Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. METHODS: One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. RESULTS: We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CONCLUSION: CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Establishment of a humanized ST6GAL1 mouse model for influenza research.

BACKGROUND: This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1. METHODS: Humanized fragments, consisting of the endothelial cell-specific K18 promoter, human ST6GAL1-encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed. RESULTS: Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range. CONCLUSION: A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Asprosin promotes vascular inflammation via TLR4-NFκB-mediated NLRP3 inflammasome activation in hypertension.

Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), NLRP3-/- and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1ß production, proliferation and migration were attenuated in NLRP3-/- VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Identifying Qingkailing ingredients-dependent mesenchymal-epithelial transition factor-axiation "π" structuring module with angiogenesis and neurogenesis effects.

OBJECTIVE: To explore the functional role of the drug-dependent mesenchymal-epithelial transition (Met)-axiation "π" structural module of neurogenesis after processing by three components of Qingkailing injection in neurogenesis and angiogenesis in cerebral ischemia. METHODS: We used a Glutathione S-transferase (GST)-pull down assay, isothermal titration calorimetry assay, and other related methods to identify the relationships among Met, inositol polyphosphate phosphatase like 1 (Inppl1), and death associated protein kinase 3 (Dapk3) in this allosteric module. The biological effects of the modules of neurons generation composed of Met, Inppl1, and Dapk3 were measured through Western blot, apoptosis analysis, and double immunofluorescence labeling. RESULTS: The GST-pull down assay revealed that proline-serine-threonine rich domain of Met binds to the Src homology domain of Inppl1 to form a protein-protein complex; Dapk3 with a C-terminal domain interacts weakly with the protein kinase C domain of Met in the intracellular region. Thus, we obtained a "π" structuring module considered a neural regeneration module. The biological effects of angiogenesis and neurogenesis modules composed of Met, Inppl1, and Dapk3 were also verified. CONCLUSION: The study suggested that understanding the functional modules that contribute to pharmaceutics might provide novel signatures that can be used as endpoints to define disease processes under stroke or cerebral ischemia conditions.

High gain differentiator based neuro-adaptive arbitrary order sliding mode control design for MPE of standalone wind power system.

In this paper, we introduce a novel Maximum Power Point Tracking (MPPT) controller for standalone Wind Energy Conversion Systems (WECS) with Permanent Magnet Synchronous Generators (PMSG). The primary novelty of our controller lies in its implementation of an Arbitrary Order Sliding Mode Control (AOSMC) to effectively overcome the challenges caused by the measurement noise in the system. The considered model is transformed into a control-convenient input-output form. Additionally, we enhance the control methodology by simultaneously incorporating Feedforward Neural Networks (FFNN) and a high-gain differentiator (HGO), further improving the system performance. The FFNN estimates critical nonlinear functions, such as the drift term and input channel, whereas the HGO estimates higher derivatives of the system outputs, which are subsequently fed back to the control inputs. HGO reduces sensor noise sensitivity, rendering the control law more practical. To validate the proposed novel control technique, we conduct comprehensive simulation experiments compared against established literature results in a MATLAB environment, confirming its exceptional effectiveness in maximizing power extraction in standalone wind energy applications.

Relationships Between Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease: Indication from Gut Microbiota Alterations.

Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alterations is rarely studied. In this study, we aim to investigate whether there were consistent changes between RBD and PD in gut microbiota, and found some specific biomarkers in RBD that might indicate phenoconversion to PD. Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among idiopathic RBD (iRBD), PD with RBD, PD without RBD and normal controls (NC). Enterotype distribution indicated iRBD, PD with RBD and PD without RBD were Ruminococcus-dominant while NC were Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Through clinical correlation analysis, Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD (RBD-HK). Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD. Our study indicates that RBD had similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be potential hallmarks of phenoconversion of RBD to PD.

Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats / 中国药理学通报

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Multisensory Conflict Impairs Cortico-Muscular Network Connectivity and Postural Stability: Insights from Partial Directed Coherence Analysis / 神经科学通报·英文版

Sensory conflict impacts postural control, yet its effect on cortico-muscular interaction remains underexplored. We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability. We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input, recorded EEG (electroencephalogram) and EMG (electromyogram) data, and constructed a directed connectivity network. The results suggest that, compared to sensory congruence, during sensory conflict: (1) connectivity among the sensorimotor, visual, and posterior parietal cortex generally decreases, (2) cortical control over the muscles is weakened, (3) feedback from muscles to the cortex is strengthened, and (4) the range of body sway increases and its complexity decreases. These results underline the intricate effects of sensory conflict on cortico-muscular networks. During the sensory conflict, the brain adaptively decreases the integration of conflicting information. Without this integrated information, cortical control over muscles may be lessened, whereas the muscle feedback may be enhanced in compensation.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.@*METHODS@#Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.@*RESULTS@#A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001).@*CONCLUSIONS@#In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Effects of Different Tidal Volumes and PEEPs on Cardiac Output in Pigs Measured by Pulmonary Artery Catheter， Pulse Contour Analysis and Transpulmonary Thermodilution / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of different tidal volumes and positive end expiratory pressures （PEEPs） during mechanical ventilation on the cardiac output of pigs measured by pulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis， and to explore their consistency in cardiac output determination. MethodsTwelve experimental pigs were selected and randomly divided into 3 groups， with 4 pigs in each. Cardiac output was measured by different methods， control group by pulmonary artery catheter， group A by transpulmonary thermodilution and group B by pulse contour analysis. Then we compared the effects of different tidal volumes and PEEPs on the cardiac output of pigs and to explore the consistency. The correlation coefficient between pulse contour analysis and pulmonary artery catheter was r=0.754， and they were positively correlated. The correlation coefficient between transpulmonary thermodilution and pulmonary artery catheter was r=0.771， and they were positively correlated. In determining cardiac output， pulse contour analysis was consistent with pulmonary artery catheter， with a relative error of 13.5% between them； transpulmonary thermodilution was consistent with pulmonary artery catheter， with a relative error of 12.9% between them. The cardiac output decreased significantly along with the increase of tidal volumes or PEEPs and the differences were statistically significant （P<0.05） ConclusionPulmonary artery catheter， transpulmonary thermodilution and pulse contour analysis are well consistent with each other in measuring the cardiac output of pigs. The pigs’cardiac output gradually decreased along with the increase of tidal volumes or PEEPs during mechanical ventilation.

Precise Clinical Positioning of Chinese Patent Medicine in Paradigm of "Target Spectral Effect of Prescription"： A Case Study of Qizhi Tongluo Capsules / 中国实验方剂学杂志

The clinical value of Chinese patent medicine is the core direction of the development of the traditional Chinese medicine industry. The precise clinical positioning determines the way to prove the value of the drug， and is a key link to highlight the clinical value. This paper presented a case study of clinical positioning for Chinese patent medicine， namely Qizhi Tongluo capsules， and the key technical framework of precise clinical positioning of Chinese patent medicine， which was manifested as a comparison of prescription target spectral effect， discovery of core value of prescription， and confirmation of clinical positioning trial. The technical framework was designed to address a range of issues in the realm of precise clinical positioning. Before the clinical positioning trial， based on the multi-component， multi-target， and multi-phenotype data of prescription and clinical indication， the multi-omics network analysis technology was used to identify the core value of the traditional Chinese medicine varieties and predict the potential clinical advantages. Then， based on the predicted clinical advantages， reasonable efficacy indicators were selected， and the clinical efficacy was judged and verified by dynamic and flexible innovative clinical trials to improve the success rate of clinical positioning. This research paradigm integrates "omics technology" with "evidence-based" principles and follows the "precise evidence-based" concept. This research aims to provide a new strategy and method for the precise medication and positioning of Chinese patent medicine with traditional Chinese medicine characteristics after being put into the market and provide more technical thinking for traditional Chinese medicine to move towards precise medicine.

Genetic analysis of two children with Coffin-Siris syndrome due to variants of ARID1B gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.

Moxibustion modulates working memory in patients with amnestic mild cognitive impairment: a functional magnetic resonance imaging study.

OBJECTIVE: To investigate the correlation between changes in brain activity associated with working memory and assessment scales of memory scores in amnestic mild cognitive impairment (aMCI) before and after moxibustion therapy. METHODS: aMCI patients were randomized into the moxibustion treatment (MT) group and the placebo moxibustion (PM) group. Each group received either moxibustion therapy or a placebo moxibustion for eight weeks. Neuropsychological performance and functional brain responses to a working memory task were assessed at baseline and at the end of treatment. Memory function was evaluated individually by the Rivermead behavioral memory test (RBMT), and working memory was assessed by the N-back task. RESULTS: Compared with the PM group, RBMT score changes were significant ( < 0.05). In the MT group, the accuracy of the N-back texts increased compared with those before the intervention. After moxibustion intervention, the right insula, postcentral gyrus, precentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, calcarine sulcus, posterior cingulate gyrus, middle frontal gyrus and anterior frontal gyrus were significantly activated (= 0.01, Cluster-level Family-Wise Error = 0.05). Pearson correlation analysis showed that the insula, lingual gyrus and posterior cingulate gyrus were associated with changes in N-back score. Spearman correlation analysis showed that the postcentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, and posterior cingulate gyrus were correlated with RBMT score changes. CONCLUSION: Moxibustion treatment improved memory in aMCI patients and was associated with the activation of the brain region of the insula, lingual gyrus, posterior cingulate gyrus, postcentral gyrus, superior temporal gyrus, and thalamus, which may be an important mechanism by which moxibustion improves the memory function.

Melatonin alleviates cisplatin-induced mice spermatogenesis defects.

Cisplatin (CDDP) is a chemotherapeutic drug that is used to treat many different types of tumors. However, it also has significant adverse effects on male reproduction, which are partially mediated oxidative damage. Melatonin (MLT) is a promising antioxidant that can be used for reproductive protection. In this paper, we investigated the effect of CDDP on spermatogenesis, as well as MLT's potential role in reproductive protection. CDDP (5 mg/kg BW) significantly reduced male mice testosterone levels and decreased sperm vitality and progressive motility. Additionally, a lower percentage of stage VII and VIII seminiferous tubules were observed in CDDP-treated mice. MLT administration significantly alleviated CDDP-induced testicular damages, CDDP-induced lowered male fertility in vivo, and enhanced in vitro embryonic development of two cells and blastocysts. These changes may be due to CDDP-mediated spermatogenesis defects in germ cell and Leydig cell proliferation, which are reflected in abnormal PCNA, SYCP3, and CYP11A1 expression levels and can be improved by MLT. CDDP treatment significantly decreased the total antioxidant capacity (TAC), as well as SOD and GSH levels, and increased MDA levels in mice testis, leading to increased apoptosis of germ cells and increased BAX/BCL2 ratios in mice testis. MLT treatment may reduce germ cell apoptosis by reducing oxidative damage in mice testis. This study demonstrated that CDDP affects sperm fertility by altering germ cell and Leydig cell proliferation via increased oxidative damage and that MLT can attenuate these damages. Our work provides potential information for further research on the toxic effects of CDDP and the protective effects of MLT on male reproduction.

Comparison of Unilateral Biportal Endoscopy Decompression and Microscopic Decompression Effectiveness in Lumbar Spinal Stenosis Treatment: A Systematic Review and Meta-analysis.

This study aimed to compare the safety and effectiveness between unilateral biportal endoscopy (UBE) technique and microscopic decompression (MD) technique in lumbar spinal stenosis treatment. PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, and other databases were used to conduct extensive literature searches. RevMan ver. 5.3 software was used for the statistical analysis. Eleven studies were included with 930 patients, including 449 patients in the UBE group and 521 in the MD group. Both techniques revealed similar operative times at -1.77 minutes (95% confidence interval [CI], -7.59 to 4.05 minutes; p =0.55), the postoperative dural expansion area at -1.27 (95% CI, -19.30 to 16.77; p =0.89), the postoperative complications at 0.76 (95% CI, 0.47 to 1.22; p =0.26), the preoperative Visual Analog Scale (VAS) for leg pain, and the last follow-up (>12 months) VAS for leg pain at -0.04 (95% CI, -0.14 to 0.06; p =0.47), the preoperative Oswestry Disability Index (ODI), and the last follow-up (>12 months) ODI scores at -0.18 (95% CI, -0.76 to 0.40; p =0.54), and patient satisfaction (the modified MacNab score) at 1.15 (95% CI, 0.54 to 2.42; p =0.72). However, intraoperative bleeding was lower following the UBE technique at -52.78 mL (95% CI, -93.47 to -12.08 mL; p =0.01) and was shorter following the UBE technique at -3.06 (95% CI, -3.84 to -2.28; p <0.01). UBE and MD technology have no significant differences in efficacy or safety in the treatment of patients with lumbar spinal stenosis based on this meta-analysis. However, the UBE technique has less intraoperative bleeding and a shorter hospital stay. It has a slight advantage and is a better surgical option than the MD technique. It can be an alternative minimally invasive spinal surgery method.

HIF-1α inhibitor YC-1 suppresses triple-negative breast cancer growth and angiogenesis by targeting PlGF/VEGFR1-induced macrophage polarization.

Triple negative breast cancer (TNBC) is an invasive and metastatic phenotype of breast cancer with limited treatment options. Published studies have demonstrated an inhibitory effect of HIF-α inhibition by its inhibitor YC-1 (lificiguat) on growth and angiogenesis of TNBC. However, the underlying mechanism remains poorly understood. In the current paper, our results show that HIF-1α inhibitor significantly inhibited TNBC growth by increasing cellular apoptosis and decreasing MVD, independent of a cell-autonomous mechanism in both endothelial and tumor cells. Genetic screening and in vivo experiments showed that a large number of M2-polarized TAMs accumulated in the hypoxic peri-necrotic region (PNR), where placental growth factor (PlGF) and its ligand, vascular endothelial growth factor receptor-1 (VEGFR-1) were upregulated. Furthermore, YC-1 skewed the polarization of TAMs away from M2 to M1 phenotype, therefore inhibiting TNBC angiogenesis and growth. This effect was further abrogated by VEGFR-1 neutralization and TAM depletion following clodronate liposome injection. These findings provide preclinical evidence for an indirect mechanism underlying YC-1-induced suppression of TNBC growth and angiogenesis, thereby offering a treatment option for TNBC.

Evaluation of the Common bile duct (CBD) Diameter After Laparoscopic Cholecystectomy (LC) and Laparoscopic Common Bile Duct Exploration (LCBDE): A Retrospective Study.

BACKGROUND: Common Bile duct (CBD) measurement is a crucial aspect in the evaluation of the biliary tree. Whether the CBD undergoes any compensatory change in diameter after laparoscopic cholecystectomy or laparoscopic common bile duct exploration is still up for discussion. The aim of this study was to investigate CBD diameter changes after laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) on magnetic resonance cholangiopancreatography (MRCP). MATERIALS AND METHODS: Our retrospective study is divided into 2 sections. The first part assessing CBD diameter changes after laparoscopic cholecystectomy due to gallstones or gallbladder polyps, involved 85 patients, who underwent MRCP procedures. These patients aged between 30 and 85 were divided into an interval LC group (group A, n=56) and a remote LC group (group B, n=29). In group A, the common CBD diameters were measured at their widest portions on MRCP obtained before and after laparoscopic cholecystectomy. Measurements of the CBD diameters were repeated on MRCP obtained twice after the surgery in group B.Section 2 consisted of 38 patients who had choledocholithiasis and were treated with laparoscopic CBD exploration and T-tube placement. These patients aged 26 to 86 formed the interval LCBDE group (group C). The CBD widest diameters were measured on MRCP before LCBDE and after T-tube cholangiography for these individuals.Patients in groups A and C were further divided into 5 and those in group B into 4 age-related subgroups to facilitate statistical analysis. The Pearson correlation test was performed to find any relationship between CBD diameters and age in groups A and B. Paired sample T test was used to compare the significant difference between the 2 sets of CBD diameters in each study group and their subgroups. RESULTS: In the interval LC group, the post-LC mean CBD diameter was significantly wider when compared with the preoperative mean diameter ( P <0.05). There was a significant difference between the first and second post-LC means CBD diameter in the remote LC group ( P <0.05). In group C, the mean CBD diameter measured on T-tube cholangiography after LCBDE was significantly smaller than the preoperative dilated mean diameter ( P <0.05). CONCLUSIONS: This study demonstrated significant dilation occurring in the common bile duct diameter after laparoscopic cholecystectomy. Furthermore, our remote LC group also supported that claim by showing significant dilation between the first and second post-cholecystectomy CBD diameter values. And lastly, our interval LCBDE sample's initial dilation of the CBD diameters was reduced after surgery and stone extraction.

Circ_SIPA1L1 Promotes Osteosarcoma Progression Via miR-379-5p/MAP3K9 Axis.

Background: Osteosarcoma (OS) is a common malignant bone tumor. Circular RNAs (circRNAs) exert important roles in the pathogenesis of human cancers, including OS. In this study, the authors focused on the role and mechanism of circRNA signal-induced proliferation-associated 1 like 1 (circ_SIPA1L1) in OS. Methods: The enrichment of SIPA1L1, circ_SIPA1L1, microRNA-379-5p (miR-379-5p), and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The colony formation capacity was assessed through colony formation assay. Transwell assays were used to detect the migration and invasion abilities. Western blot assay was used to measure the expression of metastasis-related proteins and MAP3K9. The target interactions between the genes in circ_SIPA1L1/miR-379-5p/MAP3K9 axis were predicted by StarBase and confirmed by dual-luciferase reporter assay. The in vivo role of circ_SIPA1L1 was verified by murine xenograft assay. Results: Circ_SIPA1L1 abundance was aberrantly elevated in OS tissues and cell lines. Circ_SIPA1L1 accelerated the proliferation and metastasis abilities of OS cells. Circ_SIPA1L1 promoted the malignant behaviors of OS cells through elevating MAP3K9 level. MiR-379-5p directly bound to circ_SIPA1L1 and MAP3K9. MiR-379-5p interference rescued the abilities of proliferation and metastasis in OS cells, which were suppressed by the silencing of circ_SIPA1L1. Circ_SIPA1L1 promoted the development of OS via miR-379-5p/MAP3K9 in vivo. Conclusion: Circ_SIPA1L1 promoted the progression of OS via miR-379-5p/MAP3K9 axis.