A mass event of paraquat poisoning via inhalation.

Objective: In January 2023, a rare event of collective inhalation paraquat poisoning occurred in Shandong, China. To analyze the clinical characteristics of an event of respiratory tract paraquat poisoning through inhalation. Methods: Clinical data from eight patients with paraquat inhalation poisoning were retrospectively analyzed. Results: The patients were mainly exposed to paraquat via the respiratory tract. The main clinical manifestations were ocular and respiratory irritation. Lung computed tomography (CT) showed that all eight patients had varying degrees of lung injury, mainly manifesting as exudative lesions. Laboratory tests revealed arterial blood gas hypoxemia, abnormal white blood cell count, and increased neutrophil ratio. Sufficient glucocorticoid impact therapy was effective, and all eight patients survived. Conclusion: Eight patients experienced chest tightness, shortness of breath, and varying degrees of lung injury due to inhalation of paraquat through the respiratory tract. The early use of glucocorticoids and other comprehensive treatment measures, active prevention and treatment of lung infections, and protection of organ function have beneficial effects in such cases.

The effects of surface vegetation coverage on the spatial distribution of PM2.5 in the central area of Nanchang City, China.

The frequent occurrence of haze has caused widespread concern in China, and PM2.5 is thought to be the main cause. Previous research showed that PM2.5 was not only influenced by meteorological conditions but also by land cover especially surface vegetation. It was concluded that PM2.5 concentration is significantly influenced by surface vegetation, but spatially how and in what manner are still unanswered. Taking the central area of Nanchang City, China, as a case, this study firstly applied land use regression (LUR) model to simulate the distribution of PM2.5 in 2020. Then, the dichotomous model was used to determine vegetation coverage. A statistical regression model was used to analyze the influence of vegetation cover on PM2.5 and the scale effects. The results showed that (1) vegetation coverage and PM2.5 concentration were both significantly negatively correlated at the spatial scales selected for this study. (2) The effect of vegetation coverage on PM2.5 varied with season and the 500 m had the best correlation. (3) The non-linear regression model fits better than the linear model, and the effect of vegetation coverage on PM2.5 was complex. (4) The effect of vegetation coverage on PM2.5 concentration was different with PM2.5 concentration level. The higher the PM2.5 concentration, the more pronounced the effect of vegetation coverage on it. This study proposed the idea and method of coupling vegetation coverage with PM2.5 concentration at the regional scale from gradient landscape's point of view and provided some references for mitigating PM2.5 pollution through optimizing urban vegetation patterns.

Case report: Reversible splenial lesion syndrome caused by diquat poisoning.

Diquat (DQ), chemically known as 1,1 '-ethylene-2,2' -bipyridine, is a non-selective herbicide for leaf removal and drying. It has toxic effects on central nervous system cells, and toxic neurological lesions include axonal degeneration and pontine myelolysis. At the same time, DQ can also affect the activity of dopaminergic nerve cells through oxidative stress, causing degeneration and reducing dopamine uptake. With the increasing application of DQ in agricultural production, the clinical reports of neurotoxicity caused by acute DQ poisoning are also increasing. At present, DQ rapid-phase-related toxic encephalopathy mainly involves the pons, midbrain, basal ganglia, thalamus and other brain regions. However, this case is unusual in that the lesion mainly involved the splenium of the corpus callosum. It is also the first time to be reported.

Case report: Death caused by 1, 3-dichloropropene, a novel fumigant used in China.

As an efficient and broad-spectrum soil fumigant, 1, 3-dichloropropene is widely used in the control of nematodes, soil pests, and plant pathogens. However, as a volatile chlorine-containing organic compound, 1, 3-dichloropropene is harmful to human health, although no deaths caused by inhalation of 1, 3-dichloropropene have been reported. This article describes the case of a 50-year-old man who died of acute renal failure and brain edema after inhaling 1, 3-dichloropropene at work. This case demonstrates that 1, 3-dichloropropene can be absorbed through the respiratory tract and that exposure to 1, 3-dichloropropene in a confined environment without any protective measures can cause death in humans.

Advances in the treatment of secondary and tertiary hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) and tertiary hyperparathyroidism (THPT) are common and complicated clinical endocrine diseases. The parathyroid glands maintain endocrine homeostasis by secreting parathyroid hormone to regulate blood calcium levels. However, structural alterations to multiple organs and systems occur throughout the body due to hyperactivity disorder in SHPT and THPT. This not only decreases the patients' quality of life, but also affects mortality. Since current treatments for these diseases remains unclear, we aimed to develop a comprehensive review of advances in the treatment of SHPT and THPT according to the latest relevant researches.

Can the Establishment of National Key Ecological Function Areas Enhance Vegetation Carbon Sink? A Quasi-Natural Experiment Evidence from China.

The National Key Ecological Functional Areas (NKEFAs) of China rely on the main functional area planning, with the core goal of enhancing the supply of ecological products. Carbon sink is an important ecological product, and it is necessary to understand whether the establishment of NKEFAs has enhanced vegetation carbon sink (CS). Considering the establishment of NKEFAs as a quasi-natural experiment, based on the panel data of prefecture-level cities in China from 2001 to 2019, a time-varying difference-in-differences (DID) model is used to systematically examine the impact of NKEFAs on CS. The study found that the establishment of NKEFAs has significantly enhanced the CS, and compared to the non-NKEFAs, NKEFAs has increased CS in the covered areas by an average treatment effect (ATE) of 2.1625. The establishment of NKEFAs can enhance CS through the optimization of territory spatial structure, the upgrading of industrial structure and the inter-industrial mobility of labor. The enhancement roles of NKEFAs on CS are heterogeneous across different functional area types, geospatial locations, and quantile levels, with higher enhancement of CS at windbreak-sand fixation type, northwestern region and high quantiles, respectively. In addition, NKEFAs not only have a significant positive ecological spillover effect, but also balanced with local economic growth, they achieve the goals of "lucid waters and lush mountains are invaluable assets".

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET.

BACKGROUND: Metastasis is a major determinant of death in patients with hepatocellular carcinoma (HCC). Dissecting key molecular mediators that promote this malignant feature may help yield novel therapeutic insights. Here, we investigated the role of E-twenty-six transformation-specific variant 1 (ETV1), a member of the E-twenty-six transformation-specific (ETS) family, in HCC metastasis.  METHODS: The clinical significance of ETV1 and its target genes in two independent cohorts of HCC patients who underwent curative resection were assessed by Kaplan-Meier analysis and Multivariate Cox proportional hazards model. Luciferase reporter assay and chromatin immunoprecipitation assay were used to detect the transcriptional regulation of target gene promoters by ETV1. The effect of ETV1 on invasiveness and metastasis of HCC were detected by transwell assays and the orthotopically metastatic model. RESULTS: ETV1 expression was frequently elevated in human HCC specimens. Increased ETV1 expression was associated with the malignant biological characteristics and poor prognosis of HCC patients. ETV1 facilitated invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ETV1 promoted HCC metastasis via upregulating metastasis-related genes, including protein tyrosine kinase 2 (PTK2) and MET. Down-regulated the expression of PTK2 or tyrosine protein kinase Met (c-MET) decreased ETV1-mediated HCC metastasis. Hepatocyte growth factor (HGF) upregulated ETV1 expression through activating c-MET-ERK1/2-ELK1 pathway. Notably, in two independent cohorts, patients with positive coexpression of ETV1/PTK2 or ETV1/c-MET had worse prognosis. Furthermore, the combination of PTK2 inhibitor defactinib and c-MET inhibitor capmatinib significantly suppressed HCC metastasis induced by ETV1. CONCLUSION: This study uncovers functional and prognostic roles for ETV1 in HCC and exposes a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. Targeting this pathway may provide a potential therapeutic intervention for ETV1-overexpressing HCC.

A pan-cancer bioinformatic analysis of the carcinogenic role of SMARCA1 in human carcinomas.

SMARCA1is a mammalian imitation switch (ISWI) gene that encodes for SNF2L. SNF2L is involved in regulating cell transition from a committed progenitor state to a differentiated state. Although many papers have detailed the correlation between SMARCA1 and different cancers, no pan-cancer analysis has been conducted to date. We started by exploring the potential carcinogenic role of SMARCA1 across 33 carcinomas using the cancer genome atlas (TCGA) and the genotype-tissue expression (GTEx) databases. The expression of SMARCA1 was significantly elevated in some tumor types but not in others. There was a distinct relationship between SMARCA1 expression and patient prognosis. S116 phosphorylation levels were up-regulated in both lung adenocarcinoma and uterine corpus endometrial carcinoma. The expression level of SMARCA1 was positively correlated with cancer-associated fibroblasts infiltration in a number of tumors, such as colon adenocarcinoma, cervical squamous cell carcinoma and endocervical adenocarcinoma. It was also associated with CD8+ T-cell infiltration in head and neck squamous cell carcinoma and lung adenocarcinoma. Furthermore, SMARCA1 is involved in chromatin remodeling and protein processing-associated mechanisms. Our study presents an initial assessment and illustration of the carcinogenic role of SMARCA1 in different carcinomas.

Case Report: Toxic encephalopathy caused by repeated inhalation of liquid sealant.

Short-term exposure to high levels of organic solvents, as well as long-term exposure to small doses, can damage the central nervous system, thereby leading to toxic encephalopathy. However, toxic encephalopathy caused by long-term inhalation of liquid sealant is rarely reported. This study describes the clinical data of a case of toxic encephalopathy caused by repeated inhalation of liquid sealants and discusses the pathophysiological characteristics and treatment of organic solvent toxic encephalopathy. This report aims to strengthen the understanding of this disease among clinical staff.

Evaluation of the Ecological Effects of Ecological Restoration Programs: A Case Study of the Sloping Land Conversion Program on the Loess Plateau, China.

The Sloping Land Conversion Program (SLCP) is the largest ecological restoration program in the world. Evaluating the ecological effects of the SLCP not only provides a scientific basis for China to improve the SLCP but also provides a reference for other countries in the world to evaluate the ecological effects of ecological restoration programs being implemented or to be implemented. To this end, we took the Loess Plateau, the core area for the implementation of the SLCP, as an example and, based on multi-source remote sensing data and GIS technology, we conducted a comprehensive evaluation of the ecological effects of the implementation of the SLCP on the Loess Plateau. The results showed that, first, from 2000 to 2018, a total of 12,372.05 km2 of cultivated land was converted into forest land and grassland on the Loess Plateau, and this contributed to an increase in vegetation cover from 45.09% in 2000 to 64.15% in 2018, and a decrease in the soil erosion modulus from 26.41 t·hm-2·yr-1 in 2000 to 17.92 t·hm-2·yr-1 in 2018. Second, the 6-25° slope range is the core area of the Loess Plateau for implementation of the SLCP. In this range, the area of cultivated land converted into forest land and grassland accounts for 60.16% of the total area of transferred cultivated land. As a result, the 6-25° slope range has become the most significant area for improving vegetation cover and reducing the soil erosion intensity, and it is mainly concentrated in the southwestern, central and central-eastern hilly and gully areas of the Loess Plateau. Third, from 2000 to 2018, the climate of the Loess Plateau tended to be warm and humid and was conducive to the implementation of the SLCP. Among these factors, precipitation is the dominant factor in determining the spatial distribution of vegetation on the Loess Plateau, and the increase in precipitation is also the main reason for the promotion of vegetation growth. Fourthly, from 2000 to 2018, the ecological environment of the Loess Plateau was significantly improved as a result of the combined effects of the implementation of the SLCP and climate warming and humidification, but the primary reason is still the implementation of the SLCP.

HNRNPC downregulation inhibits IL-6/STAT3-mediated HCC metastasis by decreasing HIF1A expression.

RNA-binding protein (RBP) dysregulation is functionally linked to several human diseases, including neurological disorders, cardiovascular disease, and cancer. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RBPs involved in nucleic acid metabolism. A growing body of studies has shown that the dysregulated hnRNPs play important roles in tumorigenesis. Here, we found that heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRNPC) had good performance in distinguishing between hepatocellular carcinoma (HCC) and normal liver tissues through bioinformatics analysis. Further investigation revealed that HNRNPC was significantly correlated with multiple malignant characteristics of HCC, including tumor size, microvascular invasion, tumor differentiation, and TNM stage. Patients with HCC with positive HNRNPC expression exhibited decreased overall survival and increased recurrence rate. HNRNPC downregulation inhibited HCC invasion and metastasis. The decreased expression of hypoxia inducible factor 1 subunit alpha (HIF1A) was identified as the molecular mechanism underlying HNRNPC downregulation-inhibited HCC metastasis by RNA sequencing. Mechanistically, HNRNPC downregulation decreased HIF1A expression by destabilizing HIF1A mRNA. HIF1A overexpression rescued the decrease in invasiveness and metastasis of HCC induced by HNRNPC downregulation. Additionally, interleukin (IL)-6/STAT3 signaling upregulated HNRNPC expression in HCC cells, and knockdown of HNRNPC significantly inhibited IL-6/STAT3-enhanced HCC metastasis. Furthermore, anti-IL-6 antibody siltuximab significantly inhibited IL-6-mediated HCC metastasis. In summary, our research revealed the clinical value, functional role, and molecular mechanism of HNRNPC in HCC and showed the potential of HNRNPC as a biomarker for diagnosis, prognosis, and further therapeutic targets for HCC.

Advance of SOX Transcription Factors in Hepatocellular Carcinoma: From Role, Tumor Immune Relevance to Targeted Therapy.

Sex determining region Y (SRY)-related high-mobility group (HMG) box (SOX) factors belong to an evolutionarily conserved family of transcription factors that play essential roles in cell fate decisions involving numerous developmental processes. In recent years, the significance of SOX factors in the initiation and progression of cancers has been gradually revealed, and they act as potential therapeutic targets for cancer. However, the research involving SOX factors is still preliminary, given that their effects in some leading-edge fields such as tumor immune microenvironment (TIME) remain obscure. More importantly, as a class of 'undruggable' molecules, targeting SOX factors still face considerable challenges in achieving clinical translation. Here, we mainly focus on the roles and regulatory mechanisms of SOX family members in hepatocellular carcinoma (HCC), one of the fatal human health burdens worldwide. We then detail the role of SOX members in remodeling TIME and analyze the association between SOX members and immune components in HCC for the first time. In addition, we emphasize several alternative strategies involved in the translational advances of SOX members in cancer. Finally, we discuss the alternative strategies of targeting SOX family for cancer and propose the opportunities and challenges they face based on the current accumulated studies and our understanding.

T-box transcription factor 19 promotes hepatocellular carcinoma metastasis through upregulating EGFR and RAC1.

The effect of targeted therapy for metastatic hepatocellular carcinoma (HCC) is still unsatisfactory. Exploring the underlying mechanism of HCC metastasis is favorable to provide new therapeutic strategies. T-box (TBX) transcription factor family genes, which are crucial regulators in embryo and organ development, are vital for regulating tumor initiation, growth and metastasis. Here we explored the role of TBX19 in HCC metastasis, which is one of the most upregulated TBX family genes in human HCC tissues. TBX19 expression was markedly upregulated in HCC tissues and elevated TBX19 expression predicted poor prognosis. Overexpression of TBX19 enhanced HCC metastasis through upregulating epidermal growth factor receptor (EGFR) and Rac family small GTPase 1 (RAC1) expression. Downregulation of EGFR and RAC1 inhibited TBX19-mediated HCC metastasis, while upregulation of EGFR and RAC1 restored inhibition of HCC metastasis mediated by TBX19 knockdown. Furthermore, epidermal growth factor (EGF)/EGFR signaling upregulated TBX19 expression via the extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-kB axis. Besides, the combined application of EGFR inhibitor Erlotinib and RAC1 inhibitor NSC23766 markedly inhibited TBX19-mediated HCC metastasis. In HCC cohorts, TBX19 expression was positively associated with EGFR and RAC1 expression. Patients with positive coexpression of TBX19/EGFR or TBX19/RAC1 displayed the poorest prognosis. In conclusion, EGF/EGFR signaling upregulated TBX19 expression via ERK/NF-kB pathway and TBX19 fostered HCC metastasis by enhancing EGFR and RAC1 expression, which formed an EGF-TBX19-EGFR positive feedback loop. Targeting this signaling pathway may offer a potential therapeutic strategy to efficiently restrain TBX19-mediated HCC metastasis.

Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2.

Background: Accumulating studies manifest that BTB and CNC homology 1 (BACH1) facilitates multiple malignancies progression and metastasis, and targeting the BACH1 pathway enhances antitumor efficacy. Nevertheless, the exact mechanism of BACH1 promoting growth and metastasis and its therapeutic significance in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression of BACH1 in human HCC specimens and HCC cell lines was analyzed by quantitative RT-PCR (RT-qPCR), western blot, and immunohistochemistry (IHC). The invasiveness and metastasis of HCC cells in vitro and in vivo were evaluated using transwell assays and orthotopic xenograft models. The luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were performed to explore the transcriptional regulation of insulin-like growth factor 1 receptor (IGF1R) and protein tyrosine kinase 2 (PTK2) by BACH1. Results: BACH1 was prominently upregulated in human HCC samples and elevated BACH1 expression was associated with poor overall survival (OS) and high recurrence rates of HCC patients. BACH1 facilitated growth and metastasis of HCC by upregulating cell motility-related genes IGF1R and PTK2. Notably, insulin-like growth factor 2 (IGF2), the ligand of IGF1R, in turn upregulated BACH1 expression through the IGF1R-ERK1/2-ETS1 cascades, thus forming a positive feedback loop to provoke HCC growth and metastasis. Moreover, combining IGF1R inhibitor linsitinib with PTK2 inhibitor defactinib prominently suppressed BACH1-mediated HCC growth and metastasis. Conclusions: These results demonstrated the tumorigenic and pro-metastatic role of BACH1 in HCC, which could be a promising biomarker for predicting poor prognosis and selecting patients who could benefit from combination therapy of IGF1R-targeted and PTK2-directed.

Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention.

The homeobox (HOX) genes encoding an evolutionarily highly conserved family of homeodomain-containing transcriptional factors are essential for embryogenesis and tumorigenesis. HOX genes are involved in cell identity determination during early embryonic development and postnatal processes. The deregulation of HOX genes is closely associated with numerous human malignancies, highlighting the indispensable involvement in mortal cancer development. Since most HOX genes behave as oncogenes or tumor suppressors in human cancer, a better comprehension of their upstream regulators and downstream targets contributes to elucidating the function of HOX genes in cancer development. In addition, targeting HOX genes may imply therapeutic potential. Recently, novel therapies such as monoclonal antibodies targeting tyrosine receptor kinases, small molecular chemical inhibitors, and small interfering RNA strategies, are difficult to implement for targeting transcriptional factors on account of the dual function and pleiotropic nature of HOX genes-related molecular networks. This paper summarizes the current state of knowledge on the roles of HOX genes in human cancer and emphasizes the emerging importance of HOX genes as potential therapeutic targets to overcome the limitations of present cancer therapy.

ONECUT2 facilitates hepatocellular carcinoma metastasis by transcriptionally upregulating FGF2 and ACLY.

Metastasis is the predominant reason for high mortality of hepatocellular carcinoma (HCC) patients. It is critical to explore the molecular mechanism underlying HCC metastasis. Here, we reported that transcription factor One Cut homeobox 2 (ONECUT2) functioned as an oncogene to facilitate HCC metastasis. Elevated ONECUT2 expression was positively correlated with increased tumor number, tumor encapsulation loss, microvascular invasion, poor tumor differentiation, and advanced TNM stage. Mechanistically, ONECUT2 directly bound to the promoters of fibroblast growth factor 2 (FGF2) and ATP citrate lyase (ACLY) and transcriptionally upregulated their expression. Knockdown of FGF2 and ACLY inhibited ONECUT2-mediated HCC metastasis, whereas upregulation of FGF2 and ACLY rescued ONECUT2 knockdown-induced suppression of HCC metastasis. ONECUT2 expression was positively correlated with FGF2 and ACLY expression in human HCC tissues. HCC patients with positive coexpression of ONECUT2/FGF2 or ONECUT2/ACLY exhibited the worst prognosis. In addition, FGF2 upregulated ONECUT2 expression through the FGFR1/ERK/ELK1 pathway, which formed an FGF2-FGFR1-ONECUT2 positive feedback loop. Knockdown of ONECUT2 inhibited FGF2-induced HCC metastasis. Furthermore, the combination of FGFR1 inhibitor PD173074 with ACLY inhibitor ETC-1002 markedly suppressed ONECUT2-mediated HCC metastasis. In summary, ONECUT2 was a potential prognostic biomarker in HCC and targeting this oncogenic signaling pathway may provide an efficient therapeutic strategy against HCC metastasis.

Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes.

One of the major challenges in hepatocellular carcinoma (HCC) treatment is drug resistance and low responsiveness to systemic therapies, partly due to insufficient T cell infiltration. Myeloid-derived suppressor cells (MDSCs) are immature marrow-derived cell populations with heterogeneity and immunosuppression characteristics and are essential components of the suppressive tumor immune microenvironment (TIME). Increasing evidence has demonstrated that MDSCs are indispensable contributing factors to HCC development in a T cell-dependent or non-dependent manner. Clinically, the frequency of MDSCs is firmly linked to HCC clinical outcomes and the effectiveness of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Furthermore, MDSCs can also be used as prognostic and predictive biomarkers for patients with HCC. Therefore, treatments reprograming MDSCs may offer potential therapeutic opportunities in HCC. Here, we recapitulated the dynamic relevance of MDSCs in the initiation and development of HCC and paid special attention to the effect of MDSCs on T cells infiltration in HCC. Finally, we pointed out the potential therapeutic effect of targeting MDSCs alone or in combination, hoping to provide new insights into HCC treatment.

m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Pancreatic Cancer.

Recent studies have shown that RNA N6-methyladenosine (m6A) modification plays an important part in tumorigenesis and immune-related biological processes. However, the comprehensive landscape of immune cell infiltration characteristics in the tumor microenvironment (TME) mediated by m6A methylation modification in pancreatic cancer has not yet been elucidated. Based on consensus clustering algorithm, we identified two m6A modification subtypes and then determined two m6A-related gene subtypes among 434 pancreatic cancer samples. The TME characteristics of the identified gene subtypes were highly consistent with the immune-hot phenotype and the immune-cold phenotype respectively. According to the m6A score extracted from the m6A-related signature genes, patients can be divided into high and low m6A score groups. The low score group displayed a better prognosis and relatively strong immune infiltration. Further analysis showed that low m6A score correlated with lower tumor mutation burden and PD-L1 expression, and indicated a better response to immunotherapy. In general, m6A methylation modification is closely related to the diversity and complexity of immune infiltration in TME. Evaluating the m6A modification pattern and immune infiltration characteristics of individual tumors can help deepen our understanding of the tumor microenvironment landscape and promote a more effective clinical practice of immunotherapy.