Therapeutic plasma exchange combined with ribavirin to rescue critical SFTS patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS. METHODS: A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non-TPE group). Clinical and laboratory parameters were analyzed retrospectively. RESULTS: The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme-MB, prothrombin time, activated partial thromboplastin time, D-Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non-TPE group (P = 0.033). CONCLUSIONS: Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases.

A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel Bunyavirus infection with low population immunity and high mortality rate. Lacking specific therapies, the treatment measures vary with the severity of the disease, therefore, a case control study involved 394 SFTS patients was taken to determine risk factors for mortality. Comparative clinical data from the first 24 h after admission was collected through the electronic medical record system. Independent risk factors for death of SFTS were identified through univariate and multivariate binary logistic regression analyses. The results of the logistic regression were visualized using a nomogram which was created by downloading RMS package in the R program. In our study, four independent mortality risk factors were identified: advanced age(mean 70.45 ± 7.76 years), MODS, elevated APTT, and D-dimer. The AUC of the nomogram was 0.873 (0.832, 0.915), and the model passes the calibration test namely Unreliability test with P = 0.958, showing that the model's predictive ability is excellent. The nomogram to determine the risk of death in SFTS efficiently provide a basis for clinical decision-making for treatment.

Winogradskyella marina sp. nov., isolated from marine sediment.

A Gram-stain-negative, rod-shaped (0.3-0.6 × 0.9-2.2 µm), facultatively aerobic, non-motile and yellow-coloured bacterium, designated strain F6397T, was isolated from a marine sediment in Weihai, PR China. Growth of strain F6397T occurred at 4-37 °C (optimum, 30-33 °C), pH 6.0-9.0 (optimum, 7.5) and in the presence of 1-12% (optimum, 3.0%) (w/v) NaCl. Strain F6397T showed oxidase- and catalase-positive activities. Phylogenetic analyses based on the 16S rRNA gene sequence revealed that the strain was assigned to the genus Winogradskyella. Strain F6397T exhibited 95.5-98.1% sequence similarities to recognized species of the genus Winogradskyella. The average nucleotide identity (ANI) scores with Winogradskyella ludwigii HL116T, Winogradskyella litoriviva KMM 6491 T and Winogradskyella thalassocola KMM 3907 T were 80.1, 78.9 and 82.6%, respectively. The digital DNA-DNA hybridization (dDDH) scores were 23.5, 22.9 and 25.7%, respectively. The genomic DNA G + C content was 33.5 mol%. Strain F6397T contained iso-C15:0, iso-C15:1G, iso-C15:0 3-OH and iso-C17:0 3-OH as the predominant fatty acid and MK-6 as the predominant menaquinone. The polar lipid profiles contained phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. On the basis of the evidence presented in this study, strain F6397T is considered to represent a novel species of the genus Winogradskyella, for which the name Winogradskyella marina sp. nov. is proposed. The type strain is F6397T (= KCTC 82422 T = MCCC 1H00438T).

Pontibaca salina sp. nov., isolated from marine sediment.

A Gram-stain-negative, oval or short rod-shaped, non-motile, aerobic bacterium, designated strain S1109LT, was isolated from a marine sediment in Weihai, PR China. Cells were oxidase positive and catalase positive. Growth of strain S1109LT occurred at 10-40 °C (optimum, 30-33 °C), pH 6.5-10.0 (optimum, 7.0-8.0) and in the presence of 1-21% (optimum, 4-6%) (w/v) NaCl. 16S rRNA gene sequence phylogeny indicated that strain S1109LT was associated with the genus Pontibaca of the family Rhodobacteraceae because it showed the highest sequence similarity to Pontibaca methylaminivorans KCTC 22497T (97.5%). The average nucleotide identity (ANI) and the digital DNA-DNA hybridization (dDDH) scores between strain S1109LT and Pontibaca methylaminivorans KCTC 22497T were 74.6% and 18.7%. The major cellular fatty acids of strain S1109LT were C19:0 cyclo ω8c and C18:1 ω7c. The polar lipids profiles of strain S1109LT were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and two unidentified lipids. Strain S1109LT contained ubiquinone-10 as the major respiratory quinone. The genomic DNA G + C content was 55.9 mol%. On the basis of the evidence presented in this study, strain S1109LT is considered to represent a novel species of the genus Pontibaca, for which the name Pontibaca salina sp. nov. is proposed. The type strain of is S1109LT (= KCTC 82411T = MCCC 1H00441T).

LncRNA ANCR Suppresses the Progression of Hepatocellular Carcinoma Through the Inhibition of Wnt/ß-Catenin Signaling Pathway.

OBJECTIVE: Our study aimed to investigate the effect of anti-differentiation noncoding RNA (ANCR) on hepatocellular carcinoma (HCC) and its potential molecular mechanisms. METHODS: The expression of ANCR was detected by qRT-RCR in both HCC tissues and HCC cells. Moreover, the relationship between ANCR expression and clinical parameters in HCC patients was investigated. The proliferation, cell clones, migration, invasion and apoptosis of MHCC97H and HCCLM3 cells were measured by MTT assay, colony formation assay, transwell assay and flow cytometry, respectively. The expressions of N-cadherin, vimentin, E-cadherin, cleaved caspase-3, Bax, Bcl-2, Wnt1, ß-catenin and GSK-3ß in MHCC97H and HCCLM3 cells were measured by Western blot. RESULTS: Our results showed that ANCR was lowly expressed in both HCC tissues and HCC cells. ANCR expression was closely associated with tumor size, tumor-node-metastasis (TNM) stages and vascular invasion in HCC. ANCR could dramatically inhibit cell proliferation, migration and invasion, as well as promote apoptosis in MHCC97H and HCCLM3 cells. ANCR could significantly increase the expression of cleaved caspase-3, Bax, E-cadherin and GSK-3ß but reduce the expression of Bcl-2, N-cadherin, vimentin, Wnt1 and ß-catenin in MHCC97H and HCCLM3 cells. In addition, Wnt/ß-catenin pathway inhibitor (IWP-2) partially reversed the effects of silencing ANCR on the proliferation, migration, invasion and apoptosis of HCCLM3 cells. CONCLUSION: Our study demonstrated that ANCR can suppress cell proliferation, migration and invasion, as well as promote apoptosis of HCC cells via modulation of the Wnt/ß-catenin signaling pathway.

LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

Dual turn-on fluorescence signal-based controlled release system for real-time monitoring of drug release dynamics in living cells and tumor tissues.

Controlled release systems with capabilities for direct and real-time monitoring of the release and dynamics of drugs in living systems are of great value for cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal-based controlled release system (CDox), in which the chemotherapy drug doxorubicin (Dox) and the fluorescent dye (CH) are conjugated by a hydrazone moiety, a pH-responsive cleavable linker. CDox itself shows nearly no fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N isomerization and N-N free rotation. However, when activated under acidic conditions, CDox could be hydrolyzed to afford Dox and CH, resulting in dual turn-on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox exhibits a desirable controlled release feature as the hydrolysis rate is limited by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity assays indicate that CDox shows much lower cytotoxicity relative to Dox, and displays higher cell inhibition rate to cancer than normal cells. With the aid of the dual turn-on fluorescence at different wavelengths, the drug release dynamics of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real-time fashion. Importantly, two-photon fluorescence imaging of CDox in living tumor tissues was also successfully performed by high-definition 3D imaging. We expect that the unique controlled release system illustrated herein could provide a powerful means to investigate modes of action of drugs, which is critical for development of much more robust and effective chemotherapy drugs.

Construction of a ratiometric fluorescent probe with an extremely large emission shift for imaging hypochlorite in living cells.

Hypochlorite is one of the important reactive oxygen species (ROS) and plays critical roles in many biologically vital processes. Herein, we present a unique ratiometric fluorescent probe (CBP) with an extremely large emission shift for detecting hypochlorite in living cells. Utilizing positively charged α,ß-unsaturated carbonyl group as the reaction site, the probe CBP itself exhibited near-infrared (NIR) fluorescence at 662nm, and can display strong blue fluorescence at 456nm when responded to hypochlorite. Notably, the extremely large emission shift of 206nm could enable the precise measurement of the fluorescence peak intensities and ratios. CBP showed high sensitivity, excellent selectivity, desirable performance at physiological pH, and low cytotoxicity. The bioimaging experiments demonstrate the biological application of CBP for the ratiometric imaging of hypochlorite in living cells.

A unique red-emitting two-photon fluorescent probe with tumor-specificity for imaging in living cells and tissues.

Tumor-specific imaging can provide an attractive approach for the early detection and prognosis of cancer, as well as the precise image-guided tumor-removal surgery. Herein, we describe a unique red-emitting two-photon fluorescent probe (N-BN) for tumor-specific imaging. N-BN utilized Nile Red as the red-emitting two-photon fluorophore and employed biotin as the tumor-specific ligand. In the presence of a variety of biomolecules or in different pH buffers, the fluorescence intensity of N-BN at 655nm showed no noticeable change. N-BN exhibited the remarkable two-photon absorption cross sections of 15.4g under excitation at 800nm. Under the guidance of biotin, N-BN can be applied for the imaging of biotin-receptor positive cancer cells over biotin-negative cells under red-emitting one- and two-photon manners. Assisted by high-definition three-dimensional imaging, the living tumor tissues loaded with N-BN could display strong red two-photon fluorescence with a penetration depth of about 90µm. Moreover, the in vivo and ex vivo imaging studies intuitively revealed that N-BN could track the tumor with highly tumor-specific property by a near-infrared manner.

A cancer cell-specific fluorescent probe for imaging Cu2+ in living cancer cells.

Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2+ in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2+, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581nm in response to Cu2+. The probe exhibited excellent sensitivity and high selectivity for Cu2+ over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2+ in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.

A tumor-targeting and lysosome-specific two-photon fluorescent probe for imaging pH changes in living cells.

Lysosomal pH is closely related to the metastasis and apoptosis of cancer cells. Detecting lysosomal pH changes in cancer cells could be helpful for analyzing tumor progressions and in-depth study of the roles of lysosomes in tumor invasion and metastasis. Herein, we describe a novel tumor-targeting and lysosome-specific two-photon fluorescent probe (BN-lys) for imaging pH changes for the first time. Biotin was employed as the tumor-targeting module, and morpholine was selected as the lysosome-specific group and the pH site to control the fluorescence by photoinduced electron transfer (PET) mechanism. With a pKa value of 5.36, BN-lys showed a fast and reversible fluorescence response to pH. Under the guidance of the biotin group, BN-lys displayed strong one-photon and two-photon fluorescence responses to lysosomal pH in cancer cells, while it displayed weak fluorescence in normal cells. Furthermore, BN-lys could be applied for the imaging of chloroquine-stimulated lysosomal pH changes in living cells. These features demonstrate that this probe could have practical applications in biological research.

Two-photon red-emissive fluorescent probe for imaging nitroxyl (HNO) in living cells and tissues.

Nitroxyl (HNO) plays important roles in the regulation of many physiological and pathological processes, and can serve as a potential therapeutic agent for cardiovascular disease. The development of HNO detection in living systems is greatly important for in-depth studies of its biosynthesis and activities. Herein, we describe a novel two-photon red-emissive fluorescence probe (RP) for imaging HNO in living cells and tissues. RP was based on a red-emissive dye, Rho, and showed no fluorescence. When responding to HNO, RP can emit red fluorescence with the emission wavelength at 638 nm. RP exhibited a sensitive and selective response to HNO. Theoretical calculations demonstrated that the overlaps between the HOMO and LUMO were large for Rho and tiny for RP, consistent with the absorption and fluorescence properties of Rho and RP. Assisted by three-dimensional (3D) imaging, the two-photon imaging of HNO with red emission color in living tissues was successfully performed.

Simultaneous Near-Infrared and Two-Photon In Vivo Imaging of H2 O2 Using a Ratiometric Fluorescent Probe based on the Unique Oxidative Rearrangement of Oxonium.

A new ratiometric fluorescent H2 O2 probe, benzopyrylium-coumarin (BC), is designed by using an oxonium moiety as the unique H2 O2 response site. The BC probe exhibits an extremely large emission shift of 221 nm in response to H2 O2 , and is successfully applied for the simultaneous near-infrared and two-photon imaging of H2 O2 in living cells, mouse-liver tissues, and zebrafish.

Dual Site-Controlled and Lysosome-Targeted Intramolecular Charge Transfer-Photoinduced Electron Transfer-Fluorescence Resonance Energy Transfer Fluorescent Probe for Monitoring pH Changes in Living Cells.

Acidic pH is a critical physiological factor for controlling the activities and functions of lysosome. Herein, we report a novel dual site-controlled and lysosome-targeted intramolecular charge transfer-photoinduced electron transfer-Fluorescence resonance energy transfer (ICT-PET-FRET) fluorescent probe (CN-pH), which was essentially the combination of a turn-on pH probe (CN-1) and a turn-off pH probe (CN-2) by a nonconjugated linker. Coumarin and naphthalimide fluorophores were selected as donor and acceptor to construct the FRET platform. Hydroxyl group and morpholine were simultaneously employed as the two pH sensing sites and controlled the fluorescence of coumarin and naphthalimide units by ICT and PET, respectively. The sensing mechanism of CN-pH to pH was essentially an integration of ICT, PET, and FRET processes. Meanwhile, the morpholine also can serve as a lysosome-targeted group. By combining the two data analysis approaches of the ratios of the two emission intensities (R) and the reverse ratio R' (R' = 1/R), the fluorescent ratio of CN-pH can show proportional relationship to pH values in a very broad range from pH 4.0 to 8.0 with high sensitivity. The probe has been successfully applied for the fluorescence imaging of the lysosomal pH values, as well as ratiometrically visualizing chloroquine-stimulated changes of intracellular pH in living cells. These features demonstrate that the probe can afford practical application in biological systems.

Reproductive Factors, Steroid Receptor Status, and Tumour Markers of HER2-Positive Breast Cancer in Northern China.

BACKGROUND: Although China has a breast cancer incidence that surpasses all other cancer registries, there have been few reports to evaluate the relationships of reproductive history, steroid receptor status, and tumour markers with HER2 status of breast cancer. PATIENTS AND METHODS: This project included 274 primary invasive ductal breast cancer patients. Information concerning the reproductive factors and tumour characteristics of the patients had previously been collected. HER2 and steroid receptor status were detected in tumour tissues. Serum CEA, CA15-3, and CA125 levels were analyzed for all patients. RESULTS: Younger age at menarche was observed in patients with HER2-positive than in those with HER2negative status (p = 0.03). Statistically significant differences were found between the HER2-positive group and HER2-negative group for estrogen receptor (ER) and progesterone receptor (PR) status (p < 0.01). Age of onset, other reproductive factors, tumour characteristics, and serum tumour marker level were not significantly different between those patients with HER2-positive and those with HER2-negative status. CONCLUSION: We confirm that age at menarche may plausibly be differentially correlated with the risk of HER2-positive invasive ductal breast cancer because it is presumed to impact exposure to endogenous sex hormones. HER2 is inversely related to ER and PR in invasive ductal breast cancer patients of Northern China.

HINTERGRUND: Obwohl China eine Brustkrebsrate aufweist, die sämtliche anderen Krebsregister übersteigt, gab es bislang nur wenige Arbeiten, die die Beziehung zwischen vorangegangenen Schwangerschaften, Steroidrezeptor-Status und Tumormarkern mit dem HER2-Status des Brustkrebses evaluieren. PATIENTEN UND METHODEN: Dieses Projekt umfasste 274 Patienten mit primär invasivem duktalem Brustkrebs. Informationen zu den Reproduktionsfaktoren und den Tumorcharakteristika der Patienten wurden im Vorfeld gesammelt. Der HER2- und der Steroidrezeptor-Status wurde im Tumorgewebe erfasst. Bei allen Patienten wurden die Werte von CEA, CA15-3 und CA125 im Serum analysiert. ERGEBNISSE: Ein jüngeres Alter bei der Menarche wurde bei Patienten mit HER2-positivem im Vergleich zu Patienten mit HER2-negativem Status festgestellt (p = 0.03). Statistisch signifikante Differenzen wurden zwischen der HER2-positiven und der HER2-negativen Gruppe für den Östrogenrezeptoren(ÖR)- und den Progesteronrezeptoren (PR)-Status festgestellt (p < 0.01). Alter beim Krankheitsausbruch, weitere reproduktive Faktoren, Tumorcharakteristika und der Wert der Tumormarker im Serum unterschieden sich nicht signifikant zwischen den Patienten mit HER2-positivem und denen mit HER2-negativem Status. SCHLUSSFOLGERUNG: Wir bestätigen, dass das Alter der Menarche glaubhaft differenziell mit dem Risiko des HER2-positiven invasiven duktalen Brustkrebses korrelieren mag, da angenommen wird, dass es die Einwirkung von endogenen Sexualhormonen beeinflusst. HER2 steht invers mit ÖR und PR bei nordchinesischen Patienten mit invasivem duktalem Brustkrebs in Beziehung.