Design, synthesis and biological evaluation of CDC20 inhibitors for treatment of triple-negative breast cancer.

The involvement of CDC20 in promoting tumor growth in different types of human cancers and it disturbs the process of cell division and impedes tumor proliferation. In this work, a novel of Apcin derivatives targeting CDC20 were designed and synthesized to evaluate for their biological activities. The inhibitory effect on the proliferation of four human tumor cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and A549) was observed. Among them, compound E1 exhibited the strongest inhibitory effect on the proliferation of MDA-MB-231 cells with an IC50 value of 1.43 µM, which was significantly superior to that of Apcin. Further biological studies demonstrated that compound E1 inhibited cancer cell migration and colony formation. Furthermore, compound E1 specifically targeted CDC20 and exhibited a higher binding affinity to CDC20 compared to that of Apcin, thereby inducing cell cycle arrest in the G2/M phase of cancer cells. Moreover, it has been observed that compound E1 induces autophagy in cancer cells. In 4T1 Xenograft Models compound E1 exhibited the potential antitumor activity without obvious toxicity. These findings suggest that E1 could be regarded as a CDC20 inhibitor deserved further investigation.

Fully endoscopic microvascular decompression for hemifacial spasm: a clinical study and analysis.

Fully endoscopic microvascular decompression (MVD) of the facial nerve is the main surgical treatment for hemifacial spasm. However, the technique presents distinct surgical challenges. We retrospectively analyzed prior cases to consolidate surgical insights and assess clinical outcomes. Clinical data from 16 patients with facial nerve spasms treated at the Department of Neurosurgery in the First Affiliated Hospital of Bengbu Medical College, between August 2020 and July 2023, were retrospectively examined. Preoperatively, all patients underwent magnetic resonance angiography to detect any offending blood vessels; ascertain the relationship between offending vessels, facial nerves, and the brainstem; and detect any cerebellopontine angle lesions. Surgery involved endoscopic MVD of the facial nerve using a mini Sigmoid sinus posterior approach. Various operative nuances were summarized and analyzed, and clinical efficacy, including postoperative complications and the extent of relief from facial paralysis, was evaluated. Fully endoscopic MVD was completed in all patients, with the offending vessels identified and adequately padded during surgery. The offending vessels were anterior inferior cerebellar artery in 12 cases (75%), vertebral artery in 3 cases (18.75%), and posterior inferior cerebellar artery in 1 case (6.25%). Intraoperative electrophysiological monitoring revealed that the lateral spread response of the facial nerve vanished in 15 cases and remained unchanged in 1 case. Postoperative facial spasms were promptly alleviated in 15 cases (93.75%) and delayed in 1 case (6.25%). Two cases of postoperative complications were recorded-one intracranial infection and one case of tinnitus-both were resolved or mitigated with treatment. All patients were subject to follow-up, with no instances of recurrence or mortality. Fully endoscopic MVD of the facial nerve is safe and effective. Proficiency in endoscopy and surgical skills are vital for performing this procedure.

STING mediates SU5416/hypoxia-induced pulmonary arterial hypertension in rats by regulating macrophage NLRP3 inflammasome activation.

BACKGROUND: The NLRP3 inflammasome in macrophages is known to promote infection-related vascular growth, and NLRP3 inflammasome activation interacts with PAH. STING is a crucial inflammatory reaction link that can increase the overexpression of NLRP3. However, the expression and effect of STING in PAH have not been elucidated. We examined the expression and articulation of STING in PAH and researched its hidden mechanism. METHODS: A SU5416 plus hypoxia (Su/Hy)-induced rat model of PAH was constructed to examine STING activation. Su/Hy induced PAH rats were given a prophylactic injection of STING the inhibitor C-176. After modeling, hemodynamic changes, right ventricular hypertrophy index, lung morphological features, inflammasome activation, and proinflammatory cytokine secretion levels were assessed. In addition, the STING agonist DMXAA or inhibitor C-176 was used to interfere with LPS-induced BMDMs, NLRP3 inflammasome activation and cytokine secretion were examined, and the effect on PASMCs was evaluated in a coculture system. RESULTS: STING expression increased significantly in the lung tissue of Su/Hy-treated PAH rats compared with normoxia-treated rats. Moreover, STING inhibitors can alleviate the Su/Hy-induced increase in pulmonary artery pressure and restrain the activation of the NLRP3 inflammasome and proinflammatory cytokines. In vitro experiments confirmed that STING affected the expression of the NLRP3 inflammasome and the secretion of inflammatory cytokines in BMDMs and promoted the proliferation of PASMCs in the coculture system. CONCLUSION: Our study shows that STING is activated in Su/Hy-induced PAH and boosts the actuation of the macrophage NLRP3 inflammasome to advance the inflammatory response and vascular proliferation in rats with Su/Hy-induced pulmonary hypertension.

Knowledge mapping of syringomyelia from 2003 to 2022: A bibliometric analysis.

BACKGROUND: Syringomyelia is a chronic, progressive disease of the spinal cord. Syringomyelia is an etiologically diverse affliction caused by disturbance of normal cerebrospinal fluid flow dynamics. Lesions are characterized by the formation of tubular cavities in the gray matter of the spinal cord and gliosis; however, the etiology is unknown and treatment methods differ. Many existing studies have focused on the relationship between other diseases and syringomyelia. There is a lack of comprehensive and objective reports on the research status of syringomyelia. Therefore, this study aimed to conduct a bibliometric analysis to quantify studies on Syringomyelia and trending issues in the last 20 years. METHODS: Articles were acquired from the Web of Science Core Collection database. We used the Library Metrology online analysis platform, BICOMB, gCLUTO, CiteSpace bibliometrics tools for analysis, VOSviewer 1.6.16 (Nees Jan van Eck and Ludo Waltman, 2010), and Microsoft Excel 2019 to perform bibliometric analysis and visualization. Individual impact and collaborative information were quantified by analyzing annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. We then identified the trending research areas of syringomyelia by analyzing the co-occurrence of keywords and co-cited references. RESULTS: From January 2003 to August 2022, 9,556 authors from 66 countries published a total of 1,902 research articles on syringomyelia in 518 academic journals. Most publications come from the United States, China, the United Kingdom, and Japan, with the United States dominating. Nanjing University and the University of Washington are the most active institutions, Dr. Claire Rusbridge has published the most papers, and Miholat has the most co-citations. The Journal of Neurosurgery has the highest number of co-cited articles, which are mainly in the fields of neurology, surgery, and biology. High-frequency keywords included syringomyelia, Chiari-I malformation, children, surgical treatment, and spinal cord. CONCLUSIONS: The number of articles on syringomyelia has increased steadily over the past two decades. At present, research on syringomyelia is mainly focused on the age of onset, potential therapeutic interventions, surgical treatment, avoidance of recurrence, and delay of pain. The use of surgical treatment of the disease and the mechanism of further treatment are the current hot research topics. The correlation between trauma and congenital factors, translational application, the effect of surgical treatment, postoperative recurrence, and complications are further hot research areas. These may provide ideas for further research into a radical cure for syringomyelia.

Keyhole supraorbital eyebrow approach for fully endoscopic resection of tuberculum sellae meningioma.

Background: The fully endoscopic supraorbital trans-eyebrow keyhole approach is a technique utilized for the transcranial resection of tuberculum sellae meningioma (TSM). Surgery is the first choice for TSM treatment. This study aimed to summarize and analyze the safety, feasibility, limitations, and technical requirements of the fully endoscopic supraorbital trans-eyebrow keyhole approach for TSM resection. Methods: Data of 19 TSM fully endoscopic supraorbital trans-eyebrow keyhole approach resections cases (six and 13 on the left and right eyebrows, respectively) were retrospectively analyzed at the Neurosurgery Department of the First Affiliated Hospital of Bengbu Medical College (Bengbu, China) from August 2015 to March 2022. Results: All 19 patients were diagnosed with meningioma (World Health Organization grade I), and according to the scope of tumor resection (EOR), 18 patients (94.7%) had gross total resection (GTR), and one patient (5.3%) had near-total resection (NTR). Preoperative chief complaints were symptomatic visual dysfunction (n = 12), headache and dizziness (n = 6), and accidental discovery (n = 1). Postoperative visual function improved in 83.3% of cases (10/12), and headache and dizziness were relieved in 83.3% of cases (5/6 patients). Postoperative intracranial infection occurred in one case and was cured by external drainage of the lumbar cistern and anti-infective treatment. Two cases of frontal lobe injury were discharged after conservative treatment. There was no postoperative olfactory dysfunction, eyelid ptosis, cerebrospinal fluid leakage, or death. There were no reports of disease recurrence or death during the 3-month follow-up at an outpatient clinic or by telephone. Conclusion: Fully endoscopic TSM resection through the keyhole approach is safe and feasible. It can be used to explore angles that cannot be seen under a microscope and show the true value of endoscopy technology. The endoscopic equipment and technical skills of the surgeon and surgical team are important in this technique.

Analysis of neuroendoscopy for the treatment of macroadenomas and giant pituitary adenomas.

Objective: This study investigated the use and effectiveness of endoscopic transnasal, transsphenoidal surgery, a minimally invasive method for the treatment of macroadenomas and giant pituitary a denomas, in a medical setting. The surgical results of 429 patients who received neuroendoscopic treatment of macroadenomas or giant pituitary adenomas were evaluated, and the experiences and lessons learned from treatment complications were assessed. Patients and methods: From January 2012 to December 2021, 429 patients with macroadenomas or giant pituitary adenomas, including 60 patients with giant adenomas (diameter ≥4 cm) and 369 patients with macroadenomas (diameter 1-4 cm), received a 3D head CT, a MRI with contrast enhancement, and an endocrinology examination prior to surgery. Preoperative clinical and radiological features, visual measurements, hormone levels, length of stay, length of surgery, postoperative stay, visual and hormone outcomes, resection range, complication and recurrence rates, and routine patient information were recorded. The patients were followed up for 6-72 months (median = 40 months). Results: Of 429 patients with macroadenomas or giant pituitary adenomas who received neuroendoscopic treatment, 348 (81.12%) had gross-total resections (GTR), 53 (12.35%) had near-total resections (NTR), and 28 (6.53%) had subtotal resections. There were 138 cases of post-operative diabetes insipidus (32.17%), including 7 cases of permanent diabetes insipidus (1.63%), 16 cases of nasal hemorrhage (3.73%), 39 cases of intraoperative cerebrospinal fluid leakage (9.09%), 4 cases of intracranial infection (0.9%), 16 cases of hypophysis (3.7%), and 15 cases of anosmia (3.50%). The clinical symptoms and endocrinology indices of the patients improved after surgery, and all patients were discharged 5-18 days (8.36 ± 2.65) postop. Conclusion: Neuroendoscopy is a safe operation with a short recovery period and hospital stay and is thus an effective method to treat macroadenomas and giant pituitary adenomas. Preoperative evaluation and prediction can help to accurately address possible intraoperative situations and improve GTR.

Endoscope-assisted microneurosurgery for intracranial aneurysms: A systematic review and meta-analysis.

BACKGROUND: In the surgical approach to treat deep-seated intracranial lesions, endoscopes can be used to assist microsurgical operations and improve outcomes. This technique is often called endoscope-assisted microneurosurgery (EAM). This systematic review and meta-analysis aimed to evaluate the feasibility, safety, and effectiveness of EAM. METHODS: We performed a meta-analysis of relevant articles identified using PubMed, Embase, and the Cochrane Central Register to assess the efficacy of EAM according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Primary outcomes were repositioning of the definitive clip, better surgical field, the overall and endoscope-related complication rates, mortality, and the rate of follow up. RESULTS: A total of 10 studies of 1,432 patients with 1,717 aneurysms treated with EAM were included. EAM led to repositioning of the definitive clip in 13% (95% CI, 9%-17%; I2 = 72.61%; p < 0.001); 77% of aneurysms treated with endoscopically assisted vision and information had a better outcome than that with standard surgery (95% CI, 52%-95%; I2 = 97.63%; p < 0.001). There was an overall complication rate of 6% (95% CI, 1%-13%; I2 = 91.39%; p < 0.001). The incidence of endoscope-related complications was 0% (95% CI, 0%-1%; I2 = 64%; p < 0.001). The mortality was 0% (95% CI, 0-1%; I2 = 0.0%); and 94% of patients had an excellent to good recovery and good outcome (95% CI, 88%-98%; I2 = 88.42%; p < 0.001). CONCLUSIONS: Our comprehensive study showed that EAM for intracranial aneurysms is feasible, the safety of the surgery is good, and the patients have a good prognosis, Therefore, we think EAM can be more widely adopted in the future.

An m6A/m5C/m1A/m7G-Related Long Non-coding RNA Signature to Predict Prognosis and Immune Features of Glioma.

Background: Gliomas are the most common and fatal malignant type of tumor of the central nervous system. RNA post-transcriptional modifications, as a frontier and hotspot in the field of epigenetics, have attracted increased attention in recent years. Among such modifications, methylation is most abundant, and encompasses N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1 methyladenosine (m1A), and 7-methylguanosine (m7G) methylation. Methods: RNA-sequencing data from healthy tissue and low-grade glioma samples were downloaded from of The Cancer Genome Atlas database along with clinical information and mutation data from glioblastoma tumor samples. Forty-nine m6A/m5C/m1A/m7G-related genes were identified and an m6A/m5C/m1A/m7G-lncRNA signature of co-expressed long non-coding RNAs selected. Least absolute shrinkage and selection operator Cox regression analysis was used to identify 12 m6A/m5C/m1A/m7G-related lncRNAs associated with the prognostic characteristics of glioma and their correlation with immune function and drug sensitivity analyzed. Furthermore, the Chinese Glioma Genome Atlas dataset was used for model validation. Results: A total of 12 m6A/m5C/m1A/m7G-related genes (AL080276.2, AC092111.1, SOX21-AS1, DNAJC9-AS1, AC025171.1, AL356019.2, AC017104.1, AC099850.3, UNC5B-AS1, AC006064.2, AC010319.4, and AC016822.1) were used to construct a survival and prognosis model, which had good independent prediction ability for patients with glioma. Patients were divided into low and high m6A/m5C/m1A/m7G-LS groups, the latter of which had poor prognosis. In addition, the m6A/m5C/m1A/m7G-LS enabled improved interpretation of the results of enrichment analysis, as well as informing immunotherapy response and drug sensitivity of patients with glioma in different subgroups. Conclusion: In this study we constructed an m6A/m5C/m1A/m7G-LS and established a nomogram model, which can accurately predict the prognosis of patients with glioma and provides direction toward promising immunotherapy strategies for the future.

Case Report: Langerhans Cell Sarcoma With Intracranial and Extracranial Communication on the Left Frontal Bone.

Background: Langerhans cell sarcoma (LCS) is an extremely rare type of malignant tumor that originates from Langerhans cells (LC). It is characterized by the malignant proliferation and dissemination of LC and is extremely invasive, with rapid progression and a poor prognosis. Treatment includes resection of lesions, radiotherapy, chemotherapy, immunotherapy, and transplantation of hematopoietic stem cells. However, a unified and optimized treatment plan is lacking, and individualized treatment is accepted. Case presentation: We report an 18-year-old man with intracranial and extracranial communicative LCS that occurred in only the left forehead without metastasis to other regions. Clinical and hematological data were normal. We undertook complete resection of diseased tissue, which was pathologically examined. Staining (hematoxylin and eosin) showed positivity for cluster of differentiation (CD)1a (++), S-100 protein (++), P53 (++), CD68 (+), cyclin D1 (+), cyclin A (+), cyclin B1 (+), IGF2BP3 (+), and Ki-67 (45%-50%). Recurrence or metastasis were not observed after long-term follow-up. Conclusion: LCS is a rare malignant tumor, and one that occurs with intracranial and extracranial communication is even rarer. Active adoption of an individualized treatment plan is crucial.

Hereditary intraspinal schwannomatosis with SMARCB1 gene mutation: A case report.

BACKGROUND: Schwannomatosis is the third subtype of neurofibromatosis. Schwannomatosis, particularly the familial variant, is uncommon. Recently, germline mutations of the SMARCB1 gene have been found to cause schwannomatosis. In this report, we describe a case of familial inherited intraspinal schwannomatosis. Postoperative pathology indicated a schwannoma. The results of gene testing showed that the SMARCB1 gene had a spliced mutation. CASE DESCRIPTION: A patient with a rare case of familial intraluminal schwannomatosis was admitted to our hospital. Peripheral blood gene testing was performed on the patient and her son, and a splice mutation of the SMARCB1 gene located at C. 1118+1G>A on intron 8 was identified. CONCLUSIONS: Schwannomatosis is an incomplete dominant autosomal dominant genetic disorder. The structural and functional abnormalities of proteins caused by mutations in the SMARCB1 gene may be the molecular basis for familial schwannomatosis.

Endothelial cell ferroptosis mediates monocrotaline-induced pulmonary hypertension in rats by modulating NLRP3 inflammasome activation.

Inflammation triggers pulmonary vascular remodelling. Ferroptosis, a nonapoptotic form of cell death that is triggered by iron-dependent lipid peroxidation and contributes to the pathogenesis of several inflammation-related diseases, but its role in pulmonary hypertension (PH) has not been studied. We examined endothelial cell ferroptosis in PH and the potential mechanisms. Pulmonary artery endothelial cells (PAECs) and lung tissues from monocrotaline (MCT)-induced PH rats were analysed for ferroptosis markers, including lipid peroxidation, the labile iron pool (LIP) and the protein expression of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1) and NADPH oxidase-4 (NOX4). The effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on endothelial cell ferroptosis and pulmonary vascular remodelling in MCT-induced rats were studied in vitro and in vivo. Ferroptosis was observed in PAECs from MCT-induced PH rats in vitro and in vivo and was characterized by a decline in cell viability accompanied by increases in the LIP and lipid peroxidation, the downregulation of GPX4 and FTH1 expression and the upregulation of NOX4 expression. High-mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signalling was measured by western blotting. These changes were significantly blocked by Fer-1 administration in vitro and in vivo. These results suggest that Fer-1 plays a role in inhibiting ferroptosis-mediated PAEC loss during the progression of PH. The ferroptosis-induced inflammatory response depended on the activation of HMGB1/TLR4 signalling, which activated the NLRP3 inflammasome in vivo. We are the first to suggest that pulmonary artery endothelial ferroptosis triggers inflammatory responses via the HMGB1/TLR4/NLRP3 inflammasome signalling pathway in MCT-induced rats. Treating PH with a ferroptosis inhibitor and exploring new treatments based on ferroptosis regulation might be promising therapeutic strategies for PH.

Systematic characterization of the tumor microenvironment in Chinese patients with hepatocellular carcinoma highlights intratumoral B cells as a potential immunotherapy target.

Hepatocellular carcinoma (HCC) is an immunogenic malignancy, which exhibits low responsiveness to programmed cell death protein­1 (PD­1)/programmed death ligand­1 (PD­L1) antibodies. Therefore, the identification of novel immunotherapeutic targets to treat HCC is imperative. Systematic characterization of the HCC tumor microenvironment (TME) can provide novel insight into additional therapeutic approaches. In the present study, the RNA­sequencing (RNA­seq) data of 360 patients with HCC were integrated from The Cancer Genome Atlas to assess the expression of membrane spanning 4­domains A1 (MS4A1; encoding CD20) in tumors and normal liver tissues. Immunofluorescence and multiplex tissue fluorescence analyses were performed and combined with flow cytometry staining to measure CD20/CD19 expression at the protein level. In addition, published single cell RNA­seq data of CD45+ cells were derived from 16 treatment­naïve patients from Beijing Shijitan Hospital with HCC to illustrate the characteristics of CD19+ B cells. The results indicated that the HCC TME included nuclear receptor subfamily 4 group A member 2+ (NR4A2) B cells. Patients with HCC and high density of intratumoral B cells demonstrated compromised antitumor immunity manifested by low percentages of cytotoxic CD8+ T cells and high density of regulatory T cells. Furthermore, PD­L1 expression was significantly correlated with the B cell signature marker CD20. The present study indicated that tumor­infiltrating B cells may play a negative role in antitumor immunity and serve as a promising target for HCC immunotherapy, alone or in combination with anti­PD­L1/PD­1 antibodies.

A New Stemness-Related Prognostic Model for Predicting the Prognosis in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: This study is aimed at identifying stemness-related genes in pancreatic ductal adenocarcinoma (PDAC). METHODS: The RNA-seq data of PADC patients were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The mRNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi (EREG-mRNAsi) of PADC patients were evaluated. The mRNAsi-related gene sets in PADC were identified by weighted gene coexpression network analysis (WGCNA). The key genes were further analyzed using functional enrichment analysis. The Kaplan-Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of the key genes. Prognostic hub genes were used to establish nomograms. The receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves were used to assess the discrimination and accuracy of the nomogram. Finally, these results were validated in the Gene Expression Omnibus (GEO) database. RESULTS: A total of 36 key genes related to mRNAsi were identified by WGCNA. A prognostic gene signature compromising seven genes (TPX2, ZWINT, UBE2C, CCNB2, CDK1, BUB1, and BIRC5) was established to predict the overall survival (OS) of PADC patients. The Cox regression analysis revealed that the risk score was an independent prognostic factor for PADC. Patients were then divided into the high-risk and low-risk groups. The ROC curves, C-index, and calibration curves indicated good performance of the prognostic signature in the TCGA and GEO datasets. Moreover, the nomogram incorporating clinical parameters showed better sensitivity and specificity for predicting the OS of PADC patients. CONCLUSION: The stemness-related prognostic model successfully predicted the OS of PADC patients and could be used for the treatment of PADC.

Early Prediction of Left Ventricular Reverse Remodeling in First-Diagnosed Idiopathic Dilated Cardiomyopathy: A Comparison of Linear Model, Random Forest, and Extreme Gradient Boosting.

Introduction: Left ventricular reverse remodeling (LVRR) is associated with decreased cardiovascular mortality and improved cardiac survival and also crucial for therapeutic options. However, there is a lack of an early prediction model of LVRR in first-diagnosed dilated cardiomyopathy. Methods: This single-center study included 104 patients with idiopathic DCM. We defined LVRR as an absolute increase in left ventricular ejection fraction (LVEF) from >10% to a final value >35% and a decrease in left ventricular end-diastolic diameter (LVDd) >10%. Analysis features included demographic characteristics, comorbidities, physical sign, biochemistry data, echocardiography, electrocardiogram, Holter monitoring, and medication. Logistic regression, random forests, and extreme gradient boosting (XGBoost) were, respectively, implemented in a 10-fold cross-validated model to discriminate LVRR and non-LVRR, with receiver operating characteristic (ROC) curves and calibration plot for performance evaluation. Results: LVRR occurred in 47 (45.2%) patients after optimal medical treatment. Cystatin C, right ventricular end-diastolic dimension, high-density lipoprotein cholesterol (HDL-C), left atrial dimension, left ventricular posterior wall dimension, systolic blood pressure, severe mitral regurgitation, eGFR, and NYHA classification were included in XGBoost, which reached higher AU-ROC compared with logistic regression (AU-ROC, 0.8205 vs. 0.5909, p = 0.0119). Ablation analysis revealed that cystatin C, right ventricular end-diastolic dimension, and HDL-C made the largest contributions to the model. Conclusion: Tree-based models like XGBoost were able to early differentiate LVRR and non-LVRR in patients with first-diagnosed DCM before drug therapy, facilitating disease management and invasive therapy selection. A multicenter prospective study is necessary for further validation. Clinical Trial Registration:http://www.chictr.org.cn/usercenter.aspx (ChiCTR2000034128).

Carbon Arc Lamp Therapy Enhances the Repair Potential of Chronic Soft Tissue Injury in Rats Compared with the Ability of Photobiomodulation Therapy.

Objective: The effects of photobiomodulation therapy (PBMT) and carbon arc lamp therapy (CALT) on the repair of chronic soft tissue injury were compared. Background data: PBMT improves soft tissue repair of chronic injury. However, there has been no research on the effect of CALT. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated using PBMT and CALT at 2 J/cm2 to observe their effects on cell proliferation and migration. The effects of PBMT and CALT on soft tissue injury repair were assessed using a chronic gastrocnemius injury model of the posterior limb in rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) were examined by biochemical analyses. The degree of tissue damage repair was evaluated by the immunohistochemical method [CD45, CD34, vascular endothelial growth factor (VEGF), and actin] and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Results: Treatment by PBMT and CALT significantly accelerated the proliferation and migration of HUVECs. Moreover, significant decreases in the contents of MDA and PGE2 were observed in the PBMT and CALT groups, while SOD activity was increased. The histological assessment shows that the content of inflammatory cells and apoptotic cells significantly decreased in the CALT group. However, the microvascular density, VEGF content, and actin content were increased in the CALT group. Conclusions: The results demonstrate that CALT has a stronger effect on promoting chronic soft tissue injury repair in comparison with PBMT.

Interferon regulatory factor 7 inhibits rat vascular smooth muscle cell proliferation and inflammation in monocrotaline-induced pulmonary hypertension.

AIMS: Although interferon regulatory factor 7 (IRF7) has known roles in regulating the inflammatory response, vascular smooth muscle cell proliferation, and apoptosis, its role in the pathogenesis of pulmonary hypertension (PH) is unclear. We hypothesized that IRF7 overexpression could inhibit pulmonary vascular remodeling and slow the progression of PH. MAIN METHODS: IRF7 mRNA and protein levels in the lung samples and pulmonary artery smooth muscle cells (PASMCs) isolated from monocrotaline (MCT)-induced PH rats were assessed. We evaluated the effects of IRF7 on inflammation, proliferation, and apoptosis using an in vivo MCT-induced PH rat model and in vitro methods. KEY FINDINGS: We noted decreased IRF7 mRNA and protein levels in the pulmonary vasculature of MCT-induced PH rats. IRF7 upregulation attenuated pulmonary vascular remodeling, decreased the pulmonary artery systolic pressure, and improved the right ventricular (RV) structure and function. Our findings suggest that nuclear factor kappa-Bp65 (NF-κBp65) deactivation could confer pulmonary vasculature protection, reduce proinflammatory cytokine (tumor necrosis factor-α, interleukin 6) release, and decrease PASMC proliferation and resistance to apoptosis via deactivating transcription factor 3 (ATF3) signaling. ATF3 deactivation induced the downregulation of the proliferation-dependent genes proliferating cell nuclear antigen (PCNA), cyclin D1, and survivin, coupled with increased levels of B cell lymphoma-2-associated X protein (Bax)/B cell lymphoma-2 (Bcl2) ratio, and cleaved caspase-3 in PASMCs. SIGNIFICANCE: Our findings showed that IRF7 downregulation could initiate inflammation via NF-κBp65 signaling, causing PASMC proliferation via ATF3 signaling pathway activation. Therefore, IRF7 could be a potential molecular target for PH therapy.

Endoscopic Vascular Decompression for the Treatment of Trigeminal Neuralgia: Clinical Outcomes and Technical Note.

PURPOSE: Microvascular decompression (MVD) surgery is considered as an effective method with which to treat trigeminal neuralgia (TN). However, sometimes MVD surgery fails due to incomplete decompression of the responsible vessels caused by a poor visual field. In this study, we evaluated the benefits of endoscopic visualization and the value of full endoscopic vascular decompression (EVD) by describing the surgical results of 20 patients with TN after EVD. PATIENTS AND METHODS: This was a retrospective study in a single institution of 20 patients with TN who received EVD between April 2018 and October 2019. All patients underwent EVD via the suboccipital retrosigmoid approach without microscopy at any stage. Abnormal muscle response (AMR) and brainstem auditory evoked potentials (BAEPs) were routinely monitored throughout the procedure. Follow-up was conducted by outpatient and telephone interviews. The degree of facial pain was graded using the Barrow Neurological Institute (BNI) pain intensity score; a BNI of 1 was considered as the best result while a BNI of 2 or 3 was considered as a satisfactory result. Follow-up time ranged from 8 to 24 months, with a mean of 18±4.36 months. RESULTS: All 20 patients with severe preoperative pain (BNI of 5) achieved immediate relief or complete control of pain after surgery (BNI of 1 to 2). Vascular conflicts were observed during surgery in all of the patients. None of the patients experienced hearing loss, facial paralysis, intracranial infection, cerebrospinal fluid leakage, cerebral hemorrhage, or death, following the operation. CONCLUSION: When carried out by surgeons with endoscopic experience, EVD can provide a clear surgical field of view and reduce the risk of surgical injury. Our findings indicate that EVD is a safe and effective surgical method for the treatment of TN.

E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing.

Rationale: Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and few molecularly targeted anticancer therapies have been developed to treat it. Thus, the identification of new therapeutic targets is urgent. Metabolic reprogramming is an important hallmark of cancer. However, how ubiquitin ligases are involved in the regulation of cancer metabolism remains poorly understood. Methods: RT-PCR, western blot and IHC were used to determine ZFP91 expression. RNAi, cell proliferation, colony formation and transwell assays were used to determine the in vitro functions of ZFP91. Mouse xenograft models were used to study the in vivo effects of ZFP91. Co-IP together with mass spectrometry or western blot was utilized to investigate protein-protein interaction. Ubiquitination was analyzed using IP together with western blot. RNA splicing was assessed by using RT-PCR followed by restriction digestion. Lactate production and glucose uptake assays were used to analyze cancer metabolism. Results: We identified that an E3 ligase zinc finger protein 91 (ZFP91) suppressed HCC metabolic reprogramming, cell proliferation and metastasis in vitro and in vivo. Mechanistically, ZFP91 promoted the Lys48-linked ubiquitination of the oncoprotein hnRNP A1 at lysine 8 and proteasomal degradation, thereby inhibiting hnRNP A1-dependent PKM splicing, subsequently resulting in higher PKM1 isoform formation and lower PKM2 isoform formation and suppressing HCC glucose metabolism reprogramming, cell proliferation and metastasis. Moreover, HCC patients with lower levels of ZFP91 have poorer prognoses, and ZFP91 is an independent prognostic factor for patients with HCC. Conclusions: Our study identifies ZFP91 as a tumor suppressor of hepatocarcinogenesis and HCC metabolism reprogramming and proposes it as a novel prognostic biomarker and therapeutic target of HCC.

Endoscopic band ligation for transverse colonic variceal bleeding: case report and review of the literature.

Colonic varices are lesser-known in comparison with gastroesophageal varices in a complication associated with liver cirrhosis. The ideal therapeutic intervention for a colonic varix is still unclear. We report a 42 year-old man with 20 years of alcohol use who presented with hematochezia and abdominal distension. The patient was diagnosed with alcoholic liver cirrhosis. The colonoscopy revealed a dilated and tortuous varix in the transverse colon close to the hepatic flexure with oozing blood, a communicating branch and with "red sign", evidence of acute bleeding. Endoscopic band ligation (EBL), the most useful intervention for esophageal varices, was further successfully performed to arrest the bleeding colonic varices. One month after initial treatment, the colonic varices nearly vanished and were replaced by an ulcer. It is extremely rare for colonic varices to be treated with EBL. There is only one similar case in reported literature, but it seems to be safe and effective as an intervention for EBL for acute colonic variceal bleeding. SIMILAR CASES: Second case treated by endoscopic band ligation.

T Follicular Helper Cells Regulate Humoral Response for Host Protection against Intestinal Citrobacter rodentium Infection.

Citrobacter rodentium colonizes at the colon and causes mucosal inflammation in mice. Previous studies have revealed the importance of the innate and adaptive immune response for controlling C. rodentium infection. In the present study, we examined the role of T follicular helper (Tfh) cells in intestinal C. rodentium infection using mice with Bcl6 deficiency in T cells. Tfh cells were absolutely required at the late, but not the early, phase to control infection. Compared with control mice, we observed systemic pathogen dissemination and more severe colitis in Tfh-deficient mice. Furthermore, the susceptibility of Tfh-deficient mice correlated with an impaired serum IgG1 response to infection, and serum Abs from infected wild-type mice protected Tfh-deficient mice from infection. The transfer of wild-type Tfh cells also restored the levels of IgG1 and led to effective clearance of the pathogens in Tfh-deficient mice. Moreover, during C. rodentium infection, IL-21- and IL-4-producing Tfh cells were increased obviously in wild-type mice, correlating with IgG1 as the major isotype in germinal center B cells. Taken together, our work highlights the requirement and the function of Tfh cells in regulating humoral response for the host protection against C. rodentium infection.