ABSTRACT
Objective: To explore the feasibility of constructing an objective tinnitus subtype model based on peripheral blood differentially expressed genes (DEGs) using a combination of Weighted Gene Co-expression Network Analysis (WGCNA) and Random Forest algorithm (RF). Methods: From October 2019 to June 2020, peripheral blood DEGs were obtained from 37 patients (from the Third Affiliated Hospital of Sun Yat-sen University)with chronic subjective high-frequency tinnitus (21 unbothersome type, 16 bothersome type) and 20 healthy volunteers through high-throughput sequencing. WGCNA was used to construct gene modules with different expression patterns and analyze their relationships with tinnitus characteristics. Subsequently, RF was employed to build subtype models, which were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, and F1-score. Results: A total of 12 351 intergroup DEGs were divided into 9 gene modules. Among them, MEblue, MEgreen, and MEbrown showed significant negative correlations with the healthy volunteer group, while MEpink showed a significant positive correlation with the tinnitus distress group. The "Tinnitus vs. Normal" and "Compensatory vs. Decompensatory" subtype models, based on MEblue and MEpink respectively, both had AUCs greater than 0.80, accuracies above 90%, and F1-scores above 0.90, indicating good performance. Conclusions: Peripheral blood DEGs are potential biological indicators for objective classification of subjective tinnitus. The combined application of WGCNA and the Random Forest algorithm should be a viable approach to constructing an objective tinnitus subtype model. However, further exploration and refinement are needed to validate the model's generalizability, cross-dataset performance, and algorithm optimization.
Subject(s)
Algorithms , Tinnitus , Humans , Tinnitus/genetics , Feasibility Studies , Gene Expression Profiling/methods , Gene Regulatory Networks , ROC Curve , Transcriptome , High-Throughput Nucleotide Sequencing/methodsABSTRACT
Objective: To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30+TLPD). Methods: Eight cases of pmCD30+TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results: There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed "kidney-shaped", "embryonic" and "horseshoe-shaped" cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia. Conclusions: pmCD30+TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30+TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.
Subject(s)
Ki-1 Antigen , Lymphoproliferative Disorders , Humans , Male , Female , Aged , Adult , Lymphoproliferative Disorders/pathology , Lymphoproliferative Disorders/metabolism , Ki-1 Antigen/metabolism , Middle Aged , Retrospective Studies , Diagnosis, Differential , T-Lymphocytes/pathology , T-Lymphocytes/immunology , Mouth Mucosa/pathology , Reed-Sternberg Cells/pathology , Reed-Sternberg Cells/metabolism , Epstein-Barr Virus Infections , Immunophenotyping , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/geneticsABSTRACT
Objective: To investigate the clinicopathological and genetic features of confined placental mosaicism (CPM) and its effect on fetal intrauterine growth. Methods: Fourteen CPM cases of Haidian Maternal and Children Health Hospital were collected from May 2018 to March 2022. Clinicopathological examination on placental specimens and molecular genetic analysis were performed. Results: The age of the parturient women ranged from 27 to 34 years, with an average age of (30.0±3.54) years. The gestational weeks ranged from 35+1 to 41+2 weeks. There were 4 premature births and 10 term births, among which 6 were female and 8 were male fetuses. Nine cases (9/14) had adverse pregnancy outcomes, including 7 cases of fetal growth restriction. The weight of CPM placenta decreased, with 6 cases below the 10th percentile of weight standards and 5 cases between the 10th and 25th percentile. All 14 CPM placental specimens showed morphological changes of perfusion dysfunction to varying degrees, with mainly placental-maternal vascular malperfusion followed by placental-fetal vascular malperfusion. The mosaic chromosomes in different CPM cases varied, with 16-trisomy/monosomy mosaicism being the most common followed by 7-trisomy and 21-trisomy/monosomy mosaicism. The mosaic proportion was unequal in different parts of the same CPM placenta, with the mosaic proportion of umbilical cord, fetal membranes, fetal surface, maternal surface, and edge ranging from 1% to 70%. Conclusions: The mosaic chromosomes in different CPM cases vary, and the mosaic proportion is unequal in different parts of the same CPM placenta. The pathological morphology is mainly manifested as perfusion dysfunction, which can lead to adverse pregnancy outcomes such as fetal growth restriction and preterm birth.
Subject(s)
Fetal Growth Retardation , Mosaicism , Placenta , Humans , Pregnancy , Female , Adult , Placenta/pathology , Fetal Growth Retardation/genetics , Fetal Growth Retardation/pathology , Pregnancy Outcome , Male , Placenta Diseases/pathology , Placenta Diseases/genetics , Trisomy/genetics , Infant, Newborn , Gestational AgeABSTRACT
OBJECTIVES: Tests of physical function are often thought to measure functioning that is (1) musculoskeletal, and (2) newly declining in adult life. In contrast, this study aimed to: (1) add to evidence that physical-function tests also measure brain function, and (2) test the novel hypothesis that adult physical function is associated with brain function beginning in early childhood. We investigated early childhood brain function and midlife physical function in the Dunedin Study, a 5-decade longitudinal birth cohort (nâ =â 1,037). METHODS: Brain function was measured at age 3 using 5 measures which formed a reliable composite (neurological examination, cognitive and motor tests, and temperament ratings). Physical function was measured at age 45 using 5 measures which formed a reliable composite (gait speed, step-in-place, chair stands, balance, and grip strength). RESULTS: Children with worse age-3 brain function had worse midlife physical function as measured by the age-45 composite, even after controlling for childhood socioeconomic status (ß: 0.23; 95% CI: 0.16 to 0.30; pâ <â .001). Worse age-3 brain function significantly predicted slower gait speed, fewer steps-in-place and chair-stands, worse balance, and weaker grip strength. DISCUSSION: Children with poorer brain function were more likely to have poorer physical-function scores as adults. In addition to indicating recent musculoskeletal decline, physical-function tests may also provide indications of lifelong, integrated brain-body health. By reconceptualizing the meaning of physical-function scores, clinicians can orient the use of physical-function tests in a more holistic approach to health care.
Subject(s)
Brain , Humans , Male , Female , Child, Preschool , Middle Aged , Longitudinal Studies , Brain/physiology , Physical Functional Performance , Adult , Hand Strength/physiology , Child Development/physiology , Cohort Studies , Postural Balance/physiology , Walking Speed/physiologyABSTRACT
OBJECTIVE: To investigate adherence to intravascular catheter (IVC) insertion and maintenance guidelines in Chinese tertiary hospitals. METHODS: A cross-sectional questionnaire survey of adult inpatients with IVC placements was conducted from July to September 2022 in 20 tertiary hospitals in China. One clinical staff member from each department in each hospital was assigned to participate in the survey. Questionnaires were uniformly collected and reviewed after three months. RESULTS: This study included 1815 cases (62.69%) of central venous catheter, 471 cases (16.27%) of peripherally inserted central catheter, 461 cases (15.92%) of PORT, and 147 cases (5.08%) of haemodialysis catheter insertions. Statistically significant differences in compliance were observed across the four IVC types, specifically in relation to the insertion checklist, standard operating procedure, and insertion environment (P<0.05). Practice adherence during IVC maintenance differed significantly across the four IVC types in aspects such as availability of IVC maintenance verification forms, daily scrubbing of the catheterized patients, and catheter connection methods (P<0.05). A total of 386 (13.34%) patients developed fever, 1086 (37.53%) were treated with therapeutic antibiotics, 16 (0.55%) developed central-line-associated bloodstream infections, two (0.07%) developed local skin infections, and six (0.21%) developed deep vein thrombosis. CONCLUSIONS: Adherence to guidelines regarding insertion and maintenance differed across the four IVC types; there is a gap between the recommended measures and the actual operation of the guidelines. Therefore, it is necessary to further enhance training and develop checklists to prevent central-line-associated bloodstream infections.
Subject(s)
Catheter-Related Infections , Guideline Adherence , Tertiary Care Centers , Humans , Guideline Adherence/statistics & numerical data , Cross-Sectional Studies , Catheter-Related Infections/prevention & control , Catheter-Related Infections/epidemiology , China/epidemiology , Male , Middle Aged , Female , Surveys and Questionnaires , Adult , Aged , Catheterization, Central Venous/adverse effects , Sepsis/etiology , Sepsis/prevention & control , Central Venous Catheters/adverse effects , Aged, 80 and over , Young AdultABSTRACT
AIM: Radiomics involves the extraction of quantitative data from medical images to facilitate the diagnosis, prognosis, and staging of tumors. This study provides a comprehensive overview of the efficacy of radiomics in prognostic applications for head and neck cancer (HNC) in recent years. It undertakes a systematic review of prognostic models specific to HNC and conducts a meta-analysis to evaluate their predictive performance. MATERIALS AND METHODS: This study adhered rigorously to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for literature searches. The literature databases, including PubMed, Embase, Cochrane, and Scopus were systematically searched individually. The methodological quality of the incorporated studies underwent assessment utilizing the radiomics quality score (RQS) tool. A random-effects meta-analysis employing the Harrell concordance index (C-index) was conducted to evaluate the performance of all radiomics models. RESULTS: Among the 388 studies retrieved, 24 studies encompassing a total of 6,978 cases were incorporated into the systematic review. Furthermore, eight studies, focusing on overall survival as an endpoint, were included in the meta-analysis. The meta-analysis revealed that the estimated random effect of the C-index for all studies utilizing radiomics alone was 0.77 (0.71-0.82), with a substantial degree of heterogeneity indicated by an I2 of 80.17%. CONCLUSIONS: Based on this review, prognostic modeling utilizing radiomics has demonstrated enhanced efficacy for head and neck cancers; however, there remains room for improvement in this approach. In the future, advancements are warranted in the integration of clinical parameters and multimodal features, balancing multicenter data, as well as in feature screening and model construction within this field.
ABSTRACT
The kagome metal CsV[Formula: see text]Sb[Formula: see text] is an ideal platform to study the interplay between topology and electron correlation. To understand the fermiology of CsV[Formula: see text]Sb[Formula: see text], intensive quantum oscillation (QO) studies at ambient pressure have been conducted. However, due to the Fermi surface reconstruction by the complicated charge density wave (CDW) order, the QO spectrum is exceedingly complex, hindering a complete understanding of the fermiology. Here, we directly map the Fermi surface of the pristine CsV[Formula: see text]Sb[Formula: see text] by measuring Shubnikov-de Haas QOs up to 29 T under pressure, where the CDW order is completely suppressed. The QO spectrum of the pristine CsV[Formula: see text]Sb[Formula: see text] is significantly simpler than the one in the CDW phase, and the detected oscillation frequencies agree well with our density functional theory calculations. In particular, a frequency as large as 8,200 T is detected. Pressure-dependent QO studies further reveal a weak but noticeable enhancement of the quasiparticle effective masses on approaching the critical pressure where the CDW order disappears, hinting at the presence of quantum fluctuations. Our high-pressure QO results reveal the large, unreconstructed Fermi surface of CsV[Formula: see text]Sb[Formula: see text], paving the way to understanding the parent state of this intriguing metal in which the electrons can be organized into different ordered states.
ABSTRACT
Programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, expressed on a variety of immune cells, play multiple regulatory roles in the host immune response to Mycobacterium tuberculosis infection. In this study, we reviewed that the regulatory roles of PD-1/PD-L1, PD-L2 signaling in the host adaptive immune response, such as the innate response of macrophages, and the interaction between T cells and macrophages in response to MTB. In addition, during MTB infection, PD-1/PD-L1, PD-L2 signaling is also involved in the host inflammatory response, as well as the potential roles of PD-1/PD-L1, PD-L2 in the diagnosis and treatment of tuberculosis.
Subject(s)
B7-H1 Antigen , Macrophages , Mycobacterium tuberculosis , Programmed Cell Death 1 Ligand 2 Protein , Programmed Cell Death 1 Receptor , Signal Transduction , Tuberculosis , Humans , Tuberculosis/immunology , Tuberculosis/microbiology , B7-H1 Antigen/metabolism , B7-H1 Antigen/immunology , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Ligand 2 Protein/metabolism , Mycobacterium tuberculosis/immunology , Macrophages/immunology , Macrophages/metabolism , Immunity, Innate , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , Adaptive ImmunityABSTRACT
OBJECTIVE: To explore the effect of intestinal nitrates on the growth of Klebsiella pneumoniae and its regulatory mechanisms. METHODS: K. pneumoniae strains with nitrate reductase narG and narZ single or double gene knockout or with NarXL gene knockout were constructed and observed for both aerobic and anaerobic growth in the presence of KNO3 using an automated bacterial growth analyzer and a spectrophotometer, respectively. The mRNA expressions of narG and narZ in K. pneumoniae in anaerobic cultures in the presence of KNO3 and the effect of the binary regulatory system NarXL on their expresisons were detected using qRT-PCR. Electrophoretic mobility shift assays (EMSA) and MST analysis were performed to explore the specific regulatory mechanisms of NarXL in sensing and utilizing nitrates. Competitive experiments were conducted to examine anaerobic growth advantages of narG and narZ gene knockout strains of K. pneumoniae in the presence of KNO3. RESULTS: The presence of KNO3 in anaerobic conditions, but not in aerobic conditions, promoted bacterial growth more effectively in the wild-type K. pneumoniae strain than in the narXL gene knockout strain. In anaerobic conditions, the narXL gene knockout strain showed significantly lowered mRNA expressions of narG and narZ (P < 0.0001). EMSA and MST experiments demonstrated that the NarXL regulator could directly bind to narG and narZ promoter regions. The wild-type K. pneumoniae strain in anaerobic cultures showed significantly increased expressions of narG and narZ mRNAs in the presence of KNO3 (P < 0.01), and narG gene knockout resulted in significantly attenuated anaerobic growth and competitive growth abilities of K. pneumoniae in the presence of KNO3 (P < 0.01). CONCLUSION: The binary regulatory system NarXL of K. pneumoniae can sense changes in intestinal nitrate concentration and directly regulate the expression of nitrate reductase genes narG and narZ to promote bacterial growth.
Subject(s)
Klebsiella pneumoniae , Nitrate Reductase , Nitrates , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/metabolism , Klebsiella pneumoniae/drug effects , Nitrates/metabolism , Nitrates/pharmacology , Nitrate Reductase/metabolism , Nitrate Reductase/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Intestines/microbiology , Gene Expression Regulation, Bacterial , Anaerobiosis , Gene Knockout TechniquesABSTRACT
We conducted a meta-analysis to determine the risk of infection following shoulder arthroscopy and to identify risk factors for infection. We systematically searched the PubMed/Medline, Embase and Cochrane Library databases, as well as the reference lists of previous systematic reviews and meta-analyses; manual searches were also performed. A random-effects model was employed to estimate pooled odds ratios (ORs), based on sample size, the P-value of Egger's test and heterogeneity among studies. Of the 29,342 articles screened, 16 retrospective studies comprising 74,759 patients were included. High-quality evidence showed that patients with diabetes (OR, 1.30; 95% confidence interval (CI), 1.20-1.41) or hypertension (OR, 1.26; 95% CI, 1.10-1.44) had a higher risk of infection, while moderate quality evidence showed that patients with obesity (body mass index ≥30 kg/m2) (OR, 1.42; 95% CI, 1.28-1.57), those who were male (OR, 1.65; 95% CI, 1.12-2.44), those who had an American Society of Anesthesiologists (ASA) class ≥3 (OR, 2.02; 95% CI, 1.02-3.99) and those who had a history of smoking (OR, 2.44; 95% CI, 1.39-4.28) had a higher risk of infection. The meta-analysis revealed that there was no association between age, time of surgery, or alcohol consumption and infection. This meta-analysis identified six significant risk factors for infection following shoulder arthroscopy including diabetes, obesity, hypertension, male sex, ASA class, history of smoking. These patient-related risk factors may help identify postoperative patients at higher risk for infection following shoulder arthroscopy.
Subject(s)
Arthroscopy , Humans , Arthroscopy/adverse effects , Risk Factors , Shoulder/surgery , Male , Female , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Middle Aged , AdultABSTRACT
Objective: To investigate the correlation between hematocrit (HCT) and cardiovascular events in peritoneal dialysis (PD) patients. Methods: Patients undergoing maintenance PD in the PD center of Guizhou Provincial People's Hospital from March 19, 2012 to July 9, 2020 were included. Demographic, baseline clinical and laboratory data of the patients were collected and patients were followed up until April 8, 2022. The primary endpoint was the first occurrence of a cardiovascular event. According to the tertiles of baseline HCT, the patients were divided into group Q1 (HCT≤26.6%), group Q2 (HCT>26.6%-32.4%), and group Q3 (HCT>32.4%). Laboratory indexes and cardiovascular events were compared among the three groups. Kaplan-Meier survival curve, Cox regression analysis and sensitivity analysis were used to analyze the effect of HCT on cardiovascular outcomes. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of HCT for cardiovascular events in PD patients. Results: A total of 860 PD patients were included, including 494 males (57.4%) and 366 females (42.6%), with a mean age of (41.5±15.0) years. There were 287 cases in group Q1, 289 cases in group Q2, and 284 cases in group Q3, respectively. A total of 265 (30.8%) patients experienced first cardiovascular events during the follow-up period. The incidence of cardiovascular events in groups Q1, Q2 and Q3 was 36.2% (104/287), 34.3% (99/289), and 21.8% (62/284), respectively, with a statistically significant difference (P<0.001). The incidence of cardiovascular events decreased with the increase of HCT. Multivariate Cox proportional hazards regression model analysis showed that decreased HCT was a risk factor for cardiovascular events. Compared with group Q3, the risk of cardiovascular events in group Q1 increased by 50.7% (group Q2: HR=1.444, 95%CI: 1.029-2.028, P=0.034; group Q1: HR=1.570, 95%CI: 1.096-2.250, P=0.014). In the sensitivity analysis, using kidney transplantation as the competition event, the risk of cardiovascular events was lower in group Q3 than that in group Q1 (subdistributional HR=1.413, 95%CI: 1.006-1.990, P=0.046). Kaplan-Meier survival curve showed that compared with the other two groups, the cardiovascular events-free survival rate of patients in group Q1 was significantly lower (log-rank χ2=9.722, P=0.008). ROC analysis showed that the area under the curve (AUC) of HCT for predicting cardiovascular events in PD patients was 0.583 (95%CI: 0.542-0.623, P<0.001), with the sensitivity of 40.6% and the specificity of 75.1%. Conclusion: Low-level HCT is associated with an increased risk of the first cardiovascular event in PD patients.
Subject(s)
Cardiovascular Diseases , Peritoneal Dialysis , Humans , Male , Female , Retrospective Studies , Cardiovascular Diseases/etiology , Adult , Middle Aged , Hematocrit , Risk Factors , Proportional Hazards ModelsABSTRACT
Primary membranous nephropathy (PMN) is one of the most frequent pathological subtypes of nephrotic syndrome in adults. The use of genome-wide association study (GWAS) technology has propelled the transition from conventional medicine to precision medicine, offering a fresh perspective for comprehending the pathogenesis of PMN and individual variations in greater detail. Furthermore, GWAS will aid in clinical translation, laying a firm foundation for the precise diagnosis and treatment of PMN.
Subject(s)
Genome-Wide Association Study , Glomerulonephritis, Membranous , Glomerulonephritis, Membranous/genetics , Humans , Nephrotic Syndrome/geneticsABSTRACT
Tuberculosis, caused by infection with Mycobacterium tuberculosis (MTB), remains a global public health challenge. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains make tuberculosis more difficult to control. New tools to study the biology of MTB can identify novel targets for drug discovery. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) combined with next-generation sequencing has provided many novel insights into the physiology and genetics of MTB. This review summarizes the application and optimization of CRISPRi in MTB biology.
Subject(s)
Extensively Drug-Resistant Tuberculosis , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Mycobacterium tuberculosis/genetics , Antitubercular Agents/therapeutic use , Clustered Regularly Interspaced Short Palindromic Repeats , Tuberculosis, Multidrug-Resistant/drug therapy , Extensively Drug-Resistant Tuberculosis/drug therapy , Biology , Microbial Sensitivity TestsABSTRACT
OBJECTIVE: To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. METHODS: Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson's trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. RESULTS: Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson's trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/µm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/µm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). CONCLUSIONS: E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.
Subject(s)
Echinococcosis , Endothelial Cells , Mice , Animals , Endothelial Cells/metabolism , Endothelial Cells/pathology , Mice, Inbred C57BL , Liver/pathology , Liver Cirrhosis/pathology , Echinococcosis/pathology , RNA, Messenger/metabolism , Collagen/adverse effects , Collagen/metabolismABSTRACT
Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.
Subject(s)
Gastrectomy , Neoadjuvant Therapy , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/therapy , Female , Middle Aged , Retrospective Studies , Prognosis , Aged , Adult , Survival Rate , Lymph Node Excision , Disease-Free Survival , Risk Factors , Treatment Outcome , Chemotherapy, Adjuvant , Propensity Score , Kaplan-Meier Estimate , Proportional Hazards ModelsABSTRACT
The article "MiR-221 inhibits proliferation of pancreatic cancer cells via down regulation of SOCS3", by J. Xie, J.-T. Wen, X.-J. Xue, K.-P. Zhang, X.-Z. Wang, H.-H. Cheng, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 1914-1921-DOI: 10.26355/eurrev_201804_14714-PMID: 29687843 has been retracted by the Editor in Chief for misconduct and data fabrication. An investigation conducted by the National Health Commission of the People's Republic of China, determined that the information and images presented in the paper have been manipulated, pieced together, and subjected to various fraudulent alterations. Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the articles. The corresponding authors did not respond to journal correspondence about the investigation and retraction of this article. This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14714.
Subject(s)
Audiology , Hearing Aids , United States , Humans , Infant, Newborn , Cytomegalovirus , Academies and Institutes , Risk AssessmentABSTRACT
With the increasing life expectancy and lifestyle changes of patients with chronic hepatitis B (CHB), the significance of comorbidities of chronic non-communicable diseases (NCDs) in disease progression and health prognosis of CHB patients is gaining prominence. This study aims to explore the association between CHB and NCDs comorbidities, focusing on the impact of common metabolism-related diseases, such as metabolic syndrome and diabetes, on the health outcomes of CHB patients. We also summarize studies on integrating the management of comorbidities in CHB patients and provide relevant recommendations for effective management. The findings of this study serve as a foundation for understanding the clinical characteristics and prevalence trends, reducing the disease burden of comorbidities among CHB patients, and establishing a comprehensive and coordinated management system for comorbidities.
Subject(s)
Diabetes Mellitus , Hepatitis B, Chronic , Humans , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/therapy , Comorbidity , Diabetes Mellitus/epidemiology , Prognosis , Outcome Assessment, Health Care , Hepatitis B virusABSTRACT
BACKGROUND: H101, an innovative oncolytic adenovirus, has shown potential in modifying the tumor microenvironment from immunologically 'cold' to 'hot'. When combined with nivolumab, a programmed cell death protein 1 inhibitor, this synergy may offer substantial therapeutic benefits beyond the capabilities of each agent alone. PATIENTS AND METHODS: In this pilot study, we assessed the efficacy and safety of combining H101 with nivolumab in advanced hepatocellular carcinoma (HCC) patients who failed prior systemic therapy. The participants received initial oncolytic virus (OV) pretreatment with intratumoral H101 injections (5.0 × 1011 vp/0.5 ml/vial, two vials per lesion) on days 1 and 3. Combination therapy started on day 8, with H101 administered every 2 or 4 weeks and nivolumab (240 mg) injections every 2 weeks. Treatment continued up to 12 months or until disease progression, intolerable toxicity, consent withdrawal, or study conclusion. The primary endpoint was the objective response rate (ORR). RESULTS: Between March 2020 and March 2022, 18 of 21 screened patients were assessable, showing an ORR of 11.1% [two cases of partial response (PR) and five cases of stable disease], with extrahepatic injections often leading to favorable outcomes. The disease control rate stood at 38.9%, with a 6-month survival rate of 88.9%. Median progression-free survival was 2.69 months, and overall survival (OS) was 15.04 months. Common adverse events included low-grade fever (100%) and pain related to centesis (33.3%), and no grade 3/4 events were reported. Significantly, local H101 injection showed potential in reversing immune checkpoint inhibitor resistance, evidenced by over 2.5 years of extended OS in PR cases with low α-fetoprotein. Additionally, decreasing neutrophil-to-lymphocyte ratio during OV pretreatment may predict positive outcomes. CONCLUSIONS: This study demonstrates the potential efficacy of combining H101 with nivolumab in treating refractory advanced HCC, with well-tolerated toxicities.