Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis.

Background: Marfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin-1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs). Methods: The Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation-regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co-expression network analysis was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS. Results: Our study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) exhibited a positive correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation. Conclusions: Taken together, our systems-level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

Modified Patent Hemostasis Strategy Based on the Platelet Counts for Transradial Access Chemoembolization in Patients with Hepatocellular Carcinoma: A Prospective Single-Center Study.

Objective: This study aimed to investigate the shortest compression time to achieve hemostasis and the optimal hemostasis strategy in patients treated with transradial access chemoembolization (TRA-TACE). Methods: From October 2019 to October 2021, 119 consecutive patients with hepatocellular carcinoma (HCC) who underwent 134 sessions of TRA-TACE were included in this prospective single-center study. The compression time was measured by decompressing the device for 30 min, and thereafter, every 10 min after the procedure until complete hemostasis was achieved. Results: Technical success was achieved for all TRA procedures. None of the patients experienced major TRA-related adverse events. Minor adverse events occurred in 7.5% of the patients. The mean compression time was 31.8 ± 5.0 min. Factors that may impact hemostasis were analyzed by univariate and multivariate analyses, and a platelet count < 100×109 /L (p = 0.016, odds ratio = 3.942) was found to be an independent factor that could predict the failure to achieve hemostasis within 30 min. For patients with a platelet count < 100×109 /L, the compression time required to achieve hemostasis was 60 min. For patients with a platelet count ≥ 100×109 /L, the compression time required to achieve hemostasis was 40 min. Conclusion: To achieve hemostasis in patients with HCC treated with TRA-TACE, compression for 60 min is sufficient for those with a platelet count < 100×109 /L, and compression for 40 min is sufficient for those with a platelet count ≥ 100×109 /L.

Urinary Creatinine Concentrations and Its Explanatory Variables in General Chinese Population: Implications for Creatinine Limits and Creatinine Adjustment.

Objective: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. Methods: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. Results: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. Conclusion: The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.

Coxsackievirus A6 was the most common enterovirus serotype causing hand, foot, and mouth disease in Shiyan City, central China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) has become one of the most common infectious diseases in China. Before 2016, the primary causal serotypes were enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Following the introduction of EV-A71 vaccines in China since 2016, the situation could change. CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China. However, the epidemiological characteristics of central China remain unknown. AIM: To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City, central China, in recent years. METHODS: The epidemiological, clinical, and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed. 196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020. To detect and genotype enteroviruses, real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used. In Shiyan, 168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes. Based on the logistic regression model, the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan. RESULTS: From 2016 to 2020, 35840 HFMD cases were reported in Shiyan. The number of cases decreased by 48.4% from 2016 to 2017. Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year, respectively. In 2020, a decrease of about 85.5% was reported when compared to 2019. The most common serotypes shifted from EV-A71 and CV-A16 (about 60%-80% in 2016 and 2018) to others (more than 80.0% in 2017, 2019, and 2020). EV-A71 lost its dominance in 2017 in Shiyan. Among 196 confirmed HFMD cases, 85.7% tested positive for enterovirus, with CV-A6 being the most common serotype (121/168, 72.0%). The positive rates for CV-A16 and CV-A10 were 4.8% and 3.0%, respectively. There was no EV-A71 discovered. Infection with CV-A6 was linked to fever, myocardial damage, increased creatine kinase MB isoenzyme, and lactate dehydrogenase levels. CONCLUSION: CV-A6 was the most common enterovirus serotype in Shiyan City, replacing EV-A71 and CV-A16 as the HFMD pathogen. Developing vaccines against CV-A6 or multiple pathogens, as well as rising CV-A6 surveillance, will help prevent HFMD in central China.

Correlation analysis of carotid artery intima-media thickness, serum 25(OH)D and men with erectile dysfunction.

Our goal is to investigate the connection between serum 25(OH)D and carotid artery intima-media thickness (CIMT) in men with erectile dysfunction (ED).Serum 25(OH)D and CIMT were measured in 124 participants with erectile dysfunction and 39 healthy controls. The relationship between them and different patient-related parameters and disease-related parameters was studied. Compared with the control group and mild ED group, the level of serum 25(OH)D in moderate ED group and severe ED group decreased significantly(P<0.05). The CIMT values of moderate ED group and severe ED group were higher than those of the control group(P<0.05). The CIMT value of severe ED group was significantly higher than that of mild ED group(P<0.05). IIEF-5 score was positively correlated with serum 25(OH)D level, but negatively correlated with CIMT value(P<0.05). After adjusting for the influence of confounding factors, The CIMT values, 25(OH)D and IIEF-5 score were substantially associated(P<0.05). The serum level of 25(OH)D and IIEF-5 score were positively correlated, while the CIMT values and IIEF-5 score were negatively correlated. The level of serum 25(OH)D should be analyzed in men with ED, especially in patients with vasculogenic ED, and supplementation is recommended for those who were with vitamin D deficiency.

Diverse polycyclic polyprenylated acylphloroglucinols with anti-neuroinflammatory activity from Hypericum beanii.

A phytochemical investigation on the roots of Hypericum beanii resulted in the isolation of six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperberlones A-F, along with fourteen known analogues. The structural characterization of these compounds was carried out by analyzing the HRESIMS data, 1D and 2D NMR spectroscopic data, electronic circular dichroism (ECD) calculations, and gauge-independent atomic orbital (GIAO) NMR calculations. Hyperberlone A (1) was a caged PPAP with a rare tricyclo[4.3.1.03,8]decane carbon skeleton. It was deduced to be biosynthetically generated from hyperbeanol C (8) through key Paternò-Büchi reaction, radical cascade cyclizations, and retro-aldol reaction. Compounds 4, 6, 7, 9, 14, and 16 exhibited significant nitric oxide (NO) production inhibitory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values of 6.11-25.28 µM. Moreover, compound 4 significantly decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced BV-2 microglia, as well as the phosphorylation of JNK.

Electrospun polycaprolactone nanofibrous membranes loaded with baicalin for antibacterial wound dressing.

Due to the rise in bacterial resistance, the antibacterial extractions from Chinese herbs have been used more frequently for wound care. In this work, baicalin, an extraction from the Chinese herb Scutellaria baicalensis, was utilized as the antibacterial component in the poly(ε-caprolactone)/MXene (PCL/Ti3C2TX) hybrid nanofibrous membranes for wound dressing. The results revealed that the presence of Ti3C2TX aided in the diameter reduction of the electrospun nanofibers. The PCL hybrid membrane containing 3 wt% Ti3C2TX nanoflakes and 5 wt% baicalin exhibited the smallest mean diameter of 210 nm. Meanwhile, the antibacterial tests demonstrated that the PCL ternary hybrid nanofibers containing Ti3C2TX and baicalin exhibited adequate antibacterial activity against the Gram-positive bacterial S. aureus due to the good synergistic effects of Ti3C2TX naoflakes and baicalin. The addition of Ti3C2TX nanoflakes and baicalin could significantly improve the hydrophilicity of the membranes, resulting in the release of baicalin from the nanofibers. In addition, the cytotoxicity of the nanofibers on rat skeletal myoblast L6 cells confirmed their good compatibility with these PCL-based nanofibrous membrances. This work offers a feasible way to prepare antibacterial nanofibrous membranes using Chinese herb extraction for wound dressing applications.

Suppression of JNK/ERK dependent autophagy enhances Jaspine B derivative-induced gastric cancer cell death via attenuation of p62/Keap1/Nrf2 pathways.

Gastric cancer is one of the most common cancers with few effective treatments, a new treatment agent is desperately needed. C-2, a Jaspine B derivative, has shown anti-cancer efficacy in gastric cancer cells. The anti-cancer mechanism, however, remains unknown. As a result, we investigate the anti-cancer effect and the underlying mechanism of C-2 in gastric cancer cells. The results showed that C-2 selectively reduced the proliferation of gastric cancer cells when compared to normal epithelial gastric cells. Western blotting and flow cytometry further demonstrated that Caspase9 is involved in causing cell death. Meanwhile, C-2 triggered autophagy in gastric cancer cells, inhibition of which with LY294002 can enhance the anti-proliferative activity of C-2. Next, we found that C-2 triggered autophagy through activating JNK/ERK, and that inhibitors of these proteins exacerbated C-2 induced cell death. Mechanically, enhanced phosphorylation of JNK/ERK elevated Beclin-1 by disturbing Beclin-1/Bcl-xL or Beclin-1/Bcl-2 complexes, resulting in autophagy and up-regulation of p62. Finally, p62 binds Keap1 competitively to release Nrf2, boosting Nrf2 translocation from the cytoplasm to the nucleus and triggering expression of Nrf2 target genes, so enhancing survival. C-2 inhibited the growth of gastric cancer cells, while JNK/ERK dependent autophagy antagonized C-2 induced cell growth inhibition through p62/Keap1/Nrf2 pathway.

CircFAM120B knockdown inhibits osteosarcoma tumorigenesis via the miR-1205/PTBP1 axis.

BACKGROUND: Osteosarcoma (OS) is a highly prevalent bone malignancy with poor clinical outcomes. Expression of the circular RNA, hsa_circ_0078767 (circFAM120B) is elevated in OS, however, its mechanisms in OS are unclear. METHODS: CircFAM120B levels were detected in OS tissue and cell lines. Silenced circFAM120B experiments were performed to assess its effects on OS in vitro cancer phenotypes and in vivo tumor growth. Then, bioinformatics analyses were used to predict circFAM120B target microRNAs (miRNAs) and associated genes. RESULTS: CircFAM120B and the transcription factor, PTBP1 were elevated in OS tissue and cell lines, while miR-1205 was poorly expressed. Silenced circFAM120B significantly suppressed in vitro OS cell proliferation and invasion, and inhibited in vivo tumor growth. CircFAM120B also appeared to function as an miR-1205 sponge, as miR-1205 bound to PTBP1. Interestingly, overexpressed PTBP1 (or miR-1205 inhibition) reversed the inhibitory effects mediated by circFAM120B downregulation in OS cells. CONCLUSION: We hypothesize circFAM120B functions as a miR-1205 sponge to elevate PTBP1 levels, enhancing OS progression and associated malignant phenotypes. Thus, circFAM120B may function as a crucial mediator during OS progression.

Levels of anti-oxidative molecules and inflammatory factors in patients with vascular dementia and their clinical significance.

OBJECTIVES: To explore levels of anti-oxidative molecules and inflammatory factors in patients with vascular dementia (VD) and their clinical significance. METHODS: Sixty VD patients admitted in our hospital from January 2016 to January 2019 were classified into an experimental group, while another 60 healthy patients seeking physical examinations in the corresponding period were selected as a control group. Various indexes related to serum inflammatory factors and anti-oxidative molecules were compared among patients in such two groups. For the purpose of comparing anti-oxidative molecular expression levels and inflammatory factor levels in patients with VD of different severities, 60 cases in the experimental group were divided, based on a Mini-mental State Examination (MMSE) scale, into patients with mild symptoms (n=20, score: 21~26), patients with moderate symptoms (n=22, score: 10~20) and patients with severe symptoms (n=18, score: 0~9). RESULTS: By contrast to the control group, levels of inflammatory factors (e.g., TNF-a, CRP and IL-6) in VD patients are all significantly increased and their differences show statistical significance (p<0.05); and, expression levels of anti-oxidative factors, including superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), total antioxidant capacity (TAC), catalase (CAT) and glutathione reductase (GR), in the experimental group are apparently below those of the control group (P<0.05). As dementia degree increases, expression levels of serum anti-oxidative molecules in such patients are inclined to drop in a significant way (P<0.05), while inflammatory factor levels tend to go up gradually (P<0.05). CONCLUSIONS: If compared with the normal population, inflammatory factor levels in serum of VD patients are higher; however, expression levels of anti-oxidative molecules become below those of the normal population. Additionally, levels of inflammatory factors and anti-oxidative molecules may change obviously as severity of illness increases. This suggests that inflammation and oxidation play a certain role of auxoaction in VD patients.

Voltage-Driven Flipping of Zwitterionic Artificial Channels in Lipid Bilayers to Rectify Ion Transport.

We developed a voltage-sensitive artificial transmembrane channel by mimicking the dipolar structure of natural alamethicin channel. The artificial channel featured a zwitterionic structure and could undergo voltage-driven flipping in the lipid bilayers. Importantly, this flipping of the channel could lead to their directional alignment in the bilayers and rectifying behavior for ion transport.

Delirium in Older Patients after Combined Epidural-General Anesthesia or General Anesthesia for Major Surgery: A Randomized Trial.

BACKGROUND: Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. METHODS: Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. RESULTS: Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). CONCLUSIONS: Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.

Long-term Survival after Combined Epidural-General Anesthesia or General Anesthesia Alone: Follow-up of a Randomized Trial.

BACKGROUND: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients. METHODS: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. RESULTS: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. CONCLUSIONS: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.

"Felodipine-indomethacin" co-amorphous supersaturating drug delivery systems: "Spring-parachute" process, stability, in vivo bioavailability, and underlying molecular mechanisms.

Amorphous solid dispersions (ASD) are one of most commonly used supersaturating drug delivery systems (SDDS) to formulate insoluble active pharmaceutical ingredients. However, the development of polymer-guided stabilization of ASD systems faces many obstacles. To overcome these shortcomings, co-amorphous supersaturable formulations have emerged as an alternative formulation strategy for poorly soluble compounds. Noteworthily, current researches around co-amorphous system (CAS) are mostly focused on preparation and characterization of these systems, but more detailed investigations of their supersaturation ("spring-parachute" process), stability, in vivo bioavailability and molecular mechanisms are inadequate and need to be clarified. In present study, we chose pharmacological relevant BCS II drugs to fabricate and characterize "felodipine-indomethacin" CAS. To enrich the current inadequate but key knowledge on CAS studies, we carried out following highlighted investigations including dissolution/solubility, semi-continuous "spring-parachute" process, long-term stability profile of amorphous state, in vivo bioavailability and underlying molecular mechanisms (molecular interaction, molecular miscibility and crystallization inhibition). Generally, the research provides some key information in the field of current "drug-drug" CAS supersaturable formulations.

Overexpression of Spondin-2 Is Associated with Recurrence-Free Survival in Patients with Localized Clear Cell Renal Cell Carcinoma.

BACKGROUND: The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear. METHODS: SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration in vitro were investigated. RESULTS: SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all P < 0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration in vitro. CONCLUSION: SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.

tBuOK-Promoted Cyclization of Imines with Aryl Halides.

A transition-metal-free indole synthesis using radical coupling of 2-halotoluenes and imines via the later-stage C-N bond construction was reported for the first time. It includes an aminyl radical generation by C-H cleaving addition of 2-halotoluenes to imines via the carbanion radical relay and an intramolecular coupling of aryl halides with aminyl radicals. One standard condition can be used for all halides including F, Cl, Br, and I. No extra oxidant or transition metal is required.