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ObjectivesAim of this study was to investigate the expression of interleukin (IL)-40, a new cytokine associated with B cells homoeostasis and immune response, in primary Sjögren syndrome (pSS) and in pSS-associated lymphomas.Methods29 patients with pSS and 24 controls were enrolled. Minor salivary gland (MSG) biopsies from patients, controls and parotid gland biopsies from pSS-associated lymphoma were obtained. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-40 were performed on MSG. MSG cellular sources of IL-40 were determined by flow-cytometry and immunofluorescence. Serum concentration of IL-40 was assessed by ELISA and cellular sources of IL-40 were determined by flow-cytometry. An in vitro assay with recombinant IL-40 (rIL-40) was performed to detect the effect on cytokine production from peripheral blood mononuclear cells (PBMCs).ResultsIL-40 was significantly increased in the lymphocytic infiltrated MSG of patients with pSS and correlated with focus score and with IL-4 and transforming growth factor-β expression. In addition, IL-40 was increased in the serum of pSS and its levels correlated with the EULAR Sjögren’s Syndrome Disease Activity Index score. B cells from patients were shown to be the major source of IL-40 at both tissue and peripheral level. PBMCs from patients, exposed to rIL-40 in vitro, released proinflammatory cytokines, specifically interferon-γ from B cells and T-CD8+and tumour necrosis factor-α and IL-17 from both T-CD4+and T-CD8+. IL-40 expression in parotid glands of pSS-associated lymphomas was also increased. Moreover, IL-40-driven NETosis was evidenced in neutrophils obtained from pSS.ConclusionOur results suggest that IL-40 may play a role in pSS pathogenesis and pSS-associated lymphomas.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in the world. It is known that there is a pathogenic relation between liver damage and the inflammatory and oxidative environment present in Metabolic Syndrome (MS). background: Non-alcoholic fatty liver disease (NAFLD) is the world's most frequent cause of chronic liver disease. It is known there is a pathogenic relation between liver damage and the inflammatory and oxidative environment present in Metabolic Syndrome (MS). Objective: To study the pharmacological action of atorvastatin and metformin in an experimental model of MS. objective: To study the pharmacological action of atorvastatin and metformin in an experimental model of MS. Methods: We used 40 male rats (Wistar) divided into the following groups: Control (A)(n=8), induced MS (B)(n=8), MS + atorvastatin treatment (C)(n=8), MS + metformin treatment (D)(n=8) and MS + combined treatment (E)(n=8). MS was induced by administering 10% fructose in drinking water for 45 days. Atorvastatin 0.035mg/day/rat, metformin 1.78mg/day/rat, and a combination of both drugs were administered for 45 days. Metabolic, oxidative (nitric oxide, myeloperoxidase and superoxide dismutase) and inflammatory (fibrinogen) parameters were determined. Histological sections of liver were analyzed by light microscopy. method: We used 40 male rats (Wistar) divided into the following groups: Control (A)(n=8), induced MS (B)(n=8), MS + atorvastatin treatment (C)(n=8), MS + metformin treatment (D)(n=8) and MS + combined treatment (E)(n=8). MS was induced by administering 10% fructose in drinking water for 45 days. Atorvastatin 0.035mg/day/rat, metformin 1.78mg/day/rat, and a combination of both drugs were administered for 45 days. Metabolic, oxidative (nitric oxide, myeloperoxidase, and superoxide dismutase) and inflammatory (fibrinogen) parameters were determined. Histological sections of the liver were analyzed by light microscopy. Comparisons of all possible combinations of pairs of means were made by multivariate ANOVA and Hotelling (as a post hoc test). A significance level of p Results: The glycemia, lipid profile and TG/HDL-C index were altered in MS group. After pharmacological treatment, metabolic parameters improve significantly in all treated groups. Inflammatory and oxidative stress biomarkers increase in MS. Treated groups showed an increase in NO bioavailability, no difference in MPO activity and an increase in fibrinogen. Atorvastatin showed a decrease in SOD while Metformin and combination treatment showed an increase in SOD compared to MS. In MS, we observed histological lesions consistent with NAFLD. However, after a combined treatment, we observed total regression of these lesions. Conclusion: Our results showed that there is an important synergy between atorvastatin and metformin in improving liver involvement in MS.

Background: Chamaenerion latifolium is a perennial herbaceous plant of the Onagraceae family. The purpose of this study was to evaluate and compare the volatile chemical components of the aerial parts of Chamaenerion latifolium growing in the Republic of Kazakhstan. Method: The leaves and stems of Chamaenerion latifolium were extracted with hexane and analysed by gas chromatography-mass spectrometry (GC-MS). Results: The regularisation of peak areas method was used to calculate the concentrations of the sixty-five identified compounds. Conclusion: Among them, the major components are alkanes (leaves 31.339%, stems 48.158%), esters (leaves 10.216%, stems 12.196%), alcohols (leaves 5.483% and stems 5.14%), aldehydes (leaves 3.155%, stems 1.592%), triterpenoids (leaves 2.247% stems 3.785%).

Aim: The in vitro effects of commonly used first-line anti-arthritic drugs on early stages of T-cell activation were examined. Methods: The 2B4.11 murine T cell hybridoma cell line recognizing pigeon cytochrome c (PCC) as the antigen was co-cultured with the histocompatible antigen presenting B cell hybridoma line LK35.2, PCC, and anti-arthritic drugs, including methotrexate, hydroxychloroquine, salazopyrine, cyclosporin, and leflunomide. After 16 hours of incubation, the supernatant was removed, and cytokines were assayed. Results: Anti-arthritic drugs inhibited the production of pro-inflammatory cytokines IL-2, IL-6, IFN-γ, GM-CSF, and TNF-α (Th1 cytokines) to a varying extent. Surprisingly, leflunomide, salazopyrine, prednisone and indomethacin as well as blocking Th1 cytokines, stimulated the production of the anti-inflammatory cytokine IL-10, a Th2 cytokine. Conclusion: Anti-arthritic medications can inhibit the production of pro-inflammatory cytokines and in some cases, incite a Th2 response that could potentially inhibit the progression of the immune response.

Abstract: Osteoarthritis is the most common human joint disease in the world. It is also one of the most common skeletal muscle defects, destructive joint changes, and the leading cause of disability and reduced quality of life. Destructive changes in inflammatory joints are associated with a range of biochemical events, including the overproduction of inflammatory cytokines. Cytokines are protein compounds that play an essential role in causing and regulating inflammation. A balance between pro-inflammatory and anti-inflammatory cytokines is crucial in maintaining a stable body. In some inflammatory diseases, including osteoarthritis, the balance between these compounds is disturbed, and the balance shifts to pre-inflammatory cytokines. For this reason, researchers today are trying to find an effective way to reduce inflammation and treat osteoarthritis by using certain compounds. Current treatments for osteoarthritis, including nonsteroidal antiinflammatory drugs, glucocorticoids, and hyaluronic acid, are mainly based on reducing pain and inflammation. However, they have limited effects in controlling symptoms and improving the patient's quality of life. Also, due to the high level of side effects, synthetic drugs have led to the identification of compounds of natural origin to give patients a chance to use painkillers and antiinflammatory drugs with fewer side effects. This review study aimed to present the role of quercetin as a natural compound in reducing the expression of pro-inflammatory cytokines in osteoarthritis. This study also discusses the relationship between inflammation and cartilage destruction and other inflammation-related factors caused by cytokines.

Introduction: The coronavirus pandemic has disproportionately affected older adults and has provided an incentive to find alternatives to emergency department attendance to avoid unnecessary exposure to the SARS-CoV-2 virus. To address this issue, a specialist geriatric multidisciplinary team at Queen Elizabeth Hospital set up a novel telemedicine approach to the ambulance service with the aim of reducing unnecessary emergency department attendance for older adults. This study provides a service evaluation in its first year of use. Methods: Service evaluation in the first year of the ‘Ask OPAL’ (older person Assessment and liaison) hotline for ambulance paramedics, run by a multidisciplinary acute geriatrics team at the Queen Elizabeth Hospital, Birmingham. Data on the number, patient demographics, intervention, and outcome of the calls, were recorded Results: During the study period, 2552 ‘Ask OPAL’ calls were conducted. Of the 2552 calls carried out, 1755 patients (69%) remained at home. Of the patients who remained at home, 76% received verbal advice only, while 24% were referred to community services in addition to receiving verbal advice. Conclusion: In conclusion, the use of an integrated multidisciplinary team communicating with paramedics via telemedicine appears to be successful in preventing avoidable hospital admissions in complex patients.

Background: Diabetes mellitus (DM) is a metabolic disorder characterized by progressive β cell dysfunction. Sheng-Mai Injection (SMI), a Traditional Chinese medicine preparation, is widely used for DM and its related complications. Objective: This meta-analysis aimed to summarize the applications of SMI in DM and related complications. Methods: Eight databases were searched, and meta-analyses were performed. Results: Fifteen studies, including 1273 participants, were included. All studies and participants included were from China. Pooled effects showed that SMI might reduce glycated hemoglobin (MD -0.46%; 95% CI -0.89 to -0.03; P < 0.01), fasting blood glucose (MD -0.83 mmol/L; 95% CI -1.30 to -0.36; P < 0.01), two-hour postprandial glucose (MD -1.27 mmol/L; 95% CI -1.96 to -0.58; P < 0.01), 24-hour urinary protein (MD -0.28 mg; 95% CI -0.51 to -0.06; P = 0.01), blood urea nitrogen (MD -1.31 mg; 95% CI -2.08 to -0.54; P < 0.05), Scr (MD -2.60; 95% CI -3.43 to -1.77; P < 0.05), ulnar nerve motor nerve conduction velocity (MNCV) (MD 1.45; 95% CI 0.03 to 2.87; P < 0.05), and tibial nerve sensory nerve conduction velocity (SNCV) (MD 1.84; 95% CI 0.1 to 3.58; P < 0.05). There was no evidence of an effect on common peroneal nervous MNCV and SNCV, tibial nerve MNCV, median nerve MNCV, and SNCV. Adverse effects included less frequent gastrointestinal reactions, elevated transaminase, leucopenia, fever, and rash. Conclusion: Combination use of SMI based on conventional hypoglycemic treatment can significantly improve HbA1c, FBG, and 2hPG in DM and reduce 24-hour urinary protein, Scr, and BUN in DM patients. SMI was found to have no effect on the neurological function of diabetic peripheral neuropathy.

Background: The Italian population’s habits changed dramatically during the “COVID- 19 lockdown” due to physical distancing and self-isolation. Moreover, medical consultations of patients with chronic diseases, such as type 2 diabetes (T2D), were suspended or postponed, unless urgent or semi-urgent, for several consecutive months. Thus, it is expected that the lockdown could have affected glucometabolic control in T2D. Purpose: The aim of the study was to assess changes in glucometabolic control in a cohort of T2D patients before (T1) and after (T2) the COVID-19 lockdown (March-May 2020). Methods: The study was approved by the Ethics Committee of the University of Bari, and all patients provided informed written consent to participate. Medical history, complete physical examination, and laboratory assessment were conducted as real-life clinical practice. Changes in clinical and laboratory variables between T1 and T2 were calculated. Results: In detail, 13 patients were on metformin as monotherapy, 36 on GLP-1RA, 12 on sodiumglucose transporter 2 inhibitors (SGLT-2i), and 2 on dipeptidyl-peptidase 4 inhibitors (DPP4i). The mean age was 65.3 years (43-83). Study participants were mainly men (73%). The body weight (BW) ranged from 56 to 145 kg, and the waist circumference ranged from 88 to 146 cm. The mean HbA1c was 51.0 mmol/mol. At T2, no statistically significant changes were observed from baseline except for BW [-1.6 (-2.60 to -0.62)] and HbA1c [-2.90 (-4.69; -1.12)]. Conclusion: We evaluated the effects of the COVID-19 lockdown on glucometabolic control in patients with background well-controlled T2D. We found that the lockdown had no adverse effects on metabolic profile regardless of background clinical characteristics and antihyperglycemic management. Despite limitations due to the nature of this study (sample size, retrospective observation, lack of data on lifestyle changes in our patients' everyday lives), T2D patients managed in our Diabetes Centers faced the lockdown-related restrictions without any detrimental consequence.

The objective of the study was to gain an insight into the perceptions and experiences of patients with rheumatoid arthritis and a high cardiovascular disease risk (CVD-RA) when undergoing an exercise intervention aimed at improving their cardiorespiratory fitness. This qualitative study was part of a pilot study, which investigated the effects of an exercise intervention on cardiorespiratory fitness in patients with CVD-RA. Six patients were invited to participate in face-to-face semi-structured interviews. We invited patients who completed the exercise intervention as well as patients who withdrew from the exercise intervention. The interviews were analyzed according to the method of thematic analysis. Six patients were interviewed, of whom four patients completed and two patients discontinued the exercise intervention. The mean (SD) age was 58 (9.7) years, the median disease duration was 10 years, and five patients were female. The analyses revealed seven themes that provided insight into perceptions and experiences: (1) ability to understand reasons for actions; (2) the need to be seen; (3) reaching their maximum effort; (4) experiencing their limits; (5) wanting personalized exercise therapy; (6) happy to be physically active; (7) benefits of exercise. Patients perceived that they were able to perform a cardiopulmonary exercise test with maximum effort and achieved the prescribed intensity of the exercise intervention. They also experienced an improvement in their physical activity by incorporating physical activity in their daily live. Overarching principles that re-occurred in the themes were: the need to be viewed as a person and the importance of feeling safe.

Abstract: Diaminopyrimidine compounds having the following general structure (I), compositions comprising an effective amount of a diaminopyrimidine compound, and methods for treating or preventing fibrotic liver disorders or other diseases associated with the JNK pathway are discussed in this patent study.

Abstract: Tirzepatide (mounjaro®) is a derivative of the human glucose-dependent insulinotropic polypeptide (GIP) hormone with a position-20 being modified with 1,20- eicosanedioic acid via a chemical linker. It acts as a glucagon-like peptide-1 (GLP-1) receptor and GIP receptor agonist. It has recently been approved by FDA as an adjunct therapy to exercise and diet to improve glycemic control in patients with type II diabetes mellitus (T2DM). It represents a new transforming paradigm in the management of T2DM. This mini-review will shed light on its different pharmacokinetic and pharmacodynamic aspects.

Background: Allergic asthma is a chronic inflammatory illness of the respiratory system characterized by an increase in the number of inflammatory cells in the airways and trouble breathing. Mesenchymal stem cells (MSCs) have the potential to be used in inflammatory diseases as a cellular immunosuppressive treatment. They express calcitriol receptors and communicate with other immunocytes, which increases their anti-inflammatory activity. This study aimed to determine the effects of calcitriol-treated MSC treatment on allergic asthma pathways in a mouse model. Methods: To generate a mouse model of asthma, the mice were sensitized intraperitoneally with ovalbumin (OVA) and aluminum hydroxide emulsion and then challenged intra-nasally with OVA. On day 14, experimental mice received tail vein injections of calcitriol-treated MSCs in PBS prior to allergen exposure. The cytokines assays including IL-4, 10, 12, 17, TGF-β and IFN-γ, splenocytes proliferation, and histological examination of lungs samples were performed. The mice were sensitized with OVA and the response to dexamethasone treatment was compared. Results: Calcitriol-treated MSCs significantly increased the levels of IL-12, TGF-β, and IFN-γ compared to non-treated MSCs groups. Moreover, calcitriol-treated and non-treated MSCs significantly decreased IL-4 and IL-17 compared to asthmatic groups. The results of the histopathological examination showed that calcitriol-treated MSCs reduced the accumulation of inflammatory cells and bronchial wall thickening in comparison with the asthma group. Conclusion: Using the allergic asthma model, we were able to show that calcitriol-treated MSCs had an inhibitory impact on airway inflammation. Our findings suggest that the injection of calcitrioltreated MSCs may be a viable treatment option for allergic asthma.

Aim: The study aims to show that sodium selenite (Ss) would have an immunomodulatory effect on the functional activity of proinflammatory macrophages (Mφs) during their extended extracellular activation at the onset of human type 1 diabetes (T1D). Background: Exacerbated activation of proinflammatory “M1” macrophages (Mϕs) can promote chronic local pancreatic islet inflammation and T1D development. Objective: We investigated the ex vivo effects of Ss on the immune modulation of global/extended activation of human proinflammatory M1-like Mϕs. Methods: Experiments were carried out on primary monocytes-derived Mϕs (MDMs). Results: The levels of IL-1β, TNF-α, H2O2 and intracellular free calcium ions (ifCa2+), and the ratios of IL-1β-to-IL-10 and TNF-α-to-IL-10 were markedly increased in T1D Mϕs than in healthy control Mϕs. Conversely, both IL-10 production and arginase 1 (ARG1) activity were downregulated in T1D Mϕs. Additionally, Ss treatment induced a marked downregulation of respiratory burst, ifCa2+ levels, M1-like Mϕ-associated inducible nitric oxide (NO) synthase (iNOS) activity, cell necrosis and related necroinflammation biomarkers, including IL-1β and TNF-α, CD14 expression, and the ratios of iNOS-to-ARG1, IL-1β-to-IL-10, and TNF-α-to-IL-10. Moreover, Ss upregulated anti-inflammatory “M2-like” Mϕ activity as demonstrated by ARG1 activity and IL-10 production, as well as phagocytosis capacity. Conclusions: Ss exerts a potent immunomodulatory role on functional activities of human proinflammatory T1D M1-like Mϕs subjected to extended activation, as well as on the M1-like/M2-like dichotomy. Additionally, the current study provides a novel therapeutic approach using Ss to promote the anti-inflammatory function of Mϕs at the onset of T1D.

Purpose of review: There is no widely accepted single ethical principle for the fair allocation of scarce donor organs for transplantation. Although most allocation systems use combinations of allocation principles, there is a particular tension between 'prioritizing the worst-off' and 'maximizing total benefits'. It is often suggested that empirical research on public preferences should help solve the dilemma between equity and efficiency in allocation policy-making. Recent findings: This review shows that the evidence on public preferences for allocation principles is limited, and that the normative role of public preferences in donor organ allocation policy making is unclear. The review seeks to clarify the ethical dilemma to the transplant community, and draws attention to recent attempts at balancing and rank-ordering of allocation principles. Summary: This review suggests that policy makers should make explicit the relative weights attributed to equity and efficiency considerations in allocation policies, and monitor the effects of policy changes on important ethics outcomes, including equitable access among patient groups. Also, it draws attention to wider justice issues associated not with the distribution of donor organs among patients on waiting lists, but with barriers in referral for transplant evaluation and disparities among patient groups in access to waiting lists.

The role of nutrition is increasingly recognized in the management of chronic immune diseases. However, the role of an immune-supportive diet as adjuvant therapy in the management of allergic disease has not been similarly explored. This review assesses the existing evidence for a relationship between nutrition, immune function, and allergic disease from a clinical perspective. In addition, the authors propose an immune-supportive diet to enhance dietary interventions and complementing other therapeutic options for allergic disease from early life to adulthood. A narrative review of the literature was conducted, to determine the evidence of the relationship between nutrition and immune function, overall health, epithelial barrier function, and gut microbiome, particularly in relation to allergy. Studies on food supplements were excluded. The evidence was assessed and utilized to develop a sustainable immune-supportive diet to complement other therapies in allergic disease. The proposed diet consists of a highly diverse range of fresh, whole, and minimally processed plant-based and fermented foods supplemented with moderate amounts of nuts, omega-3-rich foods and animal-based products in proportional amounts of the EAT-Lancet diet, such as (fatty) fish, (fermented) milk products which may be full-fat and eggs, lean meat or poultry, which may be free-range or organic.

Active ingredients of sunscreens, or UV filters, have increased in use because public awareness of sun safety has risen. In addition to this intentional use, unintentional exposures to UV filters also occur through application of personal care products, where the filters are incorporated into the product. There are 2 main types of UV filters: organic (chemical) filters and the 2 inorganic (mineral) filters, titanium dioxide and zinc oxide. Both allergic contact dermatitis (ACD) and photoallergic contact dermatitis (PACD) have been caused by organic filters; oxybenzone (benzophenone-3) is the most frequently reported contact and photocontact allergen compared with all other UV filters. There are no reports of ACD or PACD to the inorganic (physical) UV filters. Here, we review the categories of sunscreens available, currently marketed UV filters, and their corresponding ACD and PACD.

Aims: To describe the health-related quality of life (HRQoL) of melanoma brain metastasis (MBM) patients throughout the first 18 weeks of ipilimumab–nivolumab or nivolumab treatment. Materials & methods: HRQoL data (European Organisation for Research and Treatment of Cancer's Core Quality of Life Questionnaire, additional Brain Neoplasm Module, and EuroQol 5-Dimension 5-Level Questionnaire) were collected as a secondary outcome of the Anti-PD1 Brain Collaboration phase II trial. Mixed linear modeling assessed changes over time, whereas the Kaplan–Meier method was used to determine median time to first deterioration. Results: Asymptomatic MBM patients treated with ipilimumab–nivolumab (n = 33) or nivolumab (n = 24) maintained baseline HRQoL. MBM patients with symptoms or leptomeningeal/progressive disease treated with nivolumab (n = 14) reported a statistically significant trend toward improvement. Conclusion: MBM patients treated with either ipilimumab–nivolumab or nivolumab did not report a significant deterioration in HRQoL within 18 weeks of treatment initiation. Clinical trial registration: NCT02374242 ( ClinicalTrials.gov )

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS. The work has been supported by the Flemish Fund for Scientific Research (FWO Vlaanderen; 12J9116N, 12JG119N, 12U7718N, 1S15519N, and G099618N), the Belgian Charcot Foundation (FCS-2016-EG7, R-8676, and R-6832), the Interreg V‐A EMR program (EURLIPIDS, EMR23), and the special research fund UHasselt (BOF). JMN is supported by a National Institutes of Health Grant (R01 DK062388). MK was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (640116) and by a SALK grant from the government of Flanders and by an Odysseus grant of the Research Foundation Flanders, Belgium (FWO). We thank MP Tulleners for excellent technical assistance. We would also like to thank other members of the Biomedical Research Institute (Hasselt University) for providing feedback and suggestions during the preparation of the manuscript.

Nonpathogenic commensal microbiota and their metabolites and components are essential to maintain a tolerogenic environment and promote beneficial health effects. The metabolic environment critically impacts the outcome of immune responses and likely impacts autoimmune and allergic responses. Short-chain fatty acids (SCFAs) are the main metabolites produced by microbial fermentation in the gut. Given the high concentration of SCFAs in the gut and portal vein and their broad immune regulatory functions, SCFAs significantly influence immune tolerance and gut–liver immunity. Alterations of SCFA-producing bacteria and SCFAs have been identified in a multitude of inflammatory diseases. These data have particular significance in primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis because of the close proximity of the liver to the gut. In this focused review, we provide an update on the immunologic consequences of SCFA-producing microbiota and in particular on three dominant SCFAs in autoimmune liver diseases.

International audience; The differentiation of B cells into antibody-secreting plasma cells is a complex process that involves extensive changes in morphology, lifespan, and cellular metabolism to support the high rates of antibody production. During the final stage of differentiation, B cells undergo significant expansion of their endoplasmic reticulum and mitochondria, which induces cellular stress and may lead to cell death in absence of effective inhibition of the apoptotic pathway. These changes are tightly regulated at transcriptional and epigenetic levels, as well as at post-translational level, with protein modifications playing a critical role in the process of cellular modification and adaptation. Our recent research has highlighted the pivotal role of the serine/threonine kinase PIM2 in B cell differentiation, from commitment stage to plasmablast and maintenance of expression in mature plasma cells. PIM2 has been shown to promote cell cycle progression during the final stage of differentiation and to inhibit Caspase 3 activation, raising the threshold for apoptosis. In this review, we examine the key molecular mechanisms controlled by PIM2 that contribute to plasma cell development and maintenance.

Background: Beta blockers, mainly propranalol, are usually administered to control heart rate in patients with thyrotoxicosis, especially when congestive heart failure presents. However, when thyrotoxicosis is not controlled, heart rate may be difficult to control even with maximal doses of propranolol. This presentation alerts physicians to the possibility of using ivabradine, a selective inhibitor of the sinoatrial pacemaker, for the control of heart rate. Case presentation: We present a 37-year-old woman with thyrotoxicosis and congestive heart failure whose heart rate was not controlled with a maximal dose of beta blockers during a thyroid storm. The addition of ivabradine, a selective inhibitor of the sinoatrial pacemaker, controlled her heart rate within 48 hours. Conclusion: Ivabradine should be considered in patients with thyrotoxicosis, including those with heart failure, in whom beta blockers are insufficient to control heart rate

Aims: This work was designed to identify the subgroup of advanced hepatocellular carcinoma (HCC) patients for whom treatments containing immune checkpoint blockers (ICBs) were most effective. Materials & methods: A meta-analysis was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs. Results: A total of 2228 patients from four randomized control trials were included. Treatments containing ICBs had better overall survival, progression-free survival and higher objective response rate over treatment without ICBs. Subgroup analysis revealed that treatments containing ICBs were highly effective in improving the overall survival of males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients. Conclusion: Treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.