CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. RESULTS: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. CONCLUSIONS: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

MEMS-based two-photon microscopy with Lissajous scanning and image reconstruction under a feed-forward control strategy.

Two-photon microscopy (TPM) based on two-dimensional micro-electro-mechanical (MEMS) system mirrors shows promising applications in biomedicine and the life sciences. To improve the imaging quality and real-time performance of TPM, this paper proposes Lissajous scanning control and image reconstruction under a feed-forward control strategy, a dual-parameter alternating drive control algorithm and segmented phase synchronization mechanism, and pipe-lined fusion-mean filtering and median filtering to suppress image noise. A 10 fps frame rate (512 × 512 pixels), a 140 µm × 140 µm field of view, and a 0.62 µm lateral resolution were achieved. The imaging capability of MEMS-based Lissajous scanning TPM was verified by ex vivo and in vivo biological tissue imaging.

Upfront Umbilical Cord Blood Transplantation Versus Immunosuppressive Therapy for Pediatric Patients With Idiopathic Severe Aplastic Anemia.

Umbilical cord blood transplantation (UCBT) has been rarely reported as a first-line treatment for idiopathic severe aplastic anemia (SAA) patients lacking HLA-matched sibling donors (MSD). Our study aimed to compare the clinical outcomes of pediatric SAA patients who received UCBT and immunosuppressive therapy (IST) upfront. A retrospective analysis was performed on 43 consecutive patients who received frontline IST (n = 17) or UCBT (n = 26) between July 2017 and April 2022. The 3-year overall survival (OS) was comparable between the UCBT and IST groups (96.2% versus 100%, P = .419), while the 3-year event-free survival (EFS) was significantly better in the former than in the latter (88.5% versus 58.8%, P = .048). In the UCBT group, 24 patients achieved successful engraftment, 2 patients developed severe acute graft-versus-host disease (aGVHD), no extensive chronic GVHD (cGVHD), and a high GVHD-free, failure-free survival (GFFS) of 84.6% at 3 years. After 1 year of treatment, 12 patients in the IST group responded, while 5 patients did not achieve remission and 2 patients had disease relapse. At both 3 and 6 months after treatment, the proportion of transfusion-independent patients was higher in the UCBT group than in the IST group. Faster immune recovery and earlier transfusion independence further reduced the risk of infection and bleeding, thereby improving health-related quality of life in the UCBT-treated group. Our results suggested that UCBT as upfront therapy may be an effective and safe option for pediatric SAA patients, with favorable outcomes in experienced centers.

Core-Shell Microfiber Encapsulation Enables Glycerol-Free Cryopreservation of RBCs with High Hematocrit.

Cryopreservation of red blood cells (RBCs) provides great potential benefits for providing transfusion timely in emergencies. High concentrations of glycerol (20% or 40%) are used for RBC cryopreservation in current clinical practice, which results in cytotoxicity and osmotic injuries that must be carefully controlled. However, existing studies on the low-glycerol cryopreservation of RBCs still suffer from the bottleneck of low hematocrit levels, which require relatively large storage space and an extra concentration process before transfusion, making it inconvenient (time-consuming, and also may cause injury and sample lose) for clinical applications. To this end, we develop a novel method for the glycerol-free cryopreservation of human RBCs with a high final hematocrit by using trehalose as the sole cryoprotectant to dehydrate RBCs and using core-shell alginate hydrogel microfibers to enhance heat transfer during cryopreservation. Different from previous studies, we achieve the cryopreservation of human RBCs at high hematocrit (> 40%) with high recovery (up to 95%). Additionally, the washed RBCs post-cryopreserved are proved to maintain their morphology, mechanics, and functional properties. This may provide a nontoxic, high-efficiency, and glycerol-free approach for RBC cryopreservation, along with potential clinical transfusion benefits.

Comparative effectiveness and safety of Chinese medicine belly button application for childhood diarrhea: a Bayesian network meta-analysis of randomized controlled trials.

Background: Chinese medicine belly button application (CMBBA) has been used to treat childhood diarrhea (CD) in several randomized controlled trials (RCTs), but its effectiveness and combination strategy still need to be clarified. Therefore, we aimed to evaluate the effectiveness, safety, and the optimal combination strategy of CMBBA in treating CD. Methods: Up until January 2023, we searched for studies that met our inclusion criteria in six databases, including PubMed, the Cochrane Library, Chinese SinoMed, CNKI, VIP, and Wanfang. Heterogeneity was quantified using I2 statistics. A methodological evaluation was performed using the Cochrane Risk Bias Tool 2.0. The Confidence in Network Meta-Analysis online software was employed to evaluate evidence grading. A minimally contextualized framework was used to provide a comprehensive conclusion for the network meta-analysis. This study protocol was registered with PROSPERO. Results: We analyzed data from 33 RCTs that included 4,490 children with diarrhea. In terms of clinical effectiveness, CMBBA plus montmorillonite powder plus anti-infectives may be the most effective treatment option for children with diarrhea and concurrent infection according to a minimally contextualized framework. Either exclusive use of CMBBA or CMBBA in combination with modern medicine was beneficial in reducing the time to diarrhea disappearance (MD = -1.33 days, 95% CI: -1.59 to -1.08, Z = -10.103, p < 0.001) compared to modern medicine exclusively, and the difference was statistically significant. The combined usage of CMBBA could shorten the recovery time of dehydration by an average of 0.74 days (MD = -0.74 days, 95% CI: -1.10 to -0.37, Z = -3.931.103, p < 0.001). While some studies have reported mild allergic reactions and mild abdominal pain after CMBBA use, these symptoms can be cured in a relatively short period of time. Conclusions: The combination of CMBBA, montmorillonite powder, and anti-infectives may provide superior clinical effectiveness for children with diarrhea and concurrent infection. To treat CD, CMBBA can be used effectively and safely. However, the findings must be interpreted with cautiously due to the limited number of clinical trials and the low quality of the studies. In addition, the choice of treatment plan should also be based on the specific conditions of each patient. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022380694.

Miniature Two-Photon Microscopic Imaging Using Dielectric Metalens.

Miniature two-photon microscopy has emerged as a powerful technique for investigating brain activity in freely moving animals. Ongoing research objectives include reducing probe weight and minimizing animal behavior constraints caused by probe attachment. Employing dielectric metalenses, which enable the use of sizable optical components in flat device structures while maintaining imaging resolution, is a promising solution for addressing these challenges. In this study, we designed and fabricated a titanium dioxide metalens with a wavelength of 920 nm and a high aspect ratio. Furthermore, a meta-optic two-photon microscope weighing 1.36 g was developed. This meta-optic probe has a lateral resolution of 0.92 µm and an axial resolution of 18.08 µm. Experimentally, two-photon imaging of mouse brain structures in vivo was also demonstrated. The flat dielectric metalens technique holds promising opportunities for high-performance integrated miniature nonlinear microscopy and endomicroscopy platforms in the biomedical field.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

AIM: To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). METHODS: This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. RESULTS: A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. CONCLUSION: The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

Galectin-1 promotes gastric cancer peritoneal metastasis through peritoneal fibrosis.

BACKGROUND: Peritoneal metastasis is one of the main causes of death in patients with gastric cancer (GC). Galectin-1 regulates various undesirable biological behaviors in GC and may be key in GC peritoneal metastasis. METHODS: In this study, we elucidated the regulatory role of galectin-1 in GC cell peritoneal metastasis. GC and peritoneal tissues underwent hematoxylin-eosin (HE), immunohistochemical (IHC), and Masson trichrome staining to analyze the difference in galectin-1 expression and peritoneal collagen deposition in different GC clinical stages. The regulatory role of galectin-1 in GC cell adhesion to mesenchymal cells and in collagen expression was determined using HMrSV5 human peritoneal mesothelial cells (HPMCs). Collagen and corresponding mRNA expression were detected with western blotting and reverse transcription PCR, respectively. The promoting effect of galectin-1 on GC peritoneal metastasis was verified in vivo. Collagen deposition and collagen I, collagen III, and fibronectin 1 (FN1) expression in the peritoneum of the animal models were detected by Masson trichrome and IHC staining. RESULTS: Galectin-1 and collagen deposition in the peritoneal tissues was correlated with GC clinical staging and were positively correlated. Galectin-1 enhanced the ability of GC cells to adhere to the HMrSV5 cells by promoting collagen I, collagen III, and FN1 expression. The in vivo experiments confirmed that galectin-1 promoted GC peritoneal metastasis by promoting peritoneal collagen deposition. CONCLUSION: Galectin-1-induced peritoneal fibrosis may create a favorable environment for GC cell peritoneal metastasis.

Associations between family history of psoriatic disease and clinical characteristics on patients with psoriatic arthritis: a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR II).

OBJECTIVES: The study aimed to identify clinical characteristics in Chinese patients with psoriatic arthritis (PsA) with or without a family history of psoriasis and/or PsA. METHODS: Patients with PsA were recruited based on Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021. The demographics, clinical information relating to PsA, laboratory variables and comorbidities were collected. The association between family history of psoriatic disease and clinical characteristics on PsA was analysed using logistic regression analysis. RESULTS: Among 1074 eligible patients with PsA, 313 (29.1%) had a family history of psoriasis and/or PsA. Compared with patients without a family history, notably, patients with a family history of psoriasis and/or PsA had an earlier age of onset of psoriasis and PsA, higher proportions of enthesitis and nail involvement, a higher prevalence of positive human leukocyte antigen-B27 (HLA-B27), lower disease activity score 28-erythrocyte sedimentation rate, higher proportions of hyperlipidaemia, lower proportions of hypertension and diabetes. Furthermore, after adjusting for confounding factors, logistic regression analysis demonstrated that a positive family history of psoriasis and/or PsA was associated with more females (OR 1.514, 95% CI 1.088-2.108, p=0.014), earlier age at psoriasis onset (OR 0.971, 95%CI 0.955-0.988, p=0.001), a higher prevalence of HLA-B27 (OR 1.625 95%CI 1.089-2.426, p=0.018), more presence of nail involvement (OR 1.424, 95%CI 1.007-2.013, p=0.046) and enthesitis (OR 1.393, 95%CI 1.005-1.930, p=0.046), a higher proportion of hyperlipidaemia (OR 2.550, 95%CI 1.506-4.317, p=0.001) in PsA patients. CONCLUSIONS: This was first nationwide study to characterize patients with and without a family history of psoriatic disease in China. The findings from the present study revealed that family history of psoriasis and/or PsA had greater effects on disease phenotypes of PsA, especially nail disease and enthesitis.

Refining eligibility criteria of unit selection for myeloablative cord blood transplantation in acute leukemia: Real-world experience of a referral center.

The algorithm for cord blood (CB) unit selection is still somewhat ambiguous. We retrospectively analyzed 620 cases of acute leukemia between 2015 and 2020, who were treated with myeloablative single-unit umbilical CB transplantation (UCBT). We found that, when human leukocyte antigen (HLA) mismatch was ≤3/10, CD34+ cell dosage <0.83 × 105/kg-considerably lower than prevalent guidelines-was permissible without affecting survival. Moreover, synergy between donor killer-cell immunoglobulin-like receptors (KIR) haplotypes-B and donor-recipient HLA-C mismatch protected against relapse-related mortality. We submit that minimum required CD34+ cell dosage can possibly be relaxed to broaden access to UCBT, and donor KIR genotyping should be considered during unit selection.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR).

BACKGROUND: The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. METHODS: Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. RESULTS: In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. CONCLUSIONS: Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Dynamic comparison of early immune reactions and immune cell reconstitution after umbilical cord blood transplantation and peripheral blood stem cell transplantation.

Umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) are effective allogeneic treatments for patients with malignant and non-malignant refractory hematological diseases. However, the differences in the immune cell reconstitution and the immune reactions during initial stages post-transplantation are not well established between UCBT and PBSCT. Therefore, in this study, we analyzed the differences in the immune reactions during the early stages (days 7-100 post-transplantation) such as pre-engraftment syndrome (PES), engraftment syndrome (ES), and acute graft-versus-host disease (aGVHD) and the immune cell reconstitution between the UCBT and the PBSCT group of patients. We enrolled a cohort of patients that underwent UCBT or PBSCT and healthy controls (n=25 each) and evaluated their peripheral blood mononuclear cell (PBMC) samples and plasma cytokine (IL-10 and GM-CSF) levels using flow cytometry and ELISA, respectively. Our results showed that the incidences of early immune reactions such as PES, ES, and aGVHD were significantly higher in the UCBT group compared to the PBSCT group. Furthermore, in comparison with the PBSCT group, the UCBT group showed higher proportion and numbers of naïve CD4+ T cells, lower proportion and numbers of Tregs, higher proportion of CD8+ T cells with increased activity, and higher proportion of mature CD56dim CD16+ NK cells during the early stages post-transplantation. Moreover, the plasma levels of GM-CSF were significantly higher in the UCBT group compared to the PBSCT group in the third week after transplantation. Overall, our findings demonstrated significant differences in the post-transplantation immune cell reconstitution between the UCBT and the PBSCT group of patients. These characteristics were associated with significant differences between the UCBT and the PBSCT groups regarding the incidences of immune reactions during the early stages post transplantation.

Impact of Iron Overload and Iron Chelation with Deferasirox on Outcomes of Patients with Severe Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation.

Patients suffering from severe aplastic anemia (SAA) need frequent blood transfusions during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these transfusions can result in an excess of iron in the body tissues, which can negatively impact the success of transplantation. This study aimed to examine the impact of pretransplantation iron overload (IO) on the outcomes of allo-HSCT in patients with SAA. It also investigated whether iron chelation (IC) therapy is necessary to enhance transplantation outcomes in SAA patients by providing guidelines for determining when excess iron should be chelated. The study consisted of 2 parts. In cohort 1, which was retrospective and conducted from April 2012 to December 2018, SAA patients receiving their first allo-HSCT were divided into 2 groups based on their pretransplantation serum ferritin (SF) level: the IO group (SF >1000 ng/mL; n = 17) and the non-IO group (SF ≤1000 ng/mL; n = 48). Cohort 2, a prospective clinical trial conducted from January 2019 to July 2020, included SAA patients diagnosed with IO who were treated with IC therapy using deferasirox at a dose of 10 to 30 mg/kg. Patients were separated into 2 groups based on their pretransplantation SF level: the IC success (ICsuccess) group (SF ≤1000 ng/mL; n = 18) and the IC failure (ICfailure) group (SF >1000 ng/mL; n = 28). All participants were evaluated for the correlation between pretransplantation SF level and transplantation outcomes. A P value <.05 was considered statistically significant. There was no significant difference in the speed of engraftment among the 3 cell lineages or in the incidence of 100-day grade II-IV acute graft-versus-host disease (aGVHD), grade III-IV aGVHD, or 3-year chronic GVHD between the 2 groups in both cohorts. Of note, however, in cohort 1, both 1-year overall survival (OS) (41.2% versus 83.3%; P < .001) and 3-year OS (35.3% versus 83.3%; P < .001) were significantly worse in the IO group. Furthermore, 180-day transplantation related mortality (TRM) (47.1% versus 14.6%; P = .005) and 1-year TRM (52.9% versus 16.7%; P = .002) were significantly higher in the IO group. The IO group was significantly associated with inferior 3-year OS in both univariate and multivariate analyses. In cohort 2, 1-year OS (88.9% versus 42.9%; P = .003) and 3-year OS (83.3% versus 42.9%; P = .007) were significantly better in the ICsuccess group, whereas 180-day TRM (11.1% versus 39.3%; P = .040) and 1-year TRM (11.1% versus 57.1%; P = .003) were significantly lower in the ICsuccess group. These differences were confirmed in both univariate and multivariate analyses. This study involving 2 cohorts shows that pre-HSCT IO has a negative impact on transplantation outcomes in SAA patients. Chelating excess iron with an SF level <1000 ng/mL was found to be necessary and could potentially improve the outcomes.

Influence and effect mechanism of filler type on the physicochemical properties, microbial numbers, and digestibility of ovalbumin emulsion gels during storage.

This study was designed to investigate the influence and effect mechanism of the filler type on the physicochemical properties, microbial numbers, and digestibility of ovalbumin emulsion gels (OEGs) during storage. Sunflower oil was emulsified with ovalbumin (20 mg mL-1) and Tween 80 (20 mg mL-1) separately to prepare ovalbumin emulsion gels (OEGs) that contained active and inactive fillers, respectively. The formed OEGs were stored at 4 °C for 0, 5, 10, 15, and 20 days. The active filler enhanced the gel hardness, water holding capacity, fat holding capacity, and surface hydrophobicity and decreased the digestibility and free sulfhydryl content during storage compared to control (unfilled) ovalbumin gel, whereas the inactive filler had the opposite effects. Protein aggregation diminished, lipid particle aggregation increased, and the amide A band shifted to a higher wavenumber for all three types of gel during storage, suggesting that the compact network structure of the OEG became rough and disordered with storage. The OEG with the active filler did not inhibit microbial growth, and the OEG with the inactive filler did not significantly promote the development of bacteria. In addition, the active filler delayed the in vitro digestion of the protein in the OEG throughout storage. Emulsion gels containing active filler facilitated the retention of the gel properties during storage, whereas emulsion gels containing inactive filler exacerbated the loss of the gel properties during storage.

Formation mechanism of salted egg yolk mudding during storage: Protein oxidation, gel structure, and conformation.

The aim of this study was to investigate the formation mechanism of salted egg yolk (SEY) mudding during storage. Results showed that the soluble protein, hardness, and intrinsic fluorescence intensity of SEY decreased significantly during storage, while total volatile basic nitrogen, sulfhydryl group, dityrosine, adhesiveness, and surface hydrophobicity increased significantly, and the intrinsic fluorescence peak position red-shifted at first and then blue-shifted. In addition, from the results of infrared and microstructure analyses, there was an obvious oxidation reaction between protein and lipid in the late storage stage; the structure of SEY was destroyed, many random coils were formed, and the degree of protein-lipid binding and the crystallinity of SEY protein decreased during storage. Finally, the heatmap analysis revealed that the protein and lipid oxidation and conformational changes might be the main reasons for SEY mudding. This study can provide theoretical guidance for the control of SEY mudding.

Efficacy and safety of Janus kinase inhibitors in patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors (Jakinibs) in the treatment of psoriasis and psoriatic arthritis (PsA). METHODS: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials on the efficacy and safety of Jakinibs in treating psoriasis and PsA from inception to July 2021. A systematic review and meta-analysis were performed to estimate pooled relative risk (RR) and 95% confidence interval (CI). RESULTS: Seventeen clinical trials (16 publications) comprising 6802 patients were included. All Jakinibs demonstrated significantly higher response rates compared with placebo (ACR20: RR 2.09, 95% CI 1.90-2.30; PASI75: RR 4.03, 95% CI 3.13-5.18). Within the subgroup analysis, the response rates defined by ACR20 were highest for filgotinib (RR 2.40, 95% CI 1.67-3.45), followed by upadacitinib, tofacitinib, and deucravacitinib. The proportion of patients achieving PASI75 response in the tofacitinib 10 mg twice daily group was significantly higher than that in the tofacitinib 5 mg group. Regarding safety, the incidence of adverse events (AEs) was significantly higher for Jakinibs compared with placebo (RR 1.17, 95% CI 1.11-1.23). Of note, a considerable increase in the risk of infections including upper respiratory tract and herpes zoster infection was observed among patients in the treatment group. For tofacitinib, upadacitinib, and filgotiniband, infection was the most prevalent AE. Moreover, AEs in the 10 mg tofacitinib group were higher than those in the 5 mg tofacitinib group. CONCLUSION: Jakinibs are efficacious interventions for the treatment of psoriasis and PsA, but they are associated with an increased risk of AEs when compared with placebo. The long-term efficacy and safety data require further evaluation. Key Points • This systematic review investigated and compared the efficacy and safety of different Jakinibs including the novel selective TYK2 inhibitors. • Jakinibs are efficacious interventions for the treatment of psoriasis and PsA. • A relatively higher dosing schedule of Jakinibs is associated with increased toxicity.

Influence and effect mechanism of disulfide bonds linkages between protein-coated lipid droplets and the protein matrix on the physicochemical properties, microstructure, and protein structure of ovalbumin emulsion gels.

In this study, disulfide bonds between the interfacial protein film formed on the lipid particles and the protein in ovalbumin emulsion gels were blocked with 0, 1, 3, 5 and 10 mM of the N-ethylmaleimide (NEM) to explore the influence and effect mechanism of disulfide bonds between the interfacial proteins on the physicochemical properties, microstructure, and protein structure of sunflower oil-ovalbumin emulsion gels. Ovalbumin emulsion gels with NEM-treated ovalbumin emulsion (N-OE) had lower hardness, free sulfhydryl content, water holding capacity (WHC), and surface hydrophobicity, but higher spin-spin relaxation time (T2) than ovalbumin emulsion gels with NEM-treated ovalbumin substrate solution (N-OSS). In addition, N-OE and N-OSS had lower hardness, free sulfhydryl content, WHC and surface hydrophobicity, as well as a more coarse and disordered microstructure than non-NEM treated ovalbumin emulsion gel (control group). The free sulfhydryl content, hardness, WHC, and surface hydrophobicity of the ovalbumin emulsion gels all decreased as the NEM concentration rose (p < 0.05), whereas the amide A band changed to higher wave numbers. These results collectively indicated that the reduction of disulfide between the interfacial layer and the proteins inhibited the hydrophobic effect, the formation of hydrogen bonds, and prevented the formation of larger aggregates. Thus the disulfide bonds between the interfacial proteins contribute to the hardness enhancement and water stabilization of the ovalbumin gel.

The Composite Immune Risk Score predicts overall survival after allogeneic hematopoietic stem cell transplantation: A retrospective analysis of 1838 cases.

There has been little consensus on how to quantitatively assess immune reconstitution after hematopoietic stem cell transplantation (HSCT) as part of the standard of care. We retrospectively analyzed 11 150 post-transplant immune profiles of 1945 patients who underwent HSCT between 2012 and 2020. 1838 (94.5%) of the cases were allogeneic HSCT. Using the training set of patients (n = 729), we identified a composite immune signature (integrating neutrophil, total lymphocyte, natural killer, total T, CD4+ T, and B cell counts in the peripheral blood) during days 91-180 after allogeneic HSCT that was predictive of early mortality and moreover simplified it into a formula for a Composite Immune Risk Score. When we verified the Composite Immune Risk Score in the validation (n = 284) and test (n = 391) sets of patients, a high score value was found to be associated with hazard ratios (HR) of 3.64 (95% C.I. 1.55-8.51; p = .0014) and 2.44 (95% C.I., 1.22-4.87; p = .0087), respectively, for early mortality. In multivariate analysis, a high Composite Immune Risk Score during days 91-180 remained an independent risk factor for early mortality after allogeneic HSCT (HR, 1.80; 95% C.I., 1.28-2.55; p = .00085). In conclusion, the Composite Immune Risk Score is easy to compute and could identify the high-risk patients of allogeneic HSCT who require targeted effort for prevention and control of infection.