BHV replacement demonstrated relatively low adherence to oral anticoagulant therapy. Efforts to enhance medication adherence should consider improving patients' knowledge and medication beliefs.

The protective effect of Apelin-13 against cardiac hypertrophy through activating the PI3K-AKT-mTOR signaling pathway.

Objectives: To determine the protective effect of Apelin-13 on cardiac hypertrophy through activating the PI3K-AKT-mTOR signaling pathway. Materials and Methods: The phenylephrine-induced cardiomyocyte hypertrophy model was established in H9C2 cells in vitro. Electroporation transfection technology was utilized to prepare and screen the H9C2 cells inducing low expression of the angiotensin type one receptor-related protein (Si-APJ). H9C2 and Si-APJ cells were divided independently into five groups: the control group, the PE group, the PE+Apelin group, the PE+Rapa group, and the PE+Apelin+Rapa group. RT-PCR was performed to analyze the mRNA expression levels of myosin heavy chain 7 (MYH7). Expression of the PI3K/AKT/mTOR pathway proteins and MYH7 was investigated by western blot. Results: The expression of PI3K/AKT/mTOR phosphorylated proteins was significantly higher in the PE group compared with the PE+Apelin group in H9C2 cells (P<0.05). Conversely, in Si-APJ H9C2 cells, the expression of PI3K/AKT/mTOR phosphorylated proteins was decreased (P<0.05). In H9C2 cells, the expression of MYH7 protein was increased in the PE group compared with the control group (P<0.05). In the same cell line, the expression of MYH7 in the PE+Apelin group was decreased significantly compared with the PE group (P<0.05). In Si-APJ H9C2 cells, compared with the control group, the expression of MYH7 in the PE group still increased significantly (P<0.05). In contrast, in the same cell line, there was no statistically significant difference in MYH7 expression between the PE+Apelin, PE+Rapa, and PE+Apelin+Rapa groups compared to the PE group (P>0.05). Conclusion: Apelin-13 reduces PE-induced cardiac hypertrophy by activating the PI3K/AKT/mTOR signaling pathway.

The role of PPARγ in intermittent hypoxia-related human umbilical vein endothelial cell injury.

PURPOSE: Patients with obstructive sleep apnoea (OSA) have a high incidence of vascular endothelial injury. The most important pathophysiological feature of OSA is chronic intermittent hypoxia (CIH). This study aimed to investigate the mechanisms of CIH-related vascular endothelial injury. METHODS: IH exposure was applied to human umbilical vein endothelial cells (HUVECs). After modeling, cell viability, the expression levels of peroxisome proliferator activated receptor γ (PPARγ), apoptosis-associated proteins and mitochondrial division fusion proteins, and the levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were assessed via Cell Counting Kit-8 (CCK-8), western blotting, fluorescent microscope, and flow cytometry, respectively. Rosiglitazone (PPARγ agonist), tempo (the mitochondrial-specific antioxidant), and tempo combined with PPARγ interfering RNA were used to treat HUVECs, respectively. RESULTS: After IH exposure, cell viability and levels of MMP decreased, cell apoptosis and ROS levels increased, and the expression levels of PPARγ decreased. Both tempo and rosiglitazone pretreatment ameliorated cell apoptosis and improved cell viability. In addition, mitochondrial function became better after tempo pretreatment. PPARγ interference reversed the protective effects of tempo on IH-related mitochondrial function injury and cell injury. CONCLUSIONS: PPARγ regulated the apoptosis and cell viability of IH-treated HUVECs by altering mitochondrial function. This finding clarifies the mechanism of CIH-related vascular endothelial injury.

Study on inhibitory effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating the upstream and downstream cytokines of type Ⅱ innate lymphoid cells / 中国药房

OBJECTIVE To study the effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating upstream and downstream cytokines of type Ⅱ innate lymphoid cells （ILC2s）. METHODS Totally 40 female BABL/c mice were randomly divided into normal group， model group， positive control group （dexamethasone 1 mg/kg）， Wubao capsule low-dose and high-dose groups （0.5， 1 g/kg）， with 8 mice in each group. Asthma models were induced by ovalbumin （OVA） sensitization and nebulization. Each group was given normal saline or drug intragastrically for 7 consecutive days. The contents of IgE and OVA-IgE in serum， the contents of interleukin 5 （IL-5）， IL-9， IL-13， IL-25， IL-33， thymic stromal lymphopoietin （TSLP） and mucin 5AC （MUC5AC） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. HE staining was used to observe the pathological changes of lung tissues in mice. PAS staining was used to observe the changes of goblet cell proliferation in each group. The number of ILC2s in lung tissue was determined by flow cytometry （except for Wubao capsule low-dose group）. RESULTS Compared with model group， the contents of IgE and OVA-IgE in serum and the contents of IL-5， IL-9， IL-13， IL-25， IL-33， TSLP and MUC5AC in BALF were significantly reduced in Wubao capsule high-dose and low-dose groups （P＜0.01）. The infiltration of inflammatory cells and the thickening of basement membrane in lung tissue was alleviated to varying degrees， and the proliferation of goblet cells was inhibited； the number of ILC2s in lung tissues of mice in Wubao capsule high-dose group was significantly reduced （P＜0.01）. CONCLUSIONS Wubao capsule could effectively reduce the number of ILC2s in lung tissue， the contents of upstream and downstream cytokines of ILC2s in BALF of asthmatic model mice， so as to inhibit the airway inflammation and improve asthma.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness.@*METHODS@#We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges.@*RESULTS@#Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83).@*CONCLUSION@#Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

Effect of corilagin on cholesterol metabolism in macrophages and its mechanism / 中国药理学通报

Aim To elucidate the effect of corilagin (Cor) on cholesterol metabolism in macrophages and the underlying mechanism. Methods Molecular docking was applied to predict the protein target of Cor on cellular cholesterol metabolism. The RAW264.7 macrophage foam model induced by 80 mg • L

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Research progress on defocus technique of orthokeratology lens in the prevention and control of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

The incidence of myopia is gradually on the rise worldwide, which seriously affects the eye health of teenagers and children, causing enormous loss of socioeconomic benefits. As a result, the prevention and control of myopia is crucial and urgent. In recent years, orthokeratology lens have gradually demonstrated its superiority in the field of myopia prevention and control. At present, the principle of controlling the development of myopia by orthokeratology lens is mainly based on the theory of retinal hyperopia optical defocus, which promotes the shift of hyperopic defocus to myopic defocus in myopic patients to curb the growth of the axial length. The effect of controlling the development of myopia is related to various factors, including the total amount of defocusing, pupil diameter, optical zone design, and lens decentration. The widespread use of orthokeratology lenses will effectively reduce the incidence of myopia in teenagers and children. This paper discusses the principle of controlling the development of myopia by the defocus technique of orthokeratology lenses, and the relationship between the amount of defocusing and the position of the defocusing circle and the effect of myopia prevention and control. A specific review was conducted to clarify the research progress on defocus technique of orthokeratology lens in the prevention and control of myopia.

Exploring the potential mechanism of artesunate in intervening with U87 cells and U251 cells with distinct therapeutic effects on the basis of transcriptome sequencing and network pharmacology / 药学学报

Artesunate possesses the potential of intervening with glioma, however, its pharmacological mechanisms remain unclarified. Firstly, the effects of artesunate on cell activity, proliferation and apoptosis of U87 and U251 human glioma cells were explored. It was found that artesunate exerted stronger inhibitory effects on the activity and proliferation of U87 cells than U251 cells. It could significantly promote apoptosis in U87 cells (P < 0.05), while only high dose of artesunate can promote that of U251 cells (P < 0.01), detected by Hoechst and TUNEL cell apoptosis staining. Further, the differential expression gene sets between artesunate-sensitive and non-sensitive cell line, as well the therapeutic effects-related genes of artesunate were obtained through transcriptome sequencing and differential data analysis by using the lysates of U87 and U251 cells before and after artesunate treatment, aiming to explore the molecular mechanism of distinct artesunate sensitivity to two types of cells. Then, key putative targets that related to therapeutic effects were screened by constructing the interaction network of differential genes of three above comparison groups, and calculating their topological characteristics. Pathway enrichment analysis showed that those key putative targets were significantly enriched in several signaling pathways that were closely associated with the main pathological changes of glioma, among which apoptosis-related activating transcription factor 4 (ATF4)-DNA damage induced transcript 3 (DDIT3)- polyadenosine diphosphate ribose polymerase 1 (PARP1) signaling axis was the most enriched in. Molecular docking indicated that artesunate had fine binding affinities with ATF4 and DDIT3. Above all, this study preliminarily revealed that ATF4-DDIT3-PARP1 signaling axis is the target pathway of artesunate intervening with U87 glioma cells, and PARP1 may be an important gene for U251 cells to develop resistance to artesunate. Our results not only provide fundamental experimental evidence for artesunate as a potential therapeutic drug in glioma treatment, but shed light into overcoming drug resistance in its clinical therapy.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.