m6A- and m5C- modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A- modified LINC00893 regulates cutaneous melanoma cell metastasis.

BACKGROUND: As the most important modifications on the RNA level, N6-methyladenosine (m6A-) and 5-methylcytosine (m5C-) modification could have a direct influence on the RNAs. Long non-coding RNAs (lncRNAs) could also be modified by methylcytosine modification. Compared with mRNAs, the function of lncRNAs could be more potent to some extent in biological processes like tumorigenesis. Until now, rare reports have been done associated with cutaneous melanoma. Herein, we wonder if the m6A- and m5C- modified lncRNAs could influence the immune landscape and prognosis in melanoma, and we also want to find some lncRNAs which could directly affect the malignant behaviors of melanoma. METHODS: Systematically, we explored the expression pattern of m6A- and m5C- modified lncRNAs in melanoma from datasets including UCSC Xena and NCBI GEO, and the prognostic lncRNAs were selected. Then, according to the expression pattern of lncRNAs, melanoma samples from these datasets were divided into several subtypes. Prognostic model, nomogram survival model, drug sensitivity, GO, and KEGG pathway analysis were performed. Furthermore, among several selected lncRNAs, we identified one lncRNA named LINC00893 and investigated its expression pattern and its biological function in melanoma cell lines. RESULTS: We identified 27 m6A- and m5C- related lncRNAs which were significantly associated with survival, and we made a subtype analysis of melanoma samples based on these 27 lncRNAs. Among the two subtypes, we found differences of immune cells infiltration between these two subtypes. Then, LASSO algorithm was used to screen the optimized lncRNAs combination including ZNF252P-AS1, MIAT, FAM13A-AS1, LINC-PINT, LINC00893, AGAP2-AS1, OIP5-AS1, and SEMA6A-AS1. We also found that there was a significant correlation between the different risk groups predicted based on RS model and the actual prognosis. The nomogram survival model based on independent survival prognostic factors was also constructed. Besides, sensitivity to chemotherapeutic agents, GO and KEGG analysis were performed. In different risk groups, a total of 14 drug molecules with different distributions were obtained, which included AZD6482, AZD7762, AZD8055, camptothecin, dasatinib, erlotinib, gefitinib, gemcitabine, GSK269962A, nilotinib, rapamycin, and sorafenib. A total of 55 significantly related biological processes and 17 KEGG signaling pathways were screened. At last, we noticed that LINC00893 had a relatively lower expression in melanoma tissue and cell lines compared with adjacent tissues and epidermal melanocyte, and down-regulation of LINC00893 could promote the malignant behavior of melanoma cells in A875 and MV3. In these two melanoma cell lines, down-regulation of m6A-related molecules like YTHDF3 and METTL3 could promote the expression of LINC00893. CONCLUSION: We made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis.

Brain-derived neurotrophic factor promotes airway smooth muscle cell proliferation in asthma through regulation of transient receptor potential channel-mediated autophagy.

OBJECTIVE: Increased proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. This study aims to determine whether brain-derived neurotrophic factor (BDNF) regulates ASMC proliferation and airway remodeling via the transient receptor potential channels (TRPCs)/autophagy axis. METHODS: Human ASMCs were isolated and passively sensitized with human asthmatic serum. Protein levels of BDNF and its receptor TrkB, TRPC1/3/6, autophagy markers, intracellular Ca2+ concentration ([Ca2+]i), LC3 immunofluorescence, cell proliferation, cell cycle population were examined. Wistar rats were sensitized with OVA to establish asthma models. RESULTS: In asthmatic serum-sensitized human ASMCs, BDNF overexpression or recombinant BDNF (rhBDNF) increased TrkB/TRPC1/3/6 axis, [Ca2+]i, autophagy level, cell proliferation, cell number in the S+G2/M phase and decreased cell number in the G0/G1 phase, whereas BDNF knockdown exerted the opposite effects. Furthermore, TRPC channel blocker SKF96365 and TRPC1/3/6 knockdown reversed the effects of the rhBDNF-mediated induction of [Ca2+]i, autophagy level, cell proliferation and cell number in the S+G2/M phase. Moreover, the autophagy inhibitor (3-MA) rescued the rhBDNF-mediated induction of cell proliferation and cell number in the S+G2/M phase. Further in vivo assays revealed that BDNF altered the pathology of airway remodeling, promoted the infiltration of inflammatory cells, promoted the proliferation of ASMCs, and upregulated the protein levels of TrkB, TRPC1/3/6, and autophagy markers in asthma model rats. CONCLUSION: We conclude that BDNF promotes ASMCs proliferation in asthma through TRPC-mediated autophagy induction.

Amygdalin alleviated TGF-ß-induced epithelial-mesenchymal transition in bronchial epithelial cells.

OBJECTIVE: Transforming growth factor-beta TGF-ß-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amygdalin, an active ingredient in bitter almonds, in TGF-ß-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects. METHODS: An asthmatic mouse model was established through ovalbumin induction. Primary mouse bronchial epithelial cells and a human bronchial epithelial cell line were incubated with transforming growth factor-beta (TGF-ß) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE). RESULTS: In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expressions of EMT markers (α-SMA and vimentin). In TGF-ß-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (α-SMA, vimentin, and fibronectin) without impairing cell viability. Through the Swiss Target Prediction database, HPSE was screened as a candidate downstream target for amygdalin. HPSE overexpression further promoted TGF-ß-induced EMT while the HPSE inhibitor suppressed TGF-ß-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-ß-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination. CONCLUSION: Our study showed that amygdalin inhibited TGF-ß-induced EMT in bronchial epithelial cells and found that the anti-EMT activity of amygdalin might be related to its regulatory effect on HPSE expression.

N6-methyladenosine reader YTHDF3 regulates melanoma metastasis via its 'executor'LOXL3.

BACKGROUND: A number of studies have demonstrated that N6-methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive. METHODS: RT-qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase-like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi-omics analysis including RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR and CRISPR-Cas13b-based epitranscriptome engineering. RESULTS: In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA-binding protein 7 (CHD7) were identified by means of RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses. Besides, RT-qPCR, Western blot, RIP-qPCR and MeRIP-qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR-Cas13b-based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation. CONCLUSIONS: The YTHDF3-LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.

WDR5 is a prognostic biomarker of brain metastasis from non-small cell lung cancer.

Background: Lung cancer (LC) is the most frequent caner type and causes the most cancer-related death. Brain metastases (BM) are the deadliest complications of lung cancer, and the prognostic biomarkers of BM are urgently needed. Materials and methods: In our study, we established an inception cohort including 122 patients with asynchronous BM from NSCLC, and further selected 70 patients who received surgical resection, which compromised the validation cohort. With immunohistochemistry, we investigated the expression of WDR5 in the cohort. By chi-square method, the correlations between WDR5 and clinicopathological factors were analyzed. The prognostic indicators were analyzed with the univariate analysis, and independent prognostic factors were identified by multivariate analysis with Cox-regression model. Results: WDR5 is frequently expressed in the cytoplasm of BM from NSCLC. Patients with low or high expression of WDR5 account for 60% and 40% respectively. High expression of WDR5 indicates poor prognosis of BM from NSCLC (P=0.001). In addition to WDR5, KPS is also a prognostic factor of BM, and high KPS predicts favorable prognosis (P=0.006). WDR5 is an independent prognostic biomarker for poor prognosis of BM from NSCLC, with the cancer-related odds as 2.48. Conclusions: High expression of WDR5 can predict the poor prognosis of BM, and WDR5 is an independent prognostic biomarker of BM from NSCLC. Patients with WDR5 overexpression are more high-risk to suffer BM-related death and should receive more intense post-operational supervision.

SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a.

BACKGROUND: Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness, bronchial inflammation, and airway remodeling. Abnormal proliferation of airway smooth muscle cells (ASMCs) is the main pathological feature of asthma. This study investigated the function and mechanism of serine arginine-rich splicing factor 1 (SRSF1) in ASMC proliferation in asthma. METHODS: SRSF1 expressions in the bronchi of ovalbumin-induced asthmatic mice and IgE-treated mouse ASMCs (mASMCs) were evaluated using quantitative real-time PCR and Western blot. The localization and expression of SRSF1 in the bronchi of asthmatic mice were assessed by immunohistochemistry. Functionally, gain- and loss-of-function assays, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were conducted. Mechanistically, RNA degradation assay, RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays were carried out. RESULTS: SRSF1 was highly expressed in the bronchi of ovalbumin-induced asthma mice and IgE-treated mASMCs and was mainly located in the nucleus. Experiments on the function of SRSF1 showed that the silencing of SRSF1 induced the cell cycle of mASMC arrest and restrained mASMC proliferation. Investigations into the mechanism of SRSF1 revealed that SRSF1 and miR-135a are competitively bound to the 3'UTR region of Cyclin D2 (CCND2). SRSF1 overexpression repressed the degradation of CCND2 mRNA, and miR-135a negatively regulated CCND2 expression. Furthermore, SRSF1 knockdown inhibited ASMC proliferation in asthma mouse models by regulating the levels of miR-135a and CCND2. CONCLUSION: SRSF1 knockdown repressed ASMC proliferation in asthma by regulating miR-135a/CCND2 levels.

Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.

Correction: Overexpression of Nrdp1 in the Heart Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice.

[This corrects the article DOI: 10.1371/journal.pone.0021104.].

[Regeneration characteristics of three natural Juniperus forests in the Three-River Headwater Region of Qinghai Province, China]. / 青海三江源地区三种天然圆柏林更新特征.

The aims of this study were to clarify the regeneration characteristics and dominant factors affecting the regeneration of three natural Juniperus forests in the Three-River Headwater Region of Qinghai Province, and thus to provide a reference for the protection and management of natural forests. We evaluated the natural regeneration levels of Juniperus forests, and the effects of stand factors and soil factors on natural regeneration. The results showed that three natural Juniperus forests were poorly regenerated, with insufficient regeneration potential. The average regeneration density of J. tibetica forest, J. przewalskii forest and J. convallium forest was 332, 279 and 202 ind·hm-2, respectively. The height range of regenerate individuals was concentrated in 1-3 m. Only a few seedlings (12 ind·hm-2) were found under the J. tibetica forest, and no seedlings were found under the J. convallium and J. przewalskii forests. The regeneration density of J. tibetica forest was significantly positively correlated with stand density, soil organic matter and available phosphorus, and negatively correlated with shrub coverage. The regeneration density of J. convallium forest was significantly negatively correlated with herb coverage, human disturbance degree, woodland slope and soil total nitrogen, and positively correlated with soil water content. The regeneration density of J. przewalskii forest was significantly positively correlated with stand density, soil available potassium and available phosphorus, but negatively correlated with herb coverage. Results of multiple regression analysis showed that the regeneration of J. tibetica forest was mainly affected by understory shrub coverage and soil available phosphorus, that of J. convallium forest was mainly affected by understory herb coverage, soil total nitrogen and human disturbance, and that of J. przewalskii forest was mainly affected by understory herb coverage and soil available potassium. It was necessary to strengthen forest enclosure, management and protection, rationally regu-late the coverage of understory vegetation, increase soil fertility and improve biotope in the forest, which would promote the protection and natural regeneration of natural Juniperus forests in the Three-River Headwater Region.

[Characteristics of Bacterioplankton Community Between River and Lake/Reservoir in the Yangtze River Basin].

To explore the bacterioplankton community structure in the Yangtze River basin, water samples were collected from 177 sampling sites, including the source to the estuary along the mainstream of the Yangtze River, eight primary tributaries, and several lakes and reservoirs. The 16S rRNA genes were used to explore the bacterioplankton communities based on single molecule real-time sequencing, with the aim to study the diversity and community characteristics in a border sampling area and higher species annotation accuracy. Based on α-diversity analysis, the river area had higher species richness than that of the lake/reservoir area, resulting in these two areas having different bacterioplankton community diversities. Based on the ß diversity analysis, the bacterioplankton showed different community compositions between the river and lake/reservoir areas; temperature was the key environmental factor for the river area, and pH was the key environmental factor for the lake/reservoir area. In order to study the influence of different bacterioplankton communities, this study further investigated the species, function, and community differences between the river and lake/reservoir areas. The results were as follows:for the river area, the eutrophication level gradually increased from west to east along the mainstream of the Yangtze River, resulting in a gradually increased relative abundance of specific species. The lake/reservoir area had a higher risk of cyanobacteria bloom, and the opportunistic pathogen had a high relative abundance in the Danjiangkou Reservoir, indicating a higher ecological risk. For species composition, the river and lake/reservoir areas shared most OTUs (84%); however, some uncultured bacteria showed a high relative abundance in the Yangtze River, meaning the bacterioplankton of the Yangtze River basin still requires further study. In general, the river and lake/reservoir shared most species; however, the different bacterioplankton diversity, community composition, and enriched species made the river and lake/reservoir have different key environmental factors, and they also showed differences in ecological functions.

Effects of sand burial depth on Xanthium spinosum seed germination and seedling growth.

In desert habitats, sand burial is an important factor affecting germination of plant seeds and seedling growth. Xanthium spinosum has strong adaptability in arid desert areas, and is a common malignant invasive plant in Xinjiang, China. The effects of different sand burial depths on seed germination, seedling emergence, growth and biomass allocation were studied to provide a scientific basis for further control of X. spinosum. Six sand burial depths (1, 2, 3, 5, 7 and 9 cm) were established to explore the response of X. spinosum seed germination and seedling growth to sand burial. The first emergence time, peak emergence time, emergence rate, seedling growth height, biomass and biomass distribution of X. spinosum seeds was significantly different at sand burial depths (P < 0.05). The X. spinosum seeds had the highest emergence rate (71.5%) at 1 cm sand burial and the maximum seedling height (7.1 cm). As sand burial depth increased, the emergence rate and seedling height gradually decreased. Emergence rate (12.25%) and seedling height (2.9 cm) were lowest at 9 cm sand burial. The root length at 9 cm depth (13.6 cm) was significantly higher than that at other sand depths (P < 0.05). The sand burial depth affected the biomass accumulation and distribution of X. spinosum. As sand burial depth increased, the root biomass and rhizome ratio increased, and the most deeply buried seedlings allocated more biomass for root growth. The optimal sand burial depth for seed germination and seedling growth of X. spinosum was 1-3 cm, and high burial depth (5-9 cm) was not conducive to the germination and growth of X. spinosum seedlings. For prevention and control of X. spinosum, we suggest deeply ploughing crops before sowing to ensure X. spinosum seeds are ploughed into a deep soil layer.

Exosomal transfer of activated neutrophil-derived lncRNA CRNDE promotes proliferation and migration of airway smooth muscle cells in asthma.

Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation and migration were measured. The interplay of colorectal neoplasia differentially expressed (CRNDE), inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKß phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKß inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKß phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

Erratum: CDC20 regulates cardiac hypertrophy via targeting LC3-dependent autophagy: Erratum.

[This corrects the article DOI: 10.7150/thno.27706.].

Wheat embryo globulin nutrients ameliorate d-galactose and aluminum chloride-induced cognitive impairment in rats.

Wheat embryo globulin nutrient (WEGN), with wheat embryo globulin (WEG) as the main functional component, is a nutritional combination that specifically targets memory impairment. In this study, we explored the protective role of WEGN on Alzheimer's disease (AD)-triggered cognitive impairment, neuronal injury, oxidative stress, and acetylcholine system disorder. Specifically, we established an AD model via administration of d-galactose (d-gal) and Aluminum chloride (AlCl3) for 70 days, then on the 36th day, administered animals in the donepezil and WEGN (300, 600, and 900 mg/kg) groups with drugs by gavage for 35 days. Learning and memory ability of the treated rats was tested using the Morris water maze (MWM) and novel object recognition (NOR) test, while pathological changes and neuronal death in their hippocampus CA1 were detected via HE staining and Nissl staining. Moreover, we determined antioxidant enzymes by measuring levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum, cortex, and hippocampus, whereas changes in the acetylcholine system were determined by evaluating choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities, as well as choline acetylcholine (Ach) content. Results revealed that rats in the WEGN group exhibited significantly lower escape latency, as well as a significantly higher number of targeted crossings and longer residence times in the target quadrant, relative to those in the model group. Notably, rats in the WEGN group spent more time exploring new objects and exhibited lower damage to their hippocampus neuron, had improved learning and memory activity, as well as reversed histological alterations, relative to those in the model group. Meanwhile, biochemical examinations revealed that rats in the WEGN group had significantly lower MDA levels and AChE activities, but significantly higher GSH, SOD, and ChAT activities, as well as Ach content, relative to those in the model group. Overall, these findings indicate that WEGN exerts protective effects on cognitive impairment, neuronal damage, oxidative stress, and choline function in AD rats treated by d-gal/AlCl3.

[Criteria of "arrival of qi" of acupuncture from "reaction of spirit produces curative effect": inheriting SHI Xue-min's thoughts of treating spirit].

From "arrival of qi produces curative effect", it is considered that arrival of qi, qi reaching and acupuncture sensation cannot contain the effect attribute, location attribute and performance attribute of acupuncture at the same time, so it is necessary to find a more suitable standard to measure the arrival of qi and clinical curative effect. Inspired by "the arrival of qi should be reaction of spirit, and reaction of spirit produces curative effect", the authors propose to use the term "reaction of spirit" to summarize the numerous external manifestations of arrival of qi, and to coordinate the attributes of arrival of qi, qi reaching and acupuncture sensation. Academician SHI Xue-min guides the clinical treatment with "reaction of spirit produces curative effect", attaches importance to the spirit treatment to improve the clinical curative effect, and evaluates whether acupuncture is successful or not with "reaction of spirit".

Effect of alprostadil in the treatment of intensive care unit patients with acute renal injury.

BACKGROUND: Acute kidney injury (AKI) is a sudden or rapid decline in the filtration function of the kidneys which is marked by increased serum creatinine or blood urea nitrogen. AIM: To examine the value of alprostadil-assisted continuous venous-venous hemofiltration (CVVH) in the treatment of severe AKI in severely ill patients. METHODS: This was a retrospective study and the inclusion criteria were as follows: (1) Age of patients (≥ 18 years); (2) Admission to intensive care unit due to non-renal primary disease, APACHE II score (≥ 18 points); (3) The diagnostic criteria of AKI guidelines were formulated with reference to the Global Organization for the Improvement of Prognosis in Kidney Diseases, with AKI grades of II-III; (4) All patients were treated with CVVH; and (5) Complete basic data were obtained for all patients. RESULTS: The clinical effect of alprostadil administered in the treatment group was better than that observed in the control group (P < 0.05). The urine output of patients in the alprostadil group returned to normal time (9.1 ± 2.0 d) and was lower than that in the control group (10.6 ± 2.5 d), the difference was statistically significant (P < 0.05); adverse reactions occurred in the alprostadil group compared with the control group, but the difference was not statistically significant (P > 0.05). CONCLUSION: Alprostadil-assisted CVVH in the treatment of severely ill patients with AKI can effectively improve the renal resistance index and partial pressure of urine oxygen, and has a positive effect on improving renal function.

Iatrogenic Arsenism Characterized by Palmoplantar Hyperkeratosis and Diffused Skin Cancers for Over Decades.

ABSTRACT: Chronic arsenism usually occurs after a long-term unawareness of arsenic exposure from environment, occupation, food, and water. We here reported 3 cases with diffused arsenic keratosis and skin cancers derived from long-term arsenic medication ingestion. In these cases, hyperkeratotic skin lesions were initially found on palms and soles, slowly progressed to every part of the skin and lasted maximally for over 30 years. Skin cancers were diagnosed and removed intermittently within decades, but with no malignancies in other organs. Oral retinoids combing with topical 5- fluorouracil and photodynamic treatment yielded a desirable outcome.