Regional differences of Mycobacterium tuberculosis complex infection and multidrug resistance epidemic in Luoyang.

BACKGROUND: Tuberculosis (TB) remains a global public health event of great concern, however epidemic data on TB covering entire areas during the special period of the COVID-19 epidemic have rarely been reported. We compared the dissemination and multidrug-resistance patterns of Mycobacterium tuberculosis complex (MTBC) in the main urban area of Luoyang City, China (including six municipal jurisdictions) and nine county and township areas under its jurisdiction, aimed to establish the epidemiology of TB in this region and to provide reference for precision anti-TB in places with similar settings. METHODS: From 2020 to 2022, sputum samples were collected from 18,504 patients with confirmed, suspected and unexcluded TB in 10 designated TB medical institutions. Insertion sequence 6110 was amplified by PCR (rpoB gene detection if necessary) to confirm the presence of MTBC. PCR-positive specimens were analyzed by multicolor melting curve analysis to detect multidrug resistance. RESULTS: Among the 18,504 specimens, 2675 (14.5%) were MTBC positive. The positive rate was higher in the main urban area than in the county and township areas (29.8% vs. 10.9%, p < 0.001). Male, re-treated and smear-positive groups were high-burden carriers of MTBC. Individuals aged > 60 years were the largest group infected with MTBC in the main urban area, compared with individuals aged < 61 years in the county and township areas. The detection of multidrug-resistant TB (MDR-TB) was higher in the main urban area than in the county and township areas (13.9% vs. 7.8%, p < 0.001). In all areas, MDR-TB groups were dominated by males, patients with a history of TB treatment, and patients aged < 61 years. Stratified analysis of MDR-TB epidemiology showed that MDR4 (INH þ RIF þ EMB þ SM) was predominant in the main urban area, while MDR3 (INH þ RIF þ SM) was predominant in the county and township areas. MDR-TB detection rate and epidemiology differed among the county and township areas. CONCLUSIONS: For local TB control, it is necessary to plan more appropriate and accurate prevention and control strategies according to the regional distribution of MTBC infection.

PPIA dictates NRF2 stability to promote lung cancer progression.

Nuclear factor erythroid 2-related factor 2 (NRF2) hyperactivation has been established as an oncogenic driver in a variety of human cancers, including non-small cell lung cancer (NSCLC). However, despite massive efforts, no specific therapy is currently available to target NRF2 hyperactivation. Here, we identify peptidylprolyl isomerase A (PPIA) is required for NRF2 protein stability. Ablation of PPIA promotes NRF2 protein degradation and blocks NRF2-driven growth in NSCLC cells. Mechanistically, PPIA physically binds to NRF2 and blocks the access of ubiquitin/Kelch Like ECH Associated Protein 1 (KEAP1) to NRF2, thus preventing ubiquitin-mediated degradation. Our X-ray co-crystal structure reveals that PPIA directly interacts with a NRF2 interdomain linker via a trans-proline 174-harboring hydrophobic sequence. We further demonstrate that an FDA-approved drug, cyclosporin A (CsA), impairs the interaction of NRF2 with PPIA, inducing NRF2 ubiquitination and degradation. Interestingly, CsA interrupts glutamine metabolism mediated by the NRF2/KLF5/SLC1A5 pathway, consequently suppressing the growth of NRF2-hyperactivated NSCLC cells. CsA and a glutaminase inhibitor combination therapy significantly retard tumor progression in NSCLC patient-derived xenograft (PDX) models with NRF2 hyperactivation. Our study demonstrates that targeting NRF2 protein stability is an actionable therapeutic approach to treat NRF2-hyperactivated NSCLC.

PHF2 regulates genome topology and DNA replication in neural stem cells via cohesin.

Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC). PHF2 loss impairs DNA replication due to the activation of dormant replication origins in NSC. Notably, the PHF2/RAD21 co-bound genomic regions are characterized by CTCF enrichment and epigenomic features that resemble efficient, active replication origins, and can act as boundaries to separate adjacent domains. Accordingly, PHF2 loss weakens TADs and chromatin loops at the co-bound loci due to reduced RAD21 occupancy. The observed topological and DNA replication defects in PHF2 KO NSC support a cohesin-dependent mechanism. Furthermore, we demonstrate that the PHF2/RAD21 complex exerts little effect on gene regulation, and that PHF2's histone-demethylase activity is dispensable for normal DNA replication and proliferation of NSC. We propose that PHF2 may serve as a topological accessory to cohesin for cohesin localization to TADs and chromatin loops, where cohesin represses dormant replication origins directly or indirectly, to sustain DNA replication in NSC.

Associations of cognitive impairment and functional limitation with all-cause mortality risk in older adults: A population-based study from the National Health and Nutrition Examination Survey.

Cognitive impairment and functional limitation are commonly observed in older adults. They have a complex correlation, and both are risk factors for mortality. This prospective cohort study aimed to explore the independent and joint impact of cognitive impairment and functional limitations on all-cause mortality in older adults. A total of 3,759 participants aged ≥ 60 years who had available information on mortality data, cognitive function, physical function, and covariates were enrolled. Cox proportional hazards regression models were employed to assess the independent and joint impacts of cognitive impairment and functional limitation on all-cause mortality. Smoothing curve fitting was used to show the nonlinear relationship between the Digit Symbol Coding (DSC) score and all-cause mortality. An interaction between cognitive impairment and functional limitation was identified when examining their associations with all-cause mortality. Cognitive impairment and functional limitation independently correlated with all-cause mortality risk even after adjusting for covariates and performing mutual adjustments (HR for cognitive impairment: 1.34, 95% CI 1.15-1.56; HR for functional limitation: 1.50, 95% CI 1.32-1.70). When the DSC score was > 18, as the score increased, the risk of death significantly decreased (HR 0.99, 95% CI 0.98-0.99). Participants with both cognitive impairment and functional limitation had the highest hazard ratio for all-cause mortality (HR 1.98, 95%CI 1.63-2.40). In summary, cognitive impairment and functional limitation independently correlated with increased all-cause mortality risk. A higher DSC score was a protective factor reducing the premature mortality risk. Older adults with cognitive impairment and functional limitation demonstrated the highest all-cause mortality risk.

Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Research progress on the application of magnesium phosphate bone cement in bone defect repair: A review.

BACKGROUND: Bone defects arising from diverse causes, such as traffic accidents, contemporary weapon usage, and bone-related disorders, present significant challenges in clinical treatment. Prolonged treatment cycles for bone defects can result in complications, impacting patients' overall quality of life. Efficient and timely repair of bone defects is thus a critical concern in clinical practice. OBJECTIVE: This study aims to assess the scientific progress and achievements of magnesium phosphate bone cement (MPC) as an artificial bone substitute material. Additionally, the research seeks to explore the future development path and clinical potential of MPC bone cement in addressing challenges associated with bone defects. METHODS: The study comprehensively reviews MPC's performance, encompassing e.g. mechanical properties, biocompatibility, porosity, adhesion and injectability. Various modifiers are also considered to broaden MPC's applications in bone tissue engineering, emphasizing drug-loading performance and antibacterial capabilities, which meet clinical diversification requirements. RESULTS: In comparison to alternatives such as autogenous bone transplantation, allograft, polymethyl methacrylate (PMMA), and calcium phosphate cement (CPC), MPC emerges as a promising solution for bone defects. It addresses limitations associated with these alternatives, such as immunological rejection and long-term harm to patients. MPC can control heat release during the curing process, exhibits superior mechanical strength, and has the capacity to stimulate new bone growth. CONCLUSION: MPC stands out as an artificial bone substitute with appropriate mechanical strength, rapid degradation, non-toxicity, and good biocompatibility, facilitating bone repair and regeneration. Modification agents can enhance its clinical versatility. Future research should delve into its mechanical properties and formulations, expanding clinical applications to create higher-performing and more medically valuable alternatives in bone defect repair.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

Transcription of NOD1 and NOD2 and their interaction with CARD9 and RIPK2 in IFN signaling in a perciform fish, the Chinese perch, Siniperca chuatsi.

NOD1 and NOD2 as two representative members of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family play important roles in antimicrobial immunity. However, transcription mechanism of nod1 and nod2 and their signal circle are less understood in teleost fish. In this study, with the cloning of card9 and ripk2 in Chinese perch, the interaction between NOD1, NOD2, and CARD9 and RIPK2 were revealed through coimmunoprecipitation and immunofluorescence assays. The overexpression of NOD1, NOD2, RIPK2 and CARD9 induced significantly the promoter activity of NF-κB, IFNh and IFNc. Furthermore, it was found that nod1 and nod2 were induced by poly(I:C), type I IFNs, RLR and even NOD1/NOD2 themselves through the ISRE site of their proximal promoters. It is thus indicated that nod1 and nod2 can be classified also as ISGs due to the presence of ISRE in their proximal promoter, and their expression can be mechanistically controlled through PRR pathway as well as through IFN signaling in antiviral immune response.

SIRT6 positively regulates antiviral response in a bony fish, the Chinese perch Siniperca chuatsi.

SIRT6, a key member of the sirtuin family, plays a pivotal role in regulating a number of vital biological processes, including energy metabolism, oxidative stress, and immune system modulation. Nevertheless, the function of SIRT6 in bony fish, particularly in the context of antiviral immune response, remains largely unexplored. In this study, a sirt6 was cloned and characterized in a commercial fish, the Chinese perch (Siniperca chuatsi). The SIRT6 possesses conserved SIR2 domain with catalytic core region when compared with other vertebrates. Tissue distribution analysis indicated that sirt6 was expressed in all detected tissues, and the sirt6 was significantly induced following infection of infectious haemorrhagic syndrome virus (IHSV). The overexpression of SIRT6 resulted in significant upregulation of interferon-stimulated genes (ISGs), such as viperin, mx, isg15, irf3 and ifp35, and inhibited viral replication. It was further found that SIRT6 was located in nucleus and could enhance the expression of ISGs induced by type I and II IFNs. These findings may provide new information in relation with the function of SIRT6 in vertebrates, and with viral prevention strategy development in aquaculture.

Three coordination polymers based on 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether: Synthesis, structure and selective fluorescent sensing properties.

Three CPs [Zn2(PDA)2(BMIOPE)2·3H2O]n (1), [Co(Br-BDC)(BMIOPE)]n (2) and [Co(MIP)(BMIOPE)]n (3) were synthesized by solvothermal method based on dual-ligand strategy (H2PDA, Br-H2BDC, BMIOPE and H2MIP are 1,3-phenylenediacetic acid, 5-bromo-isophthalic acid, 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether and 5-methylisophthalic acid, respectively). Complexes 1 and 3 exhibit twofold parallel interwoven sql nets. Complex 2 is 2D layer structure. The luminescence property investigations showed that complexes 1-3 could act as multi-responsive fluorescent sensors to detect UO22+, Cr2O72- and CrO42- and nitrofurantoin (NFT) through fluorescence turn-off process, presenting excellent sensitivity and selectivity. Finally, the possible fluorescent quenching mechanisms of complexes 1-3 toward the above pollutants are also further investigated by employing spectroscopic methods and quantum chemical calculations. The fluorescence lifetime measurements manifest the mechanism of fluorescence quenching is static quenching process.

Epitranscriptomic orchestrations: Unveiling the regulatory paradigm of m6A, A-to-I editing, and m5C in breast cancer via long noncoding RNAs and microRNAs.

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.

A nomogram model of spectral CT quantitative parameters and clinical characteristics predicting lymphovascular invasion of gastric cancer.

Objective: The study established a nomogram based on quantitative parameters of spectral computed tomography (CT) and clinical characteristics, aiming to evaluate its predictive value for preoperative lymphovascular invasion (LVI) in gastric cancer (GC). Methods: From December 2019 to December 2021, 171 patients with pathologically confirmed GC were retrospectively collected with corresponding clinical data and spectral CT quantitative data. Patients were divided into LVI-positive and LVI-negative groups based on their pathological results. The univariate and multivariate logistic regression analyses were used to identify the risk factors and construct a nomogram. The calibration curve and receiver operating characteristic (ROC) curve were adopted to evaluate the predictive accuracy of nomogram. Results: Four clinical characteristics or spectral CT quantitative parameters, including Borrmann classification (P = 0.039), CA724 (P = 0.007), tumor thickness (P = 0.031), and iodine concentration in the venous phase (VIC) (P = 0.004) were identified as independent factors for LVI in GC patients. The nomogram was established based on the four factors, which had a potent predictive accuracy in the training, internal validation and external validation cohorts, with the area under the ROC curve (AUC) of 0.864 (95% CI, 0.798-0.930), 0.964 (95% CI, 0.903-1.000) and 0.877 (95% CI, 0.759-0.996), respectively. Conclusion: This study constructed a comprehensive nomogram consisting spectral CT quantitative parameters and clinical characteristics of GC, which exhibited a robust efficiency in predicting LVI in GC patients.

A novel means of capitate distraction lengthening for end-stage Kienböck's disease.

We present a patient with Kienböck's disease treated with a novel technique of capitate distraction lengthening using two wires in the proximal capitate and two in the ulna.

3-year clinical outcomes of A Singapore VenaSeal™ real world post-market evaluation Study (ASVS) for varicose vein ablation.

INTRODUCTION: Medium-term clinical outcome data are lacking for cyanoacrylate glue (CAG) ablation for symptomatic varicose veins, especially from the Asian population. OBJECTIVES: Aim was to determine the 3-year symptomatic relief gained from using the VenaSeal™ device to close refluxing truncal veins from the Singaporean ASVS prospective registry. METHODS: The revised Venous Clinical Severity Score (rVCSS) and three quality of life (QoL) questionnaires were completed to assess clinical improvement in venous disease symptoms along with a dedicated patient satisfaction survey. 70 patients (107 limbs; 40 females; mean age of 60.9 ± 13.6 years) were included at 3 years. RESULTS: At 3 years, rVCSS showed sustained improvement from baseline (5.00 to 0.00; p < 0.001) and 51/70 (72.9%) had improvement by at least 2 or more CEAP categories. Freedom from reintervention was 90% and 85.7% patients were extremely satisfied with the treatment outcome. No further reports of further hypersensitivity reactions after one year. CONCLUSION: The 3-year follow-up results of the ASVS registry demonstrated continued and sustained clinical efficacy with few reinterventions following CAG embolization in Asian patients with chronic venous insufficiency. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT03893201.

Short- and Long-term survival prediction in patients with acute type A aortic dissection undergoing open surgery.

BACKGROUND: Acute Type A aortic dissection (ATAAD) is a life-threatening cardiovascular disease associated with high mortality rates, where surgical intervention remains the primary life-saving treatment. However, the mortality rate for ATAAD operations continues to be alarmingly high. To address this critical issue, our study aimed to assess the correlation between preoperative laboratory examination, clinical imaging data, and postoperative mortality in ATAAD patients. Additionally, we sought to establish a reliable prediction model for evaluating the risk of postoperative death. METHODS: In this study, a total of 384 patients with acute type A aortic dissection (ATAAD) who were admitted to the emergency department for surgical treatment were included. Based on preoperative laboratory examination and clinical imaging data of ATAAD patients, logistic analysis was used to obtain independent risk factors for postoperative in-hospital death. The survival prediction model was based on cox regression analysis and displayed as a nomogram. RESULTS: Logistic analysis identified several independent risk factors for postoperative in-hospital death, including Marfan syndrome, previous cardiac surgery history, previous renal dialysis history, direct bilirubin, serum phosphorus, D-dimer, white blood cell, multiple aortic ruptures and age. A survival prediction model based on cox regression analysis was established and presented as a nomogram. The model exhibited good discrimination and significantly improved the prediction of death risk in ATAAD patients. CONCLUSIONS: In this study, we developed a novel survival prediction model for acute type A aortic dissection based on preoperative clinical features. The model demonstrated good discriminatory power and improved accuracy in predicting the risk of death in ATAAD patients undergoing open surgery.

Relative band power in assessing temporary neurological dysfunction post- type A aortic dissection surgery: a prospective study.

Temporary neurological dysfunction (TND), a common complication following surgical repair of Type A Aortic Dissection (TAAD), is closely associated with increased mortality and long-term cognitive impairment. Currently, effective treatment options for TND remain elusive. Therefore, we sought to investigate the potential of postoperative relative band power (RBP) in predicting the occurrence of postoperative TND, with the aim of identifying high-risk patients prior to the onset of TND. We conducted a prospective observational study between February and December 2022, involving 165 patients who underwent surgical repair for TAAD at our institution. Bedside Quantitative electroencephalography (QEEG) was utilized to monitor the post-operative brain electrical activity of each participant, recording changes in RBP (RBP Delta, RBP Theta, RBP Beta and RBP Alpha), and analyzing their correlation with TND. Univariate and multivariate analyses were employed to identify independent risk factors for TND. Subsequently, line graphs were generated to estimate the incidence of TND. The primary outcome of interest was the development of TND, while secondary outcomes included intensive care unit (ICU) admission and length of hospital stay. A total of 165 patients were included in the study, among whom 68 (41.2%) experienced TND. To further investigate the independent risk factors for postoperative TND, we conducted both univariate and multivariate logistic regression analyses on all variables. In the univariate regression analysis, we identified age (Odds Ratio [OR], 1.025; 95% CI, 1.002-1.049), age ≥ 60 years (OR, 2.588; 95% CI, 1.250-5.475), hemopericardium (OR, 2.767; 95% CI, 1.150-7.009), cardiopulmonary bypass (CPB) (OR, 1.007; 95% CI, 1.001-1.014), RBP Delta (OR, 1.047; 95% CI, 1.020-1.077), RBP Alpha (OR, 0.853; 95% CI, 0.794-0.907), and Beta (OR, 0.755; 95% CI, 0.649-0.855) as independent risk factors for postoperative TND. Further multivariate regression analyses, we discovered that CPB time ≥ 180 min (OR, 1.021; 95% CI, 1.011-1.032), RBP Delta (OR, 1.168; 95% CI, 1.105-1.245), and RBP Theta (OR, 1.227; 95% CI, 1.135-1.342) emerged as independent risk factors. TND patients had significantly longer ICU stays (p < 0.001), and hospital stays (p = 0.002). We obtained the simplest predictive model for TND, consisting of three variables (CPB time ≥ 180 min, RBP Delta, RBP Theta, upon which we constructed column charts. The areas under the receiver operating characteristic (AUROC) were 0.821 (0.755, 0.887). Our study demonstrates that postoperative RBP monitoring can detect changes in brain function in patients with TAAD during the perioperative period, providing clinicians with an effective predictive method that can help improve postoperative TND in TAAD patients. These findings have important implications for improving clinical care in this population.Trial registration ChiCTR2200055980. Registered 30th Jan. 2022. This trial was registered before the first participant was enrolled.

Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are important prognostic factors for gastric cancer (GC) that indicate an increased risk of metastasis and poor outcomes. Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment decisions. However, prior models using conventional computed tomography (CT) images to predict LVI or PNI separately have had limited accuracy. Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion. We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients. AIM: To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately. METHODS: This study used a retrospective dataset involving 257 GC patients (training cohort, n = 172; validation cohort, n = 85). First, several clinical indicators, including serum tumor markers, CT-TN stages and CT-detected extramural vein invasion (CT-EMVI), were extracted, as were quantitative spectral CT parameters from the delineated tumor regions. Next, a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters. A logistic regression (LR)-based nomogram model was subsequently constructed to predict LVI/PNI status, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: In both the training and validation cohorts, CT T3-4 stage, CT-N positive status, and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant (P < 0.05). LR analysis of the training group showed preoperative CT-T stage, CT-EMVI, single-energy CT values of 70 keV of venous phase (VP-70 keV), and the ratio of standardized iodine concentration of equilibrium phase (EP-NIC) were independent influencing factors. The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824, respectively, which were slightly greater than those of CT-T and CT-EMVI (AUC = 0.793, 0.762). The nomogram combining CT-T stage, CT-EMVI, VP-70 keV and EP-NIC yielded AUCs of 0.918 (0.866-0.954) and 0.874 (0.784-0.936) in the training and validation cohorts, which are significantly higher than using each of single independent factors (P < 0.05). CONCLUSION: The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC, with accuracy boosted by integrating clinical markers.

Electroacupuncture Promotes Angiogenesis in Mice with Cerebral Ischemia by Inhibiting miR-7.

OBJECTIVE: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it. METHODS: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex. RESULTS: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01). CONCLUSIONS: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2.