Systematic analysis of IGF2BP family members in non-small-cell lung cancer.

BACKGROUND: The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, and IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, and cancer immunity in various human cancers, including non-small cell lung cancer (NSCLC). However, the literature on NSCLC largely omits the specific context of lung squamous cell carcinoma (LUSC), an oversight we aim to address. METHODS: Our study evaluated the differential expression of IGF2BP family members in tumors and normal tissues. Meta-analyses were conducted to assess the prognostic value of IGF2BPs in lung adenocarcinoma (LUAD) and LUSC. Additionally, correlations between IGF2BPs and tumor immune cell infiltration, mutation characteristics, chemotherapy sensitivity, and tumor mutation burden (TMB) were investigated. GSEA was utilized to delineate biological processes and pathways associated with IGF2BPs. RESULTS: IGF2BP2 and IGF2BP3 expression were found to be upregulated in LUSC patients. IGF2BP2 mRNA levels were correlated with cancer immunity in both LUSC and LUAD patients. A higher frequency of gene mutations was observed in different IGF2BP1/2/3 expression groups in LUAD compared to LUSC. Meta-analyses revealed a significant negative correlation between overall survival (OS) and IGF2BP2/3 expression in LUAD patients but not in LUSC patients. GSEA indicated a positive association between VEGF and IGF2BP family genes in LUAD, while matrix metallopeptidase activity was inversely correlated with IGF2BP family genes in LUSC. Several chemotherapy drugs showed significantly lower IC50 values in high IGF2BP expression groups in both LUAD and LUSC. CONCLUSION: Our findings indicated that IGF2BPs play different roles in LUAD and LUSC. This divergence highlights the need for tailored therapeutic strategies and prognostic tools, cognizant of the unique molecular profiles of LUAD and LUSC.

Oxytocin Attenuates Sympathetic Innervation with Inhibition of Cardiac Mast Cell Degranulation in Rats after Myocardial Infarction.

Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) after myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein. Mast cells accumulated significantly in peri-infarcted tissues and were present in a degranulated state. They expressed OT receptor (OTR), and OT infusion reduced the number of degranulated cardiac mast cells post-MI. Sympathetic hyperinnervation was attenuated as assessed by immunofluorescence for tyrosine hydroxylase (TH). Seven days post-MI, the arrhythmia score of programmed electrical stimulation was higher in vehicle-treated rats with MI than in rats treated with OT. An in vitro study showed that OT stabilized mast cells via the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Further in vivo studies on OTR-deficient mice showed worsening mast cell degranulation and worsening sympathetic innervation. OT pretreatment inhibited cardiac mast cell degranulation post-MI and prevented sympathetic hyperinnervation, along with mast cell stabilization via the PI3K/Akt pathway. SIGNIFICANCE STATEMENT: This is the first study to elucidate the role and mechanism of oxytocin (OT) in inflammatory-sympathetic communication mediated sympathetic hyperinnervation after myocardial infarction (MI), providing new approaches to prevent fatal arrhythmias.

Based on 3D-PDU and clinical characteristics nomogram for prediction of lymph node metastasis and lymph-vascular space invasion of early cervical cancer preoperatively.

PURPOSE: To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. MATERIALS AND METHODS: A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. RESULTS: Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765-0.926) and 0.714 (95%CI,0.615-0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. CONCLUSION: The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population. METHODS: The three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL. RESULTS: Our research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL. CONCLUSIONS: The CD40 gene may play a role in the occurrence and development of CSCC.

Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer.

Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.

Transversal energy flow of tightly focused off-axis circular polarized vortex beams.

The transversal energy flow characteristics of tightly focused circular polarized beams carrying off-axis vortices are examined in this research work. The results reveal that the symmetry of the focal fields are destroyed and energy flow is offset by the existence of off-axis vortices. Therefore, the focal field and energy flow distribution of polygons (bar-type-like, triangle-like, and square-like) can be realized by the superposition of multiple off-axis vortices with controllable positions. Furthermore, based on off-axis vortex energy flow characteristics, the force exerted on the metal particles in polygon focal fields is found to rotate the particles clockwise along the outlines of the polygon energy flow. The results will potentially provide new ideas and theoretical guidance to explore focal field and particle control methods.

Creation of identical multiple focal spots with three-dimensional arbitrary shifting.

We propose a simple and flexible method to create identical multiple focal spots with three-dimensional arbitrary shifting without moving lenses or laser beams. The incident cylindrical vector (CV) beam superposed with predesigned phase and amplitude modulations is tightly focused by a single lens. The multiple focal spots with predetermined number and positions are generated and the identical intensity distribution as well as the polarization distribution for each individual focal spot is demonstrated. We also present a three-dimensional dynamic shifting with four identical focal spots along Pyramid-like trajectory by continuously regulating the phase and amplitude modulations on the incident CV beam. Furthermore, multiple focal spots with unique intensity profile can also be achieved when proper diffractive optical element (DOE) is associated in the focusing system. These engineered focal fields may find potential applications in 3D laser printing, moving multiple particles trapping and manipulations.

Manipulation of resonant metallic nanoparticle using 4Pi focusing system.

Metallic nanoparticles have fascinated scientists for over a century and are now heavily utilized in biomedical sciences and engineering. Due to its noncontact and holding nature, optical trapping is suitable to be combined with various applications to manipulate metallic nanoparticles. However, stable trapping of resonant metallic nanoparticles remains challenging due to the strong axial scattering force and severe optical heating effect. In this work, we propose novel optical tweezers constructed around a 4Pi focusing system that is capable of manipulating metallic nanoparticles even under the resonant condition. By properly modulating the spatial distribution of the illumination and adjusting the focusing condition, specific numbers of spherical spots with controllable locations can be generated in the focal region, providing multiple probes to interrogate the sample properties. Besides, stable three-dimensional optical trapping can be formed since the axial scattering force is canceled by the counter-propagating light. The greatly enhanced optical force arising from the extremely high focusing efficiency of the 4Pi focusing system enables to avoid the overheating effect by reducing the input power without destroying the mechanical stability. Moreover, complex motion trajectory of the metallic nanoparticles can be realized via introducing specific phase modulation to the illumination sequentially. The technique demonstrated in this work may open up new avenues for optical manipulation and their applications in various scientific fields.

Generation and manipulation of super-resolution spherical magnetization chains.

Based on the inverse Faraday effect, the light-induced magnetization field distributions are investigated for a 4π tight focusing configuration with azimuthally polarized beams. It is found that a superlong (16λ) magnetization chain, composed of 19 subwavelength (0.44λ) spherical spots with longitudinal magnetization field, can be achieved in the focal volume of the objective. Moreover, the magnetic force on a magnetic particle or particle trains produced by tightly focused azimuthally polarized beams are calculated and exploited for the stable trapping of magnetic particles. These unique focal field distributions may find potential applications in confocal microscopy, atom control, and magneto-optical data storage.

Propagation evolution of an off-axis high-order cylindrical vector beam.

The propagation characteristics of an off-axis high-order cylindrical vector beam (OHCVB) are studied in this paper. The analytic expressions for the electric field and intensity distribution of the OHCVB propagating in free space are presented, to our knowledge for the first time. The transverse intensity of the OHCVB, different from that of the input Gaussian beam, does not have an axially symmetric distribution, owing to a slight dislocation between the polarization singularity located in the vector field generator and the center point of the Gaussian beam. Numerical results show that the intensity distribution during propagation strongly depends on the propagation distance, dislocation displacement, and topological charge. Accompanied by beam expansion, the intensity distribution of the OHCVB tends to eventually become steady, and the dark core of the vector beam will disappear gradually during the process of propagation. Moreover, with the increase of the topological charge, more energy will be transferred from the x axis to the y axis, and the annular intensity is split into two parts along the y-axis direction. The results help us to investigate the dynamic propagation behaviors of the HCVB under the off-axis condition and also guide the calibration of the off-axis high-order cylindrical vector field in practice.

[Abnormality of anaplastic lymphoma kinase gene and its expression in pediatric neuroblastoma].

OBJECTIVE: To correlate the abnormal expression of anapastic lymphoma kinase (ALK) protein with the genetic and epigenetic changes of ALK, and to analyze its clinical application in pediatric neuroblastoma. METHODS: Three neuroblastoma (NB) cell lines (two ALK positive: SH-SY5Y and SK-N-SH, one ALK negative: SK-N-AS) and 43 paraffin-embedded NB tissues were included in the study. In both cell lines and clinical cases, immunohistochemistry was used to detect ALK protein expression; PCR and Sanger sequencing were used to detect ALK point mutation; fluorescence in situ hybridization (FISH) was used to detect ALK abnormality and bisulfite sequencing PCR (BSP) was used to detect methylation of CpG island in the promoter area of ALK. RESULTS: The cell lines SH-SY5Y and SK-N-SH were positive for ALK expression (cytoplasm), while the SK-N-AS was negative; among the 43 cases of NB, 26 (60.5%, 26/43) were positive for ALK protein (membrane and cytoplasm), and the rest were negative. Survival analysis showed ALK protein expression was related to survival time, with ALK positive cases having shorter survival time than ALK negative cases (P = 0.020). But ALK protein expression had no association with tumor differentiation (P = 0.503), tumor sites (P = 1.000) and age of patients (P = 0.063). FISH showed ALK amplification in two cases (4.6%, 2/43), ALK gain was found in 30 cases (69.7%, 30/43), and the remaining cases had normal ALK copy (25.6%, 11/43). The presence of extra copies (amplification and gain) of ALK was associated with ALK positive protein expression (P = 0.020), but there was no association with tumor differentiation (P = 1.000), tumor sites (P = 0.775) and age of patients (P = 0.328). No point mutation was found in all three cell lines. Of the 43 NB cases, only one case (2.3%, 1/43) showed point mutation in exon 23, and was a synonymous mutation [A1200A (G4552C)]. The case was ALK negative, but the patient died two months after diagnosis. BSP analysis showed that CpG island in ALK promoter region were all unmethylated in three cell lines and 6 NB cases (including 3 ALK positive, 3 ALK negative). CONCLUSIONS: ALK protein is expressed in most NB, and the expression indicates poor outcome. ALK expression is associated with extra copies of ALK, but there is no association with the methylation status of CpG island of ALK; the presence of extra copies of ALK is the most common genetic aberration in NB. Point mutation of ALK is rare, and may predict poor prognosis in pediatric NB.

The synaptic correlates of serial position effects in sequential working memory.

Sequential working memory (SWM), referring to the temporary storage and manipulation of information in order, plays a fundamental role in brain cognitive functions. The serial position effect refers to the phenomena that recall accuracy of an item is associated to the order of the item being presented. The neural mechanism underpinning the serial position effect remains unclear. The synaptic mechanism of working memory proposes that information is stored as hidden states in the form of facilitated neuronal synapse connections. Here, we build a continuous attractor neural network with synaptic short-term plasticity (STP) to explore the neural mechanism of the serial position effect. Using a delay recall task, our model reproduces the the experimental finding that as the maintenance period extends, the serial position effect transitions from the primacy to the recency effect. Using both numerical simulation and theoretical analysis, we show that the transition moment is determined by the parameters of STP and the interval between presented stimulus items. Our results highlight the pivotal role of STP in processing the order information in SWM.

Effects of Organic Fertilizer Addition to Vegetation and Soil Bacterial Communities in Saline-Alkali-Degraded Grassland with Photovoltaic Panels.

The Songnen grassland is an important resource for livestock production in China. Due to the intensification of anthropogenic activities in recent years, vegetation degradation has worsened, and the salinization of grassland has become increasingly serious, which severely affects the sustainable development of grassland animal husbandry. In this study, organic fertilizer addition was carried out at saline-and-alkaline-degraded Songnen grassland sites with photovoltaic panels, and we investigated the effects of organic fertilizer treatments on the vegetation and soil bacteria in these areas. The results showed that both organic fertilizer treatments increased the community composition and diversity indices of plants (p < 0.05); they also had significant effects on soil electrical conductivity and rapidly available potassium (p < 0.05). In the dominant phylum of bacteria, the relative abundance of Firmicutes increased without adding organic fertilizer under the photovoltaic panel; the addition of organic fertilizer had a significant effect on the relative abundance of Firmicutes and Desulfobacterota (p < 0.05), reducing their relative abundance, respectively. There were differences in the number of bacteria at the genus level under different treatments compared to the control, with the highest enrichment of bacteria occurring at the OFE position, and a significant difference (p < 0.05) being found between the control and the other four groups at the genus level of g_norank_f_norank_o_Actinomarinales. Organic fertilizer had a significant effect on the bacterial Simpson diversity index, with the most significant increasing trend found in OFE (the front eaves of the photovoltaic panel in fertilization area). The results of a correlation analysis showed that pH, electrical conductivity, and total nitrogen were the main factors affecting the soil bacterial community.

SGK1 aggravates idiopathic pulmonary fibrosis by triggering H3k27ac-mediated macrophage reprogramming and disturbing immune homeostasis.

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic matrix deposition and irreversible aberrant tissue remodeling. Their mechanisms of action are associated with the activation of macrophages and a disturbed immune environment. We aim to determine how these activated macrophages influenced the pathogenesis of pulmonary fibrosis. We found the fibrotic areas of IPF patients contained more serum and glucocorticoid-induced kinase 1 (SGK1)-positive and M2-type macrophages. Similarly, bleomycin (BLM)+LPS significantly triggered high expression of SGK1 in the IPF mice, accompanied by destroyed lung structure and function, increased fibrosis markers and disturbed immune microenvironment. Mechanistically, SGK1 markedly promoted the reprogramming of M2-type macrophages in fibrotic lungs by triggering glycogen synthase kinase 3beta (GSK3ß)-tat-interacting protein 60 (TIP60)- histone-3 lysine-27 acetylation (H3K27ac) signalings, which further released chemokine (C-C motif) ligand 9 (CCL9) to attract Th17 cells and delivered TGF-ß to fibroblasts for synergistically destroying immune microenvironment, which was largely reversed by macrophage depletion in mice. We took macrophages as the entry point to deeply analyze IPF pathogenesis and further provided insights for the development of novel drugs represented by SGK1.

Shouhui Tongbian Capsule in treatment of constipation: Treatment and mechanism development.

Constipation is common in the diseases of the digestive system in clinics. With the change in diet structure and the increase in life pressure, the prevalence rate increases year by year. In traditional Chinese medicine (TCM), the location of the disease of constipation is in the large intestine, which is related to the dysfunction of lung, spleen, liver, kidney and other viscera. Its pathogenesis is conductive dysfunction of large intestine. Based on the theory, Shouhui Tongbian Capsule (SHTB) is composed of eight traditional Chinese medicines, including Polygoni multiflori Radix (Heshouwu in Chinese), Aloe (Luhui in Chinese), Cassiae Semen (Juemingzi in Chinese), Ginseng Radix et Rhizoma (Renshen in Chinese), Lycii Fructus (Gouqizi in Chinese), Asini Corii Colla (Ejiao in Chinese), Aurantii Fructus Immaturus (Zhishi in Chinese), and Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), which could help to release excessive turbid, and nourishing yin and supplementing qi in the treatment. This study has been carried out to review the latest advances of SHTB in the treatment of constipation. The results showed that significant effect of SHTB was found in the treatment of constipation, such as functional constipation, and constipation associated with tumor chemotherapy, colitis, type 2 diabetes and chronic cardiac failure. Besides, obvious adverse reactions were not observed. SHTB could effectively treat five types of constipation, provide direction for the future exploration of SHTB in the treatment of other types of constipation.

Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a generic fibrous scarring event resulting from accumulation of extracellular matrix (ECM) proteins, easily progressing to end-stage liver diseases. Tao-Hong-Si-Wu-Tang (THSWT) is a traditional Chinese medicine formula applied in clinics to treat gynecological and chronic liver diseases. However, the role of THSWT on thioacetamide (TAA)-induced hepatic fibrosis and the specific mechanisms remains unclear. AIM OF THE STUDY: To investigate the improving effects of THSWT on TAA-insulted hepatic fibrosis and the underlying mechanisms. MATERIALS AND METHODS: UHPLC-MS/MS was performed to explore the chemical characterization of THSWT. Mice were orally administered with THSWT once daily for 6 weeks along with TAA challenge. Liver function was reflected through serum biomarkers and histopathological staining. RNA sequencing, non-targeted metabolomics and molecular biology experiments were applied to investigate the underlying mechanisms. RESULTS: THSWT profoundly repaired lipid metabolism dysfunction and blocked collagen accumulation both in TAA-stimulated mice and in hepatocytes. Results of RNA sequencing and non-targeted metabolomics revealed that the anti-fibrotic effects of THSWT mostly relied on lipid metabolism repairment by increasing levels of acetyl-CoA, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine, and decreasing relative abundances of acyl-CoA, total cholesterol, diacylglycerol, triacylglycerol and phosphatidylinositol. Mechanically, long-chain acyl-CoA synthetases 4 (ACSL4) was a key profibrotic target both in human and mice by disrupting lipid oxidation and metabolism in hepatic mitochondria. THSWT effectively blocked ACSL4 and promoted mitophagy to reverse above outcomes, which was verified by mitophagy depletion. CONCLUSION: THSWT may be a promising therapeutic option for treating hepatic fibrosis and its complications by modulating lipid metabolism and promoting mitophagy in livers.

Functional Upregulation of TRPM3 Channels Contributes to Acute Pancreatitis-associated Pain and Inflammation.

Transient receptor potential melastatin M3 (TRPM3) channels have been recognized as a pain transducer in dorsal root ganglion (DRG) neurons in recent years. TRPM3 activation initiates neurogenic inflammation and is required for the development of inflammatory hyperalgesia. We aimed to evaluate the role of TRPM3 in pancreas sensory afferents in pancreatic nociception, neurogenic inflammation, and acute pancreatitis (AP)-associated pain. AP was induced by intraperitoneal (i.p.) injection of L-arginine in rats. TRPM3 expression in pancreatic DRG neurons, spontaneous or mechanical-stimulation-evoked pain behaviors, and the extent of inflammation were evaluated. We found that TRPM3 channels were expressed on pancreatic primary afferent nerve terminals containing calcitonin gene-related peptide (CGRP). Activation of TRPM3 in the pancreas by injection of its specific agonist CIM0216 (10 µM) induced pain, CGRP and substance P release, and neurogenic inflammation, as evidenced by edema, plasma extravasation, and inflammatory cell accumulation in the pancreas. Increased TRPM3 functional expression was detected in pancreatic DRG neurons from AP rats, and blocking TRPM3 activity with its antagonist (Primidone, 5 mg/kg, i.p.) attenuated AP-associated pain behaviors and pancreatic inflammation. Pre-incubation of pancreatic DRG neurons with nerve growth factor (NGF) enhanced the increase in intracellular Ca2+ induced by the TRPM3 agonist (CIM0216, 1 µM). Our findings indicate that, in addition to TRPV1 and TRPA1 channels, TRPM3 is another pain channel that has a critical role in pancreatic nociception, neurogenic inflammation, and AP-associated pain behaviors. TRPM3 may be a promising pharmaceutical target for AP pain treatment.

Unraveling the global burden of inflammatory bowel disease (1990-2019): A Joinpoint regression analysis of divergent trends in 10-24 and 50-69 age cohorts.

BACKGROUND AND AIMS: The escalating prevalence of IBD within specific age cohorts, 10-24 and 50-69 years, necessitates a refined understanding of its epidemiological patterns. Prior investigations have often been constrained by their limited scope, particularly in employing age-specific analyses and utilizing advanced statistical methods such as joinpoint regression. Our research examines these demographic segments to elucidate the epidemiological trajectory of IBD. METHODS: This study analyzed GBD 2019 data on IBD, focusing on age groups 10-24 and 50-69. We integrated the socio-demographic index for socio-economic context and employed joinpoint regression to analyze time-segmented disease trends, prioritizing average annual percent change for a comprehensive view. RESULTS: A notable global decline in IBD incidence, particularly in the 50-69 age group, was observed. The 10-24 cohort, however, presented a marginal rise across three decades, with a discernible decline between 2010 and 2019. The study also revealed pivotal gender disparities, with increasing incidence rates in males, especially in the High-income Asia Pacific region. Conversely, females demonstrated decreasing trends across the board. Regional variations accentuated East Asia's escalated IBD incidence and prevalence, whereas high-income North American and Asia-Pacific regions, along with Europe, reflected the highest age-standardized incidence rates. CONCLUSION: The burden of IBD between 1990 and 2019 presents notable disparities across different regions and age demographics. While older populations are seeing a decrease in IBD incidence, young adults and adolescents in regions like East Asia and high-income Asia Pacific are experiencing a concerning uptick. This uneven distribution, influenced by both age and gender, underscores the multifaceted nature of IBD's global impact.

Research progress on hepatotoxicity mechanism of polygonum multiflorum and its main components.

As a traditional tonic Chinese medicine, Polygonum multiflorum is widely used in clinical practice. However, with the deepening of modern pharmacological research, its drug toxicity, especially hepatotoxicity, has become increasingly prominent. Based on a large number of clinical and experimental evidence, it has been confirmed that Polygonum multiflorum and its main active ingredients such as anthraquinones and diphenylethylene glucoside can cause different degrees of hepatotoxicity. Further studies have shown that the toxicological mechanisms involved in the hepatotoxicity of different extracts and components of Polygonum multiflorum may include oxidative phosphorylation, bile acid excretion, different metabolic pathways, genetic and metabolic factors, immune homeostasis, etc. By sorting out and summarizing the literature related to hepatotoxicity of Polygonum multiflorum in recent years, this paper discussed the hepatotoxicity mechanism of Polygonum multiflorum and its main components and some contradictions in related reports.

PPM1G promotes cell proliferation via modulating mutant GOF p53 protein expression in hepatocellular carcinoma.

The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p < 0.0001) and disease-free survival (p = 0.004) in HCC patients. Enhanced expression of PPM1G increases the cell proliferation rate, and knockdown of PPM1G led to a significant reduction in tumor volume in vivo. Further experiments illustrated that upregulated-PPM1G expression increased the protein expression of gain-of-function (GOF) mutant p53. Besides, the immunoprecipitation analysis revealed a direct interaction between PPM1G and GOF mutant p53. Collectively, PPM1G can be a powerful prognostic predictor and potential drug-target molecule.