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Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative. [ABSTRACT FROM AUTHOR]

Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains. Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope). The phenomenon of cross-reactivity in HLA testing, often explained as cross-reactive groups (CREGs) of antigens with antibody, can be clearly explained now by public epitopes. Since 2006, we defined and reported 194 HLA class I unique epitopes, including 56 cryptic epitopes on dissociated HLA class I heavy chains, 83 HLA class II epitopes, 60 epitopes on HLA-DRB1, 15 epitopes on HLA-DQB1, 3 epitopes on HLA-DQA1, 5 epitopes on HLA-DPB1, and 7 MICA epitopes. In this paper, we provide a summary of our findings. [ABSTRACT FROM AUTHOR]

Purpose: To examine the impact of gypenosides (Gyps) on oxidative stress damage of orbital fibroblasts (OFs) from Graves' ophthalmopathy (GO) patients.Methods: The relationship between Gyps and GO oxidative stress was understood by bioinformatics analysis. Orbital connective tissues of GO and non-GO patients were obtained for primary OF culture. The proliferation level of OFs was measured by Cell Counting Kit-8 method, and the appropriate intervention concentration of Gyps and H2O2 was obtained. The expression of apoptosis-related protein mRNA was analyzed by RT-qPCR technique. ROS and SOD test suites were employed to detect the oxidative stress level in OFs. Flow cytometry apoptosis detection, TUNEL detection, and lactate dehydrogenase detection were used to analyze the level of apoptosis. Western blotting detection was utilized to examine the regulatory pathway of oxidative stress, apoptosis, and autophagy-related proteins. The changes of cell morphology, autophagosome, and autophagy lysosome were observed by transmission electron microscope.Results: The suitable intervention concentration of Gyps is 100 μg/mL, and the suitable intervention concentration of high concentration H2O2 is 350 μM. In comparison with the blank control group, the H2O2 intervention group enhanced the expression of apoptosis-related mRNA, the expression of ROS and SOD, the apoptosis rate, the expression of autophagy activation-related protein and Nrf2/ERK/HO-1 protein, and the number of autophagosomes and autophagy lysosomes. Compared with H2O2 intervention group, the expression of apoptosis-related mRNA decreased, ROS expression decreased, SOD expression increased, apoptosis rate decreased, autophagy activation-related protein expression decreased, Nrf2/ERK/HO-1 protein expression increased, and the quantity of autophagosomes and autophagy lysosomes decreased in H2O2 + Gyps intervention group.Conclusion: Gyps can decrease the oxidative stress level of OFs generated by H2O2, reduce cell autophagy, and reduce apoptosis. Gyps may regulate the oxidative stress response of OFs in GO patients via the Nrf2/ERK/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy of intravenous thrombolysis combined with arterial thrombolysis (bridging therapy) in patients with acute cerebral infarction and its effect on serum inflammatory factors.Methods: The case data of 138 patients with acute cerebral infarction admitted to our hospital from February 2019 to February 2021 were retrospectively analyzed. According to the treatment plan they received, patients were assigned to two groups, namely, an observation group (n = 71) treated with bridging therapy and a control group (n = 67) treated with intravenous thrombolysis alone. The following indexes were recorded and compared between the two groups: treatment efficacy, National Institutes of Health Stroke Scale (NIHSS) score, activities of daily living, incidence rates of vascular recanalization, intracranial hemorrhage and reembolization after treatment, levels of inflammatory factors before and after treatment, levels of prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) before and 1 week after treatment, and modified Rankin Scale scores 1, 3, and 6 months after treatment.Results: Compared with the control group, the therapeutic efficacy, neurological function, activities of daily living, and vascular recanalization were markedly better in the observation group (P > 0.05). In addition, the incidence of intracranial hemorrhage and reembolization was statistically lower in the observation group (P < 0.05). No marked difference was found between the two groups in terms of pretreatment serum inflammatory factors and coagulation function (P > 0.05), while the above indicators improved statistically after treatment in both groups, with comparatively more obvious improvement in the observation group. It was also observed that, compared with the control group, the modified Rankin Scale score in the observation group was significantly better at 3 and 6 months after treatment (P < 0.05).Conclusion: Bridging therapy can improve the vascular recanalization rate among patients suffering from acute cerebral infarction, reduce the incidence of intracranial hemorrhage and reembolization, and improve the prognosis and neurological function of patients, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Yin-Yang 1 (YY1) has a crucial function in the development of several malignancies, according to recent research. However, nothing is known about its aberrant expression and prognostic significance in human pan-cancer. We first explored the potential carcinogenic effect of YY1 in 33 cancers using the cancer genome atlas (TCGA) project and gene expression omnibus (GEO) datasets in this research. Then, we contained a variety of elements, for instance, gene expression, the state of survival, gene alterations, protein phosphorylation, immune infiltration, and related cellular pathways, and used a series of bioinformatics methods to investigate the underlying molecular mechanism of YY1 in the etiology or clinical prognosis of various malignancies. In most malignancies, YY1 was expressed at high levels, and the level of YY1 expression was statistically associated with the prognosis of tumor patients. The S118 site of YY1 implied higher phosphorylation expression in breast cancer, colon cancer, uterine corpus endometrial carcinoma (UCEC), and lung adenocarcinoma (LUAD) tumor tissues, but lower phosphorylation levels in ovarian cancer and clear cell carcinoma tumor tissues. For S247, higher phosphorylation levels were found in colon cancer, UCEC, and LUAD tumor tissue, and lower phosphorylation expression was found in clear cell carcinoma tumor tissue. In TCGA database, YY1 expression in BRCA, BRCA-LumA, BRCA-LumB, CESC, CHOL, COAD, ESCA, HNSC, HNSC-HPV-, KIRP, LGG, LIHC, and PAAD tumor tissues was a statistically significant positive connection of the estimated infiltration value of cancer-associated fibroblasts but a negative correlation in TGCT. In addition, the functional mechanism of YY1 also involves viral carcinogenesis and ribonucleic acid (RNA) metabolism related functions. Our first pan-cancer analysis offers a pretty comprehensive knowledge of YY1's oncogenic involvement in various cancers. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis was conducted to assess the efficacy of acupuncture treatment for postprandial distress syndrome (PDS).Methods: Search the Web of Science, the Cochrane Library, PubMed, and Embase databases with acupuncture randomized controlled trials for the treatment of patients with PDS. Strictly according to inclusion and exclusion quality assessment standards, the qualified ones are used to study the optimum extraction and data by two independent reviewers. Stata 15.0 software was used for meta-analysis.Result: We initially identified 63 studies, of which five (1253 participants) were eventually included in our analysis. There were 643 cases in the experimental group and 610 cases in the control group. Acupuncture had a significant effect on the total therapeutic effect (OTE) at week 4 (OR 4.74, 95% CI 02.88-7.83, Z = 6.10, P = 0 < 0.05). Significantly improved NDI (Nepean dyspepsia index) scores of PDS patients at week 4 (SMD 0.61, 95% CI 0.48 to 0.74). Significantly improved NDI scores in PDS patients at week 16 (SMD 0.49, 95% CI 0.27 to 0.71). After acupuncture treatment, the SID (dyspepsia symptom index) score of PDS patients decreased significantly at week 4 (SMD-0.52, 95% CI -0.73 to -0.32) and week 16 (SMD-0.59, 95% CI -0.81 to -0.36). Postprandial satiety scores (SMD-0.63, 95% CI -0.76 to -0.50) and early satiety scores (SMD-0.51, 95% CI -0.64 to -0.37) were also significantly lower at week 4 after acupuncture.Conclusion: This study highlighted that the acupuncture could significantly improve the overall therapeutic effect of PDS patients, alleviate the symptoms of postprandial fullness and early satiety, and improve the quality of life of patients. Our results supported that acupuncture was an effective therapeutic strategy for postprandial distress syndrome. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical efficacy of flavonoid supplements on allergic diseases.Design: Systematic review. Data Sources. MEDLINE/PubMed, Scopus, Web of Science, and Embase databases were searched from inception to September 2021. Eligibility Criteria for Selecting Studies. Eligible study designs were randomized controlled trials that investigated the effect of flavonoids applied to allergic diseases.Results: This review included 15 randomized controlled trials, including allergic rhinitis/cedar pollinosis (n = 10), asthma (n = 3), and atopic dermatitis (n = 2). A total of 990 participants aged 6 to 69 years were included in these studies. Globally, 12 studies (80%) revealed some benefits of flavonoids (isolate or combined with other compounds) in allergic patients, while three studies (20%) reported no statistically significant impact on symptom scores and/or lung function. No severe adverse events related to treatment were reported. According to the GRADE system, the outcomes evaluated were of low to moderate quality of evidence.Conclusions: Overall, this review suggests that the administration of flavonoids may provide a viable strategy for mitigating allergic symptoms. Future trials with high methodological quality are needed to establish definitive conclusions. This trial is registered with PROSPERO registration no. CRD42021237403. [ABSTRACT FROM AUTHOR]

Background: Patients with psoriasis need long-term medication to control their condition. Recent studies suggest that changing the intestinal flora may be a potential treatment.Methods: The databases were utilized to search the randomized controlled trials (RCTs) and preclinical trials about probiotic supplement in the treatment of psoriasis. The retrieval time is from the establishment of these databases to December 2020. RevMan5.3 was used for the risk assessment of bias and meta-analysis. This systematic review was registered in PROSPERO (CRD42021232756).Results: A total of 3 RCTs involving 164 participants were included. Two RCTs showed that probiotics can improve PASI and thereby improve the condition. For inflammation-related indicators, only one RCT showed that probiotics can improve the levels of CRP and TNF-α but have no obvious improvement effect on IL6. One RCT demonstrated the total effective rate of probiotics in the treatment of psoriasis. For adverse events, one RCT showed that the incidence of adverse events of probiotic treatment was low. Preclinical studies showed that continuous intervention with oral probiotics can significantly improve the progression of psoriasis and reduce the expression of inflammatory factors. The meta-analysis showed that the PASI between two groups was of no statistical significance (SMD 1.83 [-0.41, 4.07], P = 0.11). Meanwhile, probiotics may improve skin thickness (SMD -5.87 [-11.34, -0.41], P = 0.04) in animal model.Conclusion: Prebiotics may have a positive effect on alleviating the clinical symptoms of psoriasis, but a large sample of RCTs is still needed to support its therapeutic effect in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Tacrolimus is a second-line immunosuppressant in myasthenia gravis (MG) therapy, which is mainly used in combination with corticosteroids to reduce steroid dose and maintain the effect of immunotherapy. However, few studies have focused on the effect of tacrolimus as single-agent immunotherapy on achieving minimal manifestation status (MMS). Thus, this study is aimed at exploring the efficacy and influencing factors of tacrolimus as single-agent immunotherapy in MG.Methods: Clinical data of 75 nonthymoma MG patients treated with tacrolimus single-agent as initial immunotherapy were retrospectively analyzed. The therapeutic effect was evaluated by Myasthenia Gravis Foundation of America postintervention status. Clinical factors affecting the achievement of MMS and treatment reactivity of different MG subtypes were determined by Cox regression analysis.Results: Tacrolimus was generally safe, with only two patients (2.7%) switching medications due to side effects. 32% of patients had improved symptoms after 1 month of treatment. 69.2% of patients achieved MMS or better after one year. The age < 39 years old, QMG score < 11 points, and AChR - Ab titer < 8.07 nmol/L were indicative of a favorable response, which was independent of gender, course of the disease. As for MG subtypes, ocular and seronegative MG showed better treatment sensitivity.Conclusions: Tacrolimus as single-agent immunotherapy takes effect quickly and can effectively enable nonthymoma MG patients to achieve MMS. Tacrolimus can be used alone for the initial immunotherapy of MG patients, especially for young, mild, and low antibody titer patients. [ABSTRACT FROM AUTHOR]

Purpose: To study the relationship between surface membrane-bound APRIL and ITP.Methods: The peripheral blood of all subjects, 50 patients diagnosed with ITP and 25 healthy controls, was collected. Flow cytometry was used to detect the expression of membrane-bound APRIL on immune cells and platelets. ELISA was used to detect the content of soluble APRIL in plasma.Results: Membrane-bound APRIL was only expressed on the surface of platelets in both ITP patients and controls. APRIL expression on the platelet surface was significantly lower in newly diagnosed (P < 0.001) and chronic (P < 0.001) ITP patients than in controls. Platelet surface APRIL level was significantly enhanced in patients with complete remission after treatment (P = 0.02) but not in those with no response after treatment. Platelet surface APRIL level in ITP patients was negatively correlated with serum APRIL level (r = -0.09765, P = 0.0424).Conclusions: Platelet surface APRIL may play a key immunoregulative role. Platelet surface APRIL is likely to be one source of the excessive serum APRIL in ITP patients. The effectiveness of treatment may be measured by determining the platelet surface APRIL levels in ITP patients. [ABSTRACT FROM AUTHOR]

Background: Lung transplantation has been performed worldwide and admitted as an effective treatment for patients with various end-stage lung diseases. However, limit reliable clinical indicators exist to identify patients at high risk for allograft failure in lung transplant recipients. The recent advances in the knowledge of immunological aspects of the pulmonary diseases, for that innate macrophage activation, are induced by pathogen or pathogen-derived molecules and widely accepted as the critical evidence among the pathogenesis of lung inflammation and fibrosis. This study was aimed at evaluating the clinical significance of CD86- and macrophage scavenger receptor 1- (MSR1-) positive cells during the development of idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH), and their potential roles in the prediction of the outcomes after lung transplantation were examined.Methods: Tissues from lung transplantation for 37 IPF and 15 PAH patients from the Department of Cardiothoracic Surgery in Wuxi People's Hospital from December 2015 to December 2016 were analyzed by immunohistochemistry (IHC) for detecting the expression and CD86 and MSR1 and correlated with clinical events after lung transplantation.Results: IHC results showed that the expression of MSR1, IL-13, and arginase-1 (Arg1) but not CD86 in the lung section of IPF patients was dramatically enhanced when compared with that of PAH patients. The expression of MSR1, IL-13, and Arg1 but not CD86 in the lung from IPF patients with smoking was significantly increased when compared with that from nonsmoking subjects. In addition, the expression of MSR1-positive cells in IPF subjects with Klebsiella pneumoniae infection was dramatically enhanced than that in noninfection subjects. MSR1-positive macrophages were negatively associated with FEV1 and with FVC but not associated with TLC and with TLCO. However, CD86-positive macrophages were not significantly associated with the above lung function-related factors. Furthermore, MSR1 had a higher area under the ROC curve (AUC) than CD86 for IPF diagnosis. Survival analysis indicated that high levels of MSR1-positive macrophages had a worse prognostic effect for IPF patients with lung transplantation.Conclusion: Our study indicates the clinical significance of Klebsiella pneumoniae infection-related MSR1-positive cells in IPF progression, and it could be a prognostic marker in IPF after the lung transplant; development strategies to reduce the expression of MSR1-positive macrophages in IPF may be beneficial for the lung transplant. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide. Inflammation and the nutritional status of patients with GC are important factors affecting the therapeutic effect and prognosis. Inflammatory and nutrition-related markers have been shown to be prognostic factors for patients with GC. However, few studies have investigated the relationship of the prealbumin-to-globulin ratio (PGR) with the prognosis of GC patients. The objective of the present study was to examine whether pretreatment PGR is related to the prognosis and chemotherapy outcomes of in-patients with advanced GC undergoing first-line chemotherapy. We retrospectively reviewed the data of 281 patients with unresectable GC from January 2013 to January 2018. The receiver operating characteristic curve analysis determined the cut-off values for the PGR. The relationship between the PGR and chemotherapy effectiveness was evaluated using the chi-square test. Kaplan-Meier's method was used to plot progression-free survival (PFS) and overall survival (OS) curves, using multivariable Cox regression analysis to identify promising predictors of mortality. The cut-off value for the PGR was 7.21. The high-PGR (≥7.21) group had a higher disease control rate than that of the low-PGR group (93.66% vs. 78.42%, p < 0.001). Kaplan-Meier's analysis showed significantly higher median PFS (189 vs. 125 days, p < 0.001) and OS (350 vs. 288 days, p < 0.001) in the high-PGR group. The multivariate analyses revealed that a high PGR is an independent protective factor in patients with advanced GC, both in terms of PFS (hazard ratio [HR]: 0.672; 95% confidence interval [CI]: 0.527-0.857; p < 0.001) and OS (HR: 0.675; 95% CI: 0.530-0.861; p = 0.002). In conclusion, the prechemotherapy PGR can accurately predict the chemotherapy outcome, PFS, and OS of patients with advanced GC. Therefore, medical practitioners can utilize the PGR as a novel dependable prognostic tool to weigh the prognosis of patients with GC. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases. [ABSTRACT FROM AUTHOR]

Neuroblastoma is a pediatric solid cancer of heterogeneous clinical behavior. The unique features of this type of cancer frequently hamper the process of determining clinical presentation and predicting therapy effectiveness. The tumor can spontaneously regress without treatment or actively develop and give rise to metastases despite aggressive multimodal therapy. In recent years, immunotherapy has become one of the most promising approaches to the treatment of neuroblastoma. Still, only one drug for targeted immunotherapy of neuroblastoma, chimeric monoclonal GD2-specific antibodies, is used in the clinic today, and its application has significant limitations. In this regard, the development of effective and safe GD2-targeted immunotherapies and analysis of other potential molecular targets for the treatment of neuroblastoma represents an important and topical task. The review summarizes biological characteristics of the origin and development of neuroblastoma and outlines molecular markers of neuroblastoma and modern immunotherapy approaches directed towards these markers. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is widely considered a distinct clinical entity with a well-defined molecular and genetics-based prognosis. Particularly in a younger patient, the therapeutic approach depends largely on diagnostic risk stratification, which has an impact on the outcome after therapy. We added Treg evaluation to the usual molecular and cytogenetics profile in the AML younger patients' diagnostic bone marrow aspirate (dBMA) in order to search for any correlation between Tregs and overall response (OR) as well as survival (OS) rates. We studied 23 AML young patients, all treated with standard induction chemotherapy: OR (complete remission (CR) + CR incomplete (CRi)) was documented in 10 of 23 patients (44%); there were two partial responder patients. The optimal dBMA Treg cut-off value for predicting response to treatment (≥21/μL) was obtained by ROC curve analysis. However, in multivariate analysis, apart from the expected impact of the molecular/cytogenetic risk (p = 0.049) and NPM mutation (p = 0.001), dBMA Tregs ≥ 21/μL was not correlated with OR. Actually, higher dBMA Tregs were associated with the good intermediate molecular/cytogenetic risk group (p = 0.02), whose median OS was confirmed to be better as compared with that of the poor risk group (18 versus 5 months, p = 0.05) and equal to the dBMA Tregs ≥ 21/μL group (5 versus 5 months, p = 0.902), respectively. The possible prognostic value of such an immunological player as BMA Tregs in the diagnostic and successive phases of AML needs to be confirmed in larger patient numbers. [ABSTRACT FROM AUTHOR]

Lipegfilgrastim is a long-acting, once-per-cycle, glycopegylated recombinant granulocyte colony-stimulating factor (G-CSF) used to prevent neutropenia in patients receiving myelosuppressive chemotherapy. This integrated analysis examined the immunogenicity of lipegfilgrastim and its potential clinical impact in two double-blind randomized studies (phases II and III) of patients with breast cancer receiving chemotherapy. Serum samples were analyzed using sequential assays for screening, confirmation, antibody titer, and characterization of antidrug antibodies (ADA). Neutropenia-related efficacy measures were reviewed for each ADA-positive patient. Among 255 patients receiving lipegfilgrastim (154 in phase II, 101 in phase III) and 155 patients receiving pegfilgrastim (54 in phase II, 101 in phase III), the incidence of treatment-emergent ADA was low and similar between the lipegfilgrastim (phase II: 1.3%; phase III: 1.0%) and pegfilgrastim (phase II: 1.9%; phase III: 1.0%) arms. None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against lipegfilgrastim, pegfilgrastim, or glycosylated G-CSF in a cell-based neutralizing antibody assay. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients, and no treatment-related hypersensitivity or anaphylaxis occurred. These results indicate that there is no apparent impact of ADA on lipegfilgrastim efficacy and safety. [ABSTRACT FROM AUTHOR]

This review considers the steps required to evaluate a candidate biodefense vaccine or therapy as it emerges from the research phase, in order to transition it to development. The options for preclinical modelling of efficacy are considered in the context of the FDA's Animal Rule. [ABSTRACT FROM AUTHOR]