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1.
Article in English | MEDLINE | ID: mdl-38929022

ABSTRACT

OBJECTIVE: To determine whether maternal Adverse Childhood Experiences (ACEs) are (a) associated with increased inflammatory gene expression in mother-child dyads and (b) whether a parenting intervention (ATTACH™) moderates the association between maternal ACEs and mother and/or child inflammatory gene expression. METHODS: Twenty mother-child dyads, recruited from a domestic violence shelter in Calgary, AB, Canada, were randomized into an ATTACH™ parenting intervention group (n = 9) or a wait-list control group (n = 11). Maternal ACEs were assessed. The mothers and children each provided one non-fasting blood sample after the intervention group completed the ATTACH™ program, which was assayed to quantify the Conserved Transcriptional Response to Adversity (CTRA) score, indicating inflammatory gene expression profile. Mixed-effect linear models were used, separately in mothers and children, to examine the associations between CTRA score, maternal ACEs, and the ACEs-by-intervention group interaction term. The covariates were age, sex, ethnicity, and maternal medication use. RESULTS: Higher maternal ACEs were associated with higher child CTRA scores (b = 0.123 ± SE 0.044, p = 0.005), indicating an increased pro-inflammatory gene expression profile. The ATTACH™ parenting intervention moderated this association between maternal ACEs and child CTRA scores (b = 0.328 ± SE 0.133, p = 0.014). In mothers, the ACEs-by-intervention interaction terms were insignificant (p = 0.305). CONCLUSIONS: Maternal ACEs could exert an intergenerational impact on child inflammatory activity, and this association could be moderated by participating in the ATTACH™ parenting intervention.


Subject(s)
Adverse Childhood Experiences , Humans , Female , Male , Adult , Child , Parenting , Gene Expression , Mothers/psychology , Child, Preschool , Inflammation
2.
Ocul Surf ; 33: 64-73, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705236

ABSTRACT

PURPOSE: Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution. METHODS: Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids. RESULTS: Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) were statistically significant. Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs. CONCLUSION: In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. A consistent reduction was observed across all detected lipid analytes except for ꞷ-3 docosapentaenoic acid (DPA) and its special pro-resolving mediator (SPM) metabolites in aged mice, suggesting an increased risk for LG inflammation.


Subject(s)
Aging , Fatty Acids, Unsaturated , Lacrimal Apparatus , Mice, Inbred C57BL , Animals , Mice , Fatty Acids, Unsaturated/metabolism , Aging/metabolism , Lacrimal Apparatus/metabolism , Lipid Metabolism/physiology , Female , Lipidomics/methods
3.
J Gastrointest Surg ; 2024 May 12.
Article in English | MEDLINE | ID: mdl-38744374

ABSTRACT

BACKGROUND: The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment programs. METHODS: A total of 5606 patients with gastric cancer with comprehensive clinicopathologic data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be used for further analysis. Subsequently, univariate and multivariate logistic regression analyses were performed to identify the risk factors. RESULTS: The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6%, respectively. Female (odds ratio [OR], 1.559; P = .032), lower tumor location (OR, 1.773; P = .023), tumor size of >2 cm (OR, 2.007; P < .001), mixed (OR, 2.371; P = .001) and undifferentiated histologic types (OR, 2.952; P < .001), T1b stage (OR, 2.041; P < .001), presence of ulceration (OR, 1.758; P = .027), and lymphovascular invasion (OR, 5.722; P < .001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in patients with EGC. CONCLUSION: This study identified the clinicopathologic factors associated with LNM in patients with EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing patients with EGC.

4.
Invest Ophthalmol Vis Sci ; 65(5): 21, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38739085

ABSTRACT

Purpose: Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement. Methods: Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a blunt blade. Wound size and fluorescein staining were visualized and photographed at different time points, and a re-epithelialization rate curve was calculated. Results: There were 157 differentially expressed genes in aged mice compared with young mice. Several pathways downregulated with age control cell migration, proteoglycan synthesis, and collagen trimerization, assembly, biosynthesis, and degradation. Male mice had decreased corneal sensitivity compared with female mice at 12 and 24 months of age. Aged mice, irrespective of sex, had delayed corneal re-epithelialization in the first 48 hours and worse corneal fluorescein staining intensity at day 14 than young mice. Conclusions: Aged corneal epithelium has an altered transcriptome. Aged mice regardless of sex heal more slowly and displayed more signs of corneal epithelial defects after wounding than young mice. These results indicate that aging significantly alters the corneal epithelium and its ability to coordinate healing.


Subject(s)
Aging , Epithelium, Corneal , Mice, Inbred C57BL , Transcriptome , Wound Healing , Animals , Epithelium, Corneal/metabolism , Female , Mice , Wound Healing/genetics , Wound Healing/physiology , Male , Aging/physiology , Re-Epithelialization/physiology , Re-Epithelialization/genetics , Corneal Injuries/genetics , Corneal Injuries/metabolism , Debridement , Gene Expression Regulation/physiology , Disease Models, Animal
5.
World J Surg ; 48(1): 151-162, 2024 01.
Article in English | MEDLINE | ID: mdl-38686759

ABSTRACT

OBJECTS: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. METHODS: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. RESULTS: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. CONCLUSIONS: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.


Subject(s)
Lymphatic Metastasis , Neoplasm Staging , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Male , Female , Retrospective Studies , Risk Factors , Middle Aged , Lymphatic Metastasis/pathology , Aged , Gastrectomy , Adult
6.
Aging (Albany NY) ; 16(9): 7683-7703, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38683121

ABSTRACT

Ferroptosis, an iron-triggered modality of cellular death, has been reported to closely relate to human aging progression and aging-related diseases. However, the involvement of ferroptosis in the development and maintenance of senescent cells still remains elusive. Here, we established a doxorubicin-induced senescent HSkM cell model and found that both iron accumulation and lipid peroxidation increase in senescent cells. Moreover, such iron overload in senescent cells has changed the expression panel of the ferroptosis-response proteins. Interestingly, the iron accumulation and lipid peroxidation does not trigger ferroptosis-induced cell death. Oppositely, senescent cells manifest resistance to the ferroptosis inducers, compared to the proliferating cells. To further investigate the mechanism of ferroptosis-resistance for senescent cells, we traced the iron flux in cell and found iron arrested in lysosome. Moreover, disruption of lysosome functions by chloroquine and LLOMe dramatically triggered the senescent cell death. Besides, the ferroitinophagy-related proteins FTH1/FTL and NCOA4 knockdown also increases the senescent cell death. Thus, we speculated that iron retardation in lysosome of senescent cells is the key mechanism for ferroptosis resistance. And the lysosome is a promising target for senolytic drugs to selectively clear senescent cells and alleviate the aging related diseases.


Subject(s)
Cellular Senescence , Ferroptosis , Iron , Lysosomes , Ferroptosis/drug effects , Humans , Cellular Senescence/drug effects , Cellular Senescence/physiology , Lysosomes/metabolism , Lysosomes/drug effects , Iron/metabolism , Lipid Peroxidation/drug effects , Doxorubicin/pharmacology , Nuclear Receptor Coactivators/metabolism , Nuclear Receptor Coactivators/genetics , Cell Line , Chloroquine/pharmacology , Iron Overload/metabolism , Ferritins , Oxidoreductases
7.
bioRxiv ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38585971

ABSTRACT

Micropatterned human pluripotent stem cells (hPSCs) treated with BMP4 (2D gastruloids) are among the most widely used stem cell models for human gastrulation. Due to its simplicity and reproducibility, this system is ideal for high throughput quantitative studies of tissue patterning and has led to many insights into the mechanisms of mammalian gastrulation. However, 2D gastruloids have only been studied up to 48h. Here we extended this system to 96h. We discovered a phase of highly reproducible morphogenesis during which directed migration from the primitive streak-like region gives rise to a mesodermal layer beneath an epiblast-like layer. Multiple types of mesoderm arise with striking spatial organization including lateral mesoderm-like cells on the colony border and paraxial mesoderm-like further inside the colony. Single cell transcriptomics showed strong similarity of these cells to mesoderm in human and non-human primate embryos. However, our data suggest that the annotation of the reference human embryo may need to be revised. This illustrates that extended culture of 2D gastruloids provides a powerful model for human mesoderm differentiation and morphogenesis.

8.
J Laparoendosc Adv Surg Tech A ; 34(6): 512-519, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38531051

ABSTRACT

Background: Owing to the low incidence rate and nonspecific symptoms of acute mesenteric ischemia (AMI), the identification and prediction of irreversible transmural intestinal necrosis (ITIN) and extensive bowel resection (≥100 cm) (EBR) are difficult and critical. This study aimed to investigate the risk factors for ITIN and EBR in patients with AMI. Methods: The clinical data of 254 AMI patients were retrospectively analyzed. Furthermore, the incidence of ITIN and EBR were set as dependent variables, and relevant risk factors were screened using univariate and multivariate logistic regression analyses. The comparisons of surgical characteristics and postoperative recovery outcomes between the EBR and control group were also conducted. Results: The presence of hemorrhagic (odds ratio [OR] = 28.356, P < .001) or other types ascites (OR = 13.051, P = .003), peritonitis (OR = 8.463, P = .005), intestinal diameter >2.35 cm (OR = 5.493, P = .020), and serum creatinine (CREA) >95 µmol/L (OR = 4.866, P = .048) were identified as independent risk factors for ITIN in patients with AMI. In addition, serum C-reactive protein (CRP) >15 mg/L (OR = 38.023, P = .006), and CREA >100 µmol/L (OR = 6.248, P = .035) were proved to be independently associated with EBR for ITIN cases. Compared to the control group, EBR significantly increased the likelihood of requiring enterostomy (P = .001), blood transfusion (P = .002), and transfer to intensive care unit (P = .016), while also prolonging the recovery time for intestinal function (P = .014). Conclusions: The presence of ascites, peritonitis, intestinal diameter >2.35 cm, and serum CREA >95 µmol/L were independently correlated with ITIN for AMI cases, while serum CRP >15 mg/L and CREA >100 µmol/L independently increased the risk of EBR.


Subject(s)
Mesenteric Ischemia , Necrosis , Humans , Retrospective Studies , Mesenteric Ischemia/surgery , Male , Female , Middle Aged , Aged , Risk Factors , Hospitals, High-Volume , Acute Disease , Intestines/blood supply , Intestines/pathology
9.
Brain Behav ; 14(3): e3447, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38450944

ABSTRACT

BACKGROUND AND OBJECTIVE: Persistent headache attributed to ischemic stroke (PHPIS) is increasingly acknowledged and was added to the 2018 ICHD-3. Intravenous thrombolysis (IVT) is a common treatment for acute ischemic stroke. It remains unknown whether this treatment influences the occurrence of a persistent poststroke headache. We aimed to describe the incidence and clinical characteristics of persistent headaches occurring after acute ischemic stroke in patients with or without IVT and explore the risk factors. METHODS: A prospective observational study was performed between the 234 individuals who received IVT and 226 individuals without IVT in 5 stroke units from Wuhan, China. Subjects were followed for 6 months after stroke via a structured questionnaire. RESULTS: Age, gender, vascular risk factors, and infarct location/ circulation distribution did not differ between the groups, although IVT group had higher initial NIHSS scores. At the end of the follow-up, 12.0% (55/460) of subjects reported persistent headaches after ischemic stroke. The prevalence of persistent headache was significantly higher in the IVT group than non-IVT group (15.4% vs. 8.4%, p = .021). Patients with younger age (p = .033; OR 0.97; 95% CI 0.939-0.997), female sex (p = .007; OR 2.40; 95% CI 1.269-4.520), posterior circulation infarct (p = .024; OR 2.19; 95% CI 1.110-4.311), and IVT (p = .005; OR 2.51; 95% CI 1.313-4.782) were more likely to develop persistent headache after ischemic stroke. CONCLUSION: The potential influence of IVT should be considered when assessing persistent poststroke headache. Future studies will investigate the underlying mechanisms.


Subject(s)
Ischemic Stroke , Stroke , Female , Humans , Headache/epidemiology , Headache/etiology , Infarction , Ischemic Stroke/complications , Ischemic Stroke/drug therapy , Ischemic Stroke/epidemiology , Stroke/complications , Stroke/epidemiology , Thrombolytic Therapy/adverse effects , Male
10.
Brain Sci ; 14(3)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38539657

ABSTRACT

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood-brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood-brain barrier function.

11.
HardwareX ; 17: e00507, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38327677

ABSTRACT

The combination of Virtual Reality (VR) technology and Electroencephalography (EEG) measurements has shown tremendous potential in the fields of psychology and neuroscience research. However, the majority of EEG measurement devices currently available are expensive, bulky, uncomfortable to wear, and difficult to integrate with VR headsets. These limitations have hindered the development of related research fields. This study describes a low-cost (60.07 USD), small-sized, wireless, high-precision, low-power consumption 4-channel EEG measurement system (NeuroVista) for frontal area EEG measurements, which can be used with a VR headset, enabling EEG measurements in VR environments. The system has an input-referred noise of less than 0.9480 µVrms, a common mode rejection ratio of over 96 dB, a measurement resolution of less than 0.1 µV, a bandwidth of 0.5 âˆ¼ 45 Hz, and works at a sampling rate of 250 Hz. It also supports metal dry electrodes and includes a built-in analog bandpass filter, right-leg drive circuit, and built-in digital lowpass filter and notch filter, which can reduce noise during measurement. Researchers can reconstruct the electrode system to measure regions of interest according to their needs.

12.
World J Surg Oncol ; 22(1): 46, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38321480

ABSTRACT

BACKGROUND: The short-term (≤ 1 year) recurrence (STR) is the primary determinant impacting both the life quality and survival duration in patients who have undergone surgical resection for retroperitoneal liposarcoma (RPLS), a condition with intricate and ambiguous pathogenesis. The purpose of this study was to analyze the risk factors associated with STR in cases of RPLS and primary retroperitoneal liposarcoma (PRPLS). METHODS: For this retrospective observational study, a total of 296 RPLS cases were selected as research subjects, who experienced tumor recurrence during the follow-up period. The Local recurrence-free survival (LRFS) rates were estimated using the Kaplan-Meier method and subsequently compared between groups utilizing the log-rank test. The subsequent analyses involved univariate and multivariate logistic regression to identify predictors of STR in RPLS cases. Additionally, a logistic regression model was constructed for PRPLS. RESULTS: The 1-, 3-, and 5-year LRFS rates of the 296 RPLS cases were 51.7%, 16.9%, and 7.1%, respectively. In the univariate analysis, several factors were found to be associated with STR, including preoperative neutrophil/lymphocyte ratio (NLR), smoking history, surgical frequency, combined organ excision, operative time, intraoperative bleeding, transfer to the intensive care unit (ICU), multiple primary tumors, tumor shape and capsule characteristics, histological subtype, and presence of tumor necrosis. The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, and tumor necrosis were identified as independent risk factors for STR in surgically resected RPLS. Conversely, diabetes, intact tumor capsule, and well-differentiated histological subtype appeared to be independent protective factors. Analysis for PRPLS revealed that tumor capsule and tumor necrosis were independent predictors of STR. CONCLUSIONS: The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, tumor necrosis, and tumor capsule were expected to serve as predictive factors of STR for surgical resected RPLS and PRPLS.


Subject(s)
Liposarcoma , Neoplasms, Multiple Primary , Retroperitoneal Neoplasms , Humans , Neoplasm Recurrence, Local/pathology , Retroperitoneal Neoplasms/pathology , Liposarcoma/pathology , Retrospective Studies , Necrosis
13.
World J Surg Oncol ; 22(1): 53, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38355538

ABSTRACT

BACKGROUND: Relevant reports on the surgical resection and prognosis of recurrent presacral tumors are limited. The objective of this study was to explore the outcomes associated with surgical resection of recurrent presacral tumors. METHODS: The data of patients with recurrent presacral tumors who received surgical resection in our hospital between June 2009 and November 2018 were retrospectively analyzed. RESULTS: Thirty-one patients, comprising 22 females and 9 males, with recurrent presacral lesions were included in our study. A posterior approach was utilized in 27 patients, an anterior approach in 1 patient, and a combined approach in 3 patients. Intraoperative complications occurred in 13 patients (41.9%), while postoperative complications occurred in 6 patients (19.4%). The length of hospital stay was significantly shorter in patients who underwent the posterior approach compared to those who underwent the anterior and combined approaches (P = 0.002). The operative time for the posterior approach was significantly shorter compared to both the anterior and combined approaches (P = 0.006). Temporary tamponade was performed for hemostasis in 4 patients, while staged resection was performed in 2 patients during the surgical treatment process. After a median follow-up period of 115.5 months, 5 patients with recurrent malignant presacral tumors succumbed to tumor recurrence after reoperation in our hospital. CONCLUSIONS: Surgical resection remains the mainstream treatment for recurrent presacral tumors. The outcomes for recurrent benign presacral tumors after surgery demonstrate favorable results, whereas further enhancements are required to improve the outcomes for recurrent malignant presacral tumors after surgery.


Subject(s)
Rectal Neoplasms , Male , Female , Humans , Retrospective Studies , Reoperation , Prognosis , Rectal Neoplasms/surgery , Treatment Outcome
14.
J Neurochem ; 168(2): 83-99, 2024 02.
Article in English | MEDLINE | ID: mdl-38183677

ABSTRACT

In central nervous system (CNS), demyelination is a pathological process featured with a loss of myelin sheaths around axons, which is responsible for the diseases of multiple sclerosis, neuromyelitis optica, and so on. Transforming growth factor-beta1 (TGF-ß1) is a multifunctional cytokine participating in abundant physiological and pathological processes in CNS. However, the effects of TGF-ß1 on CNS demyelinating disease and its underlying mechanisms are controversial and not well understood. Herein, we evaluated the protective potential of TGF-ß1 in a rodent demyelinating model established by lysophosphatidylcholine (LPC) injection. It was identified that supplement of TGF-ß1 evidently rescued the cognitive deficit and motor dysfunction in LPC modeling mice assessed by novel object recognition and balance beam behavioral tests. Besides, quantified by luxol fast blue staining, immunofluorescence, and western blot, administration of TGF-ß1 was found to significantly ameliorate the demyelinating lesion and reactive astrogliosis by suppressing p38 MAPK pathway. Mechanistically, the results of in vitro experiments indicated that treatment of TGF-ß1 could directly promote the differentiation and migration of cultured oligodendrocytes. Our study revealed that modulating TGF-ß1 activity might serve as a promising and innovative therapeutic strategy in CNS demyelinating diseases.


Subject(s)
Brain Injuries , White Matter , Animals , Mice , Gliosis/prevention & control , Inflammation , p38 Mitogen-Activated Protein Kinases/metabolism , Rodentia , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism , White Matter/metabolism
15.
Int J Surg ; 110(2): 1000-1007, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38085808

ABSTRACT

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.


Subject(s)
Stomach Neoplasms , Humans , Cohort Studies , Gastrectomy/adverse effects , Neoadjuvant Therapy/adverse effects , Postoperative Complications/etiology , Propensity Score , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Treatment Outcome
16.
Am J Orthopsychiatry ; 94(1): 1-14, 2024.
Article in English | MEDLINE | ID: mdl-37796597

ABSTRACT

Group-based parent training (PT) is an evidence-based approach for strengthening parenting skills and reducing child behavior problems. However, there has been little research on the social connectedness (SC) formed among PT participants, particularly in low-income communities where parents may be more socially isolated. This study describes SC formed among parents in a group-based PT program implemented in their children's school and its association with changes in child behavior. Using a convergent mixed-methods design, data collection occurred between 2020 and 2022. Parents (n = 97) completed measures of their SC to other parents in their PT group and their child's behavior. Qualitative interviews with a representative subsample of parents (n = 17) were also conducted to understand parents' perceptions and experiences of SC within their PT group. Parents reported high levels of SC (M = 4.45 [range = 3.04-5 on scale of 1-5]; SD = 0.4). From baseline to postintervention, the number of children with child behavior problems significantly decreased (32.12%, 37.5% behavior intensity and problems, respectively). The magnitude of decline in child behavior problems was significantly related to parents' SC (b = -11.52, p = .02, SE = 4.99). Qualitative data confirmed high levels of SC, which parents linked to improvements in their parenting and children's behavior. Themes focused on the building of connections, committing to a safe space with parents who share similar goals, supporting one another, and gaining connections within the school environment and during the COVID-19 pandemic. Results highlight the potential synergistic effects of SC formed in the context of group-based PT with implications for strengthening parenting skills and children's well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Parenting , Problem Behavior , Child , Humans , Pandemics , Parents , Poverty , Parent-Child Relations
17.
Molecules ; 28(19)2023 Sep 24.
Article in English | MEDLINE | ID: mdl-37836632

ABSTRACT

Iodine is a well-known oxidant that is widely used in organic syntheses. Thiol oxidation by stoichiometric iodine is one of the most commonly employed strategies for the synthesis of valuable disulfides. While recent advancements in catalytic aerobic oxidation conditions have eliminated the need for stoichiometric oxidants, concerns persist regarding the use of toxic or expensive catalysts. In this study, we discovered that iodine can be used as a cheap, low-toxicity catalyst in the aerobic oxidation of thiols. In the catalytic cycle, iodine can be regenerated via HI oxidation by O2 at 70 °C in EtOAc. This protocol harnesses sustainable oxygen as the terminal oxidant, enabling the conversion of primary and secondary thiols with remarkable efficiency. Notably, all 26 tested thiols, encompassing various sensitive functional groups, were successfully converted into their corresponding disulfides with yields ranging from >66% to 98% at a catalyst loading of 5 mol%.

18.
J Laparoendosc Adv Surg Tech A ; 33(12): 1154-1161, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37844093

ABSTRACT

Background: Postoperative gastrointestinal fistula (PGF) is one of the main causes of abdominal infection and perioperative death. This study was designed to investigate the risk factors of PGF, anastomotic fistula (AF), and duodenal stump fistula (DSF) for patients who underwent radical distal gastrectomy. Materials and Methods: In this retrospective observational study, 2652 gastric cancer cases who received radical distal gastrectomy from 2010 to 2020 were selected as research subjects. Subsequently, we adopted the univariate and multivariate logistic regression analysis as statistical method to screen the risk factors for PGF, AF, and DSF, respectively. Results: In univariate analysis, gender (P = .022), operative time (P = .013), intraoperative blood loss (P < .001), tumor diameter (P = .002), and tumor stage (P < .001) were related to PGF. Multivariate logistic regression analysis identified the male (odds ratio [OR] = 2.691, P = .042), massive intraoperative hemorrhage (OR = 1.002, P = .008), and advanced tumor (OR = 2.522, P = .019) as independent predictors for PGF. Moreover, diabetes (OR = 4.497, P = .008) and massive intraoperative hemorrhage (OR = 1.003, P = .010) were proved to be associated with AF, while massive intraoperative hemorrhage (OR = 1.001, P = .050) and advanced tumor (OR = 6.485, P = .005) were independent risk factors of DSF. Conclusions: The gender, intraoperative hemorrhage, tumor stage, and diabetes were expected to be used as predictors of PGF for radical distal gastrectomy.


Subject(s)
Diabetes Mellitus , Fistula , Stomach Neoplasms , Humans , Male , Case-Control Studies , Hospitals, High-Volume , Retrospective Studies , Stomach Neoplasms/pathology , Gastrectomy/adverse effects , Gastrectomy/methods , Blood Loss, Surgical , Diabetes Mellitus/etiology , Fistula/surgery , Postoperative Complications/etiology
19.
Surg Laparosc Endosc Percutan Tech ; 33(5): 515-521, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37678237

ABSTRACT

OBJECTIVE: To evaluate the short-term effects of Billroth I (B-I), Billroth Ⅱ (B-Ⅱ), Billroth Ⅱ+Braun (B-B), and Roux-en-Y (R-Y) reconstruction procedures in radical distal gastrectomy using propensity score matching (PSM). MATERIALS AND METHODS: The clinical data of 1994 patients who underwent radical distal gastrectomy in the past 10 years were retrospectively analyzed. Subsequently, PSM analyses were performed 3 times on the 4 reconstruction procedures, and the matching capacity was set to 0.01. Data regarding control variables and outcome indicators obtained using PSM were compared and analyzed. RESULTS: Compared with the other reconstruction procedures, patients in the B-I group had shorter operation time ( P =0.002), fewer abdominal drainage tubes ( P <0.001), and a lower risk of postoperative gastroparesis ( P =0.001) and gastrointestinal bleeding ( P =0.034), but tended to experience a longer postoperative indwelling time of bladder catheter ( P <0.001), gastrointestinal decompression ( P <0.001), fasting ( P =0.001), and hospital stays ( P =0.005). The B-B group tended to have fewer applications of the abdominal drainage tube ( P =0.014), a lower risk of postoperative gastrointestinal fistula ( P =0.040), shorter postoperative time of gastrointestinal decompression ( P =0.043), fasting ( P <0.001), and a shorter hospital stay ( P <0.001) than the R-Y group. Furthermore, the B-B group had a shorter postoperative time for gastrointestinal decompression ( P =0.014) and fasting ( P <0.001) than the B-Ⅱ group. CONCLUSION: Billroth I reconstruction has the advantages of simple operation, short operative time, and few early complications, but tends to result in a long recovery time during postoperative hospitalization. The B-B operation is associated with faster postoperative recovery than the R-Y or B-Ⅱ operation.

20.
Ocul Surf ; 30: 119-128, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37634571

ABSTRACT

Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1ß, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), IFN-γ, IL-12p40, IL-17, and IL-10 proteins in tears of aged mice. Moreover, genetic loss of the Tnf-/- in mice decreased goblet cell loss and the development of ectopic lymphoid structures in the lacrimal gland compared to wild-type mice. This was accompanied by a decrease in cytokine production. Treatment of mice at an early stage of aging (12-14-month-old) with TNF inhibitor tanfanercept eye drops for eight consecutive weeks decreased cytokine levels in tears, improved goblet cell density, and decreased the marginal zone B cell frequency in the lacrimal gland compared to vehicle-treated animals. Our studies indicate that modulation of TNF during aging could be a novel strategy for age-related dry eye disease.


Subject(s)
Dry Eye Syndromes , Lacrimal Apparatus , Animals , Mice , Cytokines/metabolism , Dry Eye Syndromes/metabolism , Lacrimal Apparatus/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/therapeutic use , Tears/metabolism , Inflammation/metabolism , Disease Models, Animal
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