PINK1/Park2-Mediated Mitophagy Relieve Non-Alcoholic Fatty Liver Disease.

Up to now, there's a limited number of studies on the relationship between PINK1/Park2 pathway and mitophagy in NAFLD. To investigate the effect of Park2-mediated mitophagy on non-alcoholic fatty liver disease (NAFLD). Oleic acid was used for the establishment of NAFLD model. Oil red-dyed lipid drops and mitochondrial alternations were observed by transmission electron microscopy. Enzymatic kit was used to test lipid content. The levels of IL-8 and TNF-alpha were determined by ELISA. Lenti-Park2 and Park2-siRNA were designed to upregulate and downregulate Park2 expression, respectively. The changing expression of PINK and Park2 was detected by RT-qPCR and Western blot. Immunofluorescence staining was applied to measure the amount of LC3. Successful NAFLD modeling was featured by enhanced lipid accumulation, as well as the elevated total cholesterol (TC), triglyceride (TG), TNF-alpha and IL-8 levels. Mitochondria in NAFLD model were morphologically and functionally damaged. Park2 expression was upregulated by lenti-Park2 and downregulated through Park2-siRNA. The PINK1 expression showed the same trend as Park2 expression. Immunofluorescence staining demonstrated that the when Park2 was overexpressed, more LC3 protein on mitochondrial autophagosome membrane was detected, whereas Park2 knockdown impeded LC3' locating on the membrane. The transmission electron microscopy image exhibited that the extent of damage to the mitochondrial in NAFLD model was revered by enhanced Park2 expression but further exacerbated by reduced Park2 expression. Park2-mediated mitophagy could relive NAFLD and may be a novel therapeutic target for NAFLD treatment. Keywords: Non-alcoholic Fatty Liver Disease (NAFLD), Mitophagy, PINK1/Park2, Park2, PINK1.

Convolutional neural network for identifying common bile duct stones based on magnetic resonance cholangiopancreatography.

AIMS: To develop an auto-categorization system based on machine learning for three-dimensional magnetic resonance cholangiopancreatography (3D MRCP) to detect choledocholithiasis from healthy and symptomatic individuals. MATERIALS AND METHODS: 3D MRCP sequences from 254 cases with common bile duct (CBD) stones and 251 cases with normal CBD were enrolled to train the 3D Convolutional Neural Network (3D-CNN) model. Then 184 patients from three different hospitals (91 with positive CBD stone and 93 with normal CBD) were prospectively included to test the performance of 3D-CNN. RESULTS: With a cutoff value of 0.2754, 3D-CNN achieved the sensitivity, specificity, and accuracy of 94.51%, 92.47%, and 93.48%, respectively. In the receiver operating characteristic curve analysis, the area under the curve (AUC) for the presence or absence of CBD stones was 0.974 (95% CI, 0.940-0.992). There was no significant difference in sensitivity, specificity, and accuracy between 3D-CNN and radiologists. In addition, the performance of 3D-CNN was also evaluated in the internal test set and the external test set, respectively. The internal test set yielded an accuracy of 94.74% and AUC of 0.974 (95% CI, 0.919-0.996), and the external test set yielded an accuracy of 92.13% and AUC of 0.970 (95% CI, 0.911-0.995). CONCLUSIONS: An artificial intelligence-assisted diagnostic system for CBD stones was constructed using 3D-CNN model for 3D MRCP images. The performance of 3D-CNN model was comparable to that of radiologists in diagnosing CBD stones. 3D-CNN model maintained high performance when applied to data from other hospitals.

[The effect of the ratio of aneurysm sac diameter to patient age on the long-term efficacy of different surgical methods for infrarenal abdominal aortic aneurysm].

Objective: To investigate the effect of the ratio of the maximum diameter of aneurysm sac to age (R) on the long-term efficacy of endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in patients with infrarenal abdominal aortic aneurysm (IAAA). Methods: This is a retrospective cohort study.The clinical data of 317 patients with IAAA who underwent surgical repair in the Department of Vascular Surgery,the Third Affiliated Hospital of Sun Yat-Sen University from January 2016 to October 2022 were retrospectively collected.There were 266 males and 51 females,aged (69.7±8.3) years (range:37 to 87 years).The R value of the patient was calculated and the receiver operating characteristic(ROC) curve was used to establish a model to calculate the optimal cut-off value.The propensity score matching method was used to match the baseline data of patients in the EVAR and OSR group by 3∶1 (the caliper value was 0.05),and the patients were stratified according to the cutoff value of R,and the postoperative efficacy and survival of the patients were analyzed.The primary endpoint was the total mortality rate,and the secondary endpoints included the occurrence of postoperative complications and reintervention.Pearson χ2 or Fisher 's exact test was used for categorical variables,and t test was used for continuous variables to compare differences between groups.The survival curves of the two groups were described by Kaplan-Meier method. Results: After propensity score matching,198 cases were in the EVAR group and 66 cases were in the OSR group.The ROC model showed that the best cut-off value of R value was 0.90,and the two groups were divided into two layers:R<0.90 and R≥0.90.Among them,112 patients with R<0.90 (84 cases of EVAR,28 cases of OSR);there were 152 patients with R≥0.90 (114 cases of EVAR and 38 cases of OSR).The follow-up time was (23.6±1.6) months (range:1 to 70 months).In the R≥0.90 stratification,the total mortality (26.3% vs.5.3%,P<0.05),complication rate (44.7% vs.26.3%,P<0.05), and secondary intervention rate (31.6% vs.13.2%,P<0.05) in the EVAR group were higher than those in the OSR group.In the R<0.90 stratification,there was no significant difference in the total mortality rate (13.1% vs.10.7%,P<0.05),complication rate (28.6% vs.35.7%,P>0.05) and secondary intervention rate (14.3% vs.21.4%, P>0.05) between the two groups. Conclusions: When R≥0.90 in IAAA patients,OSR maybe more beneficial to patients in terms of survival rate,postoperative complication rate and secondary intervention rate than EVAR.When R<0.90,there are no significant differences in survival rate,complication rate and secondary intervention rate between the two surgical methods.

[Diagnostic value of apparent diffusion coefficient histograms using multiplexed sensitivity encoding diffusion-weighted imaging for distinguishing nasopharyngeal carcinoma from benign hyperplasia].

The data of 115 patients with nasopharyngeal masses (78 males and 37 females) aged between 12 and 78 years at the Sun Yat-sen University Cancer Center from May 2022 to July 2023 were retrospectively reviewed, including 70 cases of nasopharyngeal carcinoma and 45 cases of benign hyperplasia. The mean, median, and percentiles (10th, 25th, 75th, and 90th) of the apparent diffusion coefficient (ADC) histogram derived from multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) of the benign hyperplasia group were significantly higher than those of the nasopharyngeal carcinoma group (all P<0.05). Conversely, the kurtosis and skewness of benign hyperplasia group were significantly lower than those of the nasopharyngeal carcinoma group (both P<0.05). The area under receiver operating characteristic (ROC) curve of the combined ADC histogram parameters was 0.812 (95%CI: 0.732-0.892), and the sensitivity, specificity and accuracy were 92.86%, 57.78% and 79.13%, respectively. The current study indicates ADC histogram parameters derived MUSE-DWI exhibit significant discriminatory value between nasopharyngeal carcinoma and benign hyperplasia.

[Clinical and pathological characteristics and prognosis analysis of gray zone lymphoma].

To explore the clinical and pathological characteristics as well as therapies and prognosis of gray zone lymphoma (GZL). The clinical data of 10 GZL patients admitted to the First Affiliated Hospital of Soochow University from December 2016 to December 2022 were retrospectively collected. The clinical and pathological characteristics, therapies and prognosis were analyzed. The cut-off time for follow-up visits was December 31, 2022, and the median time for follow-up visits [M(Q1, Q3)] was 40.0 (28.3, 59.8) months. Treatment efficacy was divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD).　There were 6 males and 4 females, with a median age [M(Q1, Q3)] of 33.5 (27.3-39.5) years. Among them, 8 patients had mediastinal (thymus) involvement and 7 patients were accompanied with extranodal involvement. According to Ann Arbor staging, 1 case was in the limited stage and 9 cases were in the progressive stage. The immunophenotypes of 4 patients were strong expression of CD20, expression of CD30, and no expression of CD15. The immunophenotypes of 6 patients were unequal expression of CD20 and strong expression of CD30 and CD15. One patient received classical hodgkin lymphoma(cHL)-like immunochemotherapy and only achieved PR, and then received enhanced diffuse large b-cell lymphoma (DLBCL)-like immunochemotherapy to achieve CR. Five patients received enhanced DLBCL-like immunochemotherapy for induction therapy and achieved CR. All 4 patients who did not achieve CR achieved CR after receiving second-line or third-line salvage therapy. All patients were given autologous stem cell transplantation (ASCT) for consolidation therapy. One patient relapsed and died during the follow-up visit in the 33rd month, and the remaining patients currently maintained a state of sustained remission. It is found that GZL mostly occurs in young patients, mediastinal involvement is common, and diagnosis relies on pathological morphology and immunophenotype. GZL may be more sensitive to DLBCL-like intensive immune regimens. Sequential ASCT for consolidation can reduce the risk of relapse.

[Research progress in the performance of clear aligner attachment materials].

For most patients undergoing clear aligner treatment, it could be necessary to bond multiple attachments on their tooth surfaces. The clear aligner attachment is designed to enhance aligner retention, transmit orthodontic forces, and make the programmed tooth movement more predictable. Materials such as restorative resin, orthodontic bonding adhesive, flowable resin, and resin-modified glass ionomer cement are currently used for attachment bonding. But there is currently no conclusion as to which material suits most. The objective of this review is to look into the studies published in recent years, in order to explore the optimal material option for making clear aligner attachments.

[Predicting cerebral glioma enhancement pattern using a machine learning-based magnetic resonance imaging radiomics model].

OBJECTIVE: To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery (T2-FLAIR) images for optimizing the workflow of magnetic resonance imaging (MRI) examinations of glioma patients. METHODS: We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma, who were divided into enhancing and non-enhancing groups according to the enhancement pattern. Predictive radiomics models were established using Gaussian Process, Linear Regression, Linear Regression-Least absolute shrinkage and selection operator, Support Vector Machine, Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort (n=201)and tested both in the internal (n=85) and external validation cohorts (n=99). The receiver-operating characteristic curve was used to assess the predictive performance of the models. RESULTS: The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort, with areas under the curve (AUC) of 0.88 (95% CI: 0.81-0.94) and 0.80 (95% CI: 0.71-0.88), respectively. In the external validation cohort, the model showed an AUC of 0.81 (95% CI: 0.71-0.90) with sensitivity, specificity, positive predictive value and negative predictive value of 0.98, 0.61, 0.76 and 0.96, respectively. CONCLUSION: The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Evaluation of a new dengue 3 controlled human infection model for use in the evaluation of candidate dengue vaccines.

All four serotypes of dengue virus (DENV) cause the full spectrum of disease. Therefore, vaccines must protect against all serotypes. To evaluate candidate vaccines, a human challenge model of dengue serotype 3 (rDEN30Δ30) was developed. All challenge virus recipients safely met the primary endpoint of viremia and secondary endpoints of rash and seroconversion to DENV-3.

Potential low toxic alternative for Na-Cl cotransporter inhibition: A diuretic effect and mechanism study of Pyrrosia petiolosa.

BACKGROUND: Hydrochlorothiazide, a diuretic commonly used for the treatment of hypertension, is often associated with serious metabolic side effects. Pyrrosia petiolosa (Christ) Ching is a traditional Chinese medicine that possesses diuretic properties, without any obvious side effects. AIM: To evaluate the diuretic effect of P. petiolosa (Christ) Ching and to elucidate its underlying mechanism of action. METHODS: Extracts obtained from different polar components of P. petiolosa (Christ) Ching were analyzed for toxicity in a Kunming mouse model. The diuretic effects of the extracts were compared to that of hydrochlorothiazide in rats. In addition, compound isolation procedures, cell assays of Na-Cl cotransporter inhibition and rat diuretic test of monomeric compounds were conducted to identify the active ingredients in the extract. Subsequently, homology modeling and molecular docking were performed to explain the reason behind the diuretic activity observed. Finally, LC-MS analysis was used to elucidate the underlying mechanism of action of P. petiolosa (Christ) Ching. RESULTS: No toxicity was observed in mice administered P. petiolosa (Christ) Ching extracts. The ethyl acetate fraction showed the most significant diuretic effect. Similar results were obtained during the analysis for Na+ content in rat urine. Further separation of P. petiolosa (Christ) Ching components led to the isolation of methyl chlorogenate, 2',3'-dihydroxy propyl pentadecanoate, and ß-carotene. Results from cell assays showed that the Na-Cl cotransporter inhibitory activity of methyl chlorogenate was greater than that of hydrochlorothiazide. This result was again confirmed by the diuresis tests of monomeric compounds in rats. The molecular simulations explain the stronger interactions between the methyl chlorogenate and Na-Cl cotransporter. Of the compounds determined using LC-MS analysis, 185 were identified to be mostly organic acids. CONCLUSIONS: P. petiolosa possesses significant diuretic activities without any obvious toxicity, with least two possible mechanisms of action. Further study on this herb is warranted.

Prognostic value of the baseline magnetic resonance score in patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.

AIM: To investigate the prognostic value of the composite posterior circulation Acute Stroke Prognosis Early Computed tomography (CT) Score (ASPECTS)-Collaterals (pcASCO) score, which combines diffusion-weighted imaging (DWI) posterior circulation ASPECTS (pcASPECTS) and the magnetic resonance angiography (MRA)-collateral circulation score at baseline among patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy. MATERIALS AND METHODS: Patients with acute posterior circulation ischaemic stroke who underwent mechanical thrombectomy were analysed retrospectively. The DWI-pcASPECTS and MRA-collateral circulation score before treatment and the modified Rankin Scale (mRS) at 90 days after treatment were used as the endpoints. An mRS ≤2 was defined as a good prognosis, and an mRS ≥3 was defined as a poor prognosis. Multivariate logistic regression was used to analyse independent predictors of functional outcome 90 days after mechanical thrombectomy. RESULTS: Mechanical thrombectomy was performed in 57 patients; 38 patients had a good prognosis, 19 patients had a poor prognosis, and 33 patients were successfully recanalised. Univariate logistic regression found that National Institute of Health Stroke Scale (NIHSS) score (OR: 1.18, p<0.001), pcASPECTS (OR: 1.91, p=0.028) and pcASCO score (OR: 0.51, p=0.001) were factors of good functional outcome. Receiver operating characteristic curve (ROC curve) analysis showed that the diagnostic efficiency of the NIHSS and pcASCO was better (AUC = 0.88, 0.83, p<0.05) than that of the pcASPECTS (AUC = 0.65). The prediction model was established by age, NIHSS, and pcASCO, and the diagnostic efficiency of the prediction model was better (AUC = 0.94). CONCLUSIONS: The composite MR-pcASCO score can be used as an important predictor of the prognosis of patients with acute posterior circulation ischaemic stroke after mechanical thrombectomy.

[Study on the current status and relationship between psychological capital and compassion fatigue with work engagement of clinical nurses].

Objective: To explore the relationship between clinical nurses' psychological capital, compassion fatigue with work engagement, and analyze the mediating effect of psychological capital between compassion fatigue and work engagement, so as to provide scientific evidence for reducing compassion fatigue and improving work engagement of clinical nurses. Methods: From December 2021 to February 2022, 494 clinical nurses from 7 general hospitals in Sichuan Province were selected for the study using convenience sampling. The General Information Questionnaire, the Compassion Fatigue Short Scale, the Work Engagement Short Scale and the Psychological Capital Questionnaire for Nurses were used to conduct the survey. Pearson correlation was used to analyze the correlation between compassion fatigue, work engagement and psychological capital. And stepwise regression analysis and Bootstrap method were used to analyze the effects of compassion fatigue and psychological capital on work engagement as well as the mediating effect of psychological capital between compassion fatigue and work engagement. Results: Of the 494 clinical nurses, 33 (6.7%) were male and 461 (93.3%) were female, with an average age of (31.47±6.89) years old and an average working years (9.87±7.61) years. The average scores of psychological capital, compassion fatigue and work engagement of clinical nurses were (5.01±0.76), (3.19±2.08) and (4.60±1.37) points, respectively. Compassion fatigue was negatively correlated with psychological capital and work engagement (r=-0.608, -0.580, P<0.001), and work engagement was positively correlated with psychological capital (r=0.771, P<0.001). Compassion fatigue and psychological capital together accounted for 61.3% of the variation in work engagement, with the direct effects on work engagement were -0.206 (95%CI: -0.283--0.138, P<0.001) and 0.677 (95%CI: 0.599-0.744, P=0.001), respectively. Psychological capital partially mediated the relationship between compassion fatigue and work engagement, with a mediating effect of -0.397 (95%CI: -0.456--0.340, P<0.001), accounting for 65.8% of the total effect. Conclusion: The work engagement of clinical nurses is at a high level. Managers should take targeted measures to alleviate the symptoms of clinical nurses' compassion fatigue, improve their psychological capital, and then stabilize and improve their level of work engagement.

[Technical specification for orthodontic transmission straight wire technique].

Malocclusion is an oral disease with a high prevalence. The goal of orthodontic treatment is health, aesthetics, function and stability. The transmission straight wire appliance and technique is an innovative orthodontic system with independent intellectual property rights invented by Professor Jiuxiang Lin's team based on decades of clinical experience, which provides a new solution for the non-surgical correction of skeletal malocclusions, especially class Ⅲ malocclusion, and it is also a good carrier for the implementation of the concept of healthy orthodontics. Due to the lack of guidelines, how to implement standardized application of transmission straight wire technique remains a problem to be solved. This technical specification was formed by combining the guidance from Professor Jiuxiang Lin and joint revision by a number of authoritative experts from the Orthodontic Special Committee, Chinese Stomatological Association, with reference to relevant literatures, and combined with abundant clinical experience of many experts. This specification aims to provide reference to standardize the clinical application of transmission straight wire technique, so as to reduce the risk and complications, and finally to improve the clinical application level of this technique.

[Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder].

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

[Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology].

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

[Risk prediction of metabolic syndrome and coronary artery disease in overweight and obese populations based on serum metabolomics].

Objective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.

Associations of Body-Roundness Index and Sarcopenia with Cardiovascular Disease among Middle-Aged and Older Adults: Findings from CHARLS.

OBJECTIVES: Sarcopenia and obesity may contribute to chronic disease. However, little is known about the association between sarcopenia, body roundness index (BRI), and cardiovascular disease (CVD). The aim of this study was to investigate the association of sarcopenia and BRI with CVD in middle-aged and older Chinese population. DESIGN: Cohort study with an 8-year follow-up. SETTING AND PARTICIPANTS: Data were derived from 4 waves of the China Health and Retirement Longitudinal Study, and 6152 participants aged 45 or above were included in the study. METHODS: Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. CVD was defined as the presence of physician-diagnosed heart disease, diabetes and/or stroke. The associations of BRI and sarcopenia with CVD risk were explored using Cox proportional hazards regression models. RESULTS: The mean age of the participants was 58.3 (8.9) years, and 2936 (47.7%) were males. During the 8 years follow-up, 2385 cases (38.8%) with incident CVD were identified. Longitudinal results demonstrated that compared to neither sarcopenia or high BRI, both sarcopenia and high BRI (HR: 1.49, 95%CI: 1.08, 2.07) were associated with higher risk of CVD. In the subgroup analysis, individuals with both sarcopenia and high BRI were more likely to have new onset stroke (HR: 1.93, 95%CI: 1.12, 3.32) and increased risk of multimorbidity (HR: 2.15, 95% CI: 1.14, 4.04). CONCLUSIONS: Coexistence of sarcopenia and high BRI was associated with higher risk of CVD. Early identification and intervention for sarcopenia and BRI not only allows the implementation of therapeutic strategies, but also provides an opportunity to mitigate the risk of developing CVD.

[Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension].

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

Attenuating Neuronal Autophagy Alleviates Inflammatory Injury in OGDDeprived Co-culture of HT22 with BV2.

Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1ß, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.