Globular adiponectin induces esophageal adenocarcinoma cell pyroptosis via the miR-378a-3p/UHRF1 axis.

BACKGROUND: Antiapoptosis is a major factor in the resistance of tumor cells to chemotherapy and radiotherapy. Thus, activation of cell pyroptosis may be an effective option to deal with antiapoptotic cancers such as esophageal adenocarcinoma (EAC). METHODS: Differential expression of ubiquitin-like versus PHD and ring finger structural domain 1 (UHRF1) in EAC and near normal tissues was analyzed, as well as the prognostic impact on survival in EAC. Also, the same study was done for globular adiponectin (gAD). Simultaneously, the mRNA expression of UHRF1 was observed in different EAC cell lines. Real time cellular analysis (RTCA) was used to detect cell proliferation, and flow cytometry and inverted fluorescence microscopy were used to detect pyroptosis. Biocredit analysis was conducted to observe the correlation between UHRF1 and key pyroptosis proteins. OD values and CCK8 assay were used to determine the effect of miR-378a-3p on EAC cells. Quantitative real-time polymerase chain reaction and Western blot were used to detect the correlation between UHRF1, gAD, and miR-378a-3p in EAC cells. Moreover, in vivo and in vitro experiments were performed to detect the relevant effects on tumor migration and invasion after inhibiting UHRF1 expression. RESULTS: UHRF1 was negatively correlated with the survival of patients with EAC, while miR-378a-3p showed the opposite effect. Additionally, gAD promoted EAC cell pyroptosis, upregulated miR-378a-3p, and significantly inhibited the proliferation of EAC cells. gAD directly reduced UHRF1 expression in EAC cells by upregulating miR-378a-3p. In cell migration and invasion assays, inhibition of UHRF1 expression significantly suppressed EAC cell metastasis. In animal experiments, we again demonstrated that gAD induced pyroptosis in EAC cells by inhibiting the expression of UHRF1. CONCLUSION: gAD-induced upregulation of miR-378a-3p significantly inhibited the proliferation of EAC by targeting UHRF1. Therefore, gAD may serve as an alternative therapy for chemotherapy- and radiation-refractory EAC or other cancers with the same mechanism of pyroptosis action.

The value of multimodal functional magnetic resonance imaging in differentiating p53abn from p53wt endometrial carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is the sixth most common cancer in women. P53 gene expression in patients with endometrial cancer can predict the efficacy and prognosis of patients with neoadjuvant therapy. PURPOSE: To explore the value of multimodal magnetic resonance imaging (MRI) in differentiating p53 abnormal (p53abn) from p53 wild-type (p53wt) EC. MATERIAL AND METHODS: Data from 47 EC patients, including 14 p53abn cases and 33 p53wt cases, were retrospectively analyzed. The preoperative MRI sequences included amide proton transfer weighted (APTw) imaging, T2 mapping, mDIXON-Quant imaging and diffusion-weighted imaging (DWI). After post-processing, APT, T2, transverse relaxation rate (R2*), fat fraction (FF) and apparent diffusion coefficient (ADC) maps were obtained. The APT, T2, R2*, FF and ADC values for lesions of the two groups of cases were measured by two observers who were blind to the pathological data. RESULTS: The APT value and R2* value in the p53abn group were higher than those in the p53wt group, while the ADC value was lower (all P < 0.05). There was no statistically significant difference in T2 value and FF value between the two groups (all P > 0.05). The area under curve of APT, R2*, ADC and combined APT + R2*+ADC values for identification of p53abn and p53wt EC were 0.739, 0.689, 0.718 and 0.820, respectively (all P > 0.05). CONCLUSION: APTw, mDIXON-Quant and DWI techniques can be usedfor quantitative identification of p53abn and p53wt EC. The multimodal MRI provides a new way for preoperative quantitative evaluation of EC molecular typing, which has certain clinical application value.

A novel femoral artery compression device (butterfly compress) versus manual compression for hemostasis after femoral artery puncture: a randomized comparison.

OBJECTIVE: This study aimed to investigate the hemostatic efficacy of a novel femoral artery compression device in patients undergoing an interventional procedure through femoral artery puncture. MATERIAL AND METHODS: Patients enrolled in this trial were randomly assigned 1:1 to the novel femoral artery compression device (NFACD) or the manual compression (MC) group. The primary endpoints were time to hemostasis (TTH), time to ambulation (TTA), any other complications, such as the occurrence of hematoma, bleeding, pseudoaneurysm and arteriovenous fistula at the puncture site, and time to hospital discharge. RESULTS: A total of 617 patients were included in this study (NFACD, n = 308 versus MC, n = 309) from May 2017 to September 2019, and the baseline characteristics of the groups were similar. We found that the TTH and TTA were significantly shorter in the NFACD group than in the MC group (4.4 ± 11.6 min vs. 20.1 ± 22.5 min; p < 0.001; 8.9 ± 14.2 h vs. 16.3 ± 27.5 h; p = 0.002). There were few other complications in either group. In addition, there was no significant difference in time to hospital discharge between the NFACD group and the MC group. CONCLUSION: The novel femoral artery compression device is effective in achieving hemostasis in patients undergoing femoral artery puncture and is associated with a marked shortening of the TTH and TTA.

A intermediate concentration of atmospheric nitrogen dioxide enhances PSII activity and inhibits PSI activity in expanded leaves of tobacco seedlings.

Nitrogen dioxide (NO2) is a major air pollutant that affects plant growth, development and yields. Previous studies have found that atmospheric NO2 changes plant photosynthesis in a concentration-dependent manner. Low concentrations of NO2 (4.0 µL L-1) can increase photosynthetic rates, while high concentrations of NO2 (16.0 µL L-1) can have an inhibitory effect. However, the specific effects of a critical intermediate concentration of NO2 on the photosynthetic apparatus of plants has remained unknown. Therefore, in this study, tobacco seedlings at three-leaf ages were fumigated with a intermediate concentration of 8.0 µL L-1 NO2 for 15 days to determine the effects on leaf weight, leaf number per plant, chlorophyll content, net photosynthetic rate, the reaction center activity of photosystems I and II (PSI and PSII, respectively) and core protein gene expression (PsbA and PsaA). Fumigation with 8.0 µL L-1 NO2 increased the number of leaves per plant and the weight of leaves, and the leaves became dark green and curly after 10 days of fumigation. During NO2 fumigation for 15 days, the chlorophyll content, PSII maximum photochemical efficiency (Fv/Fm), electron transfer rate (ETR) and non-photochemical quenching (NPQ) increased most in the oldest leaves (Lmax leaves), but decreased PSI activity (∆I/Io). The Fv/Fm, ETR and NPQ in the youngest leaves (Lmin leaves) were lower than those of Lmax leaves, but the actual photochemical efficiency (ΦPSII) of PSII increased most and ∆I/Io was the highest in these samples. The Fv/Fm, ETR, NPQ and ΦPSII in the leaves at the middle leaf age (Lmid leaves) were lower than those of Lmin and Lmax leaves, but the relative fluorescence intensity of point L (VL) and the relative fluorescence intensity of point K (VK) decreased the most in these samples. Thus, this critical concentration of atmospheric NO2 increased the activity of PSII and inhibited PSI activity in expanded leaves of tobacco seedlings.

Decoy receptor 2 mediation of the senescent phenotype of tubular cells by interacting with peroxiredoxin 1 presents a novel mechanism of renal fibrosis in diabetic nephropathy.

Premature senescence of renal tubular epithelial cell (RTEC), which is involved in kidney fibrosis, is a key event in the progression of diabetic nephropathy. However, the underlying mechanism remains unclear. Here we investigated the role and mechanism of decoy receptor 2 (DcR2) in kidney fibrosis and the senescent phenotype of RTEC. DcR2 was specifically expressed in senescent RTEC and associated with kidney fibrosis in patients with diabetic nephropathy and mice with streptozotocin-induced with diabetic nephropathy. Knockdown of DcR2 decreased the expression of α-smooth muscle actin, collagen I, fibronectin and serum creatinine levels in streptozotocin-induced mice. DcR2 knockdown also inhibited the expression of senescent markers p16, p21, senescence-associated beta-galactosidase and senescence-associated heterochromatic foci and promoted the secretion of a senescence-associated secretory phenotype including IL-6, TGF-ß1, and matrix metalloproteinase 2 in vitro and in vivo. However, DcR2 overexpression showed the opposite effects. Quantitative proteomics and validation studies revealed that DcR2 interacted with peroxiredoxin 1 (PRDX1), which regulated the cell cycle and senescence. Knockdown of PRDX1 upregulated p16 and cyclin D1 while downregulating cyclin-dependent kinase 6 expression in vitro, resulting in RTEC senescence. Furthermore, PRDX1 knockdown promoted DcR2-induced p16, cyclin D1, IL-6, and TGF-ß1 expression, whereas PRDX1 overexpression led to the opposite results. Subsequently, DcR2 regulated PRDX1 phosphorylation, which could be inhibited by the specific tyrosine kinase inhibitor genistein. Thus, DcR2 mediated the senescent phenotype of RTEC and kidney fibrosis by interacting with PRDX1. Hence, DcR2 may act as a potential therapeutic target for the amelioration of diabetic nephropathy progression.

Elevated air temperature damage to photosynthetic apparatus alleviated by enhanced cyclic electron flow around photosystem I in tobacco leaves.

High temperature can lead to increased production of excess light energy, thus reducing photosynthetic capacity in plants. Photosynthetic cyclic electron flow (CEF) in photosystem I (PSI) can effectively protect photosystems, but its physiological mechanism under high temperature is poorly understood. In this study, antimycin A (AA) and thenoyltrifluoroacetone (TTFA) were used to inhibit PGR5-and NDH-dependent CEF pathways, respectively, to reveal the photoprotective functions of CEF for PSII in tobacco leaves under high temperature stress (37 °C, HT). High temperatures caused decreases in maximal photochemistry efficiency (Fv/Fm) and damaged photosystem II (PSII) in tobacco leaves. Under AA inhibition of PGR5-dependent CEF, high temperature increased the fluorescence intensity of point O (Fo) in OJIP curves, i.e., the energy absorption per active reaction center (ABS/RC), the trapping rate of the reaction center (TRo/RC), and the electron transport efficiency per reaction center (ETo/RC) in tobacco leaves. High temperature induced an increase in the hydrogen peroxide content and a decrease in pigment content in tobacco leaves. Under the high temperature treatment, inhibition of PGR5-dependent CEF reduced the activities of the PSII reaction center significantly, destroyed the oxygen-evolving complex (OEC), and impeded photosynthetic electron transfer from PSII to the plastoquinone (PQ) pool in tobacco leaves. The TTFA treatment inhibited the NDH-dependent pathway under high temperature conditions, with the relative fluorescence intensity of point I (VI) decreased significantly, and the content of hydrogen peroxide and superoxide anion increased significantly. Additionally, Fo and the redox degree of the PSII donor side (Wk) increased, and pigment content decreased compared to the control, but with little change compared to high temperature treatment, indicating that the inhibition of the NDH-dependent pathway directly weakened the capacity of the PQ pool to lead to the accumulation of reactive oxygen species (ROS) in tobacco leaves. In conclusion, CEF alleviated damage to the photosynthetic apparatus in tobacco leaves by increasing PSII heat dissipation, reducing ROS production, and maintaining the stability of the PQ pool to accommodate photosynthetic electron flow.

Physiological and proteomic responses of reactive oxygen species metabolism and antioxidant machinery in mulberry (Morus alba L.) seedling leaves to NaCl and NaHCO3 stress.

In this paper, the effects of 100 mM NaCl and NaHCO3 stress on reactive oxygen species (ROS) and physiological and proteomic aspects of ROS metabolism in mulberry seedling leaves were studied. The results showed that NaCl stress had little effect on photosynthesis and respiration of mulberry seedling leaves. Superoxide dismutase (SOD) activity and the expression of related proteins in leaves increased by varying degrees, and accumulation of superoxide anion (O2·-) not observed. Under NaHCO3 stress, photosynthesis and respiration were significantly inhibited, while the rate of O2·- production rate and H2O2 content increased. The activity of catalase (CAT) and the expression of CAT (W9RJ43) increased under NaCl stress. In response to NaHCO3 stress, the activity and expression of CAT were significantly decreased, but the ability of H2O2 scavenging of peroxidase (POD) was enhanced. The ascorbic acid-glutathione (AsA-GSH) cycle in mulberry seedling leaves was enhancement in both NaCl and NaHCO3 stress. The expression of 2-Cys peroxiredoxin BAS1 (2-Cys Prx BAS1), together with thioredoxin F (TrxF), thioredoxin O1 (TrxO1), thioredoxin-like protein CITRX (Trx CITRX), and thioredoxin-like protein CDSP32 (Trx CDSP32) were significantly increased under NaCl stress. Under NaHCO3 stress, the expression of the electron donor of ferredoxin-thioredoxin reductase (FTR), together with Trx-related proteins, such as thioredoxin M (TrxM), thioredoxin M4 (TrxM4), thioredoxin X (TrxX), TrxF, and Trx CSDP32 were significantly decreased, suggesting that the thioredoxin-peroxiredoxin (Trx-Prx) pathway's function of scavenging H2O2 of in mulberry seedling leaves was inhibited. Taken together, under NaCl stress, excessive production of O2·- mulberry seedlings leaves was inhibited, and H2O2 was effectively scavenged by CAT, AsA-GSH cycle and Trx-Prx pathway. Under NaHCO3 stress, despite the enhanced functions of POD and AsA-GSH cycle, the scavenging of O2·- by SOD was not effective, and that of H2O2 by CAT and Trx-Prx pathway were inhibited; and in turn, the oxidative damage to mulberry seedling leaves could not be reduced.

Toxic effects of heavy metals Pb and Cd on mulberry (Morus alba L.) seedling leaves: Photosynthetic function and reactive oxygen species (ROS) metabolism responses.

To explore the mechanism of how lead (Pb) and cadmium (Cd) stress affects photosynthesis of mulberry (Morus alba L.), we looked at the effects of different concentrations of Pb and Cd stress (at 100 and 200 µmol L-1), which are two heavy metal elements, on leaf chlorophyll (Chl), photosynthesis gas exchange, Chl fluorescence, and reactive oxygen species (ROS) metabolism in mulberry leaves. The results showed that higher concentrations of Pb and Cd reduced leaf Chl content, especially in Chl a where content was more sensitive than in Chl b. Under Pb and Cd stress, the photosynthetic carbon assimilation capacity of mulberry leaves was reduced, which was a consequence of combined limitations of stomatal and non-stomatal factors. The main non-stomatal factors were decreased photosystem II (PSII) and photosystem I (PSI) activity and carboxylation efficiency (CE). Damage to the donor side of the PSII reaction center was greater than the acceptor side. After being treated with 100 µmol L-1 of Pb and Cd, mulberry leaves continued to be able to dissipate excess excitation energy by starting non-photochemical quenching (NPQ), but when Pb and Cd concentrations were increased to 200 µmol L-1, the protection mechanism that depends on NPQ was impaired. Excessive excitation energy from chloroplasts promoted a great increase of ROS, such as superoxide anion (O2•-) and H2O2. Moreover, under high Pb and Cd stress, superoxide dismutase (SOD) and ascorbate peroxidase (APX) were also inhibited to some extent, and excessive ROS also resulted in a significantly higher degree of oxidative damage. Compared with Cd, the effect of Pb stress at the same concentration level displayed a significantly lower impact on Chl content, photosynthetic carbon assimilation, and stomatal conductance. Meanwhile, Pb stress mainly damaged activity of the oxygen-evolving complex (OEC) located on PSII donor side, but it reduced the electronic pressure on the PSII acceptor side and PSI. Furthermore, under Pb stress, the NPQ, SOD, and APX activity were all significantly higher than those under Cd stress. Thus under Pb stress, the degree of photoinhibition and oxidative damage of PSII and PSI in mulberry leaves were significantly lower than under Cd stress.

Chlorophyll synthesis and the photoprotective mechanism in leaves of mulberry (Morus alba L.) seedlings under NaCl and NaHCO3 stress revealed by TMT-based proteomics analyses.

Chlorophyll (Chl) and effective photoprotective mechanism are important prerequisites to ensure the photosynthetic function of plants under stress. In this study, the effects of 100 mmol L-1 NaCl and NaHCO3 stress on chlorophyll synthesis and photosynthetic function of mulberry seedlings were studied by physiological combined with proteomics technology. The results show that: NaCl stress had little effect on the expression of Chl synthesis related proteins, and there were no significant changes in Chl content and Chl a:b ratio. However, 13 of the 15 key proteins in the process of Chl synthesis were significantly decreased under NaHCO3 stress, and the contents of Chl a and Chl b were significantly decreased (especially Chl a). Although stomatal conductance (Gs) decreased significantly under NaCl stress, net photosynthetic rate (Pn), PSII maximum photochemical efficiency (Fv/Fm) and electron transfer rate (ETR) did not change significantly, but under NaHCO3 stress, not only Gs decreased significantly, PSII activity and photosynthetic carbon were the same. In the photoprotective mechanism under NaCl stress, NAD(P)H dehydrogenase (NDH)-dependent cyclic electron flow (CEF) enhanced, the expression of related proteins subunit, ndhH, ndhI, ndhK, and ndhM, the key enzyme of the xanthophyll cycle, violaxanthin de-epoxidase (VDE) were up-regulated, the ratio of (A + Z)/(V + A + Z) and non-photochemical quenching (NPQ) was increased. The expressions of proteins FTR and Fd-NiR were also significant up-regulated under NaCl stress, Fd-dependent ROS metabolism and nitrogen metabolism can effectively reduce the electronic pressure on Fd. Under NaHCO3 stress, the expressions of NDH-dependent CEF related proteins subunit (ndhH, ndhI, ndhK, ndhM and ndhN), VDE, ZE, FTR, Fd-NiR and Fd-GOGAT, were significant down-regulated, and ZE, CP26, ndhK, ndhM, Fd-NiR, Fd-GOGAT and FTR genes expression also significantly decreased, the photoprotective mechanism, like the xanthophyll cycle，CEF and Fd-dependent ROS metabolism and nitrogen metabolism might be damaged, resulting in the inhibition of PSII electron transfer and carbon assimilation in mulberry leaves under NaHCO3 stress.

Elevated NO2 damages the photosynthetic apparatus by inducing the accumulation of superoxide anions and peroxynitrite in tobacco seedling leaves.

This study aimed to further understand the toxicity of high concentrations of nitrogen dioxide (NO2) to plants, especially to plant photosynthesis. Tobacco plants in the six-leaf stage were exposed to 16.0 µL L-1 NO2 to determine the activities of photosystem II (PSII) and photosystem I (PSI) reaction centers, the blocking site of PSII electron transport, the degree of membrane peroxidation and the relative expression of PsbA, PsbO and PsaA genes in the third fully expanded leaves by using gas exchange and chlorophyll fluorescence techniques, biochemical and RT-PCR analysis. The results showed that 16.0 µL L-1 NO2 caused necrotic lesions to form on leaves and significantly increased the generation rate of superoxide anions (O2-) and the content of peroxynitrite (ONOO-) in leaves of tobacco seedling, leading to damage to cell membrane, chlorophyll content and net photosynthetic rate reduction, and photosynthetic apparatus destruction. Fumigation with 16.0 µL L-1 NO2 decreased the activity of PSII reaction center and oxygen evolution complex, and the relative expression of PabA in leaves of tobacco seedlings to inhibit the electron transport from the donor side to the receptor side of PSII, especially blocking the electron transport from QA to QB on the receptor side. The activity of the PSI reaction center and the relative expression of PsaA decreased, weakening the ability to accept electrons and inhibiting the electron transfer from PSII to PSI, which further increased the damage of PSII of tobacco seedling leaves caused by 16.0 µL L-1 NO2. Therefore, 16.0 µL L-1 NO2 leaded to the accumulation of O2- and ONOO-, which damaged the cell membrane and thylakoid membrane, inhibit the electron transport, and destroyed the photosynthetic apparatus in leaves of tobacco seedlings. The results from this study emphasized the importance of reducing the NO2 concentration in the atmosphere.

[Effect of Puyu Capsules on behavior,HPA axis and CREB-BDNF pathway expression in hippocampus of depressed mice].

This study aimed to investigate the antidepressant effects of Puyu Capsules and its potential mechanism. The antidepressant activity of Puyu Capsules was evaluated by forced swimming test(FST) and tail suspension test(TST) after subchronic administration in mice. Next, the mice were subjected to a chronic unpredictable stress(CUS) protocol for a period of 28 d to induce depressive-like behaviors. Then, a sucrose preference test, open-field test and novelty-suppressed feeding test were performed to evaluate the antidepressant effect of Puyu Capsules. After the behavioral test, the adrenal index was calculated; the levels of serum corticosterone(CORT) and adrenocorticotropic hormone(ACTH) were detected by enzyme-linked immunosorbent assay(ELISA); the levels of glucocorticoid receptor(GR), protein expression of brain-derived neurotrophic factor(BDNF), and the ratio of phosphorylated cAMP response element binding protein(CREB) to total CREB were detected by Western blot to explore the antidepressant function and mechanism of Puyu Capsules. The results suggested that Puyu Capsules had significant antidepressant effects on both the depression model and CUS model. At the same time, the drug could prevent the change of adrenal index induced by CUS and reverse the abnormal activation of CORT and ACTH in the serum of depressed mice. Finally, Puyu Capsules could also reverse the lower expression of pCREB, BDNF and GR in the hippocampus of CUS mice. In conclusion, Puyu Capsules produced significant antidepressant effects, and the mechanism was closely related to hypothalamic pituitary adrenal(HPA) axis activity, GR and CREB-BDNF pathway expression.

[Mechanism of Alisma orientale in treating nonalcoholic fatty liver disease].

In this study, network pharmacology technology was combined with molecular docking technology and experimental verification to clarify the active ingredients, potential targets and mechanism of Alisma orientale for nonalcoholic fatty liver disease(NAFLD), providing a basis for its clinical application. The active ingredients of A. orientale were screened through traditional Chinese medicine systems pharmacology database(TCMSP), and the potential targets related to both active ingredients and NAFLD were predicted through protein databases by considering the oral bioavailability(OB) and drug-likeness(DL). The "active ingredient-potential target" network was constructed by using Cytoscape software, and the molecular docking was performed between active ingre-dients and potential targets. KEGG pathway analysis and enrichment analysis were performed through DAVID biological information annotation databases. ClueGO software was used to analyze target GO annotation. Western blot and immunocytochemistry were used to detect the protein expression levels, and fluorescent probe was used to detect the reactive oxygen species(ROS) generation level. The results revealed that 7 active ingredients of A. orientale were obtained from TCMSP database and analysis platform, 140 ingredient-related targets were screened, and 59 potential targets were obtained by intersecting disease targets with ingredient-related targets. Molecular docking showed that 7 active ingredients of A. orientale could act on the potential targets including 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR) and tyrosine-protein phosphatase non-receptor type 1(PTPN1). In addition, KEGG enrichment analysis showed that the potential targets were mainly enriched in inflammatory mediator regulation, insulin resistance, neuroactive ligand-receptor interaction, vascular smooth muscle contraction, FcγR-mediated phagocytosis and other related pathways of tryptophan(TRP) channel. GO enrichment analysis showed that potential targets mainly affected the biological processes of G-protein coupled receptor signaling pathway, organic hydroxyl compound transport, positive regulation of lipid biosynthesis process, positive regulation of lipid metabolic process. Western blot, immunocytochemistry and fluorescent probe confirmed that the extract of A. orientale could reduce HMGCR and PTPN1 protein expression levels effectively, and also could reduce ROS production level of HepG2 cells. This study systematically revealed the material basis and mechanism of A. orientale in regulating NAFLD through multi-component, multi-target, and multi-pathway characteristics, which provided a theoretical basis and scientific basis for the clinical application of A. orientale.

Clinical Significance of Red Blood Cell Distribution Width and Inflammatory Factors for the Disease Activity in Rheumatoid Arthritis.

BACKGROUND: To evaluate the significance of red blood cell distribution width (RDW) and other factors for the disease activity in rheumatoid arthritis (RA). METHODS: Each patient underwent clinical examination and blood sampling for assessment of serum high-sensitivity C-reactive protein (hs-CRP) levels, erythrocyte sedimentation rate (ESR), hemoglobin concentration (Hb), hematocrit (HCT), RDW, and other erythrocyte parameters (mean corpuscular volume [MCV], mean cell Hb [MCH], mean corpuscular Hb concentration [MCHC]). Rheumatoid factors (RF-IgA, -IgG, -IgM) and anti-cyclic citrullinated protein antibodies (anti-CCP) were purified from the plasma and detected by ELISA. RA patients were divided into two groups based on DAS28 scores: active RA group (DAS28 > 5.1) and inactive RA group (DAS28 2.6 - 3.2). RESULTS: Patient samples were within normal ranges for Hb (15.2 ± 1.3 g/L), HCT (29.9 ± 2.2%), and other red blood cell (RBC) parameters (MCV 80.3 ± 12.1 fL, MCH 26.6 ± 3.5 pg, MCHC 323 ± 25 g/L). The RDW was higher in the active RA group than in the inactive group (16.5 ± 3.2 vs. 13.9 ± 1.5%, p < 0.01). Similarly, the proportion of patients positive for RF and anti-CCP was higher in the active group than in the inactive group (RF 62 vs. 53%, CCP 83 vs. 61%). RF and anti-CCP were present at higher titers in patients with active RA. The bone erosion rate in the 110 RA patients was 67%. Patients with erosion had higher RDW than those without erosion (17.1 ± 2.2 vs. 13.9 ± 3.5%). High titers of anti-CCP and RF-IgM, -IgG, and -IgA were also associated with high bone erosion rates (67%, 77%, 67%, and 73%, respectively). CONCLUSIONS: Our results suggest an association between RDW and levels of inflammatory factors and autoantibodies in RA. This association may be linked to the underlying proinflammatory state and increased oxidative stress, both of which correlate with impaired erythrocyte maturation. RDW, RF, and anti-CCP are key players in the proinflammatory and proatherogenic status of RA, and they may represent useful markers to improve characterization of disease activity in RA patients, thereby helping the clinician to define more appropriate therapeutic strategies.

[Effect of Ju-Pi-Tang on Cisplatin-induced Emetic Model in Minks].

OBJECTIVE: To study the antiemetic effect of Ju-Pi-Tang from Jin Kui Yao Lue on cisplatin-induced emetic model in minks, and to observe the immunoexpression of peripheral and central c-fos and substance P. METHODS: The minks were randomly divided into blank control group, Ju-Pi-Tang blank control group, model group, ondansetron group, aprepitant group, Ju-Pi-Tang (in high-, mid-, and low-dose) groups. Every group was administered with the antiemetic agent or distilled water on 24 h before cisplatin injection. The antiemetic effect of drugs was investigated in the emetic model of minks induced by cisplatin in 72 h observation. Immunohistochemistry was used to compare the differences of c-fos and substance P expression in the area postrema of brain and distal ileum tissues. RESULTS: During observation period,compared with model group,the frequency cisplatin induced retching and vomiting was significantly reduced by Ju-Pi-Tang in high- and mid-dose groups, during the 0-24 h acute period, the number of retching of Ju-Pi-Tang in high-dose group was decreased more than aprepitant group, during the 24-72 h delayed period, the number of both retching and vomiting was decreased more than ondansetron group, after 72 h of cisplatin administration, compared with model group, the grey levels of c-fos and substance P expression in distal ileum and brain tissues of Ju-Pi-Tang groups were higher significantly. CONCLUSION: Ju-Pi-Tang has a good effect against cisplatin-induced emesis in minks.

The influence of near-infrared therapy on arteriovenous fistula patency in haemodialysis patients: A multicentre, randomised, controlled clinical trial.

BACKGROUND: Arteriovenous fistula (AVF) is the preferred vascular access for patients undergoing haemodialysis (HD). AVF malfunction remains a major clinical problem and is a significant independent risk factor for death. Although far-infrared (FIR) therapy has been shown to reduce complications and improve the patency rate of AVFs in various studies, it has been cautiously recommended by the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines for AVF care due to insufficient evidence. Therefore, it is necessary to identify more effective methods for preventing AVF dysfunction. Many in vitro studies and few clinical studies have examined the effects of near-infrared (NIR) therapy on the vasculature. This study will examine the effects of NIR therapy on AVF. METHODS: A randomised, controlled, open-label, multicentre trial will compare the effect of NIR on AVF patency after 1 year of therapy with that of a control group of patients with existing AVF. One group of patients received NIR treatment above their AVFs, whereas the control group received regular care. The primary outcome is the primary fistula patency rate within 12 months. In addition, acute changes in inflammatory, vasodilatory and haemodynamic parameters after a single treatment in the first 40 participants will be examined. This study was registered in the Clinical Trials Registry (ChiCTR2300071305) at https://register.clinicaltrials.gov/. DISCUSSIONS: This study will explore the long-term and acute effects of NIR on AVFs. The study findings will provide information that can be used to develop new technical support for the prevention of AVF dysfunction in patients undergoing haemodialysis.

Radiotherapy and surgery remain effective treatment options for retroperitoneal MPNST: a retrospective study based on SEER database.

Introduction: The proportion of retroperitoneal malignant peripheral nerve sheath tumours (RMPNST) in retroperitoneal tumors is less than 5%, but the mortality rate is very high. However, there is no relevant research focused on RMPNST only. Methods: We retrospectively analyzed data from the SEER database of patients with primary RMPNST from 2000 to 2019, by leveraging the advantages of the Seer database, we can explore the prognosis of such rare diseases. Kaplan-Meier method was used to construct the survival curve, and cox regression model was used to analyze the factors affecting the prognosis of patients. In addition, a model was developed to distinguish high-risk and low-risk patients. Results: This study included a total of 52 patients, with a median survival time of 39 months (95% CI 12.740-65.260) and a 5-year survival rate of 44.2% (95% CI 0.299-0.565). Radiotherapy (p = 0.004, OR: 1.475, 95% CI 0.718-3.033), metastasis disease (p = 0.002, OR: 5.596, 95% CI 2.449-47.079) and surgery (p = 0.003, OR: 5.003, 95% CI 0.011-0.409) were associated with overall survival (OS). The 5-year distant metastasis rate was 36% (95% CI 0.221-0.499). We used the above risk factors to separate patients into high and low groups and evaluate the results through the receiver operating characteristic (ROC) curve. This model is beneficial for guiding the selection of treatment strategies. Conclusion: The majority of RMPNST patients have a good prognosis after surgery, and the establishment of high-low group is helpful for clinical decision-making.

Regulation of survival and chemoresistance by HSP90AA1 in ovarian cancer SKOV3 cells.

Previous researches have showed that HSP90AA is important in ovarian cancer, but the mechanism of HSP90AA is still unknown. This study aimed to investigate the role of the potential therapy target protein HSP90AA1 in ovarian cancer. The level of HSP90AA1 in ovarian cancer SKOV3 cell line was altered by RNAi and overexpression. Survival of these cell lines was investigated by tetrazolium-based assay and fluorescence-activated cell sorter (FACS). The chemosensitivity to cisplatin of the cell was also tested by FACS when HSP90AA1 was overexpressed. HSP90AA1 RNAi inhibited the proliferation of ovarian cancer SKOV3 cell line and increased the apoptosis. Furthermore, overexpression of HSP90AA1 decreased the chemosensitivity to cisplatin of SKOV3 cells and overexpression of HSP90AA1 could partially rescue the survival rate of SKOV3 cells which were treated with cisplatin. HSP90AA1 is required for the survival and proliferation of SKOV3 cells. High level of HSP90AA1 can increase chemoresistance to cisplatin of SKOV3 cells.

Multi-step-ahead and interval carbon price forecasting using transformer-based hybrid model.

Accurate and stable carbon price forecasts serve as a reference for assessing the stability of the carbon market and play a vital role in enhancing investment and operational decisions. However, realizing this goal is still a significant challenge, and researchers usually ignore multi-step-ahead and interval forecasting due to the non-linear and non-stationary characteristics of carbon price series and its complex fluctuation features. In this study, a novel hybrid model for accurately predicting carbon prices is proposed. The proposed model combines multi-step-ahead and interval carbon price forecasting based on the Hampel identifier (HI), time-varying filtering-based empirical mode decomposition (TVFEMD), and transformer model. First, HI identifies and corrects outliers in carbon price. Second, TVFEMD decomposes carbon price into several intrinsic mode functions (imfs) to reduce the non-linear and non-stationarity of carbon price to obtain more regular features in series. Next, these imfs are reconstructed by sample entropy (SE). Subsequently, the orthogonal array tuning method is used to optimize the transformer model's hyperparameters to obtain the optimal model structure. Finally, after hyperparameter optimization and quantile loss function, the transformer is used to perform multi-step-ahead and interval forecasting on each part of the reconstruction, and the final prediction result is obtained by summing them up. Five pilot carbon trading markets in China were selected as experimental objects to verify the proposed model's prediction performance. Various benchmark models and evaluation indicators were selected for comparison and analysis. Experimental results show that the proposed HI-TVFEMD-transformer hybrid model achieves an average MAE of 0.6546, 1.3992, 1.6287, and 2.2601 for one-step, three-step, five-step, and ten-step-ahead forecasting, respectively, which significantly outperforms other models. Furthermore, interval forecasts almost always have a PICI above 0.95 at a confidence interval of 0.1, thereby indicating the effectiveness of the hybrid model in describing the uncertainty in the forecasts. Therefore, the proposed hybrid model is a reliable carbon price forecasting tool that can provide a dependable reference for policymakers and investors.

Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer.

OBJECTIVE: PARP inhibitors combined with antiangiogenic drugs have been reported to improve outcomes in BRCA wild-type ovarian cancer patients, the mechanism of the combination is unclear. In this study, we explored the mechanism of apatinib combined with olaparib in the treatment of ovarian cancer. METHODS: In this study, human ovarian cancer cell lines A2780 and OVCAR3 were used as experimental objects, and the expression of ferroptosis-related protein GPX4 after treatment with apatinib and olaparib was detected by Western blot. The SuperPred database was used to predict the target of the combined action of apatinib and olaparib, and the predicted results were verified by Western blot experiment to explore the mechanism of ferroptosis induced by apatinib and olaparib. RESULTS: Apatinib combined with olaparib-induced ferroptosis in p53 wild-type cells, and p53 mutant cells developed drug resistance. The p53 activator RITA sensitized drug-resistant cells to ferroptosis induced by apatinib combined with olaparib. Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis. CONCLUSION: This discovery revealed the specific mechanism of ferroptosis induced by apatinib combined with olaparib in p53 wild-type ovarian cancer cells and provided a theoretical basis for the clinical combined use of apatinib and olaparib in p53 wild-type ovarian cancer patients.

Chinese herbal injection for cardio-cerebrovascular disease: Overview and challenges.

Cardio-cerebrovascular diseases are the leading cause of death worldwide and there is currently no optimal treatment plan. Chinese herbal medicine injection (CHI) is obtained by combining traditional Chinese medicine (TCM) theory and modern production technology. It retains some characteristics of TCM while adding injection characteristics. CHI has played an important role in the treatment of critical diseases, especially cardio-cerebrovascular diseases, and has shown unique therapeutic advantages. TCMs that promote blood circulation and remove blood stasis, such as Salvia miltiorrhiza, Carthami flos, Panax notoginseng, and Chuanxiong rhizoma, account for a large proportion of CHIs of cardio-cerebrovascular disease. CHI is used to treat cardio-cerebrovascular diseases and has potential pharmacological activities such as anti-platelet aggregation, anti-inflammatory, anti-fibrosis, and anti-apoptosis. However, CHIs have changed the traditional method of administering TCMs, and the drugs directly enter the bloodstream, which may produce new pharmacological effects or adverse reactions. This article summarizes the clinical application, pharmacological effects, and mechanism of action of different varieties of CHIs commonly used in the treatment of cardio-cerebrovascular diseases, analyzes the causes of adverse reactions, and proposes suggestions for rational drug use and pharmaceutical care methods to provide a reference for the rational application of CHIs for cardio-cerebrovascular diseases.