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1.
Neurol Ther ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093538

ABSTRACT

INTRODUCTION: There remains a critical need for precise localization of the epileptogenic foci in individuals with drug-resistant epilepsy (DRE). 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) imaging can reveal hypometabolic regions during the interval between seizures in patients with epilepsy. However, visual-based qualitative analysis is time-consuming and strongly influenced by physician experience. CortexID Suite is a quantitative analysis software that helps to evaluate PET imaging of the human brain. Therefore, we aimed to evaluate the efficacy of CortexID quantitative analysis in the localization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). METHODS: A total of 102 patients with epilepsy who underwent 18F-FDG-PET examinations were included in this retrospective study. The PET visual analysis was interpreted by two nuclear medicine physicians, and the quantitative analysis was performed automatically using CortexID analysis software. The assumed epileptogenic zone was evaluated comprehensively by two skilled neurologists in the preoperative assessment of epilepsy. The accuracy of epileptogenic zone localization in PET visual analysis was compared with that in CortexID quantitative analysis. RESULTS: The diagnostic threshold for the difference in the metabolic Z-score between the right and left sides of medial temporal lobe epilepsy (MTLE) was calculated as 0.87, and that for lateral temporal lobe epilepsy (LTLE) was 2.175. In patients with MTLE, the area under the curve (AUC) was 0.922 for PET visual analysis, 0.853 for CortexID quantitative analysis, and 0.971 for the combined diagnosis. In patients with LTLE, the AUC was 0.842 for PET visual analysis, 0.831 for CortexID quantitative analysis, and 0.897 for the combined diagnosis. These results indicate that the diagnostic efficacy of CortexID quantitative analysis is not inferior to PET visual analysis (p > 0.05), while combined analysis significantly increases diagnostic efficacy (p < 0.05). Among the 23 patients who underwent surgery, the sensitivity and specificity of PET visual analysis for localization were 95.4% and 66.7%, and the sensitivity and specificity of CortexID quantitative analysis were 100% and 50%. CONCLUSION: The diagnostic efficacy of CortexID quantitative analysis is comparable to PET visual analysis in the localization of the epileptogenic zone in patients with TLE. CortexID quantitative analysis combined with visual analysis can further improve the accuracy of epileptogenic zone localization.

2.
Kidney Med ; 6(8): 100850, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39131916

ABSTRACT

Rationale & Objective: Matrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort. Study Design: In a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N = 3,827), MMP-2 was measured at baseline. In a case-cohort design, MMP-2 was additionally measured at year 2 in a randomly selected subcohort and cases of estimated glomerular filtration rate (eGFR) halving or kidney replacement therapy (KRT) (N = 1,439). Setting & Participants: CRIC is a multicenter prospective cohort of adults with CKD. Exposure: MMP-2 measured in plasma at baseline and at year 2. Outcomes: A composite kidney endpoint (KRT/eGFR halving). Analytical Approach: Weighted Cox proportional hazards models for case-cohort participants. Results: Participants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300 ng/mL at both baseline and year 2) increased the hazard of the composite kidney endpoint (HR, 1.61; 95% CI, 1.07-2.42; P = 0.09) after adjusting for covariates. The relationship of persistently elevated MMP-2 was modified by levels of inflammation, with a 2.6 times higher rate of the composite kidney endpoint in those with high-sensitivity C-reactive protein < 2.5 g/dL at study entry. Heterogeneity of effect was found with proteinuria, with a baseline MMP-2 level of ≥300 ng/mL associated with an increased risk of the composite kidney endpoint (HR, 1.30; 95% CI, 1.09-1.54) only with proteinuria ≥ 442 mg/g. Limitations: The observational study design limits causal interpretation. Conclusions: Elevated MMP-2 is associated with CKD progression, particularly among those with low inflammation and those with proteinuria. Future investigations are warranted to confirm the reduction in risk of CKD progression among these subgroups of patients with CKD.


Matrix metalloproteinase 2 (MMP-2) is a matrix-degrading protease involved in fibrosis and elevated in chronic kidney disease (CKD). Longitudinal patterns of MMP-2 have not previously been assessed as a predictor of CKD progression in a large prospective cohort. Here, we found that a higher baseline level and an increasing or persistently elevated 2-year pattern of MMP-2 were associated with CKD progression, independent of all covariates except proteinuria. The association of baseline MMP-2 with CKD progression differed by level of proteinuria, whereas levels of inflammation modified the associations of 2-year MMP-2 patterns with CKD progression.

3.
Neurosurg Rev ; 47(1): 421, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39134896

ABSTRACT

Shunt dependent hydrocephalus (SDHC) is a common sequel after aneurysmal subarachnoid hemorrhage (aSAH) and factors contributing to the development of SDHC remain obscure. The aim of this study was to identify predictors of SDHC following aSAH. We conducted a systematic review based on the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We searched electronic databases including Pubmed, Embase, and Cochrane databases from 1980 through August 2019 for studies on the risk factors of SDHC after aSAH. Inclusion criteria were: (1) SAH and hydrocephalus confirmed by CT or magnetic resonance imaging findings; (2) the odds ratios (ORs) or the relative risk (RR) with 95% confidence interval (95%CI; or crude data that allowed their calculation) were reported; and (3) languages were restricted to English and Chinese. Two independent authors collected the data including study design, characteristics of patients and potential risk factors. Random-effects models were used to estimate weighted mean differences (WMD), relative risks (RR) with corresponding 95% confidence intervals (CI). For analysis with significant heterogeneity, subgroup analyses stratified by study design and geographic area were performed. In all, 37 cohort studies met inclusion criteria. Several factors were associated with SDHC. Infection, acute hydrocephalus, placement of external ventricular drainage, older age, higher Hunt and Hess grade, intraventricular hemorrhage, rebleeding, and mechanical ventilation were associated with greater 2-fold increased risk of SDHC. Vasospasm, female gender, high Fisher grade, preexisting hypertension, aneurysm in posterior location and intracerebral hemorrhage were associated with less than 2-fold increased risk. Treatment modality and diabetes mellitus were not associated with SDHC. SDHC is a multi-factorial disease that is associated with patient and treatment factors. Acknowledgement of these potential factors could help prevent SDHC.


Subject(s)
Hydrocephalus , Observational Studies as Topic , Subarachnoid Hemorrhage , Subarachnoid Hemorrhage/complications , Humans , Hydrocephalus/surgery , Hydrocephalus/etiology , Risk Factors , Cerebrospinal Fluid Shunts/adverse effects , Cohort Studies
4.
Sci Rep ; 14(1): 18010, 2024 08 03.
Article in English | MEDLINE | ID: mdl-39097629

ABSTRACT

Prior research has identified associations between immune cells and aplastic anaemia (AA); however, the causal relationships between them have not been conclusively established. A two-sample Mendelian randomisation analysis was conducted to investigate the causal link between 731 immune cell signatures and AA risk using publicly available genetic data. Four types of immune signatures, including relative cell, absolute cell (AC), median fluorescence intensities and morphological parameters, were considered sensitivity analyses were also performed to verify the robustness of the results and assess potential issues such as heterogeneity and horizontal pleiotropy. Following multiple test adjustments using the False Discovery Rate (FDR) method, no statistically significant impact of any immunophenotype on AA was observed. However, twelve immunophenotypes exhibited a significant correlation with AA without FDR correction (p of IVW < 0.01), of which eight were harmful to AA: CD127- CD8br %T cell (Treg panel), CD25 on IgD + CD38dim (B cell panel), CD38 on naive-mature B cell (B cell panel), CD39 + resting Treg % CD4 Treg (Treg panel), CD39 + secreting Treg AC (Treg panel), CD8 on CD28 + CD45RA- CD8br (Treg panel), HLA DR + NK AC (TBNK panel), Naive DN (CD4-CD8-) AC (Maturation stages of T cell panel); and four were protective to AA: CD86 on CD62L + myeloid DC (cDC panel), DC AC (cDC panel), DN (CD4-CD8-) NKT %T cell (TBNK panel), and TD CD4 + AC (Maturation stages of T cell panel). The results of this study demonstrate a close link between immune cells and AA by genetic means, thereby improving the current understanding of the interaction between immune cells and AA risk and providing guidance for future clinical research.


Subject(s)
Anemia, Aplastic , Mendelian Randomization Analysis , Humans , Anemia, Aplastic/genetics , Anemia, Aplastic/immunology , Immunophenotyping , Genetic Predisposition to Disease , B-Lymphocytes/immunology , B-Lymphocytes/metabolism
5.
World J Diabetes ; 15(6): 1254-1262, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38983810

ABSTRACT

BACKGROUND: The FreeStyle Libre flash glucose monitoring (FGM) system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose. Due to its increased usage in clinics, the number of studies investigating its accuracy has increased. However, its accuracy has not been investigated in highland popu-lations in China. AIM: To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes (T2D) who had migrated within 3 mo from highlands to plains. METHODS: Overall, 68 patients with T2D, selected from those who had recently migrated from highlands to plains (within 3 mo), were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring (CGM) with the FreeStyle Libre FGM system for 14 d. Throughout the study period, fingertip capillary blood glucose was measured daily using the enzyme electrode method (Super GL, China), and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals. Moreover, the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to < 5 min. The accuracy of the FGM system was evaluated according to the CGM guidelines. Subsequently, the factors influencing the mean absolute relative difference (MARD) of this system were analyzed by a multiple linear regression method. RESULTS: Pearson's correlation analysis showed that the fingertip and scanned glucose levels were positively correlated (R = 0.86, P = 0.00). The aggregated MARD of scanned glucose was 14.28 ± 13.40%. Parker's error analysis showed that 99.30% of the data pairs were located in areas A and B. According to the probe wear time of the FreeStyle Libre FGM system, MARD1 d and MARD2-14 d were 16.55% and 14.35%, respectively (t = 1.23, P = 0.22). Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion (LAGE) was < 5.80 mmol/L but negatively correlated with blood glucose when the LAGE was ≥ 5.80 mmol/L. CONCLUSION: The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains. This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains. MARD is mainly influenced by glucose levels and fluctuations, and the accuracy of the system is higher when the blood glucose fluctuation is small. In case of higher blood glucose level fluctuations, deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

6.
J Adolesc Health ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39066755

ABSTRACT

PURPOSE: Patient-delivered partner therapy (PDPT) allows index patients who test positive for Chlamydia trachomatis (Ct) to provide treatment to partners directly. PDPT is contingent upon an index being able to contact their partner. The aims of this study were to assess factors related to being able to contact a partner and being able to successfully deliver their treatment. METHODS: Participants were Black men who have sex with women aged 15-26 enrolled in a community Ct screening/treatment program in New Orleans, LA who tested positive for Ct and completed a computer-assisted survey. Factors associated with the index's ability to contact their recent sex partner(s) and to successfully deliver PDPT to his partner(s) were compared by characteristics of the relationship. RESULTS: Of 104 young men who tested positive for Ct, the median age was 20.3 years and information was reported on 184 female partners, of whom 143 (77.7%) were deemed contactable by the index. Only the index wanting to have sex with the partner again was significantly associated with their ability to contact the partner (odds ratio [OR] 5.38, 95% confidence interval [CI] 2.18, 13.23). Only 72/184 (39.1%) partners received PDPT. The index being interested in sex with partner again (OR 2.54, 95% CI 1.23-5.27) was associated with greater odds of successful PDPT delivery whereas if index believed their partner had other partners, successful PDPT was less likely (OR 0.51, 95% CI 0.26-0.99). There was low agreement between an index's ability to contact their partner and the delivery of PDPT (kappa = 0.04 [-0.062, 0.143). DISCUSSION: Asking patients if they can recontact prior sexual parters may be insufficient to ensure that their partners receive PDPT.

7.
Article in English | MEDLINE | ID: mdl-39073616

ABSTRACT

CONTEXT/OBJECTIVE: Fetuin-B is a hepatokine/adipokine implicated in glucose homeostasis and lipid metabolism. We sought to assess whether cord blood fetuin-B levels are altered in gestational diabetes mellitus (GDM) and the association with fetal growth factors and lipids. STUDY DESIGN, POPULATION, AND OUTCOMES: In a nested case-control study of 153 pairs of neonates of mothers with GDM and euglycemic pregnancies in the Shanghai Birth Cohort, we assessed cord blood fetuin-B in relation to fetal growth factors and lipids [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterols (TC) and triglycerides (TG)]. RESULTS: Cord blood fetuin-B concentrations were higher in the newborns of GDM vs. euglycemic mothers (mean ± SD: 2.35±0.96 vs 2.05±0.73 mg/L, P=0.012), and were positively correlated with LDL (r=0.239, P<0.0001), TC (r=0.230, P=0.0001), insulin-like growth factor-Ⅰ [IGF-Ⅰ (r=0.137, P=0.023)] and IGF-Ⅱ (r=0.148, P=0.014) concentrations. Similar associations were observed adjusting for maternal and neonatal characteristics. CONCLUSIONS: The study is the first to demonstrate that fetuin-B levels are elevated in fetal life in GDM, and that fetuin-B affects lipid metabolic health during fetal life in humans. The secretion of fetuin-B appears to be related to the secretion of insulin-like growth factors (IGF-Ⅰ and IGF-Ⅱ).

8.
Dalton Trans ; 53(30): 12594-12603, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39007337

ABSTRACT

The rational synthesis of an electrode material with a highly active and stable architecture is very critical to achieving high-performance electrochemical energy storage. Herein, N-doped carbon restricting yolk-shell CoSe2/Ni3Se4 (CoSe2/Ni3Se4@NC) flower-like microspheres were successfully synthesized from solid CoNi-glycerate microspheres using a coating technology as an anode material for lithium-ion batteries (LIBs). The unique yolk-shell CoSe2/Ni3Se4@NC microspheres with hierarchical pores can increase the contact area with the electrolyte and provide enough transfer channels for the diffusion of Li+. The carbon layer on the surface of CoSe2/Ni3Se4@NC can not only improve the conductivity of the electrode but also provide the protective effect of active nanosheets during the process of synthesis, avoiding the overall structure collapse during the charge/discharge process of LIBs. Benefiting from the high conductivity, hollow structure, and elastic NC shell bestowed by the unique architecture, the yolk-shell CoSe2/Ni3Se4@NC anode shows excellent lithium storage performances, such as an excellent reversible specific capacity of 319 mA h g-1 at a current density of 1000 mA g-1 after 500 cycles and excellent cycling stability. This synthesis strategy provides a new way to optimize the lithium storage performance of transition metal compound electrode materials, which is helpful to the design of the next generation of high-performance LIBs.

9.
Circ Cardiovasc Qual Outcomes ; : e010396, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39027934

ABSTRACT

BACKGROUND: Globally, only 13.8% of patients with hypertension have their blood pressure (BP) controlled. Trials testing interventions to overcome barriers to BP control have produced mixed results. Type of health care professional delivering the intervention may play an important role in intervention success. The goal of this meta-analysis is to determine which health care professionals are most effective at delivering BP reduction interventions. METHODS: We searched Medline and Embase (until December 2023) for randomized controlled trials of interventions targeting barriers to hypertension control reporting who led intervention delivery. One hundred articles worldwide with 116 comparisons and 90 474 participants with hypertension were included. Trials were grouped by health care professional, and the effects of the intervention on systolic and diastolic BP were combined using random effects models and generalized estimating equations. RESULTS: Pharmacist-led interventions , community health worker-led interventions, and health educator-led interventions resulted in the greatest systolic BP reductions of -7.3 (95% CI, -9.1 to -5.6), -7.1 (95% CI, -10.8 to -3.4), and -5.2 (95% CI, -7.8 to -2.6) mm Hg, respectively. Interventions led by multiple health care professionals, nurses, and physicians also resulted in significant systolic BP reductions of -4.2 (95% CI, -6.1 to -2.4), -3.0 (95% CI, -4.2 to -1.9), and -2.4 (95% CI, -3.4 to -1.5) mm Hg, respectively. Similarly, the greatest diastolic BP reductions were -3.9 (95% CI, -5.2 to -2.5) mm Hg for pharmacist-led and -3.7 (95% CI, -6.6 to -0.8) mm Hg for community health worker-led interventions. In pairwise comparisons, pharmacist were significantly more effective than multiple health care professionals, nurses, and physicians at delivering interventions. CONCLUSIONS: Pharmacists and community health workers are most effective at leading BP intervention implementation and should be prioritized in future hypertension control efforts.

10.
Chem Biol Drug Des ; 104(1): e14597, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39044124

ABSTRACT

Early detection of lung squamous cell carcinoma (LUSC) has a significant impact on clinical outcomes, and pterostilbene (PT) is a natural compound with promising anti-oncogenic activities. This study aimed to identify potential LUSC biomarkers through a series of bioinformatic analyses and clinical verification and explored the interaction between PT and selected biomarkers during the treatment of LUSC. The analysis of the expression profile of the clinical samples of LUSC was performed to identify dysexpressed genes (DEGs) and validated by IHC. The role of KANK3 in the anti-LUSC effects of PT was assessed with a series of in vitro and in vivo assays. 4335 DEGs were identified, including 1851 upregulated genes and 2484 downregulated genes. Survival analysis showed that KANK3 was significantly higher in patients with LUSC with an advanced tumor stage. In in vitro assays, PT suppressed cell viability, induced apoptosis, and inhibited migration and invasion in LUSC cell lines, which was associated with downregulation of KANK3. After the reinduction of the KANK3 level in LUSC cells, the anti-LUSC function of PT was impaired. In mice model, reinduction of KANK3 increased tumor growth and metastasis even under the treatment of PT. The findings outlined in the current study indicated that PT exerted anti-LUSC function in a KANK3 inhibition-dependent manner.


Subject(s)
Carcinoma, Squamous Cell , Lung Neoplasms , Stilbenes , Stilbenes/pharmacology , Stilbenes/chemistry , Stilbenes/therapeutic use , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Animals , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Mice , Cell Line, Tumor , Apoptosis/drug effects , Cell Movement/drug effects , Mice, Nude , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/genetics , Male , Female , Mice, Inbred BALB C , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Survival/drug effects , Cytoskeletal Proteins/metabolism , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/antagonists & inhibitors , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Cell Proliferation/drug effects
11.
bioRxiv ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38826432

ABSTRACT

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.

12.
Eur J Med Res ; 29(1): 349, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937814

ABSTRACT

BACKGROUND: Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated. METHODS: The animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays. RESULTS: The C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1ß, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1ß and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. CONCLUSIONS: In this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.


Subject(s)
Inflammation , Intercellular Signaling Peptides and Proteins , Lipopolysaccharides , Mice, Inbred C57BL , Nerve Tissue Proteins , Signal Transduction , Tight Junctions , Animals , Lipopolysaccharides/toxicity , Mice , Signal Transduction/drug effects , Nerve Tissue Proteins/metabolism , Inflammation/metabolism , Inflammation/chemically induced , Intercellular Signaling Peptides and Proteins/metabolism , Tight Junctions/metabolism , Tight Junctions/drug effects , Male , Receptors, Cell Surface/metabolism , Receptors, Immunologic/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Intestines/drug effects , Intestines/pathology , Disease Models, Animal , Inflammasomes/metabolism
13.
Heliyon ; 10(11): e31641, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845916

ABSTRACT

Objective: To investigate the value of peripheral blood clusters of differentiation 4 (CD4+) T-lymphocyte (T cells) count and serum interleukin-6 (IL-6) and interleukin-8 (IL-8) in the treatment and prognosis of tuberculous meningitis (TBM). Methods: Sixty-five patients with TBM were prospectively included in the observation group. Sixty-five patients with pulmonary TB and a group of 65 healthy individuals served as the control groups. The differences in peripheral blood CD4+ T-cell count, serum IL-6, and IL-8 levels were compared, and changes in these indices after anti-TB treatment in the observation group were analysed. The observation group was divided into effective and ineffective groups based on their response after 24 weeks of anti-TB treatment. The study also evaluated the influence of peripheral blood CD4+ T-cell count, serum IL-6, and IL-8 levels on the adverse prognosis of TBM during anti-TB treatment. Results: Before treatment, the CD4+ T-cell count in the peripheral blood of the observation group was lower than in both the control and healthy groups, and serum IL-6 and IL-8 levels were higher than in the control group (P < 0.001). After 24 weeks of anti-TB treatment, the CD4+ T-cell count in the peripheral blood of the observation group increased, whereas the levels of IL-6 and IL-8 decreased significantly (P < 0.001). The levels of CD4+ T cells and IL-6 in the peripheral blood of patients before treatment were identified as independent factors influencing the efficacy of anti-TB treatment (odds ratio [OR] = 0.989, 95 % confidence interval [CI]: 0.980-0.997; OR = 1.010, 95 % CI: 1.003-1.017). Conclusion: In patients with TBM, the CD4+ T-cell count in the peripheral blood is decreased, whereas serum IL-6 and IL-8 are increased. The combination of CD4+ T cells and IL-8 shows a degree of predictive value for the prognosis of anti-TB treatment.

14.
Front Vet Sci ; 11: 1394290, 2024.
Article in English | MEDLINE | ID: mdl-38846790

ABSTRACT

There is a gradual transition from water to dryland rearing of geese. In this study, we performed 16S rRNA sequencing (16S rRNA-seq) and transcriptome sequencing (RNA-seq) to reveal the effects of cage rearing (CR) and floor rearing (FR) systems on the microbial composition and transcriptome of the goose ileum. Through 16S rRNA-seq, Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 2 (hgcI_clade and Faecalibacterium) and 14 (Bacteroides, Proteiniphilum, Proteiniclasticum, etc.) differential microbiota in CR and FR, respectively. The rearing system influenced 4 pathways including biosynthesis of amino acids in ileal microbiota. Moreover, we identified 1,198 differentially expressed genes (DEGs) in the ileum mucosa, with 957 genes up-regulated in CR and 241 genes up-regulated in FR. In CR, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the significant enrichment (p < 0.05) of 28 KEGG pathways, most of which were associated with amino acid metabolism. In FR, up-regulated DEGs were mainly enriched in KEGG pathways associated with cellular processes, including apoptosis, necroptosis, and cellular senescence. Spearman correlation analysis of differential microbiota and amino acid metabolism-related DEGs in CR showed a significant positive correlation. Additionally, differential microbiota of FR, Phascolarctobacterium and Sutterella, were positively correlated with FGF10 (p < 0.05) and PIK3R1 (p < 0.01), respectively. In conclusion, there might be differences in ileal amino acid metabolism levels between CR and FR geese, and the observed increase in harmful bacterial species in FR might impact the activity of ileal cells.

15.
BMC Med ; 22(1): 226, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840198

ABSTRACT

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.


Subject(s)
Autistic Disorder , Brain , Cognition , Problem Behavior , Humans , Female , Male , Child , Brain/growth & development , Adolescent , Cognition/physiology , Family Conflict , Mothers , Adult , Pregnancy , Young Adult , Pregnancy in Adolescence , Sex Factors
16.
PLoS One ; 19(6): e0304888, 2024.
Article in English | MEDLINE | ID: mdl-38829871

ABSTRACT

In order to reveal the current status and future trends of lubricant additives, this study analyzes the structured and unstructured data of 77701 lubricant additive patents recorded by Patsnap. The results show that China is the country with the largest number of patents in this field, and the United States is the main exporting country of international technology flow; the current research and development of lubricant additives is dominated by multifunctional composite additives; environmentally friendly additive compositions are the current research hotspot; and more environmentally friendly and economically degradable additives have more development potential in the future. Overall, this study provides a comprehensive understanding of the research and application of lubricant additives and contributes to the future development of the lubricant industry.


Subject(s)
Lubricants , Patents as Topic , Lubricants/chemistry , China , United States
17.
Food Funct ; 15(13): 7017-7031, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38860333

ABSTRACT

B vitamins and probiotics are commonly used dietary supplements with well-documented health benefits. However, their potential interactions remain poorly understood. This study aims to explore the effects and underlying mechanisms of the combined use of B vitamins and probiotics by liquid chromatography-triple quadrupole mass spectrometry analysis, pharmacokinetic modeling, and 16S rRNA gene sequencing. By intragastric administration of seven B vitamins and three Lactobacillus strains to healthy rats (n = 8 per group), we found that probiotics significantly promoted the absorption (by approximately 14.5% to 71.2%) of vitamins B1, B3, B5, and B12. By conducting in vitro experiments (n = 3 per group) and a pseudo-germ-free rat model-based pharmacokinetic study (n = 6 per group), we confirmed that probiotics primarily enhanced the B vitamin absorption through gut microbiota-mediated mechanisms, rather than by directly producing B vitamins. Furthermore, we evaluated the effects of B vitamins and probiotics on the colon and gut microbiota by treating the pseudo-germ-free rats with blank solution, B vitamins, probiotics, and B vitamins + probiotics (n = 5 per group), respectively. Histopathological examination showed that the combination of B vitamins and probiotics synergistically alleviated the rat colon damage. High-throughput genetic sequencing also revealed the synergistic effect of B vitamins and probiotics in modulating the gut microbiota, particularly increasing the abundance of Verrucomicrobia and Akkermansia. In summary, the combined administration of B vitamins and probiotics may have a higher efficacy than using them alone.


Subject(s)
Akkermansia , Gastrointestinal Microbiome , Probiotics , Rats, Sprague-Dawley , Vitamin B Complex , Animals , Probiotics/pharmacology , Rats , Gastrointestinal Microbiome/drug effects , Vitamin B Complex/pharmacology , Male , Colon/metabolism , Colon/microbiology , Dietary Supplements , Humans , RNA, Ribosomal, 16S/genetics
18.
Ibrain ; 10(2): 164-171, 2024.
Article in English | MEDLINE | ID: mdl-38915949

ABSTRACT

This study aimed to provide a recommendable protocol for the preparation of brain cryosections of rats to reduce and avoid ice crystals. We have designed five different dewatering solutions (Scheme 1: dehydrate with 15%, 20%, and 30% sucrose-phosphate-buffered saline solution; Scheme 2: 20% sucrose and 30% sucrose; Scheme 3: 30% sucrose; Scheme 4: 10%, 20%, and 30% sucrose; and Scheme 5: the tissue was dehydrated with 15% and 30% sucrose polyacetate I until it sank to the bottom, followed by placement in 30% sucrose polyacetate II) to minimize the formation of ice crystals. Cryosections from different protocols were stained with Nissl staining and compared with each other by density between cells and the distance of intertissue spaces. The time required for the dehydration process from Scheme 1 to Scheme 5 was 24, 23, 24, 24, and 33 h, respectively. Density between cells gradually decreased from Scheme 1 to Scheme 5, and the distance of intertissue spaces was differentiated and irregular in different schemes according to the images of Nissl staining. We recommend the dewatering method of Scheme 4 (the brain tissues were dehydrated in 10%, 20% and 30% sucrose solution in turn until the tissue samples were completely immersed in the solution and then immersed in the next concentration solution for dehydration).

19.
Clin Pharmacol Ther ; 116(2): 397-407, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38724461

ABSTRACT

Model-based meta-analysis (MBMA) can be used in assisting drug development and optimizing treatment in clinical practice, potentially reducing costs and accelerating drug approval. We aimed to assess the application and quality of MBMA studies. We searched multiple databases to identify MBMA in pharmaceutical research. Eligible MBMA should incorporate pharmacological concepts to construct mathematical models and quantitatively examine and/or predict drug effects. Relevant information was summarized to provide an overview of the application of MBMA. We used AMSTAR-2 and PRISMA 2020 checklists to evaluate the methodological and reporting quality of included MBMA, respectively. A total of 143 MBMA studies were identified. MBMA was increasingly used over time for one or more areas: drug discovery and translational research (n = 8, 5.6%), drug development decision making (n = 42, 29.4%), optimization of clinical trial design (n = 46, 32.2%), medication in special populations (n = 15, 10.5%), and rationality and safety of drug use (n = 71, 49.7%). The included MBMA covered 17 disease areas, with the top three being nervous system diseases (n = 19, 13.2%), endocrine/nutritional/metabolic diseases (n = 17, 11.8%), and neoplasms (n = 16, 11.1%). Of these MBMA studies, 138 (96.5%) were rated as very low quality. The average rate of compliance with PRISMA was only 51.4%. Our findings suggested that MBMA was mainly used to evaluate the efficacy and safety of drugs, with a focus on chronic diseases. The methodological and reporting quality of MBMA should be further improved. Given AMSTAR-2 and PRISMA checklists were not specifically designed for MBMA, adapted assessment checklists for MBMA should be warranted.


Subject(s)
Meta-Analysis as Topic , Humans , Cross-Sectional Studies , Pharmaceutical Research , Drug Development/methods , Models, Theoretical , Research Design , Drug Discovery/methods
20.
Aquat Toxicol ; 272: 106976, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38820742

ABSTRACT

Aquatic organism uptake and accumulate microplastics (MPs) through various pathways, with ingestion alongside food being one of the primary routes. However, the impact of food concentration on the accumulation of different types of MPs, particularly across various colors, remains largely unexplored. To address this gap, we selected Daphnia magna as a model organism to study the ingestion/egestion kinetics and the preference for different MP colors under varying concentrations of Chlorella vulgaris. Our findings revealed that as the concentration of Chlorella increased, the ingestion of MPs by D. magna initially increased and then showed a decline. During the egestion phase within clean medium without further food supply, an increase in food concentration during the ingestion phase led to a slower rate of MP discharge; while when food was present during the egestion phase, the discharge rate accelerated for all treatments, indicating the importance of food ingestion/digestion process on the MPs bioaccumulation. Furthermore, in the presence of phytoplankton, D. magna demonstrated a preference for ingesting green-colored MPs, especially at low and medium level Chlorella supply, possibly due to the enhanced food searching activities. Beyond gut passage, we also examined the attachment of MPs to the organism's body surface, finding that the number of adhered MPs increased with increasing food concentration, likely due to the intensified filtering current during food ingestion. In summary, this study demonstrated that under aquatic environment with increasing phytoplankton concentrations, the ingestion and egestion rates, color preferences, as well as surface adherence of MPs to filter feeding zooplanktons will be significantly influenced, which may further pose ecological risks. Our results offer novel insights into the unintentional accumulation of MPs by zooplankton, highlighting the complex interactions between food availability and MPs accumulation dynamics.


Subject(s)
Daphnia , Microplastics , Water Pollutants, Chemical , Animals , Daphnia/physiology , Chlorella vulgaris/metabolism , Eating , Color , Phytoplankton , Bioaccumulation , Daphnia magna
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