QiDongNing induces lung cancer cell apoptosis via triggering P53/DRP1-mediated mitochondrial fission.

Non-small-cell lung cancer (NSCLC) is a major cause of worldwide cancer death, posing a challenge for effective treatment. Our previous findings showed that Chinese herbal medicine (CHM) QiDongNing (QDN) could upregulate the expression of p53 and trigger cell apoptosis in NSCLC. Here, our objective was to investigate the mechanisms of QDN-induced apoptosis enhancement. We chose A549 and NCI-H460 cells for validation in vitro, and LLC cells were applied to form a subcutaneous transplantation tumour model for validation in more depth. Our findings indicated that QDN inhibited multiple biological behaviours, including cell proliferation, cloning, migration, invasion and induction of apoptosis. We further discovered that QDN increased the pro-apoptotic BAX while inhibiting the anti-apoptotic Bcl2. QDN therapy led to a decline in adenosine triphosphate (ATP) and a rise in reactive oxygen species (ROS). Furthermore, QDN elevated the levels of the tumour suppressor p53 and the mitochondrial division factor DRP1 and FIS1, and decreased the mitochondrial fusion molecules MFN1, MFN2, and OPA1. The results were further verified by rescue experiments, the p53 inhibitor Pifithrin-α and the mitochondrial division inhibitor Mdivi1 partially inhibited QDN-induced apoptosis and mitochondrial dysfunction, whereas overexpression of p53 rather increased the efficacy of the therapy. Additionally, QDN inhibited tumour growth with acceptable safety in vivo. In conclusion, QDN induced apoptosis via triggering p53/DRP1-mediated mitochondrial fission in NSCLC cells.

New evidence for a role of DANCR in cancers: a comprehensive review.

Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.

Targeting necroptosis: a promising avenue for respiratory disease treatment.

Respiratory diseases are a growing concern in public health because of their potential to endanger the global community. Cell death contributes critically to the pathophysiology of respiratory diseases. Recent evidence indicates that necroptosis, a unique form of programmed cell death (PCD), plays a vital role in the molecular mechanisms underlying respiratory diseases, distinguishing it from apoptosis and conventional necrosis. Necroptosis is a type of inflammatory cell death governed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL), resulting in the release of intracellular contents and inflammatory factors capable of initiating an inflammatory response in adjacent tissues. These necroinflammatory conditions can result in significant organ dysfunction and long-lasting tissue damage within the lungs. Despite evidence linking necroptosis to various respiratory diseases, there are currently no specific alternative treatments that target this mechanism. This review provides a comprehensive overview of the most recent advancements in understanding the significance and mechanisms of necroptosis. Specifically, this review emphasizes the intricate association between necroptosis and respiratory diseases, highlighting the potential use of necroptosis as an innovative therapeutic approach for treating these conditions.

Cell Death in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by increased pulmonary vascular resistance because of vascular remodeling and vasoconstriction. Subsequently, PAH leads to right ventricular hypertrophy and heart failure. Cell death mechanisms play a significant role in development and tissue homeostasis, and regulate the balance between cell proliferation and differentiation. Several basic and clinical studies have demonstrated that multiple mechanisms of cell death, including pyroptosis, apoptosis, autophagy, ferroptosis, anoikis, parthanatos, and senescence, are closely linked with the pathogenesis of PAH. This review summarizes different cell death mechanisms involved in the death of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs), the primary target cells in PAH. This review summarizes the role of these cell death mechanisms, associated signaling pathways, unique effector molecules, and various pro-survival or reprogramming mechanisms. The aim of this review is to summarize the currently known molecular mechanisms underlying PAH. Further investigations of the cell death mechanisms may unravel new avenues for the prevention and treatment of PAH.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

Regulatory B cells protect against chronic hypoxia-induced pulmonary hypertension by modulating the Tfh/Tfr immune balance.

Hypoxia-induced pulmonary hypertension (HPH) is a progressive and lethal disease characterized by the uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) and obstructive vascular remodelling. Previous research demonstrated that Breg cells were involved in the pathogenesis of pulmonary hypertension. This work aimed to evaluate the regulatory function of Breg cells in HPH. HPH mice model were established and induced by exposing to chronic hypoxia for 21 days. Mice with HPH were treated with anti-CD22 or adoptive transferred of Breg cells. The coculture systems of Breg cells with CD4+ T cells and Breg cells with PASMCs in vitro were constructed. Lung pathology was evaluated by HE staining and immunofluorescence staining. The frequencies of Breg cells, Tfh cells and Tfr cells were analysed by flow cytometry. Serum IL-21 and IL-10 levels were determined by ELISA. Protein levels of Blimp-1, Bcl-6 and CTLA-4 were determined by western blot and RT-PCR. Proliferation rate of PASMCs was measured by EdU. Compared to the control group, mean PAP, RV/(LV + S) ratio, WA% and WT% were significantly increased in the model group. Anti-CD22 exacerbated abnormal hemodynamics, pulmonary vascular remodelling and right ventricle hypertrophy in HPH, which ameliorated by adoptive transfer of Breg cells into HPH mice. The proportion of Breg cells on day 7 induced by chronic hypoxia was significantly higher than control group, which significantly decreased on day 14 and day 21. The percentage of Tfh cells was significantly increased, while percentage of Tfr cells was significantly decreased in HPH than those of control group. Anti-CD22 treatment increased the percentage of Tfh cells and decreased the percentage of Tfr cells in HPH mice. However, Breg cells restrained the Tfh cells differentiation and expanded Tfr cells differentiation in vivo and in vitro. Additionally, Breg cells inhibited the proliferation of PASMCs under hypoxic condition in vitro. Collectively, these findings suggested that Breg cells may be a new therapeutic target for modulating the Tfh/Tfr immune balance in HPH.

Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases.

Resistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMß, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases. Video abstract.

α1-Antitrypsin alleviates inflammation and oxidative stress by suppressing autophagy in asthma.

BACKGROUND: Asthma is considered an incurable disease, although many advances have been made in asthma treatments in recent years. Therefore, elucidating the pathological mechanisms and seeking novel and effective therapeutic strategies for asthma are urgently needed. METHODS: Airway resistance was measured by whole-body plethysmography. H&E staining was used to observe the morphological changes in the lung. Oxidative stress was assessed by measuring the levels of MDA, CAT and SOD. Gene expression was analysed by western blotting and RT-qPCR. ELISA was used to analyse the concentrations of IL-4, IL-5 and IFN-γ. RESULTS: In the present study, we successfully established in vivo and in vitro asthma models. OVA administration led to elevated lung resistance, cell counts in BALF, and cytokine secretion, impaired airway structure and enhanced oxidative stress and autophagy in a mouse model of asthma, while IL-13 induced inflammation, oxidative stress and autophagy in BEAS-2B cells. A1AT reduced lung resistance and cell counts in BALF and suppressed inflammation, oxidative stress and autophagy in a mouse model of asthma and IL-13-induced BEAS-2B cells. Mechanistic investigations revealed that autophagy activation compromised the protective effect of A1AT on IL-13-induced BEAS-2B cells. Further mechanistic studies revealed that A1AT alleviated inflammation and oxidative stress by inhibiting autophagy in the context of asthma. CONCLUSION: We demonstrated that A1AT could alleviate inflammation and oxidative stress by suppressing autophagy in the context of asthma and thus ameliorate asthma. Our study revealed novel pathological mechanisms and provided novel potential therapeutic targets for asthma treatment.

Resistin-like molecule ß acts as a mitogenic factor in hypoxic pulmonary hypertension via the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK signaling pathways.

BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule ß (RELM-ß) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-ß has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-ß in HPH remain unclear. METHODS: We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-ß in a rat HPH model and in hPASMCs. RESULTS: Overexpression of RELM-ß caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-ß partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-ß gene overexpression or silencing, respectively. Recombinant RELM-ß protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-ß on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor. CONCLUSIONS: Our findings suggest that RELM-ß acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-ß are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract.

BACKGROUND/AIMS: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. METHODS: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. RESULTS: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2α and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. CONCLUSIONS: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE.

[Allergens-induced sensitization alters airway epithelial adhesion molecules expression in mice].

To explore the relationship between the epithelial adhesion molecules and immune responses of airway epithelium, we observed the expression of integrin ß4 and intercellular adhesion molecule-1 (ICAM-1) in the mice airway epithelium after sensitization with allergens. BALB/c mice were sensitized with intraperitoneal injection of ovalbumin (OVA) or house dust mite (HDM) and then developed airway hyper-responsiveness as determined by barometric whole-body plethysmography. Both OVA and HDM sensitization led to increases of the number of peripheral leukocytes as well as inflammatory cells infiltration in lungs. OVA sensitized mice showed more severe inflammatory cells infiltration than HDM sensitized mice. Immunohistochemistry analysis of mice lung tissues revealed that sensitization with both allergens also led to a decrease of integrin ß4 expression and an increase of ICAM-1 expression in airway epithelia. OVA sensitized mice showed a more significant increase of ICAM-1 expression compared with HDM sensitized mice. siRNA mediated silencing of integrin ß4 gene in 16HBE cells resulted in an up-regulation of ICAM-1 expression. Our results indicate a possible role of airway epithelial adhesion molecules in allergen-induced airway immune responses.

[Regulatory mechanism of Siah1 in the pathogenesis of rat hypoxic pulmonary hypertension].

OBJECTIVE: To explore the regulatory mechanism of Siahl in the pathogenesis of hypoxic pulmonary hypertension (HPH) in rats. METHODS: According to the random number table, 40 adult male Wistar rats were randomly divided into 5 groups (n = 8 each). And the animals were exposed to normoxia or hypoxia for 3, 7, 14 or 21 days respectively. The HPH model was established by normobaric intermittent hypoxia. Mean pulmonary arterial pressure (mPAP), ratio of vascular wall area to total vascular area (WA%), ratio of vascular lumen area to total vascular area (LA%) and right ventricle hypertrophy index (RVHI) were measured. The mRNA and protein relative levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by in situ hybridization and immunohistochemistry respectively. Reverse transcriptase-polymerase chain reaction ( RT-PCR) and in situ hybridization were used to determine the relative expressions of mRNA of hypoxia-inducible factor-1 (FIH) and Siahl. Immunohistochemistry and Western blot were employed to determine the relative expressions of proteins of FIH and Siahl. RESULTS: The levels of mPAP, WA% and LA% were significantly higher after 7-day hypoxia than those in normoxic control (21. 3 1. 6) vs (15. 9 ± 1. 3) mmHg (1 mmHg = 0. 133 kPa), (41.4 ± 2.8)% vs (35.0 ± 2.2)%, (58.6 ± 2.8)% vs (65.0 ± 2.2)%, all P <0.05). The level of RVHI was significantly higher after 14-day hypoxia than that in normoxic control ((27. 0 ± 1. 8) % vs (3. 2 ± 2. 1) %, P <0. 05). The relative expression of HIF-1α mRNA was significantly higher after 14-day hypoxia than that in normoxic control (0. 188 ± 0. 014 vs 0. 150 ± 0. 014, P < 0. 05). The relative expression of HIF-1α protein was significantly higher after 3-day hypoxia than that in normoxic control (0. 186 ± 0.014 vs 0. 067 ± 0.008, P <0.05). The relative levels of VEGF mRNA and protein were significantly higher after 7-day hypoxia than those in normoxic control (0. 152 ± 0. 019 vs 0. 057 ± 0. 007, 0. 176 ± 0. 017 vs 0. 083 ± 0. 010, both P <0. 05). The relative expression of FIH mRNA had little changes after exposure to hypoxia compared with normoxia. However the related expression of FIH protein was markedly lower after 7-day hypoxia than that in normoxic control (0. 166 ± 0. 015 vs 0. 200 ± 0. 017, P < 0. 05). The relative levels of Siahl mRNA and protein were markedly higher after 7-day hypoxia than those in normoxic control (0. 144 ± 0. 014 vs 0. 067 ± 0. 010, 0. 136 ± 0. 017 vs 0. 084 ± 0. 019, both P <0. 05). Linear correlation analysis showed that HIF-1α protein was positively correlated with the relative levels of VEGF mRNA and VEGF protein (r = 0. 545, 0. 523, both P <0. 01) while FIH protein was negatively correlated with the relative levels of VEGF mRNA and VEGF protein (r = -0. 785, -0. 788, both P < 0. 01). There was a positive correlation between the relative levels of Siahi mRNA and Siahl protein (r = 0. 823, P <0. 01) while a negative correlation existed between the relative levels of Siahl protein and FIH protein (r = -0. 671, P <0. 01). CONCLUSIONS: Under chronic hypoxia, Siahl is transcriptionally induced in pulmonary arterioles and it facilitates the degradation and decline of FIR in rats. And deceased FIH protein in pulmonary arterioles under hypoxia may attenuate its inhibitory effect on the transactivational activity of HIF-l a and promote the transactivation of such HIF-1α target gene as VEGF. Thus it is probably implicated in the pathogenesis of HPH.

Nicotine elevated intracellular Ca²âº in rat airway smooth muscle cells via activating and up-regulating α7-nicotinic acetylcholine receptor.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with airway smooth muscle (ASM) hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca(2+) concentration ([Ca(2+)]i) plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR) activation plays a role in the elevation of [Ca(2+)]i in airway smooth muscle cells (ASMCs). METHODS: We examined the expression of nAChR and characterized the functions of α7-nAChR in ASMCs. RESULTS: RT-PCR analysis showed that α2-7, ß2, and ß3-nAChR subunits are expressed in rat ASMCs, with α7 being one of the most abundantly expressed subtypes. Chronic nicotine exposure increased α7-nAChR mRNA and protein expression, and elevated resting [Ca(2+)]i in cultured rat ASMCs. Acute application of nicotine evoked a rapid increase in [Ca(2+)]i in a concentration-dependent manner, and the response was significantly enhanced in ASMCs cultured with 1 µM nicotine for 48 hours. Nicotine-induced Ca(2+) response was reversibly blocked by the α7-nAChR nicotinic antagonists, methyllycaconitine and α-bungarotoxin. Small interfering RNA suppression of α7-nAChR also substantially blunted the Ca(2+) responses induced by nicotine. CONCLUSION: These observations suggest that nicotine elevates [Ca(2+)]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.that nicotine elevates [Ca(2+)]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.

Arctic sea ice-air interactions weaken El Niño-Southern Oscillation.

El Niño-Southern Oscillation (ENSO) over the tropical Pacific can affect Arctic climate, but whether it can be influenced by the Arctic is unclear. Using model simulations, we show that Arctic sea ice-air interactions weaken ENSO by about 12 to 17%. The northern North Pacific Ocean warms due to increased absorption of solar radiation under such interactions. The warming excites an anomalous tropospheric Rossby wave propagating equatorward into the tropical Pacific to strengthen cross-equator winds and deepen the thermocline. These mean changes dampen ENSO amplitude via weakened thermocline and zonal advective feedbacks. Observed historical changes from 1921-1960 (with strong sea ice-air interactions) to 1971-2000 (with weak interactions) are qualitatively consistent with the model results. Our findings suggest that Arctic sea ice-air interactions affect both the mean state and variability in the tropical Pacific, and imply increased ENSO amplitude as Arctic sea ice and its interactions with the atmosphere diminish under anthropogenic warming.

G6PD is a prognostic biomarker correlated with immune infiltrates in lung adenocarcinoma and pulmonary arterial hypertension.

BACKGROUND: Lung adenocarcinoma (LUAD) with Pulmonary arterial hypertension (PAH) shows a poor prognosis. Detecting related genes is imperative for prognosis prediction. METHODS: The gene expression profiles of LUAD and PAH were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, respectively. The co-expression modules associated with LUAD and PAH were evaluated using the Weighted Gene Co-Expression Network Analysis (WGCNA). The relationship between key gene expression with immune-cell infiltration and the tumor immune microenvironment (TIME) was evaluated. We confirmed the mRNA and protein levels in vivo and vitro. G6PD knockdown was used to conduct the colony formation assay, transwell invasion assay, and scratch wound assay of A549 cells. EDU staining and CCK8 assay were performed on G6PD knockdown HPASMCs. We identified therapeutic drug molecules and performed molecular docking between the key gene and small drug molecules. RESULTS: Three major modules and 52 overlapped genes were recognized in LUAD and PAH. We identified the key gene G6PD, which was significantly upregulated in LUAD and PAH. In addition, we discovered a significant difference in infiltration for most immune cells between high- and low-G6PD expression groups. The mRNA and protein expressions of G6PD were significantly upregulated in LUAD and PAH. G6PD knockdown decreased proliferation, cloning, and migration of A549 cells and cell proliferation in HPASMCs. We screened five potential drug molecules against G6PD and targeted glutaraldehyde by molecular docking. CONCLUSIONS: This study reveals that G6PD is an immune-related biomarker and a possible therapeutic target for LUAD and PAH patients.

Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.

Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.

Rising rainfall intensity induces spatially divergent hydrological changes within a large river basin.

Droughts or floods are usually attributed to precipitation deficits or surpluses, both of which may become more frequent and severe under continued global warming. Concurring large-scale droughts in the Southwest and flooding in the Southeast of China in recent decades have attracted considerable attention, but their causes and interrelations are not well understood. Here, we examine spatiotemporal changes in hydrometeorological variables and investigate the mechanism underlying contrasting soil dryness/wetness patterns over a 54-year period (1965-2018) across a representative mega-watershed in South China-the West River Basin. We demonstrate that increasing rainfall intensity leads to severe drying upstream with decreases in soil water storage, water yield, and baseflow, versus increases therein downstream. Our study highlights a simultaneous occurrence of increased drought and flooding risks due to contrasting interactions between rainfall intensification and topography across the river basin, implying increasingly vulnerable water and food security under continued climate change.

Rapid summer Russian Arctic sea-ice loss enhances the risk of recent Eastern Siberian wildfires.

In recent decades boreal wildfires have occurred frequently over eastern Siberia, leading to increased emissions of carbon dioxide and pollutants. However, it is unclear what factors have contributed to recent increases in these wildfires. Here, using the data we show that background eastern Siberian Arctic warming (BAW) related to summer Russian Arctic sea-ice decline accounts for ~79% of the increase in summer vapor pressure deficit (VPD) that controls wildfires over eastern Siberia over 2004-2021 with the remaining ~21% related to internal atmospheric variability associated with changes in Siberian blocking events. We further demonstrate that Siberian blocking events are occurring at higher latitudes, are more persistent and have larger zonal scales and slower decay due to smaller meridional potential vorticity gradients caused by stronger BAW under lower sea-ice. These changes lead to more persistent, widespread and intense high-latitude warming and VPD, thus contributing to recent increases in eastern Siberian high-latitude wildfires.

[Sublingual gland amyloidosis causing obstructive sleep apnea hypopnea syndrome: a case report and review of the literatures].

OBJECTIVE: To improve the understanding of sublingual gland amyloidosis causing obstructive sleep apnea hypopnea syndrome(OSAHS). METHODS: A case of sublingual gland amyloidosis causing OSAHS diagnosed in april 2012 was reported and the related literatures were reviewed. The literature review was carried out respectively with "amyloidosis, sublingual gland, obstructive sleep apnea hypopnea syndrome", as the search terms in Wanfang Data and PubMed by November 2012. RESULTS: A case of 74 year-old male patient was admitted to the hospital because of snoring for 5 years, sleep apnea for 1 year and arousal for 1 month. After admission, polysomnography showed severe OSAHS, physical examination showed redundant the sublingual gland. Enhanced CT scanning showed soft tissue masses at the sublingual gland. Abdominal B ultrasonic and CT also showed a spaces-occupying lesion in the left retroperitoneal. B-guided core needle biopsy was performed in the left retroperitoneal. Pathology report showed amyloidosis. Subsequently, sublingual gland mass resection was performed. Pathology report after operation showed amyloid deposits staining with Congo red, which gives it a characteristic green birefringence in polarised light. Accordingly, it was diagnosed as sublingual gland amyloidosis. The symptoms of snore and sleep apnea were disappeared after operation.So far, there was no local recurrence with 10 months follow-up. A total of 3 literatures were received in Wanfang Data, including 2 of macroglossia amyloidosis causeing OSAHS case report and one of retrospective study. There were no reports about sublingual gland amyloidosis in Wanfang Data. A total of 5 literatures were received in Pubmed, including 2 of sublingual gland amyloidosis case report, 2 of macroglossia amyloidosis causeing OSAHS case report and one of retrospective study. However, there were no reports about sublingual gland amyloidosis causing OSAHS. CONCLUSIONS: Amyloidosis rarely occurred in the sublingual gland and is easy to be misdiagnosed and missed diagnosed, which can causing severe OSAHS. To make a definite diagnosis, histopathology and staining with Congo red are needed and a characteristic green birefringence in polarised light is a reliable marker for diagnosis. After sublingual gland mass resection, the patient had good prognosis.