Retraction Note: Roles of the Nrf2/HO-1 pathway in the anti-oxidative stress response to ischemia-reperfusion brain injury in rats.

The article "Roles of the Nrf2/HO-1 pathway in the anti-oxidative stress response to ischemia-reperfusion brain injury in rats", by L.-J. Jiang, S.-M. Zhang, C.-W. Li, J.-Y. Tang, F.-Y. Che, Y.-C. Lu, published in Eur Rev Med Pharmacol Sci 2017; 21 (7): 1532-1540-PMID: 28429353 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/4C502B6EB4FCA59AC9F42A8278A3D4), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive and have not provided the study's raw data. The journal investigation revealed several figure duplications and manipulations in Figures 3 and 6. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12521.

A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

[Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease].

OBJECTIVE: To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate (NaB) in a mouse model of Parkinson's disease (PD) via the gut-brain axis. METHODS: Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group, PD model group, and NaB treatment group. In the latter two groups, PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) once daily for 5 consecutive days, and normal saline was injected in the control group. After modeling, the mice received daily gavage of NaB (300 mg/kg) or an equal volume of saline for 14 days. Behavioral tests were carried out to assess the changes in motor function of the mice, and Western blotting was performed to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in the striatum and nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and the tight junction proteins ZO-1, Occludin, and Claudinin the colon. HE staining was used to observe inflammatory cell infiltration in the colon of the mice. RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues, and their expressions were verified using qRT-PCR and Western blotting. RESULTS: The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH, Occludin, and Claudin and downregulated expressions of α-syn, NF-κB, TNF-α, and IL-6 (all P < 0.05). HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice. RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice (P < 0.05). CONCLUSION: NaB can improve motor dysfunction, reduce dopaminergic neuron loss in the striatum, and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

[Association between onset time of sepsis-associated acute kidney injury and clinical outcome in patients with sepsis].

Objective: To explore the relationship between the onset time of sepsis-associated acute kidney injury (SA-AKI) and adverse clinical outcomes. Methods: Data were derived from Beijing Acute Kidney Injure Trial (BAKIT) which investigated the epidemiology of acute kidney injury (AKI) in critically ill patients at 30 intensive care units (ICU) of 28 tertiary hospitals in Beijing from 1 March to 31 August 2012. Patients who were older than 18 years and diagnosed with sepsis and AKI, and expected to stay in ICU for at least 24 h were included in this study. A total of 653 patients were included in this study, 414 males and 239 females with a mean age of (68.2±17.0) years. According to the onset time of SA-AKI, patients were grouped into early AKI (E-AKI) (AKI occurred within 48 hours after ICU admission) and late AKI (L-AKI) (AKI occurred after 48 hours of ICU admission) group. The primary outcome was major adverse kidney events (MAKE), consisted of all-cause mortality, renal replacement therapy-dependence, and an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. Multivariable logistic regression was used to investigate the association between the onset time of SA-AKI and clinical outcomes. Results: A total of 653 patients with SA-AKI were included, 423 (64.8%) patients developed E-AKI, 230 (35.2%) cases developed L-AKI, MAKE occurred in 405 (62.0%) cases, and 301 (46.1%) patients died in hospital. Compared with E-AKI group, L-AKI patients showed higher AKI 3 level rate [55.7%(128/230) vs 40.2%(170/423), P<0.001], incidence of MAKE [72.6%(167/230) vs 56.3%(238/423,P<0.001)] and hospital mortality [55.2%(127/230) vs 44.1%(174/423), P=0.001]. The risk of MAKE and in-hospital mortality in L-AKI group increased for 2.55-fold times (OR=3.55, 95%CI: 1.94-6.04) and 1.84-fold times (OR=2.84, 95%CI: 1.44-5.60) when compared with those in E-AKI, respectively (both P<0.05). Conclusion: Late timing onset of SA-AKI is associated with poor clinical outcomes.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Clinical characteristics and research progress of ocular Merkel cell carcinoma].

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis.

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cows' energy needs for milk production. The increased lipolysis in cows presents significant health risks with unclear mechanisms. The objectives of our study were to compare the longitudinal profiles of metabolites and lipids of serum from high and low-lipolysis cows. Forty multiparous Holstein dairy cows were enrolled in the retrospective study. Serum samples were collected on d 7 before expected calving, as well as on d 5, d 7, d 14, and d 21 postpartum. Dairy cows were grouped according to mean serum nonesterified fatty acids on d 5 and 7 after parturition as low (<0.600 mmol/L; n = 8; LFM) and high (>0.750 mmol/L; n = 8; HFM), indicating fat mobilization during early lactation. Lactational performance and serum metabolic parameters related to glucose and lipid metabolism, liver functions, oxidative status, and inflammatory responses were determined. Serum samples were subjected to LC-MS-based metabolomics and lipidomics. Despite differences in postpartum BW change, there were no observed variations in milk yield and composition between 2 groups. Serum BHBA, glucose, leptin, aspartate aminotransferase, IL-6, and TNF-α were greater in cows with HFM than in LFM. Serum adiponectin, revised quantitative insulin sensitivity check index and albumin were lower in cows with HFM than LFM. Intensified fat mobilization in the HFM cows came along with reduced estimated insulin sensitivity, impaired liver functions, and increased oxidative stress and inflammatory responses. Differences in metabolic patterns were observed across the transition period when comparing serum blood matrices (e.g., in different amino acids, acylcarnitines, and sphingolipids). The serum metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum metabolic status parameters suggest that cows adopt varied metabolic adaptation strategies to cope with energy deficits postpartum. Our investigation found a comprehensive remodeling of the serum metabolic profiles in transition dairy cattle, highlighting the significance of alterations in sphingolipid species, as they play a crucial role in insulin resistance and metabolic disorders.

Diagnostic and prognostic value of parameters of erector spinae in patients with uremic sarcopenia.

AIM: This study aimed to investigate whether computed tomography (CT)-measured erector spinae parameters (ESPs) have diagnostic, severity assessment, and prognostic predictive value in uremic sarcopenia (US). MATERIALS AND METHODS: A total of 202 uremic patients were enrolled and divided into two groups: a control group and a sarcopenia group. Sarcopenia was classified into two types: severe and nonsevere. The area, volume, and density of the erector spinae (ES) were measured using chest CT images, and the relevant ESP, including the erector spinae index (ESI), total erector spinae volume (TESV), erector spinae density (ESD), and erector spinae gauge (ESG) were calculated. The occurrence of adverse events was followed-up for 36 months. The diagnostic value and severity of US were determined using the receiver operating characteristic (ROC) curve. Survival curves diagnosed using CT were plotted and compared with the curve drawn using the gold standard. Cox regression analysis was used to identify independent risk factors associated with survival in US. RESULTS: With an area under the curve (AUC) of 0.840 and 0.739, the combined ESP has diagnostic value and the ability to assess the severity of US. There was no significant difference in the survival curve between the combined ESP for the diagnosis of US and the gold standard (P > 0.05). ESI is a standalone predictor of survival in patients with US. CONCLUSION: ESP measured by CT has diagnostic values for US and its severity, as well as being a predictive value for the prognosis of US.

Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis.

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.

[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Analysis of prevalence status and influencing factors of e-cigarette use among secondary school students in Heilongjiang Province].

Objective: To describe the current situation and influencing factors of e-cigarette use among secondary school students in Heilongjiang Province to provide evidence for formulating provincial youth e-cigarette prevention and control strategies. Methods: A multi-stage stratified cluster probability sampling method was adopted in 2021, with 8 340 students in 180 classes from 56 primary and high schools in 10 monitoring districts and counties in Heilongjiang Province. The students in the selected classes filled out a unified questionnaire by themselves. SAS 9.4 software was used for data cleansing, sample weighting, and analysis. Chi-squared tests were used to compare the differences between groups, and a two-level logistic regression model was used to analyze the influencing factors of e-cigarette use among secondary school students. Results: A total of 8 329 survey questionnaires were included in the analysis. The prevalence rates of ever and current e-cigarette use among secondary school students in Heilongjiang Province were 18.27% and 5.46%, respectively. In terms of ever e-cigarette use, the rate of boys (23.94%) was higher than that of girls (12.35%). The rate of vocational high school students (39.18%) was higher than that of general high school students (24.11%) and than that of junior school students (11.27%). In terms of current e-cigarette use, the rate of boys (7.08%) was higher than that of girls (3.76%). The rate of vocational high school students (14.56%) was higher than that of general high school students (7.70%) and than that of junior school students (2.67%). The rates of ever and current e-cigarette use were relatively higher in each subgroup, including "weekly allowance more than 40 Yuan" "one of the student's parents, friends or teachers was smoker" "smoked cigarettes now" and "saw e-cigarette advertisements". A two-level logistic regression model showed that the following factors were the influencing factors of current use of e-cigarettes among secondary school students, including gender, whether they were current cigarette smokers, the smoking status of their close friends, if they saw teachers smoked in the school, noticed e-cigarette advertisements, and e-cigarette addictive cognition. Conclusions: The prevalence rates of ever and current e-cigarette use among secondary school students in Heilongjiang Province were high. E-cigarette advertisements, the smoking status of their close friends, and whether they saw teachers smoking in the school were the main factors affecting e-cigarette use among secondary school students in Heilongjiang Province. It is necessary to focus on constructing smoke-free environments and increase health education related to e-cigarette knowledge on risk in developing a smoke-free campus in the whole province.

[Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii pneumonia after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

[Clinical characteristics of hospitalized children with respiratory syncytial virus infection and risk prediction of severe illness during the post-COVID-19 era in Kunming].

Objective: To compare the epidemiological and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection in Kunming among the pre-and post-COVID-19 era, and to establish a prediction model for severe RSV infection in children during the post-COVID-19 period. Methods: This was a retrospective study. Clinical and laboratory data were collected from 959 children hospitalized with RSV infection in the Department of Pulmonary and Critical Care Medicine at Kunming Children's Hospital during January to December 2019 and January to December 2023. Patients admitted in 2019 were defined as the pre-COVID-19 group, while those admitted in 2023 were classified as the post-COVID-19 group. Epidemiological and clinical characteristics were compared between the two groups. Subsequently, comparison of the clinical severity among the two groups was performed based on propensity score matching (PSM). Furthermore, the subjects in the post-COVID-19 group were divided into severe and non-severe groups based on clinical severity. Chi-square test and Mann-Whitney U test were used for pairwise comparison between groups, and multivariate Logistic regression was applied for the identification of independent risk factors and construction of the prediction model. The receiver operating characteristic (ROC) curve and calibration curve were employed to evaluate the predictive performance of this model. Results: Among the 959 children hospitalized with RSV infection, there were 555 males and 404 females, with an onset age of 15.4 (7.3, 28.5) months. Of which, there were 331 cases in the pre-COVID-19 group and 628 cases in the post-COVID-19 group. The peak period of RSV hospitalization in the post-COVID-19 group were from May to October 2023, and the monthly number of inpatients for each of these months were as follows: 72 cases (11.5%), 98 cases (15.6%), 128 cases (20.4%), 101 cases (16.1%), 65 cases (10.4%), and 61 cases (9.7%), respectively. After PSM for general data, 267 cases were matched in each group. The proportion of wheezing in the post-COVID-19 group was lower than that in the pre-COVID-19 group (109 cases (40.8%) vs. 161 cases (60.3%), χ2=20.26, P<0.001), while the incidences of fever, tachypnea, seizures, severe case, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein and interleukin-6 levels were all higher than those in the pre-COVID-19 group (146 cases (54.7%) vs. 119 cases (44.6%), 117 cases (43.8%) vs. 89 cases (33.3%), 37 cases (13.9%) vs. 14 cases (5.2%), 69 cases (25.8%) vs. 45 cases (16.9%), 3.6 (1.9, 6.4) vs. 2.3 (1.8, 4.6), 9.9 (7.1, 15.2) vs. 7.8 (4.5, 13.9) mg/L, 20.5 (15.7, 30.4) vs. 17.2 (11.0, 26.9) ng/L, χ2=5.46, 6.36, 11.47, 6.42, Z=4.13, 3.06, 2.96, all P<0.05). There were 252 cases and 107 cases with co-infection in the post-and pre-COVID-19 groups, respectively. The proportion of triple and quadruple infection in the post-COVID-19 group was higher than that in the pre-COVID-19 group (59 cases (23.4%) vs. 13 cases (12.1%), 30 cases (11.9%) vs. 5 cases (4.7%), χ2=5.94, 4.46, both P<0.05). Among the 252 cases with co-infection in post-COVID-19 group, the most prevalent pathogens involving in co-infections, in order, were Mycoplasma pneumoniae 56 cases (22.2%), Influenza A virus 53 cases (21.0%), Rhinovirus 48 cases (19.0%), Parainfluenza virus 35 cases (13.9%), and Adenovirus 28 cases (11.1%).The result of multivariate Logistic regression showed that age (OR=0.70, 95%CI 0.62-0.78, P<0.001), underlying diseases (OR=10.03, 95%CI 4.10-24.55, P<0.001), premature birth (OR=6.78, 95%CI 3.53-13.04, P<0.001), NLR (OR=1.85, 95%CI 1.09-3.15, P=0.023), and co-infection (OR=1.28, 95%CI 1.18-1.38, P<0.001) were independently associated with the development of severe RSV infection in the post-COVID-19 group. The ROC curve of the prediction model integrating the above five factors indicated an area under the curve of 0.85 (95%CI 0.80-0.89, P<0.001), with an optimal cutoff of 0.21, a sensitivity of 0.83 and a specificity of 0.80. The calibration curve showed that the predicted probability in this model did not differ significantly from the actual probability (P=0.319). Conclusions: In the post-COVID-19 era in Kunming, the peak in pediatric hospitalizations for RSV infection was from May to October, with declined incidence of wheezing and increased incidence of fever, tachypnea, seizures, severe cases, and rates of triple and quadruple co-infections. Age, underlying diseases, premature birth, NLR, and co-infection were identified as independent risk factors for severe RSV infection in the post-COVID-19 period. In this study, a risk prediction model for severe pediatric RSV infection was established, which had a good predictive performance.

Serum squamous cell carcinoma antigen level and magnetic resonance imaging for the prognosis of locally advanced cervical cancer.

OBJECTIVE: Squamous cell carcinoma antigen (SCC-ag) and magnetic resonance imaging (MRI) were explored to serve as biomarkers to predict the prognosis of cervical cancer (CC) patients treated with neoadjuvant chemotherapy (NACT) prior to radical surgery, with the aim of identifying the subgroup that least benefits from the combined therapy. PATIENTS AND METHODS: All patients were treated with NACT prior to radical surgery and received MRI and SCC-ag examinations before and after NACT. For these three cycles of NACT, patients were treated with intravenous paclitaxel at 150 mg/m2 over a period of 3 hours and carboplatin, with the area under the sera concentration-time curve of 5 over a period of 30 minutes on the first day of each cycle. Meanwhile, the blood pressure, ECG, and blood oxygen saturation of the patients were observed during the infusion. A discovery cohort and a validation cohort were applied to examine the prognostic performance of SCC-ag, MRI, and their combination. The endpoints of our study were overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 384 patients diagnosed between August 2006 and December 2010 were enrolled in our research, with 206 patients in the discovery cohort and 178 patients in the validation cohort. The high-risk group identified by MRI had a worse OS [hazard ratio (HR), 3.567; 95% confidence interval (CI), 1.466-8.677; log-rank p=0.0027) and PFS (HR, 4.062; 95% CI, 2.171-7.6; log-rank p<0.0001) than the low-risk group. Meanwhile, the SCC-RC could serve as a strong prognostic factor to predict OS (HR, 5.614; 95% CI, 2.473-12.744; log-rank p<0.0001) and PFS (HR, 7.481; 95% CI, 4.194-13.344; log-rank p<0.0001) for CC. In addition, the combined MRI and SCC-ag had greater prognostic efficiency and were used to divide the whole patient population into three groups. Compared with patients in the low-risk group, patients in the high-risk group had a worse OS (HR, 8.216; 95% CI, 2.98-22.651; log-rank p<0.0001) and PFS (HR, 11.757; 95% CI, 5.735-24.104; log-rank p<0.0001). Multivariate analyses revealed that MRI, SCC-ag, and their combination were independent prognostic factors. CONCLUSIONS: SCC-ag and MRI, individually or in combination, were bound up with OS and PFS in CC. Additionally, the predictive efficiency improved when SCC-ag and MRI were combined in a risk model that predicted the OS and PFS of SCC compared with the predictive efficiency of either SCC-ag or MRI alone, revealing that the combination of these two biomarkers could help to ameliorate prognostic stratification and to guide personalized therapy for SCC patients.

[Clinical repair strategy for ischial tuberosity pressure ulcers based on the sinus tract condition and range of skin and soft tissue defects].

Objective: To investigate the clinical repair strategy for ischial tuberosity pressure ulcers based on the sinus tract condition and range of skin and soft tissue defects. Methods: The study was a retrospective observational study. From July 2017 to March 2023, 21 patients with stage Ⅲ or Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 13 males and 8 females, aged 14-84 years. There were 31 ischial tuberosity pressure ulcers, with an area of 1.5 cm×1.0 cm-8.0 cm×6.0 cm. After en bloc resection and debridement, the range of skin and soft tissue defect was 6.0 cm×3.0 cm-15.0 cm×8.0 cm. According to the depth and size of sinus tract and range of skin and soft tissue defects on the wound after debridement, the wounds were repaired according to the following three conditions. (1) When there was no sinus tract or the sinus tract was superficial, with a skin and soft tissue defect range of 6.0 cm×3.0 cm-8.5 cm×6.5 cm, the wound was repaired by direct suture, Z-plasty, transfer of buttock local flap, or V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. (2) When the sinus tract was deep and small, with a skin and soft tissue defect range of 8.5 cm×4.5 cm-11.0 cm×6.5 cm, the wound was repaired by the transfer and filling of gracilis muscle flap followed by direct suture, or Z-plasty, or combined with transfer of inferior gluteal artery perforator flap. (3) When the sinus tract was deep and large, with a skin and soft tissue defect range of 7.5 cm×5.5 cm-15.0 cm×8.0 cm, the wound was repaired by the transfer and filling of gracilis muscle flap and gluteus maximus muscle flap transfer, followed by direct suture, Z-plasty, or combined with transfer of buttock local flap; and transfer and filling of biceps femoris long head muscle flap combined with rotary transfer of the posterior femoral cutaneous nerve nutrient vessel flap; and filling of the inferior gluteal artery perforator adipofascial flap transfer combined with V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. A total of 7 buttock local flaps with incision area of 8.0 cm×6.0 cm-19.0 cm×16.0 cm, 21 gracilis muscle flaps with incision area of 18.0 cm×3.0 cm-24.0 cm×5.0 cm, 9 inferior gluteal artery perforator flaps or inferior gluteal artery perforator adipofascial flaps with incision area of 8.5 cm×6.0 cm-13.0 cm×7.5 cm, 10 gluteal maximus muscle flaps with incision area of 8.0 cm×5.0 cm-13.0 cm×7.0 cm, 2 biceps femoris long head muscle flaps with incision area of 17.0 cm×3.0 cm and 20.0 cm×5.0 cm, and 5 posterior femoral cutaneous nerve nutrient vessel flaps with incision area of 12.0 cm×6.5 cm-21.0 cm×10.0 cm were used. The donor area wounds were directly sutured. The survival of muscle flap, adipofascial flap, and flap, and wound healing in the donor area were observed after operation. The recovery of pressure ulcer and recurrence of patients were followed up. Results: After surgery, all the buttock local flaps, gracilis muscle flaps, gluteus maximus muscle flaps, inferior gluteal artery perforator adipofascial flaps, and biceps femoris long head muscle flaps survived well. In one case, the distal part of one posterior femoral cutaneous nerve nutrient vessel flap was partially necrotic, and the wound was healed after dressing changes. In another patient, bruises developed in the distal end of inferior gluteal artery perforator flap. It was somewhat relieved after removal of some sutures, but a small part of the necrosis was still present, and the wound was healed after bedside debridement and suture. The other posterior femoral cutaneous nerve nutrient vessel flaps and inferior gluteal artery perforator flaps survived well. In one patient, the wound at the donor site caused incision dehiscence due to postoperative bleeding in the donor area. The wound was healed after debridement+Z-plasty+dressing change. The wounds in the rest donor areas of patients were healed well. After 3 to 15 months of follow-up, all the pressure ulcers of patients were repaired well without recurrence. Conclusions: After debridement of ischial tuberosity pressure ulcer, if there is no sinus tract formation or sinus surface is superficial, direct suture, Z-plasty, buttock local flap, or V-Y advancement repair of posterior femoral cutaneous nerve nutrient vessel flap can be selected according to the range of skin and soft tissue defects. If the sinus tract of the wound is deep, the proper tissue flap can be selected to fill the sinus tract according to the size of sinus tract and range of the skin and soft tissue defects, and then the wound can be closed with individualized flap to obtain good repair effect.

Investigating a Causal Relationship Between Diabetes Mellitus and Oropharyngeal Cancer: A Mendelian Randomization Study.

OBJECTIVE: Previous observational studies reported an association of diabetes mellitus (DM) with oropharyngeal cancer (OPC), however, the potential causality of the association between them remains unclear. METHODS: To explore this causal relationship in individuals of European descent, a two-sample Mendelian randomization (MR) study was conducted. A genome-wide association study (GWAS) of DM was used to represent the exposure factor (T1DM: n = 24,840; T2DM: n = 215,654), and GWAS of OPC represented the outcome (n = 3,448). RESULTS: Forty-one single nucleotide polymorphisms (SNPs) related to T1DM and fifty-four SNPs related to T2DM were identified as effective instrumental variables (IVs) in the two-sample MR analyses. In IVW estimates, neither T1DM nor T2DM significantly contributed to an increased risk of OPC [T1DM: OR 1.0322 (95% CI 0.9718, 1.0963), P = 0.3033; T2DM: OR 0.9998 (95% CI 0.9995, 1.0002), P = 0.2858]. Four other regression models produced similar results. MR-Egger regression results [Cochran's Q statistic was 47.1544 (P = 0.1466) in T1DM, and 35.5084 (P = 0.9512) in T2DM] suggested no horizontal pleiotropy between IVs and outcomes. CONCLUSION: Our findings suggest little evidence to support the genetic role of diabetes mellitus in OPC development in the European population.