Objective To investigate the effect of Astragalus extract on oxidative stress in diabetic nephropathy rats by regulating nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods The diabetic rat model was constructed by high-fat diet combined with intraperitoneal injection of streptozotocin,and was randomly divided into model group,experimental-L group,experimental-H group,experimental-H+ML385 group,with 12 rats in each group,and 12 rats were selected as blank group.Rats in blank group and model group were intragastric with equal volume of normal saline;rats in experimental-L,-H groups were intragastric with 50 mg·kg-1 astragalus extract and 100 mg·kg-1 Astragalus extract,respectively;rats in experimental-H+ML385 group were intragastric with 100 mg·kg-1 Astragalus extract and intraperitoneally injected with 20 mg·kg-1 ML385 once a day.Eight weeks in a row.The content of oxidative stress-related indexes in rat renal tissues was detected,the expression level of reactive oxygen species was detected by dihydroethidine staining,and the protein expression level of quinone oxidoreductase 1(NQO1),heme oxygenase 1(HO-1)and nuclear Nrf2 in rat renal tissues was detected by Western blot.Results Superoxide dismutase in blank group,model group,experimental-H group and experimental-H+ML385 group were(163.89±20.28),(71.35±12.72),(132.11±19.29)and(73.04±13.28)U·mg-1,respectively;glutathione peroxidase were(12.82±1.57),(4.91±1.18),(8.54±1.09),(5.10±1.43)U·mg-1,respectively;reactive oxygen species were 0.02±0.01,0.09±0.01,0.05±0.01 and 0.08±0.01,respectively;nuclear Nrf2 values were 0.63±0.09,0.28±0.06,0.60±0.08,0.32±0.05,respectively;the NQO1 values were 0.58±0.11,0.27±0.07,0.63±0.12 and 0.31±0.08,respectively;the HO-1 values were 0.53±0.08,0.23±0.06,0.59±0.09 and 0.28±0.05,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(all P＜0.05).The above indexes of the experimental-H+ML385 group were statistically significant compared with the experimental-H group(all P＜0.05).Conclusion Astragalus extract can alleviate oxidative stress damage in diabetic nephropathy rats,and the mechanism may be achieved by regulating Nrf2/ARE signaling pathway.

The inflammatory effect of dietary is strongly related to the development of cancer,therefore,the diet-related inflammatory index was developed as a methodological tool to investigate the relationship between dietary,inflammation and tumors.In this paper,we summarized the results on diet-related inflammatory indices and common cancers of the digestive system based on relevant cancer epidemiological studies.The available epidemiological evidence suggests that pro-inflammatory diet is associated with an increased risk of gastrointestinal malignancies,with the strongest association with colorectal cancer,followed by esophageal and gastric cancers,and then pancreatic cancer,and the least evidence of studies with liver cancer.Among these studies,the level of evidence for esophageal cancer is lower than colorectal cancer,the study of gastric cancer has gender differences and problems in adjusting for confounders,and the study of pancreatic cancer has heterogeneous results.In view of the current research progress and deficiencies,prospective studies or population-based cohort studies,as well as strengthening nutritional epidemiological studies related to common tumors such as liver cancer could be considered in the future.This review is expecting to provide basic information and scientific basis for strengthening the related healthy eating behavior promotion in the prevention and control of digestive system tumors.

Less invasive transcatheter tricuspid therapies are optimal alternative for surgery in high-risk individuals with severe symptomatic tricuspid regurgitation on medical therapy. Various techniques are available with Transcatheter Edge-to-Edge Repair (TEER) having the greatest experience worldwide. When the coaptation gap becomes too large for TEER, caval valve implantation (CAVI) emerge as a better option. We described a series of 4 patients who underwent CAVI with the TricValve system and periprocedural computed tomography angiography imaging for the purpose of TricValve sizing. There were few procedural complications, with significant improvements in New York Heart Association functional class and right ventricular function post-procedure.

Among interbody implants used during anterior cervical discectomy and fusion (ACDF), structural allografts and polyetheretherketone (PEEK) are the most used spacers. Currently, no consensus has been established regarding the superiority of either implant, with US surgeons preferring structural allografts, whereas UK surgeons preferring PEEK. The purpose of this systematic review (level of evidence, 4) was to compare postoperative and patient-reported outcomes between the use of structural allografts PEEK interbody spacers during ACDF. Five electronic databases (PubMed, Embase, Scopus, Web of Science, and Cochrane) were searched for articles comparing the usage of structural allograft and PEEK interbody spacers during ACDF procedures from inception to April 10, 2023. The searches were conducted using the keywords “Spine,” “Allograft,” and “PEEK” and were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Subsequent quality and sensitivity analyses were performed on the included studies. Nine studies involving 1,074 patients were included. Compared with the PEEK group, the structural allograft group had comparable rates of postoperative pseudoarthrosis (p=0.58). However, when stratified according to the number of levels treated, the 3-level ACDF PEEK group was 3.45 times more likely to have postoperative pseudoarthrosis than the structural allograft group (p=0.01). Subsequent postoperative outcomes (rate of subsidence and change in the preoperative and postoperative segmental disc heights) were comparable between the PEEK and structural allograft groups. Patient-reported outcomes (Visual Analog Scale [VAS] of neck pain and Neck Disability Index [NDI]) were comparable. This study showed that for 3-level ACDFs, the use of structural allografts may confer higher fusion rates. However, VAS neck pain, NDI, and subsidence rates were comparable between structural allografts and PEEK cages. In addition, no significant difference in pseudoarthrosis rates was found between PEEK cages and structural allografts in patients undergoing 1- and 2-level ACDFs.

Objective:To analyze the related literature of pulmonary rehabilitation research at home and abroad, understand its research focus and development trend, and provide a reference and basis for future pulmonary rehabilitation research.Methods:Literature related to pulmonary rehabilitation published in the database of Web of Science and China National Knowledge Infrastructure from January 2015 to February 2022 was retrieved, and the contents such as the number of articles published annually, authors, research institutions, and high-frequency keywords were visually analyzed by bibliometrics and CiteSpace software.Results:The number of articles published each year showed an obvious upward trend from 2015, and the number of Chinese documents was higher than that of English documents from 2019 to 2020. MARTIJN A SPRUIT was the author with the largest number of articles published in English, with a total of 65 articles published, with close cooperation among scholars. Che Guowei was the author with the largest number of articles published in Chinese literature, with 13 articles published in total. The cooperation among the authors was relatively lacking and scattered. The main research institutions abroad were universities, and the institution with the highest number of papers was Maastricht University in the Netherlands, with a total of 85 articles. The research institutions cooperated closely and formed a cooperation network. Hospitals were the main research institutions in China, and the thoracic surgery Department of West China Hospital of Sichuan University had the highest total number of publications, with 14 articles. The cooperation among institutions was not close, and there was a lack of cooperation with universities and scientific research institutions. Through keyword co-occurrence and clustering and timeline view analysis, it was concluded that the research hotspots in this field were pulmonary rehabilitation of patients with different chronic respiratory diseases, the influence of pulmonary rehabilitation on lung function and quality of life of patients with chronic obstructive pulmonary disease, and the intervention methods of pulmonary rehabilitation. The future trend was predicted as the clinical application value of pulmonary rehabilitation in the treatment of lung cancer.Conclusions:At present, pulmonary rehabilitation research is in a stable development period. However, the cooperation between domestic authors and institutions is not close enough compared with foreign countries. In the future, China should strengthen the communication and cooperation between research teams, and learn from foreign research results to further develop the application of pulmonary rehabilitation in lung cancer patients, to promote the development of pulmonary rehabilitation research in China.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety. METHODS: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR). RESULTS: We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR. CONCLUSION Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.
Humans ; Cross-Sectional Studies ; Pandemics ; COVID-19/epidemiology* ; Burnout, Psychological ; Health Personnel

This study aims to investigate the effect and mechanism of total triterpenes of Euphorbium in treating rheumatoid arthritis(RA). The rat model of RA was established with Freund's complete adjuvant(FCA). Male rats were randomly assigned into control, model, Tripterygium glycosides(7.5 mg·kg~(-1)), and low-, medium-, and high-dose total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1), respectively) groups, with 10 rats in each group. In other groups except the control group, 0.2 mL FCA was injected into the right hind toe. Rats in the intervention groups were administrated with corresponding drugs by gavage, and the control group and the model group with the same volume of 0.5% CMC-Na solution once a day. During the treatment period, the swelling degree of the hind paw was measured and the arthritis was scored until day 30. At the end of drug administration, the pathological changes of the joint tissue were observed by hematoxylin-eosin staining. The content of malondialdehyde(MDA), glutathione(GSH), and Fe~(2+) and the activity of superoxide dismutase(SOD) in the joint tissue were measured by biochemical colorimetry. RT-PCR was performed to determine the mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), and acyl-CoA synthetase long chain family member 4(ACSL4) in the joint tissue. Western blot was employed to determine the protein levels of Nrf2, Kelch-like ECH-associated protein 1(Keap1), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), SOD2, GPX4, and ACSL4 in the joint tissue. The results showed that the treatment with Tripterygium glycosides(7.5 mg·kg~(-1)) and total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1)) alleviated the swelling degree of bilateral hind limbs, decreased the arthritis score, reduced joint tissue lesions and the content of MDA and Fe~(2+) in the joint tissue, and increased GSH content and SOD activity. Furthermore, the interventions up-regulated the protein and mRNA levels of Nrf2 and GPX4, down-regulated the protein and mRNA levels of ACSL4, and up-regulated the protein levels of Keap1, NQO1, HO-1, and SOD2 in the Nrf2/HO-1/GPX4. In summary, the total triterpenes of Euphorbium can treat RA by inhibiting lipid peroxidation and abnormal ferroptosis, which may involve the Nrf2/HO-1/GPX4 signaling pathway.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Triterpenes/pharmacology* ; Oxidative Stress ; Arthritis, Rheumatoid/genetics* ; Glutathione ; Superoxide Dismutase/metabolism* ; Glycosides/pharmacology* ; RNA, Messenger/metabolism*

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.
Humans ; Carcinoma, Renal Cell/pathology* ; Cell Proliferation ; Hypoxia ; Kidney Neoplasms ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; RNA, Circular/metabolism* ; RNA, Small Interfering ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics*