Exposure-efficacy and exposure-safety analyses of ropeginterferon alfa-2b treatment in patients with polycythaemia vera.

AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.

Silicon multi-mode micro-ring modulator for improved robustness to optical nonlinearity.

Due to the resonant nature and silicon's strong optical nonlinearity, the system's performance of silicon micro-ring modulators can be seriously affected by the input optical power. In this Letter, we proposed and experimentally demonstrated a multi-mode silicon micro-ring modulator to mitigate its optical nonlinear effects by operating in the TE1 mode. The TE1 mode features a high nonlinear threshold compared with the TE0 mode because of its larger waveguide loss and larger mode effective area. Under the condition of 10 mW optical input power, the resonance spectrum maintains a good symmetric Lorentz shape. The resonant wavelength shifts less than one resonance linewidth, showing an improved robustness to optical nonlinearity compared with regular silicon micro-ring modulators.

A phase II trial to assess the efficacy and safety of ropeginterferon α-2b in Chinese patients with polycythemia vera.

Ropeginterferon α-2b is a mono-PEGylated proline-interferon for the treatment of polycythemia vera. This drug is used biweekly with a starting dose of 100 µg (50 µg if patients receiving hydroxyurea) and 50 µg increments up to a maximum dose of 500 µg. Increasing evidence indicates that patients can tolerate higher starting doses of ropeginterferon α-2b. This phase II trial utilizes 250 µg as the starting dose, 350 µg at week 2 and 500 µg at week 4 as the target dose. Doses can be adjusted according to tolerability. This study assesses the safety, efficacy and molecular response of ropeginterferon α-2b in Chinese patients with PV utilizing the 250-350-500 µg dosing schema. This study will be used to support the application of a biologics license for polycythemia vera treatment in China.

Polycythemia vera (PV) is a slow-growing blood neoplasm (cells that grow and divide more than they should or do not die when they should). PV often has a mutation in the gene called JAK2, which causes changes in the DNA of genes that cause cells to become cancerous. PV is associated with an increased number of blood cells, debilitating symptoms, risks of thrombosis (blood clot) and bleeding and can progress to other diseases, including myelofibrosis and acute myeloid leukemia. Ropeginterferon α-2b is a new product with favorable properties, allowing a convenient dosing schedule of every 2­4 weeks. This drug has demonstrated good tolerability, safety and efficacy for PV treatment and has been approved for the treatment of PV in Europe and the USA. This article discusses the design of an ongoing study that looks at the safety and efficacy of ropeginterferon α-2b for the treatment of PV. The study follows a specific dosing schedule, with the aim of controlling the neoplasm faster, and plans to include 49 patients from 12­15 major hospitals in China. Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (identifier: NCT05485948) and in China (China National Medical Products Administration Clinical Trial Registration Number: CTR20211664).

Ultrahigh extinction ratio silicon micro-ring modulator by MDM resonance for high speed PAM-4 and PAM-8 signaling.

Due to the difficulty of controlling the waveguide loss in the doping region, high-speed silicon micro-ring modulators usually have limited extinction ratio. In this work, we present a mode-division-multiplexing (MDM) resonance-enhanced silicon micro-ring modulator with an ultrahigh extinction ratio. We used a two-mode micro-ring resonator and a mode conversion circular structure to trap the light twice within a single micro-ring resonator. Proof-of-concept high extinction ratio up to 55 dB was obtained. 30 Gb/s PAM-8 and 50 Gb/s PAM-4 signaling with a bit error rate below the hard-decision forward error correction (HD-FEC) threshold were demonstrated with the fabricated modulator, indicating great potential for high-order pulse amplitude modulation (PAM).

Nonlinear Distortion by Stimulated Brillouin Scattering in Kramers-Kronig Receiver Based Optical Transmission.

Nonlinear distortion for single-sideband (SSB) signals will significantly reduce the performance of Kramers-Kronig (KK) receiver-based optical transmission. In this work, we present a proof-of-concept study of stimulated Brillouin scattering (SBS)-induced nonlinear distortion for 10 Gbaud and 28 Gbaud SSB QAM16 transmission over 80 km standard single mode fiber (SSMF) based on a KK receiver. Significantly reduced bit error rate (BER) has been experimentally observed due to the SBS and the threshold of SBS at about 7 dBm is detected for such an 80 km SSMF link. With left sideband (LSB) modulation of SSB, together with optical filtering, reduced SBS nonlinear distortion has been achieved with ~2 dB power tolerance improvement. The results reveal an important issue of SBS-induced nonlinear distortion, which would be of great significance for KK receiver-based optical transmission applications.

Drosophila decapping protein 2 modulates the formation of cortical F-actin for germ plasm assembly.

In Drosophila, the deposition of the germ plasm at the posterior pole of the oocyte is essential for the abdomen and germ cell formation during embryogenesis. To assemble the germ plasm, oskar (osk) mRNA, produced by nurse cells, should be localized and anchored on the posterior cortex of the oocyte. Processing bodies (P-bodies) are cytoplasmic RNA granules responsible for the 5'-3' mRNA degradation. Evidence suggests that the components of P-bodies, such as Drosophila decapping protein 1 and Ge-1, are involved in the posterior localization of osk. However, whether the decapping core enzyme, Drosophila decapping protein 2 (dDcp2), is also involved remains unclear. Herein, we generated a dDcp2 null allele and showed that dDcp2 was required for the posterior localization of germ plasm components including osk. dDcp2 was distributed on the oocyte cortex and was localized posterior to the osk. In the posterior pole of dDcp2 mutant oocytes, osk was mislocalized and colocalized with F-actin detached from the cortex; moreover, considerably fewer F-actin projections were observed. Using the F-actin cosedimentation assay, we proved that dDcp2 interacted with F-actin through its middle region. In conclusion, our findings explored a novel function of dDcp2 in assisting osk localization by modulating the formation of F-actin projections on the posterior cortex.

Efficient Design for Integrated Photonic Waveguides with Agile Dispersion.

Chromatic dispersion engineering of photonic waveguide is of great importance for Photonic Integrated Circuit in broad applications, including on-chip CD compensation, supercontinuum generation, Kerr-comb generation, micro resonator and mode-locked laser. Linear propagation behavior and nonlinear effects of the light wave can be manipulated by engineering CD, in order to manipulate the temporal shape and frequency spectrum. Therefore, agile shapes of dispersion profiles, including typically wideband flat dispersion, are highly desired among various applications. In this study, we demonstrate a novel method for agile dispersion engineering of integrated photonic waveguide. Based on a horizontal double-slot structure, we obtained agile dispersion shapes, including broadband low dispersion, constant dispersion and slope-maintained linear dispersion. The proposed inverse design method is objectively-motivated and automation-supported. Dispersion in the range of 0-1.5 ps/(nm·km) for 861-nm bandwidth has been achieved, which shows superior performance for broadband low dispersion. Numerical simulation of the Kerr frequency comb was carried out utilizing the obtained dispersion shapes and a comb spectrum for 1068-nm bandwidth with a 20-dB power variation was generated. Significant potential for integrated photonic design automation can be expected.

Silicon-integrated dual-mode fiber-to-chip edge coupler for 2 × 100 Gbps/lambda MDM optical interconnection.

In this work, a silicon-integrated edge coupler supporting dual-mode fiber-to-chip coupling was designed and fabricated on 220-nm-thick SOI wafer with standard CMOS-compatible fabrication process. The proposed low-complexity structure consists of a multimode interference and triple-tip inverse taper. Both LP01 and LP11 modes in the few mode fiber (FMF) can be stimulated simultaneously by the edge coupler from TE0 and TE1 modes in silicon waveguide. Such a design is compatible with broadband wavelength division multiplexing and can be scaled up to 4-polarization-mode coupling as well. Using the proposed edge coupler, 2×100-Gbps/lambda PAM4 multimode interface through dual-mode fiber was demonstrated successfully.

Machine learning aided inverse design for few-mode fiber weak-coupling optimization.

Few-mode fiber (FMF) supporting many modes with weak-coupling is highly desired in mode division multiplexing (MDM) systems. The multi-parameter design of FMF becomes comparably difficult, inaccurate and time-consuming when it comes for complex fiber structures and many high order modes. In this work, we demonstrate a machine learning method using neural network to inversely design the desired FMF based on multiple-ring structure. By using the minimum index difference between adjacent modes as the weak-coupling optimization aim, we realize the inverse design of 4-ring step-index FMFs for supporting 4, 6 and 10 -mode operation, and 6-ring step-index FMF for supporting 20-mode operation. This method provides high-accuracy, high-efficiency and low-complexity for fast and reusable design of optical fibers, including particularly weak-coupling FMF in this work. It can be widely extended to a lot of fibers and has great potential for instantaneous applications in the optical fiber industry.

The Role of miR-539 in the Anterior Cingulate Cortex in Chronic Neuropathic Pain.

OBJECTIVE: This study explored the putative mechanisms of miRNAs in the anterior cingulate cortex (ACC) in modulation of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. DESIGN AND METHODS: MiRNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine miRNA expression profile in the ACC after CCI of the sciatic nerve. MiRNA mimics were then used to examine the role of miR-539 in the ACC in modulation of NR2B subunit expression and neuropathic pain in rats. RESULTS: The expression of nine miRNAs was enhanced, and the expression of 12 miRNAs, such as miR-539, was reduced in the ACC after CCI. We confirmed that miR-539 expression was decreased robustly in the contralateral, but mildly in the ipsilateral, ACC. This was associated with enhanced protein levels of NR2B in a similar pattern. Furthermore, administrations of miR-539 mimics into the contralateral ACC, but not the ipsilateral ACC, attenuated CCI-induced mechanical allodynia. This was associated with reduction in protein levels of NR2B in the contralateral ACC. Finally, administrations of Ro25-6981 into the contralateral ACC attenuated the CCI-induced mechanical allodynia to a greater extent than the ipsilateral ACC. CONCLUSIONS: Our results suggested that CCI induces lateralized adaptations of NR2B subunit expression in the ACC, which is likely in part contributed by alterations of miR-539 expression, and may promote the regulations of neuropathic pain via NR2B-containing NMDA receptor-mediated neuronal mechanisms.

The prognostic value of red blood cell distribution width for pulmonary infection in elderly patients received abdominal surgery with tracheal intubation and general anesthesia.

BACKGROUND: Red blood cell distribution width (RDW) has been shown to be an important predictor of the occurrence of various inflammatory and infectious diseases. However, the predictive value of RDW for pulmonary infection in elderly patients undergoing abdominal surgery under general anesthesia with endotracheal intubation remains unclear. METHODS: A total of 200 eligible elderly patients who underwent abdominal surgery with endotracheal intubation and general anesthesia in our hospital from January 2019 to January 2022 were included in this study. During hospitalization, there were 64 cases with different degrees of pulmonary infection, and 136 cases without pulmonary infection. Participants' RDW levels were analyzed on admission. Serum levels of inflammatory factors in infected patients were analyzed during hospitalization. Multivariate logistic analysis was performed to evaluate clinical factors for pulmonary infection during hospitalization following-up abdominal surgery with endotracheal intubation and general anesthesia in elderly patients. Youden's J statistic was used to define the correlation. RESULTS: RDW at admission was independently associated with the risk of pulmonary infection in elderly patients undergoing general anesthesia with endotracheal intubation for abdominal surgery ([OR 1.952, 95% confidence interval 1.604 to 2.279, p=0.006]). RDW at admission was statistically positively correlated with inflammatory factors, including procalcitonin (p<0.001), C-reactive protein (p<0.001), and tumor necrosis factor-α (p<0.001), in elderly patients with postoperative pneumonia who underwent abdominal surgery. CONCLUSION: RDW at admission had predictive value for pulmonary infection in elderly patients undergoing abdominal surgery under general anesthesia with endotracheal intubation.

Hsa_circ_0070440 promotes lung adenocarcinoma progression by SLC7A11-mediated-ferroptosis.

BACKGROUND: Circular RNA (circRNA) has recently emerged as having a key role in cancer initiation and progression. A prior study exhibited that hsa_circ_0070440 (circ_0070440) was significantly up-regulated in lung cancer cells, but the role and molecular mechanism of circ_0070440 during lung adenocarcinoma (LUAD) development remain unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR), Reverse transcription-PCR (RT-PCR), RNase R digestion, and Nuclear/cytoplasmic fractionation assay were employed to validate circ_0070440. Proliferation, apoptosis, viability, and ferrous iron level were measured by colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), Annexin V-FITC/PI double staining, Cell Counting Kit-8 (CCK-8), and iron assay in LUAD cells. A xenograft mouse model was used for tumor growth in vivo. Western blot (WB) and immunohistochemistry (IHC) assays were utilized to determine the expression of solute carrier family 7 member 11 (SLC7A11), c-myc, and bcl-xL. The interactions between the circ_0070440/SLC7A11 axis and miR-485-5p were verified by RNA pull-down assay and dual-luciferase reporter assay. RESULTS: Circ_0070440 was significantly up-regulated in LUAD cells. Knockdown of circ_0070440 inhibited growth and promoted both apoptosis and ferroptosis of LUAD cells. Moreover, our results showed that circ_0070440 contributed to malignant progression and suppressed ferroptosis of LUAD by sponging miR-485-5p and upregulating SLC7A11 expression. Furthermore, circ_0070440 and SLC7A11 levels were up-regulated, and the miR-485-5p level was more down-regulated in the tumor tissues than in normal tissues of LUAD patients. CONCLUSION: Circ_0070440 modulated LUAD malignant progression and ferroptosis via targeting SLC7A11, implying a significant role of the circ_0070440/miR-485-5p/SLC7A11 axis in the diagnosis and treatment of LUAD.

A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera.

Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 µg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 µg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

Nursing Skill Assessment of Hospital Nurses in Management of Critically Ill Patients.

Objective: To analyze the application of standardized nursing procedures in critically ill patients' nursing evaluation. Methods: 90 cases of critically ill patients aged from 18 to 65 who were treated in our hospital from April 2020 to April 2021 were selected and divided into the control group and observation group, respectively, with 45 cases according to the drawing method. The rescue time, blood pressure, heart rate before and after nursing, adverse mood, length of stay, incidence of adverse events, ICU transfer and death, and satisfaction of 2 groups were statistically analyzed and compared. Results: The rescue time of cardiopulmonary resuscitation, oxygen inhalation, venous opening, and endotracheal resuscitation in the observation group was 3.24 ± 1.01, which is lower than that in the control group, 6.65 ± 2.11, with statistical significance (P < 0.05). Similarly, the vital signs in the observation group were 2.45 ± 0.44, which is also significantly lower than that in the control group, 5.67 ± 1.56. After nursing, the blood pressure and heart rate in the observation group were lower than those in control group, with statistical significance (P < 0.05). The adverse mood of the observation group after nursing was lower than that of the control group, with statistical significance (P < 0.05). The length of stay, incidence of adverse events, intensive care unit (ICU) transfer, and death in the observation group were lower than those in the control group, with statistical significance (P < 0.05). The length of stay in the observation group was 8.87 ± 2.11, while 11.34 ± 2.45 in the observation group. The incidence of adverse events in the observation group was 1, while 8 in the observation group. The length of stay in the observation group was 8.87 ± 2.11, while 11.34 ± 2.45 in the observation group. The ICU transfer in the observation group were 2, while 9 in the observation group. There was no death in the observation group, however, 4 in the observation group. Nursing satisfaction in the observation group was higher than that in the control group, with statistical significance (P < 0.05). The number of patients that are very satisfied in the observation group was 28, while 20 in the control group. The number of patients that are satisfied in the observation group was the same as in the control group, both 15. However, the number of patients that are dissatisfied in the observation group was 2, while 10 in the control group. Conclusion: The application of the standardized nursing process in the nursing of critically ill patients can not only effectively reduce the self-rating anxiety scale (SAS) and sarcoidosis diagnostic score (SDS) of patients but also reduce the incidence of complications and improve the nursing satisfaction of patients.

Ge Ion Implanted Photonic Devices and Annealing for Emerging Applications.

Germanium (Ge) ion implantation into silicon waveguides will induce lattice defects in the silicon, which can eventually change the crystal silicon into amorphous silicon and increase the refractive index from 3.48 to 3.96. A subsequent annealing process, either by using an external laser or integrated thermal heaters can partially or completely remove those lattice defects and gradually change the amorphous silicon back into the crystalline form and, therefore, reduce the material's refractive index. Utilising this change in optical properties, we successfully demonstrated various erasable photonic devices. Those devices can be used to implement a flexible and commercially viable wafer-scale testing method for a silicon photonics fabrication line, which is a key technology to reduce the cost and increase the yield in production. In addition, Ge ion implantation and annealing are also demonstrated to enable post-fabrication trimming of ring resonators and Mach-Zehnder interferometers and to implement nonvolatile programmable photonic circuits.

Adherence to the Standards for Reporting of Diagnostic Accuracy Studies (STARD): a survey of four journals in laboratory medicine.

BACKGROUND: The Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement has been updated in 2015. Many diagnostic test accuracy (DTA) studies have been published in medical laboratory journals, but their adherence to the updated STARD statement remains unknown. METHODS: We searched the PubMed database to verify studies published in 4 laboratory journals, including Clinical Chemistry, Clinical Chemistry and Laboratory Medicine, Clinica Chimica Acta, and Clinical Biochemistry, in 2019. DTA studies were identified and their adherence to the STARD statement was assessed. RESULTS: A total of 45 studies were included in this analysis. Overall, 18 out of 34 STARD items were reported. The items (adherence rate) of sample size estimation (4%), adverse events (9%), protocol (9%), registration (16%), missing value (22%), indeterminate results (18%), and cross-tabulation (22%) were the most frequently unreported items. CONCLUSIONS: Adherence to the STARD statement in DTA articles published in laboratory medicine seems as yet unsatisfactory. Our study emphasizes the necessity to improve the reporting quality of DTA studies published in medical laboratory journals.

Changes in circulating follicular helper T cells in peripheral blood of patients with acute hepatitis C virus infection.

BACKGROUND: To investigate the changes in circulating follicular helper T cells (cTfh) in peripheral blood of patients with acute hepatitis C virus (HCV) infection and its correlation with symptom severity of the disease. METHODS: A total of 105 subjects were enrolled in this study, including 35 healthy people, 35 patients with acute HCV infection and 35 acute HCV patients with antiviral therapy. Flow cytometry was used to detect the expression of molecular markers related to the surface of cTfh cells, such as CD69, HLA-DR and CD57, and ELISA was used to detect the secretion of cytokines (IL-21, IL-4) in each group. The relationship between these markers and disease was analyzed statistically. RESULTS: Flow cytometry analysis demonstrated that the percentage of CD69 in peripheral blood of patients with acute hepatitis C infection was (18.90%±9.29%) significantly higher than that of normal control group (5.10%±4.21%) and antiviral treatment group (11.50%±5.38%). The difference was statistically significant (P<0.05). The results of HLA-DR and CD57 were consistent with CD69. The serum levels of IL-4 and IL-21 in the acute HCV infection group were significantly higher than those in the treatment and the control groups. After antiviral treatment, IL-4 and IL-21 levels significantly decreased but remained higher than those in the control group. This showed that antiviral treatment was effective, and the difference was statistically significant (P<0.05). The ratio of cTfh in infected group was negatively correlated with HCV RNA content (r=-0.6858, P=0.0028). CONCLUSIONS: Antiviral immune response in patients with acute hepatitis C infection may be related to the proportion of T helper cells in peripheral blood circulation follicles. Dynamic detection of the number of T helper cells in clinical practice is conducive to identifying more effective methods to treat acute hepatitis C infection, which has important theoretical and clinical significance.

Knockdown of LINC01694 inhibits growth of gallbladder cancer cells via miR-340-5p/Sox4.

PURPOSE: The indispensable role of long non-coding RNAs (lncRNAs) in tumorigenesis has been increasingly reported. In the present study, LINC01694 was found to regulate the proliferation, invasion, as well as apoptosis in gallbladder cancer (GBC) cells through sponging miR-340-5p. METHODS: LINC01694 level in GBC cells was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, invasion, and apoptosis were determined by Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. The expression of Sry-related high-mobility group box 4 (Sox4) was detected by Western blot (WB). The interaction between LINC01694 and miR-340-5p was measured by dual-luciferase reporter (DLR) assay, RNA immunoprecipitation (RIP) test, and RNA pull-down. Tumor formation was examined by in vivo experiment. RESULTS: qRT-PCR illustrated that cancerous tissues had higher LINC01694 than normal tissues. Survival analysis demonstrated that the prognosis of patients with high LINC01694 was significantly poorer than those with low LINC01694. Down-regulation of LINC01694 slowed down the proliferation and invasion in GBC cells and accelerated the apoptosis. DLR assay indicated that LINC01694 elevated Sox4 expression by regulating miR-340-5p. LINC01694 functioned as miR-340-5p sponge to inhibit Sox4 expression. CONCLUSION: LINC01694 level is elevated in GBC by regulating miR-340-5p/Sox4 axis, which indicates the poor prognosis of the patients.

TRIM31 promotes apoptosis via TAK1-mediated activation of NF-κB signaling in sepsis-induced myocardial dysfunction.

Sepsis is a major condition caused by an overwhelming inflammatory response to an infection. Sepsis-induced myocardial dysfunction (SIMD) is a common complication in septic patients and a major predictor of morbidity and mortality. Here, we investigated the role of tripartite motif 31 (TRIM31) protein in sepsis progression in vitro and in vivo. Quantitative real-time PCR and western blot were used to detect the expression levels of relative genes and proteins. Cell proliferation and apoptosis were evaluated to determine cell viability. H&E and IHC staining were performed to examine morphological and pathological changes in mice. ELISA assay was used to detect inflammatory factors. TRIM31 was upregulated in septic patients compared with normal people. TRIM31 depletion reduced LPS-induced apoptosis whereas TRIM31 overexpression-elevated LPS-induced apoptosis. Furthermore, TRIM31 interacted with and ubiquitinated transforming growth factor-ß-activated kinase-1 (TAK1), resulting in TAK1 activation and subsequent induction of NF-κB signaling. Of note, Trim31 depletion or blockade by PDTC treatment inhibited LPS-induced apoptosis in vivo. In conclusion, TRIM31 played an important role in SIMD by activating TAK1-mediated NF-κB signaling pathway.

MiR-215-5p inhibits the inflammation injury in septic H9c2 by regulating ILF3 and LRRFIP1.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) playing crucial roles in sepsis-induced diseases, including myocardial inflammation. Nevertheless, the expression pattern and role of miR-215-5p in myocardial inflammation are still un-investigated up to now. The purpose of our study is to further inquire the effect of miR-215-5p on lipopolysaccharide (LPS)-activated inflammation injury in H9c2 cells and the possibly associated mechanisms. First of all, LPS-induced H9c2 cells models were constructed and affirmed via detection of pro-inflammatory factors, the viability and apoptosis. MiR-215-5p was overtly down-regulated in LPS-treated H9c2 cells and miR-215-5p overexpression could suppress the inflammation injury. LRRFIP1 was proved to be the target gene of miR-215-5p and meanwhile, miR-215-5p also targeted ILF3 that experimented to bind to and stabilize LRRFIP1. Final rescue assays confirmed that the overexpression of LRRFIP1 or ILF3 rescued the repressive effect of miR-215-5p up-regulation on the inflammation injury in septic H9c2. Totally, miR-215-5p exerted protective function in the inflammation injury in septic H9c2 via targeting ILF3 and LRRFIP1, suggesting an additional treatment method for sepsis-activated myocardial inflammation.