Successful allogeneic fecal microbiota transplantation for severe diversion colitis: a case report.

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.

Impact of sequential (first- to third-generation) EGFR-TKI treatment on corrected QT interval in NSCLC patients.

Objective: To evaluate the impact of sequential (first- to third-generation) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment on top-corrected QT interval (top-QTc) in non-small cell lung cancer (NSCLC) patients. Methods: We retrospectively reviewed the medical records of NSCLC patients undergoing sequential EGFR-TKI treatment at Shanghai Chest Hospital between October 2016 and August 2021. The heart rate (HR), top-QT interval, and top-QTc of their ECGs were extracted from the institutional database and analyzed. Logistic regression was performed to identify predictors for top-QTc prolongation. Results: Overall, 228 patients were enrolled. Compared with baseline (median, 368 ms, same below), both first-generation (376 ms vs. 368 ms, p < 0.001) and sequential third-generation EGFR-TKIs (376 ms vs. 368 ms, p = 0.002) prolonged top-QT interval to a similar extent (p = 0.635). Top-QTc (438 ms vs. 423 ms, p < 0.001) and HR (81 bpm vs.79 bpm, p = 0.008) increased after first-generation EGFR-TKI treatment. Further top-QTc prolongation (453 ms vs. 438 ms, p < 0.001) and HR increase (88 bpm vs. 81 bpm, p < 0.001) occurred after treatment advanced. Notably, as HR elevated during treatment, top-QT interval paradoxically increased rather than decreased, and the top-QTc increased rather than slightly fluctuated. Moreover, such phenomena were more significant after treatment advanced. After adjusting for confounding factors, pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation during sequential third-generation EGFR-TKI treatment. Conclusion: First-generation EGFR-TKI could prolong top-QTc, and sequential third-generation EGFR-TKI induced further prolongation. Top-QT interval paradoxically increased and top-QTc significantly increased as HR elevated, which was more significant after sequential EGFR-TKI treatment. Pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation after sequential EGFR-TKI treatment.

Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry.

Background: Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods: We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results: Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16- NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16- NK cells. Conclusion: In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

Immune-like sandwich multiple hotspots SERS biosensor for ultrasensitive detection of NDKA biomarker in serum.

Developing the rapid, specific, and sensitive tumor marker NDKA biosensor has become an urgent need in the field of early diagnosis of colorectal cancer (CRC). Surface-enhanced Raman spectroscopy (SERS) with the advantages of high sensitivity, high resolution as well as providing sample fingerprint, enables rapid and sensitive detection of tumor markers. However, many SERS biosensors rely on boosting the quantity of Raman reporter molecules on individual nanoparticle surfaces, which can result in nanoparticle agglomeration, diminishing the stability and sensitivity of NDKA detection. Here, we proposed an immune-like sandwich multiple hotspots SERS biosensor for highly sensitive and stable analysis of NDKA in serum based on molecularly imprinted polymers and NDKA antibody. The SERS biosensor employs an array of gold nanoparticles, which are coated with a biocompatible polydopamine molecularly imprinted polymer as a substrate to specifically capture NDKA. Then the biosensor detects NDKA through Raman signals as a result of the specific binding of NDKA to the SERS nanotag affixed to the capture substrate along with the formation of multiple hotspots. This SERS biosensor not only avoids the aggregation of nanoparticles but also presents a solution to the obstacles encountered in immune strategies for certain proteins lacking multiple antibody or aptamer binding sites. Furthermore, the practical application of the SERS biosensor is validated by the detection of NDKA in serum with the lower limit of detection (LOD) of 0.25 pg/mL, meanwhile can detect NDKA of 10 ng/mL in mixed proteins solution, illustrating high sensitivity and specificity. This immune-like sandwich multiple hotspots biosensor makes it quite useful for the early detection of CRC and also provides new ideas for cancer biomarker sensing strategy in the future.

Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). METHODS: Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. RESULTS: Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48-2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18-2.15, P = 0.002) and stage I-IIIA (OR = 1.67, 95% CI: 1.01-2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25-3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07-2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31-2.57, P = 0.0004). CONCLUSIONS: This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.

Canagliflozin improves fatty acid oxidation and ferroptosis of renal tubular epithelial cells via FOXA1-CPT1A axis in diabetic kidney disease.

Impaired fatty acid oxidation (FAO) is a metabolic hallmark of renal tubular epithelial cells (RTECs) under diabetic conditions. Disturbed FAO may promote cellular oxidative stress and insufficient energy production, leading to ferroptosis subsequently. Canagliflozin, an effective anti-hyperglycemic drug, may exert potential reno-protective effects by upregulating FAO and inhibiting ferroptosis in RTECs. However, the mechanisms involved remain unclear. The present study is aimed to characterize the detailed mechanisms underlying the impact of canagliflozin on FAO and ferroptosis. Type 2 diabetic db/db mice were administrated daily by gavage with canagliflozin (20 mg/kg/day, 40 mg/kg/day) or positive control drug pioglitazone (10 mg/kg/day) for 12 weeks. The results showed canagliflozin effectively improved renal function and structure, reduced lipid droplet accumulation, enhanced FAO with increased ATP contents and CPT1A expression, a rate-limiting enzyme of FAO, and relieved ferroptosis in diabetic mice. Moreover, overexpression of FOXA1, a transcription factor related with lipid metabolism, was observed to upregulate the level of CPT1A, and further alleviated ferroptosis in high glucose cultured HK-2 cells. Whereas FOXA1 knockdown had the opposite effect. Mechanistically, chromatin immunoprecipitation assay and dual-luciferase reporter gene assay results demonstrated that FOXA1 transcriptionally promoted the expression of CPT1A through a sis-inducible element located in the promoter region of the protein. In conclusion, these data suggest that canagliflozin improves FAO and attenuates ferroptosis of RTECs via FOXA1-CPT1A axis in diabetic kidney disease.

LncRNA GAS5 Attenuates Cardiac Electrical Remodeling Induced by Rapid Pacing via the miR-27a-3p/HOXa10 Pathway.

Previous studies indicated long non-coding RNAs (lncRNAs) participated in the pathogenesis of atrial fibrillation (AF). However, little is known about the role of lncRNAs in AF-induced electrical remodeling. This study aimed to investigate the regulatory effect of lncRNA GAS5 (GAS5) on the electrical remodeling of neonatal rat cardiomyocytes (NRCMs) induced by rapid pacing (RP). RNA microarray analysis yielded reduced GAS5 level in NRCMs after RP. RT-qPCR, western blot, and immunofluorescence yielded downregulated levels of Nav1.5, Kv4.2, and Cav1.2 after RP, and whole-cell patch-clamp yielded decreased sodium, potassium, and calcium current. Overexpression of GAS5 attenuated electrical remodeling. Bioinformatics tool prediction analysis and dual luciferase reporter assay confirmed a direct negative regulatory effect for miR-27a-3p on lncRNA-GAS5 and HOXa10. Further analysis demonstrated that either miR-27a-3p overexpression or the knockdown of HOXa10 further downregulated Nav1.5, Kv4.2, and Cav1.2 expression. GAS5 overexpression antagonized such effects in Nav1.5 and Kv4.2 but not in Cav1.2. These results indicate that, in RP-treated NRCMs, GAS5 could restore Nav1.5 and Kv4.2 expression via the miR-27a-3p/HOXa10 pathway. However, the mechanism of GAS5 restoring Cav1.2 level remains unclear. Our study suggested that GAS5 regulated cardiac ion channels via the GAS5/miR-27a-3p/HOXa10 pathway and might be a potential therapeutic target for AF.

In-silico annotation of the chemical composition of Tibetan tea and its mechanism on antioxidant and lipid-lowering in mice.

BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

Construction and validation of a nomogram of risk factors for new-onset atrial fibrillation in advanced lung cancer patients after non-surgical therapy.

Objective: Risk factors of new-onset atrial fibrillation (NOAF) in advanced lung cancer patients are not well defined. We aim to construct and validate a nomogram model between NOAF and advanced lung cancer. Methods: We retrospectively enrolled 19484 patients with Stage III-IV lung cancer undergoing first-line antitumor therapy in Shanghai Chest Hospital between January 2016 and December 2020 (15837 in training set, and 3647 in testing set). Patients with pre-existing AF, valvular heart disease, cardiomyopathy were excluded. Logistic regression analysis and propensity score matching (PSM) were performed to identify predictors of NOAF, and nomogram model was constructed and validated. Results: A total of 1089 patients were included in this study (807 in the training set, and 282 in the testing set). Multivariate logistic regression analysis showed that age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion were independent risk factors, the last two of which were important independent risk factors as confirmed by PSM analysis. Nomogram included independent risk factors of age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion. The AUC was 0.716 (95% CI 0.661-0.770) and further evaluation of this model showed that the C-index was 0.716, while the bias-corrected C-index after internal validation was 0.748 in the training set. The calibration curves presented good concordance between the predicted and actual outcomes. Conclusion: Centric pulmonary carcinoma and pericardial effusion were important independent risk factors for NOAF besides common ones in advanced lung cancer patients. Furthermore, the new nomogram model contributed to the prediction of NOAF.

Monitoring of trace aquatic sulfonamides through hollow zinc-nitrogen-carbon electrocatalysts anchored on MXene architectures.

Herein, we designed and fabricated hollow N-doped carbon polyhedrons with atomically dispersed Zn species (Zn@HNCPs) through a topo-conversion strategy by utilising metal-organic frameworks as precursors. Zn@HNCPs achieved efficient electrocatalytic oxidation of sulfaguanidine (SG) and phthalyl sulfacetamide (PSA) sulfonamides through the high intrinsic catalytic activity of the Zn-N4 sites and excellent diffusion from the hollow porous nanostructures. The combination of the novel Zn@HNCPs with two-dimensional Ti3C2Tx MXene nanosheets resulted in improved synergistic electrocatalytic performance for the simultaneous monitoring of SG and PSA. Therefore, the detection limit of SG for this technique is much lower than those of other reported techniques; to the best of our knowledge, this is the first detection approach for PSA. Moreover, these electrocatalysts show promise for the quantification of SG and PSA in aquatic products. Our insights and findings can serve as guidelines for the development of highly active electrocatalysts for application in next-generation food analysis sensors.

Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats.

Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked (p < 0.05) antibody generation, enhanced (p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (p < 0.05) pituitary Fshb transcription and increased (p < 0.05) serum FSH and 17ß-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals.

CT radiomics model combined with clinical and radiographic features for discriminating peripheral small cell lung cancer from peripheral lung adenocarcinoma.

Purpose: Exploring a non-invasive method to accurately differentiate peripheral small cell lung cancer (PSCLC) and peripheral lung adenocarcinoma (PADC) could improve clinical decision-making and prognosis. Methods: This retrospective study reviewed the clinicopathological and imaging data of lung cancer patients between October 2017 and March 2022. A total of 240 patients were enrolled in this study, including 80 cases diagnosed with PSCLC and 160 with PADC. All patients were randomized in a seven-to-three ratio into the training and validation datasets (170 vs. 70, respectively). The least absolute shrinkage and selection operator regression was employed to generate radiomics features and univariate analysis, followed by multivariate logistic regression to select significant clinical and radiographic factors to generate four models: clinical, radiomics, clinical-radiographic, and clinical-radiographic-radiomics (comprehensive). The Delong test was to compare areas under the receiver operating characteristic curves (AUCs) in the models. Results: Five clinical-radiographic features and twenty-three selected radiomics features differed significantly in the identification of PSCLC and PADC. The clinical, radiomics, clinical-radiographic and comprehensive models demonstrated AUCs of 0.8960, 0.8356, 0.9396, and 0.9671 in the validation set, with the comprehensive model having better discernment than the clinical model (P=0.036), the radiomics model (P=0.006) and the clinical-radiographic model (P=0.049). Conclusions: The proposed model combining clinical data, radiographic characteristics and radiomics features could accurately distinguish PSCLC from PADC, thus providing a potential non-invasive method to help clinicians improve treatment decisions.

Mycoplasma genitalium infection in the female reproductive system: Diseases and treatment.

Mycoplasma genitalium is a newly emerged sexually transmitted disease pathogen and an independent risk factor for female cervicitis and pelvic inflammatory disease. The clinical symptoms caused by M. genitalium infection are mild and easily ignored. If left untreated, M. genitalium can grow along the reproductive tract and cause salpingitis, leading to infertility and ectopic pregnancy. Additionally, M. genitalium infection in late pregnancy can increase the incidence of preterm birth. M. genitalium infections are often accompanied by co-infection with other sexually transmitted pathogens (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and viral infections (Human Papilloma Virus and Human Immunodeficiency Virus). A recent study suggested that M. genitalium plays a role in tumor development in the female reproductive system. However, few studies endorsed this finding. In recent years, M. genitalium has evolved into a new "superbug" due to the emergence of macrolide-and fluoroquinolone-resistant strains leading to frequent therapy failures. This review summarizes the pathogenic characteristics of M. genitalium and the female reproductive diseases caused by M. genitalium (cervicitis, pelvic inflammatory disease, ectopic pregnancy, infertility, premature birth, co-infection, reproductive tumors, etc.), as well as its potential relationship with reproductive tumors and clinical treatment.

Application of a Tele-Ultrasound Robot During COVID-19 Pandemic: A Feasibility Study.

OBJECTIVE: To investigate the accuracy of ultrasonic diagnosis using the tele-ultrasound robot in Leishen Shan Hospital. METHOD: Twenty-two patients with novel coronavirus pneumonia from Leishen Shan Hospital voluntarily participated in this study. Their thyroids, neck vessels, hepatobiliaries and kidneys were scanned by both a tele-ultrasound robot manufactured by Imabot Co., Ltd, Wuhan and conventional method. The ultrasound diagnosis of each patient was compared, and the ultrasound images obtained by the two methods were mixed together and double-blindly diagnosed by an experienced ultrasound radiologist. RESULTS: There were 44 positive lesions in 110 sites of 22 patients. Of which the two methods, 40 positive lesions were detected by the robotic method with 4 lesions missed (2 small polyps of gallbladder, 1 small hemangioma of liver and 1 small cyst of kidney) and 1 lesion misdiagnosed (normal carotid artery was misdiagnosed as carotid atherosclerotic plaque); 44 positive lesions were detected by conventional method with 1 small cyst of the liver was missed. There was no statistically significant difference in the accuracy rate between the robotic method and the conventional method using the chi-square test of the four-grid data (P>.05). CONCLUSION: The application of tele-ultrasound robot meets the standard of patient care during the pandemic. The method is feasible to provide adequate ultrasound information to diagnose common abdominal, vascular, superficial organ pathologies in patients with COVID-19 with acceptable accuracy compared with a conventional ultrasound scan.

MEX3A Impairs DNA Mismatch Repair Signaling and Mediates Acquired Temozolomide Resistance in Glioblastoma.

MutS protein homolog 2 (MSH2) is a key element involved in the DNA mismatch repair (MMR) system, which is responsible for recognizing and repairing mispaired bases. Simultaneously, MSH2 identifies DNA adducts induced by temozolomide (TMZ) and triggers apoptosis and autophagy in tumor cells. Previous work has revealed that reduced MSH2 expression is often observed in patients with glioblastoma (GBM) who relapse after chemotherapy. Elucidation of the mechanism behind TMZ-mediated reduction of MSH2 could help improve GBM treatment. Here, we report significant upregulation of Mex-3 RNA binding family member A (MEX3A) in GBM tissues and cell lines following TMZ treatment. MEX3A bound to the MEX3 recognition element (MRE) of MSH2 mRNA, which in turn recruited CCR4-NOT complexes to target MSH2 mRNA for deadenylation and degradation. In addition, ectopic expression of MEX3A significantly decreased cellular DNA MMR activities and reduced the chemosensitivity of GBM cells via downregulation of MSH2, while depletion of MEX3A sensitized GBM cells to TMZ. In MGMT-deficient patients with GBM, MEX3A expression correlated with MSH2 levels, and high MEX3A expression was associated with poor prognosis. Overall, these findings reveal a potential mechanism by which MSH2 expression is reduced in post-TMZ recurrent GBM. SIGNIFICANCE: A MEX3A/CCR4-NOT/MSH2 axis plays a crucial role in promoting temozolomide resistance, providing new insights into the function of MEX3A and suggesting MEX3A as a potential therapeutic target in therapy-resistant glioblastoma.

Left Atrial Anterior Wall Scar-Related Atrial Tachycardia in Patients after Catheter Ablation or Cardiac Surgery: Electrophysiological Characteristics and Ablation Strategy.

Background: The mechanisms of atrial tachycardia (AT) related to the left atrial anterior wall (LAAW) are complex and can be challenging to map in patients after catheter ablation for atrial fibrillation (AF) or cardiac surgery. We aimed to investigate the electrophysiological characteristics AT and to devise an ablation strategy. Methods and Results: We identified 31 scar-related LAAW reentrant ATs in 22 patients after catheter ablation for AF or cardiac surgery. Activation maps of the left atrium (LA) or both atria were obtained using a high-density mapping system, and the precise mechanism and critical area for each AT were analyzed. Patients were followed up regularly in a clinic. After analyzing the activation and propagation of each AT, the scar-related LAAW ATs were classified into three types, based on mechanisms related to: (1) LAAW conduction gap(s) in 19 LA macro-reentrant ATs; (2) LAAW epicardial connection(s) in 11 LA or bi-atrial ATs; and (3) LAAW local micro-reentry in 1 LAAW AT. Multiple ATs were identified in seven patients. Effective ablation (termination or circuit change of AT) was obtained in 30 ATs by targeting the critical area identified by the mapping system. During 16.0 ± 7.6 months follow-up, recurrent AT occurred in two patients. Conclusions: Three mechanisms of scar-related AT of LAAW were identified, most of which were related to LAAW conduction gaps. Notably, epicardial AT or bi-atrial AT comprised a nonnegligible proportion. A high-density mapping system could make it possible to determine the accurate mechanism of AT and serve as a guide following ablation.

Neuroprotective effects of voluntary exercise and Yisaipu after traumatic brain injury in mice.

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.

A Lysosome-Targeting Self-Condensation Prodrug-Nanoplatform System for Addressing Drug Resistance of Cancer.

Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.

Development and Validation of a Concise Prediction Scoring System for Asian Lung Cancer Patients with EGFR Mutation Before Treatment.

Purpose We aimed to determine the epidermal growth factor receptor (EGFR) genetic profile of lung cancer in Asians, and develop and validate a non-invasive prediction scoring system for EGFR mutation before treatment. Methods This was a single-center retrospective cohort study using data of patients with lung cancer who underwent EGFR detection (n = 1450) from December 2014 to October 2020. Independent predictors were filtered using univariate and multivariate logistic regression analyses. According to the weight of each factor, a prediction scoring system for EGFR mutation was constructed. The model was internally validated using bootstrapping techniques and temporally validated using prospectively collected data (n = 210) between November 2020 and June 2021.Results In 1450 patients with lung cancer, 723 single mutations and 51 compound mutations were observed in EGFR. Thirty-nine cases had two or more synchronous gene mutations. We developed a scoring system according to the independent clinical predictors and stratified patients into risk groups according to their scores: low-risk (score <4), moderate-risk (score 4-8), and high-risk (score >8) groups. The C-statistics of the scoring system model was 0.754 (95% CI 0.729-0.778). The factors in the validation group were introduced into the prediction model to test the predictive power of the model. The results showed that the C-statistics was 0.710 (95% CI 0.638-0.782). The Hosmer-Lemeshow goodness-of-fit showed that χ2 = 6.733, P = 0.566. Conclusions The scoring system constructed in our study may be a non-invasive tool to initially predict the EGFR mutation status for those who are not available for gene detection in clinical practice.

An activated excretion-retarded tumor imaging strategy towards metabolic organs.

Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues. However, the application of these fluorescence contrast agents in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) was dramatically hammered as a result of lacking active targeting and poor retention time in tumor, which limited the Signal to Noise Ratio (SNR) and narrowed the imaging window for complicated surgery. Herein, we reported an activated excretion-retarded tumor imaging (AERTI) strategy, which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells, thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR. Briefly, the AERTI strategy could selectively recognize the Integrin αvß3. Afterwards, the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors. We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models. More importantly, the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC. Taken together, the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs.