Recovery Of Immune Function Research Articles

Effect of Remimazolam- Vs Propofol-Based Intravenous Anesthesia on Surgical Stress Response and Post-Operative Immune Function in Patients with Gastric Radical Surgery.

This study aimed to compare the impact of remimazolam-based versus propofol-based intravenous anesthesia on surgical stress and post-operative immune function in patients undergoing gastric radical surgery. Sixty-eight patients aged 50 to 80 undergoing gastric radical surgery were randomly assigned to the remimazolam group (group R) or the propofol group (group P), receiving remimazolam or propofol-based intravenous anesthesia, respectively. The primary outcome measured was peri-operative serum stress indicators and lymphocyte subtypes. Secondary outcomes included hemodynamic vitals, recovery quality, postoperative pain profiles and potential adverse effects. The demographic and surgical characteristics of the 60 analyzed patients were comparable. The absolute counts of CD3+CD4+ and CD3+CD8+ cell decreased significantly on POD1 compared with baseline. On POD3, the numbers of CD3+CD4+ cells in group R were lower than baseline and Group P, whereas the CD3+CD8+ cell counts in both groups were lower than baseline, with group R higher than group P. The CD3-CD16+CD56+ cell numbers in both groups on POD1 and POD3 decreased significantly compared to baseline with group P lower than group R on POD3. The serum levels of IL-1β, IL-6, TNF-α, ACTH and COR rose sharply 2hours after the beginning of surgery compared to baseline. Notably, all these parameters in group R were higher than those in group P. Additionally, blood pressure and intra-operative vasoactive drug frequency in group R were higher than that in group P. No significant differences in recovery quality, postoperative pain profiles, and potential adverse effects were observed. Remimazolam-based intravenous anesthesia might favour the recovery of cellular immune function in early postoperative period compared to propofol. On the contrary, remimazolam was inferior to propofol in suppressing surgical stress. Further studies with larger sample sizes are needed to confirm our findings.

Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Immune system diseases, malignant tumors, and traumatic injuries can directly damage the structure and function of lymphoid organs, while subsequent radiotherapy, chemotherapy, and lymph node dissection further damage the patient's immune system, leading to immune dysfunction, metabolic disorders, and increased susceptibility to infection, which seriously affect the patient's prognosis and quality of life. In this context, nanotechnology plays a key role in lymphoid organ regeneration and immune function recovery, including improving the therapeutic effect through targeted drug delivery systems, using targeted imaging probes to achieve tumor prediction and early detection, combining nanoplatforms with immunotherapy and photodynamic therapy to achieve synergistic therapeutic effects, and using nanomaterials to regulate the tumor microenvironment to enhance the sensitivity of traditional treatments. In addition, biophysical simulation strategies that simulate the microenvironment of lymphoid organs have also attracted widespread attention, aiming to construct a native cell environment to support the regeneration and functional recovery of damaged lymphoid tissues, or to simulate immune cells to regulate lymphocytes and induce specific immune responses. The multifaceted application of nanotechnology provides promising prospects for lymphoid organ regeneration and immune system repair.

Prebiotics enhance the immunomodulatory effect of Limosilactobacillus fermentum DALI02 by regulating intestinal homeostasis.

The colonization ability of Limosilactobacillus fermentum DALI02 and the promoting effect of fermented prebiotics have been studied. This study aims to evaluate the systemic immunomodulatory effects of DALI02 and DALI02 + Prebiotics on cyclophosphamide-induced immunosuppressed rats. We found that DALI02 and DALI02 + Prebiotics, especially DALI02 + Prebiotics, exhibited significant restorative effects on the immunocompromised state in rats (p < .05). Specifically, both of them promoted the recovery of body weight and immune organ function, enhanced the proliferative capacity of immune cells, and effectively reduced the levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, both of them significantly reduced the levels of lipopolysaccharide (LPS) and D-lactic acid in the blood (p < .05). Principal coordinate analysis (PCoA), principal component analysis (PCA), and unsupervised cluster analysis revealed that DALI02 and DALI02 + Prebiotics group were more similar to the blank group at the genus level of the gut microbiota. At the level of short-chain fatty acids (SCFAs), DALI02 + Prebiotics and blank group belonged to Cluster 3. These results suggested that the intervention with DALI02 and DALI02 + Prebiotics effectively modulated the structure of the gut microbiota, and DALI02 + Prebiotics restored the dysregulation of SCFAs. In summary, DALI02 and DALI02 + Prebiotics possess immunomodulatory functions, with the latter showing superior effects.

An efficient and successful outcome after haematopoietic stem cell transplantation in a patient with an LPS-responsive beige-like anchor gene mutation.

Lipopolysaccharide (LPS)-responsive beige ankyrin (LRBA) gene mutations were first reported as the cause of immunodeficiency syndromes and autoimmunity in 2012. The majority of LRBA patients have multiple organ system involvement and a complex clinical phenotype. Herein we present a comprehensive account on the disease progression and transplantation procedure in a patient with LRBA deficiency who exhibited progressive autoimmune disease symptoms along with recurrent pulmonary infections since the age of 6 years old. Despite receiving abatacept therapy and immunoglobulin replacement treatments to manage the symptoms, but the symptoms still progressed. Therefore, nine years after disease onset, patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). The patient experienced acute and chronic graft-versus-host disease (GVHD) and recurrent infections after transplantation. During one and a half years of follow-up, we found that allogeneic haematopoietic stem cell transplantation can relieve the symptoms of autoimmune disease in patients with LRBA deficiency, and marked clinical improvement and recovery of immune function were observed following stem cell transplantation.

Efficacy and mechanism of the Ermiao San series of formulas for rheumatoid arthritis based on Chinmedomics strategy

BackgroundThe Ermiao San Series of Formulas (ESSF) refers to Ermiao San (TS), Sanmiao Wan (TW), and Simiao Wan (FW), which are widely used traditional Chinese medicine (TCM) formulas for treating rheumatoid arthritis (RA). However, the therapeutic advantages and underlying mechanisms of ESSF treatment are unclear, especially regarding the improper selection of these three formulas when treating RA. PurposeTo explore the efficacy and mechanisms of ESSF treatment for RA. MethodsComplete Freund's adjuvant was used to induce RA in rats. Chinmedomics strategy, which included metabolomics, serum pharmacochemistry of TCM, molecular docking, western blotting and qPCR, was applied to reveal the therapeutic advantages, pathways, and targets of ESSF. ResultsIn the early stages of treatment, TS quickly reduced joint swelling and the arthritis score index and regulated pathways such as arachidonic acid metabolism and purine metabolism. TW increases the regulation of tryptophan metabolism and pyrimidine metabolism pathways, promoting the recovery of the thymus and spleen. FW increases the regulation of linoleic acid metabolism and has the greatest effect on immune organ and bone recovery. In addition, 54, 67, and 86 bioactive compounds were detected in the serum from TS, TW, and FW, respectively. Berberine, phellodendrine, atractylolide III, limonin, 25R-inokosterone, coixol, and stigmasterol were found to act on the key enzymes COX-2, mPGES-1, ALOX5, and XDH in arachidonic acid metabolism and purine metabolism pathways. Western blot and qPCR results showed that ESSF can reduce the activity of these targets, thereby inhibiting the expression of the inflammatory factors IL-1β, IL-6, IL-17, and TNF-α; the tissue injury factors MMP-3 and CRP; and the rheumatoid factors CCP Ab and RF, thereby achieving anti-RA efficacy. ConclusionESSF has a good therapeutic effect on RA. TS focus on rapid swelling reduction in the early stages of RA, TW focus on the recovery of immune organ function, and FW can be used for bone recovery in the later stage of RA treatment. The key mechanism of treating RA is that ESSF reduces the activity of COX-2, mPGES-1, ALOX5, and XDH. These findings provide valuable guidance for targeted therapy for RA and for the clinical application of ESSF.

Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism

BackgroundThe damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored. PurposeThis study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms. MethodsIn a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice. ResultsAPS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4+T, CD8+T, CD19+B, F4/80+CD11B+ macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80+CD11B+CD206+ cells. ConclusionAPS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.

Discovery of tricyclic PARP7 inhibitors with high potency, selectivity, and oral bioavailability

PARP7 has been recently identified as an effective drug target due to its specific role in tumor generation and immune function recovery. Herin, we report the discovery of compound 8, which contained a tricyclic fused ring, as a highly selective PARP7 inhibitor against other PARPs. In particular, compound 8 strongly inhibits PARP7 with an IC50 of 0.11 nM, and suppresses the proliferation of NCI–H1373 lung cancer cells with an IC50 of 2.5 nM. Compound 8 exhibits a favorable pharmacokinetic profile with a bioavailability of 104 % in mice, and 78 % in dogs. Importantly, daily treatment of 30 mg/kg of 8 induced 81.6 % tumor suppression in NCI–H1373 lung xenograft mice tumor models, which is significantly better than the clinical candidate, RBN-2397. These intriguing features highlight the promising advantages of 8 as an antitumor agent.

Research and Analysis of Molecules such as CD28, CD45RA, CD45RO, CD38, HLA-DR, and CD57 on T Cells in Multiple Myeloma.

For many years it has been postulated that the immune system controls the progress of multiple myeloma (MM). However, the phenotypes of T cells in MM remain to be elucidated. In this study, we compared the phenotypes of T cells, which were obtained from the peripheral blood, in MM patients with those in healthy donors (HD). The expression of CCR7, CD57, CD28, HLA-DR, CD38, CD45RA, and CD45RO were assessed on T cells from MM patients and HDs using multicolor flow cytometry (MFC). For this study, 17 newly diagnosed MM patients were selected, and 20 healthy people were selected as a control group. MFC was used to detect the markers on T cells. We detected significant increases in the expression levels of HLA-DR, CD38, and CD57on CD8+ T cells, significant decreases in the expression levels of CD28 and CD45RA on CD8+ T cells, and a decrease of CD4+ effec-tor T cells in MM patients, compared to the HD group. Our study shows that the accumulation of peripheral CD8+CD57+T cells, CD8+CD38high T cells, and CD8+HLA-DR+CD38high T cells is reflective of an ongoing antitumor T cell response and a progressive immune dysfunction in MM. During chemotherapy, the recovery of immune function can be monitored by detecting the proportion of activated molecules of T lymphocytes.

Spatial proteomics identifies a spectrum of immune dysregulation in acquired bone marrow failure syndromes.

Poor graft function (PGF), manifested by multilineage cytopenias and complete donor chimerism post-allogeneic stem cell transplantation (alloSCT), and acquired aplastic anaemia (AA) are immune-mediated acquired bone marrow (BM) failure syndromes with a similar clinical presentation. In this study, we used spatial proteomics to compare the immunobiology of the BM microenvironment and identify common mechanisms of immune dysregulation under these conditions. Archival BM trephines from patients exhibited downregulation of the immunoregulatory protein VISTA and the M2 macrophage marker and suppressor of T-cell activation ARG1 with increased expression of the immune checkpoint B7-H3 compared to normal controls. Increased CD163 and CD14 expression suggested monocyte/macrophage skewing, which, combined with dysregulation of STING and VISTA, is indicative of an environment of reduced immunoregulation resulting in the profound suppression of hematopoiesis in these two conditions. There were no changes in the immune microenvironment between paired diagnostic AA and secondary MDS/AML samples suggesting that leukaemic clones develop in the impaired immune microenvironment of AA without the need for further alterations. Of the eight proteins with dysregulated expression shared by diagnostic AA and PGF, the diagnostic AA samples had a greater fold change in expression than PGF, suggesting that these diseases represent a spectrum of immune dysregulation. Unexpectedly, analysis of samples from patients with good graft function post-alloSCT demonstrated significant changes in the immune microenvironment compared to normal controls, with downregulation of CD44, STING, VISTA, and ARG1, suggesting that recovery of multilineage haematopoiesis post-alloSCT does not reflect recovery of immune function and may prime patients for the development of PGF upon further inflammatory insult. The demonstrable similarities in the immunopathology of AA and PGF will allow the design of clinical interventions that include both patient cohorts to accelerate therapeutic discovery and translation.

Effect of perioperative acupoint electrical stimulation on macrophages in mice under operative stress

The strong perioperative stress response caused by surgical anesthesia can significantly suppress immune function, and the body is in a state of immunosuppression for 3 to 4 days after surgery, which leads to an increase in the probability of postoperative infection. Traditional Chinese medicine believes that acupuncture points can "reconcile yin and yang", promote the recovery of immune function, and help reduce the incidence of postoperative infection. Macrophages are an important type of immune cells that participate in the body's innate immunity. They have powerful phagocytosis and clearance functions. They can be polarized into M1 and M2 types under the regulation of the body, and play different roles in fighting microbial infections. Among them, the M1 type can participate in the elimination of pathogens. In this study, we will investigate the perioperative acupoint electrical stimulation to alleviate the immunosuppressive state of surgical stress mice, clarify the regulation of perioperative acupoint electrical stimulation on glucocorticoids and the relationship between NF-κB molecules and macrophage polarization.The key molecules of related pathways were verified by glucocorticoid receptor inhibitors, and it was found that electrical stimulation of acupoints during the perioperative period can affect the polarization of macrophages in surgically stressed mice to the M1 type by reducing the level of glucocorticoids and promoting the expression of NF κB molecules. Further reveal the partial mechanism of electroacupuncture regulating the anti-inflammatory and pro-inflammatory processes of macrophages in the immune response.

Recovery of host adaptive immune function promoted the reduction of hepatitis B surface antigen in nucleoside analog-experienced chronic hepatitis B patients with low hepatitis B surface antigen levels.

Hepatitis B surface antigen (HBsAg) seroclearance is an optimal therapeutic endpoint, as it reflects the amount of covalently closed circular DNA. The exact mechanisms that contribute to HBsAg reduction are not completely understood. We evaluated adaptive immunity in nucleoside analog-experienced chronic hepatitis B (CHB) patients with low HBsAg levels who received oral antiviral therapy. One hundred and ninety-five CHB patients had hepatitis B virus (HBV) DNA≤1000IU/ml and HBsAg<3000IU/ml for longer than one year of antiviral therapy. According to HBsAg levels, they were divided into Group 1 (HBsAg reduction≥0.5 log10) and Group 2 (HBsAg reduction<0.5 log10). Cytokines, adaptive immune cells, and molecular markers in peripheral blood were detected at follow-up times. In total, 38 (19.5%) of the 195 patients achieved HBsAg reduction≥0.5 log10. IL4, IL5, IL10, TGF β, IL17, and PD-1 decreased gradually in these patients. HBsAg reduction had a link to the change in ICOSL+CD19+ B cells and CD40L+CXCR5+CD4+ Tfh cells. More CD8+ naive T lymphocytes differentiated into CD4+ TCMs, CD8+ TCMs and CD8+ TEMs in Group 1. Meanwhile, Group 1 exhibited elevated Th1 and Th1/Th2 levels and reduced levels of Treg versus those in Group 2. With the reduction in HBsAg, the imbalance of T-cell subsets was partially corrected; the immune activity of T cells was enhanced, and the state of immune exhaustion was alleviated to a certain extent.

Mechanisms of Thymic Repair of In Vitro-Induced Precursor T Cells as a Haploidentical Hematopoietic Stem Cell Transplantation Regimen

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is currently an effective treatment for malignant hematological disease, but the immune deficiency and severe infection triggered by slow immune reconstitution are the main causes of high mortality and transplant failure. One of these outstanding problems is thymus damage, which is associated with graft-versus-host disease (GVHD), and preconditioning including irradiation and chemotherapy. Therefore, rapid repair of damaged thymus and rapid proliferation of thymus-derived donor T cells after transplantation are key to solving the problem. This study is designed to accelerate the recovery of thymus-derived T cells after transplantation. Wild-type mice with normal immunity were used as recipients in a haplo-HSCT mouse model to mimic clinical haplo-HSCT. A modified cell culture system using Notch ligand Delta4 and IL-7 was established that is capable of inducing and amplifying the differentiation and proliferation of hematopoietic stem cells into precursor T (preT) cells in vitro. Haplo-HSCT protocol included the preT and G-CSF mobilized donor splenic mononuclear cells (MNC) co-infusion or MNC alone. Thymic GVHD, thymic repair, and thymus-derived T cell development were compared in two groups by polychromatic immunofluorescence tracking, flow cytometry and detection of T cell receptor Vβ. The thymus homing and T-cell regeneration of allogenic preT cells were observed. The functions of preT cells in accelerating immune reconstitution, restoring thymic architecture, weakening GVH effects, and enhancing immuno-tolerance after transplantation were demonstrated. Further studies revealed that allogeneic preT cells induced by a culture system containing IL7 and Delta4 highly express ccr9 and RANKL. Interestingly, the RANK expression was promoted after preT cells' thymus homing. These results suggested that the RANK/RANKL pathway may play an important role in thymus homing. Our results provide a potential therapeutic option to optimize haplo-HSCT. It further opened up a new field of T cell therapy for artificial induction of allogeneic precursor T cells in vitro to repair the damaged thymus from irradiation and chemotherapy, and to compensate for the recovery of immune function in patients with immune deficiency caused by multiple reasons.

Abnormal Activation of T Cells in HIV-1 Infection After Antiretroviral Therapy

To investigate the relationship between abnormal activation of T cell subsets in peripheral whole blood and the recovery of immune function in persons infected with HIV-1, and to examine the relationship between the size of the viral reservoir of HIV-1 DNA and T cell subsets. HIV-1-infected persons who underwent routine testing between July 2019 and May 2020 were the target population of the study. According to whether, at the time of enrollment, their CD4+ T cells reached 500 cells/μL after antiretroviral therapy (ART), HIV-1-infected persons were divided into two groups, 76 in the deficiency group and 61 in the immune recovery group. In addition, 22 people who were not exposed to HIV-1, and who were tested negative for HIV-1 antibody were selected as the control group. For the three groups of subjects, tests of the T cell subsets were conducted. A total of 77 HIV-1-infected persons, with 44 from the deficiency group and 33 from the recovery group, were examined for HIV-1 DNA reservoir. The deficiency group and the recovery group were followed up 6 months later and the CD4+ T cell test results of 133 blood samples were collected, with 74 from the deficiency group and 59 from the recovery group. The proportions of activated CD4+ and CD8+ T cells of the deficiency group were higher than those of the recovery group and the control group. The proportions of senescent CD4+ and CD8+ T cells in the deficiency group were comparable to those of the recovery group, which were higher than those of the control group, showing significant differences only in senescent CD8+ T cells, and no significant difference in senescent CD4+ T cells. The deficiency group expressed higher levels of effector memory CD4+ T and CD8+ T cells than the control group did, and the recovery group only expressed a higher level of effect memory CD8+ T cells. Both the deficiency group and the recovery group showed lower levels of central memory CD4+ T and CD8+ T cells than the control group did, and the recovery group had an even lower level of central memory CD4+ T cells than the deficiency group did. The recovery group showed a higher expression level of naïve CD4+ T cells, and the deficiency group and the recovery group had lower expression levels of naïve CD8+ T cells than the control group did. There was no correlation between the size of the viral reservoir of HIV-1 DNA and CD4+ T cell count or the T cell subsets. Activated CD4+ T cells, activated CD8+ T cells, and central memory CD4+ T cells were negatively correlated with the follow-up findings for CD4+ T cells, with r at －0.378, －0.334, and －0.322, respectively ( P<0.05). Naïve CD4+ T cells and naïve CD8+ T cells were positively correlated with the follow-up findings for CD4+ T cell subset, with r at 0.350 and 0.267, respectively ( P<0.05). HIV-1 infected persons have varying degrees of abnormal immune activation of T cell subsets. The abnormal activation of some T-cell subsets is partly associated with the subsequent recovery of immune functions and the size of the viral reservoir of HIV-1 DNA was not associated with the T cell subsets.

Recovery of constitutive immune function after migratory endurance flight in free-living birds.

Strenuous physical activity can negatively affect constitutive innate immune function (CIF), the always present first line of defence against pathogens. CIF is non-specific, and thus vital when encountering novel pathogens. A lowered CIF likely increases the risk of infection and disease. Migratory birds engage in truly extreme physical activity during their endurance flights, however, little is known about how they deal with the negative impact this has on their immune function. By collecting both between- and within-individual data we show, for the first time, that free-flying migratory birds can recover several parameters of CIF during stopovers, which are stationary periods in between migratory flights. With this, we provide an important piece of the puzzle on how migrating birds cope with the physiological challenges they face on their biannual journeys. Furthermore, our study stresses the importance of migratory stopovers beyond fuel accumulation.

Analysis on Cellular Immune Function Recovery after HLA Mismatched Allogeneic Hematopoietic Stem Cell Micro-Transp- lantation in Elderly AML Patients

To investigate the recovery of cellular immunity in elderly patients with acute myeloid leukemia (AML) after micro-transplantation (MST) and the changes of cellular immunity during relapse, as well as their clinical significance. A total of 41 elderly AML patients who received MST treatment in a single center and 25 healthy elderly people were included. Immune function among different age groups in normal population was compared. Furthermore, immune fuction was compared between elderly AML patients of different age groups who achieved continuous complete remission (CR) after MST treatment and normal controls, between high risk group and medium-low risk group, as well as among before diagnosis, after CR, and relapse. Peripheral blood of patients and normal controls was collected, and the percentage of lymphocyte subsets was detected by multi-color flow cytometry. Thirty-five patients achieved CR after MST treatment while six patients did not. After MST treatment, CD3+ T cells, CD8+T cells and activated T cells in all age groups were higher than normal. Significant recovery of CD3+ and CD8+T cells was observed in both high risk and medium-low risk groups, and the overall recovery of immune cells in medium-low risk group was better. It was also observed that B lymphocytes and NK cells could not return to normal levels within 1 year after MST treatment. The proportion of CD3+ T cells, CD4+ T cells, and CD4/CD8 ratio were significantly decreased during relapse compared with continuous CR after MST (P<0.05). MST treatment can promote the recovery of CD3+T cells, CD8+T cells and other killer cells, so as to improve the cellular immune function of elderly patients, which provides a new immune cell therapy for elderly AML.

Efficacy of ultrasound-guided percutaneous transhepatic biliary drainage for acute obstructive suppurative cholangitis combined with septic shock

ObjectivesThis study aimed to investigate the efficacy of ultrasound-guided Percutaneous Transhepatic Biliary Drainage (PTCD) for the treatment of Acute Obstructive Suppurative Cholangitis (AOSC) combined with septic shock due to choledocholithiasis, and its effect on inflammatory factors. MethodsClinical data of 86 patients with AOSC and septic shock admitted to our hospital between January 2019 and May 2021 were retrospectively analyzed and grouped according to different treatment methods. Among them, 43 patients who underwent Endoscopic Retrograde Cholangiopancreatography (ERCP) and Endoscopic Nasobiliary Drainage (ENBD) were included in the Control Group (CNG), and 43 patients who underwent ultrasound-guided PTCD were included in the Study Group (SG). ResultsThe total effective rate in the SG (88.37%) was higher than that in the CNG (69.77%) (p < 0.05); after surgery, the serum inflammatory factors PCT, IL-6, TNF-α, CRP levels, liver function indicators such as TBIL, DBIL, AST, ALT levels, and stress response indicators including NPY, PGE2, 5-HT levels were reduced, and were lower in the SG than in the CNG (p < 0.05); postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the CNG were significantly lower than those before surgery (p < 0.05); Postoperatively, CD3+, CD4+, and CD4+/CD8+ levels in the SG were significantly higher than those in the CNG (p < 0.05); and the complication rate in the SG (6.98%) was lower than that in the CNG (25.58%) (p < 0.05). ConclusionsUltrasound-guided PTCD for AOSC combined with septic shock can facilitate the recovery of liver and immune functions with a low complication rate.

Gut Instinct: How the Microbiome Affects Traumatic Brain Injury, A Narrative Review

Objectives: Emerging evidence suggests that the gut microbiome may play a role in the pathophysiology of traumatic brain injury (TBI). The objective of this systematic review is to identify and evaluate studies that investigate the relationship between TBI and gut microbiota alterations. Methods: Using the PRISMA 2020 Checklist, we searched five databases to identify relevant studies. Two independent researchers screened titles and abstracts and identified eligible studies according to the following PICO: studies that investigated the relationship between TBI and gut microbiota AND reported outcomes related to gut microbiome alterations. We assessed the risk of bias for included studies, extracted methodological data and related results of the articles, and used them for qualitative analysis. Results: We screened the titles and abstracts of 23 identified records and assessed the full text of 10 studies. In total, 5 studies met eligibility criteria and were entered into the qualitative analysis. These studies investigated the effects of TBI on gut microbiota in animal models and human patients. Although, we planned to systematic review, lack of adequate quantitively and qualitative data compelled us to write a narrative survey. The majority of studies reported significant alterations in gut microbiota composition and function following TBI, with potential implications for immune function, inflammation, and neurological recovery. Conclusion: This systematic review provides evidence supporting a relationship between TBI and alterations in gut microbiota. While the exact mechanisms underlying this relationship remain unclear, these findings suggest that targeting the gut microbiome may represent a novel therapeutic approach for TBI. Further studies are needed to elucidate the mechanisms involved and to evaluate the potential benefits of gut microbiota-targeted interventions in TBI.

Hepatitis B functional cure and immune response.

Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may "wake up" immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the "dominant population" for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency

BackgroundX-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies and hematopoietic stem cell transplant (HSCT). However, this cohort is particularly susceptible to the chemotherapeutic regimens and acutely affected by graft-vs-host disease (GvHD), driving poor long-term survival in transplanted patients. Autologous HSC gene therapy could offer an alternative treatment option and would abrogate the risks of alloreactivity.MethodsHematopoietic progenitor (Lin−ve) cells from XIAPy/− mice were transduced with a lentiviral vector encoding human XIAP cDNA before transplantation into irradiated XIAP y/− recipients. After 12 weeks animals were challenged with the dectin-1 ligand curdlan and recovery of innate immune function was evaluated though analysis of inflammatory cytokines, body weight, and splenomegaly. XIAP patient-derived CD14+ monocytes were transduced with the same vector and functional recovery was demonstrated using in vitro L18-MDP/NOD2 assays.ResultsIn treated XIAPy/− mice, ~40% engraftment of gene-corrected Lin−ve cells led to significant recovery of weight loss, splenomegaly, and inflammatory cytokine responses to curdlan, comparable to wild-type mice. Serum IL-6, IL-10, MCP-1, and TNF were significantly reduced 2-h post-curdlan administration in non-corrected XIAPy/− mice compared to wild-type and gene-corrected animals. Appropriate reduction of inflammatory responses was observed in gene-corrected mice, whereas non-corrected mice developed an inflammatory profile 9 days post-curdlan challenge. In gene-corrected patient CD14+ monocytes, TNF responses were restored following NOD2 activation with L18-MDP.ConclusionGene correction of HSCs recovers XIAP-dependent immune defects and could offer a treatment option for patients with XIAP deficiency.

The effects of nutritional support team intervention on postoperative immune function, nutritional statuses, inflammatory responses, clinical outcomes of elderly patients with gastric cancer

BackgroundTo explore the effects of nutrition support team (NST) intervention on elderly patients with gastric cancer (GC).MethodsThe elderly GC patients (tumor stage I/II/III), admitted to our department from January 2015 to September 2021, were retrospectively analyzed and divided into NST group and traditional nutrition (TN) group according to nutritional management methods. The immune, inflammatory, nutrition-related indices, postoperative recovery and long-term prognosis of two groups were analyzed.ResultsA total of 258 elderly GC patients were included (NST group, n = 125; TN group, n = 133). After propensity score matching (PSM) in ratio of 1:1, 73 pairs of patients were matched. There were statistically significant differences in CD3 and CD4 level postoperative one month and IgG level postoperative one week between NST group and TN group (P < 0.05). There was no significant differences in serum CRP and IL-6 levels preoperative one day, postoperative one week and one month between two groups (P > 0.05). There were significant differences in body mass index (BMI) between the two groups postoperative one month (P < 0.05). The rate of infectious complications in TN group was significantly higher than that in NST group (P < 0.05). There was no statistically significant differences in 3-year relapse-free survival (RFS) or 3-year overall survival (OS) between NST group and TN group (P > 0.05).ConclusionsCompared with TN management, NST intervention might be benefit to the immune function recovery and nutritional status, but there was no evidence that NST could improve the prognosis of elderly GC patients.