3D EAGAN: 3D edge-aware attention generative adversarial network for prostate segmentation in transrectal ultrasound images.

Background: The segmentation of prostates from transrectal ultrasound (TRUS) images is a critical step in the diagnosis and treatment of prostate cancer. Nevertheless, the manual segmentation performed by physicians is a time-consuming and laborious task. To address this challenge, there is a pressing need to develop computerized algorithms capable of autonomously segmenting prostates from TRUS images, which sets a direction and form for future development. However, automatic prostate segmentation in TRUS images has always been a challenging problem since prostates in TRUS images have ambiguous boundaries and inhomogeneous intensity distribution. Although many prostate segmentation methods have been proposed, they still need to be improved due to the lack of sensibility to edge information. Consequently, the objective of this study is to devise a highly effective prostate segmentation method that overcomes these limitations and achieves accurate segmentation of prostates in TRUS images. Methods: A three-dimensional (3D) edge-aware attention generative adversarial network (3D EAGAN)-based prostate segmentation method is proposed in this paper, which consists of an edge-aware segmentation network (EASNet) that performs the prostate segmentation and a discriminator network that distinguishes predicted prostates from real prostates. The proposed EASNet is composed of an encoder-decoder-based U-Net backbone network, a detail compensation module (DCM), four 3D spatial and channel attention modules (3D SCAM), an edge enhancement module (EEM), and a global feature extractor (GFE). The DCM is proposed to compensate for the loss of detailed information caused by the down-sampling process of the encoder. The features of the DCM are selectively enhanced by the 3D spatial and channel attention module. Furthermore, an EEM is proposed to guide shallow layers in the EASNet to focus on contour and edge information in prostates. Finally, features from shallow layers and hierarchical features from the decoder module are fused through the GFE to predict the segmentation prostates. Results: The proposed method is evaluated on our TRUS image dataset and the open-source µRegPro dataset. Specifically, experimental results on two datasets show that the proposed method significantly improved the average segmentation Dice score from 85.33% to 90.06%, Jaccard score from 76.09% to 84.11%, Hausdorff distance (HD) score from 8.59 to 4.58 mm, Precision score from 86.48% to 90.58%, and Recall score from 84.79% to 89.24%. Conclusions: A novel 3D EAGAN-based prostate segmentation method is proposed. The proposed method consists of an EASNet and a discriminator network. Experimental results demonstrate that the proposed method has achieved satisfactory results on 3D TRUS image segmentation for prostates.

Biomimetic Total Synthesis of Bimagnolignan: A Natural Anti-Breast Cancer Agent.

A short scalable biomimetic route to bioactive natural product bimagnolignan (1) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol (2). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp2)-H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.

[Analysis of death cases in the oral emergency department].

In order to analyze the clinical characteristics of death cases in the oral emergency department of the stomatological hospital, and to improve the first aid technique before and in hospitals, we collected the clinical data of death cases in the Department of Oral Emergency in Peking University School and Hospital of Stomatology from January 2010 to January 2023 for retrospective analysis. General cha-racteristics, such as the patients' gender, age, chief complaint, maxillofacial diseases, systemic underlying diseases, rescue situation, cause of death and seasonal distribution of death were summarized. The results showed that a total of 8 death cases (5 males and 3 females) occurred during the 13-year period, ranging in age from 40 to 86 years, with a median age of 66 years. Among the 8 patients, 5 reported bleeding from oral cancer, 1 reported chest tightness and dyspnea after oral cancer surgery, 1 reported loss of consciousness after maxillofacial trauma, and 1 reported oral erosion and aphagia. All the 8 patients had one or more underlying diseases, such as hypertension, coronary heart disease, diabetes, renal failure, and cerebral infarction, etc. and 2 of them showed dyscrasia. Among them, the cause of death in 5 cases was respiratory and circulatory failure caused by oral cancer rupture and hemorrhage or poor surgical wound healing and hemorrhage; 1 case was uremia and hyperkalemia leading to circulatory failure; 1 case was asphyxia caused by swelling of oral floor tissue after maxillofacial trauma; and the other case was acute myocardial infarction caused circulatory failure after oral cancer surgery. According to the vital state at the time of treatment, 6 patients had loss of consciousness, respiratory and cardiac arrest before hospital, and 2 patients suffered from loss of consciousness, respiratory and cardiac arrest during treatment. All the patients received cardiopulmonary resuscitation and some advanced life support measures, and the average rescue time was 46 min. Due to the low incidence of death in the oral emergency department, medical personel have little experience in first aid. First aid training and drills and assessment should be organized regularly. First aid facilities should be always available and regularly maintained by special personnel, such as electrocardiogram (ECG) monitor, defibrillator, simple breathing apparatus, oxygen supply system, negative pressure suction system, endotracheal intubation and tracheotomy equipment. The death cases mainly occurred in the elderly patients with oral cancer bleeding and systemic underlying diseases. Education of emergency awareness for the elderly patients with oral cancer after surgery should be enhanced. Medical staff should strengthen first aid awareness and skills.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.

Neural network mapping of gelastic behavior in children with hypothalamus hamartoma.

BACKGROUND: Hypothalamus hamartomas (HHs) are rare, congenital, tumor-like, and nonprogressive malformations resulting in drug-resistant epilepsy, mainly affecting children. Gelastic seizures (GS) are an early hallmark of epilepsy with HH. The aim of this study was to explore the disease progression and the underlying physiopathological mechanisms of pathological laughter in HH. METHODS: We obtained clinical information and metabolic images of 56 HH patients and utilized ictal semiology evaluation to stratify the specimens into GS-only, GS-plus, and no-GS subgroups and then applied contrasted trajectories inference (cTI) to calculate the pseudotime value and evaluate GS progression. Ordinal logistic regression was performed to identify neuroimaging-clinical predictors of GS, and then voxelwise lesion network-symptom mapping (LNSM) was applied to explore GS-associated brain regions. RESULTS: cTI inferred the specific metabolism trajectories of GS progression and revealed increased complexity from GS to other seizure types. This was further validated via actual disease duration (Pearson R = 0.532, P = 0.028). Male sex [odds ratio (OR) = 2.611, P = 0.013], low age at seizure onset (OR = 0.361, P = 0.005), high normalized HH metabolism (OR = - 1.971, P = 0.037) and severe seizure burden (OR = - 0.006, P = 0.032) were significant neuroimaging clinical predictors. LNSM revealed that the dysfunctional cortico-subcortico-cerebellar network of GS and the somatosensory cortex (S1) represented a negative correlation. CONCLUSIONS: This study sheds light on the clinical characteristics and progression of GS in children with HH. We identified distinct subtypes of GS and demonstrated the involvement of specific brain regions at the cortical-subcortical-cerebellar level. These valuable results contribute to our understanding of the neural correlates of GS.

Electroacupuncture may alleviate diabetic neuropathic pain by inhibiting the microglia P2X4R and neuroinflammation.

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1ß and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.

Associated factors with stimulation induced seizures and the relevance with surgical outcomes.

OBJECTIVE: To analyze the associated factors with stimulation-induced seizures (SIS) and the relevant factors in predicting surgical outcomes. METHODS: We analyzed 80 consecutive epilepsy patients explored by stereo-electroencephalography with routine electrical stimulation mapping (ESM). If seizures induced by ESM, patients were classified as SIS-positive (SIS-P); otherwise, SIS-negative (SIS-N). Patients received radical surgery were further classified as favorable (Engel I) and unfavorable (Engel II-IV) groups. RESULTS: Of the 80 patients included, we identified 44 (55.0%) and 36(45.0%) patients in the SIS-P and SIS-N groups, respectively. Multivariate analysis revealed that the seizure onset pattern (SOP) of preceding repetitive epileptiform discharges following LVFA (PRED→LVFA) (OR 3.319, 95% CI 1.200-9.183, P = 0.021) and pathology of focal cortical dysplasia (FCD) type II (OR 3.943, 95% CI 1.093-14.226, P = 0.036) were independent factors influencing whether the electrical stimulation can induce a seizure. Among the patients received radical surgery, there were 55 and 15 patients in the favorable and unfavorable groups separately. Multivariate analysis revealed that the SOP of PRED→LVFA induced seizures by stimulation (OR 11.409, 95% CI 1.182-110.161, P = 0.035) and bilateral implantation (OR 0.048, 95% CI 0.005-0.497, P = 0.011) were independent factors affecting surgical outcomes. The previous epilepsy surgery had a trend to be a negative factor with SIS (OR 0.156, 95% CI 0.028-0.880, P = 0.035) and surgical outcomes (OR 0.253, 95% CI 0.053-1.219, P = 0.087). CONCLUSION: ESM is a highly valuable method for localizing the seizure onset zone. The SOP of PRED→LVFA and FCD type II were associated with elicitation of SIS by ESM, whereas a previous epilepsy surgery showed a negative association. Furthermore, the SOP of PRED→LVFA together with SIS in the same patient predicted favorable surgical outcomes, whereas bilateral electrode implantation predicted unfavorable outcomes.

Effect of vermiculite modified with nano-iron-based material on stabilization of lead in lead contaminated soil.

Lead (Pb) contamination arising from the production of lead-acid batteries is getting more severe, and research on its treatment technology reflects the increasing concern worldwide. Vermiculite is a mineral with a layered structure, containing hydrated magnesium aluminosilicate and has high porosity and large specific surface area. Vermiculite has the ability of improving soil permeability and water retention performance. However, in recent studies, vermiculite is shown to be less effective than other stabilizing agents in immobilizing heavy metal Pb. Nano-iron-based materials have been widely used to adsorb heavy metals in wastewater. Therefore, vermiculite has been modified with two nano-iron-based materials-nanoscale zero-valent iron (nZVI) and nano-Fe3O4 (nFe3O4) to improve its immobilization effect for the heavy metal lead. SEM and XRD analysis confirmed that nZVI and nFe3O4 were successfully loaded on the raw vermiculite. XPS analysis was applied to further understand the composition of VC@nZVI and VC@nFe3O4. The stability and mobility of nano-iron-based materials were improved after being loaded on raw vermiculite, and the Pb immobilization effect of modified vermiculite on Pb-contaminated soil was evaluated. Adding nZVI-modified vermiculite (VC@nZVI) and nFe3O4-modified vermiculite (VC@nFe3O4) increased the immobilization effect and decreased the bioavailability of Pb. Compared with raw vermiculite, adding VC@nZVI and VC@nFe3O4 increased the amount of exchangeable Pb by 30.8% and 6.17%. After leaching ten times in soil column leaching experiments, the total concentration of Pb in the leachate of the soil with VC@nZVI and VC@nFe3O4 were reduced by 40.67% and 11.47%, compared with raw vermiculite. These results prove that the modification with nano-iron-based materials enhances the immobilization effect of vermiculite, in which the effect of VC@nZVI is significantly better than VC@nFe3O4. Vermiculite was modified with nano-iron-based materials, resulting in a better fixing effect of the modified curing agent. This study provides a new approach for the remediation of Pb-contaminated soil, but further research is needed for soil recovery and utilization of nanomaterials.

Factors of easy and difficult cecal intubation during unsedated colonoscopy.

BACKGROUND AND AIMS: difficulty of cecal intubation should be a main indicator for the need of sedated colonoscopy and skilled endoscopists. The present study aimed to explore the factors associated with easy and difficult cecal intubation in unsedated colonoscopy. METHODS: all consecutive patients who underwent unsedated colonoscopy at our department by the same endoscopist from December 3, 2020 to August 30, 2022 were retrospectively collected. Age, gender, body mass index (BMI), reasons for colonoscopy, position change, Boston Bowel Preparation Scale score, cecal intubation time (CIT) and major colonoscopic findings were analyzed. CIT < 5 min, CIT 5-10 min and CIT > 10 min or failed cecal intubation were defined as easy, moderate and difficult cecal intubation, respectively. Logistic regression analyses were performed to identify independent factors associated with easy and difficult cecal intubation. RESULTS: overall, 1,281 patients were included. The proportions of easy and difficult cecal intubation were 29.2 % (374/1,281) and 27.2 % (349/1,281), respectively. Multivariate logistic regression analysis found that age ≤ 50 years, male, BMI > 23.0 kg/m2 and the absence of position change were independently associated with easy cecal intubation, and that age > 50 years, female, BMI ≤ 23.0 kg/m2, position change, and insufficient bowel preparation were independently associated with difficult cecal intubation. CONCLUSIONS: some convenient factors independently associated with easy and difficult cecal intubation have been identified, which will be potentially helpful to determine whether a colonoscopy should be sedated and a skilled endoscopist should be selected. The current findings should be further validated in large-scale prospective studies.

Long-term seizure outcome with the surgically remediable syndrome of frontal lobe epilepsy associated with superior frontal sulcus-related dysplasia.

Objective: To assess the long-term outcome of the surgically remediable syndrome of frontal lobe epilepsy (FLE) associated with superior frontal sulcus (SFS)-related dysplasia. Methods: We retrospectively reviewed the medical charts and surgical features of 31 patients with drug-resistant frontal lobe epilepsy in our centers between 2016 and 2018. All patients underwent surgical resection. According to the epileptogenic zone (EZ), localization and resection extent were classified as (1) pure SFS group (PS group), (2) associated SFS group (AS group), and (3) no SFS group (NS group). The general characteristics, neuroradiological findings, morbidity, pathology, and long-term seizure outcome after surgery were analyzed to extract the potential value of the surgery for SFS-related dysplasia. Results: Of 31 patients with FLE who underwent epilepsy surgery, 15 patients (nine men) were included PS group, five patients (five men) in the AS group, and 11 patients (eight men) in the NS group. Eleven patients detected abnormal focal signals in the presurgical MRI. Six patients in the PS group demonstrated the suspected focal cortical dysplasia (FCD) in the SFS detected with MRI. All patients demonstrated focal abnormal hypometabolism foci in the PET-MR co-registration. Twenty-five patients (80.6%) were seizure-free since surgery, including all 15 patients (100%) of the PS group, three in five patients (60%) of the AS group, and seven in 11 patients (63.6%) of the NS group. The difference in outcome between different groups was significant (p = 0.004, PS vs. AS group; p = 0.005, PS vs. NS group). As of the last follow-up (mean 66.2 ± 9.7months), 25 patients (80.6%) were seizure-free since surgery (Engel's class I). In addition, antiseizure medication was withdrawn in 19 patients (61.3%). Histologic examination of resected specimens revealed FCD in all 31 patients. The percentage of FCD II type was 100, 60, and 63.6% in the three different groups, respectively. Conclusion: SFS-related dysplasia is a neuropathologic entity with a favorable postoperative outcome. FCD II is the most common type of SFS-related dysplasia. FDG-PET co-registered with MRI should be performed in patients with suspected SFS-related dysplasia, since it may depict areas of hypometabolism suggestive of dysplasia in the absence of MRI abnormalities.

Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization.

BACKGROUND: Endoscopic variceal treatment (EVT) is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis. Proton pump inhibitors (PPIs) are widely used for various gastric acid-related diseases. However, the effects of PPIs on the development of post-EVT complications, especially gastrointestinal bleeding (GIB), remain controversial. AIM: To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization. METHODS: Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command, treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included. Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 143 patients were included. The incidence of post-EVT GIB and other post-EVT complications was 4.90% and 46.85%, respectively. In the overall analyses, postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB (OR = 0.525, 95%CI = 0.113-2.438, P = 0.411) or other post-EVT complications (OR = 0.804, 95%CI = 0.413-1.565, P = 0.522). In the subgroup analyses according to the enrollment period, type and route of PPIs after the index EVT, use of PPIs before the index EVT, use of vasoactive drugs after the index EVT, indication of EVT (prophylactic and therapeutic), and presence of portal venous system thrombosis, ascites, and hepatocellular carcinoma, the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant. CONCLUSION: Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7.

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.

Analgesic effect of electroacupuncture on bone cancer pain in rat model: the role of peripheral P2X3 receptor.

Upregulation of P2X3 receptor (P2X3R) has been strongly implicated in nociceptive signaling including bone cancer pain (BCP). The present study, using rat bone cancer model, aimed to explore the role of P2X3R in regulating rat pain behavior under the intervention of electroacupuncture (EA). The BCP model was successfully established by injection with MRMT-1 breast cancer cell into the medullary cavity of left tibia for 3 × 104 cells/3 µL PBS in rats as revealed by obvious bone destruction, decreased paw withdrawal thresholds (PWTs), and reduced paw withdrawal latencies (PWLs). Western blot analyses showed that P2X3R expression was significantly upregulated in ipsilateral lumbar 4-6 (L4-6) dorsal root ganglia (DRG), but the difference not seen in spinal cord dorsal horn (SCDH). With the in-depth study of P2X3R activation, we observed that intrathecal injection of P2X3R agonist α,ß-meATP aggravated MRMT-1 induced BCP, while injection of P2X3R inhibitor A-317491 alleviated pain. Subsequently, we demonstrated that BCP induced mechanical allodynia and thermal hyperalgesia were attenuated after EA treatment. Under EA treatment, total P2X3R protein expression in ipsilateral DRGs was decreased, and it is worth mentioning that decreased expression of P2X3R membrane protein, which indicated that both the expression and membrane trafficking of P2X3R were inhibited by EA. The immunofluorescence assay showed that EA stimulation exerted functions by reducing the expression of P2X3R-positive cells in ipsilateral DRGs of BCP rats. Ca2+ imaging analysis revealed that the EA stimulation decreased the percentage of α,ß-meATP responsive neurons in DRGs and inhibited calcium influx. Notably, the inhibitory effect of EA on mechanical allodynia and nociceptive flinches was abolished by intrathecal injection of α,ß-meATP. These findings demonstrated EA stimulation ameliorated mechanical allodynia and thermal hyperalgesia in rat model of MRMT-1-induced BCP. EA exerts analgesic effect on BCP by reducing the overexpression and functional activity of P2X3R in ipsilateral DRGs of BCP rats. Our work first demonstrates the critical and overall role of P2X3R in EA's analgesia against peripheral sensitization of MRMT-1-induced BCP and further supports EA as a potential therapeutic option for cancer pain in clinic.

Activation of MYO1G by lncRNA MNX1-AS1 Drives the Progression in Lung Cancer.

Lung cancer represents the most prevalent cancer worldwide and causes the death of many patients. Cancer stem cells (CSCs), a subpopulation of cancer cells, have the capacities of self-renewal, unlimited proliferation, and multiple differentiation potential. The purpose of this study was to explore the potential role of long noncoding RNA (lncRNA) MNX1-AS1 on maintaining the stemness of CSC in lung cancer. CSCs were firstly sorted by flow cytometry. After the determination of the target of the present study using Gene Expression Omnibus dataset, MNX1-AS1was found to be highly expressed in lung cancer tissues and cells. Deletion of MNX1-AS1 inhibited proliferation, migration, invasion and sphere-forming abilities of CSC. Furthermore, subcellular fractionation, fluorescence in situ hybridization, RNA immunoprecipitation, and dual-luciferase experiments demonstrated that MNX1-AS1 recruited the transcription factor POU domain class 2 transcription factor 2 (POU2F2) to the nucleus and activated the myosin IG (MYO1G) expression. MYO1G overexpression partially reversed the si-MNX1-AS1-decreased stemness of CSCs. Finally, MNX1-AS1 suppression significantly repressed the growth of xenografts in vivo. Our study highlights the importance of the MNX1-AS1/POU2F2/MYO1G axis in stem cell-like properties of lung cancer cells.

Incremental value of PET primary lesion-based radiomics signature to conventional metabolic parameters and traditional risk factors for preoperative prediction of lymph node metastases in gastric cancer.

BACKGROUND: Precise preoperative prediction of lymph node metastasis (LNM) is crucial for optimal diagnosis and treatment in patients with gastric cancer (GC), in which existing imaging methods have certain limitations. We hypothesized that PET primary lesion-based radiomics signature could provide incremental value to conventional metabolic parameters and traditional risk indicators in predicting LNM in patients with GC. METHODS: This retrospective study was performed in 127 patients with GC who underwent preoperative PET/CT. Basic clinical data and PET conventional metabolic parameters were collected. Radiomics signature was constructed by the least absolute shrinkage and selection operator algorithm (LASSO) logistic regression. Based on the postoperative histological results, the patients were divided into LNM group and non-lymph node metastasis (NLNM) group. Receiver-operating characteristic (ROC) was used to evaluate the discriminatory ability of Radiomics score (Rad-score) for predicting LNM and determine whether adding Rad-score to PET conventional metabolic parameters and traditional risk factors could improve the predictive value in LNM. The Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to further confirm the incremental value of Rad-score for predicting LNM in GC. RESULTS: The LNM group had higher Rad-score than NLNM group [(0.35 (-0.13-0.85) vs. -0.61 (-1.92-0.18), P < 0 .001)]. After adjusted for gender, age, BMI, and FBG, multivariable logistic regression analysis illustrated that Rad-score (OR: 6.38, 95% CI: 2.73-14.91, P < 0.0001) was independent risk factors for LNM in GC. Adding PET conventional parameters to traditional risk factors increased the predictive value of LNM in GC (AUC 0.751 vs 0.651, P = 0.02). Additional inclusion of Rad-score to conventional metabolic parameters and traditional risk indicators significantly improved the AUC (0.882 vs 0.751; P = 0.006). Bootstrap resampling (times = 500) was used for internal verification, 95% confidence interval (CI) was 0.802-0.948, with the sensitivity equaled to 89.5%, and positive predictive value (PPV) was 93.5%. When Rad-score was added to conventional metabolic parameters and traditional risk indicators, net reclassification improvement (NRI) was 0.293 (P = 0.0040) and integrated discrimination improvement (IDI) was 0.293 (P = 0.0045). CONCLUSION: In GC patients, PET Radiomics signature of the primary lesion-based was significantly associated with LNM and could improve the prediction of LNM above PET conventional metabolic parameters and traditional risk factors, which could provide incremental value for individual diagnosis and treatment of GC.

Information fields of written texts protect cells from oxidative damage and accelerate repair.

OBJECTIVE: Written words demonstrated specific effects on biochemical measures and cell growth in cultured mammalian cells in previous study. We examined the protection and reparative effects of Chinese texts with positive meaning and the word "Buddha" on oxidative-damaged cells, with the goal of exploring the therapeutic effect of such characters. METHODS: The human embryonic kidney cell line HEK293T was utilized, with the oxidative- damaged cell model produced by hydrogen peroxide (H2O2). Double-blind experiments were set up to ensure all operators involved in the experiments did not know the contents of the texts in envelopes. Petri-dishes (9 plates) containing oxidative-damaged cells were selected randomly for three controls, three treatments by texts with positive meaning, and another three treatment by the word "Buddha". Cells were sub-sampled at 3 h and 24 h to examine growth and mitochondrial functions. All data are expressed relative to the controls. RESULTS: Compared with the control group, mitochondrial functions were enhanced as evidenced by increased adenosine triphosphate (ATP) levels, accompanied by the significant improvement in cell growth rate for the groups treated by positive texts and the word "Buddha". Reactive oxygen species (ROS) levels were decreased significantly in positive texts treatment, which suggested that the antioxidant capacity of cells was also improved. CONCLUSIONS: This study revealed that certain texts can potentially offer protection and accelerate the cellular repair for oxidative-damaged cells.

The Incidence of Acute Pancreatitis After Device Assisted Enteroscopy: a Systematic Review and Meta-analysis.

Background: The diagnosis of small bowel diseases is challenging and device assisted enteroscopy (DAE) is a technique for visualizing the entire small bowel. DAE is considered as a safe procedure and the reported rate of adverse events associated with DAE in the literature is low. Objective: The present study tried to investigate the actual incidence of AP after DAE with a systematic review and meta-analysis of available relevant studies. Methods: Studies were searched through the PubMed, EMBASE, and Cochrane library databases. The following data were extracted from all eligible studies: author, country, publication year, publication type, study design, type of DAE used, route of DAE, number of patients with AP after DAE, and number of patients with hyperamylasemia after DAE.A random-effects model with RStudio version 4.2.0 was performed in all analyses. Heterogeneity was assessed using the I2 test. The risk of bias was assessed by the Newcastle-Ottawa Scale criteria and the publication bias was assessed by the Egger test. Results: Twenty three studies involving a total of 11145 patients were included in the analysis. The overall, pooled AP rate after DAE was 1% (95% CI:0-1%). There was significant heterogeneity among the studies (I2 = 65%; P < 0.01).The pooled AP rate was 1% (95% CI:0-2 %)in peroral route group. The pooled proportion of patients having hyperamylasemia after DAE was 29% (95% CI: 16-46%).Among the patients who had hyperamylasemia AP were identified in 2% (95% CI: 0-6%) of patients. Conclusion: The incidence of AP after DAE is about 1%. Hyperamylasemia is a common change in the patients undergoing DAE and only 2% of the patients with hyperamylasemia present with AP.

Successful treatment of acute symptomatic extensive portal venous system thrombosis by 7-day systemic thrombolysis.

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

Ubiquitin ligase RNF125 targets PD-L1 for ubiquitination and degradation.

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy.