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1.
Clin Transl Oncol ; 2024 May 17.
Article En | MEDLINE | ID: mdl-38758385

OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

2.
Chin Herb Med ; 16(2): 301-309, 2024 Apr.
Article En | MEDLINE | ID: mdl-38706827

Objective: A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory. Methods: A patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines). Results: Clinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient's medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered "highly probable" (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia. Conclusion: In summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

3.
Int J Surg ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38752497

BACKGROUND: Image-guided thermal ablation has been applied in patients with papillary thyroid microcarcinoma(PTMC) who refuse surgery or active surveillance. However, evidence to support ablation is limited by single-center designs and lack of long-term data. The purpose of this study was to compare long-term outcomes between ablation and lobectomy for patients with solitary PTMC. MATERIALS AND METHODS: This multicenter retrospective study included 1021 consecutive patients with solitary PTMC who underwent ablation(n=444) or lobectomy(n=577) at the four university-affiliated hospitals. The primary outcomes were disease progression(lymph node metastasis[LNM], recurrent tumors, persistent tumors and distant metastasis) and disease-free survival(DFS). Secondary outcomes were complications, hospitalization, procedure time, estimated blood loss and cost. The two groups were compared using propensity score matching. RESULTS: After matching, no significant differences were observed in disease progression (4.7% vs. 3.4%, P=.307), LNM (1.6% vs. 1.6%, P=1.000), recurrent tumors (2.9% vs. 1.8%, P=.269), persistent tumors(0.2% vs. 0%, P=.317) and DFS (95.5% vs. 97.1%, P=.246) between the ablation and lobectomy groups during the median follow-up of 96.5 months. The ablation group had significantly lower complication rates (0.7% vs. 5.2%, P<.001), shorter post-treatment hospitalization (median[IQR], 0 d vs. 4.0[3.0] d, P<.001), shorter procedure time (8.5[2.8] min vs. 90.0[43.8] min, P<.001), reduced estimated blood loss (0 mL vs. 20.0[10.0] mL, P<.001), and lower cost ($1873.2[254.0] vs. $2292.9[797.8], P<.001) than the lobectomy group. CONCLUSIONS: This study revealed comparable disease progression and survival outcomes between ablation and lobectomy for solitary PTMC. Imaged-guided thermal ablation could be effective and safe alternatives to lobectomy for properly selected patients with PTMC.

4.
Bioconjug Chem ; 35(5): 674-681, 2024 May 15.
Article En | MEDLINE | ID: mdl-38695582

Aptamers are widely used molecular recognition tools in targeted therapy, but their ability to effectively penetrate deep into solid tumors remains a significant challenge, leading to suboptimal treatment efficacy. Here, we developed a polyfluoroalkyl (PFA) decoration strategy to enhance aptamer recognition, cell internalization, and solid tumor penetration. Our results indicate that PFA with around 11 fluorine atoms significantly improves aptamer internalization both in vitro and in vivo settings. However, we also observed that the use of PFA tags containing 19 and 23 fluorine atoms on aptamers resulted in nonspecific cell anchoring in control cell lines, affecting the specificity of aptamers. Overall, we found that using a chemical modification strategy could enhance the deep tumor penetration ability of aptamers and validate their effectiveness in vivo. This approach has significant practical applications in targeted drug delivery for cancer treatment.


Aptamers, Nucleotide , Receptor Protein-Tyrosine Kinases , Aptamers, Nucleotide/chemistry , Humans , Animals , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , Cell Line, Tumor , Mice , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/antagonists & inhibitors , Neoplasms/drug therapy , Neoplasms/metabolism , Drug Delivery Systems/methods
5.
Hortic Res ; 11(5): uhae060, 2024 May.
Article En | MEDLINE | ID: mdl-38716228

High levels of free amino acids (AAs) in tea leaves are crucial for tea flavor and health function; however, the dynamic AA biosynthesis, transport, and turnover in tea plants remain elusive. Here we dissected whole tea plants for these dynamics by assessing AA profiles and transcriptomes of metabolic pathway genes in tea roots, stems, and leaves and revealing their distinctive features with regard to AA synthesis, transport, and degradation/recycling. Nitrogen assimilation dominated in the roots wherein glutamine (Gln), theanine, and arginine (Arg) were actively synthesized. Arg was transported into trunk roots and stems, together with Glu, Gln, and theanine as the major AAs in the xylem sap for long-distance root-to-leaf transport. Transcriptome analysis revealed that genes involved in Arg synthesis were highly expressed in roots, but those for Arg transport and degradation were highly expressed in stems and young leaves, respectively. CsGSIa transcripts were found in root meristem cells, root, stem and leaf vascular tissues, and leaf mesophyll where it appeared to participate in AA synthesis, transport, and recycling. Overexpression of CsGSIa in tea transgenic hairy roots and knockdown of CsGSIa in transgenic hairy roots and tea leaves produced higher and lower Gln and theanine than wild-type roots and leaves, respectively. This study provides comprehensive and new insights into AA metabolism and transport in the whole tea plant.

6.
Light Sci Appl ; 13(1): 101, 2024 May 06.
Article En | MEDLINE | ID: mdl-38705921

Temporal solitons have been the focus of much research due to their fascinating physical properties. These solitons can form bound states, which are fundamentally crucial modes in fiber laser and present striking analogies with their matter molecules counterparts, which means they have potential applications in large-capacity transmission and all-optical information storage. Although traditionally, second-order dispersion has been the dominant dispersion for conventional solitons, recent experimental and theoretical research has shown that pure-high-even-order dispersion (PHEOD) solitons with energy-width scaling can arise from the interaction of arbitrary negative-even-order dispersion and Kerr nonlinearity. Despite these advancements, research on the bound states of PHEOD solitons is currently non-existent. In this study, we obtained PHEOD bound solitons in a fiber laser using an intra-cavity spectral pulse shaper for high-order dispersion management. Specifically, we experimentally demonstrate the existence of PHEOD solitons and PHEOD bound solitons with pure-quartic, -sextic, -octic, and -decic dispersion. Numerical simulations corroborate these experimental observations. Furthermore, vibrating phase PHEOD bound soliton pairs, sliding phase PHEOD bound soliton pairs, and hybrid phase PHEOD bound tri-soliton are discovered and characterized. These results broaden the fundamental understanding of solitons and show the universality of multi-soliton patterns.

7.
J Fish Dis ; : e13960, 2024 May 06.
Article En | MEDLINE | ID: mdl-38708552

In this issue, we established rapid, cost-effective, and simple detection methods including recombines polymerase amplification with lateral flow dipstick (RPA-LFD) and real-time RPA for cyprinid herpesvirus 3(CyHV-3), and evaluated their sensitivity, specificity, and applicability, the real-time RPA method could achieve sensitive diagnosis of CyHV-3 within 1.3 copies per reaction, respectively. The real-time RPA method is 10-fold more sensitive than RPA-LFD method. The exact number of CyHV-3 can be calculated in each sample by real-time RPA. The sera from koi also can be tested in these methods. In addition, no cross-reaction was observed with other related pathogens, including carp oedema virus (CEV), spring viraemia of carp virus (SVCV), cyprinid herpesvirus 1(CyHV-1), cyprinid herpesvirus 2(CyHV-2), type I grass carp reovirus (GCRV-I), type II GCRV (GCRV-II), type III GCRV (GCRV-III), and Aeromonas hydrophila.

8.
Bioresour Technol ; : 130873, 2024 May 21.
Article En | MEDLINE | ID: mdl-38782192

The Escherichia coli (E.coli) degrading glucose irradiated by ultrasound irradiation (20 W, 14 min) was investigated as the model system, the glucose degradation increased by 13 % while the E.coli proliferation decreased by 10 % after culture for 18 h. It indicated a tradeoff effect between substrate degradation and cell proliferation, which drove the enhanced contaminants removal and excess sludge reduction in a weak ultrasound enhanced biological wastewater treatment. The enzymatic activities (catalase, superoxide dismutase, adenosine triphosphatases, lactic dehydrogenase, membrane permeability, intracellular reactive oxygen species and calcium ion of E. coli increased immediately by 12 %, 63 %, 124 %, 19 %, 15 %, 4-fold and 38-fold, respectively by ultrasound irradiation power of 20 W for 14 min. Furthermore, the membrane permeability of irradiated E. coli increased by 26 % even though the ultrasound stopped for 10 h. Additionally, pathways associated with glucose degradation and cell proliferation were continuously up-regulated and down-regulated, respectively.

9.
Medicine (Baltimore) ; 103(18): e38054, 2024 May 03.
Article En | MEDLINE | ID: mdl-38701253

BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.


Bibliometrics , Complementary Therapies , Neuralgia , Complementary Therapies/statistics & numerical data , Complementary Therapies/methods , Complementary Therapies/trends , Humans , Neuralgia/therapy
10.
Front Endocrinol (Lausanne) ; 15: 1348368, 2024.
Article En | MEDLINE | ID: mdl-38779450

Background: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework. Methods: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots. Results: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS. Conclusion: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.


Mendelian Randomization Analysis , Polycystic Ovary Syndrome , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/epidemiology , Humans , Female , Risk Factors , Body Mass Index , Insulin Resistance
11.
Adv Sci (Weinh) ; : e2404423, 2024 May 20.
Article En | MEDLINE | ID: mdl-38767186

Establishing an advanced ecosystem incorporating freshwater harvesting, plastic utilization, and clean fuel acquisition is profoundly significant. However, low-efficiency evaporation, single energy utilization, and catalyst leakage severely hinder sustainable development. Herein, a nanofiber-based mortise-and-tenon structural Janus aerogel (MTSJA) is strategically designed in the first attempt and supports Z-scheme catalysts. By harnessing of the upper hydrophilic layer with hydrophilic channels embedding into the hydrophobic bottom layer to achieve tailoring bottom wettability states. MTSJA is capable of a fully-floating function for lower heat loss, water supply, and high-efficiency solar-to-vapor conversion. Benefiting from the ultrasonic cavitation effect and high sensitivity of materials to mechanical forces, this is also the first demonstration of synergistic solar and ultrasound fields to power simultaneous evaporation desalination and waste plastics as reusable substrates generating fuel energy. The system enables persistent desalination with an exceptional evaporation rate of 3.1 kg m-2 h-1 and 82.3% efficiency (21 wt.% NaCl solution and 1 sun), and realizes H2, CO, and CH4 yields with 16.1, 9.5, and 3 µmol h-1 g-1, respectively. This strategy holds great potential for desalination and plastics value-added transformation toward clean energy and carbon neutrality.

12.
Discov Oncol ; 15(1): 179, 2024 May 21.
Article En | MEDLINE | ID: mdl-38772985

AIMS: The aim of this study is to enhance the accuracy of monitoring and treatment information for patients diagnosed with colorectal cancer (CRC). METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a cohort of 335,948 eligible CRC patients was included in this investigation. Conditional survival probability and actuarial overall survival were employed as methodologies to investigate the association between clinicopathological characteristics and cancer prognosis. RESULTS: Among CRC patients, the 5-year survival rate was 59%, while the 10-year survival rate was 42%. Over time, conditional survival showed a consistent increase, with rates reaching 45% and 48% for individuals surviving 1 and 2 years, respectively. Notably, patients with unfavorable tumor stages exhibited substantial improvements in conditional survival, thereby narrowing the disparity with actuarial overall survival over time. CONCLUSION: This study underscores the significance of time-dependent conditional survival probability, particularly for patients with a poorer prognosis. The findings suggest that long-term CRC survivors may experience improved cancer prognosis over time.

13.
Brain Imaging Behav ; 2024 May 08.
Article En | MEDLINE | ID: mdl-38717572

Generalized fractional anisotropy (GFA) can eliminate the crossing fiber effect, which may be more reflective of brain tissue changes in patients with cerebral small vessel disease (CSVD). This study aimed to explore the alterations of structural networks based on GFA and its relationship with cognitive performance in CSVD patients. We recruited 50 CSVD patients which were divided into two groups: cognitive impairment (CSVD-CI) and normal cognition (CSVD-NC), and 22 healthy controls (HCs). All participants underwent the Montreal Cognitive Assessment (MoCA) and MRI examinations. The structural topological properties were compared among the three groups. The correlation between these structural alterations and MoCA was analyzed. Compared with HCs, significantly decreased nodal efficiency and connectivity were detected in the corticothalamic pathways in both patient groups, of which some were significantly decreased in CSVD-CIs compared with CSVD-NCs. Moreover, both patient groups exhibited global network disruption including decreased global efficiency and increased characteristic path length compared with HCs. Furthermore, the nodal efficiency in the right pallidum positively correlated with MoCA in CSVD-NCs controlling for nuisance variables (r = 0.471, p = 0.031). The alterations in corticothalamic pathways indicated that the brain structural network underwent extensive disruption, providing evidence for the consideration of CSVD as a global brain disease.

14.
Mater Horiz ; 2024 May 20.
Article En | MEDLINE | ID: mdl-38764412

In the face of the challenges posed by global warming, traditional methods of building heating and cooling contribute significantly to electricity and coal consumption, thereby emitting considerable amounts of greenhouse gases. Here, a dual-mode thermal management structural material is created by processing sustainable cellulose and lignin derived from wood waste into gels, followed by lamination. The cellulose surface of the material exhibits the ability to scatter solar radiation backward while emitting strongly in the mid-infrared wavelengths, whereas the lignin surface absorbs visible and near-infrared light, primarily releasing energy through non-radiative transitions. Consequently, the material can achieve sub-ambient radiative cooling of 6 °C and solar heating of 27.5 °C during the daytime by simply flipping its orientation. This pioneering material showcases the potential to significantly reduce cooling energy consumption by an average of 18% and heating energy consumption by 42%. Moreover, the integration of a thermal-electric generator within the dual-layer structure optimally utilizes the temperature differential between the two layers, converting it into electrical power. Notably, the dual-mode thermal management structural material exhibits impressive mechanical strength, boasting a flexural strength of 102 MPa, surpassing that of natural wood by over 4.8 times. With its dual-mode functionality and embedded thermal-electric generator, this material represents a crucial step towards achieving both thermal comfort and energy autonomy in sustainable building practices, thereby contributing to a more environmentally friendly and efficient future.

15.
Cancer Lett ; 591: 216896, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38641309

There is growing evidence that lactate can have a wide range of biological impacts in addition to being a waste product of metabolism. Because of the Warburg effect, tumors generate lots of lactate, which create a tumor microenvironment (TME) with low nutrition, hypoxia, and low pH. As a result, the immunosuppressive network is established to gain immune escape potential and regulate tumor growth. Consequently, the tumor lactate pathway is emerging as a possible therapeutic target for tumor. Importantly, Zhao et al. first discovered histone lysine lactylation (Kla) in 2019, which links gene regulation to cell metabolism through dysmetabolic activity and epigenetic modifications, influencing TME and tumor development. Therefore, the aim of this paper is to explore the effects of lactate and lactylation on the TME and tumors, and provide theoretical basis for further research on potential therapeutic targets and biomarkers, with the view to providing new ideas and methods for tumor treatment and prognosis evaluation.


Lactic Acid , Neoplasms , Tumor Microenvironment , Humans , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/genetics , Lactic Acid/metabolism , Epigenesis, Genetic , Animals , Histones/metabolism , Lysine/metabolism , Warburg Effect, Oncologic
16.
Oncogene ; 43(21): 1594-1607, 2024 May.
Article En | MEDLINE | ID: mdl-38565944

Prostate cancer (PCa) remains a significant cause of morbidity and mortality among men worldwide. A number of genes have been implicated in prostate tumorigenesis, but the mechanisms underlying their dysregulation are still incompletely understood. Evidence has established the competing endogenous RNA (ceRNA) theory as a novel regulatory mechanism for post-transcriptional alterations. Yet, a comprehensive characterization of ceRNA network in PCa lacks. Here we utilize stringent in-silico methods to construct a large ceRNA network across different PCa stages, and provide experimental demonstration for the competing regulation among protumorigenic SEC23A, PHTF2, and their corresponding ceRNA pairs. Using machine learning, we establish a ceRNA-based signature (ceRNA_sig) predictive of androgen receptor (AR) activity, tumor aggressiveness, and patient outcomes. Importantly, we identify miR-375 as a key node in PCa ceRNA network, which is upregulated in PCa relative to normal tissues. Forced expression of miR-375 significantly inhibits, while its inhibition promotes, aggressive behaviors of both AR+ and AR- PCa cells in vitro and in vivo. Mechanistically, we show that miR-375 predominantly targets genes possessing oncogenic roles (e.g., proliferation, DNA repair, and metastasis), and thus release targets with tumor suppressive functions. This action model well clarifies why an upregulated miRNA plays a tumor suppressive role in PCa. Together, our study provides new insights into understanding of transcriptomic aberrations during PCa evolution, and nominates miR-375 as a potential therapeutic target for combating aggressive PCa.


Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , MicroRNAs , Prostatic Neoplasms , MicroRNAs/genetics , Humans , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Male , Mice , Animals , Up-Regulation/genetics , Cell Line, Tumor , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Genes, Tumor Suppressor , Cell Proliferation/genetics , RNA, Competitive Endogenous
17.
Blood ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38603632

Notch signaling regulates cell-fate decisions in several developmental processes and cell functions. However, a role for Notch in hepatic thrombopoietin (TPO) production remains unclear. We noted thrombocytopenia in mice with hepatic Notch1 deficiency, and so investigated TPO production and other features of platelets in these mice. We found that the liver ultrastructure and hepatocyte function were comparable between control mice and Notch1-deficient mice. However, the Notch1-deficient mice had significantly lower plasma TPO and hepatic TPO mRNA levels, concomitant with lower numbers of platelets and impaired megakaryocyte differentiation and maturation, which were rescued by addition of exogenous TPO. Additionally, JAK2/STAT3 phosphorylation was significantly inhibited in Notch1-deficient hepatocytes, consistent with the RNA-seq analysis. JAK2/STAT3 phosphorylation and TPO production was also impaired in cultured Notch1-deficient hepatocytes after treatment with desialylated platelets. Consistently, hepatocyte-specific Notch1 deletion inhibited JAK2/STAT3 phosphorylation and hepatic TPO production induced by administration of desialylated platelets in vivo. Interestingly, Notch1 deficiency downregulated the expression of HES5 but not HES1. Moreover, desialylated platelets promoted the binding of HES5 to JAK2/STAT3, leading to JAK2/STAT3 phosphorylation and pathway activation in hepatocytes. Hepatocyte Ashwell-Morell receptor (AMR) (asialoglycoprotein receptor 1, ASGR1) physically associates with Notch1 and inhibition of AMR impaired Notch1 signaling activation and hepatic TPO production. Furthermore, blockage of Dll4 on desialylated platelets inhibited hepatocyte Notch1 activation and HES5 expression, JAK2/STAT3 phosphorylation and subsequent TPO production. In conclusion, our study identifies a novel regulatory role of Notch1 in hepatic TPO production, indicating that it might be a target for modulating TPO level.

18.
Heliyon ; 10(6): e27845, 2024 Mar 30.
Article En | MEDLINE | ID: mdl-38560685

Objective: To study the histopathological staging of atrophic lesions of the gastric mucosa. Methods: Histology and immunohistochemistry were used to closely examine 2144 specimens of atrophic gastric mucosa that were taken from endoscopic biopsies. Results: When the gastric mucosa epithelium is affected by infection, chemical stimulation, immune factors, genetic factors, and other factors, it may cause an atrophy of gastric mucosa epithelium and a decrease in the number of glands, intestinal metaplasia, hyperplasia of smooth muscle fibers, and atrophy of stem cells in the proliferative zone. In this study, we characterized the above lesions as atrophic lesions of the gastric mucosa. Based on the morphological and histological characteristics of the lesion, as well as the law of cell proliferation and transformation during its occurrence and development, we propose five stages. We also noted the onset age, gender correlation, and histopathological characteristics of each stage of gastric mucosal atrophies. Conclusion: Understanding the pathological staging of gastric mucosal atrophy is essential for treating patients correctly and keeping track of changes in malignant cells. It is also very important in preventing the initiation of gastric cancer or from getting worse.

19.
Front Psychiatry ; 15: 1348895, 2024.
Article En | MEDLINE | ID: mdl-38651009

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNF-α, and olfactory function (via the Sniffin' Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = -2.235, P = 0.025; t = -6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = -4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis.

20.
Infect Drug Resist ; 17: 1477-1490, 2024.
Article En | MEDLINE | ID: mdl-38634066

Purpose: To analyze the time trends in the notification rates of registered tuberculosis (TB) and bacteriologically confirmed TB in Shandong Province. And analyze the changes in TB treatment outcomes during 2005-2021. Patients and Methods: The information of TB patients registered in the Shandong Information Center for Disease Control and Prevention (CDC) was collected during 2005-2021. We calculated the notification rates of registered TB and bacteriologically confirmed TB. Moreover, we calculated the year-to-year change rate of TB in treatment outcomes before and after COVID-19. The time trends were analyzed using the joinpoint regression method and illustrated as the annual percentage change (APC) of notification rates. Results: A total of 236,898 cases of TB were diagnosed during 2005-2021, of which 51.11% were bacteriologically confirmed cases. Since 2008, the notification rates of registered TB have declined. The notification rates of bacteriologically confirmed TB had been declining during 2005-2016, then remained stable after 2016. In subgroup, the notification rates of both registered TB and bacteriologically confirmed TB were higher among men, rural residents, and people aged ≥ 60 years. Compared with clinically confirmed TB, bacteriologically confirmed TB has shown higher rates of poor outcomes since 2008 and higher case fatality rate since 2005. The rate of poor outcomes remained stable during 2008-2019. However, after the COVID-19 outbreak, the rate of poor outcomes and case fatality rate of TB has risen significantly. Conclusion: After unremitting efforts to fight against TB, the notification rates of registered TB and bacteriologically confirmed TB declined in Shandong Province. The rate of poor outcomes remained stable during 2008-2019, then rise significantly after the COVID-19 outbreak. In the context of the long-term existence of COVID-19, further efforts should be made in TB diagnosis and treatment among high-risk population, especially with regard to males, rural residents and older adults.

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