Background-Cancer immunotherapy involving NK-cell infusions and administration of therapeutic agents modulating the susceptibility of tumors to NK-cell lysis has been recently proposed. Here we provide a method to expand highly cytotoxic clinical grade NK cells in vitro for adoptive transfer following bortezomib treatment in patients with advanced malignancies.

ObjectivesTo investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs).MethodsPubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patients with RA receiving Jakinibs, from inception to October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs). OR and 95% CI were calculated using the Mantel-Haenszel fixed-effect method.Results26 RCTs randomising 11 799 patients were included. No significant difference was observed regarding all CVEs risk following Jakinibs usage in general (OR 1.04 (0.61 to 1.76), p = 0.89), tofacitinib (OR 0.63 (0.26 to 1.54), p = 0.31), baricitinib (OR 1.21 (0.51 to 2.83), p = 0.66), upadacitinib (OR 3.29 (0.59 to 18.44), p = 0.18), peficitinib (OR 0.43 (0.07 to 2.54), p = 0.35) or decernotinib (OR 1.12 (0.13 to 10.11), p = 0.92). Likewise, there was no significant difference for Jakinibs treatment overall regarding occurrence of MACEs (OR 0.80 (0.36 to 1.75), p = 0.57) or VTEs (OR 1.16 (0.48 to 2.81), p = 0.74). Dose-dependent impact of Jakinibs on the risks of all CVEs, MACEs and VTEs was not observed in tofacitinib (5 mg vs 10 mg), upadacitinib (15 mg vs 30 mg), whereas baricitinib at 2 mg was found to be safer than 4 mg in all CVEs incidence (OR 0.19 (0.04 to 0.88), p = 0.03).ConclusionThe existing evidence from RCTs indicated no significant change in cardiovascular risk for Jakinib-treated patients with RA in a short-term perspective, but postmarketing data are sorely needed to ascertain their cardiovascular safety, especially at the higher dose, due to increased risk of thromboembolism events for both tofacitinib and baricitinib at higher dosage.

Selective allodepletion is a strategy to eliminate host-reactive donor T cells from hematopoietic stem cell allografts to prevent graft-versus-host disease while conserving useful donor immune functions. To overcome fluctuations in activationbased surface marker expression and achieve a more consistent and effective allodepletion, we investigated a photodepletion process targeting activationbased changes in p-glycoprotein that result in an altered efflux of the photosensitizer TH9402. Expanded lymphocytes, generated using anti-CD3 and IL-2, were

COVID-19 vaccines are of great importance in reducing SARS-CoV-2 infection and severe cases. Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) have been strongly recommended to be vaccinated according to the novel guidance because they are more vulnerable to SARS-CoV-2 infection. 1 However, patients with AIIRDs were largely excluded from vaccine trials, leading to very limited data on the safety of COVID-19 vaccines. Notably, previous studies mainly focused on mRNA and adenovirus vector vaccines; however, little is known about inactivated COVID-19 vaccines that also have been authorised by WHO and widely used in several most populated countries, for instance, China, Brazil, Turkey and Indonesia. 2 A large randomised clinical trial consisting of 40 382 participants has demonstrated two inactivated COVID-19 vaccines significantly reduced the risk of symptomatic COVID-19. 3 We conducted a real-world survey to evaluate the safety profiles and disease flare in patients with AIIRDs who received any dose of inactivated COVID-19 vaccines in China. From 1 Aug 2021 to 15 Oct 2021, eligible participants completed a predefined 25-question-based questionnaire by invitation on social media or visiting the outpatient department. There was no restriction on the time interval from vaccination to completing the survey.In total, 1507 adults patients with AIIRDs who received inactivated COVID-19 vaccine participated in this study (flow diagram in online supplemental figure 1). The median age of participants was 39 (IQR 31-51) years. There were 1166 (77.4%) female patients and 209 (13.9%) patients with self-identified allergic history. Systemic lupus erythematosus (SLE) (614, 40.7%) was the most common AIIRD among participants, followed by rheumatoid arthritis (RA) (434, 28.8%), Behcet's disease (BD, 122, 8.1%), psoriatic arthritis/psoriasis (PsA/PsO) (76, 5.0%), primary Sjogren's syndrome (74, 4.9%) and ankylosing spondylitis (44, 2.9%) (online supplemental figure 2).Among all participants, 450/1507 (29.9%) participants experienced adverse events (AEs) after vaccination (table 1). Local AEs, such as pain, redness or swelling at injection site, were reported to occur in 287 (19.0%) participants. Meanwhile, 260 (17.3%) patients reported systemic AEs after vaccination. Fatigue or sleepless (123, 8.2%) was the most reported systemic AE, followed by headache (82, 5.4%) and skin rash (55, 3.6%). The median time from vaccination shot to onset of AEs was 2 days. Most AEs were mild to moderate and self-limiting. Overall, 28 Letter *This question was described as 'Have you ever been allergic to any food, drug or environmental substance etc before?'.†Means anaphylactic shock, myocarditis, idiopathic thrombocytopenic purpura and death. ‡Three participants were not fully clear about that the side effects occured.after first or second vaccination.

Brain iron accumulation is common in patients with Parkinson's disease (PD). Iron chelators have been investigated for their ability to prevent neurodegenerative diseases with features of iron overload. Given the non-trivial side effects of classical iron chelators, lactoferrin (Lf), a multifunctional iron-binding globular glycoprotein, was screened to identify novel neuroprotective pathways against dopaminergic neuronal impairment. We found that Lf substantially ameliorated PD-like motor dysfunction in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We further showed that Lf could alleviate MPTP-triggered apoptosis of DA neurons, neuroinflammation, and histological alterations. As expected, we also found that Lf suppressed MPTP-induced excessive iron accumulation and the upregulation of divalent metal transporter (DMT1) and transferrin receptor (TFR), which is the main intracellular iron regulation protein, and subsequently improved the activity of several antioxidant enzymes. We probed further and determined that the neuroprotection provided by Lf was involved in the upregulated levels of brain-derived neurotrophic factor (BDNF), hypoxia-inducible factor 1α (HIF-1α) and its downstream protein, accompanied by the activation of extracellular regulated protein kinases (ERK) and cAMP response element binding protein (CREB), as well as decreased phosphorylation of c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. Our findings suggest that Lf may be an alternative safe drug in ameliorating MPTP-induced brain abnormalities and movement disorder.