Age-associated cortical similarity networks correlate with cell type-specific transcriptional signatures.

Human brain structure shows heterogeneous patterns of change across adults aging and is associated with cognition. However, the relationship between cortical structural changes during aging and gene transcription signatures remains unclear. Here, using structural magnetic resonance imaging data of two separate cohorts of healthy participants from the Cambridge Centre for Aging and Neuroscience (n = 454, 18-87 years) and Dallas Lifespan Brain Study (n = 304, 20-89 years) and a transcriptome dataset, we investigated the link between cortical morphometric similarity network and brain-wide gene transcription. In two cohorts, we found reproducible morphometric similarity network change patterns of decreased morphological similarity with age in cognitive related areas (mainly located in superior frontal and temporal cortices), and increased morphological similarity in sensorimotor related areas (postcentral and lateral occipital cortices). Changes in morphometric similarity network showed significant spatial correlation with the expression of age-related genes that enriched to synaptic-related biological processes, synaptic abnormalities likely accounting for cognitive decline. Transcription changes in astrocytes, microglia, and neuronal cells interpreted most of the age-related morphometric similarity network changes, which suggest potential intervention and therapeutic targets for cognitive decline. Taken together, by linking gene transcription signatures to cortical morphometric similarity network, our findings might provide molecular and cellular substrates for cortical structural changes related to cognitive decline across adults aging.

The co-activation pattern between the DMN and other brain networks affects the cognition of older adults: evidence from naturalistic stimulation fMRI data.

Brain function changes affect cognitive functions in older adults, yet the relationship between cognition and the dynamic changes of brain networks during naturalistic stimulation is not clear. Here, we recruited the young, middle-aged and older groups from the Cambridge Center for Aging and Neuroscience to investigate the relationship between dynamic metrics of brain networks and cognition using functional magnetic resonance imaging data during movie-watching. We found six reliable co-activation pattern (CAP) states of brain networks grouped into three pairs with opposite activation patterns in three age groups. Compared with young and middle-aged adults, older adults dwelled shorter time in CAP state 4 with deactivated default mode network (DMN) and activated salience, frontoparietal and dorsal-attention networks (DAN), and longer time in state 6 with deactivated DMN and activated DAN and visual network, suggesting altered dynamic interaction between DMN and other brain networks might contribute to cognitive decline in older adults. Meanwhile, older adults showed easier transfer from state 6 to state 3 (activated DMN and deactivated sensorimotor network), suggesting that the fragile antagonism between DMN and other cognitive networks might contribute to cognitive decline in older adults. Our findings provided novel insights into aberrant brain network dynamics associated with cognitive decline.

Increased regional Hurst exponent reflects response inhibition related neural complexity alterations in pediatric bipolar disorder patients during an emotional Go-Nogo task.

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.

Cortical thickness alterations are associated with astrocytes and excitatory neuron-specific transcriptome signatures in pediatric bipolar disorder.

Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morphometric studies in adults with BD are well established; however, few have examined cortical changes in pediatric BD (PBD). Additionally, the correlation between cortical thickness (CT) changes in PBD and gene expression remains elusive. Here, we performed an integrative analysis using neuroimaging data from 58 PBD individuals and the Allen human brain transcriptomic dataset. We applied partial least squares (PLS) regression analysis on structural MRI data and cortical gene expression, enrichment and specific cell type analysis to investigate the genetic correlates of CT alterations in PBD. We found the expression levels of PBD-related genes showed significant spatial correlations with CT differences. Further enrichment and specific cell type analysis revealed that transcriptome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptional changes could account for most of the observed correlations with CT differences in PBD, which offers a novel perspective to understand biological conceptualization mechanisms for the genetic correlates of CT alterations.

Sex differences in structural covariance network based on MRI cortical morphometry: effects on episodic memory.

Sex differences in episodic memory (EM), remembering past events based on when and where they occurred, have been reported, but the neural mechanisms are unclear. T1-weighted images of 111 females and 61 males were acquired from the Dallas Lifespan Brain Study. Using surface-based morphometry and structural covariance (SC) analysis, we constructed structural covariance networks (SCN) based on cortical volume, and the global efficiency (Eglob) was computed to characterize network integration. The relationship between SCN and EM was examined by SC analysis among the top-n brain regions that were most relevant to EM performance. The number of SC connections (females: 3306; males: 437, P = 0.0212) and Eglob (females: 0.1845; males: 0.0417, P = 0.0408) of SCN in females were higher than those in males. The top-n brain regions with the strongest SC in females were located in auditory network, cingulo-opercular network (CON), and default mode network (DMN), and in males, they were located in frontoparietal network, CON, and DMN. These results confirmed that the Eglob of SCN in females was higher than males, sex differences in EM performance might be related to the differences in network-level integration. Our study highlights the importance of sex as a research variable in brain science.

Comparison of Locking Plate Alone and Locking Plate Combined with 3D Printed Polymethylmethacrylate Augmentation in Treating Proximal Humerus Fractures in the Elderly.

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

Elevated galectin-3 levels detected in women with hyperglycemia during early and mid-pregnancy antagonizes high glucose - induced trophoblast cells apoptosis via galectin-3/foxc1 pathway.

OBJECTIVE: This study was to evaluate plasma galectin-3 levels from early pregnancy to delivery and explore the effects of galectin-3 on the function of trophoblast cells under high glucose exposure. METHODS: The plasma galectin-3 levels were quantified by enzyme-linked immunosorbent assay (ELISA) in the China National Birth Cohort (CNBC) at Peking University First Hospital, and the underlying signaling pathway was identified by protein-protein interaction (PPI) analysis, gene set enrichment analysis (GSEA), quantitative PCR (qPCR), western blotting, small interfering RNA (siRNA) transfections, and flow cytometry. RESULTS: Significantly higher galectin-3 levels were found in patients with gestational diabetes mellitus (GDM group; n = 77) during the first and second trimesters than that in healthy pregnant women (HP group; n = 113) (P < 0.05). No significant differences in plasma galectin-3 levels were detected between GDM and HP groups in maternal third-trimester blood and cord blood. PPI analysis suggested potential interactions between galectin-3 and foxc1. The findings of GSEA showed that galectin-3 was involved in the cytochrome P450-related and complement-related pathways, and foxc1 was associated with type I diabetes mellitus. Additionally, high glucose (25 mM) significantly increased the expression levels of galectin-3 and foxc1 and induced apoptosis in HTR-8/SVneo cells. Further in vitro experiments showed that galectin-3/foxc1 pathway could protect HTR-8/SVneo cells against high glucose - induced apoptosis. CONCLUSION: Future studies were required to validate whether plasma galectin-3 might become a potential biomarker for hyperglycemia during pregnancy. Elevated galectin-3 levels might be a vital protective mechanism among those exposed to hyperglycemia during pregnancy.

Divergent Synthesis of α-(1,3,5-Triazinylthio)-ketones and Thiazolo[3,2-a][1,3,5]triazines from 1,3-Dicarbonyl compounds or Chalcones with 1,3,5-Triazine-2-thiols.

An efficient synthesis of α-(1,3,5-triazinylthio)-ketones from 1,3-dicarbonyl compounds with 1,3,5-triazine-2-thiols has been developed. The reaction proceeds through the C-C bond cleavage and C-S bond reconstruction of 1,3-dicarbonyl compounds, and ß-keto esters, ß-keto amides, and 1,3-diones were tolerated. In addition, the annulation of 1,3,5-triazine-2-thiols with chalcones has been achieved for the synthesis of thiazolo[3,2-a][1,3,5]triazines. The method occurred in moderate to good yields and tolerated chalcone with a broad functional group.

Immediate visual reproduction negatively correlates with brain entropy of parahippocampal gyrus and inferior occipital gyrus in bipolar II disorder adolescents.

BACKGROUND: Brain entropy reveals complexity and irregularity of brain, and it has been proven to reflect brain complexity alteration in disease states. Previous studies found that bipolar disorder adolescents showed cognitive impairment. The relationship between complexity of brain neural activity and cognition of bipolar II disorder (BD-II) adolescents remains unclear. METHODS: Nineteen BD-II patients (14.63 ±1.57 years old) and seventeen age-gender matched healthy controls (HCs) (14.18 ± 1.51 years old) were enlisted. Entropy values of all voxels of the brain in resting-state functional MRI data were calculated and differences of them between BD-II and HC groups were evaluated. After that, correlation analyses were performed between entropy values of brain regions showing significant entropy differences and clinical indices in BD-II adolescents. RESULTS: Significant differences were found in scores of immediate visual reproduction subtest (VR-I, p = 0.003) and Stroop color-word test (SCWT-1, p = 0.015; SCWT-2, p = 0.004; SCWT-3, p = 0.003) between the two groups. Compared with HCs, BD-II adolescents showed significant increased brain entropy in right parahippocampal gyrus and right inferior occipital gyrus. Besides, significant negative correlations between brain entropy values of right parahippocampal gyrus, right inferior occipital gyrus and immediate visual reproduction subtest scores were observed in BD-II adolescents. CONCLUSIONS: The findings of the present study suggested that the disrupted function of corticolimbic system is related with cognitive abnormality of BD-II adolescents. And from the perspective temporal dynamics of brain system, the current study, brain entropy may provide available evidences for understanding the underlying neural mechanism in BD-II adolescents.

Which Multivariate Multi-Scale Entropy Algorithm Is More Suitable for Analyzing the EEG Characteristics of Mild Cognitive Impairment?

So far, most articles using the multivariate multi-scale entropy algorithm mainly use algorithms to analyze the multivariable signal complexity without clearly describing what characteristics of signals these algorithms measure and what factors affect these algorithms. This paper analyzes six commonly used multivariate multi-scale entropy algorithms from a new perspective. It clarifies for the first time what characteristics of signals these algorithms measure and which factors affect them. It also studies which algorithm is more suitable for analyzing mild cognitive impairment (MCI) electroencephalograph (EEG) signals. The simulation results show that the multivariate multi-scale sample entropy (mvMSE), multivariate multi-scale fuzzy entropy (mvMFE), and refined composite multivariate multi-scale fuzzy entropy (RCmvMFE) algorithms can measure intra- and inter-channel correlation and multivariable signal complexity. In the joint analysis of coupling and complexity, they all decrease with the decrease in signal complexity and coupling strength, highlighting their advantages in processing related multi-channel signals, which is a discovery in the simulation. Among them, the RCmvMFE algorithm can better distinguish different complexity signals and correlations between channels. It also performs well in anti-noise and length analysis of multi-channel data simultaneously. Therefore, we use the RCmvMFE algorithm to analyze EEG signals from twenty subjects (eight control subjects and twelve MCI subjects). The results show that the MCI group had lower entropy than the control group on the short scale and the opposite on the long scale. Moreover, frontal entropy correlates significantly positively with the Montreal Cognitive Assessment score and Auditory Verbal Learning Test delayed recall score on the short scale.

Activatable Semiconducting Polymer Pro-nanomodulators for Deep-Tissue Sono-immunotherapy of Orthotopic Pancreatic Cancer.

Immunotherapy has provided a promising modality for cancer treatment, while it often has the issues of limited response rates and potential off-target side effects in clinical practice. We herein report the construction of semiconducting polymer pro-nanomodulators (SPpMs) with ultrasound (US)-mediated activatable pharmacological actions for deep-tissue sono-immunotherapy of orthotopic pancreatic cancer. Such SPpMs consist of a sonodynamic semiconducting polymer backbone grafted with poly(ethylene glycol) chains linked with two immunomodulators (a programmed death-ligand 1 blocker and an indoleamine 2,3-dioxygenase inhibitor) via a singlet oxygen (1 O2 )-cleavable segment. In view of the excellent sonodynamic property of the semiconducting polymer core, SPpMs enable effective generation of 1 O2 under US treatment, even in a deep-tissue depth up to 12 cm. The generated 1 O2 not only ablates tumors via a sonodynamic effect and induces immunogenic cell death, but also destroys the 1 O2 -cleavable segments to allow in situ release of immunomodulators in tumors. This synergetic action results in boosted antitumor immune response via reversing two tumor immunosuppressive pathways. As such, SPpMs mediate deep-tissue sono-immunotherapy to completely eradicate orthotopic pancreatic cancer and effectively prevent tumor metastasis. Moreover, such an immune activation reduces the possibility of immune-related adverse events. This study thus provides a smart activatable nanoplatform for precise immunotherapy of deep-seated tumors.

A Photoenzymatic Strategy for Radical-Mediated Stereoselective Hydroalkylation with Diazo Compounds.

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we describe a photoenzymatic strategy for radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals through an ene reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-stereogenic carbonyl compounds in good yields and stereoselectivities. This study further expands the possible reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.

Photoenzymatic Hydrosulfonylation for the Stereoselective Synthesis of Chiral Sulfones.

Chiral sulfones are recurrent motifs in pharmaceuticals and bioactive molecules. Although chemical methods have been developed to afford α- or ß- chiral sulfones, these protocols rely heavily on the pre-synthesis of structurally complicated starting materials and chiral metal complexes. Herein, we described a photoenzymatic approach for the radical-mediated stereoselective hydrosulfonylation. Engineered variants of ene reductases provide efficient biocatalysts for this transformation, enabling to achieve a series of ß-chiral sulfonyl compounds with high yields (up to 92 %) and excellent e.r. values (up to 99 : 1).

A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma.

BACKGROUND: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. METHODS: In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m2 intravenous paclitaxel on day 1, and 60-75 mg/m2 intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). CONCLUSIONS: The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

Comparison and development of a metagenomic next-generation sequencing protocol for combined detection of DNA and RNA pathogens in cerebrospinal fluid.

BACKGROUND: The purpose of this study was to evaluate different pretreatment, extraction, amplification, and library generation methods for metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and to develop an efficient procedure for the simultaneous detection of DNA and RNA pathogens. METHODS: We generated thirteen mock CSF samples with four representative pathogens of encephalitis. Each sample was subjected to ten different methods by varying sample pretreatment/nucleic acid extraction (microbial DNA, total DNA, total NA, total RNA, Whole Transcriptome Amplification (WTA)) and library generation (Illumina or NEB). Negative extraction controls (NECs) were used for each method variation. RESULTS: We found that the quality of mNGS sequencing reads was higher from the NEB kit for library generation. Microbial DNA and total RNA increased microbial deposition by depleting the host DNA. Methods total NA and total RNA can detect gram-positive, gram-negative, RNA and DNA pathogens. We applied mNGS, including total NA and NEB library generation, to CSF samples from five patients diagnosed with infectious encephalitis and correctly determined all pathogens identified in clinical etiological tests. CONCLUSIONS: Our findings suggested that total nucleic acid extraction combined with NEB library generation is the most effective mNGS procedure in CSF pathogen detection. The optimization of positive criteria and databases can improve the specificity and sensitivity of mNGS diagnosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015425 (29/03/2018), https://www.chictr.org.cn/edit.aspx?pid=26292&htm=4 .

Video-assisted mediastinoscopic and laparoscopic transhiatal esophagectomy for esophageal cancer.

BACKGROUND: Mediastinoscopy was originally applied for lymph node biopsy and mediastinal tumor resection. Improved video imaging with spreadable working channels enabled mediastinoscopy for inspection and tissue biopsy in the superior mediastinum but it is rarely used in minimally invasive esophageal cancer surgery. In this prospective trial, the practicability and security of spreadable video-assisted mediastinoscopic combined with laparoscopic transhiatal esophagectomy (VAME) with video-assisted thoracoscopic esophagectomy (VATE) were compared. METHODS: A total of 200 eligible patients with esophageal squamous cell carcinoma were randomly divided into VAME or VATE groups. Early postoperative outcomes and lymph node dissection between the two groups were compared. RESULTS: The operation time was significantly shorter (164.3 ± 47.0 min vs. 265.4 ± 47.2 min, P < 0.001), the number of dissected lymph nodes was less (15.8 ± 4.5 vs. 20.3 ± 6.5, P < 0.001), and the intraoperative blood loss was also significantly reduced (94.7 ± 56.7 mL vs. 184.4 ± 65.2 mL, P < 0.001) in the VAME compared to the VATE group, respectively. The incidence of pneumonia was lower (7% vs. 29%; P < 0.001) and the length of hospital stay was shorter in the VAME group compared to the VATE group (18.0 ± 7.6 days vs. 23.2 ± 7.2, P < 0.001, respectively). The chyle leak incidence appeared to be lower in the VAME group but statistical significance was not reached (1% vs. 4%; P = 0.369). There were no differences in the incidence of anastomotic leakages and recurrent laryngeal nerve paralysis between the groups. No 30-day mortality occurred in any of the cases. CONCLUSION: VAME appears to be a practicable and secure method for esophagectomy but needs further proof of concept. CLINICAL REGISTRATION NUMBER: Registered at Chinese Clinical Trial Registry, ChiCTR1900022797.

Direct arterial puncture for hemodialysis, a neglected but simple and valuable vascular access.

INTRODUCTION: The purpose of this study is to present the prevalence and effects of direct arterial puncture (DAP) for hemodialysis patients, and to introduce optimal option for the vascular access (VA) in certain hemodialysis patients with poor condition of vascular or cardiac function in a compelling situation. METHODS: This was a cross-sectional study. Demographic characteristics and laboratory data were extracted from the health care system. Relevant DAP information was collected by a questionnaire. Case-control matching was performed to compare the hemodialysis adequacy between DAP and other VAs. RESULTS: A total of 526 patients were selected for analysis by convenience sampling, of which 38 patients relied https://www.baidu.com/link?url=eaDh8Hn-yZGJyDB0_h4zBenKd7qY1yX-KNxO-qU49gktQOGTJJg3slTjIbG095st4hRfprQIHRjfhfeGOZyH73y8tvSUCwMmvWbUhyix2ZK on DAP for hemodialysis. The main reasons using DAP for hemodialysis included the cost of arteriovenous access creation or maintenance in 19(50%) patients and the poor condition of vascular or cardiac function in 14 (39.5%) patients. Some complications of DAP occurred, such as aneurysm or pseudoaneurysm in 16(42.1%) patients, infiltration in 12 (31.6%) patients. Differences in hemodialysis adequacy were not statistically significant between DAP and other types of VA. CONCLUSION: In conclusion, DAP can meet the need of prescription hemodialysis, yet it has several limitations. Although the patients in our study were long-term dependent on DAP for hemodialysis with various reasons, we do not recommend DAP as a long-term vascular access if better options are available. However, DAP should not be overlooked to be a supplemental VA for hemodialysis with adequate blood flow and availability for individuals with poor condition of vascular or cardiac function in a compelling situation.

Design, Synthesis, and Biological Evaluation of N14-Amino Acid-Substituted Tetrandrine Derivatives as Potential Antitumor Agents against Human Colorectal Cancer.

As a typical dibenzylisoquinoline alkaloid, tetrandrine (TET) is clinically used for the treatment of silicosis, inflammatory pulmonary, and cardiovascular diseases in China. Recent investigations have demonstrated the outstanding anticancer activity of this structure, but its poor aqueous solubility severely restricts its further development. Herein, a series of its 14-N-amino acid-substituted derivatives with improved anticancer effects and aqueous solubility were designed and synthesized. Among them, compound 16 displayed the best antiproliferative activity against human colorectal cancer (HCT-15) cells, with an IC50 value of 0.57 µM. Compared with TET, 16 was markedly improved in terms of aqueous solubility (by 5-fold). Compound 16 significantly suppressed the colony formation, migration, and invasion of HCT-15 cells in a concentration-dependent manner, with it being more potent in this respect than TET. Additionally, compound 16 markedly impaired the morphology and motility of HCT-15 cells and induced the death of colorectal cancer cells in double-staining and flow cytometry assays. Western blot results revealed that 16 could induce the autophagy of HCT-15 cells by significantly decreasing the content of p62/SQSTM1 and enhancing the Beclin-1 level and the ratio of LC3-II to LC3-I. Further study showed that 16 effectively inhibited the proliferation, migration, and tube formation of umbilical vein endothelial cells, manifesting in a potent anti-angiogenesis effect. Overall, these results revealed the potential of 16 as a promising candidate for further preclinical studies.

SUCCESSFUL RESOLUTION OF NUTCRACKER SYNDROME WITH 3D PRINTED PEEK EXTRAVASCULAR STENT IN AN ADOLESCENT BOY.

Three-dimensional printed polyetheretherketone (PEEK) extravascular stent was applied to treat a 14-year-old boy with nutcracker syndrome. Digital subtraction angiography revealed a segment of the left renal vein (LRV) with reduced contrast filling immediately before its inflow into the inferior vena cava, and high-pressure gradient. The three-dimensional reconstruction model demonstrated that the LRV and the duodenum were contracted at the aortomesenteric angle, resulting in LRV compression from the abnormal high-level duodenal compartment. When duodenum courses between the abdominal aorta and superior mesenteric artery (duodenal interposition), the LRV entrapment occurs even at <90 aortomesenteric degrees. Three-dimensional printed PEEK extravascular stent was chosen to elevate the superior mesenteric artery and lower the duodenum position, thus relieving LRV compression. This extravascular application has significant advantages over open surgery, endovascular stenting and artificial vessel procedures with expanded polytetrafluoroethylene. It provides better cellular vitality by ensuring soft tissue proliferation. By reducing external acceleration and centrifugal force, a three-dimensional printed PEEK extravascular stent reduces adverse side effects. Such a stent has a distinctive personalized design, good stiffness, and durability that allows blood vessel growth, preventing stent migration and thrombosis. Therefore, it is suitable for both adult and pediatric patients. According to the abdominal ultrasound and multi-slice computed tomography scan, the postoperative follow-up results were satisfactory one year after surgery. The patient felt well, the blood flow in the LRV was not obstructed, and the blood flow velocity was average. The external stent was in place.

Altered spatiotemporal consistency in pediatric bipolar disorder patients with and without psychotic symptoms.

OBJECTIVE: Psychotic symptoms are quite common in patients with pediatric bipolar disorder (PBD) and may affect the symptom severity and prognosis of PBD. However, the potential mechanisms are less well elucidated until now. Thus, the purpose of this study was to investigate the brain functional differences between PBD patients with and without psychotic symptoms. METHOD: A total of 71 individuals including: 27 psychotic PBD (P-PBD), 25 nonpsychotic PBD (NP-PBD), and 19 healthy controls were recruited in the present study. Each subject underwent 3.0 Tesla functional magnetic resonance imaging scan. Four-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was employed to detect the local brain activity changes. Analyses of variance (ANOVA) were used to reveal brain regions with significant differences among three groups groups of individuals, and inter-group comparisons were assessed using post hoc tests. RESULTS: The ANOVA obtained significant among-group FOCA differences in the left triangular inferior frontal gyrus, left supplementary motor area, left precentral gyrus, right postcentral gyrus, right superior occipital gyrus, and right superior frontal gyrus. Compared with the control group, the P-PBD group showed decreased FOCA in the left supplementary motor area and bilateral superior frontal gyrus and showed increased FOCA in the left triangular inferior frontal gyrus. In contrast, the NP-PBD group exhibited decreased FOCA in the right superior occipital gyrus and right postcentral gyrus and showed increased FOCA in the left orbital inferior frontal gyrus. Compared to the NP-PBD group, the P-PBD group showed decreased FOCA in the right superior frontal gyrus. CONCLUSION: The present findings demonstrated that the two groups of PBD patients exhibited segregated brain functional patterns, providing empirical evidence for the biological basis of different clinical outcomes between PBD patients with and without psychotic symptoms.