Sleeve gastrectomy links the attenuation of diabetic kidney disease to the inhibition of renal tubular ferroptosis through down-regulating TGF-ß1/Smad3 signaling pathway.

PURPOSE: To investigate how sleeve gastrectomy (SG), a typical operation of bariatric surgery, attenuated symptom, and progression of diabetic kidney disease (DKD). METHODS: DKD model was induced by high-fat diet (HFD) combined with streptozocin in Wistar rats. SG was performed, and the group subjected to sham surgery served as control. The animals were euthanized 12 weeks after surgery, followed by sample collection for the subsequent experiment. The HK-2, a renal proximal tubular epithelial cell line derived from human, was utilized to investigate the potential mechanisms. RESULTS: SG improved metabolic parameters and glucose homeostasis, and could alleviate DKD in terms of renal function indices as well as histological and morphological structures in DM rats, accompanied with a significant reduction in renal tubular injury. Compared with sham group, SG reduced the renal tubular ferroptosis. To further clarify the mechanism involved, in vitro experiments were performed. In the presence of high glucose, renal tubular TGF-ß1 secretion was significantly increased in HK-2 cell line, which led to activation of ferroptosis through TGF-ß1/Smad3 signaling pathway. Inhibition of TGF-ß1 receptor and phosphorylation of Smad3 significantly ameliorated TGF-ß1-mediated ferroptosis. In vivo experiments also found that SG improved the hyperglycemic environment, reduced renal TGF-ß1 concentrations, and down-regulated the TGF-ß1/Smad3 signaling pathway. CONCLUSIONS: With the capacity to lower the glucose, SG could attenuate the ferroptosis by inhibiting TGF-ß1/Smad3 signaling pathway in DKD rats, and eventually attenuated DKD.

Gut microbiota, a potential cause of higher insulin sensitivity in children with Prader-Willi syndrome.

PURPOSE: Obesity is the main driving factor for comorbidities in Prader-Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls. METHODS: We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples. RESULTS: The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased Akkermansia Eubacterium, Eubacterium rectale, and Roseburia intestinalis and decreased Parabacteroides and Phascolarctobacterium. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that Achromobacter, Acidiphilium, Xylophilus, and Frisingicoccus were significantly negatively correlated with HOMA-IR. CONCLUSION: The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients.

AAV9-based PMM2 gene replacement augments PMM2 expression and improves glycosylation in primary fibroblasts of patients with phosphomannomutase 2 deficiency (PMM2-CDG).

Inherited deficiency of phosphomannomutase 2 (PMM2) (aka PMM2-CDG) is the most common congenital disorders of glycosylation (CDG) and has no cure. With debilitating morbidity and significant mortality, it is imperative to explore novel, safe, and effective therapies for the disease. Our Proof-of-Concept study showed that AAV9-PMM2 infection of patient fibroblasts augmented PMM2 expression and improved glycosylation. Thus, AAV9-PMM2 gene replacement is a promising therapeutic strategy for PMM2-CDG patients.

"Double-edged sword" effect of reactive oxygen species (ROS) in tumor development and carcinogenesis.

Reactive oxygen species (ROS) are small reactive molecules produced by cellular metabolism and regulate various physiological and pathological functions. Many studies have shown that ROS plays an essential role in the proliferation and inhibition of tumor cells. Different concentrations of ROS can have a "double-edged sword" effect on the occurrence and development of tumors. A certain concentration of ROS can activate growth-promoting signals, enhance the proliferation and invasion of tumor cells, and cause damage to biomacromolecules such as proteins and nucleic acids. However, ROS can enhance the body's antitumor signal at higher levels by initiating oxidative stress-induced apoptosis and autophagy in tumor cells. This review analyzes ROS's unique bidirectional regulation mechanism on tumor cells, focusing on the key signaling pathways and regulatory factors that ROS affect the occurrence and development of tumors and providing ideas for an in-depth understanding of the mechanism of ROS action and its clinical application.

An interpretable machine learning model for real-time sepsis prediction based on basic physiological indicators.

OBJECTIVE: In view of the important role of risk prediction models in the clinical diagnosis and treatment of sepsis, and the limitations of existing models in terms of timeliness and interpretability, we intend to develop a real-time prediction model of sepsis with high timeliness and clinical interpretability. PATIENTS AND METHODS: We used eight real-time basic physiological monitoring indicators of patients, including heart rate, respiratory rate, oxygen saturation, mean arterial pressure, systolic blood pressure, diastolic blood pressure, temperature and blood glucose, extracted three-hour dynamic feature sequences, and calculated 3 linear parameters (mean, standard deviation, and endpoint value), a 24-dimensional feature vector was constructed, and finally a real-time sepsis prediction model was constructed based on the Local Interpretable Model-Agnostic Explanation (LIME) interpretability method. RESULTS: The area under the receiver operating characteristic curve (AUROC), Accuracy and F1 scores of Extremely Randomized Trees we built were higher than those of other models, with AUROC above 0.76, showing the best performance. The Imbalance XGBoost has a high specificity (0.86) in predicting sepsis. The LIME local interpretable model we built can display a large amount of valid model prediction details for clinical workers' reference, including the prediction probability and the influence of each feature on the prediction result, thus effectively assisting the work of clinical workers and improving diagnostic efficiency. CONCLUSIONS: This model can provide real-time dynamic early warning of sepsis for critically ill patients under supervision and provide a reference for clinical decision support. At the same time, interpretive analysis of sepsis prediction models can improve the credibility of the models.

[Efficacy of video-assisted thoracoscopic surgical decortication for stage â ¢ tuberculous empyema].

Objective: To investigate the clinical efficacy, safety and feasibility of "double-portal" video-assisted thoracoscopic surgical(VATS) decortication among patients with stage Ⅲ tuberculous empyema, and then to evaluate the recovery of chest deformity. Method: This study was a single center retrospective study. A total of 49 patients with stage Ⅲ tuberculous empyema who underwent VATS pleural decortication at the Department of Thoracic Surgery, Public Health Clinical Center of Chengdu between June 2017 and April 2021 were enrolled, including 38 males, and 11 females, aged 13-60 (27.5±10.4) years. The safety and feasibility of VATS were further evaluated. The inner circumference of the chest on sternal and xiphoid planes on chest CT scans before and 1, 3, 6, 12months after decortication were collected through the measuring software of the CT. The samples in-pair test was used to compare the changes in the chest to reflect the recovery of the chest deformity. Results: In the 49 patients, The surgical time was (186±61) min, and the volume of blood loss was (366±267) ml. There were 8 cases (16.33%) with postoperative complications during the perioperative period. Constant air leak and pneumonia were the main postoperative complications. No relapse of empyema or dissemination of tuberculosis occured during the period of follow-up. Before surgery, the inner thoracic circumference of the thorax at the level of the carina plane was (655±54) mm, and the inner thoracic circumference of the thorax at the level of the xiphoid plane was (720±69) mm. Patients were followed for 12-36 months. The inner thoracic circumference of the thoracic cavity at the level of carina was (666±51), (667±47) and (671±47) mm at the 3rd, 6th and 12th months after operation, which were significantly larger than that at the level of carina before operation (all P<0.05). The inner thoracic circumference diameter of the thoracic cavity measured at the xiphoid level at the 3rd, 6th and 12th months after the operation was (730±65), (733±63) and (735±63) mm respectively(all P<0.05).The inner thoracic circumference of the thoracic cavity increased significantly than that before surgery (P<0.05). At 6 months after operation, there was significant difference in the improvement of the inner thoracic circumference of the carina plane in patients with age less than 20 years and FEV1% less than 80% (P=0.015, P=0.003). The improvement in the inner thoracic circumference of the carina plane in patients with pleural thickening≥8 mm compared with those with less than 8 mm was not statistically different(P=0.070). Conclusions: For some patients with stage Ⅲ tuberculous empyema, pleural decortication under thoracoscopy is safe and feasible, and can significantly restore the inner thoracic circumference of the patient's chest, improve the collapse of the patient's chest, and have significant clinical effect. The "double-portal VATS" surgical technology has the advantage of less trauma, wide operation field, large operation space and is easy to master, which is worth further exploring for clinical application.

[Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review].

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Current strategies in biomaterial-based periosteum scaffolds to promote bone regeneration: A review.

The role of periosteum rich in a variety of bone cells and growth factors in the treatment of bone defects has gradually been discovered. However, due to the limited number of healthy transplantable periosteum, there are still major challenges in the clinical treatment of critical-size bone defects. Various techniques for preparing biomimetic periosteal scaffolds that are similar in composition and structure to natural periosteal scaffold have gradually emerged. This article reviews the current preparation methods of biomimetic periosteal scaffolds based on various biomaterials, which are mainly divided into natural periosteal materials and various polymer biomaterials. Several preparation methods of biomimetic periosteal scaffolds with different principles are listed, their strengths and weaknesses are also discussed. It aims to provide a more systematic perspective for the preparation of biomimetic periosteal scaffolds in the future.

[Bedside monitoring of lung perfusion by electrical impedance tomography].

As a non-invasive and radiation-free bedside imaging method, electrical impedance tomography (EIT) can perform real-time regional pulmonary ventilation evaluation and pulmonary blood flow monitoring for patients, thus realizing bedside ventilation/perfusion matching visualization, effectively guiding the pathophysiological mechanism of hypoxemia, and providing a new method for the study of pulmonary blood flow. EIT has also played a unique and irreplaceable role in COVID-19 research and treatment. At the same time, as functional imaging, the operation details and image reconstruction algorithm of this technology still need to be further optimized by more researches to provide a more robust evaluation in clinical application. In this paper, EIT pulmonary blood flow monitoring methods, operation and implementation of monitoring indicators, application and related research progress will be described.

Runs of homozygosity analysis reveals population characteristics of yellow-feathered chickens using re-sequencing data.

1. To evaluate the inbreeding of yellow-feathered chickens (YFCs) and identify genes related to their unique characteristics, whole-genome re-sequencing data were applied to detect runs of homozygosity (ROH) in the genomes of 10 YFC chickens from each of 10 different YFC breeds. The number, length, distribution of ROH, and inbreeding coefficient in different YFC populations were calculated. Genomic regions with high frequency in ROH were annotated.2. In total, 25,547 ROH with an average length of 335 kb were detected, with most being <1 Mb. The domination of short ROH reflected the long breeding history of this chicken. The number, length, frequency, and distribution of ROH varied among chicken populations, and high genetic diversity was maintained.3. Numerous genes related to YFC characteristics were identified in the high-frequency ROH regions. Among these, IFNA, IFNB, IL11 RA, IL22 RA1, IFNLR1, and TRIF genes were involved in disease resistance. The AMY, G6PC, SDHB, GCNT4, and ACO genes were associated with energy material metabolism; and FABPL, AQP7, ACAA2, and RYR2 were related to meat quality and flavour. The KITLG, CREB3, RYR2, and LGR4 genes, related to pigmentation, were detected.4. This ROH-based inbreeding evaluation lays the foundation for breeding and conservation of YFC populations, and the candidate genes identified can be used for marker-assisted selection.

Context Matters: Social Psychological Factors That Underlie Academic Performance across Seven Institutions.

To enhance equity and diversity in undergraduate biology, recent research in biology education focuses on best practices that reduce learning barriers for all students and improve academic performance. However, the majority of current research into student experiences in introductory biology takes place at large, predominantly White institutions. To foster contextual knowledge in biology education research, we harnessed data from a large research coordination network to examine the extent of academic performance gaps based on demographic status across institutional contexts and how two psychological factors, test anxiety and ethnicity stigma consciousness, may mediate performance in introductory biology. We used data from seven institutions across three institution types: 2-year community colleges, 4-year inclusive institutions (based on admissions selectivity; hereafter, inclusive), and 4-year selective institutions (hereafter, selective). In our sample, we did not observe binary gender gaps across institutional contexts, but found that performance gaps based on underrepresented minority status were evident at inclusive and selective 4-year institutions, but not at community colleges. Differences in social psychological factors and their impacts on academic performance varied substantially across institutional contexts. Our findings demonstrate that institutional context can play an important role in the mechanisms underlying performance gaps.

[Advances in researches on neoadjuvant therapy for resectable colorectal liver metastasis].

Surgery is recognized as the core treatment for colorectal liver metastasis (CRLM), while its recurrence rate remains relatively high, even for resectable CRLM. This hints that the efficacy of treatment involves not only technological factors of surgery, but also biological behavior of tumor. For resectable CRLM, neoadjuvant therapy is beneficial to eliminate the micro-metastasis, reduce postoperative recurrence rate, screen tumor biological behavior and improve prognosis. However, questions about which kind of CRLM patients fits for neoadjuvant therapy and what regimen should be used are still debatable. This paper reviews stratified management of resectable CRLM, choice of neoadjuvant regimen, especially the application value of targeted therapy, based on the latest guidelines and studies.

Medical ozone induces proliferation and migration inhibition through ROS accumulation and PI3K/AKT/NF-kB suppression in human liver cancer cells in vitro

Background Hepatocellular carcinoma is one of the most common malignancies and leading cancer-associated deaths worldwide. Ozone has been proposed as a promising therapeutic agent in the treatment of various disorders. Purpose The purpose of this paper is to assess the potential anticancer effects of the ozone on liver cancer cells. Method The liver cancer cell line of bel7402 and SMMC7721 was used in this study. Proliferation was evaluated using the CCK-8 and the colony formation assay. Wond healing assay and transwell assay without Matrigel were used to evaluate their migration ability. Flow cytometry was used for cell cycle analysis and reactive oxygen species (ROS) determination. Glutathione detection kit was used for measurement of glutathione level. Protein expression was estimated by western blot analysis. Results Ozone treatment inhibited liver cancer cell proliferation, colony formation. Ozone induced G2/M phase cell cycle arrest, which could be elucidated by the change of protein levels of p53, p21, Cyclin D1, cyclin B1, cdc2, and CDK4. We also found that ozone treatment inhibited migration ability by inhibiting EMT-relating protein. Ozone also induced ROS accumulation and decreased glutathione level decreased, which contributed to the inactivation of the PI3K/AKT/NF-κB pathway. Finally, we found that pre-treatment of liver cancer cells with N-acetylcysteine resisted ozone-induced effects. Conclusions Ozone restrains the proliferation and migration potential and EMT process of liver cancer cells via ROS accumulation and PI3K/AKT/NF-κB suppression (AU)

MiR-1269a acts as an onco-miRNA in non-small cell lung cancer via down-regulating SOX6.

The article "MiR-1269a acts as an onco-miRNA in non-small cell lung cancer via down-regulating SOX6, by R.-H. Jin, D.-J. Yu, M. Zhong, published in Eur Rev Med Pharmacol Sci 2018; 22 (15): 4888-4897- DOI: 10.26355/eurrev_201808_15625-PMID: 30070324" has been withdrawn from the authors to some technical reasons (there are some errors and incorrect data). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15625.

Medical ozone induces proliferation and migration inhibition through ROS accumulation and PI3K/AKT/NF-κB suppression in human liver cancer cells in vitro.

BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies and leading cancer-associated deaths worldwide. Ozone has been proposed as a promising therapeutic agent in the treatment of various disorders. PURPOSE: The purpose of this paper is to assess the potential anticancer effects of the ozone on liver cancer cells. METHOD: The liver cancer cell line of bel7402 and SMMC7721 was used in this study. Proliferation was evaluated using the CCK-8 and the colony formation assay. Wond healing assay and transwell assay without Matrigel were used to evaluate their migration ability. Flow cytometry was used for cell cycle analysis and reactive oxygen species (ROS) determination. Glutathione detection kit was used for measurement of glutathione level. Protein expression was estimated by western blot analysis. RESULTS: Ozone treatment inhibited liver cancer cell proliferation, colony formation. Ozone induced G2/M phase cell cycle arrest, which could be elucidated by the change of protein levels of p53, p21, Cyclin D1, cyclin B1, cdc2, and CDK4. We also found that ozone treatment inhibited migration ability by inhibiting EMT-relating protein. Ozone also induced ROS accumulation and decreased glutathione level decreased, which contributed to the inactivation of the PI3K/AKT/NF-κB pathway. Finally, we found that pre-treatment of liver cancer cells with N-acetylcysteine resisted ozone-induced effects. CONCLUSIONS: Ozone restrains the proliferation and migration potential and EMT process of liver cancer cells via ROS accumulation and PI3K/AKT/NF-κB suppression.

Long non-coding RNA OR3A4 is associated with poor prognosis of human non-small cell lung cancer and regulates cell proliferation via up-regulating SOX4.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA OR3A4 is associated with poor prognosis of human non-small cell lung cancer and regulates cell proliferation via up-regulating SOX4, by M. Zhong, W.-L. Wang, D.-J. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6524-6530-DOI: 10.26355/eurrev_201908_18537-PMID: 31378892" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18537.

Long noncoding RNA CASC15 is upregulated in non-small cell lung cancer and facilitates cell proliferation and metastasis via targeting miR-130b-3p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA CASC15 is upregulated in non-small cell lung cancer and facilitates cell proliferation and metastasis via targeting miR-130b-3p, by D.-J. Yu, M. Zhong, W.-L. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (18): 7943-7949-DOI: 10.26355/eurrev_201909_19010-PMID: 31599419" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18857.