EGR3 reduces podocyte inflammatory damage in obesity related glomerulopathy by inhibiting the PRMT1/p-STAT3 pathway. / EGR3通过抑制PRMT1/p-STAT3é€šè·¯å‡è½»è‚¥èƒ–ç›¸å ³æ€§è‚¾ç— è¶³ç»†èƒžç‚Žç—‡æŸä¼¤.

OBJECTIVES: Obesity related glomerulopathy (ORG) is induced by obesity, but the pathogenesis remains unclear. This study aims to investigate the expression of early growth response protein 3 (EGR3) in the renal cortex tissues of ORG patients and high-fat diet-induced obese mice, and to further explore the molecular mechanism of EGR3 in inhibiting palmitic acid (PA) induced human podocyte inflammatory damage. METHODS: Renal cortex tissues were collected from ORG patients (n=6) who have been excluded from kidney damage caused by other diseases and confirmed by histopathology, and from obese mice induced by high-fat diet (n=10). Human and mouse podocytes were intervened with 150 µmol/L PA for 48 hours. EGR3 was overexpressed or silenced in human podocytes. Enzyme linked immunosorbent assay (ELISA) was used to detcet the levels of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Real-time RT-PCR was used to detect the mRNA expressions of EGR3, podocytes molecular markers nephrosis 1 (NPHS1), nephrosis 2 (NPHS2), podocalyxin (PODXL), and podoplanin (PDPN). RNA-seq was performed to detect differentially expressed genes (DEGs) after human podocytes overexpressing EGR3 and treated with 150 µmol/L PA compared with the control group. Co-immunoprecipitation (Co-IP) combined with liquid chromatography tandem mass spectrometry (LC-MS) was used to detect potential interacting proteins of EGR3 and the intersected with the RNA-seq results. Co-IP confirmed the interaction between EGR3 and protein arginine methyltransferases 1 (PRMT1), after silencing EGR3 and PRMT1 inhibitor intervention, the secretion of IL-6 and IL-1ß in PA-induced podocytes was detected. Western blotting was used to detect the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) after overexpression or silencing of EGR3. RESULTS: EGR3 was significantly upregulated in renal cortex tissues of ORG patients and high-fat diet-induced obese mice (both P<0.01). In addition, after treating with 150 µmol/L PA for 48 hours, the expression of EGR3 in human and mouse podocytes was significantly upregulated (both P<0.05). Overexpression or silencing of EGR3 in human podocytes inhibited or promoted the secretion of IL-6 and IL-1ß in the cell culture supernatant after PA intervention, respectively, and upregulated or downregulated the expression of NPHS1, PODXL, NPHS2,and PDPN (all P<0.05). RNA-seq showed a total of 988 DEGs, and Co-IP+LC-MS identified a total of 238 proteins that may interact with EGR3. Co-IP confirmed that PRMT1 was an interacting protein with EGR3. Furthermore, PRMT1 inhibitors could partially reduce PA-induced IL-6 and IL-1ß secretion after EGR3 silencing in human podocytes (both P<0.05). Overexpression or silencing of EGR3 negatively regulated the expression of PRMT1 and p-STAT3. CONCLUSIONS: EGR3 may reduce ORG podocyte inflammatory damage by inhibiting the PRMT1/p-STAT3 pathway.

Pulmonary Embolism in Klippel-Trenaunay-Weber Syndrome With Slipped Capital Femoral Epiphysis.

CASE: A 12-year-old boy with Klippel-Trenaunay-Weber syndrome underwent surgery for unstable slipped capital femoral epiphysis who developed pulmonary embolism postoperatively. CONCLUSION: It is important to be vigilant about pulmonary embolism in children because it is rare but potentially fatal, especially in the presence of risk factors. Early diagnosis and treatment of unstable slipped capital femoral epiphysis are crucial to minimize immobility. Close monitoring of femoral head osteonecrosis is also necessary.

Effect of cervical paraesophageal lymph node metastasis versus supraclavicular lymph node metastasis on the overall survival of patients with thoracic esophageal squamous cell carcinoma: an observational study.

Background: Esophageal cancer (EC) is a major global health burden, with a particularly high incidence in East Asia. The authors aimed to investigate the effect of metastasis in cervical paraesophageal lymph nodes (station 101) and supraclavicular lymph nodes (station 104) on the survival of patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC). Materials and Methods: Data were obtained from the database of the authors' hospital. The authors retrospectively analyzed the patients with EC who underwent esophagectomy from January 2010 to December 2017. These patients were allocated into two groups based on the presence of lymph node metastasis (LNM) in the cervical paraesophageal or supraclavicular regions. Clinical outcomes and survival data were compared using the TNM staging system of the 8th edition of the American Joint Committee on Cancer (AJCC). Results: After a median follow-up of 62.1 months, 122 patients with LNM in the supraclavicular region were included in the study. Among these patients, 53 showed cervical paraesophageal LNM and an overall survival (OS) of 19.9 months [95% confidence interval (CI): 16.3-23.5]. In contrast, 69 patients showed supraclavicular LNM with an OS of 34.9 months (95% CI 25.7-44.1). The OS rates at 1, 3, and 5 years were 77%, 29%, and 21%, respectively, for patients with cervical paraesophageal LNM. Moreover, patients with supraclavicular LNM demonstrated OS rates of 88%, 48%, and 34%, respectively [Hazard ratio (HR): 0.634, 95% CI: 0.402-1.000, P=0.042]. Conclusions: Patients with ESCC with cervical paraesophageal LNM had significantly worse OS than those with supraclavicular LNM. This study underscores the importance of accurately identifying and managing ESCC with cervical paraesophageal LNM, as it may require more tailored and aggressive treatment strategies to prolong patient survival.

Surgical vs nonsurgical treatment for esophageal squamous cell carcinoma in patients older than 70 years: a propensity score matching analysis.

PURPOSE: With the rising life expectancy and an aging population, it has become increasingly important to investigate treatments suitable for older adult patients with esophageal cancer. This study investigated whether older adult patients who underwent esophagectomy had better clinical outcomes than those who were nonsurgically treated. METHODS: We retrospectively analyzed patients with esophageal squamous cell carcinoma (ESCC) who were 70 years or older and underwent esophagectomy, radiotherapy (RT), and/or chemoradiotherapy (CRT) between January 2018 and December 2019. Patients were divided into 2 groups: the surgery group (S group) and the nonsurgery group (NS group). We then compared the clinical outcomes of the 2 groups. RESULTS: After a median follow-up duration of 36.6 months, the S group showed better overall survival (OS). The 3-year OS was 59% in the S group and 27% in the NS group (hazard ratio [HR], 0.397; 95% CI, 0.278-0.549; P < .0001). In the S group, the median progression-free survival was 38.3 months (95% CI, 30.6-46.1) compared with 12.3 months in the NS group (HR, 0.511; 95% CI, 0.376-0.695; P < .0001). In addition, the number of adverse events in the NS group was higher than that in the S group (P < .001). CONCLUSION: Overall, patients with ESCC at the age of ≥70 years who underwent esophagectomy had significantly better clinical outcomes than those who underwent nonsurgical treatment with RT and/or CRT.

Comprehensive analysis revealed P4Hs as new biomarkers for prognosis and immunotherapy in head and neck cancer.

Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.

Cellular evidence and spatial distribution of endosomal biosynthesis and autophagy in intestinal immune barrier cells of crucian carp (Carassiuscarassius).

Crucian carp (Carassius carassius) is an important aquatic economic animal, and the immune barrier function of its intestine has been a focus of research into oral vaccines and drugs. However, the histological structures of the intestinal barrier and its adjacent areas have not been clearly established, and little subcellular evidence is available to elucidate the spatial distribution of intracellular biological processes. In this study, the spatial distribution of autophagy and endosome formation in the intestinal epithelial cells (IECs) of crucian carp were analyzed. These two biological activities are closely related to intestinal homeostasis, immunity, and cell communication. Periodic acid-Schiff (PAS) and Masson's trichrome staining were employed to elucidate the distinctive histological framework of the Crucian carp's myoid cell network, which resides within the subepithelial layer and is characterized by gap junctions. Transmission electron microscopy (TEM), immunohistochemistry (IHC), and immunofluorescence (IF) were used to detect the structural and functional aspects of the IEC in different intestinal segments. TEM and immunohistochemical analyses captured the biogenesis and maturation of early and late endosomes as well as multivesicular bodies (MVBs), as well as the initiation and progression of autophagy, including macroautophagy and mitophagy. The endosome and MVBs-specific marker CD63 and autophagy-related protein LC3 were highly expressed in IECs and were correlated with autophagy and endosome biosynthesis in the apical and basal regions of individual cells, and differed between different intestinal segments. In summary, this study elucidated the ubiquity and morphological characteristics of autophagy and endosome formation across different intestinal segments of crucian carp. A unique myoid cell network beneath the intestinal epithelium in crucian carp was also identified, expanding the histological understanding of this animal's intestinal tract.

Investigation of bioactive compounds and their correlation with the antioxidant capacity in different functional vinegars.

There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

Prognostic predictive value of urothelial carcinoma of the bladder after TURBT based on multiphase CT radiomics.

OBJECTIVE: To investigate multiphase computed tomography (CT) radiomics-based combined with clinical factors to predict overall survival (OS) in patients with bladder urothelial carcinoma (BLCA) who underwent transurethral resection of bladder tumor (TURBT). METHODS: Data were retrospectively collected from 114 patients with primary BLCA from February 2016 to February 2018. The regions of interest (ROIs) of the plain, arterial, and venous phase images were manually segmented. The Cox regression algorithm was used to establish 3 basic models for the plain phase (PP), arterial phase (AP), and venous phase (VP) and 2 combination models (AP + VP and PP + AP + VP). The highest-performing radiomics model was selected to calculate the radiomics score (Rad-score), and independent risk factors affecting patients' OS were analyzed using Cox regression. The Rad-score and clinical risk factors were combined to construct a joint model and draw a visualized nomogram. RESULTS: The combined model of PP + AP + VP showed the best performance with the Akaike Information Criterion (AIC) and Consistency Index (C-index) in the test group of 130.48 and 0.779, respectively. A combined model constructed with two independent risk factors (age and Ki-67 expression status) in combination with the Rad-score outperformed the radiomics model alone; AIC and C-index in the test group were 115.74 and 0.840, respectively. The calibration curves showed good agreement between the predicted probabilities of the joint model and the actual (p < 0.05). The decision curve showed that the joint model had good clinical application value within a large range of threshold probabilities. CONCLUSION: This new model can be used to predict the OS of patients with BLCA who underwent TURBT.

Synthesis, characterization, and sensitivity tests of La0.8Ba0.1Bi0.1FeO3 nanoparticles towards a few parts-per-billion of acetone gas.

In the present paper, the La0.8Ba0.1Bi0.1FeO3 powders were synthesized via the auto-combustion method. The optical, the positron annihilation spectroscopy and the gas sensing properties of our sample were investigated simultaneously. FTIR spectrum revealed the antisymmetric deformation vibrations of the Fe-O and Fe-O-Fe bonds inside the octahedron FeO6. The optical bandgap (Egap) of the La0.8Ba0.1Bi0.1FeO3 compound was found to be equal to 2.23 eV. We confirmed by the positron annihilation studies, the existence of open volume defects and vacancy sized defects, at the grain/interfaces between vacancy clusters and grains at the interfaces intersection (triple-lines). Notably, the La0.8Ba0.1Bi0.1FeO3 perovskite exhibits an excellent response toward acetone gas, with ultra-fast response and recovery times to some parts-per-billion (ppb) of this tested gas.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

Effect of liver cancer on the accumulation and hepatobiliary transport of per- and polyfluoroalkyl substances.

In this study, we examined the distribution of per- and polyfluoroalkyl substances (PFASs) in liver and bile tissues from the patients with liver cancer (n = 202) and healthy controls (n = 30), and calculated the hepatobiliary transport efficiency (TB-L) of PFASs. Among 21 PFASs, 13 PFASs were frequently detected in the liver (median: 8.80-16.3 ng/g) and bile (median: 11.03-14.26 ng/mL) samples. PFAS concentrations in liver were positively correlated with age, with higher levels of PFASs in the older. Variance analysis showed that gender and BMI (Body Mass Index) have an important impact on the distribution of PFASs. A U-shaped trend in TB-L of PFASs with the increasing of carbon chain length was found for the first time, and the TB-L of most PFASs in the control was higher than that of those in cases (p < 0.05), suggesting that hepatic injury would affect their transport. PFASs were positively associated with liver injury biomarkers, including γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), and total bilirubin (TB) levels (p < 0.05). This is the first study on examining the hepatobiliary transport characteristics of PFASs, which may help understand the connection between PFAS accumulation and liver cancer risk.

Combined modified Valsalva maneuver with adenosine supraventricular tachycardia: A comparative study.

BACKGROUND AND IMPORTANCE: Paroxysmal supraventricular tachycardia (PSVT) is an arrhythmia commonly seen in the emergency department. Both modified Valsalva maneuver (MVM) and intravenous adenosine are the first line treatment, of which the former has e lower success rate while the latter has a higher success rate but some risks and adverse effects. Given both of these reverse rhythms quickly, combining them may achieve a better effect. OBJECTIVE: The objective of this study is to evaluate the success rate and potential risk of combining the use of intravenous adenosine while patients were doing MVM as a treatment for paroxysmal supraventricular tachycardia(pSVT). DESIGN, SETTINGS AND PARTICIPANTS: We recruited patients with pSVT from 2017 to 2022, and randomly assigned them into 3 groups, MVM group, intravenous adenosine group, and combination therapy group, in which MVM was allowed to be performed twice, while intravenous adenosine was given in a titration manner to repeat three times, recorded the success rate and side effects in each group. MAIN RESULTS: The success rate of the MVM group, adenosine group, and combination group are 42.11%, 75.00 and 86.11%, respectively. The success rate of the adenosine group and combination group is significantly higher than the n MVSM group (p < 0.01, p < 0.001), while the success rate of the combination group is higher than the adenosine group, it has no significant difference (p = 0.340). In terms of safety, the longest RR durations (asystole period) are 1.61 s, 1.60s, and 2.27 s, there is a statistical difference among the three groups (p < 0.01) and between the adenosine and combination group (0.018). CONCLUSION: Therefore, we can conclude that combination therapy has a relatively high success rate and good safety profile, but the current study failed to show its superiority to adenosine.

Optimal Time-to-Surgery Recommendations Based on Primary Tumor Volume Regression for Patients with Resectable Esophageal Cancer after Neoadjuvant Chemoradiotherapy: A Retrospective Study.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. METHODS: This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). RESULTS: We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). CONCLUSIONS: For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.